High-grade serous ovarian carcinoma (HGSOC) remains the most common and deadly form of ovarian cancer. However, available cell lines usually fail to appropriately represent its complex molecular and histological features. To overcome this drawback, we established OVAR79, a new cell line derived from the ascitic fluid of a patient with a diagnosis of HGSOC, which adds a unique set of properties to the study of ovarian cancer.
View Article and Find Full Text PDFOvarian cancer often develops resistance to conventional therapies, hampering their effectiveness. Here, using ex vivo paired ovarian cancer ascites obtained before and after chemotherapy and in vitro therapy-induced secretomes, we show that molecules secreted by ovarian cancer cells upon therapy promote cisplatin resistance and enhance DNA damage repair in recipient cancer cells. Even a short-term incubation of chemonaive ovarian cancer cells with therapy-induced secretomes induces changes resembling those that are observed in chemoresistant patient-derived tumor cells after long-term therapy.
View Article and Find Full Text PDFAmong the various stromal cell types within the tumor microenvironment, cancer-associated fibroblasts (CAFs) emerge as the predominant constituent, exhibiting a diverse array of oncogenic functions not intrinsic to normal fibroblasts. Their involvement spans across all stages of tumorigenesis, encompassing initiation, progression, and metastasis. Current understanding posits the coexistence of distinct subpopulations of CAFs within the tumor microenvironment across a spectrum of solid tumors, showcasing both pro- and antitumor activities.
View Article and Find Full Text PDFOvarian cancer is known to be the most lethal malignancy among all gynecological cancers affecting a large number of women worldwide. The treatment of ovarian cancer is challenging due to the high recurrence rate of the disease and is further complicated by acquired chemoresistance. Most ovarian cancer deaths are the result of the metastatic spread of drug-resistant cells.
View Article and Find Full Text PDFDysregulation of pre-mRNA splicing is a common hallmark of cancer cells and it is associated with altered expression, localization, and mutations of the components of the splicing machinery. In the last few years, it has been elucidated that spliceosome components can also influence cellular processes in a splicing-independent manner. Here, we analyze open source data to understand the effect of the knockdown of splicing factors in human cells on the expression and splicing of genes relevant to cell proliferation, migration, cell cycle regulation, DNA repair, and cell death.
View Article and Find Full Text PDFCancer-associated fibroblasts (CAFs) have long been known as one of the most important players in tumor initiation and progression. Even so, there is an incomplete understanding of the identification of CAFs among tumor microenvironment cells as the list of CAF marker genes varies greatly in the literature, therefore it is imperative to find a better way to identify reliable markers of CAFs. To this end, we summarized a large number of single-cell RNA-sequencing data of multiple tumor types and corresponding normal tissues.
View Article and Find Full Text PDFGlioblastoma (GBM) is characterized by exceptionally high intratumoral heterogeneity. However, the molecular mechanisms underlying the origin of different GBM cell populations remain unclear. Here, we found that the compositions of ribosomes of GBM cells in the tumour core and edge differ due to alternative RNA splicing.
View Article and Find Full Text PDFCognitive Processing Therapy (CPT) is efficacious in treating PTSD, but there remains a need to improve outcomes for individuals who do not fully respond to treatment. Differences between patient-therapist dyads in the fidelity (i.e.
View Article and Find Full Text PDFThe Posttraumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5) is a widely used, self-report measure that is employed to assess PTSD symptom severity and determine the presence of probable PTSD in various trauma-exposed populations. The PCL-5 is often administered in clinical settings as a screening tool for PTSD, with a suggested cutoff score of 33 indicating a probable PTSD diagnosis. Recent research indicates that a higher cutoff may be required in psychiatric samples.
View Article and Find Full Text PDFEmotion regulation difficulties (difficulty regulating the experience, occurrence, and expression of emotions) are associated with the severity of posttraumatic stress disorder (PTSD) symptoms across trauma types (e.g., childhood abuse, sexual assault, combat trauma).
View Article and Find Full Text PDFBackground: The role of interpersonal relationship functioning in trauma recovery is well-established. However, much of this research has been done with cross-sectional samples, often years after trauma exposure, using self-report methodology only, and is focused on intimate relationship adjustment.
Methods: The current study investigated the longitudinal associations between interpersonal (intimate and non-intimate) relationship functioning and clinician- and self-reported posttraumatic stress disorder (PTSD) symptoms in 151 recently (within the past 6 months) traumatized individuals.
This article describes the initial validation of the Diagnostic Assessment Research Tool (DART), a modular semistructured interview to facilitate diagnosis of various disorders among adults corresponding with the , 5th edition (DSM-5). In this study, the construct, convergent, and discriminant validity of DART modules for anxiety disorders, depressive disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and substance-related and addictive disorders was assessed among a sample of 610 participants in a clinical outpatient setting. The data indicated excellent construct validity among DART modules assessed.
View Article and Find Full Text PDFThe malignant tumor is a complex heterogeneous set of cells functioning in a no less heterogeneous microenvironment. Like any dynamic system, cancerous tumors evolve and undergo changes in response to external influences, including therapy. Initially, most tumors are susceptible to treatment.
View Article and Find Full Text PDFHyperthermia has been used as an adjuvant treatment for radio- and chemotherapy for decades. In addition to its effects on perfusion and oxygenation of cancer tissues, hyperthermia can enhance the efficacy of DNA-damaging treatments such as radiotherapy and chemotherapy. Although it is believed that the adjuvant effects are based on hyperthermia-induced dysfunction of DNA repair systems, the mechanisms of these dysfunctions remain elusive.
View Article and Find Full Text PDFIntroduction: There is mixed evidence regarding how posttraumatic stress disorder (PTSD) symptom clusters are associated with sexual dysfunction (SD), and most studies to date have failed to account for potentially confounding variables. Our study sought to explore the unique contribution of PTSD symptom clusters on (a) lack of sexual desire or pleasure, and (b) pain or problems during sexual intercourse, after adjusting for comorbidities and medication usage.
Materials And Methods: Participants included 543 male treatment-seeking veterans and Canadian Armed Forces (CAF) personnel (aged <65 years), referred for treatment between September 2006 and September 2014.
Objective: Posttraumatic stress disorder (PTSD) is often accompanied by other mental health conditions, including major depressive disorder (MDD), substance misuse disorders, and anxiety disorders. The objective of the current study is to delineate classes of comorbidity and investigate predictors of comorbidity classes amongst a sample of Canadian Armed Forces (CAF) Regular Force personnel.
Methods: Latent class analyses (LCAs) were applied to cross-sectional data obtained between April and August 2013 from a nationally representative random sample of 6700 CAF Regular Force personnel who deployed to the mission in Afghanistan.
PON2 belongs to the paraoxonase protein family that consists of lactone hydrolyzing enzymes with different substrate specificities. Unlike other members of the family, PON2 exhibits substantial antioxidant activity, is localized predominantly inside the cell, and is ubiquitously expressed in all human tissues. Previously, it was proffered that defense against pathogens, such as , is the main function of paraoxonases.
View Article and Find Full Text PDFThis randomized controlled hybrid implementation/effectiveness trial aimed to compare the impact of three different models of training and consultation by examining the PTSD treatment outcomes achieved by therapists who were learning a front-line recommended psychotherapy for posttraumatic stress disorder (PTSD), Cognitive Processing Therapy (CPT; Resick, Monson, & Chard, 2017). Therapists (N = 134) were randomized into one of three conditions after attending a standard CPT training workshop: No Consultation with delayed feedback on CPT fidelity, Standard Consultation involving discussion and conceptualization of cases without session audio review, and Consultation Including Audio Review, which included a review of segments of audiorecorded CPT sessions. Across all training conditions, the patients treated by these therapists (N = 188) evidenced statistically significant reductions in PTSD symptoms, (d = -0.
View Article and Find Full Text PDFBackground: Abnormal pre-mRNA splicing regulation is common in cancer, but the effects of chemotherapy on this process remain unclear.
Methods: To evaluate the effect of chemotherapy on slicing regulation, we performed meta-analyses of previously published transcriptomic, proteomic, phosphoproteomic, and secretome datasets. Our findings were verified by LC-MS/MS, western blotting, immunofluorescence, and FACS analyses of multiple cancer cell lines treated with cisplatin and pladienolide B.
This study investigated comorbidity patterns in treatment-seeking veterans and currently-serving Canadian Forces members of an outpatient mental health clinic from September 2006-September 2014. Using a retrospective cohort design, latent class analysis was conducted to determine latent classes of comorbidity (including posttraumatic stress disorder [PTSD], major depressive disorder [MDD], generalized anxiety disorder, panic disorder, and alcohol use disorder [AUD]). Multiple logistic regression was used to determine which covariates (age, gender, number of deployments, and service duration) were predictors of latent class membership.
View Article and Find Full Text PDFThe current study examined the effect of total, as well as different sources (i.e., family, friends, significant other) of, pretreatment/baseline social support on posttraumatic stress disorder (PTSD) severity and treatment response to cognitive-behavioral conjoint therapy (CBCT) for PTSD.
View Article and Find Full Text PDFThere are well-documented associations between posttraumatic stress disorder (PTSD) symptoms and intimate relationship impairments, including dysfunctional communication at times of relationship conflict. To date, the extant research on the associations between PTSD symptom severity and conflict communication has been cross-sectional and focused on military and veteran couples. No published work has evaluated the extent to which PTSD symptom severity and communication at times of relationship conflict influence each other over time or in civilian samples.
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