Targeting valine catabolism to inhibit metabolic reprogramming in prostate cancer.

Metabolic reprogramming and energetic rewiring are hallmarks of cancer that fuel disease progression and facilitate therapy evasion. The remodelling of oxidative phosphorylation and enhanced lipogenesis have previously been characterised as key metabolic features of prostate cancer (PCa). Recently, succinate-dependent mitochondrial reprogramming was identified in high-grade prostate tumours, as well as upregulation of the enzymes associated with branched-chain amino acid (BCAA) catabolism.

Patient-Derived Xenograft Models for Translational Prostate Cancer Research and Drug Development.

Patient-derived xenografts (PDXs) are a valuable preclinical research platform generated through transplantation of a patient's resected tumor into an immunodeficient or humanized mouse. PDXs serve as a high-fidelity avatar for both precision medicine and therapeutic testing against the cancer patient's disease state. While PDXs show mixed response to initial establishment, those that successfully engraft and can be sustained with serial passaging form a useful tool for basic and translational prostate cancer (PCa) research.

Patterns of spread and genetic alterations of primary endometrioid carcinomas of the ovary.

Objective: The primary objective was to characterize the rate of lymph node involvement in a cohort of patients with primary ovarian endometrioid adenocarcinoma. Additionally, we sought to quantify the recurrence rate, genetic alterations, and impact of lymphadenectomy on survival in this group of patients.

Methods: Patients diagnosed with primary endometrioid adenocarcinoma of the ovary without synchronous carcinomas of the female genital tract between 2012 and 2021 were identified.

The evolving role of DNA damage response in overcoming therapeutic resistance in ovarian cancer.

Epithelial ovarian cancer (EOC) is treated in the first-line setting with combined platinum and taxane chemotherapy, often followed by a maintenance poly (ADP-ribose) polymerase inhibitor (PARPi). Responses to first-line treatment are frequent. For many patients, however, responses are suboptimal or short-lived.

Impact of ACE2 on the susceptibility and vulnerability to COVID-19.

Angiotensin-converting enzyme 2 (ACE2) is not only the viral receptor for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) but is also classically known as a key carboxypeptidase, which through multiple interacting partners plays vital physiological roles in the heart, kidney, lung, and gastrointestinal tract. An accumulating body of evidence has implicated the dysregulation of ACE2 abundance and activity in the pathophysiology of multiple disease states. ACE2 has recently regained attention due to its evolving role in driving the susceptibility and disease severity of coronavirus disease 2019 (COVID-19).

Black and hispanic women have less support during cancer evaluation and treatment: results from a prospective patient reported outcomes program in gynecologic malignancy.

Objective: Race remains a significant predictor of poor outcomes in women with gynecologic cancer and minority patients consistently report worse quality of life during cancer treatment. Disparities between patients in strength of social and emotional supports may contribute to these outcomes. This study's objective was to describe the racial differences in patient reported outcomes of women being evaluated or treated for a gynecologic malignancy at a large tertiary cancer hospital.

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer.

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs.

Patient-reported outcomes and chemotherapy-related cognitive impairment in gynecologic malignancy.

Objective: Chemotherapy has multiple adverse effects, including chemotherapy-related cognitive impairment, the phenomenon colloquially referred to as 'chemobrain'. The objective of this study was to understand patient-reported experiences of this phenomenon in relation to chemotherapy administration among gynecologic oncology patients.

Methods: A prospective patient-reported outcomes program was implemented in the Gynecologic Oncology clinic of a tertiary academic institution in January 2018.

Patient reported outcomes after risk-reducing surgery in patients at increased risk of ovarian cancer.

Objective: To describe the quality of life of women at an increased risk of ovarian cancer undergoing risk-reducing bilateral salpingo-oophorectomy (RRBSO).

Methods: Patients evaluated in our gynecologic oncology ambulatory practice between January 2018-December 2019 for an increased risk of ovarian cancer were included. Patients received the EORTC QLQ-C30 and PROMIS emotional and instrumental support questionnaires along with a disease-specific measure (PROM).

Effect of Mismatch Repair Status on Outcome of Early-Stage Grade 1 to 2 Endometrial Cancer Treated With Vaginal Brachytherapy.

Objectives: The objective of this study was to determine if deficiency of mismatch repair (dMMR) proteins in patients with early-stage favorable endometrial cancer treated with vaginal brachytherapy (VB) is associated with increased recurrence.

Materials And Methods: A multi-institutional retrospective cohort study of 141 patients with stage I to II grade 1 and 2 endometrioid adenocarcinoma treated with surgery and adjuvant VB was performed to compare recurrence risk in dMMR (n=41) versus MMR-preserved (pMMR) (n=100). Additional clinical and pathologic risk factors were also collected.

Lymphadenectomy for high-grade endometrial cancer: Does it impact lymph node recurrence?

Introduction: The diagnostic role of lymph node (LN) assessment is established in endometrial cancer. Our study assesses whether surgical removal of metastatic LNs has oncologic benefit in high-grade endometrial cancer.

Materials And Methods: High-grade endometrial cancer cases (2000-2010) were collected from two tertiary cancer centres.

Initial findings from a prospective, large scale patient reported outcomes program in patients with gynecologic malignancy.

Introduction: Patient reported outcome measures (PROMs) are associated with improved overall survival in patients with metastatic malignancy; however, routine collection of PROMs is nascent. Little is known about PROs in women with gynecologic malignancy outside of a trial setting, limiting our understanding of how routine populations experience treatment, disease and morbidity. The goal of this study was to prospectively collect and describe disease-specific PROs in a non-trial population of women with gynecologic malignancy.

Lymph node assessment at the time of hysterectomy has limited clinical utility for patients with pre-cancerous endometrial lesions.

Objective: The objective of this study was to determine the proportion of patients with a pre-invasive endometrial lesion who meet Mayo criteria for lymph node dissection on final pathology to determine if the use of sentinel lymph node biopsy in patients with pre-invasive lesions would be warranted.

Methods: All women who underwent hysterectomy for a pre-invasive endometrial lesion (atypical hyperplasia or endometrial intra-epithelial neoplasia) between 2009 and 2019 were included for analysis. Relevant statistical tests were utilized to test the associations between patient, operative, and pathologic characteristics.

Utility of Three Nebulizers in Investigating the Infectivity of Airborne Viruses.

Laboratory-generated bioaerosols are widely used in aerobiology studies of viruses; however, few comparisons of alternative nebulizers exist. We compared aerosol production and virus survival for a Collison nebulizer, vibrating mesh nebulizer (VMN), and hydraulic spray atomizer (HSA). We also measured the dry size distribution of the aerosols produced and calculated the droplet sizes before evaporation and the dry size distribution from normal saline solution.

An integrated augmented reality surgical navigation platform using multi-modality imaging for guidance.

An integrated augmented reality (AR) surgical navigation system that potentially improves intra-operative visualization of concealed anatomical structures. Integration of real-time tracking technology with a laser pico-projector allows the surgical surface to be augmented by projecting virtual images of lesions and critical structures created by multimodality imaging. We aim to quantitatively and qualitatively evaluate the performance of a prototype interactive AR surgical navigation system through a series of pre-clinical studies.

Leptin antagonism inhibits prostate cancer xenograft growth and progression.

Hyperleptinaemia is a well-established therapeutic side effect of drugs inhibiting the androgen axis in prostate cancer (PCa), including main stay androgen deprivation therapy (ADT) and androgen targeted therapies (ATT). Given significant crossover between the adipokine hormone signalling of leptin and multiple cancer-promoting hallmark pathways, including growth, proliferation, migration, angiogenesis, metabolism and inflammation, targeting the leptin axis is therapeutically appealing, especially in advanced PCa where current therapies fail to be curative. In this study, we uncover leptin as a novel universal target in PCa and are the first to highlight increased intratumoural leptin and leptin receptor (LEPR) expression in PCa cells and patients' tumours exposed to androgen deprivation, as is observed in patients' tumours of metastatic and castrate resistant (CRPC) PCa.

The use of neoadjuvant chemotherapy in advanced endometrial cancer.

The objective of this retrospective cohort study was to review the use of neoadjuvant chemotherapy followed by interval cytoreductive surgery in patients presenting with advanced, unresectable endometrial cancer at two large cancer centers. Patients with advanced endometrial cancer treated with neoadjuvant chemotherapy between 2008 and 2015 were identified from an institutional database. Clinical and surgical variables were analyzed and time to recurrence and death was calculated and compared between surgical groups.

Effect of surgical approach on risk of recurrence after vaginal brachytherapy in early-stage high-intermediate risk endometrial cancer.

Objective: The objective was to determine if surgical approach affects time to recurrence in early-stage high-intermediate risk endometrial cancer (HIR-EC) treated with adjuvant vaginal brachytherapy (VBT).

Methods: In this retrospective cohort study, HIR-EC patients treated with VBT between 2005 and 2017 were identified and those who received open or minimally invasive hysterectomies (MIS) were included. Clinical and surgical variables were analyzed and time to recurrence was compared between surgical groups.

Patient reported outcome measures among patients with vulvar cancer at various stages of treatment, recurrence, and survivorship.

Objective: Our goal was to pragmatically describe patient reported outcomes (PROs) in a typical clinic population of vulvar cancer patients, as prior studies of vulvar cancer PROs have examined clinical trial participants.

Methods: A prospective PRO program was implemented in the Gynecologic Oncology clinic of a tertiary academic institution in January 2018. Vulvar cancer patients through September 2019 were administered the European Organization for the Research and Treatment of Cancer Quality of life Questionnaire, the Patient Reported Outcome Measurement Information System Instrumental and Emotional Support Scales, and the Functional Assessment of Cancer Therapy-Vulvar questionnaire.

Adiponectin receptor activation inhibits prostate cancer xenograft growth.

Adiponectin is an adipokine originally identified as dysregulated in obesity, with a key role in insulin sensitisation and in maintaining systemic energy balance. However, adiponectin is progressively emerging as having aberrant signalling in multiple disease states, including prostate cancer (PCa). Circulating adiponectin is lower in patients with PCa than in non-malignant disease, and inversely correlates with cancer severity.

Exploiting the Prevalence of Homologous Recombination Deficiencies in High-Grade Serous Ovarian Cancer.

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecologic cancer in the United States. Genomic analysis revealed roughly half of HGSOC display homologous repair deficiencies. An improved understanding of the genomic and somatic mutations that influence DNA repair led to the development of poly(ADP-ribose) polymerase inhibitors for the treatment of ovarian cancer.

A challenging case of twin pregnancy with complete hydatidiform mole and co-existing normal live fetus - A case report and review of the literature.

Hydatidiform mole coexisting with a normal live fetus in a twin pregnancy is extremely rare. Management of these cases is challenging due to the risk of severe antepartum and post-partum complications. Herein, we report the case of a 24-year-old gravida 2 para 1 who presented at 28 weeks gestation with severe preeclampsia, vulvar edema and a serum β-HCG of 285,000 IU/mL.

An Orthotopic Endometrial Cancer Model with Retroperitoneal Lymphadenopathy Made From In Vivo Propagated and Cultured VX2 Cells.

Endometrial cancer is the most common gynecologic malignancy in North America and the incidence is rising worldwide. Treatment consists of surgery with or without adjuvant therapy depending on lymph node involvement as determined by lymphadenectomy. Lymphadenectomy is a morbid procedure, which has not been shown to have a therapeutic benefit in many patients, and thus a new method to diagnose lymph node metastases is required.

Use of Porphysomes to detect primary tumour, lymph node metastases, intra-abdominal metastases and as a tool for image-guided lymphadenectomy: proof of concept in endometrial cancer.

: To investigate Porphysome fluorescence image-guided resection (PYRO-FGR) for detection of uterine tumour, metastatic lymph nodes and abdominal metastases in a model of endometrial cancer. : White New Zealand rabbits were inoculated with VX2 cells via intra-myometrial injection. At 30 days, Porphysomes were administered intravenously.

Lipid Uptake Is an Androgen-Enhanced Lipid Supply Pathway Associated with Prostate Cancer Disease Progression and Bone Metastasis.

lipogenesis is a well-described androgen receptor (AR)-regulated metabolic pathway that supports prostate cancer tumor growth by providing fuel, membrane material, and steroid hormone precursor. In contrast, our current understanding of lipid supply from uptake of exogenous lipids and its regulation by AR is limited, and exogenous lipids may play a much more significant role in prostate cancer and disease progression than previously thought. By applying advanced automated quantitative fluorescence microscopy, we provide the most comprehensive functional analysis of lipid uptake in cancer cells to date and demonstrate that treatment of AR-positive prostate cancer cell lines with androgens results in significantly increased cellular uptake of fatty acids, cholesterol, and low-density lipoprotein particles.