[Implementation of psychotherapeutic consultation at work (PT-A): expectations, announcement, and use : Results of the friaa-study].

Introduction: Psychotherapeutic consultation at work (PT-A) offers easily accessible, short-term support for employees experiencing psychological stress. The aim of the study was to evaluate aspects of the implementation regarding announcement, access, and use of the PT‑A.

Methods: The study was conducted as part of a randomized controlled trial (RCT) called "Early Intervention in the Workplace".

STAG2 mutations regulate 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme.

Inactivating mutations of genes encoding the cohesin complex are common in a wide range of human cancers. STAG2 is the most commonly mutated subunit. Here we report the impact of stable correction of endogenous, naturally occurring STAG2 mutations on gene expression, 3D genome organization, chromatin loops, and Polycomb signaling in glioblastoma multiforme (GBM).

USP13 promotes development and metastasis of high-grade serous ovarian carcinoma in a novel mouse model.

Epithelial ovarian cancer is the most lethal gynecologic malignancy and one of the most common causes of cancer mortality among women worldwide. Ubiquitin-Specific Peptidase 13 (USP13) gene copy is strongly amplified in human epithelial ovarian cancer, and high USP13 expression is correlated with poor survival outcomes. Yet, its pathological contribution to ovarian tumorigenesis remains unknown.

STAG2 as a prognostic biomarker in low-grade non-muscle invasive bladder cancer.

Objective: Improvements to bladder cancer risk stratification guidelines are needed to better tailor post-operative surveillance and adjuvant therapy to individual patients. We previously identified STAG2 as a commonly mutated tumor suppressor gene in bladder cancer and an independent predictor of progression in NMIBC. Here we test the value of combining STAG2 immunostaining with other risk stratification biomarkers in NMIBC, and as an individual biomarker in MIBC.

Emerging themes in cohesin cancer biology.

Mutations of the cohesin complex in human cancer were first discovered ~10 years ago. Since then, researchers worldwide have demonstrated that cohesin is among the most commonly mutated protein complexes in cancer. Inactivating mutations in genes encoding cohesin subunits are common in bladder cancers, paediatric sarcomas, leukaemias, brain tumours and other cancer types.

STAG2 Is a Biomarker for Prediction of Recurrence and Progression in Papillary Non-Muscle-Invasive Bladder Cancer.

Most bladder cancers are early-stage tumors known as papillary non-muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression.

Synthetic lethality between the cohesin subunits and in diverse cancer contexts.

Recent genome analyses have identified recurrent mutations in the cohesin complex in a wide range of human cancers. Here we demonstrate that the most frequently mutated subunit of the cohesin complex, , displays a strong synthetic lethal interaction with its paralog . Mechanistically, STAG1 loss abrogates sister chromatid cohesion in mutated but not in wild-type cells leading to mitotic catastrophe, defective cell division and apoptosis.

Correction of PTEN mutations in glioblastoma cell lines via AAV-mediated gene editing.

PTEN is among the most commonly mutated tumor suppressor genes in human cancer. However, studying the role of PTEN in the pathogenesis of cancer has been limited, in part, by the paucity of human cell-based isogenic systems that faithfully model PTEN loss. In an effort to remedy this problem, gene editing was used to correct an endogenous mutant allele of PTEN in two human glioblastoma multiforme (GBM) cell lines- 42MGBA and T98G.

Inhibition of DNA damage repair by the CDK4/6 inhibitor palbociclib delays irradiated intracranial atypical teratoid rhabdoid tumor and glioblastoma xenograft regrowth.

Background: Radiation therapy is the most commonly used postsurgical treatment for primary malignant brain tumors. Consequently, investigating the efficacy of chemotherapeutics combined with radiation for treating malignant brain tumors is of high clinical relevance. In this study, we examined the cyclin-dependent kinase 4/6 inhibitor palbociclib, when used in combination with radiation for treating human atypical teratoid rhabdoid tumor (ATRT) as well as glioblastoma (GBM).

Cohesin mutations in human cancer.

Cohesin is a highly-conserved protein complex that plays important roles in sister chromatid cohesion, chromatin structure, gene expression, and DNA repair. In humans, cohesin is a ubiquitously expressed, multi-subunit protein complex composed of core subunits SMC1A, SMC3, RAD21, STAG1/2 and regulatory subunits WAPL, PDS5A/B, CDCA5, NIPBL, and MAU2. Recent studies have demonstrated that genes encoding cohesin subunits are somatically mutated in a wide range of human cancers.

Intact Cohesion, Anaphase, and Chromosome Segregation in Human Cells Harboring Tumor-Derived Mutations in STAG2.

Somatic mutations of the cohesin complex subunit STAG2 are present in diverse tumor types. We and others have shown that STAG2 inactivation can lead to loss of sister chromatid cohesion and alterations in chromosome copy number in experimental systems. However, studies of naturally occurring human tumors have demonstrated little, if any, correlation between STAG2 mutational status and aneuploidy, and have further shown that STAG2-deficient tumors are often euploid.

Do women with statin-related myalgias have low vitamin D levels?

Background: Statin intolerance is often due to myalgias. Severe vitamin D deficiency is characterized by musculoskeletal pain. We hypothesized that statin-intolerance is associated with vitamin D deficiency.

Calcium Supplements and Cardiovascular Disease: A Review.

Dietary or supplemental calcium intake has long been encouraged for optimal bone health. However, more recently, the safety of calcium supplementation has been questioned because of a possible association between supplemental calcium and cardiovascular risk. Whereas calcium may have a beneficial or neutral effect on cardiovascular risk factors such as blood pressure, cholesterol, weight, and diabetes, available evidence does not provide a definitive answer for an association with cardiovascular disease (CVD).

Female-specific factors for IHD: across the reproductive lifespan.

Ischemic heart disease (IHD) is the number one health threat to women in the USA. While significant advances in female-specific symptoms and pathophysiology have begun to improve mortality rates, a closer look at risk factors across a woman's lifespan needs to be explored. This review targets three time frames: premenopause, pregnancy, and postmenopause.

Pharmacologic inhibition of histone demethylation as a therapy for pediatric brainstem glioma.

Pediatric brainstem gliomas often harbor oncogenic K27M mutation of histone H3.3. Here we show that GSKJ4 pharmacologic inhibition of K27 demethylase JMJD3 increases cellular H3K27 methylation in K27M tumor cells and demonstrate potent antitumor activity both in vitro against K27M cells and in vivo against K27M xenografts.

Mutational and functional analysis of the tumor-suppressor PTPRD in human melanoma.

Protein tyrosine phosphatases (PTPs) tightly regulate tyrosine phosphorylation essential for cell growth, adhesion, migration, and survival. We performed a mutational analysis of the PTP gene family in cutaneous metastatic melanoma and identified 23 phosphatase genes harboring somatic mutations. Among these, receptor-type tyrosine-protein phosphatase delta (PTPRD) was one of the most highly mutated genes, harboring 17 somatic mutations in 79 samples, a prevalence of 21.

The genomic landscape of the Ewing Sarcoma family of tumors reveals recurrent STAG2 mutation.

The Ewing sarcoma family of tumors (EFT) is a group of highly malignant small round blue cell tumors occurring in children and young adults. We report here the largest genomic survey to date of 101 EFT (65 tumors and 36 cell lines). Using a combination of whole genome sequencing and targeted sequencing approaches, we discover that EFT has a very low mutational burden (0.

Cohesin gene mutations in tumorigenesis: from discovery to clinical significance.

Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3, RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister chromatids following DNA replication until its cleavage during mitosis thereby enabling faithful segregation of sister chromatids into two daughter cells. Recent cancer genomics analyses have discovered a high frequency of somatic mutations in the genes encoding the core cohesin subunits as well as cohesin regulatory factors (e.g.

Glioblastoma cells containing mutations in the cohesin component STAG2 are sensitive to PARP inhibition.

Recent data have identified STAG2, a core subunit of the multifunctional cohesin complex, as a highly recurrently mutated gene in several types of cancer. We sought to identify a therapeutic strategy to selectively target cancer cells harboring inactivating mutations of STAG2 using two independent pairs of isogenic glioblastoma cell lines containing either an endogenous mutant STAG2 allele or a wild-type STAG2 allele restored by homologous recombination. We find that mutations in STAG2 are associated with significantly increased sensitivity to inhibitors of the DNA repair enzyme PARP.

Frequent truncating mutations of STAG2 in bladder cancer.

Here we report the discovery of truncating mutations of the gene encoding the cohesin subunit STAG2, which regulates sister chromatid cohesion and segregation, in 36% of papillary non-invasive urothelial carcinomas and 16% of invasive urothelial carcinomas of the bladder. Our studies suggest that STAG2 has a role in controlling chromosome number but not the proliferation of bladder cancer cells. These findings identify STAG2 as one of the most commonly mutated genes in bladder cancer.