Hedegaardadcock9594

Meanwhile, mitochondrial autophagy was observed in MQ-treated KYSE150 cells. More importantly, patient-derived xenograft mouse models of ESCC with SDHC high expression were more sensitive to MQ treatment than low SDHC-expressing xenografts. Taken together, mefloquine inhibits ESCC tumor growth by inducing mitochondrial autophagy and SDHC plays a vital role in MQ-induced anti-tumor effect on ESCC.Background Limited evidence exists on the incidence of gastric cancer (GC), and contradictory results exist for the prognosis of GC based on the Lauren classification. We analyzed the incidence and survival of GC based on the Lauren classification. Methods The Surveillance, Epidemiology, and End Results (SEER) database from 1975 through 2015 was used to identify all patients with surgically resected, histologically diagnosed intestinal or diffused-type GC. Propensity score matching was used to analyze the association between the Lauren classification type and prognosis. Results The trend of total GC incidence showed an obvious decrease (APC = -1.51, 95% CI -2.31 to -1.01) as well as that of the intestinal type (APC = -1.43, 95% CI -2.01 to -1.12). However, we found that the relative incidence of the diffused type was increased (APC = 0.6, 95% CI 0.41-0.82). The trend of the total incidence of GC (APC = -1.31, 95% CI -1.91 to -1.03) and that of the intestinal type (APC = -1.11, 95% CI -1.53 to -0.98) was decre Diffused types of GCs may have a different prognosis compared to intestinal-type GCs in different patient cohorts. Nevertheless, these results should be interpreted with caution in assessing the prognosis in combination with other factors.This study was designed to identify an immune-related gene signature (IRGS) associated with breast cancer (BC) patient outcomes. Transcriptomic data from 1411 BC patients in the TCGA and GEO databases were used to identify differentially expressed immune-related genes (DEIGs) when comparing BC tumor and normal tissue samples. We were able to construct a 27-gene IRGS that was able to effectively separate BC patients into high- and low-risk groups that corresponded to significant differences in overall and recurrence-free survival (OS and RFS, respectively). Besides, the relevance of this signature to immune response and immune cell infiltration of BC tumors was evaluated. These high- and low-risk BC patients were found to exhibit significantly different immune responses and functional enrichment. We also identified patients in the high-risk group exhibited significantly reduced immune cell infiltration of tumors relative to low-risk patients. Together, the results of this analysis offer a novel overview of the immune microenvironment within BC tumors and highlight key immunological genes associated with patient survival outcomes.Surgeries of pelvic bone tumors are very challenging due to the complexity of anatomical structures and the irregular bone shape. CT and MRI are used in clinic for tumor evaluation, each with its own advantages and shortcomings. Combining the data of both CT and MRI images would take advantage of the merits of both images and provide better model for preoperative evaluation. We utilized an artificial intelligence (AI)-assisted CT/MRI image fusion technique and built a personalized 3-D model for preoperative tumor margin assessment. A young female patient with pelvic osteosarcoma was evaluated with our novel image fusion 3-D model in comparison with the 3-D model based solely on CT images. The fusion image model showed more detailed anatomical information and discovered multiple emboli within veins which were previously neglected. The discovery of emboli implied abysmal prognosis and discouraged any attempts for complex reconstruction after tumor resection. Based on the experience with this pelvic osteosarcoma, we believe that our image fusion model can be very informative with bone tumors. Though further validation with a large number of clinical cases is required, we propose that our model has the potential to benefit the clinic in the preoperative evaluation of bone tumors.Objective To investigate predictors of patient-reported urinary incontinence (PRUI) in the first 2 years after post-prostatectomy radiotherapy (PORT) with particular emphasis on possible dose-effect relationships. Patients and Methods Two-hundred-thirteen patients, whose clinical and dosimetric data were prospectively collected within a registered multi-institutional cohort study, underwent PORT with adjuvant (n = 106) or salvage (n = 107) intent with conventional (n = 123, prescribed dose to the prostatic bed 66.6-79.8Gy in 1.8-2.0Gy/fr) or moderately hypo- (n = 90, 65.8-76.8Gy in 2.1-2.7Gy/fr) fractionation during the period 2011-2017. PRUI was evaluated through the ICIQ-SF questionnaire filled in at baseline and every 6 months thereafter. CPI-613 price The analysis focused on three ICIQ-based clinically relevant endpoints (a) very frequent leakage (FREQUENCY, ICIQ3 score >3), (b) moderate to severe amount of urine loss (AMOUNT, ICIQ4>2) (c) objective severe symptoms (OBJECTIVE, ICIQ3+4>5). Predictors of the incidence wi Both FREQUENCY and OBJECTIVE were significantly influenced also by EQD2(α/β = 0.8Gy). The goodness of fit was excellent, as was the calibration; internal calibration confirmed apparent performance. Conclusion Baseline mild urinary incontinence symptoms strongly modulate the 2-year risk of PRUI. In addition, FREQUENCY is characterized by a marked dose-effect relationship also influencing the trend of OBJECTIVE, with results more reliable than AMOUNT as an objective index. A strong impact of fractionation on severe PRUI after post-prostatectomy radiotherapy also emerged.Patients with triple-negative breast cancer (TNBC) have a poor prognosis, partly because of the absence of targeted therapies. Recognition of the key role of immune responses against cancer has allowed the advent of immunotherapy, focused on the inhibition of negative immune checkpoints, such as CTLA-4. CTLA-4 is also expressed in some cancer cells, but its activity in tumor cells is not completely understood. Thus, the aim of the present work was to determine the biological landscape and functions of CTLA-4 expressed in TNBC cells through preclinical and in silico analysis. Exploration of CTLA-4 by immunohistochemistry in 50 TNBC tumors revealed membrane and cytoplasmic expression at different intensities. Preclinical experiments, using TNBC cell lines, showed that stimulation of CTLA-4 with CD80 enhances activation of the ERK1/2 signaling pathway, while CTLA-4 blockade by Ipilimumab induces the activation of AKT and reduces cell proliferation in vitro. We then developed an analytic pipeline to define the eferapy. This work sheds new light on the roles of activated CLTA-4 in the tumor compartment and suggests an important interplay between tumor CLTA-4-activated portraits and immune-infiltrating cell populations.Background Macroscopic vascular invasion (MVI) is a terminal manifestation of hepatocellular carcinoma (HCC) and carries an extremely poor prognosis. In Chinese and Korean HCC guidelines, transarterial chemoembolization (TACE), or/and radiotherapy (RT) is adopted for treatment of MVI. In the current study, we aimed to compare the long-term outcome of TACE + RT to that of RT alone in patients with local advanced HCC with MVI. Methods In this retrospective study, 148 treatment-naive patients of HCC with MVI were enrolled. Of the patients enrolled, 49 received TACE + RT treatment, whereas 99 patients received RT alone as a monotherapy. Overall survival (OS), progression-free survival (PFS), and intrahepatic control were evaluated using univariable and propensity score-matched analyses. Results During follow-up, 126 patients (85.1%) died. The median follow-up time was 55.0 months in the RT group and 57.0 months in the TACE + RT group. The TACE + RT group showed better OS and PFS than the RT group, but intrahepatic control was comparable in these two groups. Of 41 cases well-pairs after propensity score matching, the associations between TACE + RT and better OS and PFS remained (15.0 vs. 8.0 months, and 8.0 vs. 4.0 months, all P less then 0.05). The 1-, 2-, 3-, and 5-years OS rates in the TACE + RT group were 56.1, 28.6, 20.8, and 15.7 vs. 31.5%, 13.1%, 9.8%, and 6.7% in the RT group, respectively (P = 0.017). The 6-, 12-, and 24-months rates in the TACE + RT group were 51.2, 39.0, and 23.1% vs. 36.6%, 13.9%, and 11.1% in the RT group, respectively (P = 0.04). Two patients (4.1%) experienced radiation-induced liver disease (RILD), and one (2.0%) experienced RT-related gastrointestinal (GI) bleed in the TACE + RT groups. Nine patients (9.1%) experienced RILD, and two (2.0%) experienced RT-related GI bleed in the RT groups. Conclusion Transarterial chemoembolization + RT had well-complementarity with no more complications than RT alone, providing a better PFS and OS compared with RT-alone treatment for HCC with MVI.Background The efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) as a maintenance therapy in patients with newly diagnosed advanced ovarian cancer remains unclear. We conducted a meta-analysis to assess the benefits and safety of PARPi maintenance therapy in patients with newly diagnosed advanced ovarian cancer. Methods We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs), which assessed the efficacy of PARPi as a maintenance therapy for newly diagnosed advanced ovarian cancer. Progression-free survival (PFS) was the primary endpoint, which was assessed using hazard ratios (HRs) with 95% confidence intervals (95% CI). Progression-free survival was extracted independently, and the pooled results were used to compare the prognoses of patients who received PARPi maintenance therapy and those who received a placebo. Results Three RCTs, SOLO1, VELIA/GOG-3005, and PRIMA, which included 1,881 patients with newly diagnosed advanced ovarian cancer, were included in the meta-analysis. The overall analysis showed that PARPi maintenance therapy significantly increased PFS (HR, 0.51; 95% CI, 0.33-0.80; P = 0.004) compared to placebo. Subgroup analyses confirmed this result. We also observed an improved PFS in patients with homologous recombination deficiency (HR, 0.50; 95% CI, 0.38-0.66; P less then 0.001) and in patients with BRCA mutations (HR, 0.42; 95% CI, 0.31-0.57; P less then 0.001). Moreover, there were no significant differences in health-related quality of life between the PARPi and placebo groups. Conclusions Patients with newly diagnosed advanced ovarian cancer who received PARPi maintenance therapy had a better prognosis than did those who received a placebo. Moreover, no significant changes in health-related quality of life were seen in PARPi-treated individuals.Cancer stem cells play an essential role in therapy response and aggressiveness of various cancers, including lung adenocarcinoma (LUAD). Interestingly it also shares many features of embryonic stem cells (ESCs). Recently, long non-coding RNAs (lncRNAs) have emerged as a critical regulator of cell physiology. Here, we used expression data of ESCs, LUAD, and normal lung to identify 198 long non-coding hESC-associated lncRNAs (hESC-lncRNAs). Intriguingly, K-means clustering of hESC-associated lncRNAs identified a subgroup of LUAD patients [undifferentiated LUAD (uLUAD)] with high stem cell-like characteristic, decreased differentiation genes expression, and poor survival. We also observed that the uLUAD patients had overexpression of proteins associated with cell proliferation. Interestingly, uLUAD patients were highly enriched with the stemness-related gene sets, and had higher mutation load. A notable result observed was high infiltration of T cells and a higher level of neopeptides in uLUAD patients, making these patients an optimal candidate for immunotherapy.