ATR inhibition increases reliance on PARP-mediated DNA repair revealing an improved therapeutic strategy for cervical cancer.

Objective: Cervical cancer results from persistent infection with high-risk human papillomavirus (HR-HPV) and the expression of E6 and E7 oncoproteins. E6 and E7 compromise the activity of p53 and Rb, the G1-S cell cycle checkpoint, and ATM-mediated DNA damage repair (DDR), which in turn increases reliance on ATR- and PARP-mediated DDR at the G2 cell cycle checkpoint. This study aimed to determine the effects of an ATR inhibitor (ATRi, AZD6738) and a PARP-inhibitor (PARPi, AZD2281) on HR-HPV+ cervical cancer cell lines.

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Advanced-stage endometrial cancer patients typically receive a combination of platinum and paclitaxel chemotherapy. However, limited treatment options are available for those with recurrent disease, and there is a need to identify alternative treatment options for the advanced setting. Our goal was to evaluate the pre-clinical efficacy and mechanism of action of Oklahoma Nitrone 007 (OKN-007) alone and in combination with carboplatin and paclitaxel in endometrial cancer.

Targeting doublecortin-like kinase 1 reveals a novel strategy to circumvent chemoresistance and metastasis in ovarian cancer.

Ovarian cancer (OvCa) has a dismal prognosis because of its late-stage diagnosis and the emergence of chemoresistance. Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase known to regulate cancer cell "stemness", epithelial-mesenchymal transition (EMT), and drug resistance. Here we show that DCLK1 is a druggable target that promotes chemoresistance and tumor progression of high-grade serous OvCa (HGSOC).

A diminutive snake species can maintain regional heterothermy in both homogeneous and heterogeneous thermal environments.

Regional heterothermy is a pattern whereby different body regions are maintained at different temperatures, often to prioritize the function of certain body parts over others, or to maximize the function of organs and tissues that vary in thermal sensitivity. Regional heterothermy is relatively well understood in endotherms, where physiological mechanisms maintain heterogeneity. However, less is known about regional heterothermy in ectotherms, where behavioral mechanisms are more important for generating thermal variation.

Improving Risk Assessment for Metastatic Disease in Endometrioid Endometrial Cancer Patients Using Molecular and Clinical Features: An NRG Oncology/Gynecologic Oncology Group Study.

A risk assessment model for metastasis in endometrioid endometrial cancer (EEC) was developed using molecular and clinical features, and prognostic association was examined. Patients had stage I, IIIC, or IV EEC with tumor-derived RNA-sequencing or microarray-based data. Metastasis-associated transcripts and platform-centric diagnostic algorithms were selected and evaluated using regression modeling and receiver operating characteristic curves.

Sequencing and p53 Immunohistochemistry Predict Outcomes When Bevacizumab Is Added to Frontline Chemotherapy in Endometrial Cancer: An NRG Oncology/Gynecologic Oncology Group Study.

Purpose: The status of p53 in a tumor can be inferred by next-generation sequencing (NGS) or by immunohistochemistry (IHC). We examined the association between p53 IHC and sequence and whether p53 IHC alone, or integrated with NGS, predicts the outcome.

Methods: From GOG-86P, a randomized phase II study of chemotherapy combined with either bevacizumab or temsirolimus in advanced endometrial cancer, 213 cases had p53 protein expression data measured by IHC and NGS data.

A Profile and Three-Year Follow-Up of Patients with Basal Cell Carcinoma in the Western Cape, South Africa.

Background: Basal cell carcinoma (BCC) is an important malignancy in sub-Saharan Africa. There is a paucity of data regarding BCC in South Africa.

Aims: To describe the clinicopathological features of patients presenting with BCC in a cohort of South African patients.

A phase II trial of bevacizumab and rucaparib in recurrent carcinoma of the cervix or endometrium.

Objective: The aim of this study was to examine the tolerability and efficacy of combination bevacizumab rucaparib therapy in patients with recurrent cervical or endometrial cancer.

Patients & Methods: Thirty-three patients with recurrent cervical or endometrial cancer were enrolled. Patients were required to have tumor progression after first line treatment for metastatic, or recurrent disease.

Sera Protein Signatures of Endometrial Cancer Lymph Node Metastases.

The presence of lymph node metastases in endometrial cancer patients is a critical factor guiding treatment decisions; however, surgical and imaging methods for their detection are limited by morbidity and inaccuracy. To determine if sera can predict the presence of positive lymph nodes, sera collected from endometrial cancer patients with or without lymph node metastases, and benign gynecology surgical patients (N = 20 per group) were subjected to electron spray ionization mass spectrometry (ES-MS). Peaks that were significantly different among the groups were evaluated by leave one out cross validation (LOOCV) for their ability to differentiation between the groups.

Olaparib With or Without Cediranib Versus Platinum-Based Chemotherapy in Recurrent Platinum-Sensitive Ovarian Cancer (NRG-GY004): A Randomized, Open-Label, Phase III Trial.

Purpose: Platinum-based chemotherapy is the standard of care for platinum-sensitive ovarian cancer, but complications from repeated platinum therapy occur. We assessed the activity of two all-oral nonplatinum alternatives, olaparib or olaparib/cediranib, versus platinum-based chemotherapy.

Patients And Methods: NRG-GY004 is an open-label, randomized, phase III trial conducted in the United States and Canada.

Patient-Derived Xenografts of High-Grade Serous Ovarian Cancer Subtype as a Powerful Tool in Pre-Clinical Research.

(1) Background. PDX models have become the preferred tool in research laboratories seeking to improve development and pre-clinical testing of new drugs. PDXs have been shown to capture the cellular and molecular characteristics of human tumors better than simpler cell line-based models.

Patient reported outcomes for cisplatin and radiation followed by carboplatin/paclitaxel versus carboplatin/paclitaxel for locally advanced endometrial carcinoma: An NRG oncology study.

Introduction: Chemotherapy plus radiation (Cis-RT + CP) did not demonstrate superiority in prolonging relapse-free survival compared to chemotherapy alone in patients with stage III or IVA endometrial carcinoma. The impact of treatment on quality of life (QOL), neurotoxicity (NTX) and psychometric properties of the gastrointestinal (GI) symptoms subscale during treatment and up to 1 year are described herein.

Methods: QOL assessments were scheduled at baseline, 6 weeks (post completion of RT (Cis-RT + CP) or prior to cycle 3 (CP)), then 18 weeks (end of treatment) and 70 weeks (1 year after the end of treatment) after starting treatment.

Profile of the current psychiatrist workforce in South Africa: establishing a baseline for human resource planning and strategy.

The World Health Organization Global Health Observatory Data Repository reports South Africa with 1.52 psychiatrists per 100 000 of the population among other countries in Africa with 0.01 psychiatrists per 100 000 (Chad, Burundi and Niger) to more than 30 per 100 000 for some countries in Europe.

Prognostic significance of ethnicity and age in advanced stage epithelial ovarian cancer: An NRG oncology/gynecologic oncology group study.

Background: Age and ethnicity are among several factors that influence overall survival (OS) in ovarian cancer. The study objective was to determine whether ethnicity and age were of prognostic significance in women enrolled in a clinical trial evaluating the addition of bevacizumab to front-line therapy.

Methods: Women with advanced stage ovarian, primary peritoneal, or fallopian tube cancer were enrolled in a phase III clinical trial.

Self-identification, mode of diagnosis and treatment, and perceptions of relationships with medical providers of South African Xhosa-speaking traditional healers.

There is widespread use of traditional medicine in treating common mental disorders in South Africa. We aimed to (i) explore the self-identification of traditional healers (THs; how they refer to themselves, e.g.

Factors Affecting Specialist Psychiatry Training in South Africa: Are Psychiatry Residents Satisfied with Their Training?

Objective: The authors investigated South African psychiatry residents' satisfaction with their training, physical, and mental health to inform the development of a strategy to improve the quality and experiences of training.

Method: A cross-sectional online survey was undertaken to assess the factors affecting residents' satisfaction with their current training program. The authors conducted a comparative analysis of residents across the training institutions in South Africa.

The clinical and demographic profile of women living with HIV admitted to the acute unit at Stikland Psychiatric Hospital.

Background: There is a paucity of research on the clinical profile of women living with human immunodeficiency virus (HIV) (WLWH) admitted with acute mental health illness. Existing studies are small and did not look at factors that could have an impact on medication adherence. As a first step to inform service delivery for this vulnerable population, a thorough understanding of the composition and needs of these patients should be identified.

Mutated p53 portends improvement in outcomes when bevacizumab is combined with chemotherapy in advanced/recurrent endometrial cancer: An NRG Oncology study.

Background: Successfully combining targeted agents with chemotherapy is an important future goal for cancer therapy. However, an improvement in patient outcomes requires an enhanced understanding of the tumor biomarkers that predict for drug sensitivity. NRG Oncology/Gynecologic Oncology Group (GOG) Study GOG-86P was one of the first attempts to combine targeted agents (bevacizumab or temsirolimus) with chemotherapy in patients with advanced endometrial cancer.

Environmental DNA bioassays corroborate field data for detection of overwintering species at risk Blanding's turtles ().

Environmental DNA (eDNA) is gaining traction in conservation ecology as a powerful tool for detecting species at risk. We developed a quantitative polymerase chain reaction assay to detect a DNA amplicon fragment of the mitochondrial nicotinamide adenine dinucleotide locus of the Blanding's turtle () for detecting overwintering individuals. Seventy-eight water samples were collected from 17 wetland sites in Ontario, Canada.

Multi-kinase targeted therapy as a promising treatment strategy for ovarian tumors expressing sfRon receptor.

The sfRon kinase is an important therapeutic target in ovarian cancer that contributes to prominent tumor growth and disease progression. We reasoned that a multi-kinase inhibition of sfRon pathway might be an effective strategy to achieve a sustained anti-tumor response, while simultaneously preventing treatment resistance. We performed a detailed dissection of sfRon signaling and demonstrated that S6K1 is a key component of a multi-kinase targeting strategy in sfRon expressing ovarian tumors.

The prevalence and spectrum of mucocutaneous disease in South African people living with HIV and accessing care at a district-level hospital.

Background: Although the association between human immunodeficiency virus (HIV) and mucocutaneous diseases has been well studied within South African specialist centres, there is limited data from district-level hospitals. Available data may, therefore, fail to reflect the prevalence and full spectrum of dermatoses seen in people living with HIV (PLWH).

Objectives: To determine the prevalence and spectrum of dermatoses seen in PLWH.

Demographic and clinical profile of patients utilising a transitional care intervention in the Western Cape, South Africa.

Background: The World Health Organization's action plan for 2020 has identified the need for service-based data to motivate for more appropriate community-based services. To date, there is no published data from step-up or step-down facilities in South Africa.

Aim: To describe the demographic and clinical profile of all patients admitted to New Beginnings between 01 January 2011 and 31 December 2015.

Results of an early safety analysis of a study of the combination of pembrolizumab and pelvic chemoradiation in locally advanced cervical cancer.

Background: Immune checkpoint inhibitors are being considered for locally advanced cervical cancer (LACC) together with standard-of-care pelvic chemoradiation (CRT). However, the safety of the combination and its optimal schedule are unknown. Defining the safety of the combination is a primary objective of a study examining concurrent and sequential schedules.

Immune Activation in Patients with Locally Advanced Cervical Cancer Treated with Ipilimumab Following Definitive Chemoradiation (GOG-9929).

Purpose: A phase I clinical trial (GOG-9929) examined the safety and efficacy of adjuvant immune-modulation therapy with the checkpoint inhibitor ipilimumab [anti-CTL antigen-4 (anti-CTLA-4)] following chemoradiation therapy (CRT) for newly diagnosed node-positive human papillomavirus (HPV)-related cervical cancer. To better understand the mechanism of action and to identify predictive biomarkers, immunologic and viral correlates were assessed before, during, and after treatment.

Patients And Methods: Twenty-one patients who received CRT and ≥2 doses of ipilimumab and 5 patients who received CRT only were evaluable for translational endpoints.