Calcification: A Disregarded or Ignored Issue in the Gynecologic Tumor Microenvironments

2018 ◽  
Vol 28 (3) ◽  
pp. 486-492 ◽  
Author(s):  
Jirui Wen ◽  
Yali Miao ◽  
Shichao Wang ◽  
Ruijie Tong ◽  
Zhiwei Zhao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Degenerative Change ◽  
Uterine Fibroids ◽  
Morphological Characteristics ◽  
Good Prognosis ◽  
Gynecological Tumors ◽  
Tumor Microenvironments ◽  
Gynecologic Tumor ◽  
Gynecological Tumor ◽  
Clinically Significant

AbstractAlthough calcification in the gynecologic tumor microenvironments is a common phenomenon, doctors and researchers still disregard or ignore the issue. In fact, this change in the gynecologic tumor microenvironments is clinically significant and a number of studies have reported an association between calcification and gynecological tumor progression. In ovarian cancer, calcification is predominantly psammomatous and largely occurs in serous papillary ovarian tumors. In addition, calcification in ovarian cancer correlated with lower histologic grade and may indicate a poorer survival rate. In uterine fibroids, calcification occurs as a degenerative change and is predictive of a good prognosis. As for endometrial cancer and cervical cancer, calcification rarely occurs in these cancers. The mechanism of calcification in the gynecologic tumor microenvironments is not currently clear. One theory is that calcification occurs due to degeneration of the tumor cells; another theory is that calcification occurs in response to secretions from cells in the tumor microenvironment. Although previous studies have revealed a direct association between calcifications and gynecological tumors, this association has not been fully clarified. To better clarify the significance of calcification in terms of diagnosing and treating gynecological tumors, the associations between calcification and the different histologic stages and prognosis in gynecological tumors should be further studied. In particular, more attention should be paid to the morphological characteristics, chemical nature, and mechanism of calcifications in the gynecological tumor microenvironments.

scholarly journals Molecular Biology of Ovarian Cancer: From Mechanisms of Intraperitoneal Metastasis to Therapeutic Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1661
Author(s):  
Krzysztof Książek
Keyword(s):  
Ovarian Cancer ◽  
Molecular Biology ◽  
Cause Of Death ◽  
Genital Tract ◽  
Female Genital Tract ◽  
Gynecological Tumors ◽  
Female Genital

Ovarian cancer (OC) is one of the most frequent malignancies of the female genital tract, and is still the leading cause of death from gynecological tumors [...]

National Cancer Institute–United States strategy regarding intraperitoneal chemotherapy for ovarian cancer

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 26-28 ◽  
Author(s):  
E. L. Trimble ◽  
M. C. Christian
Keyword(s):  
Ovarian Cancer ◽  
National Cancer Institute ◽  
Phase Iii ◽  
Cooperative Groups ◽  
Advocacy Organizations ◽  
Increased Risk ◽  
Phase Iii Trials ◽  
Educational Campaign ◽  
Clinically Significant ◽  
Further Development

On the basis of three large randomized phase III trials, the National Cancer Institute (NCI) issued a Clinical Announcement in January 2006 recommending that women with optimally debulked stage III ovarian cancer and their physicians consider a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy. The combination of IV and IP chemotherapy is associated with a clinically significant benefit in survival, although it does also confer an increased risk of toxicity compared to IV chemotherapy alone. The NCI Clinical Announcement was issued as part of a broader educational campaign, designed in conjunction with professional societies, cancer centers, Clinical Trials Cooperative Groups, and cancer advocacy organizations. The further development of IP chemotherapy in ovarian cancer requires additional clinical and translational research

scholarly journals A Novel Defined Risk Signature of the Ferroptosis-Related Genes for Predicting the Prognosis of Ovarian Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Ying Ye ◽  
Qinjin Dai ◽  
Shuhong Li ◽  
Jie He ◽  
Hongbo Qi
Keyword(s):  
Ovarian Cancer ◽  
High Risk ◽  
Risk Model ◽  
Cox Regression ◽  
Ovarian Tissue ◽  
Gene Signature ◽  
High Risk Group ◽  
Cancer Prognosis ◽  
Consensus Clustering ◽  
Gynecologic Tumor

Ferroptosis is an iron-dependent, regulated form of cell death, and the process is complex, consisting of a variety of metabolites and biological molecules. Ovarian cancer (OC) is a highly malignant gynecologic tumor with a poor survival rate. However, the predictive role of ferroptosis-related genes in ovarian cancer prognosis remains unknown. In this study, we demonstrated that the 57 ferroptosis-related genes were expressed differently between ovarian cancer and normal ovarian tissue, and based on these genes, all OC cases can be well divided into 2 subgroups by applying consensus clustering. We utilized the least absolute shrinkage and selection operator (LASSO) cox regression model to develop a multigene risk signature from the TCGA cohort and then validated it in an OC cohort from the GEO database. A 5-gene signature was built and reveals a favorable predictive efficacy in both TCGA and GEO cohort (P < 0.001 and P = 0.03). The GO and KEGG analysis revealed that the differentially expressed genes (DEGs) between the low- and high-risk subgroup divided by our risk model were associated with tumor immunity, and lower immune status in the high-risk group was discovered. In conclusion, ferroptosis-related genes are vital factors predicting the prognosis of OC and could be a novel potential treatment target.

scholarly journals Identification of a gene set correlated with immune status in ovarian cancer by transcriptome-wide data mining

2020 ◽  
Author(s):  
Lili Fan ◽  
Han Lei ◽  
Ying Lin ◽  
Zhengwei Zhou ◽  
Guang Shu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Immune Cell ◽  
Good Prognosis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Survival Prognosis ◽  
Immune Activity ◽  
Gene Set ◽  
Immune Infiltration ◽  
Keywords Ovarian Cancer

Abstract Background : Ovarian cancer (OC) is a serious tumor disease in gynecology. Many papers have reported that high tumor mutational burden (TMB) can generate many neoantigens to result in a higher degree of tumor immune infiltration, so our study aims to predict the key molecules in OC immunotherapy by combined TMB with immunoactivity-related gene. Method: We divided OC cases into two groups: the low & high TMB group hinged on the somatic mutation data from the Cancer Genome Atlas (TCGA). We also used single-sample gene set enrichment analysis (ssGSEA) scores of immune cell types to conduct unsupervised clustering of OC patients in the TCGA cohort and some of them were defined as the low & high immunity group. Besides, to further understand the function of these genes, we conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, protein-protein interaction network, survival prognosis analysis and immune infiltration analysis. Finally, the effects on prognosis and immunotherapy in OC patients were explored by the Group on Earth Observations verification the patients' responses to immunotherapy. Results: We found that the higher the TMB was associated with the higher OC grades. Moreover, both high TMB and high immunity were significantly correlated with a good prognosis of OC. Then, 14 up-regulated differential expression genes (Up-DEGs) that were closely related to the prognosis of OC patients were screened according to the high TMB group and the high immunity group. Next, pathway analysis revealed that Up-DGEs were mainly involved in immune response and T cell proliferation. Finally, four genes had a good prognosis and were validated in the GEO dataset which included CXCL13, FCRLA, PLA2G2D, and MS4A1. We also identified that four genes had a good prognosis in melanoma patients treated with anti-PD-L1 and anti-CTLA-4 in the TIDE database. Conclusion: High TMB can promote immune cell infiltration and increases immune activity. And our analysis also demonstrated that the higher the TMB, the higher the immune activity, the better the prognosis of OC. Altogether, we found that CXCL13, FCRLA, PLA2G2D, and MS4A1 may be biomarkers for OC immunotherapy. Keywords: ovarian cancer, TMB, immune cells infiltration, survival prognosis.

Docetaxel in combination with carboplatin for chemo-naive patients with epithelial ovarian cancer

2002 ◽  
Vol 12 (6) ◽  
pp. 704-709
Author(s):  
Y. Aoki ◽  
T. Sato ◽  
I. Tsuneki ◽  
M. Watanabe ◽  
H. Kase ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
University Hospital ◽  
Time Curve ◽  
Randomized Controlled Clinical Trials ◽  
Highly Active ◽  
Gynecology And Obstetrics ◽  
Major Toxicity ◽  
Clinically Significant ◽  
Low Incidence ◽  
Grade 3

We conducted a study of docetaxel-carboplatin combination therapy to confirm the efficacy and toxicity in chemotherapy-naive patients with ovarian cancer. Docetaxel 70 mg/m2 and carboplatin (area under the concentration-vs.-time curve of 5) were administered consecutively on day 1 of a 21-day cycle for five planned cycles in chemo-naive patients with the International Federation of Gynecology and Obstetrics stage IC to IV ovarian cancer with or without successful cytoreductive surgery at staging laparotomy. Twenty-six patients (median age, 53 years; range, 34–76 years) were enrolled into this trial at Niigata University Hospital. The major toxicity with this regimen was neutropenia. The incidence of grade 3 and 4 neutropenia were 27% (7/26) and 69% (18/26), respectively. However, the neutropenia was brief and reversible with G-CSF support. Nausea/emesis, fatigue, arthralgia/myalgias, and alopecia were the most common nonhematologic toxicities, in which no grade 3 or 4 toxicity was observed. Neurotoxicity was infrequently observed. Nine of 11 assessable patients responded to the regimen. We conclude that the combination of carboplatin and docetaxel seems to be highly active in ovarian cancer with the major toxicity of neutropenia, and the extremely low incidence of clinically significant neurotoxicity. Randomized controlled clinical trials should be conducted to define a role for this regimen in ovarian cancer.

Antibody Therapeutics for Ovarian Carcinoma and Translation to the Clinic

2018 ◽  
Author(s):  
Debra H. Josephs ◽  
Heather J. Bax ◽  
Giulia Pellizzari ◽  
James F. Spicer ◽  
Ana Montes ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibodies ◽  
Tumor Antigens ◽  
Ovarian Carcinomas ◽  
Immune Effector ◽  
Effector Cells ◽  
Tumor Microenvironments ◽  
Specific Tumor ◽  
Anti Cancer ◽  
Reduced Toxicity

Despite improvements over the past decade in the treatment of ovarian cancer, many patients are at risk of recurrent disease and emerging drug resistance. The increased selectivity and reduced toxicity of molecularly targeted anti-cancer agents renders them attractive for development in ovarian cancer, and monoclonal antibodies targeting ovarian cancer-specific tumor antigens represent the largest such group investigated in this clinical setting. This chapter describes examples of monoclonal antibodies clinically evaluated for efficacy in ovarian cancer. These agents recognize molecular targets expressed on tumors or within tumor microenvironments that may be essential for tumor cell survival and proliferation. Recently, antibodies targeting checkpoint molecules on immune cells have shown efficacy in modulating anti-tumor immunity, and applications in ovarian carcinomas are evaluated. The chapter focuses on therapeutic agents’ attributes on targeting key cancer growth and progression pathways, and propensity to engender effector functions by activating immune effector cells in tumors and the circulation.

scholarly journals The Role of MicroRNAs in Ovarian Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Yasuto Kinose ◽  
Kenjiro Sawada ◽  
Koji Nakamura ◽  
Tadashi Kimura
Keyword(s):  
Ovarian Cancer ◽  
Tumor Suppressor Genes ◽  
Target Genes ◽  
Early Stage ◽  
Noncoding Rnas ◽  
Circulating Micrornas ◽  
Gynecological Tumors ◽  
Prevention And Treatment ◽  
Prognostic And Predictive Markers

Ovarian cancer is the most lethal of malignant gynecological tumors. Its lethality may be due to difficulties in detecting it at an early stage and lack of effective treatments for patients with an advanced or recurrent status. Therefore, there is a strong need for prognostic and predictive markers to diagnose it early and to help optimize and personalize treatment. MicroRNAs are noncoding RNAs that regulate target genes posttranscriptionally. They are involved in carcinogenesis, cell cycle, apoptosis, proliferation, invasion, metastasis, and chemoresistance. The dysregulation of microRNAs is involved in the initiation and progression of human cancers including ovarian cancer, and strong evidence that microRNAs can act as oncogenes or tumor suppressor genes has emerged. Several microRNA signatures that are unique to ovarian cancer have been proposed, and serum-circulating microRNAs have the potential to be useful diagnostic and prognostic biomarkers. Various microRNAs such as those in the miR-200 family, the miR-199/214 cluster, or the let-7 paralogs have potential as therapeutic targets for disseminated or chemoresistant ovarian tumors. Although many obstacles need to be overcome, microRNA therapy could be a powerful tool for ovarian cancer prevention and treatment. In this review, we discuss the emerging roles of microRNAs in various aspects of ovarian cancer.

Clinically significant long-term maintenance treatment with olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5533-5533 ◽  
Author(s):  
Charlie Gourley ◽  
Michael Friedlander ◽  
Ursula A. Matulonis ◽  
Vadim Shirinkin ◽  
Frédéric Selle ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Parp Inhibitor ◽  
Final Analysis ◽  
Term Treatment ◽  
Tolerability Profile ◽  
Treatment Benefit ◽  
Platinum Based Chemotherapy ◽  
Long Term Treatment ◽  
Clinically Significant

5533 Background: In Study 19 (NCT00753545), a RCT in 265 pts with PSR SOC, the oral PARP inhibitor olaparib significantly improved progression-free survival (PFS) vs placebo (PBO), with the greatest benefit seen in pts with a BRCA1/2 mutation ( BRCAm); an interim overall survival (OS) analysis suggested an advantage for olaparib-treated pts (DCO: Sep 30, 2015; Ledermann et al, 2016). We report a planned final analysis of the long-term benefit of olaparib in pts with PSR SOC in Study 19. Methods: Pts who had received ≥2 prior regimens of platinum-based chemotherapy and were in response to their most recent regimen received olaparib (400 mg bid; capsules) or PBO until disease progression. Retrospective germline or tumor testing resulted in a known BRCAm status for 254/265 pts (96%). Results: At final DCO (May 9, 2016) median OS follow-up was 78.0 months. A long-term treatment benefit and the final hazard ratio (HR) for OS vs PBO (unadjusted for crossover: 13% of PBO pts – full analysis set [FAS]; 23% of PBO pts – BRCAm subgroup) is shown (Table). Details of BRCAwt pts on treatment for ≥6 years will be presented. No new safety signals or changes in olaparib tolerability profile were seen. Conclusions: The Study 19 final analysis shows that olaparib provides clinically significant, long-term treatment benefit in pts with PSR SOC. A durable benefit was seen in ≥10% of BRCAm and BRCAwt pts, who continued to receive and benefit from olaparib for ≥6 years–unprecedented in the relapsed ovarian cancer setting. Olaparib is well tolerated in this pt population and the analysis suggests olaparib confers an OS benefit in BRCAm pts. Clinical trial information: NCT00753545. [Table: see text]

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