Female Reproductive Tract Cancers Research Articles

MiRNAs: Emerging Agents for Therapeutic Effects of Polyphenols on Ovarian Cancer.

In terms of female reproductive tract cancers, ovarian cancer remains the principal reason for mortality globally and is notably difficult to identify in its early stages. This fact highlights the critical need to establish prevention strategies for patients with ovarian cancer, look for new robust diagnostic and prognostic markers, and identify potential targets of response to treatment. MicroRNAs (miRNAs) are one of the novel treatment targets in cancer treatment. Thus, understanding the part of miRNAs in the pathogenesis and metastasis of ovarian cancer is at the center of researchers' attention. MiRNAs are suggested to play a role in modulating many essential cancer processes, like cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition (EMT), and invasion. In two recent decades, natural polyphenols' anti-cancer features have been a focal point of research. Meanwhile, polyphenols are good research subjects for developing new cancer treatments. Polyphenols can modify miRNA expression and impact the function of transcription factors when used as dietary supplements. Multiple works have indicated the impact of polyphenols, including quercetin, genistein, curcumin, and resveratrol, on miRNA expression in vitro and in vivo. Here, we provide an in-depth description of four polyphenols used as dietary supplements: quercetin, genistein, curcumin, and resveratrol, and we summarize what is currently known about their regulatory abilities on influencing the miRNA functions in ovarian tumors to achieve therapeutic approaches.

Systematic review of the association between talc and female reproductive tract cancers.

Talc is a hydrous magnesium sheet silicate used in cosmetic powders, ceramics, paints, rubber, and many other products. We conducted a systematic review of the potential carcinogenicity of genitally applied talc in humans. Our systematic review methods adhere to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and incorporated aspects from the US Institute of Medicine (IOM, now the National Academy of Medicine) and several US EPA frameworks for systematic reviews, evaluating and integrating the epidemiological, animal, and mechanistic literature on talc and cancer. We conducted a comprehensive literature search. Detailed data abstraction and study quality evaluation, adapting the Toxic Substances Control Act (TSCA) framework, were central to our analysis. The literature search and selection process identified 40 primary studies that assessed exposure to talc and female reproductive cancer risks in humans (n = 36) and animals (n = 4). The results of our evaluation emphasize the importance of considering biological plausibility and study quality in systematic review. Integrating all streams of evidence according to the IOM framework yielded classifications of suggestive evidence of no association between perineal application of talcum powders and risk of ovarian cancer at human-relevant exposure levels. We also concluded that there is suggestive evidence of no association between genital talc application and endometrial cancer, and insufficient evidence to determine whether a causal association exists between genital talc application and cervical cancer based on a smaller but largely null body of literature.

The Application of Nanoparticle-Based Imaging and Phototherapy for Female Reproductive Organs Diseases.

Various female reproductive disorders affect millions of women worldwide and bring many troubles to women's daily life. Let alone, gynecological cancer (such as ovarian cancer and cervical cancer) is a severe threat to most women's lives. Endometriosis, pelvic inflammatory disease, and other chronic diseases-induced pain have significantly harmed women's physical and mental health. Despite recent advances in the female reproductive field, the existing challenges are still enormous such as personalization of disease, difficulty in diagnosing early cancers, antibiotic resistance in infectious diseases, etc. To confront such challenges, nanoparticle-based imaging tools and phototherapies that offer minimally invasive detection and treatment of reproductive tract-associated pathologies are indispensable and innovative. Of late, several clinical trials have also been conducted using nanoparticles for the early detection of female reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics. However, these nanoparticle trials are still nascent due to the body's delicate and complex female reproductive system. The present review comprehensively focuses on emerging nanoparticle-based imaging and phototherapies applications, which hold enormous promise for improved early diagnosis and effective treatments of various female reproductive organ diseases.

Biotherapy using Sperm Cell-oriented Transportation of Therapeutics in Female Reproductive Tract Cancer.

Female reproductive tract cancers like ovarian, cervical, vaginal, etc. have led to a serious concern for reproductive health as well as an increase in physical and psychological stresses amongst women. Various conventional techniques like surgery, radiation and chemotherapy are employed but possess limitations such as organ toxicity, infection, nausea, vomiting, etc. Also, several nanotechnology-based synthetic vehicle delivery systems like liposomes, nanoparticles, etc. are used but they lack targeting efficiency that results in poor propulsion and control. Therefore, there is a need for naturally-driven drug carriers to overcome such limitations. Sperm-based drug delivery is the new area for targeted delivery that offers self-propulsion to tumor sites, higher biocompatibility, longer lifespan and increased tissue penetration with enhanced localization. Drug-loaded sperm cells are harnessed with micro/nanomotor that will guide them to the intended target site. The critical analysis of the sperm-based drug delivery system was executed and summarized along with the current challenges. This article deals with the art of delivering the anticancer drug to female reproductive cancer sites with proof-of-concept-based research data and critical discussion on challenges in formulating the sperm-based delivery with a future perspective.

RON Mediates Tumor-Promoting Effects in Endometrial Adenocarcinoma.

Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d'origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma in vivo. This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma.

Factors Affecting Survival in Egyptian Patients with Advanced Vulval Cancer

INTRODUCTION: Vulvar carcinoma accounts for about 4% of the female reproductive tract cancers and a total of 0.6% of all malignant cancers in females. PATIENTS AND METHODS: This retrospective study aimed to identify the possible risk factors which can impact survival in Egyptian patients with vulval cancer who received treatment at Ain Shams University department of clinical oncology and nuclear medicine in the period from 1-1-2007 till 1-1-2012. RESULTS: Our study included 64 patients [median age 63 years, median overall survival (OS) was 16.5 months]. The factors associated with favourable impact on OS were: Rural residence (17 versus 10 months for patients from urban residence, p=0.002), premenopausal status (19 versus 16 months in post menopausal patients, p<0.001), low grade histology (19 versus 10 months in patients with high grade, p<0.001) and negative resection margins (19 versus 10 months in case of positive margin, p<0.001). The factors associated with poor OS were: higher number of offspring (≥5 offspring, OS 10 versus 19 months if less than 5 offspring, p<0.001), patients presenting with ulcer rather than mass (11 versus 19 months, p<0.001 and those with bilateral disease (10 versus 17 months in unilateral disease, p=0.04), presence of ≥4 positive groin lymph nodes metastases (OS =16 months versus 17 months, p=0.047) tumor size ≥ 4 cm (10 versus 17 months in case of <4 cm, p=0.001) and depth of stromal invasion (17 versus 16 months in case of <1 cm and ≥ 1 cm respectively, p=0.015) CONCLUSION: Urbanization has been linked with more aggressive disease leading to decrease of OS. The age of onset of intercourse did not affect survival as was expected however multiple offspring which could be related to more frequent intercourse had an effect on survival. The offered treatment modalities did not show a superiority probably because all the patients presented in an advanced stage. The anatomical nature of this cancer might be the cause in delayed diagnosis which warrants health education projects for early detection. Further studies are required to assess the risk factors for development of vulval cancer in Egyptian patients.

Dendritic cell engineering for selective targeting of female reproductive tract cancers.

Female reproductive tract cancers (FRCs) are considered as one of the most frequently occurring malignancies and a foremost cause of death among women. The late-stage diagnosis and limited clinical effectiveness of currently available mainstay therapies, primarily due to the developed drug resistance properties of tumour cells, further increase disease severity. In the past decade, dendritic cell (DC)-based immunotherapy has shown remarkable success and appeared as a feasible therapeutic alternative to treat several malignancies, including FRCs. Importantly, the clinical efficacy of this therapy is shown to be restricted by the established immunosuppressive tumour microenvironment. However, combining nanoengineered approaches can significantly assist DCs to overcome this tumour-induced immune tolerance. The prolonged release of nanoencapsulated tumour antigens helps improve the ability of DC-based therapeutics to selectively target and remove residual tumour cells. Incorporation of surface ligands and co-adjuvants may further aid DC targeting (in vivo) to overcome the issues associated with the short DC lifespan, immunosuppression and imprecise uptake. We herein briefly discuss the necessity and progress of DC-based therapeutics in FRCs. The review also sheds lights on the future challenges to design and develop clinically effective nanoparticles-DC combinations that can induce efficient anti-tumour immune responses and prolong patients’ survival.

Role of microRNAs in cancers of the female reproductive tract: insights from recent clinical and experimental discovery studies.

microRNAs (miRNAs) are small RNA molecules that represent the top of the pyramid of many tumorigenesis cascade pathways as they have the ability to affect multiple, intricate, and still undiscovered downstream targets. Understanding how miRNA molecules serve as master regulators in these important networks involved in cancer initiation and progression open up significant innovative areas for therapy and diagnosis that have been sadly lacking for deadly female reproductive tract cancers. This review will highlight the recent advances in the field of miRNAs in epithelial ovarian cancer, endometrioid endometrial cancer and squamous-cell cervical carcinoma focusing on studies associated with actual clinical information in humans. Importantly, recent miRNA profiling studies have included well-characterized clinical specimens of female reproductive tract cancers, allowing for studies correlating miRNA expression with clinical outcomes. This review will summarize the current thoughts on the role of miRNA processing in unique miRNA species present in these cancers. In addition, this review will focus on current data regarding miRNA molecules as unique biomarkers associated with clinically significant outcomes such as overall survival and chemotherapy resistance. We will also discuss why specific miRNA molecules are not recapitulated across multiple studies of the same cancer type. Although the mechanistic contributions of miRNA molecules to these clinical phenomena have been confirmed using invitro and pre-clinical mouse model systems, these studies are truly only the beginning of our understanding of the roles miRNAs play in cancers of the female reproductive tract. This review will also highlight useful areas for future research regarding miRNAs as therapeutic targets in cancers of the female reproductive tract.

Endocrine disruption of oestrogen action and female reproductive tract cancers

Endocrine disrupting chemicals (EDC) are ubiquitous and persistent compounds that have the capacity to interfere with normal endocrine homoeostasis. The female reproductive tract is exquisitely sensitive to the action of sex steroids, and oestrogens play a key role in normal reproductive function. Malignancies of the female reproductive tract are the fourth most common cancer in women, with endometrial cancer accounting for most cases. Established risk factors for development of endometrial cancer include high BMI and exposure to oestrogens or synthetic compounds such as tamoxifen. Studies on cell and animal models have provided evidence that many EDC can bind oestrogen receptors and highlighted early life exposure as a window of risk for adverse lifelong effects on the reproductive system. The most robust evidence for a link between early life exposure to EDC and adverse reproductive health has come from studies on women who were exposed in utero to diethylstilbestrol. Demonstration that EDC can alter expression of members of the HOX gene cluster highlights one pathway that might be vulnerable to their actions. In summary, evidence for a direct link between EDC exposure and cancers of the reproductive system is currently incomplete. It will be challenging to attribute causality to any single EDC when exposure and development of malignancy may be separated by many years and influenced by lifestyle factors such as diet (a source of phytoestrogens) and adiposity. This review considers some of the evidence collected to date.

High incidence of female reproductive tract cancers in FA-deficient HPV16-transgenic mice correlates with E7's induction of DNA damage response, an activity mediated by E7's inactivation of pocket proteins.

Fanconi anemia (FA) is a rare genetic disorder caused by defects in a DNA damage repair system, the FA pathway. FA patients frequently develop squamous cell carcinoma (SCC) at sites that are associated with HPV-driven cancer including the female reproductive tract. To assess experimentally whether FA deficiency increases susceptibility to HPV-associated cervical/vaginal cancer, we monitored cancer incidence in the female lower reproductive tract of FA-deficient mice expressing HPV16 oncogenes, E6 and/or E7. FA deficiency specifically increased the incidence of cancers in mice expressing E7; but, this effect was not observed in mice just expressing E6. We also observed that E7, but not E6, induced DNA damage as scored by induction of γ-H2AX and 53BP1 nuclear-foci, and this induction was heightened in FA-deficient tissue. Finally, we discovered that this induction of DNA damage responses was recapitulated in mice deficient in expression of ‘pocket’ proteins, pRb, p107, and p130, which are established targets of E7. Our findings support the hypothesis that E7 induces cancer by causing DNA damage at least in part through the inactivation of pocket proteins. This hypothesis explains why a deficiency in DNA damage repair would increase susceptibility to E7-driven cancer.

Developing a Curriculum for Evolutionary Medicine: Case Studies of Scurvy and Female Reproductive Tract Cancers

Most early evolutionary thinkers came from medicine, yet evolution has had a checkered history in medical education. It is only in the last few decades that serious efforts have begun to be made to integrate evolutionary biology into the medical curriculum. However, it is not clear when, where (independently or as part of preclinical or clinical teaching courses) and, most importantly, how should medical students learn the basic principles of evolutionary biology applied to medicine, known today as evolutionary or Darwinian medicine. Most clinicians are ill-prepared to teach evolutionary biology and most evolutionary biologists ill-equipped to formulate clinical examples. Yet, if evolutionary science is to have impact on clinical thought, then teaching material that embeds evolution within the clinical framework must be developed. In this paper, we use two clinical case studies to demonstrate how such may be used to teach evolutionary medicine to medical students in a way that is approachable as well as informative and relevant.

Genes involved in the immediate early response and epithelial–mesenchymal transition are regulated by adipocytokines in the female reproductive tract

Obesity increases the risk of female reproductive tract cancers, but the underlying mechanistic link between the two is ill-defined. Thus, the objective of the current study was to identify obesity-dependent changes in the expression of immediate early (IE) genes that contribute to cell proliferation and differentiation, and epithelial-mesenchymal transition (EMT) genes that promote cell migration. When HeLa cells were treated for 0-48 hr with IGF-1, leptin, TNFα, or IL-6, each individual adipocytokine altered the abundance of IE (cJUN, cFOS, and cMYC) and EMT (SNAI1, SNAI2, and TWIST1) mRNA abundance. For example, IGF-1 increased cJUN and cFOS and decreased cMYC; leptin increased cFOS; IL-6 increased cFOS and cMYC; and TNFα increased cJUN and cFOS mRNA abundance. Likewise, EMT gene expression was altered by IGF-1, TNFα, and IL-6. SNAI1 was increased by IGF-1 and IL-6; SNAI2 was increased by IGF-1 and TNFα; and TWIST1 was increased by TNFα and IL-6. Chronic exposure to adipocytokines also altered EMT gene expression in the whole uterus of obese compared to normal-weight mice. Specifically, there was no difference in cJun, cFos, or cMyc mRNA abundance between normal-weight and obese animals. Snai1, Snai2, and Twist1 mRNA abundance, however, was increased in the uterus of obese females and correlated with increased circulating IGF-1 levels. These data indicate that obesity-dependent alterations in adipocytokine levels regulate the expression of genes associated with cell proliferation and migration, and therefore may provide a plausible mechanism for obesity-dependent increases in cancers of the female reproductive tract.

Emerging drugs for ovarian cancer

Importance of the field: Ovarian cancer has the highest mortality of all female reproductive tract cancers, which reflects both the absence of proven ovarian cancer screening tests and the development of drug-resistant cancer cell. Apart from varying the dosages, schedules, mode of delivery and combinations of existing drugs, efforts must continue to identify signaling pathways in tumor cells sufficiently different from normal cells that can be a target for maximizing tumor kill and minimizing toxicity.Areas covered in this review: Some of the most important cellular pathways are analyzed and discussed and the most interesting clinical trials, both closed and ongoing, described.What the reader will gain: The reader will gain a panoramic vision of all the most active drugs in clinical investigations in ovarian cancer. The reader will also better understand what the unresolved problems of molecular research are and how complicated the process ‘from the bench to the bedside’ is.Take home message: It is only with a strong commitment, cooperation and collaboration from the international ovarian cancer community that significant improvement in patient outcomes can be attained beyond the marginal gains achieved so far.

Should we modify the current FIGO staging system for stage IIIC ovarian cancer?

Should we modify the current FIGO staging system for stage IIIC ovarian cancer?

Angiotensin-converting enzyme inhibitors and the risk of cancer: a population-based cohort study in Denmark.

A recent observational study suggested that the use of angiotensin-converting enzyme (ACE) inhibitors protects against cancer in general and against breast and female reproductive tract cancers in particular. To explore these hypotheses, the authors examined cancer risk among users of ACE inhibitors in North Jutland County, Denmark. Using data from the population-based Prescription Database of North Jutland County and the Danish Cancer Registry, cancer incidence among 17,897 individuals prescribed ACE inhibitors was compared with expected incidence based on county specific cancer rates during an 8-year study period with a mean follow-up of 3.7 years. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (95% CIs) were calculated for cancers overall and at selected sites. In addition, the authors performed a direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers (n = 47,579 individuals) by means of a Cox proportional hazards model. Overall, 909 cancer cases were observed among users of ACE inhibitors, with 846 expected based on general population rates, yielding an SIR of 1.07 (95% CI, 1.01-1.15). No risk reductions were observed for cancers of the breast and female reproductive tract, whereas nonsignificantly decreased SIRs were observed for cancers of the esophagus, stomach, and liver. Cancer of the kidney was found in significant excess (SIR, 1.6; 95% CI, 1.1-2.2). Stratification by duration of follow-up or number of prescriptions revealed no apparent trends, except for a tendency toward decreasing risk with increasing length of follow-up for smoking-related cancers. The direct comparison of users of ACE inhibitors with users of beta-blockers or calcium channel blockers yielded results comparable to those derived from the comparison with the general population, with a hazard ratio for cancer overall of 1.01 (95% CI, 0.93-1.09). This large, population-based cohort study did not confirm a protective effect of ACE inhibitors on the development of cancer. The excess of kidney cancer observed likely reflects a correlation between hypertension and kidney cancer. Further investigation is needed to evaluate the long-term effects of ACE inhibitors beyond the observation period of this and previous studies. Also, the suggestive evidence of decreased risks for upper digestive system cancers and for smoking-related cancers over time may warrant additional investigation.

Social Work with Challenged Women:

The existence of cancer in a woman usually provokes irrevocable changes in both her body and psyche. When these changes involve an integral part of one's self concept, as in the cases of female breast or reproductive tract cancers, problems of redefinition and transformation of self-image result. Important issues in the care of female cancer patients cannot be divorced from health care procedures for women in general. This article is an exploration of the daily reality of women who confront the horror and challenge of cancer in areas of their bodies that are intricately related to their sexuality. While attempting to define the problems and discover some feasible social work interventions to alleviate these difficulties, two major issues emerged: the sexual politics of medicine and the psychosocial trauma of cancer. This study will have as its primary focus the second of these two issues.