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The pivotal regulatory factor circBRWD1 inhibits arsenic exposure-induced lung cancer occurrence by binding mRNA and regulating its stability.

Multiple studies have indicated that circular RNAs (circRNAs) play a regulatory role in different stages of tumors by interacting with various molecules. With continuous in-depth research on the biological functions of circRNAs, increasing evidence has shown that circRNAs play important roles in carcinogenesis caused by environmental pollutants. However, the function and mechanism of circRNAs in arsenic exposure-induced lung cancer occurrence have not been reported. In this study, RNA sequencing and qPCR assays revealed that the expression of circBRWD1 was decreased in BEAS-2B-As cells and multiple lung cancer cell lines. Silencing circBRWD1 promoted cell viability and proliferation, inhibited cell apoptosis, and accelerated the G0G1 phase transition in BEAS-2B-As cells however, these functions were abrogated by circBRWD1 overexpression. Mechanistically, under arsenic exposure, expression of decreased circBRWD1 led to enhanced stability of the mRNA to which it directly binds (c-JUN, c-MYC, and CDK6 mRNA), increasing its expression. This mechanism promotes the malignant transformation of lung cells and ultimately leads to lung cancer. Our findings thus reveal the molecular mechanism of arsenic carcinogenesis.

Transcriptome Profiling of A549 Xenografts of Nonsmall-cell Lung Cancer Treated with Qing-Re-Huo-Xue Formula.

Lung cancer is one of the most common malignant tumors, and non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases. Chinese herbal formula Qing-Re-Huo-Xue (QRHXF) has shown antitumor effects in the NSCLC xenograft mouse model of Lewis cells. However, the molecular mechanisms underlying the antitumor effects of QRHXF remain unknown. In this study, an A549 xenograft mouse model was established, and the mice were then treated with QRHXF or vehicle through oral gavage. Tumor growth was monitored. Tumors were subsequently harvested, and RNA sequencing was performed. Compared with the control group, mice treated with QRHXF showed smaller tumor size and slower tumor growth. RNA sequencing results indicated 36 differentially expressed genes between QRHXF treated and control groups. 16 upregulated and 20 downregulated genes were identified. Enrichment analysis showed four differential expression genes (DEGs) related to tumor growth pathways RASAL2, SerpinB5, UTG1A4, and PDE3A. In conclusion, this study revealed that QRHXF could inhibit tumor growth in an A549 xenograft mouse model, and the target genes of QRHXF may include PDE3A, RASAL2, SERPIB5, and UTG1A4.

Evaluation of lncRNA FOXD3-AS1 as a Biomarker for Early-Stage Lung Cancer Diagnosis and Subtype Identification.

Lung cancer (LC) is the most commonly diagnosed cancer and the leading cause of cancer-related deaths. More and more long noncoding RNA (lncRNA) are associated with cancer. This study aimed to assess whether plasma lncRNA could be used to diagnose early-stage LC and identify subtypes of LC. For bioinformatic analysis, we used genetic data from the Cancer Genome Atlas, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC) datasets and a small cell lung cancer (SCLC) dataset from the Gene Expression Omnibus. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to examine the relative expression of lncRNA in LC tissues and plasma samples. The patients clinical information was obtained at the time of sample collection. According to public datasets, the lncRNA forkhead box D3 antisense 1 (FOXD3-AS1) was significantly upregulated in LUAD, LUSC, and SCLC tissues over controls. RT-qPCR assays confirmed this finding in LUAD, LUSC, and SCLC tissues and plasma samples. Even early-stage receiver operating characteristic analysis showed that plasma FOXD3-AS1 could be used to discriminate LUAD, LUSC, and SCLC from normal controls and identify LC subtypes SCLC. FOXD3-AS1 is significantly upregulated in LC tissues and plasma. FOXD3-AS1 could be a potential biomarker for LC subtype identification and early diagnosis.

Papillary thyroid carcinoma occurring with undifferentiated pleomorphic sarcoma A case report.

Papillary thyroid cancer (PTC) is the most common malignant tumor of the thyroid. However, the coexistence of PTC and sarcoma in one patient is rare. In this article, we report the case of a patient who presented with both PTC and undifferentiated pleomorphic sarcoma (UPS), which has not been previously reported in the online Medline database (PubMed). A 71-year-old man was admitted to our hospital for a mass on the right side of his neck for one month, which rapidly enlarged within 2 wk with distending pain. The patient was diagnosed with a thyroid malignancy by fine-needle aspiration and underwent total thyroidectomy and bilateral central lymph node dissection. Histology and immunohistochemistry revealed features of both PTC and UPS. The thyroid cancer 8 gene detection kit results showed BRAF and telomerase reverse transcriptase mutations. The disease progressed rapidly, and the patient died four months after surgery from extensive lung metastasis. Our report highlights the patients pathological characteristics and related genetic mutations. Due to the rapid development and poor prognosis of cooccurring PTC and sarcoma, it is important for clinical physicians and pathologists to raise awareness of this type of tumor.

Bronchogenic cysts with infection in the chest wall skin of a 64-year-old asymptomatic patient A case report.

Skin bronchogenic cysts are extremely rare congenital bronchocystic changes caused by the abnormal development of the trachea, bronchial trees or lung buds during the embryonic period. The first case of skin bronchogenic cysts was reported in 1945. Since then, this disease has attracted increasing attention, but due to the low incidence, its pathogenesis is still not clear. Here, we report another case of skin bronchogenic cysts with infection in a 64-year-old female patient. The patient had no symptoms for more than 60 years until her chest wall was recently found to be swollen, and she felt pain and discomfort. At the same time, secretions were found on the surface of the swelling. Color Doppler ultrasound examination showed abnormal echoes in the soft tissue under the frontal chest wall, suggesting the presence of cysts. Cytological puncture resulted in about 2 mL of pus and showed the presence of more acute inflammatory cells. The final clinical diagnosis was skin cyst with infection, and surgery was carried out. The pathological results obtained after surgery showed that the cystic wall was covered with column-like cilia epithelial cells, and the interstitial structure was partially inundated with inflammatory cells. After a variety of examinations and clinical diagnoses, we finally confirmed that the patient was suffering from bronchogenic cyst. This article not only describes the case of an elderly patient with rare skin bronchogenic cysts with infection but also provides a detailed and correct diagnosis and a successful treatment process, which is of great value for the diagnosis and treatment of the disease.

Primary ascending colon cancer accompanying skip metastases in left shoulder skin and left neck lymph node A case report.

Lymph node skip metastases are common in lung, breast, and thyroid cancer patients, but are rare in colon cancer patients. Specifically, lymph node skip metastases occur in 1%-3% of colon cancer patients. Previous reports have demonstrated colon cancer skip metastases involving the retropancreatic and portocaval lymph nodes and Virchows node however, reports involving skip metastases into the left neck lymph nodes and left shoulder skin are extremely rare, as are related reports of clinical treatment and prognosis. A 44-year-old Chinese man was admitted to the hospital for evaluation of persistent shoulder pain for 3 d and a cutaneous mass (3.0 cm × 2.0 cm) on the left shoulder. The left shoulder cutaneous mass was excised and bisected, revealing tissues with a fish-like appearance. The pathologic diagnosis of the cutaneous mass suggested a signature CDX-2 (), CK20 (), Ki-67 () > 50% of infiltrating or metastatic colorectal adenocarcinoma. An enhanced computed tomography scan of the abdomen revealed chronic appendicitis with fecal stone formation, cecal edema, and a pelvic effusion. A colonoscopy revealed a cauliflower-like mass within the ascending colon area that involved the lumen. The surface of the ascending colon mass was eroded and bleeding a biopsy was performed. The pathologic diagnosis of the colonoscopy biopsy was an ascending colon mucinous adenocarcinoma. The patient underwent a laparoscopic radical resection of the right colon based on the pathological diagnosis. The tumor was 5.0 cm × 4.5 cm × 1.8 cm in size and infiltrated the entire thickness of the intestinal wall with vascular tumor thrombi. No nerve tissue involvement was noted. The ileum and colon resection margins were negative. The postoperative pathologic analysis revealed non-metastatic involvement of ileocecal, pericolic, or peri-ileal lymph nodes. The postoperative medical examination revealed palpably enlarged lymph nodes in the left neck, and the following color Doppler ultrasound examination of the neck confirmed enlarged lymph nodes in the left neck. After surgical resection and pathologic diagnosis, a common pathologic signature consistent with resected cutaneous mass and right colon was identified, suggesting skip metastasis of left cervical lymph nodes. The patient was then treated with eight courses of chemotherapy and under follow-up evaluations for 4 years currently, no tumor recurrences or metastases have been noted. We report an abnormal skip metastasis involving the left shoulder skin and left neck lymph node in a patient with ascending colon adenocarcinoma. Specifically, we observed non-metastatic involvement of the lymph nodes around the tumor site but with metastases to the cervical lymph nodes. The standard surgical operations were performed to resect the cutaneous mass, tumor tissue, and cervical lymph nodes, followed by chemotherapy for eight courses. The patient is healthy with no tumor recurrences or metastases for 4 years. This clinical case will contribute to future research about the abnormal skip metastasis in colon cancers and a better clinical treatment design.

Comparison of demographic features and laboratory parameters between COVID-19 deceased patients and surviving severe and critically ill cases.

Coronavirus disease 2019 (COVID-19) has been far more devastating than expected, showing no signs of slowing down at present. Heilongjiang Province is the most northeastern province of China, and has cold weather for nearly half a year and an annual temperature difference of more than 60ºC, which increases the underlying morbidity associated with pulmonary diseases, and thus leads to lung dysfunction. The demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province, China with such climatic characteristics are still not clearly illustrated. To illustrate the demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province by comparing with those of surviving severe and critically ill cases. COVID-19 deceased patients from different hospitals in Heilongjiang Province were included in this retrospective study and compared their characteristics with those of surviving severe and critically ill cases in the COVID-19 treatment center of the First Affiliated Hospital of Harbin Medical University. The surviving patients were divided into severe group and critically ill group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (the seventh edition). Demographic data were collected and recorded upon admission. Laboratory parameters were obtained from the medical records, and then compared among the groups. Twelve COVID-19 deceased patients, 27 severe cases and 26 critically ill cases were enrolled in this retrospective study. No differences in age, gender, and number of comorbidities between groups were found. Neutrophil percentage (NEUT%), platelet (PLT), C-reactive protein (CRP), creatine kinase isoenzyme (CK-MB), serum troponin I (TNI) and brain natriuretic peptides (BNP) showed significant differences among the groups ( Compared with surviving severe and critically ill cases, no special demographic features of COVID-19 deceased patients were observed, while some laboratory parameters including NEUT%, PLT, CRP, CK-MB, TNI and BNP showed significant differences. COVID-19 deceased patients had higher CRP, D-dimer and NEUT% levels and lower LYMPH and PLT counts.

Follicular carcinoma of the thyroid with a single metastatic lesion in the lumbar spine A case report.

The bone is the second most common site of thyroid cancer metastasis, after the lung. Treatment options for bone metastasis of thyroid cancer include surgery, radioiodine therapy (RAIT), external radiation therapy, thyroid-stimulating hormone (TSH) inhibition, bisphosphonates, and small-molecule targeted therapies. In most cases, thyroid carcinoma is found in the thyroid tissue reports of follicular thyroid carcinoma with a single metastasis to the lumbar spine are rare. We report a case of bone metastasis as the only clinical manifestation of thyroid cancer. The patient was a 67-year-old woman with lumbar pain for 7 years and aggravation with intermittent claudication who had previously undergone partial thyroidectomy of a benign thyroid lesion. No abnormal nodules were found in the bilateral thyroid glands. However, imaging studies were consistent with a spinal tumor, and the lesion was diagnosed as a metastatic follicular carcinoma of thyroid origin. We adopted a multidisciplinary collaboration and comprehensive treatment approach. The patient underwent lumbar spine surgery, total resection of the thyroid, postoperative TSH suppression therapy, and RAIT. There were no complications associated with the operation, and the patient had good postoperative recovery. She has experienced no recurrence. Follicular thyroid carcinoma is associated with early hematogenous metastasis, and the bone is a typical site of metastasis. Single bone metastasis is not a contraindication to medical procedures, and providing the appropriate therapy can result in better outcomes and quality of life for these patients.

The nomograms for predicting overall and cancer-specific survival in elderly patients with early-stage lung cancer A population-based study using SEER database.

Lung cancer is the leading cause of death from cancer and the number of operable elderly lung cancer patients is increasing, with advanced age being associated with a poorer prognosis. However, there is no easy and comprehensive prognostic assessment method for these patients. Clinicopathological data of patients aged 65 years or older with TNM stage I-II lung cancer from 2004 to 2018 were downloaded from the SEER database. Patients from 2004 to 2015 were randomized into a training group ( A total of 29,736 patients were included. Univariate and multivariate analyses suggested that age, race, gender, marriage, disease grade, AJCC stage, T-stage, surgery, radiotherapy, chemotherapy, and tumor size were independent risk factors for patient prognosis. These 11 variables were included in nomogram to predict OS and CSS of patients. C-indexes of OS for the training, validation and external validation sets were 0.730 (95% CI, 0.709-0.751), 0.734 (95% CI, 0.722-0.746), and 0.750 (95% CI, 0.734-0.766), respectively. The AUC results for the training and validation sets indicated good accuracy for this nomogram. The calibration curves demonstrated a high degree of concordance between actual and anticipated values, and the DCA demonstrated that the nomograms had better clinical application than the traditional TNM staging approach. This study identified risk factors for survival in operable elderly lung cancer patients and established a new column line graph for predicting OS and CSS in these patients. The model has good clinical application and can be a good clinical decision-making tool for physicians and patients.

Metaplastic carcinoma of the breast real-world outcome from a tertiary cancer centre in India.

Metaplastic carcinoma (MPC) is a rare subgroup of breast tumours accounting for <5% of all invasive breast cancers. Histologically confirmed 40 MPC from January 2001 to December 2018 were identified from our electronic database stage I 2.5% (

SH005S7 Overcomes Primary and Acquired Resistance of Non-Small Cell Lung Cancer by Combined METEGFRHER3 Inhibition.

In this study, we have examined the anticancer effects of SH005S7 on MET-amplified and (HCC827GR) NSCLC cells and their primary HCC827 cells.

Network Pharmacology-Integrated Molecular Docking Reveals the Expected Anticancer Mechanism of

This study sought to explore the anticancer mechanism of

Scleroderma-like Syndrome in the Setting of Pembrolizumab Therapy for Non-Small Cell Lung Cancer Diagnosis and Dermatologic Management.

Immune checkpoint inhibitors play an important role in the treatment of malignancies. ICIs consist of monoclonal antibodies directed against inhibitory immune receptors cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), or programmed cell death-ligand 1 (PD-L1). PD-1 is a receptor expressed by T lymphocytes and has the role of inhibiting their activation. Pembrolizumab is a humanized anti-PD-1 monoclonal antibody. It can improve the immune function of T-cells, which results in significant clinical benefit in the treatment of cancer. Despite its wide use, immunotherapy is associated with a spectrum of side effects known as immune-related adverse events. We present a case of an 82-year-old patient with widespread fibroatrophic skin areas that occurred during a treatment with pembrolizumab for non-small cell lung cancer. Clinical, serological, and histopathological examinations led to the diagnosis of generalized morphea. The patient discontinued pembrolizumab and switched to chemotherapy with pemetrexed and carboplatin. A good therapeutic response was obtained with phototherapy, corticosteroids, and topical calcineurin inhibitors. A focus on the therapeutic management of this skin toxicity in oncological patients is provided.

Association of lung function with the risk of cardiovascular diseases and all-cause mortality in patients with diabetes Results from NHANES III 1988-1994.

The potential effects of pulmonary dysfunction on cardiovascular diseases (CVD) and all-cause mortality are receiving attention. The current study aimed to explore whether reduced lung function predicts CVD and all-cause mortality in people with diabetes. A total of 1,723 adults with diabetes (mean age 60.2 years) were included in the National Health and Nutrition Examination Survey (NHANES III). Death outcomes were ascertained by linkage to the database records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coronary heart disease (CHD), CVD, and all-cause mortalities. We conducted stratified analyses based on age, body mass index (BMI), history of hypertension, and dyslipidemia. During a mean follow-up of 14.62 years (25,184 person-year), a total of 1,221 deaths were documented, of which 327 were CHD, 406 were CVD, and 197 were cancer. After multi-factor adjustment, participants with lower FEV1 and FVC had a higher risk of CHD, CVD, and all-cause mortality. This association was also found in lower FVC and a higher risk of cancer mortality HR 3.85 (1.31-11.32) P for trend 0.040, but the association of FEV1 was attenuated after adjustment for covariates HR2.23 (0.54-9.17) P for trend 0.247. In subgroup analysis, we found that the adverse associations of FEV1 and FVC with CVD mortality were observed in subgroups of age, BMI, and history of hypertension and dyslipidemia. Declined lung function was associated with a higher risk of CVD and all-cause mortality in people with diabetes. Lung function tests, especially FEV1 and FVC, should be encouraged to provide prognostic and predictive information for the management of CVD and all-cause mortality in patients with diabetes.

Outcomes of enhanced recovery after surgery in lung cancer A systematic review and meta-analysis.

To assess the effect of ERAS on clinical prognosis in perioperative patients following lung cancer surgery. PubMed, Web of Science, MEDLINE, EMBASE, and other databases were systematically searched from inception to December 2021. Randomized controlled trials and peer-reviewed cohort studies on the use of ERAS in lung cancer surgery patients were included. Primary outcomes comprised visual analog scale scores after treatment and quality of life. Secondary outcomes comprised complication rate, function-related outcomes (chest tube indwelling time and first ambulation), and length of stay. Statistical analysis was performed using RevMan 5.4.1 software. Finally, 23 studies were included (12 cohort studies and 11 randomized controlled trials) with a total of 8094 patients. Meta-analysis showed that ERAS significantly reduced visual analog scale scores (mean difference MD -1.99, 95% confidence interval CI -2.45, -1.54, ERAS can accelerate postoperative recovery and improve quality of life. These findings support the use of ERAS as a standard of care for lung cancer surgery patients. However, the evidence quality was moderate and there were significant differences among studies. More high-quality studies incorporating relevant outcomes are needed for confirmation.

Sintilimab maintenance therapy post first-line cytokine-induced killer cells plus chemotherapy for extensive-stage small cell lung cancer.

Despite recent progress in treating advanced non-small cell lung cancer, clinical intervention in extensive-stage small-cell lung cancer (ES-SCLC) remains stagnant. The purpose of this study was to evaluate the clinical efficacy of cytokine-induced killer (CIK) cells combined with cytotoxic chemotherapy, followed by anti-programmed death 1 antibody (sintilimab) maintenance, in ES-SCLC patients. To explore a new method for safe treatment of ES-SCLC patients, thirteen ES-SCLC patients were enrolled between June 2019 and December 2021. All patients received first-line chemotherapy (etoposide plus platinum) combined with CIK cell therapy. Patients who reached a stable disease state or responded well to treatment received sintilimab maintenance treatment. The primary objective of this study was to determine the median overall survival (OS) the secondary objective was to assess the objective response rate (ORR), progression-free survival 1 and 2 (PFS1 was defined as the duration from the signing of informed consent to the date of tumor progression, or death, or the last follow-up. PFS2 was defined as the duration from the first day of sintilimab treatment to the date of tumor progression, death, or the last follow-up.), and adverse reactions. At a 24.1-month follow-up, the median OS was 11.8 (95% confidence interval CI 10.6-13.0) months, median PFS1 was 5.5 (95% CI 5.0-6.0) months, and the median PFS2 was 2.3 (95% CI 0.5-4.1) months. The ORR was 76.9% (1013), the disease control rate was 100% (1313), and the 20-month survival rate was 41.7%. Eight participants exhibited grade 3 or 4 adverse events after combination therapy. During maintenance treatment with sintilimab, level 3 adverse events occurred in 1 patient (19). In conclusion, adding CIK cells to standard chemotherapy regimens, followed by maintenance therapy with sintilimab, may represent a new safe and effective treatment strategy. ClinicalTrials.gov (NCT03983759).

Differentiation between spinal multiple myeloma and metastases originated from lung using multi-view attention-guided network.

Multiple myeloma (MM) and metastasis originated are the two common malignancy diseases in the spine. They usually show similar imaging patterns and are highly demanded to differentiate for precision diagnosis and treatment planning. The objective of this study is therefore to construct a novel deep-learning-based method for effective differentiation of two diseases, with the comparative study of traditional radiomics analysis. We retrospectively enrolled a total of 217 patients with 269 lesions, who were diagnosed with spinal MM (79 cases, 81 lesions) or spinal metastases originated from lung cancer (138 cases, 188 lesions) confirmed by postoperative pathology. Magnetic resonance imaging (MRI) sequences of all patients were collected and reviewed. A novel deep learning model of the Multi-view Attention-Guided Network (MAGN) was constructed based on contrast-enhanced T1WI (CET1) sequences. The constructed model extracts features from three views (sagittal, coronal and axial) and fused them for a more comprehensive differentiation analysis, and the attention guidance strategy is adopted for improving the classification performance, and increasing the interpretability of the method. The diagnostic efficiency among MAGN, radiomics model and the radiologist assessment were compared by the area under the receiver operating characteristic curve (AUC). Ablation studies were conducted to demonstrate the validity of multi-view fusion and attention guidance strategies It has shown that the diagnostic model using multi-view fusion achieved higher diagnostic performance ACC (0.79), AUC (0.77) and F1-score (0.67) than those using single-view (sagittal, axial and coronal) images. Besides, MAGN incorporating attention guidance strategy further boosted performance as the ACC, AUC and F1-scores reached 0.81, 0.78 and 0.71, respectively. In addition, the MAGN outperforms the radiomics methods and radiologist assessment. The highest ACC, AUC and F1-score for the latter two methods were 0.71, 0.76 0.54, and 0.69, 0.71, 0.65, respectively. The proposed MAGN can achieve satisfactory performance in differentiating spinal MM between metastases originating from lung cancer, which also outperforms the radiomics method and radiologist assessment.

Impact of the interval between neoadjuvant immunochemotherapy and surgery on surgical-pathological outcomes in non-small cell lung cancer.

The interval between neoadjuvant immunochemotherapy and surgery in patients with non-small cell lung cancer (NSCLC) has not been well characterized. This study investigated the association between the time-to-surgery (TTS) interval and surgical-pathological outcomes. Clinical data of patients who received neoadjuvant immun-ochemotherapy followed by surgery for NSCLC between January 2019 and September 2021 were collected. The patients were divided into three groups based on TTS interval the early-surgery group (ESG), the standard-surgery group (SSG), and the delayed-surgery group (DSG). The primary outcomes were objective response rate (ORR), major pathological response (MPR), and pathological complete response (pCR). The secondary endpoint was surgical outcome. Of the 171 patients, 16 (9.4%) received surgery in ≤28 days, 49 (28.7%) received surgery within 29-42 days, and 106 (61.9%) received surgery in ≥43 days after neoadjuvant immunochemotherapy, with a median TTS of 46 days. The postoperative drainage of the ESG group (455.1 ml) was significantly less than that of the SSG group (680.7 ml) and the DSG group (846.5 ml p 0.037). However, the TTS interval did not influence the duration of the operation ( This retrospective study indicated that TTS exerts no significant effect on the feasibility and safety of surgery in the neoadjuvant immunochemotherapy setting of NSCLC. Analysis of the TTS interval revealed a tendency for delayed surgery to be associated with a pathological response in NSCLC, although this association was not statistically significant.

Pembrolizumab monotherapy for untreated PD-L1-Positive non-small cell lung cancer in the elderly or those with poor performance status A prospective observational study.

We investigated the efficacy and safety of pembrolizumab monotherapy as first-line treatment for poor Eastern Cooperative Oncology Group performance status (PS) and elderly patients with programmed cell death-ligand 1 (PD-L1)-positive advanced non-small cell lung cancer (NSCLC). We also investigated clinical prognostic factors for the efficacy of pembrolizumab monotherapy, based on patient characteristics. In this prospective observational study, PS-2 and elderly NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1% who received first-line pembrolizumab monotherapy, from October 2019 to March 2021, at 10 institutions in Japan were enrolled. Patients judged eligible by their physicians for combined chemotherapy and PD-1PD-L1 inhibitors as first-line treatment were excluded. Clinicopathological characteristics and adverse events were investigated for correlation with clinical outcomes. Forty patients were enrolled in the study. The median progression-free survival (PFS) of patients with PS 2 and those aged ≥ 75 years were 4.4 (95% confidence interval CI 0.9-14.4) months and 5.3 (95% CI 2.9-9.4) months, respectively. The median overall survival (OS) of patients with PS 2 and those aged ≥ 75 years were 11.6 (95% CI 1.4-not evaluable NE) months and 11.6 (95% CI 7.4-18.1) months, respectively. Immune-related adverse events (irAEs) were observed in 19 patients 6 patients had severe irAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher. Patients who achieved stable disease or better, had a statistically significant increase in PFS (p < 0.001) and OS (p < 0.001). In the multivariate analysis, the acquisition of disease control with pembrolizumab monotherapy was an independent prognostic factor for PFS and OS. Pembrolizumab monotherapy was relatively effective and tolerable as a first-line treatment for patients with PD-L1-positive advanced NSCLC who had poor PS or were elderly. Our results suggest that disease control might be an independent prognostic factor for PFS and OS in this population. (UMIN000044052 httpscenter6.umin.ac.jpcgi-open-binctrectrview.cgirecptnoR000050176).

Transformation of adenocarcinoma to squamous cell carcinoma as a source of EGFR-TKI resistance A case report and literature review.

In general, non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations respond to tyrosine kinase inhibitors (TKIs). However, most patients experience resistance within 1-2 years after treatment. The histological explanation for the acquired resistance is that malignant transformation occurs during cancer treatment. To date, the transformation from adenocarcinoma to squamous cell carcinoma associated with EGFR-TKI use remains poorly reported. We report a case of stage IV lung adenocarcinoma with EGFR mutations that converted to squamous cell carcinoma due to long-term administration of EGFR-TKIs. This report strengthens histological evolution as a source of acquired drug resistance.

Cost-effectiveness analysis of adjuvant therapy with atezolizumab in Chinese patients with stage IB-IIIA resectable NSCLC after adjuvant chemotherapy.

Atezolizumab was first shown to significantly improve progression-free survival (PFS) after platinum-based chemotherapy in early-stage non-small cell lung cancer (NSCLC) in the IMpower010 Phase 3 trial. However, the cost-effectiveness and potential economic impact of atezolizumab treatment in Chinese patients are unknown. Markov models were constructed based on follow-up data from the IMpower010 trial and assessed separately in the programmed cell death receptor ligand-1 (PD-L1) tumor cells (TC) ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the intention-to-treat (ITT) group (stage IB-IIIA). Efficacy and safety data were obtained from the IMpower010 trial, and costs and utility values were derived from the literature and local surveys to estimate their incremental cost-effectiveness ratios (ICERs) compared with willingness-to-pay (WTP) thresholds in scenarios implementing patient assistance programs (PAP) or drug price negotiations. Univariate sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to investigate the stability of the model results. Compared with best supportive care (BSC), atezolizumab produced an additional 0.45 quality-adjusted life-years (QALYs), 0.04 QALYs, and -0.0028 QALYs in the PD-L1 TC ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the ITT group, and the ICERs were 108,825.37QALY, 1,028,538.22QALY, and -14,381,171.55QALY, respectively. The ICERs all exceeded the WTP threshold of $27,354 per QALY (three times the per capita gross domestic product of China in 2022), and univariate sensitivity analysis showed that the price of atezolizumab played a crucial role in the model results. PSA showed that the probability of cost-effectiveness of atezolizumab in the PD-L1 TC ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the ITT group increased with the increasing WTP threshold. From the perspective of Chinas health care system, in the PD-L1 TC ≥ 1% stage II - IIIA group, all stage II - IIIA groups, and the ITT group, the use of atezolizumab in the adjuvant treatment of patients with early-stage NSCLC after platinum-based chemotherapy is unlikely to be cost-effective. The implementation of PAP or price reduction negotiations for atezolizumab might be among the most effective measures to improve its cost-effectiveness.

Plasma-first accelerating lung cancer diagnosis and molecular profiling through liquid biopsy.

Molecular profiling of tumor tissue is the gold standard for treatment decision-making in advanced non-small cell lung cancer (NSCLC). Results may be delayed or unavailable due to insufficient tissue, prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma testing in the initial diagnostic workup for patients with suspected advanced lung cancer. Patients with ⩽15 pack-year smoking history and suspected advanced lung cancer referred to the lung cancer rapid diagnostic program underwent plasma circulating-tumor DNA testing using a DNA-based mutation panel. Tissue testing was performed per standard of care, including comprehensive next-generation sequencing (NGS). The primary endpoint was time from diagnostic program referral to cancer treatment in stage IV NSCLC patients (Cohort A) compared to a contemporary cohort not enrolled in the study (Cohort B) and an historical pre-COVID cohort referred to the program between 2018 and 2019 (Cohort C). From January to June 2021, 20 patients were enrolled in Cohort A median age was 70.5 years (range 33-87), 70% were female, 55% Caucasian, 85% never smokers, and 75% were diagnosed with NSCLC. Seven had actionable alterations detected in plasma or tissue (47 concordant). Fusions, not tested in plasma, were identified by immunohistochemistry for three patients. Mean result turnaround time was 17.8 days for plasma NGS and 23.6 days for tissue ( Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC can lead to faster molecular results and shorten time to treatment even with smaller DNA panels. An expansion study using comprehensive NGS plasma testing with faster turnaround time is ongoing (NCT04862924).

Non-secretory multiple myeloma expressed as multiple extramedullary plasmacytoma with an endobronchial lesion mimicking metastatic cancer A case report.

Non-secretory multiple myeloma (MM) is a rare condition that accounts for only 3% of MM cases and is defined by normal serum and urine immunofixation and a normal serum free light chain ratio. Non-secretory MM with multiple extramedullary plasmacytomas derived from endobronchial lesions is extremely rare and can be misdiagnosed as metastasis of solid cancer. A 36-year-old man presented with progressive facial swelling and nasal congestion with cough. Various imaging studies revealed an endobronchial mass in the left bronchus and a large left maxillary mass with multiple destructive bone metastatic lesions. He initially presented with lung cancer and multiple metastases. However, pathologic reports showed multiple extramedullary plasmacytomas in the left maxilla and the left bronchus. There was no change in the serum and urine monoclonal protein levels, and no abnormalities were observed in laboratory examinations, including hemoglobin, calcium, and creatinine levels. The bone marrow was hypercellular, with 13.49% plasma cells. The patient was diagnosed with non-secretory MM expressed as multiple extramedullary plasmacytomas with endobronchial lesions in a rare location. Radiation therapy for symptomatic lesions with high-dose dexamethasone was started, and the size of the left maxillary sinus lesion dramatically decreased. In the future, chemotherapy will be administered to control lesions in other areas. We present a rare case of non-secretory MM with multiple extramedullary plasmacytoma with an endobronchial lesion.

Prognostic role of multiple abnormal genes in non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) has the highest morbidity and mortality rates among all malignant tumor types. Although therapies targeting the mutated genes such as To explore the impact of simultaneous abnormalities of multiple genes on the prognosis and survival of patients. We used R packages to analyze gene expression data and clinical data downloaded from The Cancer Genome Atlas (TCGA) database. We also collected samples from 85 NSCLC patients from the First Peoples Hospital of Jingzhou City and retrospectively followed the patients. Multivariate Cox regression analysis and survival analysis were performed. Analysis of gene expression data from TCGA revealed that the overexpression of the following single genes affected overall survival Co-occurring mutation or overexpression of different genes has different effects on the overall survival and prognosis of NSCLC patients. Combined with TKI treatment, the co-occurring mutation of some genes may have a synergistic effect on the survival and prognosis of NSCLC patients.

Early detection of circulating tumor DNA and successful treatment with osimertinib in thr790met-positive leptomeningeal metastatic lung cancer A case report.

Patients diagnosed with non-small-cell lung cancer with activated epidermal growth factor receptor mutations are more likely to develop leptomeningeal (LM) metastasis than other types of lung cancers and have a poor prognosis. Early diagnosis and effective treatment of leptomeningeal carcinoma can improve the prognosis. A 55-year-old female with a progressive headache and vomiting for one month was admitted to Peking University First Hospital. She was diagnosed with lung adenocarcinoma with osseous metastasis 10 months prior to admittance. epidermal growth factor receptor (EGFR) mutation was detected by genomic examination, so she was first treated with gefitinib for 10 months before acquiring resistance. Cell-free cerebrospinal fluid (CSF) circulating tumor DNA detection by next-generation sequencing was conducted and indicated the EGFR-Thr790Met mutation, while biopsy and cytology from the patients CSF and the first enhanced cranial magnetic resonance imaging (MRI) showed no positive findings. A month later, the enhanced MRI showed linear leptomeningeal enhancement, and the cytology and biochemical examination in CSF remained negative. Therefore, osimertinib (80 mgd) was initiated as a second-line treatment, resulting in a good response within a month. This report suggests clinical benefit of osimertinib in LM patients with positive detection of the EGFR-Thr790Met mutation in CSF and proposes that the positive findings of CSF circulating tumor DNA as a liquid biopsy technology based on the detection of cancer-associated gene mutations may appear earlier than the imaging and CSF findings and may thus be helpful for therapy. Moreover, the routine screening of chest CT with the novel coronavirus may provide unexpected benefits.

The Great Mimicker Cutaneous Metastatic Melanoma Presenting as a Non-resolving Pleural Effusion.

Although melanoma starts as a local disease, it can metastasize to other sites of the body including the lung, brain, liver, and intestines. However, pleural involvement is a rare presentation. Here, we present a case of a 57-year-old man with a history of stage IIA cutaneous melanoma, that relapsed 3 years after cutaneous resection, presenting with a non-resolving pleural effusion. Pleural fluid analysis was consistent with an exudative effusion, and pleural biopsy confirmed metastatic melanoma. The patient was treated with dual therapy of ipilimumab and nivolumab, as per National Comprehensive Cancer Network guidelines, with good response. Thus, we recommend having a high index of clinical suspicion for metastatic pleural melanoma when a patient with a history of cutaneous melanoma presents with a non-resolving pleural effusion.

Distance of Residence From the Cancer Center Influences Perioperative Outcomes After Robotic-Assisted Pulmonary Lobectomy

Introduction Increased distance of residence from the hospital has been previously associated with worse postoperative outcomes, especially increased hospital length of stay (LOS) after elective surgery in the USA as well as after pulmonary lobectomy in Japan. We sought to determine if the distance from our cancer center affects postoperative outcomes after robotic-assisted pulmonary lobectomy. Methods We retrospectively analyzed 449 patients who underwent robotic-assisted pulmonary lobectomy by one surgeon for known or suspected lung cancer. Two patients were excluded due to incomplete data. Each patients residential ZIP code was used to determine the distance of their primary residence from our cancer center. Group 1 consisted of patients living less than 120 miles away while Group 2 consisted of patients living more than 120 miles away. Demographic factors, preoperative comorbidities, the incidence of postoperative complications, chest tube duration, and hospital LOS were compared by the Pearson chi-square or Kruskal-Wallis tests, and Kaplan-Meier survival was compared by Cox regression. Statistical significance was established as

Thrombotic Thrombocytopenic Purpura and Metastatic Malignancy-Like Presentation Secondary to Hypervirulent Strain of Klebsiella pneumoniae A Case Series.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially fatal disease. The majority of cases are caused by a significant enzyme deficiency in the blood called the von Willebrand factor (VWF) cleaving protease (also called ADAMTS13). TTP is classified as a hematologic emergency because of the high mortality rate. The diagnosis is difficult due to the extensive overlap in the clinical manifestations of TTP and other illnesses. Klebsiella pneumoniae infection can in very rare instances present with TTP andor a metastatic-like presentation where the patient might have prostate, liver, brain, and lung abscesses mimicking late-stage solid organ malignancy. In this paper, we report a case of TTP secondary to

A case of cerebral infarction due to aplastic or twig-like middle cerebral artery after lung cancer surgery.

Aplastictwig-like middle cerebral artery is a rare vascular abnormality. We report a case of postoperative cerebral infarction caused by this disease. The patient is a male in his 40s. A 9-cm tumour was revealed to have invaded the superior vena cava from his right lung. He underwent right upper and middle bilobectomy. Due to the vascular invasion, the intraoperative bleeding exceeded 2 litres. Mechanical ventilation was required for postoperative pneumonia. After extubation, he was unable to write and was found to have cerebral infiltration in the left middle cerebral artery region. The cause of the cerebral infarction was investigated, but no thrombus in the left atrium or arteriosclerosis was found. No atrial fibrillation was observed during or after the surgery. Magnetic resonance angiography of the brain revealed an aplastictwig-like middle cerebral artery.

Cyclodextrin nanoparticles for diagnosis and potential cancer therapy A systematic review.

Cancer is still one of the worlds deadliest health concerns. As per latest statistics, lung, breast, liver, prostate, and cervical cancers are reported topmost worldwide. Although chemotherapy is most widely used methodology to treat cancer, poor pharmacokinetic parameters of anticancer drugs render them less effective. Novel nano-drug delivery systems have the caliber to improve the solubility and biocompatibility of various such chemical compounds. In this regard, cyclodextrins (CD), a group of natural nano-oligosaccharide possessing unique physicochemical characteristics has been highly exploited for drug delivery and other pharmaceutical purposes. Their cup-like structure and amphiphilic nature allows better accumulation of drugs, improved solubility, and stability, whereas CDs supramolecular chemical compatibility renders it to be highly receptive to various kinds of functionalization. Therefore combining physical, chemical, and bio-engineering approaches at nanoscale to specifically target the tumor cells can help in maximizing the tumor damage without harming non-malignant cells. Numerous combinations of CD nanocomposites were developed over the years, which employed photodynamic, photothermal therapy, chemotherapy, and hyperthermia methods, particularly targeting cancer cells. In this review, we discuss the vivid roles of cyclodextrin nanocomposites developed for the treatment and theranostics of most important cancers to highlight its clinical significance and potential as a medical tool.

Advances and development of prostate cancer, treatment, and strategies A systemic review.

The most common type of cancer in the present-day world affecting modern-day men after lung cancer is prostate cancer. Prostate cancer remains on the list of top three cancer types claiming the highest number of male lives. An estimated 1.4 million new cases were reported worldwide in 2020. The incidence of prostate cancer is found predominantly in the regions having a high human development index. Despite the fact that considerable success has been achieved in the treatment and management of prostate cancer, it remains a challenge for scientists and clinicians to curve the speedy advancement of the said cancer type. The most common risk factor of prostate cancer is age men tend to become more vulnerable to prostate cancer as they grow older. Commonly men in the age group of 66 years and above are the most vulnerable population to develop prostate cancer. The gulf countries are not far behind when it came to accounting for the number of individuals falling prey to the deadly cancer type in recent times. There has been a consistent increase in the incidence of prostate cancer in the gulf countries in the past decade. The present review aims at discussing the development, diagnostics

Effects of Thoracic Paravertebral Block on Postoperative Anxiety and Depression for Patients Undergoing Thoracoscopic Lung Cancer Radical Surgery.

This study is aimed at investigating the effect of thoracic paravertebral block (TPVB) on the occurrence of chronic postoperative pain, postoperative anxiety, and depression in patients undergoing thoracoscopic radical lung cancer surgery. A total of 120 patients who underwent thoracoscopic radical lung cancer surgery in our hospital from June 2019 to March 2021 were included. There were 62 males and 58 females, with an age of 18-75 years old and a body mass index of 20-28 kgm

Effects of Peripherally Inserted Central Catheter (PICC) Catheterization Nursing on Bloodstream Infection in Peripheral Central Venous Catheters in Lung Cancer A Single-Center, Retrospective Study.

Peripherally inserted central catheter (PICC), as one of the important intravenous routes for the rescue and treatment of critically ill patients, has been widely used in the fluid resuscitation of critically ill patients in intensive care. In particular, PICC can be widely used in the treatment of cancer patients. With the wide application of peripheral central venous catheterization, the clinical findings of bloodstream infection complications caused by PICC have gradually attracted the attention of doctors and patients. To investigate the effect of specialized placement and PICC placement care on patients with lung cancer who underwent PICC puncture. Patients were selected and divided into a comparison group and an observation group of 40 patients each according to the randomized residual grouping method. In the comparison group, routine PICC placement and catheter maintenance were performed, while the observation group was provided with specialized placement and PICC placement care. The differences in immune and tumor marker levels and nursing compliance between the two groups were observed and compared before and after nursing care. There was no significant difference in the comparison of tumor marker levels between the two groups of patients before care, while the levels of CYFRA21-1, CA125, and VGEF in the observation group were significantly lower than those in the comparison group after care, and this difference was statistically significant ( PICC placement care is more effective in patients with lung cancer and performing PICC puncture, significantly improves patients immune and tumor marker levels, improves patients negative emotions, reduces disease uncertainty, and improves nursing compliance.

TAOK1 Promotes Proliferation and Invasion of Non-Small-Cell Lung Cancer Cells by Inhibition of WWC1.

For patients with advanced non-small-cell lung cancer (NSCLC), targeted therapy significantly improves the therapeutic effect of NSCLC patients. With the development of molecular targeted therapy, more and more NSCLC-related genes have been found. Thousand and one amino-acid kinase 1 (TAOK1) has been identified as a potential target for drug research in various cancers. The main objective of this study was to explore the expression and function of TAOK1 in NSCLC. Western blotting was employed to assess TAOK1 expression in NSCLC cell lines. The effects of TAOK1 on biological behaviors, including proliferation, invasion, and apoptosis of NSCLC cells, were assessed. The relationship between TAOK1 and WW and C2 domain containing 1 (WWC1) was assessed by Co-IP assay. The subcutaneous injection of tumor cells in nude mice was used to verify it in vivo. As expected, TAOK1 was increased in NSCLC cell lines. Following TAOK1 knockdown, NSCLC cells exhibited a significant decrease in the invasion and increased apoptosis in vitro. Instead, the TAOK1 elevation showed the opposite results. The Co-IP assay identified that TAOK1 specifically interacted with WWC1. Knockdown of WWC1 overturned TAOK1 silencing-mediated malignant phenotype of NSCLC cells. Additionally, subcutaneous tumorigenesis assays in nude mice confirmed that TAOK1 knockdown markedly restrained the proliferation capacity of NSCLC cells in vivo. Surprisingly, TAOK1 overexpression in NSCLC promotes tumor cell growth and invasion, which is associated with downregulation of its downstream protein WWC1, and this result might provide a robust research basis to inquire about the precise therapeutic targets for NSCLC.

PKC signal amplification suppresses non-small cell lung cancer growth by promoting p21 expression and phosphorylation.

Protein kinase C (PKC) activation was previously associated with oncogenic features. However, small molecule inhibitors targeting PKC have so far proved ineffective in a number of clinical trials for cancer treatment. Recent progresses have revealed that most PKC mutations detected in diverse cancers actually lead to loss-of-function, thus suggesting the tumor-suppressive roles of PKC proteins. Unfortunately, the development of chemicals to enhance PKC activity is lagging behind relative to its small molecular inhibitors. Here, we report that a bisindolylmaleimide derivative (3,4-bis(1-(prop-2-ynyl)-1

Comparison of involved-field intensity-modulated radiotherapy combined with S-1

It is estimated that about 30% of esophageal cancer (EC) patients are over 70 years old. Therefore, there is less evidence on the diagnosis and management of elderly EC patients. It is important to explore how elderly EC patients benefit from radical radiochemotherapy regimens, including the target area of radiotherapy (RT), radiation dose and fraction, and choice of chemotherapy drugs. To compare the efficacy of involved-field intensity-modulated RT (IF-IMRT) combined with S-1 Thirty-four EC patients aged > 70 years were prospectively enrolled between December 2017 and December 2019. Based on the random number table, they were divided into an IF-IMRT S-1 group and an IF-IMRT alone group, with 17 patients in each group. All patients were treated with IF-IMRT at a dose of 50.4-56 Gy in 28-30 fractions (1.8-2 Gyfraction, 5 fractionswk). Oral S-1 was administered concomitantly in the IF-IMRT S-1 group for 14 consecutive days, and a second cycle was started 7 d after drug withdrawal. After RT, 4 cycles of S-1 treatment were offered as the consolidation chemotherapy. The safety, short-term response, and survival were observed after the treatment. As of April 2022, these 34 patients had been followed up for 15.2-32.5 mo, with a median follow-up period of 24.5 mo. Complete efficacy indicators were obtained from all the patients. The objective response rate was 88.2% Compared with IF-IMRT alone, IF-IMRT S-1 shows the benefits of preventing PD and prolonging survival without increasing adverse reactions. Therefore, this concurrent radiochemotherapy deserves clinical application.

Chronic urticaria associated with lung adenocarcinoma - a paraneoplastic manifestation A case report and literature review.

Urticaria is one of the most common causes of emergency room visits. It is defined as an acute inflammatory dermatosis, characterized by localized degranulation of mast cells, with consequent dermal microvascular and formation of edematous and pruritic plaques called hives. Urticaria affects the skin and tissues of the superficial mucosa. Sometimes it is accompanied by angioedema, which is characterized by deeper edema of the dermis and subcutaneous cellular tissue known as the urticarial-angioedema syndrome. About 15%-25% of the general population has suffered at least one type of urticaria at some point during their lifetime and hyperpermeability estimated at 7.6%-16% and has experienced acute urticaria that is usually self-limited and spontaneously resolves without requiring medical attention. We present the case of a young male patient who was referred to our department with a clinical picture of 4 mo of pruritus associated with hives of variable sizes, irregular borders, with interlesional confluence, that were non-painful, without involvement of the palms and soles of the feet but with a tendency to progression in a generalized manner. He had multiple emergency room visits and poor response to antihistamines and systemic corticosteroids. Imaging studies demonstrated nodules in the lower lingula segment, at the level of the greater fissure and in the anterior contour of the left anterior basal segment associated with parahiliar adenopathies in the absence of findings suggestive of infectious or autoimmune etiology. Segmental lobectomy was performed by thoracoscopy with resection of a lung nodule in the lingula and biopsy of the para-aortic mediastinal ganglion. The histopathological report showed the presence of poorly differentiated invasive adenocarcinoma with a solid morphological and acinar pattern with immunohistochemical description of lung tissue that expresses strong positive and diffuse reaction for thyroid transcription factor 1 (TTF-1) with negativity to P40 for a histopathological diagnosis of malignant epithelial neoplasia with expression of infiltrating adenocarcinoma. Spontaneous chronic urticaria is considered possibly secondary to lung adenocarcinoma. Chronic spontaneous urticaria is considered a paraneoplastic dermatosis with a controversial association in the literature. In the presented case, a young patient presented with chronic refractory urticaria and after an exhaustive clinical work-up was found to have a diagnosis of poorly differentiated lung adenocarcinoma with high expression of TTF-1. According to the Curth criteria, the urticaria presented by the patient is related to the oncological diagnosis. In addition, the high expression of TTF-1 documented in this case could be acting as an autoantigen that would cause chronic spontaneous urticaria. Further research evaluating a causal relationship between the TFF-1 protein and urticaria in lung cancer is needed.

Programmed cell death-1 inhibitor combination treatment for recurrent proficient mismatch repair miscrosatellite-stable type endometrial cancer A case report.

Endometrial cancer (EC) is one of the most common cancers of the female reproductive tract, and the incidence is increasing rapidly. Immunotherapy using programmed cell death-1 (PD-1) inhibitors is an emerging research topic and treatment strategy for refractory gynecological malignancies. However, clinical management of EC with checkpoint inhibitors requires improvement. Herein, we discuss a case of refractory proficient mismatch repair (pMMR)miscrosatellite-stable (MSS) EC treated with a combination of PD-1 and angiogenesis inhibitors and offer a review of the pathophysiology and clinical outcomes based on previous studies. A 62-year-old woman diagnosed with invasive or metastatic EC in 2015 was treated with six courses of chemotherapy and refused further radiotherapy. Four years later, she developed chest pain, and lung biopsy indicated thyroid transcription factor-1 (-), Napsin A (-), estrogen receptor (), progesterone receptor (), anaplastic lymphoma kinase (D5F3) (-), and receptor tyrosine kinase (D4D6) (-) metastatic EC. Genetic testing results showed low tumor mutation burden, pMMR, PD ligand 1 (-), MSS, and HLA-class 1 heterogeneous disease. The patient was started on toripalimab combined with nab-paclitaxel for seven cycles (every 3 wk), but this regimen was terminated because of an intolerable chemotherapy adverse event. The disease progressed in 2020, and the patients treatment was switched from nab-paclitaxel to anlotinib, while immunotherapy using toripalimab was continued. The patient achieved a major partial response with well-tolerated toxicities, and treatment is ongoing. Molecular testing is advised for clinical classifications of EC owing to its high heterogeneity. In this case, the patient had pMMRMSS EC and achieved a positive outcome with combination PD-1 inhibitor treatment. These results warrant further clinical exploration.

Intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm harboring a

Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life. They usually occur in the mediastinum or lung, but there are very rare cases of ectopic bronchogenic cysts that develop in the abdominal cavity. A unique intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm that was producing carcinoembryonic antigen (CEA), harboring a In 2007, a man in his 50s was incidentally found to have an intra-abdominal cystic mass, 8 cm in diameter. Surgical resection was recommended, but he preferred to remain under observation. In 2020, his serum CEA level increased to 26.7 ngmL, and abdominal computed tomography showed a 15 cm × 12 cm, multifocal, cystic mass located predominantly on the lesser curvature of the stomach. Since malignancy could not be ruled out, he finally underwent surgical resection. Histologically, the cystic wall was lined by ciliated columnar epithelium, accompanied by bronchial gland-like tissue, bronchial cartilage, and smooth muscle. Part of the cyst consisted of atypical columnar epithelium with an MIB-1 index of 5% and positive for CEA. Moreover, a An extremely rare case of an abdominal bronchogenic cyst with a low-grade mucinous neoplasm harboring a

Pulmonary Lymphangitis Carcinomatosa Mimicking Immunotherapy-Related Interstitial Pneumonitis A Case Report.

While immunotherapy with immune checkpoint inhibitors has achieved promising effects in advanced lung cancer treatment, it can induce some unique adverse events, known as immunotherapy-related adverse events (irAEs). Immunotherapy-related interstitial pneumonitis is one of the irAEs, and its incidence is reported as 3.5-8.3% in phase III trials of nivolumab with or without ipilimumab for advanced non-small cell lung cancer patients. However, in the real-world setting, pathology is not routinely used in the diagnostic process of interstitial pneumonitis because diagnosis is usually made using chest computed tomography (CT). Here, we report an educational case of pathologically diagnosed pulmonary lymphangitis carcinomatosa mimicking immunotherapy-related interstitial pneumonitis. The patient was diagnosed with advanced adenocarcinoma of the right lung (stage IVA) and received immunochemotherapy for 6 months. He manifested acute respiratory failure, and a chest CT scan revealed the emergence of diffuse grand-grass opacity predominantly in the left lung. Immunotherapy-induced interstitial pneumonitis was clinically suspected because the primary lesion was stable, and the level of the serum carcinoembryonic antigen decreased. However, the detection of adenocarcinoma cells in the bronchoalveolar lavage sample from the left lung confirmed the diagnosis of pulmonary lymphangitis carcinomatosa. Clinicians assumptions can sometimes mislead treatment methods hence, this case draws attention to the perils of misdiagnoses.

Sotorasib Shows Intracranial Activity in Patients with

Treatment with sotorasib has shown intracranial complete responses and continued intracranial stabilization in

Extracorporeal membrane oxygenation for lung cancer-related life-threatening hypoxia A case report.

Life-threatening hypoxia can occur in patients with lung cancer due to bronchial obstruction. Extracorporeal membrane oxygenation (ECMO) can be used as a bridge therapy for patients with severe hypoxia not relieved by conventional mechanical treatment. However, the usefulness of chemotherapy in patients with lung cancer receiving ECMO therapy is not well known. A 53-year-old man visited the emergency room with worsening dyspnea for 1 mo. A series of imaging and diagnostic tests were performed, and stage IIIB (cT4N2M0) lung cancer was eventually diagnosed. On hospital day 3, he experienced dyspnea and hypoxia that was not relieved with oxygen support ECMO is a potential bridge therapy for respiratory failure in patients with central airway obstruction secondary to lung cancer.

tRNA-derived small RNAs Mechanisms and potential roles in cancers.

Transfer RNAs (tRNAs) are essential for protein synthesis. Mature or pre-tRNAs may be cleaved to produce tRNA-derived small RNAs (tsRNAs). tsRNAs, divided into tRNA-derived stress-induced RNA (tiRNAs) and tRNA-derived fragments (tRFs), play versatile roles in a number of fundamental biological processes. tsRNAs not only play regulatory roles in gene silencing, RNA stability, reverse transcription, and translation, but are also closely related to cell proliferation, migration, cell cycle, and apoptosis. Their abnormal expression is associated with the occurrence and development of various human diseases, especially cancer. This paper reviews the classification, biogenesis, and mechanism of action of tsRNAs, and the research progress to date on tsRNAs in cancers. These findings provide new opportunities for diagnostic biomarkers and treatment targets of several types of cancers including gastric cancer, colorectal cancer, hepatocellular carcinomas, pancreatic cancer, breast cancer, prostate cancer, renal cell carcinoma, ovarian cancer, lung cancer, bladder cancer, thyroid cancer, oral cancer, and leukemia.

Network Pharmacology and Bioinformatics Analysis Identifies Potential Therapeutic Targets of Paxlovid Against LUADCOVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a pandemic in many countries around the world. The virus is highly contagious and has a high fatality rate. Lung adenocarcinoma (LUAD) patients may have higher susceptibility and mortality to COVID-19. While Paxlovid is the first oral drug approved by the U.S. Food and Drug Administration (FDA) for COVID-19, its specific drug mechanism for lung cancer patients infected with COVID-19 remains to be further studied. COVID-19 related genes were obtained from NCBI, GeneCards, and KEGG, and then the transcriptome data for LUAD was downloaded from TCGA. The drug targets of Paxlovid were revealed through BATMAN-TCM, DrugBank, SwissTargetPrediction, and TargetNet. The genes related to susceptibility to COVID-19 in LUAD patients were obtained through differential analysis. The interaction of LUADCOVID-19 related genes was evaluated and displayed by STRING, and a COX risk regression model was established to screen and evaluate the correlation between genes and clinical characteristics. The Venn diagram was drawn to select the candidate targets of Paxlovid against LUADCOVID-19, and the functional analysis of the target genes was performed using KEGG and GO enrichment analysis. Finally, Cytoscape was used to screen and visualize the Hub Gene, and Autodock was used for molecular docking between the drug and the target. Bioinformatics analysis was performed by combining COVID-19-related genes with the gene expression and clinical data of LUAD, including analysis of prognosis-related genes, survival rate, and hub genes screened out by the prognosis model. The key targets of Paxlovid against LUADCOVID-19 were obtained through network pharmacology, the most important targets include IL6, IL12B, LBP. Furthermore, pathway analysis showed that Paxlovid modulates the IL-17 signaling pathway, the cytokine-cytokine receptor interaction, during LUADCOVID-19 treatment. Based on bioinformatics and network pharmacology, the prognostic signature of LUADCOVID-19 patients was screened. And identified the potential therapeutic targets and molecular pathways of Paxlovid Paxlovid in the treatment of LUADCOVID. As promising features, prognostic signatures and therapeutic targets shed light on improving the personalized management of patients with LUAD.

Pleural and pulmonary dissemination patterns from gastric adenocarcinoma among patients with treated primary disease in Latin America.

Latin America is one of the regions with the highest incidence of gastric cancer. Even though, there are not reports about the patterns of pleuro-pulmonary metastases in patients with gastric adenocarcinoma treated with curative intent and the prognosis according to each dissemination pattern. We conducted a retrospective analysis of patients with gastric adenocarcinoma treated with curative intent at the National Cancer Institute (INC) between 2010 and 2017. Demographic variables, variables associated with the primary disease and variables associated with the presence of pleuro-pulmonary opacities and metastases were collected. A univariate and multivariate logistic regression analysis was performed and survival curves were presented using the Kaplan Meier method and compared using the log-rank test. A Cox regression model was performed for multivariate analysis for overall survival. The study included 450 patients, 51.3% were male and the median age was 63 years. Intestinal adenocarcinoma was the most frequent histological subtype, in 261 cases (58.0%). Gastric cancer initial pathological stage was stage I in 23.3% of the patients, stage II in 19.3% and stage III in 53.6%. During a median follow-up of 31.9 months, 37 (8.2%) patients developed pleuro-pulmonary opacities among those, 14 (3.1%) met the criteria for pleuro-pulmonary metastases 6 (1.3%) had lymphangitic metastasis, 4 (0.9%) had a mixed pattern of pleural and lung nodules, 3 (0.7%) had pleural metastasis, and only one (0.2%) had hematogenous metastasis. The median OS was 114.5 months for the entire cohort and 38.2 (95%CI, 19.2-57.2) months for patients with pleuro-pulmonary metastases. Patients with pleural metastasis and lymphangitic carcinomatosis had median survival of 24.3 (95%CI, 0.01-51.0) and 26.4 (95%CI, 18.2-34.7) months, respectively. incidence of pleuro-pulmonary metastases in patients with gastric adenocarcinoma treated with curative intention was low. In our series, lymphangitic carcinomatosis was the main pattern of dissemination meanwhile, hematogenous metastasis was rare and patients with pleural carcinomatosis had the lowest median survival.

A long waiting time from diagnosis to treatment decreases the survival of non-small cell lung cancer patients with stage IA1 A retrospective study.

The prognostic effect of delayed treatment on stage IA1 non-small cell lung cancer (NSCLC) patients is still unclear. This study aimed to explore the association between the waiting time before treatment and the prognosis in stage IA1 NSCLC patients. Eligible patients diagnosed with pathological stage IA1 NSCLC were included in this study. The clinical endpoints were overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method, the Log-rank test, univariable, and multivariable Cox regression analyses were used in this study. Propensity score matching was used to reduce the bias of data distribution. There were eligible 957 patients in the study. The length of waiting time before treatment stratified the survival in patients <3 months vs. ≥3-months, unadjusted hazard ratio (HR) 0.481, A long waiting time before treatment may decrease the survival of stage IA1 NSCLC patients. We propose that the waiting time for those patients preferably is less than one month and should not exceed two months.

CDCNet multi-classification convolutional neural network model for detection of COVID-19, pneumothorax, pneumonia, lung Cancer, and tuberculosis using chest X-rays.

Coronavirus (COVID-19) has adversely harmed the healthcare system and economy throughout the world. COVID-19 has similar symptoms as other chest disorders such as lung cancer (LC), pneumothorax, tuberculosis (TB), and pneumonia, which might mislead the clinical professionals in detecting a new variant of flu called coronavirus. This motivates us to design a model to classify multi-chest infections. A chest x-ray is the most ubiquitous disease diagnosis process in medical practice. As a result, chest x-ray examinations are the primary diagnostic tool for all of these chest infections. For the sake of saving human lives, paramedics and researchers are working tirelessly to establish a precise and reliable method for diagnosing the disease COVID-19 at an early stage. However, COVID-19s medical diagnosis is exceedingly idiosyncratic and varied. A multi-classification method based on the deep learning (DL) model is developed and tested in this work to automatically classify the COVID-19, LC, pneumothorax, TB, and pneumonia from chest x-ray images. COVID-19 and other chest tract disorders are diagnosed using a convolutional neural network (CNN) model called CDC Net that incorporates residual network thoughts and dilated convolution. For this study, we used this model in conjunction with publically available benchmark data to identify these diseases. For the first time, a single deep learning model has been used to diagnose five different chest ailments. In terms of classification accuracy, recall, precision, and f1-score, we compared the proposed model to three CNN-based pre-trained models, such as Vgg-19, ResNet-50, and inception v3. An AUC of 0.9953 was attained by the CDC Net when it came to identifying various chest diseases (with an accuracy of 99.39%, a recall of 98.13%, and a precision of 99.42%). Moreover, CNN-based pre-trained models Vgg-19, ResNet-50, and inception v3 achieved accuracy in classifying multi-chest diseases are 95.61%, 96.15%, and 95.16%, respectively. Using chest x-rays, the proposed model was found to be highly accurate in diagnosing chest diseases. Based on our testing data set, the proposed model shows significant performance as compared to its competitor methods. Statistical analyses of the datasets using McNemars, and ANOVA tests also showed the robustness of the proposed model.

Association between CA 15‑3 and progression of interstitial lung disease in a case of coexisting systemic sclerosis and recurrent breast cancer A case report.

Carbohydrate antigen 15-3 (CA 15-3) is known as a specific tumor marker for breast cancer, the main use of which is monitoring therapy in patients with advanced breast cancer. Either systemic sclerosis (SSc)-interstitial lung disease (ILD) or pulmonary arterial hypertension is currently the leading cause of disease-related morbidity and mortality in patients with scleroderma. Although CA 15-3 has been investigated as a biomarker in SSc-ILD, its role remains unclear. The current report presented a case of recurrent breast cancer diagnosed with SSc-ILD during treatment. The patient, at 63 years old, experienced shortness of breath with minimal exertion after four cycles of perutuzumab, trastuzumab and weekly paclitaxel. Computed tomography (CT) revealed ground-glass opacities and linear shadows in the peripheral lower lobes of both lungs. Although the development of lung involvement associated with breast cancer, such as carcinomatous lymphangitis, was initially suspected, because of the increase in CA 15-3, skin biopsies were taken from the left index finger base and extension side of the left elbow, which demonstrated increased thickness of the dermis, leading to a diagnosis of SSc-ILD. The findings in this case suggested the importance of considering a differential diagnosis, including ILD, concurrently while screening for the progression of recurrent breast cancer when encountering patients with breast cancer and elevated levels of CA 15-3.

A tumor cell membrane-coated self-amplified nanosystem as a nanovaccine to boost the therapeutic effect of anti-PD-L1 antibody.

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as eat me signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

Comprehensive Exploration of M2 Macrophages and Its Related Genes for Predicting Clinical Outcomes and Drug Sensitivity in Lung Squamous Cell Carcinoma.

M2 macrophages play an important role in cancers. However, the role of M2 macrophages has not been clarified in lung squamous cell carcinoma. All the open-accessed data were downloaded from The Cancer Genome Atlas database. All the analysis was performed in the R software. The CIBERSORT algorithm was utilized to quantify the immune cell infiltration in the tumor microenvironment. LASSO regression and multivariate Cox regression analysis were carried out for the creation of the prognostic model. Pathway enrichment analysis was performed using the single sample Gene Set Enrichment Analysis (ssGSEA) and clueGO algorithm. In our study, we comprehensively explored the role of M2 macrophages and its related genes in LUSC patients. We found that the patients with high M2 macrophage infiltration tend to have a worse prognosis. Also, some oncogenetic pathways were activated in the patients with high M2 macrophage infiltration. Further, a prognosis model based on six M2 macrophage-related genes was established, including TRIM58, VIPR2, CTNNA3, KIAA0408, CLEC4G, and MATN4, which showed a good prognosis prediction efficiency in both training and validation cohort. Pathway enrichment analysis showed that the pathway of allograft rejection, bile acid metabolism, coagulation, inflammatory response, IL6JAKSTAT3 signaling, hedgehog signaling, peroxisome, and myogenesis were significantly activated in the high-risk patients. Based on the results of an investigation of immune infiltration, risk score was found to have a positive correlation with M2 macrophages and resting CD4 memory T cells, but a negative correlation with follicular helper T cells, M1 macrophages, and Tregs. In addition, we discovered that patients in high-risk groups may respond better to immunotherapy than individuals in lower-risk groups. However, low-risk patients might be more sensitive to cisplatin. Our model is a powerful tool to predict LUSC patient prognosis and could indicate the sensitivity of immunotherapy and chemotherapy.

Hesperidin Inhibits the p53-MDMXInteraction-Induced Apoptosis of Non-Small-Cell Lung Cancer and Enhances the Antitumor Effect of Carboplatin.

This study aimed to observe the effect of hesperidin on the apoptosis, proliferation, and invasion of non-small-cell lung cancer, as well as to explore the possible mechanism. The inhibitory effect of hesperidin combined with carboplatin on non-small-cell lung cancer was also investigated. A549 and NCI-H460 cells were treated with different concentrations of hesperidin (10, 50, and 100 Hesperidin significantly inhibited the activity and invasion of A549 and NCI-H460 cells in a dose-dependent manner. Hesperidin also induced the apoptosis of A549 and NCI-H460 cells. Hesperidin further inhibited the interaction between p53 and MDMX, increased the expression of p53, and played an anticancer role. The combination of hesperidin and carboplatin showed the most obvious antitumor effect. Hesperidin can inhibit lung cancer by inhibiting the interaction between p53 and MDMX. Moreover, the combination of hesperidin and carboplatin can inhibit the migration and invasion of lung cancer cell lines through p53 upregulation, thereby increasing the antitumor effect of carboplatin.

EIF3C Promotes Lung Cancer Tumorigenesis by Regulating the APPHSPA1ALMNB1 Axis.

This study was designed to explore the role and mechanism of eukaryotic initiation factor 3C (EIF3C) in the proliferation and apoptosis of lung cancer cells. EIF3C expression in clinic lung cancer tissues was detected by immunohistochemistry assay. Cell transfection with lentivirus EIF3C short hairpin RNA (shRNA) was performed with Lipofectamine 2000. Cell proliferation was evaluated by Celigo and MTT assays. Caspase-37 activity was assessed using caspase-37 assay kit for cell apoptosis detection. The apoptosis rate of lung cancer cells was assessed by flow cytometry. A transplanted tumor nude-mouse model was established to clarify the role of EIF3C in lung cancer. The potential mechanism of EIF3C was explored by mRNA microarray analysis. Among the top 30 up- and downregulated mRNAs selected for RT-qPCR, 5 were chosen for western blot analysis. EIF3C was abnormally overexpressed in lung cancer cell lines and tissues. Silencing EIF3C suppressed the proliferation and promoted the apoptosis of lung cancer cells. EIF3C overexpression may facilitate the proliferation and hamper the apoptosis of lung cancer cells by regulating the APPHSPA1ALMNB1 axis.

Afatinib Targeted Therapy Affects the Immune Function and Serum Levels of EGFR and Gastrin-Releasing Peptide Precursor (pro-GRP) in Patients with Non-Small-Cell Lung Cancer (NSCLC).

This study is aimed at investigating the clinical intervention effect of afatinib targeted therapy in patients with non-small-cell lung cancer. The research object was a retrospective analysis of 86 patients with non-small-cell lung cancer who were admitted to our hospital from 1 After afatinib targeted therapy intervention, the total intervention effective rate of patients in treatment group B was significantly higher than that in patients in treatment group A. Compared with the treatment group A, the CD3, CD4, CD8, and CD4CD8 of the treatment group were significantly upregulated. After the intervention, the serum EGFR levels of patients in treatment groups A and B were significantly decreased, and the serum EGFR levels in patients in treatment group B were significantly lower than those in patients in treatment group A. The serum pro-GRP level in group B patients was significantly decreased. The overall incidence of adverse reactions in treatment group B was significantly lower than that in treatment group A. Afatinib targeted therapy has a significant clinical intervention effect on patients with non-small-cell lung cancer, which not only helps to improve the immune function of patients but also effectively improves the serum EGFR and pro-GRP levels of patients.

Artificial Intelligence Algorithm-Based Feature Extraction of Computed Tomography Images and Analysis of Benign and Malignant Pulmonary Nodules.

This study was aimed to explore the effect of CT image feature extraction of pulmonary nodules based on an artificial intelligence algorithm and the image performance of benign and malignant pulmonary nodules. In this study, the CT images of pulmonary nodules were collected as the research object, and the lung nodule feature extraction model based on expectation maximization (EM) was used to extract the image features. The Dice similarity coefficient, accuracy, benign and malignant nodule edges, internal signs, and adjacent structures were compared and analyzed to obtain the extraction effect of this feature extraction model and the image performance of benign and malignant pulmonary nodules. The results showed that the detection sensitivity of pulmonary nodules in this model was 0.955, and the pulmonary nodules and blood vessels were well preserved in the image. The probability of burr sign detection in the malignant group was 73.09% and that in the benign group was 8.41%. The difference was statistically significant (

Applying a clinical lens to animal models of CAR-T cell therapies.

Chimeric antigen receptor (CAR)-T cells have emerged as a promising treatment modality for various hematologic and solid malignancies over the past decade. Animal models remain the cornerstone of pre-clinical evaluation of human CAR-T cell products and are generally required by regulatory agencies prior to clinical translation. However, pharmacokinetics and pharmacodynamics of adoptively transferred T cells are dependent on various recipient factors, posing challenges for accurately predicting human engineered T cell behavior in non-human animal models. For example, murine xenograft models did not forecast now well-established cytokine-driven systemic toxicities of CAR-T cells seen in humans, highlighting the limitations of animal models that do not perfectly recapitulate complex human immune systems. Understanding the concordance as well as discrepancies between existing pre-clinical animal data and human clinical experiences, along with established advantages and limitations of each model, will facilitate investigators ability to appropriately select and design animal models for optimal evaluation of future CAR-T cell products. We summarize the current state of animal models in this field, and the advantages and disadvantages of each approach depending on the pre-clinical questions being asked.

Association between the Lymphocyte-to-C-Reactive Protein Ratio and Survival Outcomes in Cancer Patients with GLIM-Defined Malnutrition A Multicenter Study.

This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators-LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio-were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.

Growing Mixed Squamous Cell and Glandular Papilloma Difficult to Differentiate from Primary Lung CancerReport of a Case.

A 76-year-old woman was referred to our hospital due to abnormal chest radiography findings. Chest computed tomography (CT) revealed a nodule in the right lower lobe. Fluorodeoxyglucose-positronemission tomography (FDG-PET) showed abnormal accumulation in the nodule. Bronchoscopy did not provide a definitive diagnosis. Since the nodule tended to increase in size, primary lung cancer was suspected and surgery was performed. During the surgery, pathological diagnosis of squamous cell carcinoma was made, and a right lower lobectomy was performed. Subsequently, a pathological diagnosis of mixed squamous cell and glandular papilloma (mixed papilloma) was made. She has had no sign of recurrence for approximately four years since the surgery.

Thoracoscopic Surgery for Lung Cancer Invading the Superior Chest Wall.

We herein report a case of a 73-year-old man with lung cancer who underwent thoracoscopic right upper lobectomy with combined resection of the superior chest wall. His tumor was 48 mm in diameter and located in the posterior right lung apex involving the chest wall between ribs 1 and 3. The anterior aspects of the ribs 2 and 3 were separated using forceps under thoracoscopic vision. The first rib could be released from the tumor by peeling off the parietal pleura. An 8 cm incision was made posteriorly between the scapula and vertebrae to obtain the posterior aspect of the ribs 2 and 3. After separating the pulmonary vessels and bronchus, en bloc resection of the superior sulcus tumor was completed. Thoracoscopic chest wall resection of the superior sulcus tumor can be an alternative to the Paulson posterolateral-paravertebral thoracotomy approach, which can cause severe postoperative pain and limited range of motion of the shoulder joint.

Inclusion of patients with chronic kidney disease in randomized phase 3 clinical trials in patients with prostate, breast, lung, and colorectal cancer.

The objective of this study was to determine the proportion of phase 3 clinical trials investigating a systemic therapy for patients with prostate, breast, lung, or colorectal cancer that excluded patients with Chronic Kidney Disease (CKD) and the exclusion criteria chosen, if any. A search was conducted using the ClinicalTrials.gov database to identify eligible studies. Of the 268 included trials, 185 (69%) had at least one renal exclusion criteria. Of these 185 trials, 116 (63%) had an undefined exclusion criterion. Only disease site was associated with exclusion of patients with CKD in the univariate analysis, but no factors in the multivariate analysis. There are several potential barriers to including patients with CKD in clinical trials. Nevertheless, solutions can be proposed to allow the inclusion of these patients. This would allow them to access to innovative therapeutic strategies, but also allow a better applicability of trial results to this patient population.

Prediagnostic BMI trajectories in relation to pancreatic cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

It remains elusive whether prediagnostic BMI trajectory is associated with pancreatic cancer. This study investigated this question among 145,489 participants who gave rise to 696 incident cases of pancreatic cancer over a median follow-up of 12 years in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. At baseline, participants were asked to recall their weight at ages 20, 50, and 55 to 74 years (at enrollment), as well as their height. At age 50 years, people with obesity had a significantly increased risk of pancreatic cancer compared with those with a normal weight after adjustment for confounders (hazard ratio 95% CI 1.27 1.01-1.60). Individuals who had overweight at age 20 years experienced a marginally significant elevated risk of pancreatic cancer (hazard ratio 95% CI 1.22 0.99-1.50). Compared with individuals who maintained a steady normal weight during follow-up, no significantly altered risk of pancreatic cancer was observed for those whose weight status changed from normal weight to overweight, from normal weight to obesity, and from overweight to obesity. The present study revealed that prediagnostic adulthood BMI trajectory was not associated with pancreatic cancer risk, but overweight at young adulthood and obesity at middle adulthood may confer an elevated risk of this malignancy.

The efficacy of immune checkpoint inhibitors in elderly patients a meta-analysis and meta-regression.

Immune checkpoint inhibitor (ICI) therapy has improved patient survival in advanced cancers however, the efficacy of ICIs in elderly patients is still elusive. This study assessed the efficacy of ICIs in elderly patients with advanced cancer in terms of overall survival (OS) and progression-free survival (PFS). We carried out a systematic review and identified 30 head-to-head phase IIIII randomized controlled trials that compared immunotherapy with the standard of care in advanced solid tumor patients. The data on patients younger or over 65 years of age were indexed from PubMed-Medline, Embase, and Scopus and obtained for meta-analysis. The subgroup analyses were stratified by primary tumor type, line of treatment, or type of immunotherapy, and a meta-regression analysis was carried out after adjusting for all other variables. The study included 17 476 patients, comprising 58% (10 119) younger (<65 years old) and 42% (7357) elderly (≥65 years old) patients. The hazard ratio (HR) for OS was 0.77 95% confidence interval (CI) 0.70-0.85 and 0.77 (95% CI 0.70-0.85) in the younger and elderly groups, respectively, suggesting similar efficacies of ICIs in these two age groups. The subgroup analyses revealed no significant relationship between age and treatment outcomes, except for the PFS benefit in younger patients with melanoma than in elderly patients (HR 0.44 in younger patients versus 0.65 in elderly patients, P 0.04). These results were further supported by meta-regression analysis, which showed no statistically significant difference in OS (P 0.954) and PFS (P 0.555) between the two age groups. The findings suggest that age-associated impairments of the immune system did not affect the efficacy of ICIs in elderly patients compared to younger patients. Therefore, the choice of ICIs for elderly patients can be considered, regardless of chronological age.

Rapid artificial intelligence solutions in a pandemic-The COVID-19-20 Lung CT Lesion Segmentation Challenge.

Artificial intelligence (AI) methods for the automatic detection and quantification of COVID-19 lesions in chest computed tomography (CT) might play an important role in the monitoring and management of the disease. We organized an international challenge and competition for the development and comparison of AI algorithms for this task, which we supported with public data and state-of-the-art benchmark methods. Board Certified Radiologists annotated 295 public images from two sources (A and B) for algorithms training (n199, source A), validation (n50, source A) and testing (n23, source A n23, source B). There were 1,096 registered teams of which 225 and 98 completed the validation and testing phases, respectively. The challenge showed that AI models could be rapidly designed by diverse teams with the potential to measure disease or facilitate timely and patient-specific interventions. This paper provides an overview and the major outcomes of the COVID-19 Lung CT Lesion Segmentation Challenge - 2020.

MCU controls melanoma progression through a redox-controlled phenotype switch.

Melanoma is the deadliest of skin cancers and has a high tendency to metastasize to distant organs. Calcium and metabolic signals contribute to melanoma invasiveness however, the underlying molecular details are elusive. The MCU complex is a major route for calcium into the mitochondrial matrix but whether MCU affects melanoma pathobiology was not understood. Here, we show that MCU

Rapid intraoperative Ki-67 immunohistochemistry for lung cancer using non-contact alternating current electric field mixing.

Locoregional recurrence of non-small cell lung cancer (NSCLC) occurs even among patients with stage I disease, as a result of tumor proliferative activity. The aim of this study was to evaluate the clinical reliability of a new rapid immunohistochemistry (IHC) technique for assessing malignant potential through detection of tumoral Ki-67 expression. The rapid IHC method uses non-contact alternating current (AC) mixing to achieve more rapidstable staining within 20 min during surgery. First, to investigate the association between clinical outcomes and tumoral Ki-67 labeling with rapid IHC, 21 pairs of surgical patients treated between 2012 and 2020 for pStage IA1-3 NSCLC withwithout recurrence were retrospectively reviewed. Second, 40 frozen section (FS) samples in patients with NSCLC for whom radical surgery was planned between April 2021 and February 2022 were deemed eligible for comparison of the clinical performance of conventional IHC and intraoperative rapid Ki-67 IHC with FS. Detection of tumoral Ki-67 expression using rapid IHC with formalin-fixed, paraffin-embedded (FFPE) blocks was significantly associated with clinical outcomes in R0 pStage IA NSCLC surgical patients, including overall and recurrence-free survival (P 0.0043 and P lt 0.0001, respectively). Levels of Ki-67 expression among resectable NSCLC patients detected using rapid IHC with FS significantly correlated with those detected using conventional FFPE-IHC (p lt 0.001). An intraoperative cut-off of gt 7.5 % tumor cell Ki-67 positivity accurately predicted pathological stage more advanced than IA3 P 0.0185, Odds ratio 20.477, 95 % confidence interval (CI) 1.660-252.55. Rapid Ki-67 IHC with AC mixing could potentially serve as a clinical tool for intraoperative determination of tumor malignancy status. The present study suggests that segmentectomy for early small NSCLCs is oncologically safe and a reasonable alternative to lobectomy, but only when there is adequate intraoperative selection for primary tumors with low-grade malignancy, which could be verified using intraoperative rapid Ki-67 IHC with FS.

Prevalence and breakdown of non-small cell lung cancer BRAF driver mutations in a large UK cohort.

BRAF inhibitors have been shown in clinical trials to improve patient outcomes in non-small cell lung cancer (NSCLC) patients harbouring selected BRAF driver mutations with a limited side effect profile, and therefore show potential as therapeutics in clinical practice. To utilise BRAF inhibitors effectively, understanding the prevalence of BRAF mutations within the local patient population is crucial, especially since NSCLC driver mutation rates have been observed to vary in different populations around the world. We interrogated a clinical archive of next generation sequencing (NGS) data representative of 7 years of routine UK practice in the National Health Service (NHS) to investigate the frequency of BRAF mutations, the breakdown of mutation classes and co-occurrence of other oncogenic driver mutations. Tissue biopsies from NSCLC cases referred to the Sarah Cannon Molecular Diagnostics Laboratory between January 2015 and February 2022 from multiple centres across UK were included in this study. Somatic mutation hotspots in relevant cancer-associated genes were analysed using ampliconion-torrent based NGS assays, and all NSCLC samples which harboured recognised BRAF driver mutations were identified through a combination of automated and manual data retrieval. Data regarding any other detected mutations and basic demographic information were also collected. Over the 7-year period, 5384 NSCLC samples were sequenced, with BRAF mutation identified in 185 (3.44%) of cases. These 185 cases represented a total of 73 Class I BRAF mutations (39.5%), 61 Class II mutations (33.0%) and 51 Class III mutations (27.6%). Of the 73 identified Class I mutations, 69 (69185, 37.3%) were V600E and four (4185, 2.16%) were non-V600E mutations. Five V600E cases had co-mutations (5185, 2.7%). Various other known driver mutations were also identified in these 185 tumour samples, with KRAS (18185, 9.73%) and PIK3CA (7185, 3.78%) occurring at the highest frequency. This is the first large cohort-level study in the UK to profile the breakdown of BRAF-positive NSCLC biopsy samples using NGS in routine clinical practice. This study defines the proportion of NSCLC patients that may be expected to benefit from BRAF inhibitors and highlights the utility of using NGS as a diagnostic tool to improve targeted therapy stratification for NSCLC patients.

Characterization of lung cancers in patients with BRCA germline variants A multicenter series.

BRCA1 and BRCA2 (BReast CAncer susceptibility genes) are two tumor-suppressor genes associated with the hereditary breast and ovarian cancer susceptibility syndrome. Recent studies also suggest an increased lung adenocarcinoma risk in carriers. We conducted a multi-center retrospective study in 18 different French pulmonology andor oncology departments on medico-administrative and clinical data prospectively collected in the Clinical Data Warehouse (CDW) of Greater Paris University Hospitals (Assistance Publique-Hôpitaux de Paris, AP-HP). Clinical characteristics and outcomes of patients with LC and a previously known BRCA12gl variant were retrospectively evaluated. 17 patients with LC and known BRCA12gl variant were included. Patients were most women, former smokers with localized disease and BRCA2 variants. All LC were adenocarcinoma. For patients with medical history of cancer, median time from the first cancer in the BRCA spectrum and the LC occurrence was 20 years. Median disease-free survival (DFS) and overall survival (OS) in localized tumor (Stage I and II) was not reached and 78.6 months, respectively. In advanced cancer (Stade III and IV) median progression free survival was 9.7 months and median OS was 17.8 months. Univariate OS and DFSPFS analyses by BRCA status did not find significant differences. Results seem to show particular LC features in carriers of BRCA2 variants adenocarcinoma subtype, woman, former or non-smoker.

Long response to immune checkpoint inhibitors in metastatic NSCLC despite EGFR germline mutation. A case report.

First-line therapy in advanced non-small-cell-lung-cancer (NSCLC) is based on chemotherapy except for patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab is administrated. However, patients with somatic-EGFR-mutated tumors had usually been excluded from clinical applications of immune checkpoint inhibitors (ICIs). Germline-EGFR-mutated-patients are known to not respond to EGFR-Tyrosine-Kinase-inhibitors (TKIs). But what about germline EGFR mutations and response to ICIs Herein, we describe the case of a long response to ICIs treatment in a complex metastatic NSCLC with co-occuring EGFR germline and KRAS somatic mutations, high PD-L1 score and a smoking history.

Smoking-induced microbial dysbiosis in health and disease.

Smoking is associated with an increased risk of cancer, pulmonary and cardiovascular diseases, but the precise mechanisms by which such risk is mediated remain poorly understood. Additionally, smoking can impact the oral, nasal, oropharyngeal, lung and gut microbiome composition, function, and secreted molecule repertoire. Microbiome changes induced by smoking can bear direct consequences on smoking-related illnesses. Moreover, smoking-associated dysbiosis may modulate weight gain development following smoking cessation. Here, we review the implications of cigarette smoking on microbiome community structure and function. In addition, we highlight the potential impacts of microbial dysbiosis on smoking-related diseases. We discuss challenges in studying host-microbiome interactions in the context of smoking, such as the correlations with smoking-related disease severity versus causation and mechanism. In all, understanding the microbiomes role in the pathophysiology of smoking-related diseases may promote the development of rational therapies for smoking- and smoking cessation-related disorders, as well as assist in smoking abstinence.

Transient Systemic Autophagy Inhibition Is Selectively and Irreversibly Deleterious to Lung Cancer.

Autophagy is a conserved catabolic process that maintains cellular homeostasis. Autophagy supports lung tumorigenesis and is a potential therapeutic target in lung cancer. A better understanding of the importance of tumor cell-autonomous versus systemic autophagy in lung cancer could facilitate clinical translation of autophagy inhibition. Here, we exploited inducible expression of Atg5 shRNA to temporally control Atg5 levels and to generate reversible tumor-specific and systemic autophagy loss mouse models of KrasG12Dp53-- (KP) non-small cell lung cancer (NSCLC). Transient suppression of systemic but not tumor Atg5 expression significantly reduced established KP lung tumor growth without damaging normal tissues. In vivo13C isotope tracing and metabolic flux analyses demonstrated that systemic Atg5 knockdown specifically led to reduced glucose and lactate uptake. As a result, carbon flux from glucose and lactate to major metabolic pathways, including the tricarboxylic acid cycle, glycolysis, and serine biosynthesis, was significantly reduced in KP NSCLC following systemic autophagy loss. Furthermore, systemic Atg5 knockdown increased tumor T-cell infiltration, leading to T-cell-mediated tumor killing. Importantly, intermittent transient systemic Atg5 knockdown, which resembles what would occur during autophagy inhibition for cancer therapy, significantly prolonged lifespan of KP lung tumor-bearing mice, resulting in recovery of normal tissues but not tumors. Thus, systemic autophagy supports the growth of established lung tumors by promoting immune evasion and sustaining cancer cell metabolism for energy production and biosynthesis, and the inability of tumors to recover from loss of autophagy provides further proof of concept that inhibition of autophagy is a valid approach to cancer therapy. Transient loss of systemic autophagy causes irreversible damage to tumors by suppressing cancer cell metabolism and promoting antitumor immunity, supporting autophagy inhibition as a rational strategy for treating lung cancer. See related commentary by Gan, p. 4322.

Development and External Validation of a Mortality Prediction Model for Community-Dwelling Older Adults With Dementia.

Estimating mortality risk in older adults with dementia is important for guiding decisions such as cancer screening, treatment of new and chronic medical conditions, and advance care planning. To develop and externally validate a mortality prediction model in community-dwelling older adults with dementia. This cohort study included community-dwelling participants (aged ≥65 years) in the Health and Retirement Study (HRS) from 1998 to 2016 (derivation cohort) and National Health and Aging Trends Study (NHATS) from 2011 to 2019 (validation cohort). Candidate predictors included demographics, behavioralhealth factors, functional measures (eg, activities of daily living ADL and instrumental activities of daily living IADL), and chronic conditions. The primary outcome was time to all-cause death. We used Cox proportional hazards regression with backward selection and multiple imputation for model development. Model performance was assessed by discrimination (integrated area under the receiver operating characteristic curve iAUC) and calibration (plots of predicted and observed mortality). Of 4267 participants with probable dementia in HRS, the mean (SD) age was 82.2 (7.6) years, 2930 (survey-weighted 69.4%) were female, and 785 (survey-weighted 12.1%) identified as Black. Median (IQR) follow-up time was 3.9 (2.0-6.8) years, and 3466 (81.2%) participants died by end of follow-up. The final model included age, sex, body mass index, smoking status, ADL dependency count, IADL difficulty count, difficulty walking several blocks, participation in vigorous physical activity, and chronic conditions (cancer, heart disease, diabetes, lung disease). The optimism-corrected iAUC after bootstrap internal validation was 0.76 (95% CI, 0.75-0.76) with time-specific AUC of 0.73 (95% CI, 0.70-0.75) at 1 year, 0.75 (95% CI, 0.73-0.77) at 5 years, and 0.84 (95% CI, 0.82-0.85) at 10 years. On external validation in NHATS (n 2404), AUC was 0.73 (95% CI, 0.70-0.76) at 1 year and 0.74 (95% CI, 0.71-0.76) at 5 years. Calibration plots suggested good calibration across the range of predicted risk from 1 to 10 years. We developed and externally validated a mortality prediction model in community-dwelling older adults with dementia that showed good discrimination and calibration. The mortality risk estimates may help guide discussions regarding treatment decisions and advance care planning.

A Case of Advanced Squamous Cell Carcinoma of the Lung 19 Years after Chemoradiotherapy of Limited-Disease Small-Cell Lung Cancer.

A 65-year-old man was referred to our hospital because of a fever and cough 19 years after chemoradiotherapy for small-cell lung cancer(SCLC)in the right middle lobe. Computed tomography(CT)revealed a normal right middle lobe, but found pneumonia and a tumor at the bronchial entrance of the right upper lobe. After treating the pneumonia with antibiotics and prednisolone, transbronchial biopsies(TBBs)revealed the tumor to be squamous cell carcinoma(SCC). Eight lines of chemotherapy including immune checkpoint inhibitors(ICIs)were completed with a 42-month survival following the initiation of chemotherapy for SCC, after which he ultimately died of hemoptysis. Survival of over 10 years from small- cell cancer is rare. We herein report the prognosis of SCLC and the treatment of subsequent primary lung cancer.

β-Catenin Expression in Non-Small Cell Lung Cancer and Therapeutic Effect of Immune Checkpoint Inhibitors.

Recently, β-catenin mediated immune escape mechanism has been reported in several cancers. We investigated whether β-catenin is associated with resistance to immune checkpoint inhibitor therapy in non-small cell lung cancer. Non-small cell lung cancer patients expressing high levels of β-catenin showed poor progression-free survival and overall survival after single agent anti-PD-1 therapy. They had less infiltration of CD8-positive cells and antigen-presenting cells. Microarray analysis also showed low gene expression of CD8A and IFNG. siRNA knockdown of CTNNB1 in the β-catenin-positive lung cancer cell line LK-2 tended to decrease CTNNB1 and ATF3 expression and increase CCL4 expression. The results suggest that β- catenin suppresses tumor infiltration by antigen-presenting cells and confers resistance to immune checkpoint inhibitors in non-small cell lung cancer via downregulation of CCL4 production.

Resistance Mechanisms to Immune Checkpoint Inhibitor and Its Overcome with Focus on β-Catenin in Lung Cancer.

Although the indications for immune checkpoint inhibitors are expanding rapidly, the disease will eventually progress in many patients. Elucidating and overcoming the resistant mechanisms to immune checkpoint inhibitors is a major challenge. WNTβ-catenin pathway has long been known as one of the mechanisms involved in cell proliferation and epithelial-mesenchymal transition in cancer development. Recently, it has become clear that WNTβ-catenin pathway also plays a role in cancer immune escape, as reported in melanoma. We have also studied WNTβ-catenin pathway as a mechanism of immune escape in lung cancer. In this article, we review how WNTβ-catenin pathway is involved in immune escape and resistance to immune checkpoint inhibitors, mainly in non-small cell lung cancer. In addition, we discuss how to overcome the tumor immune mechanism caused by WNTβ-catenin pathway in the context of current combination therapies and therapies in development.

Prognostic value of Quality of life (QoL) assessment among Tunisian lung cancer patients.

Etudier la valeur pronostique de lévaluation de la qualité de vie (QDV) pour la survie chez les patients Tunisiens atteints du CDP. Méthodes Une étude prospective de cohorte a été réalisée entre Janvier 2018 et Juin 2019. Le Performance status (PS), QoL questionnairecore30 (QLQ-C30), QoL questionnaire-Lung Cancer 13 (QLQ-LC13) et European QoL-5 dimensions-3level version questionnaire (EQ-5D-3L) ont été utilisés pour lévaluation de la QDV. Les patients ont été divisés en 2 groupes selon le score global QLQ-C30, un Déficit Cliniquement Significatif (DCS) a été considéré si le score était ≤50. Les modèles de régression de Cox et Stepwise ont été réalisée pour évaluer la signification pronostique de la QDV. La survie globale (SG) a été calculée à laide de la méthode de Kaplan-Meier. Le test du log-rank a été utilisé pour comparer les courbes de survie. Le seuil de valeur de p pour la signification statistique était de 0,05. Résultats Cent patients ont été inclus. La médiane de SG des patients avec DCS en qualité de vie était significativement inférieure à celle des patients sans déficit respectivement 365 jours versus 467 jours, (test du log-rank, p 0,036). De même pour la médiane de survie sans progression 122 jours versus 326 jours pour ceux qui nont pas signalé de différence significative en QDV (test du log-rank, p 0,05). Lanalyse de régression multivariée stepwise a montré que le score global de QDV (QLQ-C30) était un facteur prédictif significatif de SG (coefficient estimate (CE) 0.336, p0.005), ainsi que le stade IV (CE-0.193, p0.033) et la progression tumorale (CE -0.238, p0.047). La QDV était un facteur prédictif de survie dans notre cohorte de patients atteints de CDP. Cela devrait recommander une intervention active en soins palliatifs précoces pour les patients présentant un déficit significatif en QDV.

OSW-1 induces apoptosis and cyto-protective autophagy, and synergizes with chemotherapy on triple negative breast cancer metastasis.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. As yet, chemotherapy with drugs such as doxorubicin is the main treatment strategy. However, drug resistance and dose-dependent toxicities restrict their clinical use. Natural products are major sources of anti-tumor drugs. OSW-1 is a natural compound with strong anti-cancer effects in several types of cancer, but its effects on the efficacy of chemotherapy in TNBC and its underlying mechanism remain unclear. The inhibitory activities of OSW-1 and its combination with several chemotherapy drugs were tested using in vitro assays and in vivo subcutaneous and metastatic mouse TNBC models. The effects of the mono- and combination treatments on TNBC cell viability, apoptosis, autophagy and related signaling pathways were assessed using MTT, flow cytometry, RNA sequencing and immunology-based assays. In addition, the in vivo inhibitory effects of OSW-1 and (combined) chemotherapies were evaluated in subcutaneous and metastatic mouse tumor models. We found that OSW-1 induces Ca Our data revealed the mode of action and molecular mechanism underlying the effect of OSW-1 against TNBC, and provided a useful guidance for improving the sensitivity of TNBC cells to conventional chemotherapeutic drugs, which warrants further investigation.

Development and Validation of a Nomogram for Predicting Postoperative Pulmonary Infection in Patients Undergoing Lung Surgery.

To develop and validate a nomogram for predicting postoperative pulmonary infection (PPI) in patients undergoing lung surgery. Single-center retrospective cohort analysis. A university-affiliated cancer hospital PARTICIPANTS A total of 1,501 adult patients who underwent lung surgery from January 2018 to December 2020. Observation for PPI within 7 days after lung surgery. A complete set of demographics, preoperative variables, and postoperative follow-up data was recorded. The primary outcome was PPI a total of 125 (8.3%) out of 1,501 patients developed PPI. The variables with p < 0.1 in univariate logistic regression were included in the multivariate regression, and multivariate logistic regression analysis showed that surgical procedure, surgical duration, the inspired fraction of oxygen in one-lung ventilation, and postoperative pain were independent risk factors for PPI. A nomogram based on these factors was constructed in the development cohort (area under the curve 0.794, 95% CI 0.744-0.845) and validated in the validation cohort (area under the curve 0.849, 95% CI 0.786-0.912). The calibration slope was 1 in the development and validation cohorts. Decision curve analysis indicated that when the threshold probability was within a range of 0.02-to-0.58 and 0.02-to-0.42 for the development and validation cohorts, respectively, the nomogram model could provide a clinical net benefit. The authors developed and validated a nomogram for predicting PPI in patients undergoing lung surgery. The prediction model can predict the development of PPI and identify high-risk groups.

New methodology of TMB assessment from tissue and liquid biopsy in NSCLC.

Immunotherapy has dramatically influenced and changed therapeutical approach in non-small cell lung cancer (NSCLC) in recent five years. Even though we can reach long-term response to this treatment in approximately 20% of patients with NSCLC, we are still not able to identify this cohort of patients based on predictive biomarkers. In our study we have focused on tumor mutation burden (TMB), one of the potential biomarkers which could predict effectiveness of check-point inhibitors, but has several limitations, especially in multiple approaches to TMB quantification and ununiform threshold. We determined the value of TMB in tumor tissue (tTMB) and blood (bTMB) in 20 patients with early stage NSCLC using original custom gene panel LMBTMB1. We evaluated various possibilities of TMB calculation and concluded that TMB should be counted from both somatic non-synonymous and synonymous mutations. Considering various factors, we established cut-offs of tTMB inexcluding HLA genes as ≥22 mutMb and 12 mutMb respectively, and cut-offs of bTMB were defined as ≥21 mutMb and ≥5 mutMb, respectively. We also observed trend in correlation of somatic mutations in HLA genes with overall survival of patients.

N-phenethyl-5-phenylpicolinamide alleviates inflammation in acute lung injury by inhibiting HIF-1αglycolysisASIC1a pathway.

Acute lung injury (ALI) is triggered by an acute inflammatory response. Lipopolysaccharide (LPS) is recognized as an important participant in the pathogenesis of sepsis, which may induce ALI. N-phenethyl-5-phenylpicolinamide (N5P) is a newly synthesized HIF-1α inhibitor. The purpose of the present study was to investigate the potential protective effects of N5P on LPS-induced ALI and the underlying mechanisms. In vivo experiment, the ALI rat model was induced by intratracheal injection of LPS, and various concentrations of N5P were injected intraperitoneally before LPS administration. In vitro experiment, RAW264.7 macrophages were administrated LPS and N5P to detect inflammatory cytokine changes. HIF-1α overexpression plasmid (HIF1α-OE) and granulocyte-macrophage colony-stimulating factor (GM-CSF), a glycolysis agonist, were used to examine the relationship between the HIF-1αglycolysisASIC1a pathway. Pretreatment with N5P inhibited not only the histopathological changes that occurred in the lungs but also lung dysfunction in LPS-induced ALI. N5P also decreased the levels of lactic acid in lung tissue and arterial blood, and inflammatory factors IL-1β and IL-6 levels in serum. LPS increased HIF-1α, glycolysis proteins GLUT1, HK2, ASIC1a, IL-1β, IL-6, and these changes were reversed by N5P in primary alveolar macrophages and RAW264.7 macrophages. Overexpression of HIF-1α significantly increased glycolysis genes and ASIC1a as well as inflammatory cytokines. Excessive glycolysis levels weaken the ability of N5P to inhibit inflammation. N5P may alleviate inflammation in ALI through the HIF-1αglycolysisASIC1a signaling pathway. The present findings have provided pertinent information in the assessment of N5P as a potential, future therapeutic drug for ALI.

Novel Ru(II)-bipyridinephenanthroline-lapachol complexes as potential anti-cancer agents.

For the first time, we herein report on the syntheses of two new Ru(II)bipyridinephenanthroline complexes containing lapachol as ligand complex (1), Ru (bipy)

Whats Current and Whats New in Mesothelioma

Malignant mesothelioma is a rare disease with limited treatment options. In malignant pleural mesothelioma (MPM), radical trimodality approaches, including surgery, radiotherapy and systemic chemo- and immunotherapy, have been delivered in some countries but remain controversial due to a lack of randomised evidence. Even in the unresectable scenario, surgery and radiotherapy play an important role in managing pleural effusions and pain, which may optimise wellbeing and maintain performance status. From the systemic treatment point of view, the recent incorporation of anti-angiogenics and, more importantly, immunotherapy has changed the standard of care in a space where chemotherapy with platinum and pemetrexed was the only therapeutic intervention with demonstrated benefits in overall survival. Histology is essential in determining an initial treatment plan as non-epithelioid MPMs may have a higher substantial survival improvement with dual immunotherapy compared with chemotherapy, whereas chemotherapy remains an option for epithelioid MPM however, predictive biomarkers for systemic therapy are not entirely validated to guide the selection, as a subgroup of MPM patients might not benefit from immunotherapy. This overview approaches how the overall management of mesothelioma is evolving to incorporate the recent changes in the standards of care.

Plasma exchange and glucocorticoids to delay death or end-stage renal disease in anti-neutrophil cytoplasm antibody-associated vasculitis PEXIVAS non-inferiority factorial RCT.

Anti-neutrophil cytoplasm antibody-associated vasculitis is a multisystem, autoimmune disease that causes organ failure and death. Physical removal of pathogenic autoantibodies by plasma exchange is recommended for severe presentations, along with high-dose glucocorticoids, but glucocorticoid toxicity contributes to morbidity and mortality. The lack of a robust evidence base to guide the use of plasma exchange and glucocorticoid dosing contributes to variation in practice and suboptimal outcomes. We aimed to determine the clinical efficacy of plasma exchange in addition to immunosuppressive therapy and glucocorticoids with respect to death and end-stage renal disease in patients with severe anti-neutrophil cytoplasm antibody-associated vasculitis. We also aimed to determine whether or not a reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen with respect to death and end-stage renal disease. This was an international, multicentre, open-label, randomised controlled trial. Patients were randomised in a two-by-two factorial design to receive either adjunctive plasma exchange or no plasma exchange, and either a reduced or a standard glucocorticoid dosing regimen. All patients received immunosuppressive induction therapy with cyclophosphamide or rituximab. Ninety-five hospitals in Europe, North America, AustraliaNew Zealand and Japan participated. Participants were aged ≥ 16 years with a diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, and either proteinase 3 anti-neutrophil cytoplasm antibody or myeloperoxidase anti-neutrophil cytoplasm antibody positivity, and a glomerular filtration rate of < 50 mlminute1.73 m Participants received seven sessions of plasma exchange within 14 days or no plasma exchange. Oral glucocorticoids commenced with prednisolone 1 mgkgday and were reduced over different lengths of time to 5 mgkgday, such that cumulative oral glucocorticoid exposure in the first 6 months was 50% lower in patients allocated to the reduced-dose regimen than in those allocated to the standard-dose regimen. All patients received the same glucocorticoid dosing from 6 to 12 months. Subsequent dosing was at the discretion of the treating physician. The primary outcome was a composite of all-cause mortality and end-stage renal disease at a common close-out when the last patient had completed 10 months in the trial. The study recruited 704 patients from June 2010 to September 2016. Ninety-nine patients died and 138 developed end-stage renal disease, with the primary end point occurring in 209 out of 704 (29.7%) patients 100 out of 352 (28%) in the plasma exchange group and 109 out of 352 (31%) in the no plasma exchange group (adjusted hazard ratio 0.86, 95% confidence interval 0.65 to 1.13 Plasma exchange did not prolong the time to death andor end-stage renal disease in patients with anti-neutrophil cytoplasm antibody-associated vasculitis with severe renal or pulmonary involvement. A reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen and was associated with fewer serious infections. A meta-analysis examining the effects of plasma exchange on kidney outcomes in anti-neutrophil cytoplasm antibody-associated vasculitis is planned. A health-economic analysis of data collected in this study to examine the impact of both plasma exchange and reduced glucocorticoid dosing is planned to address the utility of plasma exchange for reducing early end-stage renal disease rates. Blood and tissue samples collected in the study will be examined to identify predictors of response to plasma exchange in anti-neutrophil cytoplasm in antibody-associated vasculitis. The benefits associated with reduced glucocorticoid dosing will inform future studies of newer therapies to permit further reduction in glucocorticoid exposure. Data from this study will contribute to updated management recommendations for anti-neutrophil cytoplasm antibody-associated vasculitis. This study had an open-label design which may have permitted observer bias however, the nature of the end points, end-stage renal disease and death, would have minimised this risk. Despite being, to our knowledge, the largest ever trial in anti-neutrophil cytoplasm antibody-associated vasculitis, there was an insufficient sample size to assess clinically useful benefits on the separate components of the primary end-point end-stage renal disease and death. Use of a fixed-dose plasma exchange regimen determined by consensus rather than data-driven dose ranging meant that some patients may have been underdosed, thus reducing the therapeutic impact. In particular, no biomarkers have been identified to help determine dosing in a particular patient, although this is one of the goals of the biomarker plan of this study. This trial is registered as ISRCTN07757494, EudraCT 2009-013220-24 and Clinicaltrials.gov NCT00987389. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Anti-neutrophil cytoplasm antibody vasculitis is a rare and severe disease in which the patient makes antibodies that damage their blood vessels. It can cause lung damage, kidney failure and early death. Treatment aims to suppress the harmful effects of the antibodies and associated inflammation. In particular Plasma exchange aims to remove the antibodies from the bloodstream.Steroids aim to reduce the harmful activity of the antibodies. Unfortunately, plasma exchange is expensive and time-consuming, and we do not know if it really works long term to reduce kidney damage or the risk of death. We know steroids work, but they have many severe side effects that are related to higher doses. Again, we do not know if lower doses are equally effective. We conducted a randomised trial, PEXIVAS (Plasma Exchange In VASculitis), to measure the clinical effectiveness of plasma exchange and of reduced steroid doses. Anti-neutrophil cytoplasm antibody vasculitis patients with severe kidney or lung disease were allocated randomly to either plasma exchange or no plasma exchange. The same patients were then randomly allocated to a ‘reduced’ or ‘standard’ steroid dose. All patients received an immunosuppressive drug cyclophosphamide or rituximab. The primary end point for both trials was the occurrence of either kidney failure or death. A total of 704 patients were recruited between 2010 and 2016, and they were followed up until the end of the trial in July 2017. Ninety-nine patients died and 138 developed kidney failure. Plasma exchange did not reduce the chances of death or kidney failure. There was also no difference between the two steroid dose groups in the number of deaths or patients developing kidney failure. However, there were fewer serious infections in the reduced steroid dose group. These results do not support the routine use of plasma exchange for all patients with severe vasculitis. They do show that the reduced-dose steroid regimen is just as effective as, and safer than, a ‘standard’-dose steroid regimen. These results have the potential to save money and make the treatment of vasculitis patients safer in the future.

EGFR-mutation testing and TKI treatment patterns in locally advanced and metastatic NSCLC in Norway - A nationwide retrospective cohort study.

Testing for epidermal growth factor receptor mutation (EGFRm) status is a prerequisite to identify eligible patients for tyrosine kinase inhibitors (TKI) treatment. However, EGFR testing of patients with non-small cell lung cancer (NSCLC) is suboptimal in many parts of the world. The aim of this study was to describe real-world EGFR testing practice, EGFRm prevalence, and subsequent TKI treatment patterns in Norway. This retrospective, observational, cohort study included all incident locally advanced and metastatic non-squamous NSCLC patients registered in the Norwegian Cancer Registry during 2010-2017. A cohort with follow-up through 2018 was formed with linkage to nationwide registries on comorbidities, prescribed drugs and causes-of-death. A total of 10,717 patients were included, of which 35% (3782) with locally advanced NSCLC and 65% (6935) with metastatic disease. Mean age at diagnosis was 71 years and 47% were female. EGFR testing among patients with metastatic NSCLC increased from 41% to >64% between 2010 and 2017, with a relative stable incidence of EGFRm (∼9%). More than 85% of EGFRm patients received TKI treatment. Patients with the most dismal prognosis (>80 age, comorbidities) and with diagnosis based on cytologyimaging were less likely to be tested. Differences in testing were observed between regions. Despite increased test rates over the study period, in Norway, a significant proportion of patients with non-squamous metastatic NSCLC are still not tested for EGFR. To maximize the identification of eligible patients for targeted therapies, increased testing is recommended, regardless of age, comorbidity rate and place of residence.

Drebrin promotes lung adenocarcinoma cell migration through inducing integrin β1 endocytosis.

Lung adenocarcinoma (LUAD) is the most common type of lung cancers, which remains the leading cause of cancer-related death worldwide. Drebrin can promote cell migration and invasion with poor prognosis, but its roes in LUAD tumor progression remains unknown. We showed that the expression of Drebrin was upregulated in clinical LUAD samples. A Kaplan-Meier survival analysis showed that a high expression of Drebrin predicated poor prognosis in LUAD. In vitro, Drebrin promoted anchorage-independent growth and migration of LUAD cells. Drebrin interacted with dynamin through CT domain, and served as an adaptor to promote LUAD cell migration through inducing integrin β1 endocytosis. Thus, this study demonstrated the critical role of Drebrin in LUAD and associated mechanism.

Exploring the relationship between autophagy and Gefitinib resistance in NSCLC by silencing PDLIM5 using ultrasound-targeted microbubble destruction technology.

Ultrasound-targeted microbubble destruction (UTMD) technology is a new drug and gene delivery strategy. This study investigates novel ultrasound (US) sensitive siRNA-loaded nanobubbles (siRNA-NBs) to explore the relationship between PDLIM5 mediated autophagy and drug resistance development using epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of non-small cell lung cancer (NSCLC). US sensitive siRNA-NBs were designed to inhibit the expression of PDLIM5 in gefitinib-resistant human NSCLC PC9GR cells in vitro. The expression of autophagy-related proteins (P62 and LC3-III) and autophagosomes in PC9GR cells after PDLIM5 gene silencing were explored. US-sensitive PDLIM5-targeted siRNA-NBs were effectively delivered into PC9GR cells, inhibiting PDLIM5 expression, increasing LC3-III and p62 expressions and increasing autophagosomes in PC9GR cells in vitro. Using UTMD, US-sensitive siRNA-NBs have the potential as an ideal delivery vector to mediate highly effective RNA interference for NSCLC cells. Furthermore, PDLIM5 plays a role in the autophagy-mediated resistance in gefitinib-resistant PC9GR cells.

Validation of a highly sensitive Sanger sequencing in detecting EGFR mutations from circulating tumor DNA in patients with lung cancers.

The novel method, named blocker displacement amplification (BDA) Sanger, was applied to detect low variant allele frequency mutations in the circulating tumor DNA (ctDNA). This study aimed to evaluate the performance of the BDA Sanger method for the EGFR mutation detection in the ctDNA from lung cancer patients. A total of 195 plasma samples of lung cancer patients were included. The EGFR mutation status in the ctDNA was detected by the BDA Sanger and Super-ARMS assays. Next-generation sequencing (NGS) was further used to verify the mutant of EGFR with inconsistencies. BDA Sanger assay was capable of detecting EGFR mutations with a 0.20% VAF from plasma samples. Among treatment-naive patients with paired tissue and plasma samples, the EGFR positive percent agreement (PPA) was 79% by BDA sanger. EGFR mutation was detected in 34.4% (67195) ctDNA samples by the Super-ARMS and in 41.0% (80195) ctDNA samples by the BDA Sanger assay. The overall concordance rate between the BDA Sanger and Super-ARMS assays was 82% (160195). The BDA Sanger also enabled the detection of rare EGFR mutations, which were not discovered by the Super-ARMS. The results supported the validity and efficiency of the BDA Sanger method for EGFR detection in patients with lung cancer, indicating that BDA Sanger has a great potential for application in detecting mutations in the ctDNA.

Gene Therapy Cargos Based on Viral Vector Delivery.

Viral vectors have proven useful in a broad spectrum of gene therapy applications due to their possibility to accommodate foreign genetic material for both local and systemic delivery. The wide range of viral vectors has enabled gene therapy applications for both acute and chronic diseases. Cancer gene therapy has been addressed by delivery of viral vectors expressing anti-tumor, toxic, and suicide genes for destruction of tumors. Delivery if immunostimulatory genes such as cytokines and chemokines has also been applied for cancer therapy. Moreover, oncolytic viruses specifically replicating in and killing tumor cells have been used as such for tumor eradication or in combination with tumor killing or immunostimulatory genes. In a broad meaning, vaccines against infectious diseases and various cancers can be considered as gene therapy, which has been highly successful not the least for development of effective COVID-19 vaccines. Viral vector-based gene therapy has also demonstrated encouraging and promising results for chronic diseases such as severe combined immunodeficiency (SCID), muscular dystrophy, and hemophilia. Preclinical gene therapy studies in animal models have demonstrated proof-of-concept for a wide range of disease indications. Clinical evaluation of drugs and vaccines in humans has showed high safety levels, good tolerance, and therapeutic efficacy. Several gene therapy drugs such as the adenovirus-based drug Gendicine® for non-small-cell lung cancer, the reovirus-based drug Reolysin® for ovarian cancer, lentivirus-based treatment of SCID-X1 disease, and the rhabdovirus-based vaccine Ervebo against Ebola virus disease, and adenovirus-based vaccines against COVID-19 have been developed.

In vitro and in vivo anti-lung cancer activity of emodin A RNA-seq transcriptome analysis.

Emodin is a natural anthraquinone extract of Chinese medicinal herbs. Several studies demonstrated the antitumor activity of this extract, particularly for lung cancer. However, the mode of action of emodin remains obscure. In this study we evaluated in vitro and in vivo anti-lung cancer properties of emodin in human lung adenocarcinomas and the underlying molecular mechanism involved. Our results demonstrated emodin caused a significant inhibition of cell viability and induced apoptosis in lung cancer cells to a level that is relative to that of normal epithelial cells. Furthermore, RNA-seq transcriptome analysis revealed 65 common genes(>2-fold change) with a significant expression in A549, and H1650 cells under emodin treatment. In vitro qRT-PCR results confirmed that 4 genes (ATP6V0D2, C11orf96, TIPARP, and CDKN1A) were up-regulated, and 9 genes (TNFSF10, IFIT1, EGLN3, RCOR2, ARRB1, FLVCR2, BAIAP2-DT, FAM111B, and TGFB2) were down-regulated in A549 and H1650 adenocarcinoma cell lines. The in vivo experiment demonstrated emodin could significantly decrease tumor volume and tumor weight of mice compared with the control group. However, emodin treatment has no obvious effect on body weight of mice. Moreover, in vivo qRT-PCR results revealed that 3 genes (ATP6V0D2, C11orf96, and TIPARP) were up-regulated, and 6 genes (TNFSF10, IFIT1, EGLN3, BAIAP2-DT, FAM111B, and TGFB2) were down-regulated in tumor tissues compared with the control group. These findings suggested that emodin could help treat lung cancer and has a potential for further investigations as an anti-lung cancer drug.

COVID-19 and lung cancer update on the latest screening, diagnosis, management and challenges.

Lung cancer, considered one of the most common causes of cancer deaths worldwide, is a complex disease with its own challenges. The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), compounded these challenges and forced the medical healthcare system to alter its approach to lung cancer. This narrative review aims to identify the effect of the COVID-19 pandemic on lung cancer screening, diagnosis and management. During this public health crisis, various medical societies have worked on developing guidelines to protect patients with lung cancer from the deleterious effects of SARS-CoV-2 infection, as well as from the complications imposed by treatment delays. The different therapeutic approaches, such as surgery, radiation oncology and immune checkpoint inhibitor therapy, along with the latest international recommendations, will be discussed. Protecting patients with lung cancer from COVID-19 complications, while avoiding barriers in treatment delays, has brought unique challenges to healthcare facilities. Prompt modifications to guidelines, and constant evaluation of their efficacy, are thus needed.

Selective Immune Modulating Activities of

Video-assisted thoracoscopic versus open sleeve lobectomy for non-small cell lung cancer A systematic review and meta-analysis from six comparative studies.

Lung sleeve resection is indicated for centrally located lung tumors, especially for patients who cannot tolerate pneumonectomy. With video-assisted thoracoscopic surgery (VATS) being increasingly implemented for a wide variety of thoracic pathologies, this study aims to compare the intraoperative, postoperative, and long-term outcomes of VATS and open bronchial sleeve lobectomy for non-small cell lung cancer (NSCLC). The MEDLINE (via PubMed), Cochrane Library, and Scopus databases were searched. Original clinical studies, comparing VATS and open sleeve lobectomy for NSCLC were included. Evidence was synthesized as odds ratios for categorical and weighted mean difference (WMD) for continuous variables. Our analysis included six studies with non-overlapping populations reporting on 655 patients undergoing bronchial sleeve lobectomy for NSCLC (229 VATS and 426 open). VATS sleeve lobectomy was associated with significantly longer operative time ((WMD) 45.85 min, 95% confidence interval (CI) 12.06 to 79.65, The limitation of our study arises mainly due to the heterogeneity of the included studies. Nevertheless, VATS bronchial sleeve lung resection constitutes a feasible and safe alternative to the open sleeve lung resection surgery for the management of centrally located lung tumors.

Discovery and Optimization of the First Highly Effective and Orally Available Galectin-3 Inhibitors for Treatment of Fibrotic Disease.

Galectin-3 is a carbohydrate-binding protein central to regulating mechanisms of diseases such as fibrosis, cancer, metabolic, inflammatory, and heart disease. We recently found a high affinity (nM) thiodigalactoside GB0139 which currently is in clinical development (PhIIb) as an inhaled treatment of idiopathic pulmonary fibrosis. To enable treatment of systemically galectin-3 driven disease, we here present the first series of selective galectin-3 inhibitors combining high affinity (nM) with oral bioavailability. This was achieved by optimizing galectin-3 specificity and physical chemical parameters for a series of disubstituted monogalactosides. Further characterization showed that this class of compounds reduced profibrotic gene expression in liver myofibroblasts and displayed antifibrotic activity in CCl

Cross-Ancestry Investigation of Venous Thromboembolism Genomic Predictors.

Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources. We present new cross-ancestry meta-analyzed GWAS results involving up to 81 669 VTE cases from 30 studies, with replication of novel loci in independent populations and loci characterization through in silico genomic interrogations. In our genetic discovery effort that included 55 330 participants with VTE (47 822 European, 6320 African, and 1188 Hispanic ancestry), we identified 48 novel associations, of which 34 were replicated after correction for multiple testing. In our combined discovery-replication analysis (81 669 VTE participants) and ancestry-stratified meta-analyses (European, African, and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. A genetic risk score of the significantly associated loci in Europeans identified a 6-fold increase in risk for those in the top 1% of scores compared with those with average scores. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein quantitative-trait locus Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 GWAS loci provided insights to biological pathways contributing to VTE, with some loci contributing to VTE through well-characterized coagulation pathways and others providing new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis. Our cross-ancestry GWAS meta-analyses identified new loci associated with VTE. These findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.

Daphnoretin Arrests the Cell Cycle and Induces Apoptosis in Human Breast Cancer Cells.

Emerging evidence has shown that daphnoretin, one of the main active ingredients of

Internal Wireless Electrical Stimulation from Piezoelectric Barium Titanate Nanoparticles as a New Strategy for the Treatment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive BC subtype with a higher metastatic rate and a worse 5-year survival ratio than the other BC. It is an urgent need to develop a noninvasive treatment with high efficiency to resist TNBC cell proliferation and invasion. Internal wireless electric stimulation (ES) based on piezoelectric materials is an emerging noninvasive strategy, with adjustable ES intensity and excellent biosafety. In this study, three different barium titanate nanoparticles (BTNPs) with different crystal phases and piezoelectric properties were studied. Varying intensities of internal ES were generated from the three BTNPs (

Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer.

Lung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is quite poor. Although low-dose computed tomography (LDCT) is a routine clinical examination for early detection of LC, the false-positive rate is over 90%. As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in various diseases, including cancer and other diseases. Hypermethylation in tumor suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Remarkably, DNA methylation usually occurs in the very early stage of malignant tumors. Thus, DNA methylation analysis may provide some useful information about the early detection of LC. In recent years, liquid biopsy has developed rapidly. Liquid biopsy can detect and monitor both primary and metastatic malignant tumors and can reflect tumor heterogeneity. Moreover, it is a minimally invasive procedure, and it causes less pain for patients. This review summarized various liquid biopsies based on DNA methylation for LC. At first, we briefly discussed some emerging technologies for DNA methylation analysis. Subsequently, we outlined cell-free DNA (cfDNA), sputum, bronchoalveolar lavage fluid, bronchial aspirates, and bronchial washings DNA methylation-based liquid biopsy for the early detection of LC. Finally, the prognostic value of DNA methylation in cfDNA and sputum and the diagnostic value of other DNA methylation-based liquid biopsies for LC were also analyzed.

Isolated adrenocorticotropic hormone deficiency associated with sintilimab therapy in a patient with advanced lung adenocarcinoma a case report and literature review.

Several immune checkpoint inhibitors have been implemented for cancer treatment which have shown some degree of antitumor effcacy, while immune-related adverse events (irAEs) that affect multiple organ functions ensue which obviously should not be neglected. Though less common than other kinds of irAEs, Immune checkpoint inhibitors (ICIs) related Isolated ACTH deficiency (IAD) may cause long-term damage to pituitary-adrenal axis. Several case reports are available about IAD during anti-PD-1 therapy. We report the first case of immune checkpoint inhibitor-induced IAD following 3 month of sintilimab therapy. A 66-year-old Chinese man was diagnosed with stage IIIB lung adenocarcinoma with involving ipsilateral intrapulmonary and hilar lymph node metastasis. After 3 months of combination therapy of nedaplatin, pemetrexed and sintilimab, the patient presented with general fatigue, nausea and vomiting. Laboratory investigation at admission revealed hyponatremia and hypokalemia. Further investigation revealed adrenocorticotropic hormone and cortisol levels were far below than normal limits. His other pituitary hormone levels were normal, except for mild elevation of follicle stimulating hormone and estradiol. Cranic magnetic resonance imaging showed a normal pituitary gland. Isolated adrenocorticotropic hormone deficiency was diagnosed, and corticosteroid replacement therapy was administered, leading to a significant improvement of his symptoms while ACTH level maintaining low level. Our patient developed isolated ACTH deficiency during combination cancer treatment with chemotherapy and sintilimab. Although isolated ACTH deficiency due to anti-PD-1 including sintilimab therapy is rare occurrence, it can often cause severe clinical symptoms. Its diagnosis basically relies on clinical symptoms and endocrinological examination. Unlike traditional hypophysitis diagnosed by cranial MRI, pituitary MRI of IAD due to anti-PD-1 often indicates normal pituitary gland implying that over-reliance on imaging findings is not recommended. Even if clinical symptoms have relieved after corticosteroid replacement therapy was commenced, low levels of ACTH or cortisol could maintain for a long period which highlights the need for long term corticosteroid therapy. The purpose of the current report was to provide increased awareness of early detection and therapy of IAD.

Deep whole genome sequencing identifies recurrent genomic alterations in commonly used breast cancer cell lines and patient-derived xenograft models.

Breast cancer cell lines (BCCLs) and patient-derived xenografts (PDXs) are the most frequently used models in breast cancer research. Despite their widespread usage, genome sequencing of these models is incomplete, with previous studies only focusing on targeted gene panels, whole exome or shallow whole genome sequencing. Deep whole genome sequencing is the most sensitive and accurate method to detect single nucleotide variants and indels, gene copy number and structural events such as gene fusions. Here we describe deep whole genome sequencing (WGS) of commonly used BCCL and PDX models using the Illumina X10 platform with an average 60 × coverage. We identify novel genomic alterations, including point mutations and genomic rearrangements at base-pair resolution, compared to previously available sequencing data. Through integrative analysis with publicly available functional screening data, we annotate new genomic features likely to be of biological significance. CSMD1, previously identified as a tumor suppressor gene in various cancer types, including head and neck, lung and breast cancers, has been identified with deletion in 50% of our PDX models, suggesting an important role in aggressive breast cancers. Our WGS data provides a comprehensive genome sequencing resource of these models.

Emerging nanotechnology-based therapeutics to combat multidrug-resistant cancer.

Cancer often develops multidrug resistance (MDR) when cancer cells become resistant to numerous structurally and functionally different chemotherapeutic agents. MDR is considered one of the principal reasons for the failure of many forms of clinical chemotherapy. Several factors are involved in the development of MDR including increased expression of efflux transporters, the tumor microenvironment, changes in molecular targets and the activity of cancer stem cells. Recently, researchers have designed and developed a number of small molecule inhibitors and derivatives of natural compounds to overcome various mechanisms of clinical MDR. Unfortunately, most of the chemosensitizing approaches have failed in clinical trials due to non-specific interactions and adverse side effects at pharmacologically effective concentrations. Nanomedicine approaches provide an efficient drug delivery platform to overcome the limitations of conventional chemotherapy and improve therapeutic effectiveness. Multifunctional nanomaterials have been found to facilitate drug delivery by improving bioavailability and pharmacokinetics, enhancing the therapeutic efficacy of chemotherapeutic drugs to overcome MDR. In this review article, we discuss the major factors contributing to MDR and the limitations of existing chemotherapy- and nanocarrier-based drug delivery systems to overcome clinical MDR mechanisms. We critically review recent nanotechnology-based approaches to combat tumor heterogeneity, drug efflux mechanisms, DNA repair and apoptotic machineries to overcome clinical MDR. Recent successful therapies of this nature include liposomal nanoformulations, cRGDY-PEG-Cy5.5-Carbon dots and CdsZnS core-shell quantum dots that have been employed for the effective treatment of various cancer sub-types including small cell lung, head and neck and breast cancers.

Computer grading of lung disease severity in patients with lymphangioleiomyomatosis referred for transplantation.

Lymphangioleiomyomatosis (LAM) patients with severe lung disease may be considered for lung transplantation. Clinical, physiologic, and quality of life data are usually employed for referral. The aim of this study was to determine whether computed tomographic measurement of lung volume occupied by cysts (cyst score) complemented clinical and physiologic data in supporting referral for transplantation. Forty-one patients were studied. Pre-referral clinical data, pulmonary function tests, exercise testing, and high-resolution computed tomography (HRCT) scans were obtained. From HRCT, a computer-aided diagnostic program was employed to calculate cyst scores. These data were compared to those of 41 age-matched LAM patients not referred for lung transplantation. Cyst score, and % predicted FEV LAM patients referred for lung transplantation had nearly 50% of lungs occupied by cysts. Correlations between cyst score and FEV

Real-world analysis of different intracranial radiation therapies in non-small cell lung cancer patients with 1-4 brain metastases.

Stereotactic radiosurgery (SRS) has become a standard approach for the treatment of patients with few metastatic brain lesions. However, the optimal treatment approach for the use radiotherapy in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) remain unclear. This study aimed to compare the survival outcomes and intracranial local control in NSCLC patients with 1-4 BMs who are treated with SRS using linear accelerators (LINAC-SRS), whole-brain radiotherapy (WBRT), or WBRT plus radiotherapy boost (WBRT RTB). We retrospectively analyzed 156 NSCLC patients with 1-4 BMs who received LINAC-SRS, WBRT, and WBRT RTB. The median overall survival (OS), intracranial progression-free survival (iPFS), and distant brain failure-free survival (DBF-FS) and related prognostic factors were analyzed. The median follow-up period was 31.6 months. The median OS times in the LINAC-SRS, WBRT, and WBRT RTB groups were not reached, 33.3 months and 27.9 months, respectively. The difference in survival rate was non-significant (P 0.909). The 2-year iPFS and DBF-FS rates in the LINAC-SRS, WBRT and WBRT RTB groups were 51.6% and 37.5% 42.0% and 50.4% and 51.1% and 56.1%, respectively. There was no significant difference in 2-year iPFS or DBF-FS among the three groups (P 0.572 for iPFS, P 0.628 for DBF-FS). Multivariate analysis showed that the independent adverse prognostic factors for OS, iPFS, and DBF-FS were neurological symptoms, recursive partitioning analysis (RPA) class, and targeted therapy. LINAC-SRS did not result in significantly superior survival times or intracranial local control compared to WBRT or WBRT RTB in the treatment of NSCLC patients with 1-4 BMs.