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Simple Summary: A chest CT via central vein enhancement not only eliminates peripheral vein regurgitation but also provides better image quality that facilitates precise clinical staging. A chest CT via central vein enhancement may be considered after tissue proof in order to better discriminate disease severity. The differences in chest computed tomography (CT) image quality may affect the tumor stage. The aim of this study was to compare the image quality and accuracy of chest CT via central vein and peripheral vein enhancement. Fifty consecutive patients were enrolled from a tertiary medical center in Taiwan from May 2016 to March 2019. All the patients received a chest CT via central vein enhancement prior to neoadjuvant concurrent chemoradiation in order to compare the chest CT that was obtained via the peripheral vein. In addition, blind independent central reviews of chest CT via central vein and peripheral vein enhancement were conducted. For T and N stage, chest CT via central vein enhancement had a greater consistency with endoscopic ultrasonography and positron-emission tomography-computed tomography findings (kappa coefficients 0.4471 and 0.5564, respectively). In addition, chest CT via central vein enhancement also showed excellent agreement in the blind independent central review (kappa coefficient 0.9157). The changes in the T and N stage resulted in stage migration in 16 patients. Chest CT via central vein enhancement eliminated peripheral vein regurgitation and also provided more precise clinical staging. This study is registered under the registered NCT number 02887261. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor (CAR) T cells have shown promising results in cancer treatment. They can be generated with T cells from patients for personalized therapy or donors for off-the-shelf products. A critical step in producing the allogeneic CAR T cells is to knock out the endogenous T cell receptor (TCR). The objective of this study is to determine if inhibition of caspase activities in T cells could increase the cell viability after the TCR knockout mediated by the electrotransfer technology. We observed that inhibition of caspases, especially caspase 3, could significantly improve the cell viability and electrotransfer efficiency. Treatment of cells with caspase inhibitors post electrotransfer could also improve the efficiency of TCR knockout in primary human T cells using electrotransferred ribonucleoprotein. Our data suggest that inhibition of caspases is a promising strategy for improving CAR T cell production. T cell receptor (TCR) knockout is a critical step in producing universal chimeric antigen receptor T cells for cancer immunotherapy. A promising approach to achieving the knockout is to deliver the CRISPR/Cas9 system into cells using electrotransfer technology. However, clinical applications of the technology are currently limited by the low cell viability. In this study, we attempt to solve the problem by screening small molecule drugs with an immortalized human T cell line, Jurkat clone E6-1, for inhibition of apoptosis. The study identifies a few caspase inhibitors that could be used to simultaneously enhance the cell viability and the efficiency of plasmid DNA electrotransfer. Additionally, we show that the enhancement could be achieved through knockdown of caspase 3 expression in siRNA treated cells, suggesting that the cell death in electrotransfer experiments was caused mainly by caspase 3-dependent apoptosis. Finally, we investigated if the caspase inhibitors could improve TCR gene-editing with electrotransferred ribonucleoprotein, a complex of Cas9 protein and a T cell receptor-α constant (TRAC)-targeting single guide RNA (sgRNA). Our data showed that inhibition of caspases post electrotransfer could significantly increase cell viability without compromising the TCR disruption efficiency. These new findings can be used to improve non-viral T cell engineering. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton pump inhibitors (PPIs) are commonly used for acid reduction in peptic ulcer diseases and esophageal reflux diseases. The effects of changing gut microbiota, and prolonged hypergastrinemia were reported. This study demonstrated that long-term PPI use in CRC patients was associated with an increased risk of death with dose–response effect but not for recurrence. PPIs may play a complex role in CRC patients. The dose–response effect of proton pump inhibitors on colorectal cancer prognosis is still under exploration. This population-based study in Taiwan was designed to examine the effect of proton pump inhibitors on overall death, colorectal cancer-specific death, and recurrence in colorectal cancer patients with different cumulative proton pump inhibitor dose levels. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2005 to 2020. After frequency matching with a 1:1 ratio, a total of 20,889 users with proton pump inhibitors and 20,889 without proton pump inhibitors were analyzed. The cumulative defined daily dose level of proton pump inhibitor was stratified to explore the dose–response relationship. A proton pump inhibitor exposure cumulative defined daily dose > 60 after colorectal cancer diagnosis had higher risk of all-cause death than non-proton pump inhibitor users with adjusted hazard ratios of 1.10 (95% CIs: 1.04–1.18). For recurrence, a proton pump inhibitor exposure cumulative defined daily dose > 60 had reduced recurrence risk with an adjusted hazard ratio of 0.84 (95% CIs: 0.76–0.93). This study demonstrated that the long-term use of proton pump inhibitors in patients with colorectal cancer was associated with an increased risk of death that related to the proton pump inhibitor exposure cumulative defined daily dose > 60 and had different dose–response effect in various dose level. [ABSTRACT FROM AUTHOR]

Simple Summary: Molecular target therapy, i.e., antiangiogenesis with bevacizumab, was found to be effective in some patients of epithelial ovarian cancer. Considering the cost, potential adverse effects, including hypertension, proteinuria, bleeding, thromboembolic events, poor wound healing and gastrointestinal perforation, and no confirmed and accessible biomarkers for routine clinical use to direct patient selection for bevacizumab treatment, the identification of new predictive methods remains an urgent unmet medical need. This study identifies an effective biomarker and presents an automatic weakly supervised deep learning framework for patient selection and guiding ovarian cancer treatment. Ovarian cancer is a common malignant gynecological disease. Molecular target therapy, i.e., antiangiogenesis with bevacizumab, was found to be effective in some patients of epithelial ovarian cancer (EOC). Although careful patient selection is essential, there are currently no biomarkers available for routine therapeutic usage. To the authors' best knowledge, this is the first automated precision oncology framework to effectively identify and select EOC and peritoneal serous papillary carcinoma (PSPC) patients with positive therapeutic effect. From March 2013 to January 2021, we have a database, containing four kinds of immunohistochemical tissue samples, including AIM2, c3, C5 and NLRP3, from patients diagnosed with EOC and PSPC and treated with bevacizumab in a hospital-based retrospective study. We developed a hybrid deep learning framework and weakly supervised deep learning models for each potential biomarker, and the experimental results show that the proposed model in combination with AIM2 achieves high accuracy 0.92, recall 0.97, F-measure 0.93 and AUC 0.97 for the first experiment (66% training and 34%testing) and high accuracy 0.86 ± 0.07, precision 0.9 ± 0.07, recall 0.85 ± 0.06, F-measure 0.87 ± 0.06 and AUC 0.91 ± 0.05 for the second experiment using five-fold cross validation, respectively. Both Kaplan-Meier PFS analysis and Cox proportional hazards model analysis further confirmed that the proposed AIM2-DL model is able to distinguish patients gaining positive therapeutic effects with low cancer recurrence from patients with disease progression after treatment (p < 0.005). [ABSTRACT FROM AUTHOR]

Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7' antigen (E7') as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7' (ADSC-E7'-eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer. [ABSTRACT FROM AUTHOR]

This study investigated the clinical outcome of locally advanced cervical esophageal squamous cell carcinoma (ESCC) patients who received curative concurrent chemoradiotherapy (CCRT) and their differences from thoracic ESCC patients. Among 411 enrolled ESCC patients, including 63 with cervical and 348 with thoracic ESCC, 63 thoracic patients were propensity score-matched to the 63 cervical patients. For cervical ESCC, T4b and high tumor grade were independent prognostic factors of a worse overall survival (OS) in univariate and multivariate analyses. The response rates to curative CCRT between cervical and the matched thoracic ESCC groups were similar but cervical ESCC had a better OS than that of the matched thoracic group (21.4 versus 10.1 months, p = 0.012). Better OS was mentioned to be in the patients with complete response (CR), whether in the cervical or matched thoracic ESCC group. For patients without CR, patients who underwent esophagectomy had superior OS than those without operation in the matched thoracic ESCC group (11.6 versus 11.9 months, p = 0.73). Only three patients received operation in the cervical ESCC group, thus the survival difference was not significant. Curative CCRT may be a reasonable treatment for cervical ESCC in clinical practice, and the role of surgery should be considered as salvage therapy if residual disease is evident. [ABSTRACT FROM AUTHOR]