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INT6eIF3e represses E-cadherin expression through HIF2α in lung carcinoma A549 cells.

Hypoxia-inducible factor 2 α (HIF2α), a transcription factor playing a vital role in hypoxia, promotes cancer metastasis. We had previously reported that the cancer-related gene integration site 6eukaryotic translation initiation factor 3 subunit e (INT6eIF3e) negatively regulates the protein stability of HIF2α in an oxygen-independent manner. Presently, the downstream targets for INT6eIF3e-regulated HIF2α are unknown. Given the roles of HIF2α and INT6eIF3e in epithelial-mesenchymal transition (EMT) that promotes cancer metastasis, we hypothesized that INT6eIF3e-regulated HIF2α controls EMT. This study shows that INT6eIF3e knockdown in lung carcinoma A549 cells led to increased expression of HIF2α protein and an EMT-like phenotypic change. The increased HIF2α subsequently repressed the E-cadherin gene. Mechanistically, HIF2α interacts with the twist family bHLH transcription factor 1 (TWIST1) known to regulate EMT process, and binds to the proximal promoter region of E-cadherin, repressing it. Collectively, our work demonstrates that HIF2α, regulated by INT6eIF3e, represses the E-cadherin gene through TWIST1 to enhance EMT, suggesting a role of the INT6eIF3e-HIF2α axis in cancer metastasis.

Expression of phosphorylated ribosomal protein S6 in mesothelioma patients - correlation with clinico-pathological characteristics and outcome results from the European Thoracic Oncology Platform (ETOP) Mesoscape project.

Pleural mesothelioma (PM) is an aggressive malignancy with poor prognosis. Although histology and pathologic stage are important prognostic factors, better prognostic biomarkers are needed. The ribosomal protein S6 is a downstream target of the phosphatidylinositol 3-kinase (PI3K) pathway involved in protein synthesis and cell proliferation. In previous studies, low phosphorylated S6 (pS6) immunoreactivity was significantly correlated with longer progression-free survival (PFS) and overall survival (OS) in PM patients. We aimed to correlate pS6 expression to clinical data in a large multi-centre PM cohort as part of the European Thoracic Oncology Platform (ETOP) Mesoscape project. Tissue Micro Arrays (TMAs) of PM were constructed and expression of pS6 was evaluated by a semi-quantitatively aggregate H-score. Expression results were correlated to patient characteristics as well as OSPFS. pS6 IHC results of 364 patients from 9 centres, diagnosed between 1999 and 2017 were available. The primary histology of included tumours was epithelioid (70.3%), followed by biphasic (24.2%) and sarcomatoid (5.5%). TMAs included both treatment-naïve and tumour tissue taken after induction chemotherapy. High pS6 expression (181 patients with H-score>1.41) was significantly associated with less complete resection. In the overall cohort, OSPFS were not significantly different between pS6-low and pS6-high patients. In a subgroup analysis non-epithelioid (biphasic and sarcomatoid) patients with high pS6 expression showed a significantly shorter OS (p < 0.001, 10.7 versus 16.9 months) and PFS (p < 0.001, 6.2 versus 10.8 months). In subgroup analysis, in non-epithelioid PM patients high pS6 expression was associated with significantly shorter OS and PFS. These exploratory findings suggest a clinically relevant PI3K pathway activation in non-epithelioid PM which might lay the foundation for future targeted treatment strategies.

Follistatin-like 1 mitigates intermittent hypoxia-induced melanoma lung metastasis in mice.

Intermittent hypoxia (IH) mimicking obstructive sleep apnea (OSA) has been confirmed to induce tumor lung metastasis via oxidative stress and inflammation responses. Follistatin-like 1 (Fstl1), as a matricellular protein, plays critical roles in inflammatory diseases and cancer. This study aimed to investigate the effect and mechanism of Fstl1 on OSA-IH-induced tumor lung metastasis. Fstl1 Fstl1 levels are decreased in lung tissues from OSA-IH injured mice inoculated with melanoma cells. Fstl1-deficient mice were highly susceptible to the OSA-IH model of melanoma lung metastasis, as assessed by increased number and area of lung metastatic colonies, and by the elevated levels of HIF-1α, Vegf, N-cadherin, and E-cadherin. Lung melanoma tissue in Fstl1 These results suggest that Fstl1 may protect against OSA-IH-induced tumor lung metastasis through oxidative stress and inflammatory responses. Fstl1 may serve as a promising target for OSA-related cancer.

The speckle-type POZ protein (SPOP) inhibits breast cancer malignancy by destabilizing TWIST1.

Epithelial-mesenchymal transition (EMT) inducing transcription factor TWIST1 plays a vital role in cancer metastasis. How the tumor-suppressive E3 ligase, speckle-type POZ protein (SPOP), regulates TWIST1 in breast cancer remains unknown. In this study, we report that SPOP physically interacts with, ubiquitinates, and destabilizes TWIST1. SPOP promotes K63-and K48-linked ubiquitination of TWIST1, predominantly at K73, thereby suppressing cancer cell migration and invasion. Silencing SPOP significantly enhances EMT, which accelerates breast cancer cell migration and invasiveness in vitro and lung metastasis in vivo. Clinically, SPOP is negatively correlated with the levels of TWIST1 in highly invasive breast carcinomas. Reduced SPOP expression, along with elevated TWIST1 levels, is associated with poor prognosis in advanced breast cancer patients, particularly those with metastatic triple-negative breast cancer (TNBC). Taken together, we have disclosed a new mechanism linking SPOP to TWIST1 degradation. Thus SPOP may serve as a prognostic marker and a potential therapeutic target for advanced TNBC patients.

PFKFB4 interacts with FBXO28 to promote HIF-1α signaling in glioblastoma.

Glioblastoma is a highly aggressive brain tumor for which there is no cure. The metabolic enzyme 6-Phosphofructo-2-KinaseFructose-2,6-Biphosphatase 4 (PFKFB4) is essential for glioblastoma stem-like cell (GSC) survival but its mode of action is unclear. Understanding the role of PFKFB4 in tumor cell survival could allow it to be leveraged in a cancer therapy. Here, we show the importance of PFKFB4 for glioblastoma growth in vivo in an orthotopic patient derived mouse model. In an evaluation of patient tumor samples of different cancer entities, PFKFB4 protein was found to be overexpressed in prostate, lung, colon, mammary and squamous cell carcinoma, with expression level correlating with tumor grade. Gene expression profiling in PFKFB4-silenced GSCs revealed a downregulation of hypoxia related genes and Western blot analysis confirmed a dramatic reduction of HIF (hypoxia inducible factor) protein levels. Through mass spectrometric analysis of immunoprecipitated PFKFB4, we identified the ubiquitin E3 ligase, F-box only protein 28 (FBXO28), as a new interaction partner of PFKFB4. We show that PFKFB4 regulates the ubiquitylation and subsequent proteasomal degradation of HIF-1α, which is mediated by the ubiquitin ligase activity of FBXO28. This newly discovered function of PFKFB4, coupled with its cancer specificity, provides a new strategy for inhibiting HIF-1α in cancer cells.

Inhaled marijuana and the lung, a toxic cocktail.

Unlike the well-documented effects of tobacco smoke on the lung, the effects of cannabis smoke remain controversial, the main bias consisting in co-consumption of tobacco. That said, the composition of joint smoke is close to that of cigarettes, containing many compounds that are carcinogenic andor alter the respiratory epithelium. Confirmed respiratory effects in chronic cannabis smokers include aggravated chronic bronchitis symptoms, a cumulative effect with tobacco on COPD and emphysema occurrence, an increased risk of bullous emphysema, and pneumothorax with heightened risk of recurrence after pleural symphysis. Recent prospective studies have shown a negative impact on lung function, with not only damage to the airways, but also DLCO alteration and an accelerated drop in FEV1. Finally, cannabis smoking is very common among young patients with lung cancer. Its consumption could lead to a different lung cancer profile, potentially more undifferentiated and less accessible to targeted therapy. Questioning about cannabis consumption must be systematic and targeted medical care should be offered.

The Use of Palliative Radiotherapy in the Treatment of Lung Cancer.

There have been significant advances in the systemic treatment of stage IV lung cancer, which is now recommended first line in patients with adequate fitness. This includes some patients with brain metastases due to the increased understanding of the central nervous system penetration of targeted therapies. The trials evidence base for palliative radiotherapy pre-dated this routine use of systemic therapy in our practice, which means that the sequence and role of palliative radiotherapy are not currently well defined in the first-line treatment setting. However, due to its efficacy in symptom control, radiotherapy remains a core component in the palliative management of lung cancer, particularly in the second-line setting and those unsuited to primary systemic treatment. This overview focuses on the evidence behind palliative radiotherapy to the thorax and brain for non-small cell and small cell lung cancer and the potential for future studies, including the TOURIST Trial Platform, to guide the future direction of these treatments.

Pulmonary artery wave reflection and right ventricular function after lung resection.

Lung resection has been shown to impair right ventricular function. Although conventional measures of afterload do not change, surgical ligation of a pulmonary artery branch, as occurs during lobectomy, can create a unilateral proximal reflection site, increasing wave reflection (pulsatile component of afterload) and diverting blood flow through the contralateral pulmonary artery. We present a cardiovascular magnetic resonance imaging (MRI) observational cohort study of changes in wave reflection and right ventricular function after lung resection. Twenty-seven patients scheduled for open lobectomy for suspected lung cancer underwent cardiovascular MRI preoperatively, on postoperative Day 2, and at 2 months. Wave reflection was assessed in the left and right pulmonary arteries (operative and non-operative, as appropriate) by wave intensity analysis and calculation of wave reflection index. Pulmonary artery blood flow distribution was calculated as percentage of total blood flow travelling in the non-operative pulmonary artery. Right ventricular function was assessed by ejection fraction and strain analysis. Operative pulmonary artery wave reflection increased from 4.3 (2.1-8.8) % preoperatively to 9.5 (4.9-14.9) % on postoperative Day 2 and 8.0 (2.3-11.7) % at 2 months (P<0.001) with an associated redistribution of blood flow towards the nonoperative pulmonary artery (r>0.523 P<0.010). On postoperative Day 2, impaired right ventricular ejection fraction was associated with increased operative pulmonary artery wave reflection (r-0.480 P0.028) and pulmonary artery blood flow redistribution (r-0.545 P0.011). At 2 months, impaired right ventricular ejection fraction and right ventricular strain were associated with pulmonary artery blood flow redistribution (r-0.634, P0.002 r0.540, P0.017). Pulsatile afterload increased after lung resection. The unilateral increase in operative pulmonary artery wave reflection resulted in redistribution of blood flow through the nonoperative pulmonary artery and was associated with right ventricular dysfunction. NCT01892800.

Role of intratumoral and peritumoral CT radiomics for the prediction of EGFR gene mutation in primary lung cancer.

To determine the added value of combining intratumoral and peritumoral CT radiomics for the prediction of epidermal growth factor receptor (EGFR) gene mutations in primary lung cancer (PLC). This study included 478 patients with PLC (348 adenocarcinomas and 130 other histological types) who underwent surgical resection and EGFR gene testing. Two radiologists performed segmentation of tumors and peritumoral regions using precontrast high-resolution CT images, and 398 radiomic features (212 intra- and 186 peritumoral features) were extracted. The peritumoral region was defined as the lung parenchyma within a distance of 3 mm from the tumor border. Model performance was estimated using Random Forest, a machine-learning algorithm. EGFR mutations were found in 162 tumors 161 adenocarcinomas, and one pleomorphic carcinoma. After exclusion of poorly reproducible and redundant features, 32 radiomic features remained (14 intra- and 18 peritumoral features) and were included in the model building. For predicting EGFR mutations, combining intra- and peritumoral radiomics significantly improved the performance compared to intratumoral radiomics alone (AUC area under the receiver operating characteristic curve, 0.774 Combining intra- and peritumoral radiomics improves the predictive accuracy of EGFR mutations and could be used to aid in decision-making of whether to perform biopsy for gene tests. Adding peritumoral to intratumoral radiomics yields greater accuracy than intratumoral radiomics alone in predicting EGFR mutations and may serve as a non-invasive method of predicting of the gene status in PLC.

Polymeric photothermal nanoplatform with the inhibition of aquaporin 3 for anti-metastasis therapy of breast cancer.

Metastasis, as one of major challenges in the cancer treatment, is responsible for the high mortality of breast cancer. It has been reported that breast cancer cell invasion and metastasis are related to aquaporin 3 (AQP3), which is the transmembrane transport channel for H

Consensus Quality Measures and Dose Constraints for Breast Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

Using evidence-based radiation therapy to direct care for patients with breast cancer is critical to standardize practice, improve safety, and optimize outcomes. To address this need, the Veterans Affairs (VA) National Radiation Oncology Program (NROP) established the VA Radiation Oncology Quality Surveillance Program to develop clinical quality measures (QMs). The VA NROP contracted with the American Society for Radiation Oncology to commission 5 Blue Ribbon Panels for breast, lung, prostate, rectal, and head and neck cancers. The Breast Cancer Blue Ribbon Panel experts worked collaboratively with the NROP to develop consensus QMs for use throughout the VA system, establishing a set of QMs for patients in several areas, including consultation and work-up simulation, treatment planning, and treatment and follow-up care. As part of this initiative, consensus dose-volume histogram (DVH) constraints were outlined. In total, 36 QMs were established. Herein, we review the process used to develop QMs and final consensus QMs pertaining to all aspects of radiation patient care, as well as DVH constraints. The QMs and expert consensus DVH constraints are intended for ongoing quality surveillance within the VA system and centers providing community care for Veterans. They are also available for use by greater non-VA community measures of quality care for patients with breast cancer receiving radiation.

Clinically significant distress and physical problems in living with cancer are associated with survival in lung cancer patients.

The distress thermometer (DT) is a well-established screening tool to detect clinically significant distress in cancer patients. It is often administered in combination with the problem list (PL), differentiating further between various (e.g., physical and emotional) sources of distress. The present study aimed to extend previous research on the association between distress and overall survival. Further exploratory analysis aimed to evaluate the predictive value of the PL for overall survival. Patients (n323) with newly diagnosed lung cancer were recruited from a large cancer center. Patients were split into two groups, those with (DT score ≥5) and those without significant distress. Overall survival time was illustrated by a Kaplan Meier curve and compared with a log rank test. Univariable Cox proportional hazard models were built to control the association of distress with overall survival for age, gender, disease stage,comorbidity and their interaction terms. A multiple linear regression was used to investigate the association of the items from the problem list with survival time. Patients with significant distress had a shorter survival time compared to patients without significant distress (25 vs. 43 months). Regression analysis revealed more problems with both bathing and dressing and eating, as well as absence of diarrhea and increased nervousness to negatively impact overall survival time. Our results show that estimation of the survival function using cancer-related distress is possible. However, when using Cox regression, distress shows no significant value for survival as a predictor. Moreover, our study did not reveal an interaction effect between disease stage, comorbidity, and distress. Overall, results suggest that physical and emotional problems that arise from lung cancer may be useful to identify patients at risk for poor prognosis.

Design, synthesis and biological evaluation of novel tumor hypoxia-activated EGFR tyrosine kinase inhibitors.

Hypoxia is widespread in solid tumors, such as NSCLC, and has become a very attractive target. On the basis of AZD9291 scaffold, novel hypoxia-targeted EGFR inhibitors without the acrylamide warhead but containing hypoxic reductive activation groups were described. Among them, compound JT21 exhibited impressive inhibitory activity (IC

Anemoside B4 prevents chronic obstructive pulmonary disease through alleviating cigarette smoke-induced inflammatory response and airway epithelial hyperplasia.

Cigarette smoke (CS) is one of the major risk factors for chronic obstructive pulmonary disease (COPD) and increases the risk of lung cancer (LC). Anemoside B4 (B4) is the main bioactive ingredient in Pulsatilla chinensis (P. chinensis), a traditional medicinal herb for various diseases. It has a wide range of anti-inflammatory, anti-oxidation and anti-cancer activities. However, in recent years, there is no relevant literature report on the therapeutic effect of B4 on COPD, and the anti-inflammatory and inhibitory effects of anemoside B4 on basal cell hyperplasia in CS-induced COPD have not been clearly established. In the present study, we investigated whether anemoside B4 could alleviate CS or cigarette smoke extract (CSE) induced inflammation of COPD and further prevent basal cell hyperplasia, hoping to find its possible mechanism. In this study, a COPD mouse model was established in C57BL mice by CS exposure 3 months. Bronchial pathology and basal cell hyperplasia were observed by HE staining and immunostaining. The contents of glutathione peroxidase catalase (GSH-PX), malondialdehyde (MDA) and superoxide dismutase (MPO) were determined by GSH-PX, MDA and SOD assay kits, respectively. 16HBE cells were cultured with 5% CSE with or without treatment with B4 (1, 10, 100 μM) or DEX (20 μM) in vitro. Cell viability was assessed by a cell counting kit 8 (CCK-8). Reactive oxygen species (ROS) generation was tested by DCFH-DA. Moreover, anti-inflammatory mechanism of anemoside B4 was further determined by pro-inflammatory cytokines production using RT-PCR. Protein expression levels of MAPKAP-1TGF-β signaling pathway were measured by western blot. Anemoside B4 improved the lung function of mice, relieved lung inflammation and reduced the MDA, MPO and GSH-Px in the plasma. At the same time, B4 repressed the oxidative stress response and played a role in balancing the levels of protease and anti-protease. During the process of bronchial basal cell hyperplasia, B4 alleviated the degree of cell hyperplasia, and prevented further deterioration of hyperplasia through increased P53 and inhibited FHIT protein. In addition, B4 reduced ROS levels in human bronchial epithelial cells stimulated by CSE in vitro study. Meanwhile, B4 treatment also significantly attenuated increased IL-1β, TGF-β, IL-8 and TNF-α from CSE treated human bronchial epithelial cells. The expression of p-P38, AP-1(c-fos, and c-Jun), TGF-β proteins in MAPKAP-1TGF-β signaling pathway were decreased and the signal cascade reaction was blocked. Anemoside B4 protects against CS-induced COPD. These findings indicated that B4 may have therapeutic potential for the prevention and treatment of COPD.

Methylation patterns of Lys9 and Lys27 on histone H3 correlate with patient outcome and tumor progression in lung cancer.

Histone methylation is recognized as an important component of the epigenetic mechanisms of cancer initiation and progression. Previous studies have demonstrated that aberrant alterations in histone methylation are associated with lung cancer. However, novel and specific epigenetic biomarkers for monitoring lung adenocarcinoma remain unknown. A retrospective clinicopathological analysis was performed on 71 lung adenocarcinoma (LUAD) patients who received complete ablative surgical treatment. Tissue arrays were made from the paraffin-embedded LUAD tumor tissues, and these, together with corresponding normal tissues, were examined through immunohistochemistry for several markers histone 3 lysine 9 di-methylation (H3K9me2), histone 3 lysine 9 tri-methylation (H3K9me3), and histone 3 lysine 27 tri-methylation (H3K27me3). The expression level of each marker was analyzed according to the histological classification and clinical prognosis data. Compared with peri-cancerous tissues, cancerous tissues distinctly expressed higher proportions of H3K9me2, H3K9me3, and H3K27me3. A higher expression pattern of H3K27me3 was associated with the poorly differentiation and unfavorable prognosis in LUAD. Based on histological types, it was found that the H3K27me3 level of patients with micropapillary type is high, and it is related to worse prognosis. The findings of this study show that the H3K27me3 and micropapillary type are malignant clinical factors of LUAD. H3K27me3 reduction is a novel epigenetic biomarker for defining high-risk LUAD and predicting worse prognosis. Immunohistochemical evaluation of H3K27me3 expression is an economic, easily available, and readily adaptable method.

Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases an international multicenter study of 697 patients.

Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival. This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PETCT, or MR spectroscopy, and consensus by local clinical providers was required. The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58-73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18-20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS HR 0.98, p < 0.001), TRICs (HR 0.67, p 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p 0.006), and RCC histology (OR 3.10, p 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p 0.03, log-rank test). TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

Rural-urban survival disparities for patients with surgically treated lung cancer.

Nonsmall-cell lung cancer (NSCLC) is a common diagnosis among patients living in rural areas and small towns who face unique challenges accessing care. We examined differences in survival for surgically treated rural and small-town patients compared to those from urban and metropolitan areas. The National Cancer Database was used to identify surgically treated NSCLC patients from 2004 to 2016. Patients from ruralsmall-town counties were compared to urbanmetro counties. Differences in patient clinical, sociodemographic, hospital, and travel characteristics were described. Survival differences were examined with Kaplan-Meier curves and Cox proportional hazards models. The study included 366 373 surgically treated NSCLC patients with 12.4% (n 45 304) categorized as ruralsmall-town. Ruralsmall-town patients traveled farther for treatment and were from areas characterized by lower income and education(all p < 0.001). Survival probabilities for ruralsmall-town patients were worse at 1 year (85% vs. 87%), 5 years (48% vs. 54%), and 10 years (26% vs. 31%) (p < 0.001). Travel distance >100 miles (hazard ratio HR 1.11, 95% confidence interval CI 1.07-1.16, vs. <25 miles) and living in a ruralsmall-town county (HR 1.04, 95% CI 1.01-1.07) were associated with increased risk for death. Rural and small-town patients with surgically treated NSCLC had worse survival outcomes compared to urban and metropolitan patients.

Resection of isolated pancreatic metastases from pulmonary neoplasia a systematic review.

Several types of cancers have been reported to metastasize to the pancreas. Lung cancer with isolated pancreatic metastasis is extremely rare. In selected patients, surgery is advocated. The aim of our study is to carry out a systematic review of the articles published on the surgical treatment of these patients. Our goal was to realize a systematic review in accordance with PRISMA guidelines. We conducted a literature search using MEDLINE (PubMed), EMBASE and SCOPUS databases to identify all studies published from 1967 to 2020 reporting patients with pancreatic resection for metastatic lung cancer to the pancreas. The data of the articles finally selected were represented in tables. The median age of included patients was calculated as well as the median survival. The proportion of patients was calculated according to sex, type of surgery performed and location of the lesion. 3150 articles were included at the beginning. After the screening process, 20 articles were selected for the systematic review. These articles reported data on 23 patients. Presentation was mainly metachronous, with a disease-free interval of 10 (0-54) months. Of these patients, 43.5% were symptomatic at diagnosis and 34.8% had extrapancreatic metastases. Mean overall survival was 17.65 (± 14.56) months. Based in this review, there is limited evidence on the treatment due to the small number of published articles, most of them being case report. Surgical resection of pancreatic metastases from lung cancer could be a safe procedure and it could improve survival rates in selected patients.

Benzimidazole-linked pyrazolo1,5-apyrimidine conjugates synthesis and detail evaluation as potential anticancer agents.

A library of benzimidazole briged pyrazolo1,5-apyrimidine (6a-q) was designed, synthesized and subjected for evaluation for cytotoxic potential. Antiproliferative activity, ranging from 3.1-51.5 μM, was observed against a panel of cancer cell lines which included MCF-7 (breast cancer), A549 (lung cancer), HeLa (cervical cancer) and SiHa (cervical cancer). Among them, 6k, 6l, 6n and 6o have shown significant cytotoxicity and were investigated further to study their probable mechanism of action against MCF-7 cell line. Accumulation of cells at sub-G1 phase was observed in flow cytometric analysis. The detachment of cells from substratum and membrane blebbing seen under bright field microscopy supports the ability of these conjugates to induce apoptosis. Immunostaining and western blot analysis showed EGFR, p-EGFR, STAT3, and p-STAT3 significant downregulation. Western blot analysis demonstrated an elevated level of apoptotic proteins such as p53, p21, Bax, whereas a decrease in the antiapoptotic protein Bcl-2 and procaspase-9, confirming the ability of these conjugates to trigger cell death by apoptosis. EGFR kinase assay confirms the specific activity of conjugates. Molecular docking simulation study disclosed that these molecules fit well in ATP-binding pocket of EGFR. The analysis of docking poses and the atomic interactions of different conjugates rationalize the structural-activity relationship in this series. Benzimidazole-linked pyrazolo1,5-apyrimidine conjugates were synthesized and evaluated for their anticancer potential. All the conjugates have significant anticancer potential. Further mechanistic studies revealed that these conjugates arrest cancer cell growth by EGFRSTAT3 inhibition.

Evaluation of pulmonary artery bleeding during thoracoscopic pulmonary resection for lung cancer.

Bleeding from the pulmonary artery (PA) can be fatal in video-assisted thoracoscopic surgery (VATS) for lung cancer. We evaluated intraoperative PA injury and assessed precautions for thoracoscopic anatomic pulmonary resection. We retrospectively analyzed a total of 1098 patients who underwent radical surgery for lung cancer utilizing complete VATS from January 2010 to December 2021. A total of 16 patients (1.5%) had PA injury during VATS, while hemostasis was performed by conversion to thoracotomy in eight patients (50.0%). Although there was a significantly greater operation time and blood loss for patients in the PA injury group (318.4 vs. 264.9 min, p 0.001 550.3 vs. 60.5 g, p ≤ 0.001, respectively), there was no significant different for the chest tube insertion duration and length of postoperative hospital stay (4.9 vs. 7.8 days, p 0.157 10.6 vs. 9.9 days, p 0.136, respectively). There was a significant difference observed for the surgical procedure related to the left upper lobectomy in the PA injury group (43.8 vs. 18.8%, p 0.012), with the primary causative PA determined to be the left anterior segmental PA (A VATS is both feasible and safe for lung cancer treatment provided the surgeon performs appropriate hemostasis, although fatal vascular injury could potentially occur during VATS. Surgeons need to be aware of the pitfalls regarding PA dissection management.

METTL3-mediated m6A mRNA contributes to the resistance of carbon-ion radiotherapy in non-small-cell lung cancer.

Lung cancer is one of the leading causes of death among cancer patients worldwide. Carbon-ion radiotherapy is a radical nonsurgical treatment with high local control rates and no serious adverse events. N6-methyladenosine (m6A) modification is one of the most common chemical modifications in eukaryotic messenger RNA (mRNA) and has important effects on the stability, splicing, and translation of mRNAs. Recently, the regulatory role of m6A in tumorigenesis has been recognized more and more. However, the dysregulation of m6A and its role in carbon-ion radiotherapy of non-small-cell lung cancer (NSCLC) remains unclear. In this study, we found that the level of methyltransferase-like 3 (METTL3) and its mediated m6A modification were elevated in NSCLC cells with carbon-ion radiotherapy. Knockdown of METTL3 in NSCLC cells impaired proliferation, migration, and invasion in vitro and in vivo. Moreover, we found that METTL3-mediated m6A modification of mRNA inhibited the decay of H2A histone family member X (H2AX) mRNA and enhanced its expression, which led to enhanced DNA damage repair and cell survival.

Genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients noninvolved lung tissue.

Emerging evidence suggests that the prognosis of patients with lung adenocarcinoma can be determined from germline variants and transcript levels in nontumoral lung tissue. Gene expression data from noninvolved lung tissue of 483 lung adenocarcinoma patients were tested for correlation with overall survival using multivariable Cox proportional hazard and multivariate machine learning models. For genes whose transcript levels are associated with survival, we used genotype data from 414 patients to identify germline variants acting as cis-expression quantitative trait loci (eQTLs). Associations of eQTL variant genotypes with gene expression and survival were tested. Levels of four transcripts were inversely associated with survival by Cox analysis (CLCF1, hazard ratio HR 1.53 CNTNAP1, HR 2.17 DUSP14, HR 1.78 and MT1F HR 1.40). Machine learning analysis identified a signature of transcripts associated with lung adenocarcinoma outcome that was largely overlapping with the transcripts identified by Cox analysis, including the three most significant genes (CLCF1, CNTNAP1, and DUSP14). Pathway analysis indicated that the signature is enriched for ECM components. We identified 32 cis-eQTLs for CNTNAP1, including 6 with an inverse correlation and 26 with a direct correlation between the number of minor alleles and transcript levels. Of these, all but one were prognostic the six with an inverse correlation were associated with better prognosis (HR < 1) while the others were associated with worse prognosis. Our findings provide supportive evidence that genetic predisposition to lung adenocarcinoma outcome is a feature already present in patients noninvolved lung tissue.

CT patterns and serial CT Changes in lung Cancer patients post stereotactic body radiotherapy (SBRT).

To evaluate computed tomography (CT) patterns of post-SBRT lung injury in lung cancer and identify time points of serial CT changes. One hundred eighty-three tumors in 170 patients were evaluated on sequential CTs within 29 months (median). Frequencies of post-SBRT CT patterns and time points of initiation and duration were assessed. Duration of increase of primary lesion or surrounding injury without evidence of local recurrence and time to stabilization or local recurrence were evaluated. Post-SBRT CT patterns could overlap in the same patient and were nodule-like pattern (69%), consolidation with ground glass opacity (GGO) (41%), modified conventional pattern (39%), peribronchialpatchy consolidation (42%), patchy GGO (24%), diffuse consolidation (16%), orbit sign (21%), mass-like pattern (19%), scar-like pattern (15%) and diffuse GGO (3%). Patchy GGO started at 4 months post-SBRT. Peribronchialpatchy consolidation and consolidation with GGO started at 4 and 5 months respectively. Diffuse consolidation, diffuse GGO and orbit sign started at 5, 6 and 8 months respectively. Mass-like, modified conventional and scar-like pattern started at 8, 12 and 12 months respectively. Primary lesion (n 11) or surrounding injury (n 85) increased up to 13 months. Primary lesion (n 119) or surrounding injury (n 115) started to decrease at 4 and 9 months respectively. Time to stabilization was 20 months. The most common CT pattern at stabilization was modified conventional pattern (49%), scar-like pattern (23%) and mass-like pattern (12%). Local recurrence (n 15) occurred at a median time of 18 months. Different CT patterns of lung injury post-SBRT appear in predictable time points and have variable but predictable duration. Familiarity with these patterns and timeframes of appearance helps differentiate them from local recurrence.

A review on the role of MEG8 lncRNA in human disorders.

Maternally expressed 8 (MEG8) is a long non-coding RNA which is expressed in the nucleus. It is highly expressed in adrenal, placenta and brain. Recent studies have shown contribution of MEG8 in different disorders ranging from neoplastic ones to diabetic nephropathy, atherosclerosis, ischemic stroke, trophoblast dysfunction and abortion, Henoch-Schonlein purpura and osteoarthritis. It has an oncogenic role in the development of lung, pancreatic and liver cancer. In the current review, we summarize the role of this lncRNA in mentioned disorders, based on the evidence obtained from in vitro, in vivo and human studies.

Prognostic Value of Geriatric Nutritional Risk Index for Patients with Non-Small Cell Lung Cancer A Systematic Review and Meta-Analysis.

The purpose of this review was to collate evidence on the prognostic ability of the geriatric nutritional risk index (GNRI) for predicting overall survival (OS) and disease-free survival (DFS) in non-small cell lung cancer (NSCLC). The datasets of PubMed, Scopus, Embase, CENTRAL, and Google Scholar were searched up to 24 May 2022 for English-language studies reporting the association between GNRI and OS or DFS in NSCLC patients. Eleven studies with 2865 patients were included. We noted that low GNRI was a significant predictor of poor OS (HR 1.96 95% CI 1.66, 2.30 I Data indicate that GNRI has good prognostic ability in patients with NSCLC. Individuals with low GNRI are at an increased risk of poor OS and DFS. GNRI could be incorporated as a simple, easy-to-use tool for the initial stratification of patients thereby allowing focused treatment plans.

Autoimmune retinopathy with onconeuronal antibodies Case report.

We present a case of autoimmune retinopathy in a patient with unknown small cell lung cáncer (SCLC), which was diagnosed after ophthalmological examination. Serology was positive for CV2CRMP5 onconeuronal antibodies. Autoimmune retinopathy is a rare entity that can be missed and underdiagnosed. It is produced by an immune-mediated reaction against retinal antigens. The importance of its early diagnosis lies in the fact that in many of the patients, ocular symptoms appear before the diagnosis of the primary cancer, so its early identification and referral for an extension study may lead to the diagnosis of a hidden primary neoplasm.

Nab-Paclitaxel for Previously Treated Advanced Non-Small Cell Lung Cancer Analysis of Safety and Efficacy for Patients With Renal Impairment.

Renal impairment can affect treatment tolerability and outcome in individuals with cancer. We aimed to assess the safety and efficacy of nab-paclitaxel for previously treated patients with advanced non-small cell lung cancer (NSCLC) and renal impairment enrolled in a phase 3 trial of nab-paclitaxel vs. docetaxel. Previously treated NSCLC patients were randomly allocated (11) to receive docetaxel (60 mgm²) on day 1 or nab-paclitaxel (100 mgm²) on days 1, 8, and 15 of a 21-day cycle. Safety and efficacy outcomes of treatment were evaluated according to renal function. Among the 503 patients enrolled in the phase 3 trial, 17.3% had moderate renal impairment (creatinine clearance of ≤50 mLmin, n 49 for docetaxel and n 38 for nab-paclitaxel) and 53.1% had mild renal impairment (creatinine clearance of >50 to ≤80 mLmin, n 133 for docetaxel and n 134 for nab-paclitaxel). For patients with renal impairment, the incidence of febrile neutropenia was lower in the nab-paclitaxel group than in the docetaxel group. The difference in treatment efficacy for nab-paclitaxel vs. docetaxel among patients with moderate or mild renal impairment was similar to that among the overall study population. Nab-paclitaxel was found to be tolerable and beneficial for previously treated patients with advanced NSCLC and mild or moderate renal impairment.

The safety and acceptability of using telehealth for follow-up of patients following cancer surgery A systematic review.

Although virtual consultations have played an increasing role in delivery of healthcare, the COVID-19 pandemic has hastened their adoption. Furthermore, virtual consultations are now being adopted in areas that were previously considered unsuitable, including post-operative visits for patients undergoing major surgical procedures, and surveillance following cancer operations. This review aims to examine the feasibility, safety, and patient satisfaction with virtual follow-up appointments after cancer operations. A systematic review was conducted along PRISMA guidelines. Studies where patients underwent surgical resection of a malignancy with at least one study arm describing virtual follow-ups were included. Studies were assessed for quality. Outcomes including adverse events, detection of recurrence and patient and provider satisfaction were assessed and compared for those undergoing virtual or in-person post-operative visits. Eleven studies, with 3369 patients were included. Cancer types included were gynecological, colorectal, esophageal, lung, thyroid, breast, prostate and major HPB resections. Detection of recurrence and readmission rates were similar when comparing virtual consultations with in-person visits. Most studies showed high patient and healthcare provider satisfaction with virtual consultations following cancer resection. Concerns were raised about the integration of virtual consultations into workflows in fee-for-service settings, where reimbursement for virtual care may be an issue. Virtual follow-up care can provide timely and safe consultations in surgical oncology. Virtual consultations are as safe as in-person visits for assessing complications and recurrence. Where appropriate, virtual consultations can safely be integrated into the post-operative care pathway for those undergoing resection of malignancy.

The mediating role of decision-making conflict in the association between patients participation satisfaction and distress during medical decision-making among Chinese patients with pulmonary nodules.

When diagnosed as having pulmonary nodules, patients may be mired in the conflict of medical decision-making and suffered from distress. The purpose of this study was to investigate the mediating role of decision-making conflict in the relationship between participation satisfaction in medical decision-making (PSMD) and distress among Chinese patients with incidental pulmonary nodules. A total of 163 outpatients with incidental pulmonary nodules detected in a tertiary hospital were recruited and investigated by Impact of Event Scale (IES), Decision Conflict Scale (DCS), participation satisfaction in medical decision-making Scale (PSMDS), and demographic questionnaire. The mean IES score was 37.35 ± 16.65, representing a moderate level. PSMD was negatively associated with distress, while decision-making conflict was positively associated with distress. The final regression model contained three factors having a first-degree relative diagnosed with lung cancer, worrying about getting lung cancer someday, and decision-making conflict. These three factors explained 49.4 % of the variance of distress. The total effect of PSMD on distress and indirect effect of SPMD on distress caused-by decision-making conflict were significant (P < 0.05). However, the direct effect of PSMD on distress was not significant. Participation of patients in medical decision-making can lower their distress by reducing patients decision-making conflict. Interventions targeting at the decision-making conflict will help alleviate the distress level of patients with pulmonary nodules. The data that support the findings of this study are available on request from the corresponding author.

Impact of CT screening in lung cancer Scientific evidence and literature review.

The treatment of lung cancer has improved significantly in recent years however, lung cancer remains as a leading cause of cancer-related mortality worldwide. Lung cancer screening has been explored, over the past several decades, as a means of reducing lung cancer mortality, to identify asymptomatic disease when it is potentially curable. The National Lung Screening Trial (NLST) established that low-dose computed tomography (LDCT) scans of the chest can be instrumental in reducing lung cancer mortality but the criteria for screening implemented in this trial may not be equitably sensitive across racial and sex subpopulations. Furthermore, the high false detection rate reported in this trial has raised concerns regarding overdiagnosis with LDCT alone. The aim of this review is to summarize the history of lung cancer screening trials, limitations of lung cancer screening, the impact of alternative risk prediction models in reducing disparities, and the use of biomarkers in conjunction with imaging to improve diagnostic authenticity.

Sex-specific associations of cardiorespiratory fitness and galectin-3 in the general population.

Low cardiorespiratory fitness (CRF) is associated with greater mortality and morbidity. Galectin-3 (Gal-3) is a prognostic biomarker for fibrosis and heart failure. Gal-3 is also associated with a greater risk for cardiovascular mortality. Whether CRF is related with Gal-3 is unclear. The objective of this study was to assess the sex-specific associations of CRF and Gal-3 levels in the general population. Gal-3 concentrations were determined using a sandwich enzyme immunoassay in the population-based Study of Health in Pomerania (SHIP-TREND-0). Sex-stratified linear regression models adjusted for age, current smoking status, and renal function were used. Individuals with left ventricular ejection fraction (LVEF) <40%, previous myocardial infarction, atrial fibrillation, chronic lung disease, severe renal disease (estimated glomerular filtration rate <30 mLminmm A total of n 1515 participants with a median age of 49 (IQR 39-60 years, 48% males) were included. In men, a 1 Lmin greater VO VO

Site-Specific Polyplex on CCR7 Down-Regulation and T Cell Elevation for Lymphatic Metastasis Blocking on Breast Cancer.

Tumor metastasis contributes to high cancer mortality. Tumor cells in lymph nodes (LNs) are difficult to eliminate but underlie uncontrollable systemic metastasis. The CC chemokine receptor 7 (CCR7) is overexpressed in tumor cells and interacts with CC chemokine ligand 21 (CCL21) secreted from LNs, potentiating their lymphatic migration. Here, a site-specific polyplex is developed to block the CCR7-CCL21 signal and kill tumor cells toward LNs, greatly limiting their lymphatic infiltration. A CCR7-targeting small interfering RNA (siCCR7) is condensed by mPEG-poly-(lysine) with chlorin e6 (Ce6) modification (PPLC) to form PPLCsiCCR7. The knockdown of CCR7 by siCCR7 in tumor cells significantly reduced their response on CCL21 and LN tropism. Additionally, photodynamic therapy-mediated immune activation precisely targets and kills tumor cells released from the primary foci before they reaches the LNs, reducing the number of tumor cells entering the LNs. Consequently, the PPLCsiCCR7 polyplexes inhibited up to 92% of lung metastasis in 4T1 tumor bearing mice and reduced tumor cell migration to LNs by up to 80%. This site-specific strategy optimized anti-metastasis efficacy and promotes the clinical translational development of anti-metastatic therapy.

Cancer burden and status of cancer control measures in fragile states a comparative analysis of 31 countries.

Information on cancer statistics and cancer control policies is limited in fragile states. This paper describes the cancer burden and status of cancer control measures in these countries. In this comparative analysis, fragile states presenting with a Fragile States Index (FSI) score of 90·0 or more (alert for fragility) for at least 10 years during the 2006-20 period were selected. States with fewer than 10 years of data were selected if they were in alert for fragility during all years. Information on cancer burden, prevalence of cancer risk factors, population-attributable fraction, and on political commitment, health financing, and health system capacity was collected. Cancer incidence and mortality was calculated on the basis of data from population-based cancer registries, estimated with modelling that used mortality-to-incidence ratios and incidence-to-mortality ratios derived from cancer registries in neighbouring countries, or average of rates in selected neighbouring countries. For statistical comparison, fragile states were grouped according to the annual percent change (APC) of the FSI, with group 1 showing an increasing fragility trend (APC 0·2% or higher), group 2 a relatively stable fragility trend (APC between 0·2% and -0·2%), and group 3 a decreasing fragility trend (APC of -0·2% or lower). Overall, the estimated cancer burden in the 31 selected fragile states was lower than worldwide rates, except for cervical and prostate cancer. Cancer cases were attributed to infections (22·40% in group 1, 21·20% in group 2, and 18·80% in group 3) at a higher proportion in fragile states than globally (13·0%). Group 1 and 2 showed a significantly higher exposure to household air pollution (97·70% in group 1 and 94·90% in group 2), whereas current tobacco use in men increased from group 1 to group 3, with lung cancer incidence and mortality being higher in group 3. However, 25 countries had implemented only one or no MPOWER measures for tobacco control. Countries showed an out-of-pocket expenditure of 48·72% in group 1, 42·68% in group 2, and 51·07% in group 3, and only half of the countries had an updated cancer control plan or cancer management guidelines. Fragile states have started the epidemiological transition but are still not implementing enough cancer control measures. There is a need to develop reliable cancer control plans and guidelines, and to create financial mechanisms for implementation. None. For the Arabic and French translations of the abstract see Supplementary Materials section.

Analyses of rare predisposing variants of lung cancer in 6,004 whole genomes in Chinese.

We present the largest whole-genome sequencing (WGS) study of non-small cell lung cancer (NSCLC) to date among 6,004 individuals of Chinese ancestry, coupled with 23,049 individuals genotyped by SNP array. We construct a high-quality haplotype reference panel for imputation and identify 20 common and low-frequency loci (minor allele frequency MAF ≥ 0.5%), including five loci that have never been reported before. For rare loss-of-function (LoF) variants (MAF < 0.5%), we identify BRCA2 and 18 other cancer predisposition genes that affect 5.29% of individuals with NSCLC, and 98.91% (181 of 183) of LoF variants have not been linked previously to NSCLC risk. Promoter variants of BRCA2 also have a substantial effect on NSCLC risk, and their prevalence is comparable with BRCA2 LoF variants. The associations are validated in an independent case-control study including 4,410 individuals and a prospective cohort study including 23,826 individuals. Our findings not only provide a high-quality reference panel for future array-based association studies but depict the whole picture of rare pathogenic variants for NSCLC.

Vaccination-based immunotherapy to target profibrotic cells in liver and lung.

Fibrosis is the final path of nearly every form of chronic disease, regardless of the pathogenesis. Upon chronic injury, activated, fibrogenic fibroblasts deposit excess extracellular matrix, and severe tissue fibrosis can occur in virtually any organ. However, antifibrotic therapies that target fibrogenic cells, while sparing homeostatic fibroblasts in healthy tissues, are limited. We tested whether specific immunization against endogenous proteins, strongly expressed in fibrogenic cells but highly restricted in quiescent fibroblasts, can elicit an antigen-specific cytotoxic T cell response to ameliorate organ fibrosis. In silico epitope prediction revealed that activation of the genes Adam12 and Gli1 in profibrotic cells and the resulting self-peptides can be exploited for T cell vaccines to ablate fibrogenic cells. We demonstrate the efficacy of a vaccination approach to mount CD8

Unsupervised contrastive learning based transformer for lung nodule detection.

Laparoscopic adrenalectomy for a giant adrenal teratoma A case report and review of the literature.

Teratomas typically are benign gonadal neoplasms, arising from more than one embryonic germ layer. Extragonadal teratomas are rare and primary adrenal teratomas more so, with few documented cases. We present one such case, diagnosed via CT, resected via laparoscopic adrenalectomy, and confirmed on histology. To the best of our knowledge, this is the first case documented in the Caribbean. A 38-year-old obese female with restrictive lung disease presented with right backflank pain due to a non-functional 10.5 cm right adrenal mass on CT, likely a giant myelolipoma. Further radiologic review suggested this was instead a mature adrenal teratoma. She underwent a laparoscopic adrenalectomy and histology confirmed a mature adrenal teratoma. Most adrenal tumours are incidentalomas and are usually benign adenomas. Primary adrenal teratomas account for 1 % of teratomas and 0.13 % of adrenal tumours. They may be mature or immature the latter carries a greater risk of malignancy. Benign adrenal teratomas are typically non-functional and commonly mistaken for myelolipomas on imaging. Adrenalectomy is required due to the risk of malignant transformation. The laparoscopic approach depends on size, localized tissue invasion and technical considerations, but offers advantages for the patient if possible. Though uncommon, preoperative radiologic diagnosis of an adrenal teratoma is possible and should be completely resected after a functional workup. A laparoscopic adrenalectomy is preferred once this can be done safely, even when very large, with surgical and oncologic outcomes equivalent to an open approach combined with the known advantages of laparoscopic surgery.

The differential immune response in mild versus fatal SARS-CoV2 infection.

This study compared the immune response in mild versus fatal SARS-CoV2 infection. Forty nasopharyngeal swabs with either productive mild infection (n 20) or negative for SARS-CoV2 (n 20) were tested along with ten lung sections from people who died of COVID-19 which contained abundant SARS-CoV2 and ten controls. There was a 25-fold increase in the CD3T cell numbers in the viral positive nasopharyngeal swabs compared to the controls (p < 0.001) and no change in the CD3T cell count in the fatal COVID-19 lungs versus the controls. CD11b and CD206 macrophage counts were significantly higher in the mild versus fatal disease (p 0.002). In situ analysis for SARS-CoV2 RNA found ten COVID-19 lung sections that had norare detectable virus and also lacked the microangiopathy typical of the viral positive sections. These viral negative lung tissues when compared to the viral positive lung samples showed a highly significant increase in CD3 and CD8 T cells (p < 0.001), equivalent numbers of CD163 cells, and significantly less PDL1, CD11b and CD206 cells (p 0.002). It is concluded that mild SARS-CoV2 infection is marked by a much stronger CD3CD8 T cell, CD11b, and CD206 macrophage response than the fatal lung disease where viral RNA is abundant.

XS-2, a novel potent dual PI3KmTOR inhibitor, exhibits high in vitro and in vivo anti-breast cancer activity and low toxicity with the potential to inhibit the invasion and migration of triple-negative breast cancer.

Breast cancer has become the most commonly diagnosed cancer, surpassing lung cancer, with 2.26 million new breast cancers worldwide in 2020. Hence, there is an urgent need to develop effective molecularly targeted therapeutic drugs to treat breast cancer. In this paper, we designed, synthesized and screened a novel thiophene-triazine derivative, XS-2, as a potent dual PI3KmTOR inhibitor for the treatment of breast cancer. Also, XS-2 was found to be potentially effective against triple-negative breast cancer (TNBC) in vitro during the investigation. We evaluated the in vitro inhibitory effect of XS-2 on 10 cancer cell lines by MTT and 6 kinases to investigated its in vivo antitumor activity in MCF-7 xenograft tumor-bearing BALBc nude mice. In addition, the in vitroin vivo toxicity to mice was also assessed by hemolytic toxicity, HE staining and blood biochemical analysis. In order to investigate the antitumor mechanism of XS-2, a series of experiments were carried out in vitroin vivo animal model and molecular biological levels such as the cell cycle and the apoptosis assay, real-time PCR, western blot, docking and molecular simulations analysis, etc. Whats more, wound healing assay, Transwell and Western Blot were applied to explore the ability of XS-2 to inhibit the cell invasion and migration. The results showed that XS-2 exhibited strong antitumor activity both in vitro and in vivo. The inhibitory activities of XS-2 on ten cancer cell lines were ranging from 1.07 ± 0.11 to 0.002 ± 0.001 μM, which were 1565 times better than that of the lead compound GDC-0941, inhibitory activities against PI3Kα and mTOR kinases were 291.0 and 60.8 nM, respectively. Notably, XS-2 not only showed significant in vivo antitumor activity and low toxicity, with the tumor inhibition rate of 57.0 %, but also exhibited strong inhibitory in the expression of related proteins of PI3K pathway in tumor tissues. In addition, XS-2 significantly inhibited breast cancer MCF-7 and MDA-MB-231 cells in a concentration- and time-dependent manner, and inhibited the migration and invasion ability of MDA-MB-231 and MCF-7 cells. More than that, XS-2 could inhibit the increase of the expression levels of N-cadherin and vimentin upregulated by EGF and reversed the E-cadherin expression down regulated by EGF, resulting in inhibiting EMT in MCF-7 and MDA-MB-231 cells. The results showed that XS-2 was expected to be successfully developed as a high-efficiency and low-toxicity breast cancer therapeutic drug with the potential to inhibit the invasion and migration of TNBC. This provides a new research idea for the treatment of TNBC, which is of great significance.

Non-small cell lung cancer diagnosis aid with histopathological images using Explainable Deep Learning techniques.

Lung cancer has the highest mortality rate in the world, twice as high as the second highest. On the other hand, pathologists are overworked and this is detrimental to the time spent on each patient, diagnostic turnaround time, and their success rate. In this work, we design, implement, and evaluate a diagnostic aid system for non-small cell lung cancer detection, using Deep Learning techniques. The classifier developed is based on Artificial Intelligence techniques, obtaining an automatic classification result between healthy, adenocarcinoma and squamous cell carcinoma, given an histopathological image from lung tissue. Moreover, a report module based on Explainable Deep Learning techniques is included and gives the pathologist information about the images areas used to classify the sample and the confidence of belonging to each class. The results show a system accuracy between 97.11 and 99.69%, depending on the number of classes classified, and a value of the area under ROC curve between 99.77 and 99.94%. The classification results obtain a substantial improvement according to previous works. Thanks to the given report, the time spent by the pathologist and the diagnostic turnaround time can be reduced.

Multicomponent Self-Assembly of Diaminobenzoquinonato-Bridged Manganese(I) Metallosupramolecular Rectangles Host-Guest Interactions, Anticancer Activity, and Visible-Light-Induced CO Releasing Studies.

The one-pot self-assembly of Mn

Feline pulmonary carcinoma Gross, histological, metastatic, and immunohistochemical aspects.

Feline pulmonary carcinoma (FPC) is an uncommon neoplasm with unique morphological features. We describe the gross, histological, metastatic, and immunohistochemical aspects of FPC, based on postmortem examinations from an 11-year retrospective study. Thirty-nine cases were selected. Predispositions were observed in senior (

Combination of available topical beta-blockers and antibiotic ointment for epidermal growth factor receptor tyrosine kinase inhibitor-induced paronychia and pseudopyogenic granulomas in Taiwan.

Painful paronychia and pseudopyogenic granuloma (PG) are common adverse drug reactions (ADRs) associated with the use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to treat non-small cell lung cancer (NSCLC). Multiple local management approaches have been tested with unsatisfactory results. We have introduced an occlusion therapy technique through which available topical drugs for longer than 2 years. Based on the cancer registry and case management system of our hospital, from July 2019 to July 2020, we retrospectively enrolled patients with NSCLC who were treated with EGFR-TKIs and received applications of 0.5% timolol ophthalmic solution (TIMOPTOL XE 0.5%®) combined with a neomycintyrothricin ointment ( A total of 22 patients were enrolled, with a mean age of 66.5 years, most of whom were women (72.7%). Periungual lesion-related pain was reported by all patients, and periungual bleeding and PG were reported in 14% (322) and 64% (1422) of patients, respectively. After the occlusion therapy application of timolol ophthalmic solution combined with neomycintyrothricin ointment twice daily, the overall response rate was 83.3%, including complete response in 18% (422) of cases and partial response in 68% (1522) of cases. We presented an occlusion method using available topical beta-blockers and antibiotic ointment for EGFR-TKI-induced paronychia and PG in Taiwan. The result is favorable. Further randomized control trial is urgent to validate our findings.

Development of a Molecular Blood-Based Immune Signature Classifier as Biomarker for Risks Assessment in Lung Cancer Screening.

Low-dose CT (LDCT) screening trials have shown that lung cancer early detection saves lives. However, a better stratification of the screening population is still needed. In this respect, we generated and prospectively validated a plasma miRNA signature classifier (MSC) able to categorize screening participants according to lung cancer risk. Here, we aimed to deeply characterize the peripheral immune profile and develop a diagnostic immune signature classifier to further implement blood testing in lung cancer screening. Peripheral blood mononuclear cell (PBMC) samples collected from 20 patients with LDCT-detected lung cancer and 20 matched cancer-free screening volunteers were analyzed by flow cytometry using multiplex panels characterizing both lymphoid and myeloid immune subsets. Data were validated in PBMC from 40 patients with lung cancer and 40 matched controls and in a lung cancer specificity set including 27 subjects with suspicious lung nodules. A qPCR-based gene expression signature was generated resembling selected immune subsets. Monocytic myeloid-derived suppressor cell (MDSC), polymorphonuclear MDSC, intermediate monocytes and CD8PD-1 T cells distinguished patients with lung cancer from controls with AUCs values of 0.940.720.88 in the training, validation, and lung cancer specificity set, respectively. AUCs raised up to 1.000.840.92 in subgroup analysis considering only MSC-negative subjects. A 14-immune genes expression signature distinguished patients from controls with AUC values of 0.76 in the validation set and 0.83 in MSC-negative subjects. An immune-based classifier can enhance the accuracy of blood testing, thus supporting the contribution of systemic immunity to lung carcinogenesis. Implementing LDCT screening trials with minimally invasive blood tests could help reduce unnecessary procedures and optimize cost-effectiveness.

Transposon Mutagenesis Reveals RBMS3 Silencing as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis.

Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty-mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers. Among the genes identified was Rbms3, which encodes an RNA-binding protein previously implicated as a putative tumor suppressor. Silencing of RBMS3 via CRISPRCas9 gene editing promoted growth of BRAFV600E lung organoids and promoted development of malignant lung cancers with a distinct micropapillary architecture in BRAFV600E and EGFRL858R GEM models. BRAFV600ERBMS3Null lung tumors displayed elevated expression of Ctnnb1, Ccnd1, Axin2, Lgr5, and c-Myc mRNAs, suggesting that RBMS3 silencing elevates signaling through the WNTβ-catenin signaling axis. Although RBMS3 silencing rendered BRAFV600E-driven lung tumors resistant to the effects of dabrafenib plus trametinib, the tumors were sensitive to inhibition of porcupine, an acyltransferase of WNT ligands necessary for their secretion. Analysis of The Cancer Genome Atlas patient samples revealed that chromosome 3p24, which encompasses RBMS3, is frequently lost in non-small cell lung cancer and correlates with poor prognosis. Collectively, these data reveal the role of RBMS3 as a lung cancer suppressor and suggest that RBMS3 silencing may contribute to malignant NSCLC progression. Loss of RBMS3 cooperates with BRAFV600E to induce lung tumorigenesis, providing a deeper understanding of the molecular mechanisms underlying mutant BRAF-driven lung cancer and potential strategies to more effectively target this disease.

FDA Approval Summary Mobocertinib for Metastatic Non-Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations.

On September 15, 2021, the FDA granted accelerated approval to mobocertinib (Exkivity, Takeda Pharmaceuticals USA, Inc.) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. The approval was based on data from Study AP32788-15-101 (NCT02716116), an international, non-randomized, multi-cohort clinical trial that included patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. The overall response rate in 114 patients whose disease had progressed on or after platinum-based chemotherapy was 28% 95% confidence interval (CI), 20%-37% with a median duration of response of 17.5 months (95% CI, 7.4-20.3). The most common adverse reactions (>20%) were diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain. Product labeling includes a Boxed Warning for QTc prolongation and torsades de pointes. This is the first approval of an oral targeted therapy for patients with advanced EGFR exon 20 insertion mutation-positive NSCLC.

Postoperative Plasmacytoid Dendritic Cells Secrete IFNα to Promote Recruitment of Myeloid-Derived Suppressor Cells and Drive Hepatocellular Carcinoma Recurrence.

Patients with hepatocellular carcinoma (HCC) confront a high incidence of tumor recurrence after curative surgical resection. Hepatic ischemia-reperfusion injury (IRI) is the major consequence of surgical stress during hepatectomy. Although it has been suggested that hepatic IRI-induced immunosuppression could contribute to tumor relapse after surgery, the underlying mechanisms have not been fully defined. Here, using a multiplex cytokine array, we found that levels of postoperative IFNα serve as an independent risk factor for tumor recurrence in 100 patients with HCC with curative hepatectomy. Plasmacytoid dendritic cells (pDC), the major source of IFNα, were activated after surgery and correlated with poor disease-free survival. Functionally, IFNα was responsible for mobilization of myeloid-derived suppressor cells (MDSC) following hepatic IRI. Conditioned medium from IFNα-treated hepatocytes mediated the migration of MDSCs in vitro. Mechanistically, IFNα upregulated IRF1 to promote hepatocyte expression of CX3CL1, which subsequently recruited CX3CR1 monocytic MDSCs. Knockdown of Irf1 or Cx3cl1 in hepatocytes significantly inhibited the accumulation of monocytic MDSCs in vivo. Therapeutically, elimination of pDCs, IFNα, or CX3CR1 could restore the tumor-killing activity of CD8 T cells, hence limiting tumor growth and lung metastasis following hepatic IRI. Taken together, these data suggest that IFNα-producing pDCs drive CX3CR1 MDSC recruitment via hepatocyte IRF1CX3CL1 signaling and lead to tumor recurrence after hepatectomy in HCC. Targeting pDCs and the IFNαCX3CL1CX3CR1 axis could inhibit surgical stress-induced HCC recurrence by attenuating postoperative immunosuppression. IFNα secreted by plasmacytoid dendritic cells drives postoperative immunosuppression and early recurrence of hepatocellular carcinoma, providing new biomarkers and therapeutic targets to improve patient outcomes after surgical resection.

Interstitial lung disease associated with anti-HER2 anti-body drug conjugates results from clinical trials and the WHOs pharmacovigilance database.

Interstitial lung disease (ILD) events associated with anti-human epidermal growth factor receptor 2 (HER2) antibody-drug conjugates (ADCs) have aroused wide attention. In meta-analysis, we systematically reviewed literatures, and the outcomes were the proportion and risk of ILD related to anti-HER2 ADCs. A disproportionality analysis based on data from VigiBase was conducted to characterize the main features of anti-HER2 ADC-related ILDpneumonitis. Two hundred and forty-five all-grade and 47 grade ≥ 3 ILD events with the proportion of 4.4% (95% confidence interval (CI) 2.0%, 6.8%) and 0.5% (95% CI 0.3%, 0.8%) were observed for anti-HER2 ADCs, respectively. Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine significantly increased the risk of all-grade and grade ≥ 3 ILD events with Peto odd ratios of 2.62 (95% CI 1.71, 4.04, P < 0.0001) and 2.82 (95% CI 1.07, 7.42, P 0.04), respectively. In VigiBase, 271 cases of ILDpneumonitis related to trastuzumab emtansine and trastuzumab deruxtecan were extracted. The median time to the onset of event was 86 days and 54.95% of events occurred within 3 months. Trastuzumab emtansine, trastuzumab deruxtecan and trastuzumab duocarmazine increased the risk of ILD, which can lead to serious outcomes and tends to occur early.

Meeting the New Commission on Cancer Operative Standards Where Do We Stand Now

The 2020 Commission on Cancer accreditation standards 5.7 and 5.8 address total mesorectal excision for rectal cancer and lymph node sampling for lung cancer. The purpose of this review was to assess our institutions compliance with these operative standards, which will be required in 2022 and 2023, and provide recommendations to other military training facilities seeking to comply with these standards. A 2018-2020 single institution chart review was performed of operative and pathology reports. Identified deficits were addressed in meetings with colorectal and thoracic surgery leadership, and cases were followed to reassess compliance. A total of 12 rectal and 48 lung cancer cases met the inclusion criteria and were examined. Pre-intervention compliance for standards 5.7 and 5.8 was 58% and 35%, respectively, because of inadequate synoptic reporting and lymph node sampling. After intervention, compliance was 100%. Our institution requires changes to comply with new standards, including in areas of documentation and systematic pulmonary lymph node sampling. We provide lessons learned from our own institutional experience, including practical tips and recommendations to achieve compliance. All military training facilities performing lung and rectal oncologic resections should conduct an internal review of applicable cases in preparation for upcoming American College of Surgeons Commission on Cancer site visits.

The left upper lobe challenge in video-assisted thoracoscopic surgery-use of a composite score to improve the assessment of simulated lobectomy.

The aim of this study is to develop a reliable composite score based on simulator metrics to assess competency in virtual reality video-assisted thoracoscopic surgery lobectomy and explore the benefits of combining it with expert rater assessments. Standardized objective assessments (time, bleeding, economy of movement) and subjective expert rater assessments from 2 previous studies were combined. A linear mixed model including experience level, lobe and the number of previous simulated procedures was applied for the repeated measurements. Reliability for each of the 4 assessments was calculated using Cronbachs alpha. The Nelder-Mead numerical optimization algorithm was used for optimal weighting of scores. A pass-fail standard for the composite score was determined using the contrasting groups method. In total, 123 virtual reality video-assisted thoracoscopic surgery lobectomies were included. Across the 4 different assessments, there were significant effects (P lt 0.01) of experience, lobe, and simulator experience, but not for simulator attempts on bleeding (P 0.98). The left upper lobe was significantly more difficult compared to other lobes (P 0.02). A maximum reliability of 0.92 could be achieved by combining the standardized simulator metrics with standardized expert rater scores. The passfail level for the composite score when including 1 expert rater was 0.33. Combining simulator metrics with 1 or 2 raters increases reliability and can serve as a more objective method for assessing surgical trainees. The composite score may be used to implement a standardized and feasible simulation-based mastery training program in video-assisted thoracoscopic surgery lobectomy.

Metastasectomy in renal cell carcinoma where are we now

Metastatic RCC has a variable natural history. Treatment choice depends on disease and patient factors, but most importantly disease burden and site of metastasis. This article highlights key variables to consider when contemplating metastasectomy for RCC and provide a narrative review on the evidence for metastasectomy in these patients. Tumour subtype is associated with differing patterns of recurrence. Patients with single or few metastatic sites have better outcomes, and those with greater time interval from initial nephrectomy. Local recurrence is particularly amenable to minimally invasive surgical resection and is oncologically sound. Very well selected cases of liver or brain metastases may benefit from metastectomy, although lung and endocrine metastases have more favourable outcomes. Although site and burden of disease is important, the key determinate of outcome in metastasectomy depends mostly on the ability to achieve a complete resection. Adjuvant treatment is not currently advocated. Metastasectomy should be generally reserved for cases where complete resection is achievable, unless the goal of treatment is to palliate symptoms. This field warrants ongoing research, particularly as systemic therapy and minimally invasive surgical techniques evolve. Elucidating tumour biology to inform patient selection will be important in future research.

Cellular dissociation grading on biopsies of pulmonary squamous cell carcinoma provides prognostic information across all stages and is congruent with resection specimen grading.

Grading of squamous cell carcinomas (SCCs) based on tumour budding and cell nest size has been termed cellular dissociation grading (CDG) and was suggested as a robust outcome predictor when assessed in biopsies and resections of various extrapulmonary SCCs. In pulmonary SCC (pSCC), this has so far been shown only for resected cancers. As most lung cancers are inoperable, it is of utmost importance to clarify whether the prognostic impact of CDG is retained in the biopsy setting. Two independent pSCC biopsy cohorts from Munich (n 134, non-resected) and Heidelberg (n 135, resected) were assessed. Tumour budding and cell nest size measures were assembled into the three-tiered CDG system (G1-G3). Data were correlated with clinicopathological parameters and overall- (OS), disease-specific- (DSS), and disease-free survival (DFS). Interobserver variability and concordance between biopsy and resection specimen were also investigated. CDG was highly congruent between biopsy and resection specimens (κ 0.77, p < 0.001). In both pSCC cohorts, biopsy-derived CDG strongly impacted on OS, DSS, and DFS (e.g. DFS p < 0.001). In multivariate survival analyses, CDG remained a stage independent predictor of survival in both cohorts (DFS p < 0.001 respectively hazard ratio Munich cohort CDG-G2 4.31, CDG-G3 5.14 Heidelberg cohort CDG-G2 5.87, CDG-G3 9.07). Interobserver agreement for CDG was almost perfect (κ 0.84, p < 0.001). We conclude that assessment of CDG based on tumour budding and cell nest size is feasible on pSCC biopsies and harbours stage independent prognostic information in resectable as well as non-resectable pSCC. Integration of this grading approach into clinicopathological routine should be considered.

BCAT1 promotes lung adenocarcinoma progression through enhanced mitochondrial function and NF-κB pathway activation.

Lung cancer is one of the most prevalent and malignant cancers, among which lung adenocarcinoma (LUAD) accounts for the majority and remains a major cause of cancer-related mortality worldwide (Cui et al., 2019). Despite the growing intensity of research on the pathobiology and progression of lung cancer and the fact that many genes have been identified as potential drivers and targets for therapy (Luo et al., 2019 Zhang et al., 2019), the treatment and prognosis of lung cancer patients have hardly improved. Therefore, this study aimed to investigate the precise mechanism of lung cancer development and explore efficient diagnostic and therapeutic methods for clinical treatment.

Elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poorer progression-free survival in unresectable stage III NSCLC treated with consolidation durvalumab.

Sustained elevation in neutrophil-to-lymphocyte ratio (NLR) after initial chemoradiotherapy (CRT) has been shown to correlate with worse prognosis in a number of solid organ malignancies. Here, we conducted a retrospective observational cohort study involving six sites across Sydney, Australia, including all patients with unresectable stage III NSCLC treated with CRT and consolidation durvalumab between January 2018 and September 2021. Patients had NLR collected prior to CRT and prior to cycle one of durvalumab. We used an NLR value of 3 to stratify patients into high and low groups. Patients with sustained NLR were defined as those with values ≥3 at both timepoints. A total of 145 patients were included in the study. The median age of patients was 66 years with median follow-up of 15.1 months. The median PFS was 17.6 months in the pre-CRT NLR high cohort and not reached (NR) in the pre-CRT NLR low cohort (HR 1.99 p 0.01). The median OS was 35.5 months in the high pre-CRT NLR cohort compared with 42.0 months in the low pre-CRT NLR cohort (HR 2.62 95% CI 1.23-5.56, p < 0.01). Median PFS for sustained NLR elevation was 17.1 months versus NR (HR 1.5 p < 0.01). Pre-CRT NLR and sustained NLR remained independently prognostic for PFS on multivariate analysis (p 0.04, p 0.01) respectively. Pre-CRT NLR and sustained NLR is associated with worse PFS outcomes in unresectable stage III NSCLC treated with CRT and durvalumab. Pre-CRT NLR is also associated with worse OS.

The pathogenesis of organ fibrosis Focus on necroptosis.

Fibrosis is a common process of tissue repair response to multiple injuries in all chronic progressive diseases, which features with excessive deposition of extracellular matrix. Fibrosis can occur in all organs and tends to be nonreversible with the progress of the disease. Different cells types in different organs are involved in the occurrence and development of fibrosis, that is, hepatic stellate cells, pancreatic stellate cells, fibroblasts and myofibroblasts. Various types of programmed cell death, including apoptosis, autophagy, ferroptosis and necroptosis, are closely related to organ fibrosis. Among these programmed cell death types, necroptosis, an emerging regulated cell death type, is regarded as a huge potential target to ameliorate organ fibrosis. In this review, we summarize the role of necroptosis signalling in organ fibrosis and collate the small molecule compounds targeting necroptosis. In addition, we discuss the potential challenges, opportunities and open questions in using necroptosis signalling as a potential target for antifibrotic therapies.

A heterozygous p.S143P mutation in

Lamins A and C are nuclear intermediate filament proteins that form a proteinaceous meshwork called lamina beneath the inner nuclear membrane. Mutations in the

Datasets for gene expression profiles of head and neck squamous cell carcinoma and lung cancer treated or not by PD1PD-L1 inhibitors.

Identification of tumors harboring an overall active immune phenotype may help for selecting patients with advanced head and neck squamous cell carcinomas (HNSCC) and non-small cell lung cancer (NSCLC) who may benefit from immunotherapies. In this context, we generated targeted gene expression profiles in three and two independent cohorts of patients with HNSCC or NSCLC respectively, treated or not by PD-1PD-L1 inhibitors. Notably, we generated two datasets including 102 and 82 patients with HNSCC or NSCLC treated with PD-1PD-L1 inhibitors. Clinical information, including detailed survival raw data, is available for each patient, allowing to test association between gene expression data and patient survival (overall and progression-free survival). Moreover, we also generated gene expression datasets of 27 paired HNSCC samples from diagnostic biopsies and versus surgically resected specimens as well as 33 paired HNSCC samples at initial diagnosis (untreated) and at recurrence. Those datasets may allow to test the stability of a given biomarker across paired samples.

Study on the Potential Mechanism of miR-22-5p in Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) ranks among one of the most lethal malignancies worldwide. A better and comprehensive understanding of the mechanism of its malignant progression will be helpful for clinical treating NSCLC. The miRNA expression profiles and target gene profiles downloaded from the Gene Expression Omnibus and TargetScan databases were used to identify the key regulatory pattern in NSCLC by bioinformatic analysis. The regulation of miRNA to target mRNA was verified by luciferase reporter assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. A series of the in vitro and in vivo experiments were conducted to examine the mechanism of the overexpression or knockdown of the miRNA andor target gene. In this study, miR-22-5p was remarkably downregulated in NSCLC than in normal lung cells. The in vitro experiments showed that it could substantially inhibit NSCLC cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) progression. The results of luciferase reporter assay, qRT-PCR, and Western blot revealed that TWIST2 was a direct target gene of miR-22-5p. The results of in vitro and in vivo feedback experiments further demonstrated that miR-22-5p relied on TWIST2-induced malignant progression to regulate NSCLC proliferation, metastasis, and EMT progression. This study revealed that miR-22-5p downregulation contributed to the malignant progression of NSCLC by targeting TWIST2. The findings highlight a potential novel pathway that could be therapeutically targeted in treating NSCLC.

A new detection method for canine and feline cancer using the olfactory system of nematodes.

Cancer is the leading cause of death in dogs and cats. Early diagnosis of cancer is critical for effective treatment and improving survival rates. Nematode-NOSE (N-NOSE) is a commercially available non-invasive human cancer screening test that uses the sense of smell of the nematode

Clinical features and prognostic indicators in upper-tract urothelial carcinoma with bone metastasis.

With the gradual increase in the incidence of upper-tract urothelial carcinoma (UTUC), its metastatic disease has attracted much attention. The prognosis of UTUC patients with bone metastasis is worse than that of UTUC patients with other metastases. Therefore, the current study is performed to analyze the clinicopathologic features and survival predictors among UTUC patients with bone metastasis. We reviewed the Surveillance, Epidemiology, and End Results (SEER) database to select cases diagnosed with UTUC and bone metastasis at present from 2010 to 2016. Overall survival (OS) and cancer-specific survival (CSS) were first performed by applying univariate Cox regression analysis. Then we performed multivariate Cox analysis to determine independent predictors of survival. Forest plots were drawn by GraphPad 8.0.1 and used to visually display the results of multivariate analysis. Kaplan-Meier method was applied to intuitively show the prognosis difference of each independent risk factor. We finally identified 380 UTUC patients with bone metastasis for survival analysis, of which 230 males (60.5%) and 150 females (39.5%). The mean and median age at diagnosis were 71 and 72 years, respectively. Simultaneous lung metastasis (33.4%) and liver metastasis (31.1%) were more common in UTUC patients with bone metastasis. The 1-year OS and CSS rates of this research population were 23.8% and 26.6%, respectively. Multivariate Cox proportional hazards modeling controlling for surgery, chemotherapy, brain metastasis, liver metastasis, lung metastasis, and marital status, revealed that surgery, chemotherapy, no liver metastasis, no lung metastasis, and married status predicted for better OS and CSS. Surgery and chemotherapy are optimal management of UTUC patients with bone metastasis. Active treatments on lung and liver metastases should be performed. The prognosis of patients with unmarried status or others should be further improved.

Survival benefit of primary and metastatic tumor resection for colon cancer with liver metastases A population based, propensity score-matched study.

Colon cancer remains one of the most common malignancies and we aimed to evaluate whether surgery has an effect on the survival of metastatic colon patients. We analyzed 7,583 metastatic colon patients from the Surveillance, Epidemiology, between January 2010 and December 2015. Using Cox proportional hazards models and Kaplan-Meier curves, the overall survival rate (OS) and cancer-specific survival rate and End Results (SEER) registry (CSS) months (m) were evaluated with corresponding 95% confidence intervals (95% CIs). Propensity score matching (PSM) was performed to adjust for potential baseline confounding of all comparison groups. In general, receiving both primary and metastatic tumor resection (PMTR) remarkably improved OS and CSS compared with only primary tumor resection (PTR) after PS matching (PSM) ( The results from this large SEER cohort supported PMTR might improve the survival of colon patients with liver metastases on the basis of chemotherapy.

StatPearls

One of the most difficult challenges for any prescriber is distinguishing between the legitimate prescription of controlled substances versus the prescription potentially used for illegitimate purposes. To discern the difference, prescribers need to understand the signs, symptoms, and treatment of acute and chronic pain and the signs and symptoms of patients misusing controlled substances. A common reason people seek the care of medical professionals is pain relief. While many categories of pain medications are available, opioid analgesics are FDA-approved for moderate to severe pain. As such, they are a common choice for patients with acute, cancer-related, neurologic, and end-of-life pain. Prescribing opioid analgesics for chronic pain is controversial and fraught with inconclusive standards. In the 1990s, due to the chronic failure of health professionals to undertreat severe pain, opioid analgesic prescribing was expanded. Unfortunately, this led to increased overuse, diversion of drugs, opioid use disorder, and overdose. The Catch-22 seems to be either health professionals undertreat, and there is needless suffering, or they overtreat, with a potential to cause adverse effects like increased opioid analgesic use disorder and potential overdose. The prescribing of opioid analgesics peaked in 2011. Since then, both prescribing and overdose have been declining, yet as a society, in both the lay and scientific literature, there are grave concerns that we are still in the middle of an opioid crisis. Perhaps the biggest challenge of caring for patients with pain is that individuals have different tolerance levels and require variable opioid doses to obtain adequate pain relief. Patients may have a range of behavioral, cultural, emotional, and psychologic responses to pain versus a substance use disorder often, it is challenging to tell the difference. All health professionals engaged in pain management need an understanding of the treatment recommendations and safety concerns in prescribing opioid analgesics. Appropriate opioid prescribing requires a thorough patient assessment, short and long-term treatment planning, close follow-up, and continued monitoring. All providers need to be aware of appropriate patient assessment and treatment planning, and the possibility of use disorder, diversion, and potentially dangerous behavioral responses to controlled substances, e.g., opioid analgesics differ from pseudoaddiction and physical dependence. It is unfortunately clear that many clinicians know little about opioid use disorder. They do not understand it is a disease, and many believe opioid dependence is the same as opioid use disorder. Lack of a clear understanding results in clinicians confusing a patient with chronic non-use disorder with the one misusing their prescribed opioid. Lack of training and educational deficits often interfere with the appropriate prescription of opioid analgesic agents. To prevent the misuse of controlled substances, providers that prescribe controlled substances should learn prescribing practices that minimize or prevent adverse consequences.

StatPearls

Pneumonectomy, while effective at removing lung tumors, can carry high morbidity and mortality by removing an entire half of a persons lung volume. Pulmonary resection techniques are varied and categorized by the extent of lung resected. Pulmonary sleeve resection (PSR) is a broad term to describe circumferential excision of a part of the bronchus andor pulmonary vessels during lung parenchyma resection while preserving the uninvolved portions of the lung. Bronchoplasty or vascular reconstructions are incorporated techniques where the two separate pieces of remaining bronchus or vessels are re-anastomosed. The most common indication is for lung neoplasm. When discussing PSR with lobectomy, or one lobe of the lung, the term sleeve lobectomy (SL) is commonly used. Some papers have also used the terms extended to describe sleeve resection characteristics when more than one lobe is resected. PSR was first attempted in the late 1940s for a benign mass to preserve lung function. In the mid-late 1950s, the feasibility of PSR for lung cancer was proven. By the early 1980s, SL was gaining traction with the technique used to treat low-grade lung malignancies. The oncologic and functional results after SL are predominantly studied in patients with centrally located non-small cell lung cancer. A meta-analysis demonstrated better survival and quality of life in patients with early-stage locally advanced lung cancer who underwent PSR, as compared to traditional pneumonectomy. With advancements in perioperative care and a better understanding of lung-sparing surgeries oncologic benefits for locally advanced central lung cancers, PSR techniques are now the preferred approach, even in patients with good pre-operative pulmonary reserve. Improvement in video-assisted thoracic surgery (VATS) and robotic surgery platforms have allowed complex lung resections such as SL to be performed via minimally invasive approaches. There is now mounting literature establishing the safety and feasibility of SL using minimally invasive surgical techniques. PSR is already considered a technically challenging thoracic surgical procedure, so only certain centers will have the necessary expertise in performing PSR using minimally invasive techniques. It is notable that even though minimally invasive techniques are becoming more common for lobectomies, SL is still a smaller portion of all lobectomies performed. Compared to pneumonectomy, PSR has improved survival, quality of life, improved pulmonary function, and lower mortality rates. Although initially used for patients unable to tolerate pneumonectomy, PSR is now a preferred approach for anatomically suitable tumors.