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Abstract Background Small cell lung cancer (SCLC) is a lethal and recalcitrant malignancy with early metastases. However, the molecular and cellular mechanisms underlying its aggressive characteristics remain relatively elusive. Methods In this study, we conducted a comprehensive proteomic analysis of 90 primary tumors, 15 patient-matched lymph node metastatic tumors, and 15 brain metastatic tumors derived from a cohort of 105 SCLC patients. The potential mechanism for SCLC metastasis was investigated based on the variety of protein expression profiles. Results Primary tumors were divided into two categories according to the their different protein expression profiles, using metastatic tumors as reference. Proteomic comparisons across different groups revealed that lipid metabolism, especially phospholipid metabolism, and immune response had a critical role in SCLC metastasis. Additionally, it was shown that high- and low-density lipoprotein cholesterol were both independent prognostic factors for disease free survival of SCLC patients. To identify critical regulators of metastasis in SCLC, support vector machine was adopted to generate a biomarker combination of ten proteins, all of which significantly correlated with the infiltration of immune cells. Furthermore, it was demonstrated that high expression of phospholipase A2 group IIA in stroma was associated with delayed disease recurrence in limited stage SCLC. Conclusions This study highlighted the critical significance of lipid metabolism, especially phospholipid metabolism in the disease recurrence and metastasis of SCLC.

Abstract Background Although low-dose computed tomography (LDCT) screening effectively reduces LC mortality in high-risk individuals with a history of smoking in China, the feasibility and efficacy of lung cancer screening (LCS) in individuals who never smoked versus individuals who smoked remains unclear. Methods We conducted a retrospective analysis of prospective cohort studies at the National Cancer Center (NCC) in China from January 2006 to December 2022. A comprehensive LCS initiative was undertaken, involving 30,468 participants (54.5% male). Participants underwent LCS using LDCT. Potential malignancies were managed through joint consensus between patients and their physicians. Epidemiology, screening eligibility criteria, and LC detection rates and survival outcomes were compared between individuals who smoked and individuals who never smoked. Results Among 30,468 participants, 339 LCs were pathologically confirmed in 289 patients. The LC detection rate was 0.9% (289/30,468) overall, 0.8% in individuals who smoked (71/9,042), and 1.0% in individuals who never smoked (218/21,426). In individuals who smoked, LC detection rates were 0.5% (21/4516) and 1.1% (50/4526) in the

Abstract Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC. Methods Data of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018. Results The incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of

Abstract Background Real‐world application of osimertinib with antiangiogenic agents in non‐small cell lung cancer (NSCLC) is common, but the efficacy data are rarely reported. Methods To obtain an objective efficacy report of different real‐world treatment models of osimertinib and antiangiogenic agents. Results A total of 54 patients with NSCLC were enrolled into the study. Twelve (22.2%) who received a combination of antiangiogenic agents, when there was a trend of osimertinib resistance but did not reach imageology progressive disease (PD), were assigned to Group A, with a median overall survival (OS) and progression‐free survival (PFS) of 48.0 (95% CI, not reached) and 21.0 (95% CI: 16.7–25.3) months, respectively. Thirty (55.6%) who received a combination of antiangiogenic agents when there was imageology PD during treatment with osimertinib were assigned to Group B, with a median OS and PFS of 31.8 (95% CI: 26.6–37.1) and 9.2 (95% CI: 5.9–12.6) months, respectively. Twelve (22.2%) who received a combination of antiangiogenic agents at the initial treatment with osimertinib were assigned to Group C, with a median OS and PFS of 28.5 (95% CI: 15.2–41.8) and 15.3 (95% CI: 7.9–22.7) months, respectively. Patients in Group A achieved a significant prolonged median PFS (p

Purpose This study aimed to investigate the feasibility of biomarkers based on dynamic circulating tumor DNA (ctDNA) to classify small cell lung cancer (SCLC) into different subtypes. Materials and Methods Tumor and longitudinal plasma ctDNA samples were analyzed by next-generation sequencing of 1,021 genes. PyClone was used to infer the molecular tumor burden index (mTBI). Pre-treatment tumor tissues (T1) and serial plasma samples were collected (pre-treatment [B1], after two [B2], six [B3] cycles of chemotherapy and at progression [B4]). Results Overall concordance between T1 and B1 sequencing (n=30) was 66.5%, and 89.5% in the gene of RB1. A classification method was designed according to the changes of RB1 mutation, named as subtype I (both positive at B1 and B2), subtype II (positive at B1 but negative at B2), and subtype III (both negative at B1 and B2). The median progressive-free survival for subtype I patients (4.5 months [95% confidence interval (CI), 2.6 to 5.8]) was inferior to subtype II (not reached, p < 0.001) and subtype III (10.8 months [95% CI, 6.0 to 14.4], p=0.002). The median overall survival for subtype I patients (16.3 months [95% CI, 5.3 to 22.9]) was inferior to subtype II (not reached, p=0.01) and subtype III (not reached, p=0.02). Patients with a mTBI dropped to zero at B2 had longer median overall survival (not reached vs. 19.5 months, p=0.01). The changes of mTBI from B4 to B1 were sensitive to predict new metastases, with a sensitivity of 100% and a specificity of 85.7%. Conclusion Monitoring ctDNA based RB1 mutation and mTBI provided a feasible tool to predict the prognosis of SCLC. [ABSTRACT FROM AUTHOR]

Antimicrobial use (AMU) is the major driver of antimicrobial resistance (AMR) among bacteria in dairy herds. There have been numerous studies on AMU and AMR in dairy cows; however, studies on AMU and AMR in dairy calves are limited. A comprehensive overview of the current state of knowledge of AMU and AMR among pathogens in dairy calves is important for the development of scientifically supported and applicable measures to curb antimicrobial use and the increasing risk of AMR. Therefore, we performed a systematic review of research on AMU and AMR in dairy calves. A total of 75 publications were included, of which 19 studies reported AMU data for dairy calves and 68 described AMR profiles of the four most prevalent bacteria that are associated with calf diarrhea and calf pneumonia. Large variation in AMU was found among herds across different regions. There seems to be a positive association between exposure to antimicrobials and occurrence of resistance. Most AMU was accounted for by treatment of diseases, while a small proportion of AMU was prophylactic. AMU was more common in treating calf diarrhea than in treating pneumonia, and the resistance rates in bacteria associated with diarrhea were higher than those in pathogens related to pneumonia. Organic farms used significantly fewer antimicrobials to treat calf disease; however, the antimicrobial resistance rates of bacteria associated with calf diarrhea and pneumonia on both types of farms were comparable. Feeding waste or pasteurized milk was associated with a higher risk of AMR in pathogens. Altogether, this review summarizes AMU and AMR data for dairy calves and suggests areas for future research, providing evidence for the design of antimicrobial use stewardship programs in dairy calf farming.