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Simple Summary: In the United States, ovarian cancer (OCa) is the most lethal of all gynecologic malignancies. Survival rates for OCa with clinically localized disease have been enhanced by presently approved therapies; however, the majority (~90%) of patients with high-grade serous OCa (HGSOC) relapse with incurable metastases. In this investigation, we explored the hypothesis that the elevated basal endoplasmic reticulum stress (ERS) in OCa could be a significant vulnerability, offering a potential strategy to address OCa heterogeneity. We specifically tested the utility of targeting increased ERS in OCa cells by engaging the novel target lysosomal acid lipase A (LIPA) using the unique compound ERX-41. Our findings indicate that ERX-41 is a new targeted therapy that specifically targets the LIPA protein through a distinct mechanism of action. Furthermore, our results reveal that the binding of ERX-41 to LIPA leads to the induction of ERS and cell death in OCa cells. Ovarian cancer (OCa) is the most lethal form of gynecologic cancer, and the tumor heterogeneities at the molecular, cellular, and tissue levels fuel tumor resistance to standard therapies and pose a substantial clinical challenge. Here, we tested the hypothesis that the heightened basal endoplasmic reticulum stress (ERS) observed in OCa represents an exploitable vulnerability and may overcome tumor heterogeneity. Our recent studies identified LIPA as a novel target to induce ERS in cancer cells using the small molecule ERX-41. However, the role of LIPA and theutility of ERX-41 to treat OCa remain unknown. Expression analysis using the TNMplot web tool, TCGA data sets, and immunohistochemistry analysis using a tumor tissue array showed that LIPA is highly expressed in OCa tissues, compared to normal tissues. ERX-41 treatment significantly reduced the cell viability and colony formation ability and promoted the apoptosis of OCa cells. Mechanistic studies revealed a robust and consistent induction of ERS markers, including CHOP, elF2α, PERK, and ATF4, upon ERX-41 treatment. In xenograft and PDX studies, ERX-41 treatment resulted in a significant reduction in tumor growth. Collectively, our results suggest that ERX-41 is a novel therapeutic agent that targets the LIPA with a unique mechanism of ERS induction, which could be exploited to treat heterogeneity in OCa. [ABSTRACT FROM AUTHOR]

Context: Coronary heart disease (CHD) refers to a disease where coronary atherosclerosis induces stenosis or obstruction of the blood vessels. Endothelial progenitor cells (EPCs) function to protect and repair the vascular endothelium, and their functional activity state reflects the ability of the body to repair vascular damage. In the peripheral blood of patients with CHD, the density of EPCs decreases, and the function of EPCs is low.Objective: This study aimed to investigate the effects of a China Food and Drug Administration (CFDA)-approved prescription medicine, Tongxin, on the density and function of endothelial progenitor cells (EPCs) in peripheral blood.Design: In this study, a randomized, single blind, parallel controlled clinical trial was used. The single blind subjects were subjects.Setting: The study took place in the Cardiology and Emergency Departments at Shanghai Municipal Hospital of Traditional Chinese Medicine in Shanghai, China.Participants: Participants were 48 patients with coronary heart disease at the hospital.Intervention: Participants were randomly divided into 2 groups (n = 24 each): a control group and an intervention group. Both groups received routine drug treatments, such as platelet inhibitors, nitrates, β-receptor blockers, statins, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), and calcium blockers. The control group was treated with the Shexiang Baoxin Pill, while the intervention group was treated with prescription Tongxin. The course of treatment was 3 months for both groups.Outcome Measures: Changes in the density and function of EPCs in the peripheral blood of the 2 groups were measured at baseline and postintervention, and the clinical efficacy of the 2 treatments was statistically analyzed.Results: The density of EPCs was significantly higher in both groups after 3 months of treatment, compared to the densities at baseline (P < .05). The change in density between baseline and postintervention was significantly greater for the intervention group than for the control group (P < .05). For the control group, the proliferative vitality [optical density (OD)] value of the EPCs was significantly higher than that at baseline from the fourth day of treatment (P < .05). In the intervention group, the OD value was significantly higher than that at baseline from the first day of treatment (P < .05). Furthermore, the intervention group's cells began to enter the logarithmic growth phase of increase from the fifth day of treatment, and the group's increase as significantly higher than the control group's from the fifth to the seventh dayof treatment (P < .05 for all 3 days). Moreover, the total effective rate was higher in the intervention group than in the control group (P < .05).Conclusions: Prescription Tongxin can stimulate the release of EPCs from the bone marrow to the peripheral blood of patients with CHD, can significantly increase the proliferation of EPCs in the peripheral blood, and can improve the clinical symptoms of patients. Its curative effect was greater than that of the control treatment. [ABSTRACT FROM AUTHOR]

Introduction: Cancer patients are prone to infections, but the mortality of fatal infections remains unclear. Understanding the patterns of fatal infections in patients with cancer is imperative. In this study, we report the characteristics, incidence, and predictive risk factors of fatal infections among a population-based cancer cohort. Methods: A total of 8,471,051 patients diagnosed with cancer between 1975 and 2016 were retrospectively identified from the Surveillance, Epidemiology, and End Results (SEER) program. The primary outcome was dying from fatal infections. Mortality rates and standardized mortality ratios (SMRs) adjusted for age, sex, race, and calendar year were calculated to characterize the relative risks of dying from fatal infections and to compare with the general population. Furthermore, cumulative mortality rates and the Cox regression models were applied to identify predictive risk factors of fatal infections. Results: In cancer patients, the mortality rate of fatal infections was 260.1/100,000 person-years, nearly three times that of the general population [SMR, 2.92; 95% (confidence interval) CI 2.91–2.94]. Notably, a decreasing trend in mortality rate of fatal infections was observed in recent decades. SMRs of fatal infections were highest in Kaposi sarcoma (SMR, 162.2; 95% CI 159.4–165.1), liver cancer (SMR, 30.9; 95% CI 30.0–31.8), acute lymphocytic leukemia (SMR, 19.1; 95% CI 17.0–21.4), and acute myeloid leukemia (SMR, 13.3; 95% CI 12.4–14.3). Patients aged between 20 and 39 years old exhibited a higher cumulative mortality rate in the first few years after cancer diagnosis, whereas the cumulative mortality rate of those > 80 years old was rapidly increasing and became the highest approximately 3 years post-cancer diagnosis. Predictive risk factors of dying from fatal infections in cancer patients were the age of 20–39 or > 80 years, male sex, black race, diagnosed with cancer before 2000, unmarried status, advanced cancer stage, and not receiving surgery and radiotherapy, but receiving chemotherapy. Conclusion: Cancer patients were at high risks of dying from infectious diseases. Certain groups of cancer patients, including those aged between 20 and 39 or > 80 years, as well as those receiving chemotherapy, should be sensitized to the risk of fatal infections. [ABSTRACT FROM AUTHOR]

Background: This study aimed to establish a novel nomogram prognostic model to predict death probability for non-small cell lung cancer (NSCLC) patients who received surgery..Methods: We collected data from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute in the United States. A nomogram prognostic model was constructed to predict mortality of NSCLC patients who received surgery.Results: A total of 44,880 NSCLC patients who received surgery from 2004 to 2014 were included in this study. Gender, ethnicity, tumor anatomic sites, histologic subtype, tumor differentiation, clinical stage, tumor size, tumor extent, lymph node stage, examined lymph node, positive lymph node, type of surgery showed significant associations with lung cancer related death rate (P < 0.001). Patients who received chemotherapy and radiotherapy had significant higher lung cancer related death rate but were associated with significant lower non-cancer related mortality (P<0.001). A nomogram model was established based on multivariate models of training data set. In the validation cohort, the unadjusted C-index was 0.73 (95% CI, 0.72-0.74), 0.71 (95% CI, 0.66-0.75) and 0.69 (95% CI, 0.68-0.70) for lung cancer related death, other cancer related death and non-cancer related death.Conclusions: A prognostic nomogram model was constructed to give information about the risk of death for NSCLC patients who received surgery. [ABSTRACT FROM AUTHOR]

Background. Portal vein tumor thrombosis (PVTT) is one of the major predictive factors for patients with hepatocellular carcinoma (HCC). The objective of this study was to establish a prognostic nomogram for identifying individual survival outcomes in patients with HCC and PVTT on conservative treatment based on specific factors. Methods. Two hundred and ten patients with HCC and PVTT on conservative treatment in Beijing Ditan Hospital between June 2008 and May 2017 were studied retrospectively as a derivation cohort. We built a nomogram based on independent risk factors for survival prediction. The concordance index (c-index) and a calibration curve were used to evaluate the predictive accuracy. During the study, 102 patients were included at the Putuo Hospital and Third People's Hospital of Changzhou as a validation cohort. Results. In the derivation cohort, the independent factors for overall survival were identified by multivariate analysis, namely, aspartate aminotransferase ≥119 IU/L, gamma-glutamyl transferase ≥115 IU/L, Child–Pugh class C liver function, creatinine ≥91 μmoI/L, α-fetoprotein ≥400 ng/ml, and largest tumor diameter ≥5 cm. The nomogram had a c-index of 0.737 (95% confidence interval, 0.692–0.782) and the calibration curves fitted well. The median survival time was 4.2 months in the derivation cohort, with an MST of 5 months for BCLC C stage and 1.8 months for BCLC D stage patients. Kaplan–Meier analysis showed significant statistical differences in the 6-month overall survival rates of the primary and validation cohorts after the total scores were divided into three quartiles (low risk: 0–85; intermediate risk: 86–210; high risk: ≥211; p < 0.0001 in both cohorts). Conclusions. The nomogram can be a more accurate and individualized prediction for 6-month overall survival of patients with HCC and PVTT on conservative treatment, and it is possible to consider further active interventions for patients in the low-risk group (0–85 scores) to achieve the aim of prolonging survival. [ABSTRACT FROM AUTHOR]