Ovarian cancer is the sixth leading cause of cancer-related mortality among individuals with ovaries, and high-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype. Characterized by a distinct and aggressive metastatic pattern, HGSOC can originate in the fallopian tube with the transformation of fallopian tube epithelial (FTE) cells, which metastasize to the ovary and subsequently to the omentum and peritoneal cavity. The omentum is a privileged metastatic site, and the metabolic exchange underlying omental metastasis could provide enzyme or receptor targets to block spread. In this study, we adapted a mass spectrometry imaging (MSI) protocol to investigate spatial location of 3D cocultures of tumorigenic FTE cells when grown in proximity to murine omental explants as a model of early metastatic colonization. Our analysis revealed several altered metabolites in tumorigenic FTE/omentum cocultures, namely changes in branched-chain amino acids (BCAA), including valine. We quantified the heightened consumption of valine, other BCAAs, and other amino acid-derived metabolites in omental cocultures using LC-MS assays. Our analysis revealed that metabolite concentrations when monitored with MSI from cell culture media in living culture systems have notable considerations for how MSI data may produce signatures that induce ionization suppression. Supplementation with valine enhanced proliferation and mTOR signaling in tumorigenic FTE cells, suggesting the potential of BCAA's as a nutrient utilized by tumor cells during omental colonization and a possible target for metastasis.
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http://dx.doi.org/10.1158/2767-9764.CRC-24-0532 | DOI Listing |
Sci Transl Med
March 2025
Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, China.
The benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer remains controversial, hindering the development of rational combination therapies based on hyperthermia (HT). This study reports the preliminary results of the neoadjuvant HIPEC (NHIPEC) trial (ChiCTR2000038173), demonstrating enhanced tumor response in high-grade serous ovarian cancer with NHIPEC. Through single-cell RNA sequencing analysis, we identified both homogeneous and heterogeneous cellular responses to HT within the tumor and microenvironment.
View Article and Find Full Text PDFCancer
March 2025
Department of Oncology, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan, USA.
Background: Prior studies of participants with breast and other obesity-associated cancers in the Women's Health Initiative (WHI) showed worse mortality and cardiovascular disease (CVD) outcomes for individuals with a higher number of cardiometabolic risk factors at study entry. The purpose of this analysis is to compare the relationship between cardiometabolic abnormalities and mortality among women with and without cancer in the WHI.
Methods: Women with one of five early-stage obesity-associated cancers (breast, colorectal, endometrial, ovarian, and non-Hodgkin lymphoma) and controls without any new or prior history of cancer were selected from the WHI-Life and Longevity after Cancer ancillary study.
Reprod Sci
March 2025
Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, the C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Glyphosate-based herbicides (GBHs) are the most widely used herbicides in the United States, accounting for 19% of estimated global use. Although the Environmental Protection Agency (EPA) has reaffirmed that the active ingredient glyphosate (GLY) is safe for humans, recent studies on exposure have suggested association with cancer, metabolic disorders, endocrine disruption and infertility, Alzheimer's and Parkinson's disease, and psychological disorders. Current literature on the effects of GLY exposure on reproductive function suggests potential clinical implications on women's reproductive health, including polycystic ovarian syndrome (PCOS), endometriosis, infertility, and adverse pregnancy outcomes.
View Article and Find Full Text PDFEur J Cancer Prev
March 2025
Department of Oncology and Hemato-Oncology, University of Milan.
Endometriosis is one of the most common gynecological benign disease. Epidemiological evidence suggests a potential association between endometriosis and cancer risk. Accumulating evidence highlighted the risk of ovarian cancer, particularly endometrioid and clear cell subtypes.
View Article and Find Full Text PDFCells
March 2025
Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Ovarian cancer survival depends strongly on the time of diagnosis. Detection at stage 1 must be the goal of liquid biopsies for ovarian cancer detection. We report the development and validation of graphene-based optical nanobiosensors (G-NBSs) that quantify the activities of a panel of proteases, which were selected to provide a crowd response that is specific for ovarian cancer.
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