Dysregulation of Cholesterol Homeostasis in Ovarian Cancer

Cholesterol plays an essential role in maintaining the rigidity of cell membranes and signal transduction. Various investigations confirmed empirically that the dysregulation of cholesterol homeostasis positively correlates with tumor progression. More specifically, recent studies suggested the distinct role of cholesterol in ovarian cancer cell proliferation, metastasis and chemoresistance. In this review, we summarize the current findings that suggest the contribution of cholesterol homeostasis dysregulation to ovarian cancer progression and resistance to anti-cancer agents. We also discuss the therapeutic implications of cholesterol-lowering drugs in ovarian cancer

Next‐Generation Sequencing in the Diagnosis of Metastatic Lesions: Reclassification of a Glioblastoma as an Endometrial Cancer Metastasis to the Brain

Endometrial cancer is the most common gynecologic cancer in the U.S., but metastasis to the brain is rare, and diagnosis can be challenging. Traditional tools for determining if a tumor is a primary or metastatic lesion include pan‐imaging, histopathologic studies, and immunohistochemistry. Molecular testing with next‐generation sequencing has been increasingly used to augment these tests. We present a case of a patient who initially presented with a brain lesion diagnosed as glioblastoma on histology and immunohistochemistry, but whose diagnosis was later changed to metastasis from an endometrial primary based on molecular findings. The two tumors shared a common microsatellite instability signature and 51 DNA variants, including oncogenic driver mutations KRAS p.G13D, PIK3CA p.E545A, and PTEN p.I135V and p.K267Rfs*9. This highlights the power of molecular analysis in making the diagnosis in cases of rare metastases.Key PointsBrain metastasis from endometrial primary is rare, and histopathological features may be augmented with molecular analysis to aid in diagnosis.Comparison of the molecular makeup of the primary endometrial lesion with the metastatic lesion may reveal high‐risk molecular features that may be indicative of metastatic potential.Metastasis of endometrial cancer to the brain is rare, and diagnosis can be challenging. This case report highlights the power of molecular analysis in making the diagnosis in cases of rare metastases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171228/1/onco13927_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171228/2/onco13927.pd

Human Papillomavirus (HPV) Education and Knowledge Among Medical and Dental Trainees

Persistent human papillomavirus (HPV) infection is responsible for the majority of oropharyngeal and cervical cancers in the USA. Currently, HPV curricula within medical and dental schools are not standardized. As such, we implemented a brief online educational intervention to increase medical and dental trainees' knowledge of the HPV vaccine and the association between HPV and cancer. The objectives of this study were to (1) assess medical and dental trainees' baseline knowledge regarding HPV and HPV vaccine, (2) determine the willingness to recommend the HPV vaccine to patients, and (3) evaluate the impact of an online intervention on HPV-related knowledge. Medical and dental trainees from two large academic centers in the USA were asked to fill out an online pre-intervention questionnaire, followed by a 10-min HPV educational intervention based on the Center of Disease Control and Prevention (CDC) resources, and then a post-intervention questionnaire. There were 75 participants (67.4% females; median age 18-30 years). When asked about HPV-related cancer types, the correct response increased from 28.4% (pre-intervention) to 51.9% (post-intervention; p < 0.01). When asked about the prevalence of HPV infections, the correct response improved from 36 to 72% (p < 0.01). There was also a 25.2% improvement in identifying the correct HPV vaccination dosing schedule (p < 0.01). Eighty-seven percent of the participants mentioned that the online education improved their HPV knowledge, and 68.5% reported that they were more likely to recommend HPV vaccine after the online intervention. The proposed online educational intervention was effective at improving HPV-related cancer and HPV vaccine knowledge as well as attitudes towards vaccine recommendation among dental and medical trainees and could be implemented in medical and dental school curricula in the future

Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary

Abstract Cancer cells need constant supplies of lipids to survive and grow. Lipid dependence has been observed in various types of cancer, including high-grade serous ovarian carcinomas (HGSOC), which is a lethal form of gynecological malignancy. ANGPTL3, PCSK9, and Apo CIII are pivotal lipid-modulating factors, and therapeutic antibodies have been developed against each one (Evinacumab, Evolocumab and Volanesorsen, respectively). The roles -if any- of ANGPTL3, PCSK9, and Apo CIII in HGSOC are unclear. Moreover, levels of these lipid-modulating factors have never been reported before in HGSOC. In this study, circulating levels of ANGPTL3, PCSK9, and Apo CIII, along with lipid profiles, are examined to verify whether one or many of these lipid-regulating factors are associated with HGSOC. Methods ELISA kits were used to measure ANGPTL3, PCSK9 and Apo CIII levels in plasma samples from 31 women with HGSOC and 40 women with benign ovarian lesions (BOL) before treatment and surgery. A Roche Modular analytical platform measured lipid panels, Apo B and Lp(a) levels. Results ANGPTL3 levels were higher in women with HGSOC (84 ng/mL, SD: 29 ng/mL, n = 31) than in women with BOL (67 ng/mL, SD: 31 ng/mL, n = 40; HGSOC vs. BOL P = 0.019). Associations between the lipid panel and ANGPTL3, and the inverse relationship between HDL-cholesterol and triglycerides, were present in women with BOL but not with HGSOC. PCSK9 and Apo CIII were not associated with HGSOC. Conclusions In this cohort of 71 women, ANGPTL3 levels were increased in HGSOC patients. The presence of HGSOC disrupted the classic inverse relationship between HDL and triglycerides, as well as the association between the lipid panel and ANGPTL3. These associations were only maintained in cancer-free women. Given the availability of Evinacumab, a therapeutic antibody against ANGPTL3, the current finding prompts an assessment of whether ANGPTL3 inhibition has therapeutic potential in HGSOC

COVID-19 as a catalyst for reimagining cervical cancer prevention

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally

Additional file 1 of Pre-operative levels of angiopoietin protein-like 3 (ANGPTL3) in women diagnosed with high-grade serous carcinoma of the ovary

Additional file 1: Fig. S1. Flow chart of analyses performed on the study population. Fig. S2. Pairwise Spearman’s partial correlation analyses between all variables, with age-adjustment. Partial correlations based on age-adjustment are presented for (A) benign ovarian lesions (BOL), (B) high-grade serous ovarian carcinoma (HGSOC) and (C) the entire cohort (overall). Correlation coefficients (rho) are displayed in each matrix lower half-panel with color hues indicative of relationship strength (see rho coefficient scale). Correlation significance is expressed in upper half-panel (ns: non-significant, *: P < 0.05; **: P < 0.01; ***: P < 0.001; ****: P < 0.000 1). Fig. S3. CA125 and HE4 plasma levels between BOL and HGSOC. Significant level increase of tumor markers CA125 (BOL: n = 40, HGSOC: n = 31, P = 1.4E-7) and HE4 (BOL: n = 38, HGSOC: n = 23, P = 2.2E-7) was found in HGSOC compared to BOL. ****: P < 0.000 1

COVID-19 as a catalyst for reimagining cervical cancer prevention.

Peer reviewed: TrueCervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic - especially in vaccination, self-administered testing, and coordinated mobilization on a global scale - may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally