scholarly journals Bipolar Tumor-Associated Macrophages in Ovarian Cancer as Targets for Therapy

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 366 ◽  
Author(s):  
Vijayalaxmi Gupta ◽  
Fiona Yull ◽  
Dineo Khabele
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Peritoneal Metastasis ◽  
Gynecological Cancer ◽  
Malignant Ascites ◽  
Tumor Associated Macrophages ◽  
Fatal Disease ◽  
Cancer Tumor

Ovarian cancer, a rare but fatal disease, has been a challenging area in the field of gynecological cancer. Ovarian cancer is characterized by peritoneal metastasis, which is facilitated by a cross-talk between tumor cells and other cells in the tumor microenvironment (TME). In epithelial ovarian cancer, tumor-associated macrophages (TAMs) constitute over 50% of cells in the peritoneal TME and malignant ascites, and are potential targets for therapy. Here, we review the bipolar nature of TAMs and the evolving strategies to target TAMs in ovarian cancer.

scholarly journals Carrier-Free Multifunctional Nanomedicine For Intraperitoneal Disseminated Ovarian Cancer Therapy

2022 ◽  
Author(s):  
Xiuyu Huang ◽  
Miaojuan Qiu ◽  
Tianqi Wang ◽  
Binbin Li ◽  
Shiqiang Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Self Assembly ◽  
Gynecological Cancer ◽  
Advanced Ovarian Cancer ◽  
Malignant Ascites ◽  
Tumor Cell Migration ◽  
Average Size

Abstract Background: Ovarian cancer is the most lethal gynecological cancer which is characterized by extensive peritoneal implantation metastasis and malignant ascites. Despite advances in diagnosis and treatment in recent years, the five-year survival rate is only 25 - 30%. Therefore, developing multifunctional nanomedicine with abilities of promoting apoptosis and inhibiting migration on tumor cells would be a promising strategy to improve the antitumor effect.Methods and results: In this study, we developed a novel ACaT nanomedicine composed of alendronate, calcium ions and cyclin-dependent kinase 7 (CDK7) inhibitor THZ1. With the average size of 164 nm and zeta potential of 12.4 mV, the spherical ACaT nanoparticles were selectively internalized by tumor cells and effectively accumulated in the tumor site. Results of RNA-sequencing and in vitro experiments showed that ACaT promoted tumor cell apoptosis and inhibited tumor cell migration by arresting the cell cycle, increasing ROS and affecting calcium homeostasis. Weekly intraperitoneally administered of ACaT for 8 cycles significantly inhibited the growth of tumor and prolonged the survival of intraperitoneal xenograft mice.Conclusion: In summary, this study presents a new self-assembly nanomedicine with favorable tumor targeting, antitumor activity and good biocompatibility, providing a novel therapeutic strategy for advanced ovarian cancer.

scholarly journals The Impact of Mesothelin in the Ovarian Cancer Tumor Microenvironment

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 277 ◽  
Author(s):  
Tyvette Hilliard
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Survival Rates ◽  
Ca 125 ◽  
Specific Expression ◽  
Stage Disease ◽  
Cancer Tumor ◽  
Gynecological Disease ◽  
The Impact

Ovarian cancer is the deadliest gynecological disease among U.S. women. Poor 5-year survival rates (<30%) are due to presentation of most women at diagnosis with advanced stage disease with widely disseminated intraperitoneal metastasis. However, when diagnosed before metastatic propagation the overall 5-year survival rate is >90%. Metastasizing tumor cells grow rapidly and aggressively attach to the mesothelium of all organs within the peritoneal cavity, including the parietal peritoneum and the omentum, producing secondary lesions. In this review, the involvement of mesothelin (MSLN) in the tumor microenvironment is discussed. MSLN, a 40kDa glycoprotein that is overexpressed in many cancers including ovarian and mesotheliomas is suggested to play a role in cell survival, proliferation, tumor progression, and adherence. However, the biological function of MSLN is not fully understood as MSLN knockout mice do not present with an abnormal phenotype. Conversely, MSLN has been shown to bind to the ovarian cancer antigen, CA-125, and thought to play a role in the peritoneal diffusion of ovarian tumor cells. Although the cancer-specific expression of MSLN makes it a potential therapeutic target, more studies are needed to validate the role of MSLN in tumor metastasis.

Epithelial ovarian cancer tumor microenvironment is a favorable biomarker resource

2011 ◽  
Vol 120 ◽  
pp. S48-S49
Author(s):  
E. Hoskins ◽  
B. Hood ◽  
M. Sun ◽  
T. Krivak ◽  
T. Conrads ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
Cancer Tumor

scholarly journals Characterizing Endocrine Status, Tumor Hypoxia and Immunogenicity for Therapy Success in Epithelial Ovarian Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Madison Pereira ◽  
Kathy Matuszewska ◽  
Colin Jamieson ◽  
Jim Petrik
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Epithelial Ovarian Cancer ◽  
Tumor Heterogeneity ◽  
Tumor Hypoxia ◽  
Therapy Response ◽  
Treatment Resistance ◽  
Malignant Ascites ◽  
Response To Therapy ◽  
Vascular Density

Epithelial ovarian cancer is predominantly diagnosed at advanced stages which creates significant therapeutic challenges. As a result, the 5-year survival rate is low. Within ovarian cancer, significant tumor heterogeneity exists, and the tumor microenvironment is diverse. Tumor heterogeneity leads to diversity in therapy response within the tumor, which can lead to resistance or recurrence. Advancements in therapy development and tumor profiling have initiated a shift from a “one-size-fits-all” approach towards precision patient-based therapies. Here, we review aspects of ovarian tumor heterogeneity that facilitate tumorigenesis and contribute to treatment failure. These tumor characteristics should be considered when designing novel therapies or characterizing mechanisms of treatment resistance. Individual patients vary considerably in terms of age, fertility and contraceptive use which innately affects the endocrine milieu in the ovary. Similarly, individual tumors differ significantly in their immune profile, which can impact the efficacy of immunotherapies. Tumor size, presence of malignant ascites and vascular density further alters the tumor microenvironment, creating areas of significant hypoxia that is notorious for increasing tumorigenesis, resistance to standard of care therapies and promoting stemness and metastases. We further expand on strategies aimed at improving oxygenation status in tumors to dampen downstream effects of hypoxia and set the stage for better response to therapy.

scholarly journals E-Cadherin fragments as potential mediators for peritoneal metastasis in advanced epithelial ovarian cancer

2016 ◽  
Vol 114 (2) ◽  
pp. 213-220 ◽  
Author(s):  
Fabian Trillsch ◽  
Sascha Kuerti ◽  
Christine Eulenburg ◽  
Eike Burandt ◽  
Linn Woelber ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Peritoneal Metastasis ◽  
Advanced Epithelial Ovarian Cancer ◽  
E Cadherin

scholarly journals Regional and temporal heterogeneity of epithelial ovarian cancer tumor biopsies: implications for therapeutic strategies

Oncotarget ◽  
2016 ◽  
Vol 0 (0) ◽  
Author(s):  
Lara Paracchini ◽  
Laura Mannarino ◽  
Ilaria Craparotta ◽  
Chiara Romualdi ◽  
Robert Fruscio ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Therapeutic Strategies ◽  
Temporal Heterogeneity ◽  
Cancer Tumor ◽  
Tumor Biopsies

scholarly journals Development and Validation for Prognostic Nomogram of Epithelial Ovarian Cancer Recurrence based on Circulating Tumor Cells and Epithelial–Mesenchymal Transition

2020 ◽  
Author(s):  
Jiani Yang ◽  
Jun Ma ◽  
Yue Jin ◽  
Shanshan Cheng ◽  
Shan Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Risk Stratification ◽  
Epithelial Ovarian Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Ca 125 ◽  
Mesenchymal Transition ◽  
Cox Regression Analysis ◽  
Significant Difference

Abstract We aimed to determine prognosis value of circulating tumor cells(CTCs) undergoing epithelial–mesenchymal transition(EMT) in epithelial ovarian cancer(EOC) recurrence. We used CanPatrol CTC-enrichment technique to detect CTCs from blood samples and classify subpopulations into epithelial, mesenchymal and hybrids. To construct nomogram, prognostic factors were selected by Cox regression analysis. Risk stratification was performed through Kaplan–Meier analysis among training group(n=114) and validation group(n=38). By regression screening, both CTC counts(HR 1.187; 95%CI 1.098-1.752; p=0.012) and M-CTC(HR 1.098; 95%CI 1.047-1.320; p=0.009) were demonstrated as independent factors for recurrence. Other variables including pathological grade, FIGO stage, lymph node metastasis, ascites and CA-125 were also collected(p < 0.005) to construct nomogram. The C-index of internal and external validation for nomogram was 0.913 and 0.874. We found significant predictive value for nomogram with/without CTCs (AUC 0.8705 and 0.8097). Taking CTC counts and M-CTC into separation, the values were 0.8075 and 0.8262. Finally, survival curves of risk stratification based on CTC counts(p=0.0241), M-CTC(p=0.0107) and the nomogram(p=0.0021) were drawn with significant difference. In conclusion, CTCs could serve as a novel factor for EOC prognosis. Nomogram model constructed by CTCs and other clinical parameters could predict EOC recurrence and perform risk stratification for clinical decision-making.Trial registration: Chinese Clinical Trial Registry, ChiCTR-DDD-16009601, October 25, 2016

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