Uterine teratoma and the role of short-tandem repeat genotyping in understanding origins.

Background: Uterine teratomas are a rare entity with a debated origin. Given its rarity and limitations of diagnostic imaging, diagnosis is typically determined pathologically following surgical resection based on the presence of tissue derived from all germ cell layers. Unlike its ovarian counterpart, the developmental origins are poorly understood; however, recently introduced molecular testing has revolutionized our understanding of these rare tumors.

Top Ten Tips Palliative Care Clinicians Should Know About Addressing Patient Sexuality and Intimacy in Serious Illness.

Patient sexuality and intimacy comprise important dimensions of quality of life (QOL), making them essential topics for palliative care (PC) clinicians to address. Created with interprofessional input from PC, urology, gynecology, sexual health, oncology, psychiatry, psychology, nursing, and social work, this article offers 10 high-yield, evidence-based tips to better equip PC clinicians to address sexuality and intimacy for patients with serious illness. These tips highlight skills such as opening discussions, assessing concerns through a biopsychosocial model, and thinking through appropriate interventions to improve QOL.

Comparing Social Isolation in Older Adults With and Without Physical Health Challenges During COVID-19: Church and Church Friends Matter.

Older adults were disproportionately affected by COVID-19. The purpose of this study was to explore experiences of sudden-onset social isolation and factors that influenced it among social isolation in two groups of older adults. A qualitative thematic study with a survey component was conducted comparing 18 older adults in two groups: 12 reporting physical health challenges and 6 reporting no physical health challenges.

A systematic review of phenotypic and epigenetic clocks used for aging and mortality quantification in humans.

Aging is the leading driver of disease in humans and has profound impacts on mortality. Biological clocks are used to measure the aging process in the hopes of identifying possible interventions. Biological clocks may be categorized as phenotypic or epigenetic, where phenotypic clocks use easily measurable clinical biomarkers and epigenetic clocks use cellular methylation data.

Preclinical activity of datopotamab deruxtecan, a novel TROP2 directed antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (TROP2) in ovarian carcinoma.

Introduction: Epithelial ovarian cancer (EOC) is associated with the highest gynecologic cancer mortality. The development of novel, effective combinations of targeted therapeutics remains an unmet medical need. We evaluated the preclinical activity of datopotamab deruxtecan (Dato-Dxd), a novel TROP2 targeting antibody drug conjugate (ADC) in ovarian cancer cell lines and xenografts with variable TROP2 expression.

Predictive modeling of gene mutations for the survival outcomes of epithelial ovarian cancer patients.

Epithelial ovarian cancer (EOC) has a low overall survival rate, largely due to frequent recurrence and acquiring resistance to platinum-based chemotherapy. EOC with homologous recombination (HR) deficiency has increased sensitivity to platinum-based chemotherapy because platinum-induced DNA damage cannot be repaired. Mutations in genes involved in the HR pathway are thought to be strongly correlated with favorable response to treatment.

Targetable ERBB2/HER2 Mutations in Gynecologic Malignancies: Clinicopathological, Immunohistochemical, and Molecular Correlations.

Targeted anti-HER2 therapy has been recently added to the standard treatment recommendations in endometrial serous carcinoma. Current eligibility requires testing for HER2 overexpression and/or gene amplification by immunohistochemistry and by fluorescence in situ hybridization. However, clinical trials have also demonstrated the efficacy of anti-HER2 drugs against activating ERBB2/HER2 mutations in a variety of solid tumor types, and fam-trastuzumab deruxtecan is now approved by the US Food and Drug Administration for HER2-mutant non-small cell lung cancer.

Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial.

Purpose: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC).

Methods: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks).

Preclinical in vitro and in vivo activity of the RAF/MEK clamp avutometinib in combination with FAK inhibition in uterine carcinosarcomas.

Objectives: Uterine carcinosarcomas (UCS) are rare, biologically aggressive tumors. Since UCS may harbor mutations in RAS/MAPK pathway genes we evaluated the preclinical in vitro and in vivo efficacy of the RAF/MEK clamp avutometinib in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718 against multiple primary UCS cell lines and xenografts.

Methods: Whole-exome-sequencing (WES) was used to evaluate the genetic landscape of 5 primary UCS cell lines.

Integrated mutational landscape analysis of poorly differentiated high-grade neuroendocrine carcinoma of the uterine cervix.

High-grade neuroendocrine cervical cancers (NETc) are exceedingly rare, highly aggressive tumors. We analyzed 64 NETc tumor samples by whole-exome sequencing (WES). Human papillomavirus DNA was detected in 65.

Randomized Phase II Trial of Imiquimod with or without 9-Valent HPV Vaccine versus Observation in Patients with High-grade Pre-neoplastic Cervical Lesions (NCT02864147).

Purpose: We report the results of a randomized phase II trial of imiquimod, a topical immune-response modulator versus imiquimod plus a 9-valent human papillomavirus (HPV) vaccine (9vHPV) versus clinical surveillance in cervical intraepithelial neoplasia (CIN2/3) patients.

Patients And Methods: We randomly allocated 133 patients with untreated CIN2/3 in equal proportions to a 4-month treatment with self-applied vaginal suppositories containing imiquimod (Arm B) or imiquimod plus a 9vHPV (Arm C) versus clinical surveillance (Arm A). The main outcome was efficacy, defined as histologic regression to CIN1 or less.

Semaglutide 6-months therapy of type 2 diabetes mellitus restores adipose progenitors potential to develop metabolically active adipocytes.

Background: Nowadays type 2 diabetes mellitus (T2DM) leads to population mortality growth. Today glucagon-like peptide type 1 receptor agonists (GLP-1 RA) are one of the most promising glucose-lowered drugs with anorexigenic and cardioprotective effects. The present study aims to determine the effects of GLP-1 RA semaglutide 6-month therapy on T2DM patient metabolic parameters and adipose progenitor cell health.

Preclinical efficacy of RAF/MEK clamp avutometinib in combination with FAK inhibition in low grade serous ovarian cancer.

Objectives: Low-grade-serous-ovarian-carcinoma (LGSOC) is characterized by a high recurrence rate and limited therapeutic options. About one-third of LGSOC contains mutations in MAPK pathway genes such as KRAS/NRAS/BRAF. Avutometinib is a dual RAF/MEK inhibitor while defactinib and VS-4718 are focal-adhesion-kinase-inhibitors (FAKi).

Novel FOXL2 Mutation in an Ovarian Adult Granulosa Cell Tumor: Report of a Case With Diagnostic and Clinicopathologic Implications.

Adult granulosa cell tumor, the most common malignant ovarian sex cord-stromal tumor, harbors the characteristic mutation c.402C>G (p.C134W) in the FOXL2 gene in ~90% to 95% of cases.

Urokinase-Type Plasminogen Activator Receptor Regulates Prosurvival and Angiogenic Properties of Cardiac Mesenchymal Stromal Cells.

One of the largest challenges to the implementation of cardiac cell therapy is identifying selective reparative targets to enhance stem/progenitor cell therapeutic efficacy. In this work, we hypothesized that such a target could be an urokinase-type plasminogen activator receptor (uPAR)-a glycosyl-phosphatidyl-inositol-anchored membrane protein, interacting with urokinase. uPAR is able to form complexes with various transmembrane proteins such as integrins, activating intracellular signaling pathway and thus regulating multiple cell functions.

Gene expression of non-homologous end-joining pathways in the prognosis of ovarian cancer.

Ovarian cancer is the deadliest gynecologic malignancy in women, with a 46% five-year overall survival rate. The objective of the study was to investigate the effects of non-homologous end-joining (NHEJ) genes on clinical outcomes of ovarian cancer patients. To determine if these genes act as prognostic biomarkers of mortality and disease progression, the expression profiles of 48 NHEJ-associated genes were analyzed using an array of statistical and machine learning techniques: logistic regression models, decision trees, naive-Bayes, two sample t-tests, support vector machines, hierarchical clustering, principal component analysis, and neural networks.

In Vivo and In Vitro Efficacy of Trastuzumab Deruxtecan in Uterine Serous Carcinoma.

Uterine serous carcinoma (USC) is a rare, biologically aggressive variant of endometrial cancer with a high recurrence rate and poor prognosis. HER2 overexpression (3+ positivity) by IHC and/or FISH ERBB2 gene amplification is detected in approximately one-third of patients with USC. Clinical trials incorporating trastuzumab with standard chemotherapy have recently demonstrated improved progression-free and overall survival in advanced-stage or recurrent USC that overexpresses HER2.

Surgical and oncologic outcomes in surgically treated women 80 years and older with endometrioid endometrial cancer as a function of their comorbidities.

Objective: To describe the surgical and oncologic outcomes in surgically treated oldest old women (≥80 years) with endometrioid endometrial cancer as a function of their comorbidities.

Methods: In this retrospective cohort study, patients aged 80-99 years who underwent surgical management of stage I endometrioid endometrial cancer between 2006 and 2018 were included. Low- and high-intermediate risk disease was defined using the Gynecologic Oncology Group-99 criteria.

Transforming Growth Factor Beta and Epithelial to Mesenchymal Transition Alter Homologous Recombination Repair Gene Expression and Sensitize BRCA Wild-Type Ovarian Cancer Cells to Olaparib.

Epithelial ovarian cancer (EOC) remains the most lethal gynecologic malignancy, largely due to metastasis and drug resistant recurrences. Fifteen percent of ovarian tumors carry mutations in BRCA1 or BRCA2, rendering them vulnerable to treatment with PARP inhibitors such as olaparib. Recent studies have shown that TGFβ can induce "BRCAness" in BRCA wild-type cancer cells.