Cancer Res
Vaccine and Immunotherapy Center, Infectious Diseases Medicine, Massachusetts General Hospital, Charlestown, MA.
Published: August 2011
The chemokine CXCL12 and its receptor CXCR4 are expressed widely in human cancers, including ovarian cancer, in which they are associated with disease progression at the levels of tumor cell proliferation, invasion, and angiogenesis. Here, we used an immunocompetent mouse model of intraperitoneal papillary epithelial ovarian cancer to show that modulation of the CXCL12/CXCR4 axis in ovarian cancer has multimodal effects on tumor pathogenesis associated with induction of antitumor immunity. siRNA-mediated knockdown of CXCL12 in BR5-1 cells that constitutively express CXCL12 and CXCR4 reduced cell proliferation in vitro, and tumor growth in vivo. Similarly, treatment of BR5-1-derived tumors with AMD3100, a selective CXCR4 antagonist, resulted in increased tumor apoptosis and necrosis, reduction in intraperitoneal dissemination, and selective reduction of intratumoral FoxP3(+) regulatory T cells (Treg). Compared with controls, CXCR4 blockade greatly increased T-cell-mediated antitumor immune responses, conferring a significant survival advantage to AMD3100-treated mice. In addition, the selective effect of CXCR4 antagonism on intratumoral Tregs was associated with both higher CXCR4 expression and increased chemotactic responses to CXCL12, a finding that was also confirmed in a melanoma model. Together, our findings reinforce the concept of a critical role for the CXCL12/CXCR4 axis in ovarian cancer pathogenesis, and they offer a definitive preclinical validation of CXCR4 as a therapeutic target in this disease.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959864 | PMC |
http://dx.doi.org/10.1158/0008-5472.CAN-10-3143 | DOI Listing |
Anal Chem
January 2025
State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
As the most common and lethal cancer of the female gonads, ovarian cancer (OC) has a grave impact on people's health. OC is asymptomatic, insidious in onset, difficult to diagnose and treat, fast-growing, and easy to metastasize and has poor prognosis and high mortality. How to detect OC as early as possible and treat it without side effects has become a challenging medical problem.
View Article and Find Full Text PDFJ Hum Genet
January 2025
Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi, Japan.
Large-scale population cohort studies that collect genomic information are tasked with returning an assessment of genetic risk for hereditary cancers to participants. While several studies have applied to return identified genetic risks to participants, comprehensive surveys of participants' understanding, feelings, and behaviors toward cancer risk remain to be conducted. Here, we report our experience and surveys of returning genetic risks to 100 carriers of pathogenic variants for hereditary cancers identified through whole genome sequencing of 50 000 individuals from the Tohoku Medical Megabank project, a population cohort study.
View Article and Find Full Text PDFChem Biol Interact
January 2025
Institute of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria. Electronic address:
A series of eight gold(I) N-heterocyclic carbene (NHC) complexes [Au(IMes)(HLn)] based on 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes) and 7-azaindole derivatives (HLn), where n = 1-8 for HL1 = 5-flouro-7-azaindole, HL2 = 5-bromo-7-azaindole, HL3 = 3-chloro-7-azaindole, HL4 = 3-iodo-7-azaindole, HL5 = 5-bromo-3-chloro-7-azaindole, HL6 = 5-bromo-3-iodo-7-azaindole, HL7 = 4-chloro-2-methyl-7-azaindole and HL8 = 7-azaindole, was prepared, characterised and studied for their in vitro anti-cancer and anti-inflammatory effects. The complexes showed significant cytotoxicity on human ovarian cancer cell lines (A2780, IC ≈ 8-19 μM and A2780R, IC ≈ 8-19 μM) and lowered toxicity in normal HaCat and MRC-5 cells. Cellular effects of the selected complexes 1 and 7 were evaluated in A2780 cells using flow cytometry.
View Article and Find Full Text PDFAm J Obstet Gynecol
January 2025
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; CPRIT Scholar in Cancer Research. Electronic address:
Background: Adult-type granulosa cell tumors are a rare form of ovarian cancer, 30% of which will recur. Cytoreductive surgery is often performed at the time of a first recurrence, but little is known about the impact of open versus minimally invasive surgical approaches on survival outcomes.
Objective: To examine associations between surgical approach, clinical variables, and survival outcomes among patients with adult-type granulosa cell tumors who underwent cytoreductive surgery at the time of first recurrence.
Reprod Toxicol
January 2025
Developmental Biology Laboratory, Department of Morphology and Genetic, Federal University of Sao Paulo (UNIFESP), Sao Paulo, Sao Paulo, Brazil. Electronic address:
Nicotine is one of the most toxic substances found in cigarettes, but also found in chewing tobacco gum, patches and vaping products (electronic cigarettes). In addition to being a highly addictive chemical, it is capable of reducing fertility in men and women. In the ovaries, it can induce morphological changes and impair the formation of follicles, being a possible cause of changes in the reproductive cycle and anticipation of menopause in women whose mothers smoked during pregnancy.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!
© LitMetric 2025. All rights reserved.