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Activity-Based Self-Enriched SERS Sensor for Blood Metabolite Monitoring.

The monitoring of metabolites in biofluids provides critical clues for disease diagnosis and evaluation. Yet, the quantitative detection of metabolites remains challenging for surface-enhanced Raman spectroscopy (SERS) due to poor reproducibility in preparation and manipulation of SERS nanoprobes. Herein, we develop an activity-based, slippery liquid-infused porous surface SERS (abSLIPSERS) sensor for facile quantification of metabolites with unmodified naked metal nanoparticles (NPs) by integrating biocatalysis-boronate oxidation cascades with SLIPS-driven self-concentration and delivering. Upon mixing the target metabolite with a specific oxidase, a H

Neoadjuvant alectinib in locally advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement case series and literature review.

In view of the success of targeted therapy in the field of advanced lung cancer, it is gradually pushed further to neoadjuvant therapy. Alectinib has been recommended for advanced anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) in first-line therapy. Here, we report two cases of neoadjuvant alectinib in locally advanced lung adenocarcinoma with ALK rearrangement. Case 1 was a 64-year-old man with no history of smoking who was diagnosed with the clinical stage as IIIB, with ALK fusion-positive. Chest-enhanced computed tomography (CT) revealed marked regression and achieved partial response (PR) incorporated with grade 3 interstitial pneumonia after 44 days of alectinib neoadjuvant therapy. Interstitial pneumonia improved after methylprednisolone therapy, then thoracoscopic lobe resection with lymph node dissection was performed with blood loss. The pathological assessment was a pathologic complete response(pCR). Case 2 was a 66-year-old man who had a routine physical examination and then diagnosed with a clinical-stage IIIB by CT-guided percutaneous cutting needle biopsy (PCNB). Chemotherapy with 1 cycle of pemetrexed combined with nedaplatin was performed in the interval waiting for next-generation sequencing (NGS) results. NGS testing revealed an EML4-ALK fusion mutation. After 109 days of alectinib treatment, radiographic evaluation was classified as PR and then he underwent thoracoscopic upper lobectomy smoothly with pathological assessment as a major pathological response (MPR). To date, neoadjuvant alectinib has only been reported in a few cases in locally advanced lung adenocarcinoma with ALK-rearranged. Neoadjuvant alectinib may be feasible in locally advanced disease for complete resection. The duration and safety of neoadjuvant therapy with alectinib still need further study.

Risk prediction models for endometrial cancer development and validation in an international consortium.

Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. We developed endometrial cancer risk prediction models using data on postmenopausal white women aged 45-85 years from 19 case-control studies in the Epidemiology of Endometrial Cancer Consortium. Relative risk estimates for predictors were combined with age-specific endometrial cancer incidence rates and estimates for the underlying risk factor distribution. We externally validated the models in three cohorts Nurses Health Study (NHS), Nurses Health Study II (NHS II) and the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Area under the receiver operating characteristic curves for the epidemiologic model ranged from 0.64 (95% CI 0.62, 0.67) to 0.69 (95% CI 0.66, 0.72). Improvements in discrimination from the addition of genetic factors were modest (no change in AUC in NHS, PLCO 0.64 to 0.66). The epidemiologic model was well calibrated in NHS II (overall EO 1.09 95% CI 0.98, 1.22) and PLCO (overall EO 1.04 95% CI 0.95, 1.13) but poorly calibrated in NHS (overall EO 0.55 95% CI 0.51, 0.59). Using data from the largest, most heterogeneous study population to date, prediction models based on epidemiologic factors alone successfully identified women at high risk of endometrial cancer. Genetic factors offered limited improvements in discrimination. Further work is needed to refine this tool for clinical or public health practice and expand these models to multiethnic populations.

Efficacy and Safety of East Asian Herbal Medicine for Brain Metastases in Non-small Cell Lung Cancer A Systematic Review and Meta-analysis Protocol to Identify Specific Herbs.

Brain metastasis (BM) is a significant risk factor for survival and prognosis in non-small cell lung cancer (NSCLC). While surgical resection and radiotherapy are the primary treatment modalities, the overall prognosis in NSCLC patients with BM remains poor, and all therapies lead to adverse events. East Asian herbal medicine (EAHM) has broad prospects as an adjuvant treatment, but its efficacy and safety remain controversial. We propose to conduct a systematic review and meta-analysis to summarize the clinical efficacy and safety of EAHM for the treatment of NSCLC with BMs and to identify specific herbs that can improve the prognosis. The PubMed, EMBASE, CENTRAL, Web of Science, CBM, CNKI, Wanfang, VIP, Evidence Reports on Kampo Treatment, ICHUSHI, and Oriental Medicine Advanced Searching Integrated System databases will be searched from their inception to October 2022. Randomized controlled trials will be included. Two authors will evaluate the eligibility and quality of the included trials. The methodological quality will be assessed using the RoB 2 tool, and Stata 16 will be used for data synthesis. Publication bias will be assessed using funnel plots and Egger tests. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) system will evaluate the quality of the synthesized evidence. Further sensitivity analyses will be performed to determine the efficacies of specific herbs in EAHM. Given there are currently no systematic reviews and meta-analyses of the efficacy of EAHM as a treatment for NSCLC with BMs, a compilation and analysis of the available high-quality clinical research evidence are essential. The results will help establish guidelines for the application of specific herbs as a complementary alternative therapy for BMs in NSCLC. The findings will be published in a peer-reviewed journal. CRD42022300527.

Metabolic and Metabolomic Effects of Metformin in Murine Model of Pulmonary Adenoma Formation.

Epidemiologic studies of diabetic patients treated with metformin identified significantly lower incidences of cancer. From this, there is growing interest in the use of metformin to treat and prevent cancer. Studies have investigated chemopreventive mechanisms including alterations in calorie intake, cancer metabolism, and cell signaling. Repurposing the drug is challenging due to its metabolic effects and non-uniform effects on different types of cancer. In our previously published studies, we observed that benzoapyrene treated mice receiving metformin significantly reduced lung adenomas however, mice had reduced weight gain. In this study, we compared chemoprevention diets with and without metformin to evaluate the effects of diet vs. effects of metformin. We also performed tandem mass spectrometry on mouse serum to assess metabolomic alterations associated with metformin treatment. In metformin cohorts, the rate of weight gain was reduced, but weights did not vary between diets. There was no weight difference between diets without metformin. Interestingly, caloric intake was increased in metformin treated mice. Metabolomic analysis revealed metabolite alterations consistent with metformin treatment. Based on these results, we conclude that previous reductions in lung adenomas may have been occurred from anticancer effects of metformin rather than a potentially toxic effect such as calorie restriction.

Identification of Key Biomarkers and Candidate Molecules in Non-Small-Cell Lung Cancer by Integrated Bioinformatics Analysis.

Non-small cell lung cancer (NSCLC) is the most prevalent malignant tumor of the lung cancer, for which the molecular mechanisms remain unknown. In this study, we identified novel biomarkers associated with the pathogenesis of NSCLC aiming to provide new diagnostic and therapeutic approaches for NSCLC by bioinformatics analysis. From the Gene Expression Omnibus database, GSE118370 and GSE10072 microarray datasets were obtained. Identifying the differentially expressed genes (DEGs) between lung adenocarcinoma and normal samples was done. By using bioinformatics tools, a protein-protein interaction (PPI) network was constructed, modules were analyzed, and enrichment analyses were performed. The expression and prognostic values of 14 hub genes were validated by the GEPIA database, and the correlation between hub genes and survival in lung adenocarcinoma was assessed by UALCAN, We found three genes (PIK3R1, SPP1, and PECAM1) that have a clear correlation with OS in the lung adenocarcinoma patient. It has been found that lung adenocarcinoma exhibits high expression of SPP1 and that this has been associated with poor prognosis, while low expression of PECAM1 and PIK3R1 is associated with poor prognosis ( The results indicated that SPP1 is a cancer promoter (oncogene), while PECAM1 and PIK3R1 are cancer suppressor genes. These genes take part in the regulation of biological activities in lung adenocarcinoma, which provides a basis for improving detection and immunotherapeutic targets for lung adenocarcinoma.

Assessing Potential Factors Influencing the Efficacy of Immune Checkpoint Inhibitors with Radiation in Advanced Non-Small-Cell Lung Cancer Patients A Systematic Review and Meta-Analysis.

Recent evidence suggests that combining radiotherapy (RT) with immune checkpoint inhibitors (ICIs) may result in better outcomes. In this study, we assessed the efficacy and safety of ICI plus radiation versus ICI alone and explored potential factors affecting its efficacy in advanced non-small-cell lung cancer (NSCLC) patients. The databases including PubMed and Embase were searched to retrieve eligible studies comparing the efficacy and safety outcomes in advanced NSCLC patients after ICIs ± RT treatments. We performed subgroup analyses to identify potential prognostic factors from radiation details and study types. The odds ratio (OR) of objective response rate (ORR) and disease control rate (DCR), hazard ratio (HR) of progression-free survival (PFS) and overall survival (OS), and risk ratio (RR) of adverse events were used to represent the outcome effects. 26 eligible studies with 14192 cases were included. The results showed that the ORR (OR 0.63, 95% CI 0.42, 0.93 RT plus ICIs is associated with improved survival for advanced NSCLC patients, especially for those with non-palliative RT. Further clinical trials are needed to validate its effect on survival outcomes.

Early impairment of food intake in patients newly diagnosed with cancer.

Patients with gastrointestinal or lung cancer often suffer from a loss of appetite (anorexia), resulting in reduced food intake (hypophagia) and body weight loss. This study evaluated the prevalence of anorexia, hypophagia, pre-cachexia and cachexia in patients with cancer at time of diagnosis. Patients with newly diagnosed gastrointestinal or lung cancers were included. Body mass index (BMI) and weight loss over the prior 6 months were recorded. Patients were assessed for (pre-)cachexia and for anorexia using the Functional Assessment of AnorexiaCachexia Therapy (FAACT) and a specific anorexia questionnaire (AQ). Energy and protein intake were calculated through food diaries. Patients were considered hypophagic if intake was ≤70% of guideline-recommended levels. Overall, 102 patients 53 male median age 67 (range, 21-88) years were enrolled. Mean BMI (± standard deviation) was 23.1 ± 3.4 kgm Anorexia, inadequate nutritional intake and cachexia are highly prevalent in patients with gastrointestinal or lung cancer at diagnosis. Negative protein and energy balance may play an important role in the pathogenesis of cachexia. Early multimodal strategies to improve food intake are urgently needed.

Immune Checkpoint Inhibitors in Patients With Cancer and Infection by Hepatitis B or C Virus A Perspective Through the Results of a European Survey.

Patients with cancer and hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are underrepresented in several clinical trials testing immune checkpoint inhibitors (ICIs). Consequently, safety and efficacy of ICI therapy in this population have not been completely defined. We aimed to evaluate the attitudes of oncologists on this topic. We conducted a 14-item European anonymous online survey. Physicians from 56 oncology departments (26 from Italy, 15 from France, and 15 from Spain) took part in the survey. They mainly used to prescribe ICIs for treating patients with lung cancer, melanoma, and renal cell carcinoma. Of them, 95% recognized the need for specific guidelines addressing the management of patients with cancer and HBV or HCV treated with ICIs. Just 63% of the respondents screened patients for HBV and HCV status before ICIs initiation, although the risk of immune-related hepatotoxicity or viral reactivation was a major concern for most of them. Only 9% of the surveyed oncologists considered HBV and HCV infection a major exclusion criterion for receiving ICIs. Furthermore, 29% of the respondents would start a prophylactic treatment of active infection at ICIs initiation. ICIs administration in patients with cancer and HBV or HCV infection is of concern for most of the surveyed European oncologists. Nonetheless, active screening and treatment of viral hepatitis should be improved. Data in this specific setting are needed for an evidence-based management and should be generated by broadening inclusion criteria of clinical trials to allow the enrollment of patients with HBV and HCV.

Association of cardiac calcium burden with overall survival after radiotherapy for non-small cell lung cancer.

Coronary calcifications are associated with coronary artery disease in patients undergoing radiotherapy (RT) for non-small cell lung cancer (NSCLC). We quantified calcifications in the coronary arteries and aorta and investigated their relationship with overall survival (OS) in patients treated with definitive RT (Def-RT) or post-operative RT (PORT). We analyzed 263 NSCLC patients treated from 2004 to 2017. Calcium burden was ascertained with a Hounsfield unit (HU) cutoff of > 130 in addition to a deep learning (DL) plaque estimator. The HU cutoff volumes were defined for coronary arteries (Plaque The median Plaque Coronary artery calcification assessed from RT planning CT scans was significantly associated with OS in patients who underwent Def-RT for NSCLC. This HU thresholding method can be straightforwardly implemented such that the role of calcifications can be further explored.

The Choice of Healthy Source of Energy for Cooking Among Households in Ghana Does Financial Inclusion Matter

Air pollution resulting from the use of unhealthyunclean energy sources for cooking causes illnesses such as lung cancer, stroke, chronic obstructive pulmonary disease and ischaemic heart disease. In Ghana, each year, about 18 000 deaths are recorded due to the use of unhealthy energy sources for cooking. While financial inclusion can influence the adoption of healthy energy sources for cooking, less attention has been paid to it. This study, therefore, investigates the effect of financial inclusion on the choice of healthy source of energy for cooking among households in Ghana. Doing so reveals whether financial inclusion can be employed as a tool to decrease the use of unhealthy sources of energy for cooking in Ghana. We employ the Ghana Living Standards Survey round 7 (GLSS7) as the data source for the study whiles the binary logistic regression is used as the estimation technique. The findings show that, households with financial inclusion (using a single indicator) are more likely to choose healthy sources of energy for cooking relative to those without financial inclusion (OR 2.52,

Effect of Smoking on Lung Function Decline in a Retrospective Study of a Health Examination Population in Chinese Males.

China has established a goal of reducing adult smoking prevalence from 27.7% to 20% by 2030. Understanding the possible ongoing impairment in lung function in smokers, is critically important to encourage the populations to change their smoking behavior. A total of 14,273 males joined the health examination at Huadong Sanatorium from Jan 2012 to Dec 2019 were included. In cross-sectional analysis, we used multiple linear regression to evaluate the association between baseline lung function and smoking status. Then, 3,558 males who received ≥2 spirometry exams were analyzed in longitudinal study. Annual lung function decline was compared using mixed linear models adjusted for confounders. In cross-sectional analysis, compared with never-smokers, decreases of -133.56 mL (95% CI -167.27, -99.85) and -51.44 mL (-69.62, -33.26) in FEV The harms of current smoking on lung function emphasize the necessity of smoking cessation, especially for those with comorbidities.

Clinical imaging of primary pulmonary nucleoprotein of the testis carcinoma.

Primary pulmonary nucleoprotein of the testis (NUT) carcinoma is very rare in the clinic. In this study, the clinicopathological manifestations and imaging features of the primary pulmonary NUT carcinoma were investigated to improve the diagnosis of this disease. Six patients with pathologically diagnosed pulmonary NUT carcinoma were analyzed, including three males and three females, aged 19-64 (49.00 ± 16.40) years, with clinical manifestations of cough in two cases, hoarseness in one case, blood in sputum in one case, chest pain in one case, and physical examination findings in one case, with a disease duration of 5 days to 4 months. The clinical and imaging data including CT and PETCT were retrospectively analyzed. Further literature reviews were analyzed in both pulmonary and extrapulmonary NUT carcinoma cases who performed Most of the patients with pulmonary NUT carcinomas presented as heterogeneous lobulated masses (83.33%), four cases (66.67%) were located in the upper lobe of the left lung, one case (16.67%) in the middle lobe of the right lung, and one case (16.67%) in the lower lobe of the right lung, with the maximum diameter ranging from 1.30 to 8.90 cm and the median of 3.55 cm, most of them were irregularly shaped, with more lobulated margins and more heterogeneous density (83.33%), and the enhancement was mild. PETCT showed increased In patients with central lung masses, rapid disease progression, and poor response to initial treatment, the possibility of NUT cancer should be considered and anti-NUT monoclonal antibody immunohistochemical staining, combined with genetic detection, if necessary, should be performed as soon as possible. CT and PETCT imaging are essential for the staging, management, treatment response assessment, and monitoring of pulmonary NUT cancer.

Operative versus Nonoperative Treatment in Patients with Advanced Non-Small-Cell Lung Cancer Recommended for Surgery.

There is currently limited evidence for a correlation between the recommended operation and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC). NSCLC patients with stages III and IV, recommended for operation, were identified in the US National Cancer Institute Surveillance, Epidemiology, and End Results database (SEER).We used propensity score matching (PSM) and multivariable Cox proportional hazards regression to ensure the robustness of our findings. The cumulative rates of death were compared between patients with and without recommended operations using the Kaplan-Meier curves. Operation was recommended for 3331 patients but was not performed in 912 (27.4%) patients (then on-operative group). After PSM, 553 pairs matched. Compared to the nonoperative group, the hazard ratios (HRs) in the operative group were 0.46 (95% CI 0.23-0.95 and Compared to the nonoperative group, recommended operation improved survival in NSCLC patients with stage IIIA-N0, stage IIIA-N1, stage IVA-N0, and stage IVA-N2. However, in stages IIIA-N2, IIIB, IIIC, IVA-N1, IVA-N3, and IVB, recommended operation did not lead to significantly improved survival time.

Role of Salvage Surgery in Gestational Trophoblastic Neoplasia a Regional Cancer Centre Experience.

Gestational trophoblastic neoplasia (GTN) is a curable cancer with chemotherapy. However, some develop chemoresistance to standard chemotherapy and surgery can be a useful option in them. Our study aimed to assess the role of salvage surgery in GTN with chemoresistance. It is a retrospective hospital-based study from 2000 to 2021. Case sheets of women who underwent salvage surgery for chemoresistance were reviewed and clinical parameters like preoperative hCG, antecedent pregnancy, WHO risk score, multiple chemotherapy regimens prior surgery, presence of > 1 disease site, and presence of residual choriocarcinoma that predicted the effect of surgery on serological response were assessed using Fishers exact test. A total of 19 patients with high-risk GTN developed chemoresistance and underwent salvage surgery. Eight underwent hysterectomy, 3 underwent hysterectomy plus adnexal tumour resection, six received fertility-sparing surgery, and two underwent segmental resection of the lung. Histopathological examination revealed viable tumour in 719 patients, but significant fall in median hCG level from 161.5 mIUml (preoperatively) to 15.5 mIUml (postoperatively) was noted. Preoperative hCG < 100 mIUml (

Malignant transformation of pulmonary bronchiolar adenoma into mucinous adenocarcinoma A case report.

Bronchiolar adenoma (BA) and ciliated muconodular papillary tumor are rare tumors that have bilayered cell proliferation and continuous expression of p40 and CK56 in the basal cell layer. Diagnosis is difficult because of the limited knowledge of these tumors and their morphological similarities to malignant tumors, including invasive mucinous adenocarcinoma, especially based on the histopathology of intraoperative frozen sections. These tumors are now considered to be benign neoplasms, with malignant transformation reported in only a few cases. A 57-year-old woman presented with a 17.0 mm × 7.0 mm nodule in the lower lobe of the left lung. Hematoxylin-eosin staining and immunohistochemistry of a surgical specimen were performed. The tumor consisted of a BA area and a mucinous adenocarcinoma (MA) area. In the BA area, the tumor had a bilayered structure of luminal cells and basal cells. The basal cells were positive for CK56 and p40, but the MA area was negative for these biomarkers. The Ki-67 proliferation index was low (1%-2%). The patient was diagnosed with BA accompanied by MA, and had a favorable outcome. The present study indicated that BA may be carcinogenic, and suggests that clinicians should be aware of its potential for malignant transformation.

Structure Elucidation of 16 Undescribed Steroidal Glycosides from the Underground Parts of

To explore new candidates for anticancer agents from natural products, the underground parts of

Lung cancer patients are at risk for brain metastases and often succumb to their intracranial disease. Chimeric Antigen Receptor (CAR) T-cells emerged as a powerful cell-based immunotherapy for hematological malignancies however, it remains unclear whether CAR T-cells represent a viable therapy for brain metastases. Here, we established a syngeneic orthotopic cerebral metastasis model in mice by combining a chronic cranial window with repetitive intracerebral two-photon laser scanning-microscopy. This approach enabled

Is Periodontitis a Risk Factor for Lung Cancer A Meta-Analysis and Detailed Review of Mechanisms of Association.

Numerous studies have explored the correlation of periodontal disease (PD) with the risk of lung cancers, but the findings were inconsistent. Therefore, we did a meta-analysis to ascertain the correlation of PD with the risk of incident lung cancer. The authors searched relevant studies in databases (PubMed, Web of Science, Scopus, Embase, and MEDLINE) till November 2020. We registered the study at the International database of Prospectively Registered Systemic Reviews under the CRD42020198119. The summary relative risk (RR) along with a 95% confidence interval (CI) was calculated using fixed-effects models. Twelve studies were included in the qualitative synthesis. The pooled analysis revealed that PD was significantly associated with an increased risk of lung cancer (RR 1.71 95%CI 1.61-1.81 From this current evidence, PD is a potential risk factor for the development of lung cancer. The risk for incidence of lung cancer is surged twice in the patients with PD, even though age and smoking are controlled in the studies.

Influencing factors of LDCT recommendation by physicians in Sichuan Province, China.

The study aimed to investigate the influencing factors of physicians in recommending low-dose computed tomography (LDCT) for lung cancer screening to high-risk groups. A total of 1767 participants with good knowledge of LDCT were included in a cross-sectional study. Data about physicians demographics, perception of barriers on LDCT screening, medical conditions for practicing medicine and the behavior of recommending LDCT were collected by a questionnaire. Physicians who care about the transportation convenience of patients were less likely to recommend LDCT (OR 0.568, 95% CI (0.423 to 0.763),

Case Report Pituitary metastasis as a presenting manifestation of silent gastric cardia adenocarcinoma.

Pituitary metastases are very rare in cancer patients and often originate from lung or breast tumors. They usually occur in patients with known metastatic disease, but rarely may be the first presentation of the primary tumor. We present the case of a 58 years-old-man who reported a three-month history of polyuria-polydipsia syndrome, generalized asthenia, panhypopituitarism and bitemporal hemianopsia. Brain-MRI showed a voluminous pituitary mass causing posterior sellar enlargement and compression of the surrounding structures including pituitary stalk, optic chiasm, and optic nerves. The patient underwent neurosurgical removal of the mass. Histological examination revealed a poorly differentiated adenocarcinoma of uncertain origin. A total body CT scan showed a mass in the left kidney that was subsequently removed. Histological features were consistent with a clear cell carcinoma. However, endoscopic examination of the digestive tract revealed an ulcerating and infiltrating adenocarcinoma of the gastric cardia. Total body PETCT scan with 18F-FDG confirmed an isolated area of accumulation in the gastric cardia, with no hyperaccumulation at other sites. To the best of our knowledge, there are no reports of pituitary metastases from gastric cardia adenocarcinoma. Our patient presented with symptoms of sellar involvement and without evidence of other body metastases. Therefore, sudden onset of diabetes insipidus and visual deterioration should lead to the suspicion of a rapidly growing pituitary mass, which may be the presenting manifestation of a primary extracranial adenocarcinoma. Histological investigation of the pituitary mass can guide the diagnostic workup, which must however be complete.

Correlation between lung cancer probability and number of pulmonary nodules in baseline computed tomography lung cancer screening A retrospective study based on the Chinese population.

Screening for lung cancer with LDCT detects a large number of nodules. However, it is unclear whether nodule number influences lung cancer probability. This study aimed to acquire deeply insight into the distribution characteristics of nodule number in the Chinese population and to reveal the association between the nodule number and the probability of lung cancer (LC). 10,167 asymptomatic participants who underwent LDCT LC screening were collected. Noncalcified nodules larger than 4 mm were included. The nodule number per participant was determined. We defined five categories according to the number of nodules (based on nodule type and size) one, two, three, four, and more than four nodules. We stratified the nodules as groups A, B, and C and participants as Amax, Bmax, and Cmax groups, and explored the association between nodule number and the probability of LC on nodule and participant levels. 97 participants were confirmed to have LC. The probabilities of LC were 491719, 22689, 11327, 6166, and 9175 in participants with one, two, three, four, and more than four nodules (p>0.05), respectively. In the Bmax group, the probability of LC was significantly higher in participants with one nodule than those with >4 nodules (p<0.05), and the probability of LC showed a negative linear trend with increasing nodule numbers (p<0.05). Based on the nodule-level analyses, in Group B, LC probability was significantly higher when participants had a solitary nodule than when they had >4 nodules (p<0.05). LC probability does not significantly change with the number of nodules. However, when stratified by the nodule size, the effect of nodule number on LC probability was nodule-size dependent, and greater attention and active follow-up are required for solitary nodules especially SNssolid component of PSNs measuring 6-15 mm or NSNs measuring 8-15 mm. Assessing the nodule number in conjunction with nodule size in baseline LDCT LC screening is considered beneficial.

NcRNA-regulated CAPZA1 associated with prognostic and immunological effects across lung adenocarcinoma.

Recent discoveries have suggested that the F-actin capping protein α1 subunit (CAPZA1) in various human tumors could play a significantly important role in regulating cell proliferation, metastasis, and epithelial-mesenchymal transition. However, the immune-regulating role of CAPZA1 in the initiation and development of lung adenocarcinoma (LUAD) remains unclear. In our research, we first found that CAPZA1 serves as an oncogene in pan-cancers from the TCGA data and higher CAPZA1 expression process unfavorably prognostic value in LUAD based on starBase database, PrognoScan, and LOGpc database. Then, in our analyses, lncRNAs AC026356.1 in LUAD acted as a competitive endogenous RNA (ceRNA) of miR-30d-5p, which might be the possible regulatory miRNA of CAPZA1 based on the starBase database. Finally, we confirmed that CAPZA1 expression had a tightly positive correlation with immune infiltration cells, immune infiltration markers, TMB, MSI, immune score, stromal score, and immune checkpoints, indicating that CAPZA1 was a markedly reliable therapeutic target for immunological antitumor strategies. In conclusion, our investigations revealed that CAPZA1 might function as an immune-associated biomarker in the development and treatment of LUAD, thereby acting as a promising prognostic and therapeutic target against LUAD.

Investigation of the prevalence and clinical implications of

Although rare, We retrospectively screened 40996 patients, spanning 19 cancer types, who had available genomic profiles acquired with DNA-based next-generation sequencing (NGS). We characterized the clinical and molecular features of the A total of 22 patients were detected with Our study identified an overall

Crosstalk between protein kinases AKT and ERK12 in human lung tumor-derived cell models.

There is no doubt that cell signaling manipulation is a key strategy for anticancer therapy. Furthermore, cell state determines drug response. Thus, establishing the relationship between cell state and therapeutic sensitivity is essential for the development of cancer therapies. In the era of personalized medicine, the use of patient-derived ex vivo cell models is a promising approach in the translation of key research findings into clinics. Here, we were focused on the non-oncogene dependencies of cell resistance to anticancer treatments. Signaling-related mechanisms of response to inhibitors of MEKERK and PI3KAKT pathways (regulators of key cellular functions) were investigated using a panel of patients lung tumor-derived cell lines with various stemness- and EMT-related markers, varying degrees of ERK12 and AKT phosphorylation, and response to anticancer treatment. The study of interactions between kinases was the goal of our research. Although MEKERK and PI3KAKT interactions are thought to be cell line-specific, where oncogenic mutations have a decisive role, we demonstrated negative feedback loops between MEKERK and PI3KAKT signaling pathways in all cell lines studied, regardless of genotype and phenotype differences. Our work showed that various and distinct inhibitors of ERK signaling - selumetinib, trametinib, and SCH772984 - increased AKT phosphorylation, and conversely, inhibitors of AKT - capivasertib, idelalisib, and AKT inhibitor VIII - increased ERK phosphorylation in both control and cisplatin-treated cells. Interaction between kinases, however, was dependent on cellular state. The feedback between ERK and AKT was attenuated by the focal adhesion kinase inhibitor PF573228, and in cells grown in suspension, showing the possible role of extracellular contacts in the regulation of crosstalk between kinases. Moreover, studies have shown that the interplay between MEKERK and PI3KAKT signaling pathways may be dependent on the strength of the chemotherapeutic stimulus. The study highlights the importance of spatial location of the cells and the strength of the treatment during anticancer therapy.

Upregulation of complement proteins in lung cancer cells mediates tumor progression.

Studies used four murine cell lines implanted into the lungs of syngeneic mice. Cancer cells were recovered using FACS, and transcriptional changes compared to cells grown in culture were determined by RNA-seq. Changes in interferon response, antigen presentation and cytokine signaling were observed in all tumors. In addition, we observed induction of the complement pathway. We previously demonstrated that activation of complement is critical for tumor progression in this model. Complement can play both a pro-tumorigenic role through production of anaphylatoxins, and an anti-tumorigenic role by promoting complement-mediated cell killing of cancer cells. While complement proteins are produced by the liver, expression of complement proteins by cancer cells has been described. Silencing cancer cell-specific C3 inhibited tumor growth Based on these data we propose that localized induction of complement in cancer cells is a common feature of lung tumors that promotes tumor progression, with induction of complement regulatory proteins protecting cells from complement mediated-cell killing.

Inhibition of RNF182 mediated by Bap promotes non-small cell lung cancer progression.

Ubiquitylation that mediated by ubiquitin ligases plays multiple roles not only in proteasome-mediated protein degradation but also in various cellular process including DNA repair, signal transduction and endocytosis. RING finger (RNF) proteins form the majority of these ubiquitin ligases. Recent studies have demonstrated the important roles of RNF finger proteins in tumorigenesis and tumor progression. Benzoapyrene (BaP) is one of the most common environmental carcinogens causing lung cancer. The molecular mechanism of Bap carcinogenesis remains elusive. Considering the critical roles of RNF proteins in tumorigenesis and tumor progression, we speculate on whether Bap regulates RNF proteins resulting in carcinogenesis. We used GEO analysis to identify the potential RING finger protein family member that contributes to Bap-induced NSCLC. We next used RT-qPCR, Western blot and ChIP assay to investigate the potential mechanism of Bap inhibits RNF182. BGS analyses were used to analyze the methylation level of RNF182. Here we reported that the carcinogen Bap suppresses the expression of ring finger protein 182 (RNF182) in non-small cell lung cancer (NSCLC) cells, which is mediated by abnormal hypermethylation in an AhR independent way and transcriptional regulation in an AhR dependent way. Furthermore, RNF182 exhibits low expression and hypermethylation in tumor tissues. RNF182 also significantly suppresses cell proliferation and induces cell cycle arrest in NSCLC cell lines. These results demonstrated that Bap inhibits RNF182 expression to promote lung cancer tumorigenesis through activating AhR and promoting abnormal methylation.

Prognostic relevance of rib invasion and modification of T description for resected NSCLC patients A propensity score matching analysis of the SEER database.

The impact of rib invasion on the non-small cell lung cancer (NSCLC) T classifications remains unclear. Our study aims to verify the impact of rib invasion on survival in patients with NSCLC through multicenter data from the Surveillance, Epidemiology, and End Results (SEER) database, and proposed a more appropriate pT for the forthcoming 9 The SEER database was used to collect T Survival outcomes of the rib invasion group were worse than the other pT3 group (OS 40.5% The rib invasion group had a worse prognosis than the other pT3 groups, but was similar to the pT4 group. Our recommendation is to change the classification of rib invasion to pT4 disease and further validate this in the forthcoming 9

The function of natural compounds in important anticancer mechanisms.

The existence of malignant tumors has been a threat to human life, health, and safety. Although the rapid development of radiotherapy, drug therapy, surgery, and local therapy has improved the quality of life of tumor patients, there are still some risks. Natural compounds are widely used in cancer because they are easy to obtain, have a good curative effects and have no obvious side effects, and play a vital role in the prevention and treatment of various cancers. Phenolic, flavonoids, terpenoids, alkaloids, and other natural components of traditional Chinese medicine have certain anti-tumor activities, which can promote apoptosis, anti-proliferation, anti-metastasis, inhibit angiogenesis, change the morphology of cancer cells and regulate immune function, etc., and have positive effects on breast cancer, liver cancer, lung cancer, gastric cancer, rectal cancer and so on. To better understand the effects of natural compounds on cancer, this paper screened out four important pathways closely related to cancer, including cell death and immunogenic cell death, immune cells in the tumor microenvironment, inflammation and related pathways and tumor metastasis, and systematically elaborated the effects of natural compounds on cancer.

Targeted ferroptotic potency of ferrous oxide nanoparticles-diethyldithiocarbamate nanocomplex on the metastatic liver cancer.

Existing treatments are frequently ineffective in combating liver cancer (LC) due to its rapid growth, high metastatic potential, and chemoresistance. Thus, inducing ferroptosis, a new non-apoptotic regulated cell death-dependent massive iron overload-mediated lipid peroxidation, is an alternative effective approach for treating LC. The efficient trigger of ferroptosis requires blocking cellular antioxidant (anti-ferroptosis) response and selectivity to avoid harming other healthy tissues. In this study, green chemically synthesized ferrous oxide nanoparticles (F(II) NPs) were used for enhancing selective iron accumulation in tumor tissue, while diethyldithiocarbamate (DE) was for inhibiting the antioxidant system (glutathione and aldehyde dehydrogenase (ALDH) 2) which protects the tumor from damage-dependent lipid peroxides. Thus, F(II) NPs were used with DE as nanocomplex (DF(II) NPs) and its anti-LC activity compared to ferrous oxide DF(II). DF(II) NPs outperformed the typical complex of DF(II) in eradicating metastatic LC cells in HepG2 cells and a chemically induced metastatic LC animal model, as evidenced by flow cytometry, histological and immunohistochemical analyses, and α-fetoprotein depletion. The superior therapeutic potency-dependent ferroptotic activity of DF(II) NPs, attributed to their higher selective accumulation (∼77%) than DF(II) in tumor tissues (liver and lung), resulted in a strong elevation of cellular lipid peroxidation with extreme suppression of nuclear related factor 2 (Nrf2) transcriptional activity, glutathione (GSH), glutathione peroxidase 4, and ALDH2. Subsequently, a severe inhibition in the expression of oncogenes and metastatic cancer stem cell genes was recorded in DF(II) NPs-treated LC animal group. In contrast to DF(II), DF(II) NPs were able to normalize liver functions and did not show any variations in hematological and histological parameters in the blood and tissues of DF(II) NPs-treated normal mouse group. These findings validate the potency and safety of DF(II) nanocomplex as a promising nanodrug for combating metastatic LC.

A novel nomogram and prognostic factor for metastatic renal cell carcinoma survival in the era of immune checkpoint inhibitors (ICIs).

Patients with metastatic renal cell cancer (mRCC) for whom surgery is ineffective may experience a poor prognosis. The different sites where cancer has spread, and the different ways to treat it in the immune checkpoint inhibitors era could help clinical decision-making. In this study, individuals with mRCC were selected from the SEER database between 2015 and 2016 based on the Food and Drug Administration (FDA) approval of ICIs. A total of 4011 mRCC patients were studied (2239 with lung metastasis vs. 797 with liver metastasis in the immune checkpoint inhibitors period). The age

Institutional experience of using active breathing control for paediatric and teenage patients receiving thoraco-abdominal radiotherapy.

Active Breathing Control (ABC) is a motion management strategy that facilitates reproducible breath-hold for thoracic radiotherapy (RT), which may reduce radiation dose to organs at risk (OARs). Reduction of radiation-induced toxicity is of high importance in younger patients. However, there is little published literature on the feasibility of ABC in this group. The purpose of this study was to report our experience of using ABC for paediatric and teenage patients. Patients ≤18 years referred for thoracic RT using ABC at our centre from 2013-2021 were identified. Electronic records were retrospectively reviewed to obtain information on diagnosis, RT dose and technique, OAR dosimetry, tolerability of ABC, post-treatment imaging and early toxicity rates. 12 patients completed RT and were able to comply with ABC during planning and for the duration of RT. Median age was 15.5 years (10-18 years). Diagnoses were Hodgkin lymphoma (n 5), mediastinal B-cell lymphoma (n 1), Ewing sarcoma (n 5) and rhabdomyosarcoma (n 1). For mediastinal RT cases (n 6), median dose delivered was 30.6Gy(19.8-40Gy), median mean heart dose was 11.4Gy(4.8-19.4Gy), median mean lung dose was 9.9Gy(5.7-14.5Gy) and mean lung V20 was 10.9%. For ipsilateral RT cases, (n 6), median hemithorax and total doses to primary tumour were 18Gy(15-20Gy) and 52.2Gy(36-60Gy) respectively. Median mean heart dose was 19.5Gy(10.6-33.2Gy) and median mean lung dose was 17.7Gy(16.3-30.5Gy). Mean bilateral lung V20 was 39.6%. Median mean contralateral lung dose was 5.2Gy(3.5-11.6Gy) and mean contralateral lung V20 was 1.5%. At a median follow-up of 36 months, only 1 patient had symptomatic radiation pneumonitis having received further thoracic RT following relapse. ABC is feasible and well tolerated in younger patients receiving RT. Children as young as 10 years are able to comply. Use of ABC results in OAR dosimetry which is comparable to similar data in adults and can facilitate RT for extensive thoracic sarcoma.

A clinical prediction model for predicting the risk of liver metastasis from renal cell carcinoma based on machine learning.

Renal cell carcinoma (RCC) is a highly metastatic urological cancer. RCC with liver metastasis (LM) carries a dismal prognosis. The objective of this study is to develop a machine learning (ML) model that predicts the risk of RCC with LM, which is used to assist clinical treatment. The retrospective study data of 42,547 patients with RCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. ML includes algorithmic methods and is a fast-rising field that has been widely used in the biomedical field. Logistic regression (LR), Gradient Boosting Machine (GBM), Extreme Gradient Boosting (XGB), random forest (RF), decision tree (DT), and naive Bayesian model Naive Bayes Classifier (NBC) were applied to develop prediction models to predict the risk of RCC with LM. The six models were 10-fold cross-validated, and the best-performing model was selected based on the area under the curve (AUC) value. A web online calculator was constructed based on the best ML model. Bone metastasis, lung metastasis, grade, T stage, N stage, and tumor size were independent risk factors for the development of RCC with LM by multivariate regression analysis. In addition, the correlation of the relative proportions of the six clinical variables was shown by a heat map. In the prediction models of RCC with LM, the mean AUC of the XGB model among the six ML algorithms was 0.947. Based on the XGB model, the web calculator (httpsshare.streamlit.ioliuwencai4renallivermainrenalliver.py) was developed to evaluate the risk of RCC with LM. This XGB model has the best predictive effect on RCC with LM. The web calculator constructed based on the XGB model has great potential for clinicians to make clinical decisions and improve the prognosis of RCC patients with LM.

Gefitinib improves severe bronchorrhea and prolongs the survival of a patient with lung invasive mucinous adenocarcinoma A case report.

Lung invasive mucinous adenocarcinoma (LIMA), formerly referred to as mucinous bronchioloalveolar carcinoma, is a rare disease that usually presents as bilateral lung infiltration, is unsuitable for surgery and radiotherapy, and shows poor response to conventional chemotherapy. We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia, but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography -guided percutaneous lung biopsy. Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d. After more than 11 months of treatment, there is no evidence of recurrence or severe adverse events. Although the precise mechanism of the antitumor effects of gefitinib are not clear, our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.

Profiling of amines in biological samples using polythioester-functionalized magnetic nanoprobe.

Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment.

Relationship between the image characteristics of artificial intelligence and EGFR gene mutation in lung adenocarcinoma.

Lung Adenocarcinoma (LUAD) is a kind of Lung Cancer (LCA) with high incidence rate, which is very harmful to human body. It is hidden in the human body and is not easy to be discovered, so it brings great inconvenience to the treatment of LUAD. Artificial Intelligence (AI) technology provides technical support for the diagnosis and treatment of LUAD and has great application space in intelligent medicine. In this paper, 164 patients with primary LUAD who underwent surgery in Hospital A from January 2020 to December 2021 were selected as the study subjects, and the correlation between the imaging characteristics of LUAD and Epidermal Growth Factor Receptor (EGFR) gene mutation was analyzed. Finally, the conclusion was drawn. In terms of the study on the correlation between EGFR mutation of LUAD and the imaging characteristics of Computed Tomography (CT), it was concluded that there were significant differences between the patients sex, smoking history, pulmonary nodule morphology and the EGFR gene, and there was no significant difference between the patients tumor size and EGFR gene in the study of the relationship between EGFR gene mutation and CT signs of LUAD lesions, it was found that there were significant differences between the symptoms of cavity sign, hair prick sign and chest depression sign and EGFR gene, but there was no significant difference between the symptoms of lobulation sign and EGFR gene in the study of pathological subtype and EGFR gene mutation status of LUAD patients, it was concluded that the pathological subtype was mainly micropapillary. The mutation rate was 44.44%, which was the highest in terms of CT manifestations of adjacent structures of lung cancer and the study of EGFR gene mutation status, it was found that there was a statistical difference between the tumor with vascular convergence sign and EGFR gene mutation, and pleural effusion, pericardial effusion, pleural thickening and other signs in tumor imaging were not significantly associated with EGFR gene mutation in terms of the study of CT manifestations of adjacent structures of LCA and EGFR gene mutation status, it was concluded that pleural effusion, pericardial effusion, pleural thickening and other signs in tumor images were not significantly associated with EGFR gene mutation in terms of analysis and cure of LUAD, it was concluded that the cure rate of patients was relatively high, and only a few people died of ineffective treatment. This paper provided a reference for the field of intelligent medicine and physical health.

Transcriptome and pan-cancer system analysis identify PM2.5-induced stanniocalcin 2 as a potential prognostic and immunological biomarker for cancers.

Epidemiological studies have shown that air pollution and particulate matter (PM) are closely related to the occurrence of cancer. However, the potential prognostic and immunological biomarkers for air pollution related cancers are lacking. In this study, we proved PM2.5 exposure was correlated with lung cancer through transcriptome analysis. Importantly, we identified STC2 as a key gene regulated by PM2.5, whose expression in epithelial cells was significantly increased after PM2.5 treatment and validated by using RT-qPCR and immunofluorescence. Kaplan-Meier OS curves suggested that high STC2 expression positively correlated with a poor prognosis in lung cancer. Furthermore, we discovered that STC2 was associated with multiple cancers and pathways in cancer. Next, Pan-Cancer Expression Landscape of STC2 showed that STC2 exhibited inconsistent expression across 26 types of human cancer, lower in KIRP in cancer versus adjacent normal tissues, and significantly higher in another cancers. Cox regression results suggested that STC2 expression was positively or negatively associated with prognosis in different cancers. Moreover, STC2 expression was associated with clinical phenotypes including age, gender, stage and grade. Mutation features of STC2 were also analyzed, in which the highest alteration frequency of STC2 was presented in KIRC with amplification. Meanwhile, the effects of copy number variation (CNV) on STC2 expression were investigated across various tumor types, suggesting that STC2 expression was significantly correlated with CNV in tumors. Additionally, STC2 was closely related to tumor heterogeneity, tumor stemness and tumor immune microenvironment like immune cell infiltration. In the meantime, we analyzed methylation modifications and immunological correlation of STC2. The results demonstrated that STC2 expression positively correlated with most RNA methylation genes and immunomodulators across tumors. Taken together, the findings revealed that PM2.5-induced STC2 might be a potential prognostic and immunological biomarker for cancers related to air pollution.

Whole-genome characterization of large-cell lung carcinoma A comparative analysis based on the histological classification.

Spontaneous Complete Regression of Colon Cancer Liver Metastases in a Lung Transplant Patient A Case Report.

Cancer has become an important cause of death in solid organ transplant patients. The cause of malignancies in patients with solid organ transplants is multifactorial, but the use of intensive immunosuppression is regarded as an important factor. We describe the spontaneous, complete regression of colon cancer liver metastases, without initiation of antitumor therapy, in a solid organ transplant patient after modulation of immunosuppressants. Disinhibition and reset of the host immune response could have led to immune destruction of the liver metastases of this patients immunogenic dMMR colon carcinoma. This case underscores the huge impact that temporary relief from immunosuppressive therapy could have on tumor homeostasis. Balanced management of care for organ transplant recipients with malignancies requires a multidisciplinary approach involving medical oncologists and transplant physicians to reach the best quality of care in these complex cases.

Identification of Comorbidities, Genomic Associations, and Molecular Mechanisms for COVID-19 Using Bioinformatics Approaches.

Several studies have been done to identify comorbidities of COVID-19. In this work, we developed an analytical bioinformatics framework to reveal COVID-19 comorbidities, their genomic associations, and molecular mechanisms accomplishing transcriptomic analyses of the RNA-seq datasets provided by the Gene Expression Omnibus (GEO) database, where normal and infected tissues were evaluated. Using the framework, we identified 27 COVID-19 correlated diseases out of 7,092 collected diseases. Analyzing clinical and epidemiological research, we noticed that our identified 27 diseases are associated with COVID-19, where hypertension, diabetes, obesity, and lung cancer are observed several times in COVID-19 patients. Therefore, we selected the above four diseases and performed assorted analyses to demonstrate the association between COVID-19 and hypertension, diabetes, obesity, and lung cancer as comorbidities. We investigated genomic associations with the cross-comparative analysis and Jaccards similarity index, identifying shared differentially expressed genes (DEGs) and linking DEGs of COVID-19 and the comorbidities, in which we identified hypertension as the most associated illness. We also revealed molecular mechanisms by identifying statistically significant ten pathways and ten ontologies. Moreover, to understand cellular physiology, we did protein-protein interaction (PPI) analyses among the comorbidities and COVID-19. We also used the degree centrality method and identified ten biomarker hub proteins (IL1B, CXCL8, FN1, MMP9, CXCL10, IL1A, IRF7, VWF, CXCL9, and ISG15) that associate COVID-19 with the comorbidities. Finally, we validated our findings by searching the published literature. Thus, our analytical approach elicited interconnections between COVID-19 and the aforementioned comorbidities in terms of remarkable DEGs, pathways, ontologies, PPI, and biomarker hub proteins.

A case report of steroid-refractory bullous pemphigoid induced by immune checkpoint inhibitor therapy.

The widespread use of immune checkpoint inhibitors in several malignancies has revealed new immune-related adverse events. Bullous pemphigoid (BP) is an antibody-driven autoimmune disease characterized by skin inflammation and fluid-filled bullae. Herein, a 69-year-old man with lung squamous cell carcinoma developed multiple vesicles and tense bullae 3 weeks after the initiation of a programmed death-1 (PD-1) inhibitor, pembrolizumab, and chemotherapy. Biopsy revealed a subepidermal bulla with lymphocytic and eosinophil infiltration, and immunohistochemical studies predominantly showed CD4

Deep dive into the immune response against murine mesothelioma permits design of novel anti-mesothelioma therapeutics.

Given the need to improve the efficacy of standard-of-care immunotherapy (anti-CTLA-4 anti-PD-1) in human malignant pleural mesothelioma (hMPM), we thoroughly characterized the immunobiology of the AB12 murine mesothelioma (MM) model, aiming to increase its accuracy in predicting the response of hMPM to immunotherapy and in designing novel anti-hMPM treatments. Specifically, we used immunologic, transcriptomic and survival analyses, to synchronize the MM tumor growth phases and immune evolution with the histo-molecular and immunological characteristics of hMPM while also determining the anti-MM efficacy of standard-of-care anti-hMPM immunotherapy as a benchmark that novel therapeutics should meet. We report that early-, intermediate- and advanced- AB12 tumors are characterized by a bell-shaped anti-tumor response that peaks in intermediate tumors and decays in advanced tumors. We further show that intermediate- and advanced- tumors match with immune active (hot) and immune inactive (cold) hMPM respectively, and that they respond to immunotherapy in a manner that corresponds well with its performance in real-life settings. Finally, we show that in advanced tumors, addition of cisplatin to anti CTLA-4 anti PD-1 can extend mice survival and invigorate the decaying anti-tumor response. Therefore, we highlight this triple combination as a worthy candidate to improve clinical outcomes in hMPM.

Functional status and spatial interaction of T cell subsets driven by specific tumor microenvironment correlate with recurrence of non-small cell lung cancer.

The anti-tumoral or pro-tumoral roles of CD4 We performed multiplex immunofluorescence using a tissue microarray of samples from 99 patients with locally advanced NSCLC to elucidate the distributions of tumor cell, T cell subpopulations (CD4conventional CD4regulatory CD4CD8cytotoxic CD8pre-dysfunctional CD8dysfunctional CD8), microvessel density (MVD), cancer-associated fibroblasts (CAFs) and hypoxia-inducible factor-1α (HIF-1α) in TC and IM tissues. Cell-to-cell nearest neighbor distances and interactions were analyzed using the phenoptrreports R package. Cox regression was used to evaluate the associations between T cell subsets density and proximity to tumor cells and recurrence-free survival (RFS). Correlations between different cell subsets were examined by Spearmans or Kruskal-Wallis tests. In the locally advanced NSCLC, the proportion of tumor cells and CAFs in IM is lower than in the TC, while MVD, CD4 In locally advanced NSCLC, the functional status of T cells in the IM region is closely related to recurrence. The density of dysfunctional CD8 and the proximity of regulatory CD4 to tumor cells were independent risk factors for recurrence, and are positively correlated with the hypoxia response of CD8

Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer A cost-effectiveness analysis.

The ASTRUM-005 trial (NCT04063163) revealed that combination serplulimab plus chemotherapy (etoposide and carboplatin EC) treatment was associated with survival advantages relative to chemotherapy alone in patients diagnosed with extensive-stage small-cell lung cancer (ES-SCLC). As these immuno-chemotherapeutic regimens are extremely expensive, however, it is critical that the relative cost-effectiveness of combination serplulimab and chemotherapy treatment as a first-line treatment for ES-SCLC patients be examined in detail. The cost-effectiveness of combined serplulimab plus chemotherapeutic treatment was examined using a comprehensive Markov model with a 10-year boundary, enabling the calculation of overall cost, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Model instability was interrogated through one-way and probabilistic sensitivity analyses. Serplulimab plus chemotherapy or chemotherapy alone respectively yielded 1.217 QALYs (2.243 LYs) and 0.885 QALYs (1.661 LYs) with corresponding total costs of $11,202 and $7,194, with an ICER of $12,077 per QALY ($6,883 per LY). This model was most strongly influenced by the utility of progression-free survival. Probabilistic sensitivity analysis showed that serplulimab plus chemotherapy had a 91.6% probability of being cost-effective at a willingness-to-pay (WTP) of $37,653 per QALY (3 × capita gross domestic product of China in 2021). In subgroup analyses, this combination treatment regimen was found to be most cost-effective in patients who were former smokers, had an ECOG performance status of 0, and were diagnosed with brain metastases. From a payer perspective in China, combination serplulimab plus chemotherapy treatment represents a cost-effective first-line intervention for ES-SCLC patients.

The roles of long noncoding RNA-mediated macrophage polarization in respiratory diseases.

Macrophages play an essential role in maintaining the normal function of the innate and adaptive immune responses during host defence. Macrophages acquire diverse functional phenotypes in response to various microenvironmental stimuli, and are mainly classified into classically activated macrophages (M1) and alternatively activated macrophages (M2). Macrophage polarization participates in the inflammatory, fibrotic, and oncogenic processes of diverse respiratory diseases by changing phenotype and function. In recent decades, with the advent of broad-range profiling methods such as microarrays and next-generation sequencing, the discovery of RNA transcripts that do not encode proteins termed noncoding RNAs (ncRNAs) has become more easily accessible. As one major member of the regulatory ncRNA family, long noncoding RNAs (lncRNAs, transcripts >200 nucleotides) participate in multiple pathophysiological processes, including cell proliferation, differentiation, and apoptosis, and vary with different stimulants and cell types. Emerging evidence suggests that lncRNAs account for the regulation of macrophage polarization and subsequent effects on respiratory diseases. In this review, we summarize the current published literature from the PubMed database concerning lncRNAs relevant to macrophage polarization and the underlying molecular mechanisms during the occurrence and development of respiratory diseases. These differentially expressed lncRNAs are expected to be biomarkers and targets for the therapeutic regulation of macrophage polarization during disease development.

Role for the metalloproteinase ADAM28 in the control of airway inflammation, remodelling and responsiveness in asthma.

Asthma is characterized by morphological modifications of the airways (inflammation and remodelling) and bronchial hyperresponsiveness. Mechanisms linking these two key features of asthma are still poorly understood. ADAM28 (a disintegrin and metalloproteinase 28) might play a role in asthma pathophysiology. ADAM28 exists as membrane-bound and soluble forms and is mainly expressed by lymphocytes and epithelial cells. ADAM28 The expression of the soluble form of ADAM28 was lower in the lungs of OVA-exposed mice (as compared to PBS-exposed mice) and progressively increased in correlation with the duration of allergen exposure. In lungs of ADAM28 These results suggest that ADAM28 might be a key contributor to the pathophysiology of asthma.

Cerebral mucormycosis masquerading as brain metastasis from lung cancer A case report.

We report a rare case of concurrent pulmonary and cerebral mucormycosis initially misdiagnosed as a metastatic tumor. A 66-year-old man with a complaint of progressive right-sided limb weakness for 3 days. Head MRI showed a left parietal occupying lesion with severe edema, and a chest CT scan showed a parenchymal mass with speculation and pleural invasion in his left lung. The patient was initially diagnosed with brain metastases from lung cancer and underwent a craniotomy. Many fungal hyphae were found in the left parietal lesion, and the final pathological diagnosis of intracranial mucormycosis. After craniotomy and an entire course of treatment with liposomal amphotericin B, the patient was completely cured of both intracranial and pulmonary occupying lesions. We hope that this case experience will help expand neurosurgeons differential diagnosis and treatment of such diseases.

Xanthine oxidase, a therapeutic target of realgar for non-small cell lung cancer.

The effects of realgar against non-small cell lung cancer (NSCLC) have been massively studied, but the direct therapeutic targets of realgar remain unclear. This study aimed to identify the molecular targets of realgar against NSCLC and explore their therapeutic mechanisms based on a network pharmacology approach and experimental validations. The BATMAN-TCM and Digsee databases were used to predict realgar targets and NSCLC-related genes, respectively. A protein-protein interaction network was constructed for each gene set, and the overlapping genes were identified as potential targets of realgar against NSCLC. The correlation between potential targets and NSCLC was analyzed using The Cancer Genome Atlas and International Cancer Genome Consortium databases, and the key target was validated by in-silico and in-vitro experiments. Twenty-three overlapping genes, including xanthine oxidase (XO), were identified as potential targets of realgar against NSCLC. XO was selected as the key target for validation, as it was found to be upregulated in NSCLC tumor tissue, which correlated with poor overall survival. A possible interaction between realgar and XO was revealed by molecular docking which was further validated experimentally. Realgar treatment suppressed the activity of XO in NSCLC cells, as demonstrated by the unchanged XO protein levels. Finally, the mechanism of action of XO as a target against NSCLC through the cell-cell junction organization pathway was investigated. Overall, this study proposes a potential molecular mechanism illustrating that XO is a target of realgar against NSCLC and highlights the usefulness of XO as a therapeutic target for NSCLC.

Gefitinib-loaded starch nanoparticles for battling lung cancer Optimization by full factorial design and

Lung cancer is the number one killer among all cancer types. For decades, clinicians have been using conventional chemotherapeutics, but they cant rely on them alone anymore, because they poison bad cells and good cells as well. Researchers exploited nanotechnology as a potential tool to develop a platform for drug delivery to improve therapeutic efficiency. A quality by design synthesis of gefitinib-loaded starch nanoparticles (Gef-StNPs) has emerged as an essential tool to study and optimize the factors included in their synthesis. Therefore, we applied design of experiment (DOE) tools to attain the essential knowledge for the synthesis of high-quality Gef-StNPs that can deliver and concentrate the gefitinib (Gef) at A549 cells, thereby improving therapeutic efficacy and minimizing adverse effects. The

Construction and stable gene expression of AGR2xPD1 bi-specific antibody that enhances attachment between

There has been a substantial and consistent rise in the number of clinical trials to develop advanced and potent bispecific antibodies (BsAb) over the past two decades with multiple targets to improve the efficacy or tissue specificity of monoclonal antibodies (mAb) treatment for diseases with multiple determining factors or widely-expressed targets. In this study, we designed and synthesized BsAb AGR2xPD1 targeting extracellular AGR2, a paracrine signal, and PD1, an immune checkpoint protein. Our design is intended to use AGR2 binding to guide PD1 targeting for AGR2

Resection of a giant thoracic solitary fibrous tumor treated with preoperative arterial coiling followed by a double-level thoracotomy.

Solitary fibrous tumor (SFT) are rare pleura neoplasms often localized to middle or inferior hemithorax. A middle-aged woman presents to the emergency department following a motor vehicle accident, the computed tomography scan revealed a giant tumor occupying the entire left pleural cavity with a complete collapse of the left lung and substantial right deviation of heart and mediastinum. Using preoperative arterial coiling followed by a double-level thoracotomy we successfully resected the giant tumor. The SFT weighed 10 lbs. At 2-month follow-up visit patient reports mild discomfort during strenuous movementheavy lifting but denies any shortness of breath.

Prognostic value of long non-coding RNA

Streptococcus pneumoniae promotes lung cancer development and progression.

Dose Estimation Using Optically Stimulated Luminescence Dosimeter and EBT3 Films for Various Treatment Techniques in Alderson Rando Phantom and Estimation of Secondary Cancer Incidence for Carcinoma of Left Breast.

The aim of this study was to measure the dose to planning target and organ at risk (OAR) using Alderson Rando phantom for various treatment techniques in left breast radiotherapy and to estimate the secondary cancer incidence. Eleven different combinations of plans containing four techniques (three dimensional conformal radiotherapy, intensity-modulated radiation therapy IMRT, volumetric modulated arc therapy VMAT, and combination of 3DCRT and VMAT plans (HYBRID)) were created with 6 MV FF and 6 MV FFF (flattening filter and flattening filter-free) photon energies in phantom. Planned target volume and OAR doses in 23 different locations were measured using optically stimulated luminescence dosimeter (OSLD) and EBT3 films. Assuming the age of exposure as 30 years, lifetime attributable risk (LAR) was estimated based on excess absolute risk (EAR) models outlined in the Biological Effects of Ionizing Radiation VII report. Film showed maximum deviations of 6.15% with IMRTCFF plan when compared with treatment planning system (TPS). The maximum percentage difference of 1.7% was found with OSLD measurement when compared with TPS for VMATTFFF plan. EAR estimation was done for all the OARs including target. The LARs for left lung, right lung, and right breast were evaluated. The maximum LAR values of 2.92 ± 0.14 were found for left lung with VMATCFFF plans. This study shows that both OSLD and EBT3 films are suitable for dose measurements using Rando phantom. OSLD shows superior results when compared with films, especially with relatively larger distances. Maximum LAR values were found with VMATCFFF plans. Considering the secondary cancer risk associated with the patients treated in the younger age group, it is suggested that

Remifentanil modulates the TLR4‑mediated MMP‑9TIMP1 balance and NF‑κBSTAT3 signaling in LPS‑induced A549 cells.

Remifentanil is a widely used in general anesthetic that has been found to suppress the inflammatory response in aortic endothelial cells. Therefore, it was hypothesized that remifentanil can inhibit inflammatory dysfunction in lung epithelial cells to alleviate acute lung injury (ALI). The present study aimed to examine the effects of remifentanil on inflammatory injury, MMP-9tissue inhibitor of metalloproteinase 1 (TIMP1) balance and the potential associated regulatory pathways in A549 cells. Lipopolysaccharide (LPS) was used to treat A549 cells to establish ALI models. The possible roles of different concentrations of remifentanil in cell viability was then determined by CCK-8 and Lactate dehydrogenase release assay. Apoptosis was assessed by flow cytometry analysis and western blotting. Inflammation and oxidative stress were measured by ELISA and corresponding kits respectively. Subsequently, the effects of remifentanil on Toll-like receptor 4 (TLR4) expression and the MMP-9TIMP1 balance were assessed by western blotting and ELISA. In addition, the effects of remifentanil on NF-κBSTAT3 signaling were evaluated by measuring the protein expression levels of associated pathway components and the degree of NF-κB nuclear translocation using western blotting and immunofluorescence respectively. Remifentanil was found to increase cell viability whilst reducing apoptosis, inflammation and oxidative stress in the LPS-treated cells. In addition, TLR4 inhibitor CLI-095 suppressed MMP-9 expression and secretion while potentiating TIMP1 expression and secretion in LPS-challenged cells. Remifentanil treatment was able to modulate TLR4 to mediate LPS-induced MMP-9TIMP1 imbalance and suppress the phosphorylation of NF-κBSTAT3 signaling components, in addition to inhibiting NF-κB nuclear translocation. Taken together, remifentanil downregulated TLR4 to reduce MMP-9TIMP1 imbalance to inhibit inflammatory dysfunction in LPS-treated A549 cells, by regulating NF-κBSTAT3 signaling.

Hemoptysis due to a lung metastasis of renal cell carcinoma A case report.

A 53-year-old man with a history of surgery for renal cancer was referred to our hospital due to massive hemoptysis. Contrast-enhanced CT revealed a well-enhanced pulmonary nodule suggestive of a tumor (diameter of 16 mm), which was considered a causal lesion. Bronchial artery embolization was successfully performed and subsequently hemoptysis disappeared. However, hemoptysis recurred 6 months later, and the tumor was surgically resected. Pathological examination revealed the resected tumor was a lung metastasis of renal cell carcinoma, which directly invaded into pulmonary bronchus. Hemoptysis secondary to lung metastasis of renal cell carcinoma has rarely been reported in the literature.

Identification of h-TERT Promoter Mutations in Germline DNA from North Indian Lung Carcinoma Patients.

Lung cancer is a severe and the leading cause of cancer related deaths worldwide. The recurrent h-TERT promoter mutations have been implicated in various cancer types. Thus, the present study is extended to analyze h-TERT promoter mutations from the North Indian lung carcinoma patients. Total 20 histopathologically and clinically confirmed cases of lung cancer were enrolled in this study. The genomic DNA was extracted from venous blood and subjected to amplification using appropriate h-TERT promoter primers. Amplified PCR products were subjected for DNA Sanger sequencing for the identification of novel h-TERT mutations. Further, these identified h-TERT promoter mutations were analysed for the prediction of pathophysiological consequences using bioinformatics tools such as Tfsitescan and CIIDER. The average age of patients was 45 ± 8 years which was categorized in early onset of lung cancer with predominance of male patients by 5.6 fold. Interestingly, h-TERT promoter mutations were observed highly frequent in lung cancer. Identified mutations include c. G272A, c. T122A, c. C150A, c. 123 del C, c. C123T, c. G105A, c. 107 Ins A, c. 276 del C corresponding to -168 G>A, -18 T>A, -46 C>A, -19 del C, -19 C>T, -1 G>A, -3 Ins A, -172 del C respectively from the translation start site in the promoter of the telomerase reverse transcriptase gene which are the first time reported in germline genome from lung cancer. Strikingly, c. -18 T>A C.T122A was found the most prevalent variant with 75% frequency. Notwithstanding, other mutations viz c. -G168A c. G272A and c. -1 G>A c. G105A were found to be at 35% and 15% frequency respectively whilst the rest of the mutations were present at 10% and 5% frequency. Additionally, bioinformatics analysis revealed that these mutations can lead to either loss or gain of various transcription factor binding sites in the h-TERT promoter region. Henceforth, these mutations may play a pivotal role in h-TERT gene expression. Taken together, these identified novel promoter mutations may alter the epigenetics and subsequently various transcription factor binding sites which are of great functional significance. Thereby, it is plausible that these germline mutations may involve either as predisposing factor or direct participation in the pathophysiology of lung cancer through entangled molecular mechanisms.

An effective tool for predicting survival in breast cancer patients with

An effective tool for forecasting the survival of BCLM is lacking. This study aims to construct nomograms to predict overall survival (OS) and breast cancer-specific survival (BCSS) in breast cancer patients with We gathered clinical data of 2,537 patients with BCLM between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Cox regression analysis was employed to identify independent prognostic parameters for BCLM, which were integrated to establish nomograms by R software. The discriminative ability and predictive accuracy of the nomograms were assessed using the concordance index (C-index), receiver operating characteristic (ROC) curves, and calibration plots. Kaplan-Meier analyses were applied to evaluate the clinical utility of the risk stratification system and investigate the survival benefit of primary site surgery, chemotherapy, and radiotherapy for BCLM patients. Two nomograms shared common prognostic indicators including age, marital status, race, laterality, grade, AJCC T stage, subtype, bone metastasis, brain metastasis, liver metastasis, surgery, and chemotherapy. The results of the C-index, ROC curves, and calibration curves demonstrated that the nomograms exhibited an outstanding performance in predicting the prognosis of BCLM patients. Significant differences in the Kaplan-Meier curves of various risk groups corroborated the nomograms excellent stratification. Primary site surgery and chemotherapy remarkably improved OS and BCSS of BCLM patients whether the patients were at low-risk or high-risk, but radiotherapy did not. We successfully developed prognostic stratification nomograms to forecast prognosis in BCLM patients, which provide important information for indicating prognosis and facilitating individualized treatment regimens for BCLM patients.

Subsegmentectomy versus segmentectomy resection for the treatment of operable patients with stage IA non-small cell lung cancer A meta-analysis.

There were new points of interest in performing subsegmentectomy and segmentectomy for patients with early stage non-small cell lung cancer (NSCLC). However, whether patients who underwent subsegmentectomy could obtain satisfactory clinical outcomes remains unclear. The present study aimed to compare the clinical outcomes and security of surgical procedures between subsegmentectomy and segmentectomy. A systematic review and meta-analysis was performed through five online databases to identify the included literatures which presented intact clinical outcome data among different surgical procedures. The included studies were evaluated based on precise and predefined inclusion criteria. There were 4 published studies identified in this meta-analysis. A total of 325 patients who underwent subsegmentectomy and 904 patients who underwent segmentectomy were involved in this analysis. The duration of drainage MD -0.19 95%CI (-0.36, -0.02), The meta-analysis was firstly performed to compare perioperative outcomes among surgical procedures. The perioperative outcomes were comparable between subsegmentectomy and segmentectomy. Subsegmentectomy might be an alternative treatment for the deep tumor with size less than 1.5 cm and mainly composed of Ground Glass Opacity (GGO).

Monitoring of postoperative neutrophil-to-lymphocyte ratio, D-dimer, and CA153 in Diagnostic value for recurrent and metastatic breast cancer.

This stydy aims to assess the value of monitoring of postoperative neutrophil-to-lymphocyte ratio (NLR), D-dimer, and carbohydrate antigen 153 (CA153) for diagnosis of breast cancer (BC) recurrence and metastasis. A cohort of 252 BC patients who underwent surgery at the First Affiliated Hospital of Anhui Medical University between August 2008 and August 2018 were enrolled in this retrospective study. All patients were examined during outpatient follow-ups every 3 months for 5 years postoperation and every 6 months thereafter. Recurrence or metastasis was recorded for 131 patients but not for the remaining 121. Retrospective analysis of hematological parameters and clinicopathological characteristics allowed comparison between the two groups and evaluation of these parameters for the recurrent and metastatic patients. Lymph node metastasis, higher tumor node metastasis (TNM) staging, and higher histological grade correlated with BC recurrence and metastasis ( Monitoring postoperative NLR, D-dimer, and CA153 is a convenient, practical method for diagnosing BC recurrence and metastasis. These metrics have good predictive value in terms of sites of recurrence and metastasis and the likelihood of multiple metastases.

Polo-like kinase (PLK) 5, a new member of the PLK family, serves as a biomarker to indicate anabatic tumor burden and poor prognosis for resectable non-small cell lung cancer.

A review argues that polo-like kinase 5 (PLK5) may be linked to unfavorable prognosis in non-small cell lung cancer (NSCLC) patients, which contradicts the discoveries from The Human Protein Atlas database (derived from TCGA analysis). This study intended to comprehensively confirm the association of PLK5 with clinical characteristics and prognosis in NSCLC patients. This two-center, retrospective, cohort study enrolled 210 NSCLC patients receiving surgical resection. PLK5 protein and mRNA were detected by immunohistochemistry and RT-qPCR in tumor and nontumor tissues. Moreover, RNA FPKM data for 994 lung cancer patients were obtained from The Human Protein Atlas database. PLK5 protein was decreased in tumor tissue compared to nontumor tissue ( A PLK5 decrement reflects anabatic tumor burden and poor prognosis in NSCLC patients.

Recurrent lung adenocarcinoma benefits from microwave ablation following multidisciplinary treatments A case with long-term survival.

Lung cancer has become the leading cause of cancer death all over the world. Nowadays, there is a consensus that the treatment of non-small cell lung cancer (NSCLC) prefers a combination of multidisciplinary comprehensive treatment and individualized treatment, which can significantly improve the prognosis of patients. Here, we report a female patient with recurrence-prone NSCLC. She had a decade-long disease course, during which the lesion recurred twice and finally cured with Multi-Disciplinary Treatment (MDT). An elderly female patient was admitted to the hospital after diagnosis of lung cancer, and treated with surgery and postoperative adjuvant chemotherapy. Five years later, suspicious lesions were found by computed tomography (CT) reexamination, and then confirmed tumor recurrence by puncture biopsy. Based on the genetic test results, gefitinib was used for subsequent targeted therapy, and the lesion gradually shrunk to disappear. However, the lesion appeared again two years later, after consultation the microwave ablation was adopted and the curative effect was excellent. At last, regular reexamination showed no abnormality, the patient has survived so far. The case proves the great benefit of multidisciplinary comprehensive treatment, especially microwave ablation for patient with recurrence-prone NSCLC. And the effect of systemic anti-tumor immune response induced by microwave ablation on lung cancer also needs to be further explored.

Exosomal miRNA-profiling of pleural effusion in lung adenocarcinoma and tuberculosis.

Pleural effusion (PE) caused by lung cancer is prevalent, and it is difficult to differentiate it from PE caused by tuberculosis. Exosome-based liquid biopsy offers a non-invasive technique to diagnose benign and malignant PE. Exosomal miRNAs are potential diagnostic markers and play an essential role in signal transduction and biological processes in tumor development. We hypothesized that exosomal miRNA expression profiles in PE would contribute to identifying its diagnostic markers and elucidating the molecular basis of PE formation in lung cancer. The exosomes from PE caused by lung adenocarcinoma (LUAD) and pulmonary tuberculosis were isolated and verified by transmission electron microscopy. The exosomal miRNA profiles were identified using deep sequencing and validated with quantitative real-time PCR (qRT-PCR). We performed bioinformatic analysis for differentially expressed miRNAs to explore how exosomal miRNAs regulate pleural effusion. We identified 99 upregulated and 91 downregulated miRNAs in malignant pleural effusion (MPE) compared to tuberculous pleural effusion (TPE). Seven differentially expressed miRNAs (DEmiRNAs) were validated by qRT-PCR, out of which 5 (71.4%) were confirmed through sequencing. Gene Ontology (GO) analysis revealed that most exosomal miRNAs target genes were involved in regulating cellular processes and nitrogen compound metabolism. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the exosomal miRNAs target genes were mainly involved in Fc gamma R-mediated phagocytosis, Rap1 signaling pathway, and breast cancer. The hub genes, including ITGAM, FOXO1, MAPK14, YWHAB, GRIN1, and PRF1, were screened through plug-in cytoHubba. The PFR1 was identified as a critical gene in MPE formation using single-cell sequencing analysis. Additionally, we hypothesized that tumor cells affected natural killer cells and promoted the generation of PE in LUAD We identified exosomal miRNA profiles in LUAD-MPE and TPE, which may help in the differential diagnosis of MPE and TPE. Bioinformatic analysis revealed that these miRNAs might affect PE generation through tumor immune response in LUAD. Our results provided a new theoretical basis for understanding the function of exosomal miRNAs in LUAD-MPE.

Construction of a mortality risk prediction model for elderly people at risk of lobectomy for NSCLC.

An increasing number of lung cancer patients are opting for lobectomy for oncological treatment. However, due to the unique organismal condition of elderly patients, their short-term postoperative mortality is significantly higher than that of non-elderly patients. Therefore, there is a need to develop a personalised predictive tool to assess the risk of postoperative mortality in elderly patients. Information on the diagnosis and survival of 35,411 older patients with confirmed lobectomy NSCLC from 2009 to 2019 was screened from the SEER database. The surgical group was divided into a high-risk mortality population group (≤90 days) and a non-high-risk mortality population group using a 90-day criterion. Survival curves were plotted using the Kaplan-Meier method to compare the differences in overall survival (OS) and lung cancer-specific survival (LCSS) between the two groups. The data set was split into modelling and validation groups in a ratio of 7.52.5, and model risk predictors of postoperative death in elderly patients with NSCLC were screened using univariate and multifactorial logistic regression. Columnar plots were constructed for model visualisation, and the area under the subject operating characteristic curve (AUC), DCA decision curve and clinical impact curve were used to assess model predictiveness and clinical utility. Multi-factor logistic regression results showed that sex, age, race, histology and grade were independent predictors of the risk of postoperative death in elderly patients with NSCLC. The above factors were imported into R software to construct a line graph model for predicting the risk of postoperative death in elderly patients with NSCLC. The AUCs of the modelling and validation groups were 0.711 and 0.713 respectively, indicating that the model performed well in terms of predictive performance. The DCA decision curve and clinical impact curve showed that the model had a high net clinical benefit and was of clinical application. The construction and validation of a predictive model for death within 90 days of lobectomy in elderly patients with lung cancer will help the clinic to identify high-risk groups and give timely intervention or adjust treatment decisions.

Prognostic significance of preoperative C-reactive protein to albumin ratio in non-small cell lung cancer patients A meta-analysis.

We aimed to assess whether C-reactive protein to albumin ratio (CAR) is associated with the clinicopathology and prognosis of patients with non-small cell lung cancer (NSCLC) after surgery. Several literature databases were searched for eligible studies in English and Chinese published before September 1, 2022, according to the inclusion and exclusion criteria. The pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated to assess the association of CAR in lung cancer with clinicopathological characteristics including age, sex, smoking status, lymph node metastasis, and American Association of Cancer (AJCC) stage. The pooled hazard ratios (HRs) with 95% CI were calculated to assess the association of CAR with prognosis in lung cancer. Publication bias was assessed using Eggers test. Overall, 9 studies involving 3,359 NSCLC patients were included in this meta-analysis. The CAR was observed to be higher in males, smokers, and patients with lymph node metastasis and correlated with advanced AJCC stage but not with age. Moreover, a high CAR correlated with poor survival. No publication bias was observed in this meta-analysis. CAR was observed to be a significant biomarker for prognosis and associated with clinicopathological characteristics in patients with NSCLC after surgery.

Application and practice of trimodal prehabilitation model in preoperative management of patients with lung cancer undergoing video-assisted thoracoscopic surgery.

Lung cancer is one of the malignant tumors with high mortality worldwide. To date, the most effective treatment of non-small cell lung cancer (NSCLC) is still surgical resection. Video-assisted thoracoscopic surgery has become the main surgical approach. Tumor patients are the high-risk perioperative population. At present, how to optimize perioperative management measures to improve the patients body function and promote the rehabilitation after video-assisted thoracoscopic surgery is a hot research topic for medical staff. In this study, 148 patients with lung cancer were selected as the research object, to analyze and discuss the application value of trimodal prehabilitation model in preoperative management of patients with lung cancer undergoing video-assisted thoracoscopic surgery.

Preoperative lung immune prognostic index predicts survival in patients with pancreatic cancer undergoing radical resection.

Lung immune prognostic index (LIPI), a combination of derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH), is currently attracting considerable interest as a potential prognostic indicator in many malignancies. Our study aimed to investigate the prognostic value of preoperative LIPI in patients with pancreatic ductal adenocarcinoma (PDAC) undergoing radical resection. We retrospectively reviewed PDAC patients treated with radical resection from February 2019 to April 2021 at Chinese Peoples Liberation Army (PLA) general hospital. Based on the cut-off value of dNLR and LDH identified by X-tile, patients were divided into LIPI good and LIPI intermediatepoor group. Kaplan-Meier curve and log-rank test were used to compare the recurrence-free survival (RFS) and overall survival (OS) of the two groups. Univariate and multivariate Cox regression was used to identify the independent prognostic value of LIPI. Subgroup analysis was performed to identify specific population benefited from radical resection. A total of 205 patients were included and the median RFS and OS was 10.8 and 24.3 months, respectively. Preoperative LIPI intermediatepoor was related to worse RFS and OS ( Preoperative LIPI intermediatepoor can be an indicator of poor prognosis in patients with PDAC undergoing radical resection. LIPI good could be an effective marker of benefit from adjuvant chemotherapy. Larger studies are warranted for further validation.

A pulmonary nodule mislocated in dorsal segment due to tri-lobed left lung.

The left lung has two lobes and one fissure, while the right lung has three lobes and two fissures. Accessory fissures are usually found in imaging examinations and autopsies however, finding an actual accessory lobe is rare. In a lung nodule resection surgery, a 68-year-old male patient was found with three lobes and two fissures in his left lung. The lung nodule was misdiagnosed as being located in the lower lobe because the accessory fissure was misregarded as the oblique fissure. The lung nodule was found in the upper lobe, and this anatomical variation changed the surgical plan. The pathology of the lung nodule was granulomatous inflammation with caseous necrosis with the positive antacid stain. The patient was eventually diagnosed with tuberculosis. Cases involving the lung accessory fissure and lung accessory lobe variants were reviewed. In 10 autopsy and dissection studies, the incidence of accessory fissure in the left lung was 13.5% (79587, ranging from 2.7% to 50.0%), and in the right lung, it was 7.3% (42575, ranging from 3.1% to 30.4%). The incidence of accessory lobes in the left lung was 2.0% (11547, ranging from 0.0% to 7.4%), and in the right lung was 2.6% (14539, ranging from 0.0% to 17.4%). The incidence of accessory fissures in bilateral lungs identified by chest x-ray or computed tomography ranged from 7.3% to 32.0%. Three surgical case reports inferred accessory lobes, including a left upper lobectomy, left lung transplantation, and an open thoracotomy. This is the first clinical case report that shows that lung accessory lobe caused the mislocation of a lung nodule. Therefore, radiologists and surgeons should be aware of the possibility of an accessory lobe in the lung.

Analysis of prognostic factors of metastatic endometrial cancer based on surveillance, epidemiology, and end results database.

To explore the risk factors for survival and prognosis of patients with metastatic endometrial cancer and to build and verify a reliable prediction model. We retrospectively analyzed patients diagnosed with metastatic endometrial cancer in the US Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Univariate and multivariate Cox regression analyses were used to assess clinical variables impact on survival and to construct nomograms. The results of the consistency index (C-index), subject operating characteristic (ROC) curve, and calibration curve were used to evaluate the predictive ability of the nomogram. This study included 3,878 patients with metastatic endometrial cancer. In the univariate analysis, variables associated with overall survival (OS) and cancer-specific survival (CSS) included age, race, marital status, pathological type, pathological grade, T-stage, N-stage, surgery, radiotherapy, chemotherapy, bone metastasis, brain metastasis, liver metastasis, and lung metastasis. In the multivariate analysis, age, race, pathological type, pathological grade, T-stage, N-stage, surgery, radiotherapy, chemotherapy, brain metastasis, liver metastasis, and lung metastasis were independent risk factors for OS and CSS (all Our SEER-based nomograms for predicting survival in patients with metastatic endometrial cancer were helpful for the clinical evaluation of patient prognosis.

Clathrin light chain-conjugated drug delivery for cancer.

Targeted drug delivery systems hold the remarkable potential to improve the therapeutic index of anticancer medications markedly. Here, we report a targeted delivery platform for cancer treatment using clathrin light chain (CLC)-conjugated drugs. We conjugated CLC to paclitaxel (PTX) through a glutaric anhydride at high efficiency. Labeled CLCs localized to 4T1 tumors implanted in mice, and conjugation of PTX to CLC enhanced its delivery to these tumors. Treatment of three different mouse models of cancer-melanoma, breast cancer, and lung cancer-with CLC-PTX resulted in significant growth inhibition of both the primary tumor and metastatic lesions, as compared to treatment with free PTX. CLC-PTX treatment caused a marked increase in apoptosis of tumor cells and reduction of tumor angiogenesis. Our data suggested HSP70 as a binding partner for CLC. Our study demonstrates that CLC-based drug-conjugates constitute a novel drug delivery platform that can augment the effects of chemotherapeutics in treating a variety of cancers. Moreover, conjugation of therapeutics with CLC may be used as means by which drugs are delivered specifically to primary tumors and metastatic lesions, thereby prolonging the survival of cancer patients.

Risk factors, prognostic predictors, and nomograms for pancreatic cancer patients with initially diagnosed synchronous liver metastasis.

Liver metastasis (LM) remains a major cause of cancer-related death in patients with pancreatic cancer (PC) and is associated with a poor prognosis. Therefore, identifying the risk and prognostic factors in PC patients with LM (PCLM) is essential as it may aid in providing timely medical interventions to improve the prognosis of these patients. However, there are limited data on risk and prognostic factors in PCLM patients. To investigate the risk and prognostic factors of PCLM and develop corresponding diagnostic and prognostic nomograms. Patients with primary PC diagnosed between 2010 and 2015 were reviewed from the Surveillance, Epidemiology, and Results Database. Risk factors were identified using multivariate logistic regression analysis to develop the diagnostic mode. The least absolute shrinkage and selection operator Cox regression model was used to determine the prognostic factors needed to develop the prognostic model. The performance of the two nomogram models was evaluated using receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA), and risk subgroup classification. The Kaplan-Meier method with a log-rank test was used for survival analysis. We enrolled 33459 patients with PC in this study. Of them, 11458 (34.2%) patients had LM at initial diagnosis. Age at diagnosis, primary site, lymph node metastasis, pathological type, tumor size, and pathological grade were identified as independent risk factors for LM in patients with PC. Age > 70 years, adenocarcinoma, poor or anaplastic differentiation, lung metastases, no surgery, and no chemotherapy were the independently associated risk factors for poor prognosis in patients with PCLM. The C- index of diagnostic and prognostic nomograms were 0.731 and 0.753, respectively. The two nomograms could accurately predict the occurrence and prognosis of patients with PCLM based on the observed analysis results of ROC curves, calibration plots, and DCA curves. The prognostic nomogram could stratify patients into prognostic groups and perform well in internal validation. Our study identified the risk and prognostic factors in patients with PCLM and developed corresponding diagnostic and prognostic nomograms to help clinicians in subsequent clinical evaluation and intervention. External validation is required to confirm these results.

Paraneoplastic arthritides an up-to-date case-based systematic review.

Among the rheumatic diseases whose symptoms are more often associated with the possibility of cancer and other malignancies are systemic sclerosis, dermatomyositis and rheumatic polymyalgia. However, a differential diagnosis should be performed in each case of non-typical rheumatic disease andor other neoplastic disease risk factors. The articles aim was based on a literature review of this subject and presentation own a case description and discussion about arthritis as a paraneoplastic syndrome. The conclusions of our analysis were as follows more often paraneoplastic arthritis occurs in men, in ages higher than 50 years old, in patients who poorly respond to treatment of arthritis with polyarticular symmetrical involvement of the limbs, seronegative type of inflammatory joint disease. In this group of patients, complete remission after treatment of the primary tumor and recurrence of the symptoms in the presence of metastasis was observed.

Pulmonary pattern in systemic vasculitis granulomatosis, lung cancer or both

As clinical manifestations of systemic vasculitides share many common features with other conditions, the rate of diagnostic errors and delayed diagnoses is high. Hence we performed an analysis of the available data regarding misdiagnosis of vasculitis as lung cancer and vice versa, as well as coexistence of vasculitis and lung cancer. The present case-based review highlights the diagnostic challenges encountered when granulomatosis with polyangiitis (GPA) mimics lung cancer. The importance of a multidisciplinary team approach to patients with pulmonary involvement and multisystem manifestations is essential for appropriate planning of further diagnostic steps and for minimizing the delay in correct diagnosis and treatment. In the present case, although computed tomography raised suspicion for lung cancer, further biopsies and laboratory screening for systemic vasculitides rejected malignancy and confirmed the diagnosis of GPA.

Classification of rectal cancer according to recurrence types - comparison of Japanese guidelines and Western guidelines.

Rectal cancer is characterized by more local recurrence (LR) and lung metastasis than colon cancer. However, the diagnosis of rectal cancer is not standardized as there is no global consensus on its definition and classification. The classification of rectal cancer differs between Japanese and Western guidelines. To clarify the characteristics of rectal cancer by comparing the tumor location and characteristics of rectal cancer with those of colon cancer according to each set of guidelines. A total of 958 patients with Stage II and III colorectal cancer were included in the analysis 607 with colon cancer and 351 with rectal cancer. Localization of rectal cancers was assessed by enema examination and rigid endoscopy. According to Japan guidelines, rectal cancer is classified as Rb (below the peritoneal inversion), Ra (between the inferior margin of second sacral vertebrae and Rb) or RS (between Ra and sacral promontory). There were no significant differences between RS rectal cancer and colon cancer in the rates of liver and lung metastasis or LR. Lung metastasis and LR were significantly more common among Rb rectal cancer (in Japan) than in colon cancer ( High rectal cancer may be treated with the same treatment strategies as colon cancer. There was no difference in the classification of colorectal cancer between Japan and Western countries.

Endobronchial ultrasound-guided transbronchial needle aspiration in intrathoracic lymphadenopathy with extrathoracic malignancy.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of mediastinal and hilar lymph is poorly studied in patients with extrathoracic malignancies. To evaluate the value of EBUS-TBNA for the diagnosis of enlarged intrathoracic lymph nodes in patients with extrathoracic malignancies. This was a retrospective study of patients with extrathoracic malignancies who were referred to Peking University Cancer Hospital from January 2013 to December 2018 for EBUS-TBNA due to intrathoracic lymphadenopathy. The specimens were defined as positive for malignancy, negative for non-malignancy (tuberculosis, sarcoidosis, A total of 80 patients underwent EBUS-TBNA and had a final diagnosis, among which 50 (62.5%) were diagnosed with extrathoracic malignancy with intrathoracic lymph nodes metastasis, 14 (17.5%) were diagnosed with primary lung cancer with nodal involvement, and 16 (20.0%) exhibited benign behavior including tuberculosis, sarcoidosis and reactive lymphadenitis or who had benign follow-up. The diagnostic sensitivity, NPV, and accuracy of EBUS-TBNA for intrathoracic lymphadenopathy in patients with extrathoracic malignancy were 93.8% ( EBUS-TBNA is a simple and accurate procedure for the diagnosis of intrathoracic lymphadenopathy with extrathoracic malignancy.

PD-L1 expression and CD8 positive lymphocytes in human neoplasms A tissue microarray study on 11,838 tumor samples.

Programmed death ligand 1 (PD-L1) is the target of immune checkpoint inhibitor therapies in a growing number of tumor types, but a unanimous picture on PD-L1 expression across cancer types is lacking. We analyzed immunohistochemical PD-L1 expression in 11,838 samples from 118 human tumor types and its relationship with tumor infiltrating CD8 positive lymphocytes. At a cut-off level of 10% positive tumor cells, PD-L1 positivity was seen in 85 of 118 (72%) tumor types, including thymoma (100% positive), Hodgkins lymphoma (93%), anaplastic thyroid carcinoma (76%), Kaposi sarcoma (71%), sarcomatoid urothelial carcinoma (71%), and squamous cell carcinoma of the penis (67%), cervix (65%), floor of the mouth (61%), the lung (53%), and pharynx (50%). In immune cells, PD-L1 positivity was detectable in 103 (87%) tumor types, including tumors of haematopoetic and lymphoid tissues (75% to 100%), Warthin tumors of the parotid glands (95%) and Merkel cell carcinoma (82%). PD-L1 positivity in tumor cells was significantly correlated with the number of intratumoral CD8 positive lymphocytes across all tumor types as well as in individual tumor types, including serous carcinoma of the ovary, invasive breast carcinoma of no special type, intestinal gastric adenocarcinoma, and liposarcoma (p< 0.0001 each). PD-L1 expression in tumor and inflammatory cells is found in a wide range of human tumor types. Higher rates of tumor infiltrating CD8 positive lymphocytes in PD-L1 positive than in PD-L1 negative cancers suggest that the antitumor immune response may trigger tumoral PD-L1 expression.

Analysis on methylation and expression of

Our research provides a new and robust method to select biomarkers based on the tumor immune microenvironment. Our research finds that a new epigenomic and transcriptomic biomarker could independently distinguish the types of tumor immune microenvironment and predict immunotherapy effects in patients with lung adenocarcinoma.

Derivation and External Validation of a Risk Prediction Model for Pulmonary Embolism in Patients With Lung Cancer A Large Retrospective Cohort Study.

To investigate the risk factors of pulmonary embolism in patients with lung cancer and develop and validate a novel nomogram scoring system-based prediction model. We retrospectively analyzed the clinical data and laboratory characteristics of 900 patients with lung cancer who were treated, including patients with lung cancer without pulmonary embolism (LC) and patients with lung cancer with pulmonary embolism (LC PE). The patients were randomly divided into derivation and internal validation groups in a 73 ratio. Using logistic regression analysis, a diagnostic model of the nomogram scoring system was developed by incorporating selected variables in the derivation group and validated in the internal and external validation groups (n 108). Seven variables (adenocarcinoma, stage III-IV LC, indwelling central venous catheter, chemotherapy, and the levels of serum albumin, hemoglobin, and D-dimer) were identified as valuable parameters for developing the novel nomogram diagnostic model for differentiating patients with LC and LC PE. The scoring system demonstrated good diagnostic performance in the derivation (area under the curve AUC 95% confidence interval CI, 0.918 0.893, 0.943 sensitivity, 88.5% specificity, 80.5%), internal validation (AUC 95% CI, 0.921 0.884, 0.958 sensitivity, 90.5% specificity, 80.4%), and external validation (AUC 95% CI, 0.929 0.875, 0.983 sensitivity 85.0% specificity 87.5%) groups. In this study, we constructed and validated a nomogram scoring system based on 7 clinical parameters. The scoring system exhibits good accuracy and discrimination between patients with LC and LC PE and can effectively predict the risk of PE in patients with LC.

Can depressed cancer patients with a borderline thiamine concentration develop deficiency within a short time period

Despite increasing reports of thiamine deficiency (TD) among cancer patients, there remain some patients with borderline thiamine concentrations (BTC). However, it is unclear whether such patients subsequently develop TD. Here, we report cases of cancer patients progressing to TD within a short time period after presentation with BTC (24-28 ngml). A 49-year-old female with lung cancer. During treatment for depression, the patient showed a decreased appetite, and a blood sample revealed BTC (25 ngml). Fourteen days later, she reported a continued loss of appetite, and despite the absence of the 3 classical signs of Wernicke encephalopathy (WE), additional testing showed a thiamine level of 23 ngml, leading to a diagnosis of TD. A 65-year-old female developed depression during chemotherapy for angiosarcoma. Her blood sample revealed BTC (25 ngml). Seven days later, despite the absence of the classical signs of WE, a further testing revealed a thiamine level of 20 ngml. A 41-year-old female developed depression during chemotherapy for ovarian cancer. No loss of appetite was observed, but a blood sample revealed BTC (25 ngml). Seven days later, despite the absence of the classical signs of WE or decreased appetite, further testing revealed a thiamine level of 19 ngml. Depressed cancer patients with BTC may develop TD within a short time frame. To prevent TD, health-care professionals should maintain an awareness of its potential and the need for regular testing of thiamine level or prophylactic replacement therapy.

Survival impact of unexpected N2 in stage IIIBN2 non-small cell lung cancer patients.

We investigated the effect of unexpected N2 on survival in stage IIIBN2 cases. We retrospectively analyzed 1803 non-small cell lung cancer patients between 2010 and 2016. There were 89 patients (4.9%) with unexpected N2 (pathological (p) IIIBN2 group), whereas 49 patients (2.7%) with cN2 (clinical (c) IIIBN2 group). Although pIIIBN2 group underwent surgery followed by adjuvant therapy, the cIIIBN2 group of patients had multimodality treatment including induction chemotherapy ± radiotherapy followed by surgery. The five-year overall survival (OS) for all patients was 36.0% median survival time (MST) 27.9 months, and disease-free survival (DFS) was 28.9% (MST, 18.2 months). The OS was 39.6% (MST 34.4 months) and the median DFS time was 31.1% (Median 23.1 months) in the pIIIBN2 group, whereas it was 29.2% (MST 23.0 months) for OS and 22% (median 12.4 months) for DFS in the cIIIBN2 group. There were no significant OS and DFS differences between the pIIIBN2 group and the cIIIBN2 group ( In stage IIIBN2 cases, the fact that N2 could not be detected preoperatively with minimally invasive or invasive methods and was detected in the pathological examination after surgery does not provide a survival advantage.

Boosting the Potential of Chemotherapy in Advanced Breast Cancer Lung Metastasis via Micro-Combinatorial Hydrogel Particles.

Breast cancer cell colonization of the lungs is associated with a dismal prognosis as the distributed nature of the disease and poor permeability of the metastatic foci challenge the therapeutic efficacy of small molecules, antibodies, and nanomedicines. Taking advantage of the unique physiology of the pulmonary circulation, here, micro-combinatorial hydrogel particles (µCGP) are realized via soft lithographic techniques to enhance the specific delivery of a cocktail of cytotoxic nanoparticles to metastatic foci. By cross-linking short poly(ethylene glycol) (PEG) chains with erodible linkers within a shape-defining template, a deformable and biodegradable polymeric skeleton is realized and loaded with a variety of therapeutic and imaging agents, including docetaxel-nanoparticles. In a model of advanced breast cancer lung metastasis, µCGP amplified the colocalization of docetaxel-nanoparticles with pulmonary metastatic foci, prolonged the retention of chemotoxic molecules at the diseased site, suppressed lesion growth, and boosted survival beyond 20 weeks post nodule engraftment. The flexible design and modular architecture of µCGP would allow the efficient deployment of complex combination therapies in other vascular districts too, possibly addressing metastatic diseases of different origins.

Kaposiform lymphangiomatosis Diagnosis, pathogenesis, and treatment.

Kaposiform lymphangiomatosis (KLA) is a life-threatening rare disease that can cause substantial morbidity, mortality, and social burdens for patients and their families. Diagnosis often occurs long after initial symptoms, and there are few centers in the world with the expertise to diagnose and care for patients with the disease. KLA is a lymphatic anomaly and significant advancements have been made in understanding its pathogenesis and etiology since its first description in 2014. This review provides multidisciplinary, comprehensive, and state-of-the-art information on KLA patient presentation, diagnostic imaging, pathology, organ involvement, genetics, and pathogenesis. Finally, we describe current therapeutic approaches, important areas for research, and challenges faced by patients and their families. Further insights into the pathogenesis of KLA may advance our understanding of other vascular anomalies given that similar signaling pathways may be involved.

Cancer-related knowledge, beliefs, and behaviors among HispanicLatino residents of Indiana.

Cancer is the leading cause of death for Hispanics in the USA. Screening and prevention reduce cancer morbidity and mortality. This study administered a cross-sectional web-based survey to self-identified Hispanic residents in the state of Indiana to assess their cancer-related knowledge, beliefs, and behaviors, as well as to identify what factors might be associated with cancer screening and prevention. Chi-square and Fishers exact test were used to compare associations and logistic regression used to develop both univariate and multivariate regression models. A total of 1520 surveys were completed, median age of respondents was 53, 52% identified as men, 50.9% completed the survey in Spanish, and 60.4% identified the USA as their country of birth. Most were not able to accurately identify ages to begin screening for breast, colorectal, or lung cancer, and there were significant differences in cancer knowledge by education level. US-born individuals with higher income and education more often believed they were likely to develop cancer and worry about getting cancer. Sixty eight percent of respondents were up-to-date with colorectal, 44% with breast, and 61% with cervical cancer screening. Multivariate models showed that higher education, lack of fatalism, older age, lower household income, and unmarried status were associated with cervical cancer screening adherence. Among a Hispanic population in the state of Indiana, factors associated with cervical cancer screening adherence were similar to the general population, with the exceptions of income and marital status. Younger Hispanic individuals were more likely to be adherent with breast and colorectal cancer screening, and given the higher incidence of cancer among older individuals, these results should guide future research and targeted outreach.

Modified signal-to-noise ratio in the liver using the background-to-lung activity ratio to assess image quality of whole-body

The signal-to-noise ratio in the liver (SNR liver) is commonly used to assess the quality of positron emission tomography (PET) images however, it is weakly correlated with visual assessments. Conversely, the noise equivalent count (NEC) density showed a strong correlation with visual assessment but did not consider the effects of image reconstruction conditions. Therefore, we propose a new indicator, the modified SNR liver, and plan to verify its usefulness by comparing it with conventional indicators. We retrospectively analyzed 103 patients who underwent whole-body PETcomputed tomography (CT). Approximately 60 min after the intravenous injection of

Mesothelioma-associated fibroblasts enhance proliferation and migration of pleural mesothelioma cells via c-MetPI3K and WNT signaling but do not protect against cisplatin.

Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Unlike many other cancers, PM is mostly characterized by inactivation of tumor suppressor genes. Its highly malignant nature in absence of tumor driving oncogene mutations indicates an extrinsic supply of stimulating signals by cells of the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are an abundant cell type of the TME and have been shown to drive the progression of several malignancies. The aim of the current study was to isolate and characterize patient-derived mesothelioma-associated fibroblasts (Meso-CAFs), and evaluate their impact on PM cells. Meso-CAFs were isolated from surgical specimens of PM patients and analyzed by array comparative genomic hybridization, next generation sequencing, transcriptomics and proteomics. Human PM cell lines were retrovirally transduced with GFP. The impact of Meso-CAFs on tumor cell growth, migration, as well as the response to small molecule inhibitors, cisplatin and pemetrexed treatment was investigated in 2D and 3D co-culture models by videomicroscopy and automated image analysis. Meso-CAFs show a normal diploid genotype without gene copy number aberrations typical for PM cells. They express CAF markers and lack PM marker expression. Their proteome and secretome profiles clearly differ from normal lung fibroblasts with particularly strong differences in actively secreted proteins. The presence of Meso-CAFs in co-culture resulted in significantly increased proliferation and migration of PM cells. A similar effect on PM cell growth and migration was induced by Meso-CAF-conditioned medium. Inhibition of c-Met with crizotinib, PI3K with LY-2940002 or WNT signaling with WNT-C59 significantly impaired the Meso-CAF-mediated growth stimulation of PM cells in co-culture at concentrations not affecting the PM cells alone. Meso-CAFs did not provide protection of PM cells against cisplatin but showed significant protection against the EGFR inhibitor erlotinib. Our study provides the first characterization of human patient-derived Meso-CAFs and demonstrates a strong impact of Meso-CAFs on PM cell growth and migration, two key characteristics of PM aggressiveness, indicating a major role of Meso-CAFs in driving PM progression. Moreover, we identify signaling pathways required for Meso-CAF-mediated growth stimulation. These data could be relevant for novel therapeutic strategies against PM.

Prevalence and Predictability of Occult Satellite Nodules in Clinical Stage Ia Non-small Cell Lung Cancer following Lobectomy.

We sought to assess the prevalence and clinical predictors of satellite nodules in patients undergoing lobectomy for clinical stage Ia disease. The National Cancer Database was queried for patients who underwent lobectomy for clinical stage cT1N0 NSCLC. Collaborative staging information was used to identify patients who were pathologically upstaged based on having separate tumor nodules in the same lobe as the primary tumor. Multivariable logistic regression was used to assess the association of clinical factors with the detection of separate nodules. A separate tumor nodule was recorded in 2.8% (n 1284) of 45,842 clinical stage Ia patients treated with lobectomy or bilobectomy. Female gender (3.1% vs. male 2.5% P .002) and non-squamous histology (adenocarcinoma 3.2% and large cell neuroendocrine 3.0% vs. squamous cell 1.9% tumors P < .001) were associated with the presence of separate nodules. The frequency increased for tumors larger than 3 cm (≤ 3cm, 2.7% vs. > 3cm, 3.8% P < .001). Other factors associated with separate nodules were upper lobe location, pleural andor lymphovascular invasion and occult lymph node disease. The best predictive model for separate nodules based on the available clinical variables resulted in an area under the curve of 0.645 (95% CI 0.629-0.660). Separate tumor nodules may be detected with a low but relatively consistent frequency across the spectrum of patients with clinical stage Ia NSCLC. The predictive ability using basic clinical factors in the database is limited.

TREATMENT OF BLADDER UROTHELIAL CARCINOMA WITH LUNG METASTASIS AFTER RENAL TRANSPLANTATION.

We report a case of bladder cancer in a 54-year-old woman who underwent renal transplantation for chronic renal failure. Six years after the transplantation, she was diagnosed with muscle-invasive bladder cancer with multiple lung metastases. She received gemcitabinecisplatin therapy for Stage IV bladder cancer, and the dose of the immunosuppressants was reduced to prevent adverse effects. Since lung metastatic lesions disappeared after four courses of chemotherapy and no new lesions were found, we performed radical cystectomy and right nephroureterectomy with ileal conduit construction. Although she was followed closely without therapy, multiple lung metastases appeared 6 months after the radical cystectomy. Gemcitabinecarboplatin therapy was administered, and the lung metastasis improved slightly until the end of the 4th course, but aggressive growth was observed after the 5th course. She switched to palliative treatment without requesting additional treatment and died of cancer 1 year and 9 months after total cystectomy.There is no evidence-based treatment strategy for advanced bladder cancer after kidney transplantation. It is necessary to recognize that the patient had renal dysfunction and was in an immunosuppressed state. Thus, it is crucial to select appropriate drug and surgical treatments for each patient.

Six first-line tyrosine kinase inhibitors reveal novel inhibition potential for the EGFR S768I mutation.

Lung cancer, the leading cause of cancer-related mortality, is the most commonly diagnosed cancer. Tyrosine kinase inhibitors (TKIs) are considered a drug-targeted therapy for non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, limited data are available involving the activity of EGFR TKIs against rare EGFR mutations. Here, based on an endogenous EGFR-depleted cell Line H3255 by CRISPR, H3255 cells with rare mutant EGFR

Source-oriented risk and lung-deposited surface area (LDSA) of ultrafine particles in a Southeast Asia urban area.

Submicron and ultrafine particle (UFP) exposure may be epidemiologically and toxicologically linked to pulmonary, neurodegenerative, and cardiovascular diseases. This study explores UFP and fine particle sources using a positive matrix factorization (PMF) model based on PM

Predictors of Survival After Stereotactic Radiosurgery for Untreated Single Non-Small Cell Lung Cancer Brain Metastases 5- and 10-year Results.

Stereotactic radiosurgery (SRS) presents as a good treatment option for smaller, deep-seated brain metastases (BMs). This study aims to determine predictors of SRS failure for patients with non-small cell lung cancer BMs. This was a retrospective study of single non-small cell lung cancer BMs treated using SRS. We included patients >18 years with a single, previously untreated lesion. Primary outcome was treatment failure, defined as BMs dimension increase above the initial values. Demographic, clinical, and radiological data were collected to study potential predictors of treatment failure. Worse rates of progression-free survival (PFS) were associated with heterogeneous contrast enhancement (18.1 ± 4.1 vs. 41.9 ± 4 months P < 0.001). Better rates of PFS were associated with volumes <1.06 cm Contrast-homogeneous metastases and lesions <1.06 cm

Artificial intelligence in lung cancer diagnosis and prognosis Current application and future perspective.

Lung cancer is one of the malignant tumors with the highest incidence and mortality in the world. The overall five-year survival rate of lung cancer is relatively lower than many leading cancers. Early diagnosis and prognosis of lung cancer are essential to improve the patients survival rate. With artificial intelligence (AI) approaches widely applied in lung cancer, early diagnosis and prediction have achieved excellent performance in recent years. This review summarizes various types of AI algorithm applications in lung cancer, including natural language processing (NLP), machine learning and deep learning, and reinforcement learning. In addition, we provides evidence regarding the application of AI in lung cancer diagnostic and clinical prognosis. This review aims to elucidate the value of AI in lung cancer diagnosis and prognosis as the novel screening decision-making for the precise treatment of lung cancer patients.

The role of self-perceived age in older adults considering adjuvant chemotherapy.

Aging-related concerns can increase the risk of treatment toxicities among older adults considering adjuvant chemotherapy. We previously demonstrated that older adults with cancer who reported feeling older than their chronological age (i.e., self-perceived age) were more likely to have aging-related concerns identified during a geriatric assessment. We explored how decisions about adjuvant chemotherapy vary with or are related to older adults self-perceived age. We conducted a secondary analysis of a multi-phased feasibility pilot using semi-structured interviews that were conducted to explore the patient decision-making process for adjuvant chemotherapy. Interviews incorporated questions about chronological and perceived age as factors for decision-making. Patient eligibility for the study included (1) age ≥ 70 years and older, (2) a diagnosis of breast, colon, or lung cancer and considering adjuvant chemotherapy, and (3) able to read size 18 font in English. Interview data were analyzed using constant comparative method. Twenty-one patients were enrolled. The mean chronological age was 78 years (range 71-91). The average perceived age of patients was 57 years (range 21-80). Eleven patients chose to receive treatment while ten patients did not. Aging-related themes illustrated that self-perceived age plays an important role when patients make decisions about adjuvant chemotherapy. More specifically, patients who reported their self-perceived age as younger than their chronological age also reported better perceived health status and chose to receive adjuvant chemotherapy. Patients experiences of aging and self-perceived age may have different implications for decision-making.

Hierarchical multimodal fusion framework based on noisy label learning and attention mechanism for cancer classification with pathology and genomic features.

Classification of subtype and grade is imperative in the clinical diagnosis and prognosis of cancer. Many deep learning-based studies related to cancer classification are based on pathology and genomics. However, most of them are late fusion-based and require full supervision in pathology image analysis. To address these problems, we present an integrated framework for cancer classification with pathology and genomics data. This framework consists of two major parts, a weakly supervised model for extracting patch features from whole slide images (WSIs), and a hierarchical multimodal fusion model. The weakly supervised model can make full use of WSI labels, and mitigate the effects of label noises by the self-training strategy. The generic multimodal fusion model is capable of capturing deep interaction information through multi-level attention mechanisms and controlling the expressiveness of each modal representation. We validate our approach on glioma and lung cancer datasets from The Cancer Genome Atlas (TCGA). The results demonstrate that the proposed method achieves superior performance compared to state-of-the-art methods, with the competitive AUC of 0.872 and 0.977 on these two datasets respectively. This paper establishes insight on how to build deep networks on multimodal biomedical data and proposes a more general framework for pathology image analysis without pixel-level annotation.

Structure optimization, synthesis, and biological evaluation of 6-(2-amino-1H-benzodimidazole-6-yl)-quinazolin-4(3H)-one derivatives as potential multi-targeted anticancer agents via Aurora A PI3KBRD4 inhibition.

Aurora A (Aurora kinase A), a critical regulator of cell mitosis, is frequently overexpressed in many malignant cancers, and has been considered as a promising drug target for cancer therapy. Likewise, Phosphatidylinositol 3-kinase alpha (PI3Kα) is also regarded as one of the most important targets in cancer therapy by mediating the cell growth and angiogenesis of various human cancers. In addition, Bromodomain-containing protein 4 (BRD4) modulates oncogene expressions of Myc, Aurora kinase and various RTKs. Recently, accumulating evidences indicated that hyperactivated or abnormally expressed Aurora A, PI3Kα or BRD4 are closely associated with drug resistance and poor prognosis of non-small cell lung cancer (NSCLC). Hence, simultaneous inhibition of Aurora A, PI3Kα, and BRD4 is expected to be a new strategy for NSCLC therapy. In this study, we performed further structure optimization of 6-(2-amino-1H-benzodimidazole-6-yl)-quinazolin-4(3H) -one based on previous study to obtain a series of derivatives for discovering potential Aurora A, PI3Kα and BRD4 multi-targeted inhibitors. MTT assay showed that most of the newly synthesized compounds exhibited an evident anticancer activity against the NSCLC cells. Among them, the IC

Reaching multidisciplinary consensus on the management of non-bulkynon-infiltrative stage IIIA N2 non-small cell lung cancer.

The optimal management of patients with non-bulkynon-infiltrative stage IIIA N2 non-small cell lung cancer (NSCLC) remains controversial. In this modified Delphi study from France, we aimed to generate agreement through multidisciplinary decision-making on the clinical management of patients with non-bulkynon-infiltrative N2 NSCLC. An expert panel of 30 physicians from different specialities completed two Delphi rounds of a 76-item questionnaire, pertaining to pathological confirmation of N2 disease initial treatment approach treatment approach in case of disease progressionstability following neoadjuvant chemotherapy treatment approach taking into account various patient and tumour characteristics. Each questionnaire item was scored using a 9-point Likert scale. Consensus in agreement was achieved if ≥ 80 % of responses to a questionnaire item were scored between 7 and 9 and if the median value of the score to the item was ≥ 7. Regarding the pathologic confirmation of N2 disease, agreement (up to 100 %) was reached on endobronchial ultrasoundendoscopic ultrasound as the preferred method of initial mediastinal staging for paratracheal lymph nodes. There was also panellist agreement (up to 93 %) on the adoption as first-line treatment of surgery and (neo)adjuvant chemotherapy in patients with single-station disease, and of concurrent chemoradiotherapy followed by adjuvant immunotherapy in those with multi-station N2 disease. Panellists further agreed on the use of a non-surgical strategy, i.e., concurrent chemoradiotherapy with adjuvant immunotherapy, in patients with single-station N2 disease in case of involvement of ≥ 2 mediastinal lymph nodes disease progression following neoadjuvant chemotherapy compromised cardiopulmonary function if compatible with radiotherapy anticipated right pneumonectomy. This Delphi study reinforces the importance of multidisciplinary discussions leading to the best individual approach to the clinical management of patients with non-bulkynon-infiltrative N2 NSCLC, a challenging heterogeneous population.

Virtual fluoroscopic preprocedural planning using Ziostation2 for transbronchial biopsy A prospective self-controlled study.

Bronchoscopes cannot reach the periphery of the lung because the bronchi are tapered. Therefore, selectively advancing a device-e.g., an endobronchial ultrasonography (EBUS) probe-to the targets can be challenging. Virtual fluoroscopic preprocedural planning (VFPP) is a method in which the route to the target is superimposed on an X-ray fluoroscopy-like image reconstructed from CT images, facilitating the advancement of the EBUS probe to the target. The VFPP method was integrated into the Ziostation2 bronchoscopic navigation system (Ziosoft, Inc., Tokyo, Japan) in 2018. Here, we prospectively examined the feasibility of the VFPP method using Ziostation2 (Zio-VFPP). Thirty-six patients who had pulmonary lesions with long axes ≤30 mm and who underwent thin-slice CT with ≤0.625-mm thickness were enrolled. We initiated bronchoscopy using EBUS with a guide sheath (EBUS-GS) while referring to Ziostation2 bronchoscopic navigation. When the probe was not within a lesion, we attempted to correct its position based on Zio-VFPP. EBUS findings before and after Zio-VFPP were compared. Zio-VFPP was performed in 24 patients, and EBUS findings improved in nine patients. Before Zio-VFPP, 18 patients were outside, but after Zio-VFPP, the number decreased to ten. Statistically, this difference was significant (p 0.0392). There were no cases in which EBUS findings worsened with Zio-VFPP. Zio-VPFPP improves EBUS findings and significantly reduces outside cases. However, further investigation is necessary to verify its effectiveness.

Radiomics feature analysis and model research for predicting histopathological subtypes of non-small cell lung cancer on CT images A multi-dataset study.

Classifying the subtypes of non-small cell lung cancer (NSCLC) is essential for clinically adopting optimal treatment strategies and improving clinical outcomes, but the histological subtypes are confirmed by invasive biopsy or post-operative examination at present. Based on multi-center data, this study aimed to analyze the importance of extracted CT radiomics features and develop the model with good generalization performance for precisely distinguishing major NSCLC subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We collected a multi-center CT dataset with 868 patients from eight international databases on the cancer imaging archive (TCIA). Among them, patients from five databases were mixed and split to training and test sets (560140). The remaining three databases were used as independent test sets TCGA set (n 97) and lung3 set (n 71). A total of 1409 features containing shape, intensity, and texture information were extracted from tumor volume of interest (VOI), then the ℓ After feature selection, 401 features were obtained. Features of intensity, texture GLCM, GLRLM, and GLSZM had higher classification weight coefficients than other features (shape, texture GLDM, and NGTDM), and the filtered image features exhibited significant importance than original image features (p-value 0.0210). Moreover, five ensemble learning algorithms (Bagging, AdaBoost, RF, XGBoost, GBDT) had better generalization performance (p-value 0.00418) than other non-ensemble algorithms (MLP, LR, GNB, SVM, KNN). The Bagging-AdaBoost-SVM model had the highest AUC value (0.815 ± 0.010) on three test sets. It obtained AUC values of 0.819, 0.823, and 0.804 on test set, TCGA set and lung3 set, respectively. Our multi-dataset study showed that intensity features, texture features (GLCM, GLRLM, and GLSZM) and filtered image features were more important for distinguishing ADCs from SCCs. The method of ensemble learning can improve the prediction and generalization performance on the complicated multi-center data. The Bagging-AdaBoost-SVM model had the strongest generalization performance, and it showed promising clinical value for non-invasively predicting the histopathological subtypes of NSCLC.

Prediction of transcript structure and concentration using RNA-Seq data.

Alternative splicing (AS) is a key post-transcriptional modification that helps in increasing protein diversity. Almost 90% of the protein-coding genes in humans are known to undergo AS and code for different transcripts. Some transcripts are associated with diseases such as breast cancer, lung cancer and glioblastoma. Hence, these transcripts can serve as novel therapeutic and prognostic targets for drug discovery. Herein, we have developed a pipeline, Finding Alternative Splicing Events (FASE), as the R package that includes modules to determine the structure and concentration of transcripts using differential AS. To predict the correct structure of expressed transcripts in given conditions, FASE combines the AS events with the information of exons, introns and junctions using graph theory. The estimated concentration of predicted transcripts is reported as the relative expression in terms of log2CPM. Using FASE, we were able to identify several unique transcripts of EMILIN1 and SLK genes in the TCGA-BRCA data, which were validated using RT-PCR. The experimental study demonstrated consistent results, which signify the high accuracy and precision of the developed methods. In conclusion, the developed pipeline, FASE, can efficiently predict novel transcripts that are missed in general transcript-level differential expression analysis. It can be applied selectively from a single gene to simple or complex genome even in multiple experimental conditions for the identification of differential AS-based biomarkers, prognostic targets and novel therapeutics.