Network Medicine-Based Analysis of Association Between Gynecological Cancers and Metabolic and Hormonal Disorders

Gynecological cancers pose an important public health issue, with a high incidence among women of all ages. Gynecological cancers such as malignant germ-cell tumors, sex-cord-stromal tumors, uterine sarcomas and carcinosarcomas, gestational trophoblastic neoplasia, vulvar carcinoma and melanoma of the female genital tract, are defined as rare with an annual incidence of <6 per 100,000 women. Rare gynecological cancers (RGCs) are associated with poor prognosis, and given the low incidence of each entity, there is the risk of delayed diagnosis due to clinical inexperience and limited therapeutic options. There has been a growing interest in the field of microRNAs (miRNAs), a class of small non-coding RNAs of ∼22 nucleotides in length, because of their potential to regulate diverse biological processes. miRNAs usually induce mRNA degradation and translational repression by interacting with the 3′ untranslated region (3′-UTR) of target mRNAs, as well as other regions and gene promoters, as well as activating translation or regulating transcription under certain conditions. Recent research has revealed the enormous promise of miRNAs for improving the diagnosis, therapy and prognosis of all major gynecological cancers. However, to date, only a few studies have been performed on RGCs. In this review, we summarize the data currently available regarding RGCs.

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Direct and Indirect endocrine-mediated suppression of human endometrial CD8+T cell cytotoxicity

Scientific Reports ◽

10.1038/s41598-021-81380-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Z. Shen ◽

M. Rodriguez-Garcia ◽

M. V. Patel ◽

C. R. Wira

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Cytotoxic Activity ◽

Cd8 T Cells ◽

Immune Cells ◽

Cd8 T Cell ◽

Gynecological Cancers ◽

Protective Strategies ◽

T Cell Cytotoxicity

AbstractRegulation of endometrial (EM) CD8+T cells is essential for successful reproduction and protection against pathogens. Suppression of CD8+T cells is necessary for a tolerogenic environment that promotes implantation and pregnancy. However, the mechanisms regulating this process remain unclear. Sex hormones are known to control immune responses directly on immune cells and indirectly through the tissue environment. When the actions of estradiol (E2), progesterone (P) and TGFβ on EM CD8+T cells were evaluated, cytotoxic activity, perforin and granzymes were directly suppressed by E2 and TGFβ but not P. Moreover, incubation of polarized EM epithelial cells with P, but not E2, increased TGFβ secretion. These findings suggest that E2 acts directly on CD8+T cell to suppress cytotoxic activity while P acts indirectly through induction of TGFβ production. Understanding the mechanisms involved in regulating endometrial CD8+T cells is essential for optimizing reproductive success and developing protective strategies against genital infections and gynecological cancers.

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Vascular and Cardiac Prognostic Determinants in Patients with Gynecological Cancers: A Six-Year Follow-up Study

Applied Sciences ◽

10.3390/app11136091 ◽

2021 ◽

Vol 11 (13) ◽

pp. 6091

Author(s):

Pietro Scicchitano ◽

Marco Tucci ◽

Gabriella Ricci ◽

Michele Gesualdo ◽

Santa Carbonara ◽

...

Keyword(s):

Brachial Artery ◽

Cox Regression ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Controlled Study ◽

Gynecological Cancers ◽

Roc Curve Analysis ◽

Cox Regression Analysis ◽

All Cause Mortality

Background: The aim of this study was to assess the role of cardiac and vascular parameters as all-cause mortality determinants in patients suffering from gynecological cancers. Methods: This was an observational, prospective, non-randomized, and non-controlled study. Forty-seven consecutive patients (mean age: 58 ± 13 years) were enrolled after cancer staging. All patients underwent evaluation of vascular (common carotid intima-media thickness (mean C-IMT), flow-mediated dilation of the brachial artery (FMD), and antero-posterior diameter of the infrarenal abdominal aorta (APAO)) and cardiac function and morphology before cancer-related interventions. A 6-year follow-up was carried out to assess the overall survival of the whole population. Results: Twenty patients (42%) died by the time of the 6-year follow-up. The brachial artery FMD values were higher in the survivors than the non-survivors (9.71 ± 3.53% vs. 6.13 ± 2.62%, p < 0.001), as well as the LVEF (60.8 ± 3.0% vs. 57.8 ± 4.4%, p = 0.009). There were no differences in the mean C-IMT, APAO, and other echocardiographic parameters. ROC curve analysis identified a baseline LVEF < 57% and FMD value < 5.8% as the best cut-offs. Kaplan–Meier evaluation showed that the LVEF, tricuspid annular plane systolic excursion, and FMD were the best predictors of all-cause mortality, although only the LVEF and FMD were confirmed in multivariate Cox regression analysis. Conclusions: The LVEF and brachial artery FMD are independent prognostic determinants in patients with gynecological cancers.

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Emotion episodes during psychotherapy sessions among women newly diagnosed with gynecological cancers

Psycho-Oncology ◽

10.1002/pon.3737 ◽

2014 ◽

Vol 24 (9) ◽

pp. 1189-1196 ◽

Cited By ~ 3

Author(s):

Shannon Myers Virtue ◽

Sharon L. Manne ◽

Kathleen Darabos ◽

Carolyn J. Heckman ◽

Melissa Ozga ◽

...

Keyword(s):

Newly Diagnosed ◽

Gynecological Cancers

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Estimation of the Optimal Brachytherapy Utilization Rate in the Treatment of Gynecological Cancers and Comparison With Patterns of Care

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2012.04.014 ◽

2013 ◽

Vol 85 (2) ◽

pp. 400-405 ◽

Cited By ~ 3

Author(s):

Stephen R. Thompson ◽

Geoff P. Delaney ◽

Gabriel S. Gabriel ◽

Susannah Jacob ◽

Prabir Das ◽

...

Keyword(s):

Patterns Of Care ◽

Utilization Rate ◽

Gynecological Cancers

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Biomolecular Network-Based Synergistic Drug Combination Discovery

BioMed Research International ◽

10.1155/2016/8518945 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Xiangyi Li ◽

Guangrong Qin ◽

Qingmin Yang ◽

Lanming Chen ◽

Lu Xie

Keyword(s):

Drug Combination ◽

Complex Disease ◽

Recent Decade ◽

Drug Combinations ◽

Network Medicine ◽

Disease Therapy ◽

Biomolecular Network ◽

Disease Related Genes ◽

Disease Specific ◽

Synergistic Drug Combinations

Drug combination is a powerful and promising approach for complex disease therapy such as cancer and cardiovascular disease. However, the number of synergistic drug combinations approved by the Food and Drug Administration is very small. To bridge the gap between urgent need and low yield, researchers have constructed various models to identify synergistic drug combinations. Among these models, biomolecular network-based model is outstanding because of its ability to reflect and illustrate the relationships among drugs, disease-related genes, therapeutic targets, and disease-specific signaling pathways as a system. In this review, we analyzed and classified models for synergistic drug combination prediction in recent decade according to their respective algorithms. Besides, we collected useful resources including databases and analysis tools for synergistic drug combination prediction. It should provide a quick resource for computational biologists who work with network medicine or synergistic drug combination designing.

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