Cancers Of Reproductive System Research Articles

Surgical management of brain metastases following female reproductive system cancers: analysis of 37 cases

To demonstrate an appropriateness and role of neurosurgical care in the complex management of women with brain metastases following reproductive system cancers. There were 78 women with brain metastases following reproductive system cancer. All patients were treated at the Blokhin National Cancer Medical Research Center for the period 2004-2019. We have also reviewed the literature data for the last 30 years. Selective surgical approach should be essential in the treatment of patients with brain metastases following reproductive system cancer. A multidisciplinary approach ensures the best treatment outcomes.

A Potential Pathogenic Link Between Cancer of Female Reproductive System and Infertile Women Treated With Assisted Reproduction Techniques.

Prevention and treatment of infertility remains a priority for developed countries where a large proportion of women undergo in vitro fertilization (IVF) after ovarian stimulation. Latest data suggest that, in the USA alone, almost eight million women of fertile age will have sought medical advice for fertility problems by 2025. However, over the last years, attention has been increasingly focused, and questions have risen, on the long-term health effects in women who underwent assisted reproductive technologies (ARTs). Since the emergence of ART, reports highlight a possible connection of ovarian stimulation and several types of gynaecological cancer, including ovarian, endometrial and cervical types, but due to limited scientific evidence, such a speculation is still under investigation. The objective of this review is to summarize the latest data of ovarian hyperstimulation and IVF, associated with the risk of gynecological tract cancer development.

Combination of Sodium Cantharidinate with Cisplatin Synergistically Hampers Growth of Cervical Cancer.

BackgroundSodium cantharidinate (SC) has been broadly applied in lung cancer treatment in China, while its specific function in cervical cancer (CC), a great contributor to death of female reproductive system cancers, remains unclear. Our research evaluated the anti-tumor effects of SC in CC and the mechanism involved.MethodsFirst, cisplatin (DDP)-resistant Caski-1 and ME180 cell lines were developed and treated with SC. The effects of SC on CC cell growth were then evaluated. Subsequently, the genes targeted by SC were predicted via the bioinformatics website. The correlations between PTPN1 expression and tumor stage, lymph node metastasis and tumor differentiation were examined. We further conducted rescue experiments by overexpressing PTPN1 in CC cells, followed by SC and cisplatin treatments. The activation of the PI3K/AKT pathway in CC cells, and the effect of SC on the growth and drug resistance of Caski-1 cells in vivo were investigated.ResultsThe sensitivity of Caski-1 and ME180 cells to DDP was increased after SC treatment, which also enhanced the inhibitory effect of DDP on the cell growth. By prediction, we found that SC could target PTPN1. Patients with high expression of PTPN1 had higher clinical stage, lymph node metastasis and lower tumor differentiation. SC inhibited PTPN1 expression. Overexpression of PTPN1 attenuated the effect of SC. Furthermore, PTPN1 activated the PI3K/AKT pathway. Moreover, SC treatment inhibited the growth and drug resistance of Caski-1 cells in vivo.ConclusionSC promotes drug sensitivity of CC cells to DDP by targeting PTPN1, thereby impairing the PI3K/AKT pathway.

Betel Nut Arecoline Induces Different Phases of Growth Arrest between Normal and Cancerous Prostate Cells through the Reactive Oxygen Species Pathway.

Prostate cancer (PCa) is a reproductive system cancer in elderly men. We investigated the effects of betel nut arecoline on the growth of normal and cancerous prostate cells. Normal RWPE-1 prostate epithelial cells, androgen-independent PC-3 PCa cells, and androgen-dependent LNCaP PCa cells were used. Arecoline inhibited their growth in dose- and time-dependent manners. Arecoline caused RWPE-1 and PC-3 cell cycle arrest in the G2/M phase and LNCaP cell arrest in the G0/G1 phase. In RWPE-1 cells, arecoline increased the expression of cyclin-dependent kinase (CDK)-1, p21, and cyclins B1 and D3, decreased the expression of CDK2, and had no effects on CDK4 and cyclin D1 expression. In PC-3 cells, arecoline decreased CDK1, CDK2, CDK4, p21, p27, and cyclin D1 and D3 protein expression and increased cyclin B1 protein expression. In LNCaP cells, arecoline decreased CDK2, CDK4, and cyclin D1 expression; increased p21, p27, and cyclin D3 expression; had no effects on CDK1 and cyclin B1 expression. The antioxidant N-acetylcysteine blocked the arecoline-induced increase in reactive oxygen species production, decreased cell viability, altered the cell cycle, and changed the cell cycle regulatory protein levels. Thus, arecoline oxidant exerts differential effects on the cell cycle through modulations of regulatory proteins.

The Role of Exosomes in the Female Reproductive System and Breast Cancers.

Exosomes are nanoscale extracellular vesicles released by nearly all cell types. Exosomes were originally considered as waste receptacles for discarding unwanted cellular products; however, these organelles are now considered to be important for cell communication by delivering biologically active molecules such as proteins, DNA, non-coding RNA and mRNA. Studies have revealed that exosomes are closely related to several diseases, especially cancers. Exosomes are indispensable for the emergence and progression of tumor. Here, we review the status of research on exosomes in the female reproductive system cancers and breast cancer, focusing on their biological roles in chemical resistance and immune responses, as well as their underlying applications in drug delivery and nanotherapy and as biological markers for tumor diagnosis.

Fertility issue in early stage endometrial cancer patients.

Endometrial cancer (EC) is the most common cancer of the female reproductive system in developed countries. The incidence of EC has been increasing in young women. Approximately 4% of cases are aged <40 years. These young women may wish to delay therapy until after they have children. Common complaints in patients with EC include irregular vaginal bleeding, pelvic pain, and enlarged uterus. Imaging techniques such as transvaginal ultrasound (TVUS) or magnetic resonance imaging (MRI) can be utilized in detecting EC. Although the recommended treatment of EC is hysterectomy and bilateral salpingo-oophorectomy with or without systemic lymph node dissection, loss of reproductive function is the primary limiting factor of this surgical approach. Some studies have reported favorable results with high-dose oral progestins or levonorgestrel-releasing intrauterine system or hysteroscopic tumor resection followed by treatment with high-dose oral progestins. The most widely utilized medical treatment regimens are medroxyprogesterone acetate (MPA) 250–600 mg/day or megestrol acetate (MA) 160–480 mg/day. However, there is still a lack of evidence to establish the optimal dose and duration of progestin treatment. Patients with complete remission (CR) who wish to conceive must be encouraged, and referral to a fertility clinic should be offered as soon as possible. The key aspect of fertility-sparing management in women with EC appears to be the selection of appropriate candidates. Owing to the rarity of this condition, management may often be suboptimal. The aim of this review is to assess the current approaches to management of young women with EC who wish to preserve their fertility.

Analysis of the Trends in Publications on Clinical Cancer Research in Mainland China from the Surveillance, Epidemiology, and End Results (SEER) Database: Bibliometric Study.

BackgroundThe application of China’s big data sector in cancer research is just the beginning. In recent decades, more and more Chinese scholars have used the Surveillance, Epidemiology, and End Results (SEER) database for clinical cancer research. A comprehensive bibliometric study is required to analyze the tendency of Chinese scholars to utilize the SEER database for clinical cancer research and provide a reference for the future of big data analytics.ObjectiveOur study aimed to assess the trend of publications on clinical cancer research in mainland China from the SEER database.MethodsWe performed a PubMed search to identify papers published with data from the SEER database in mainland China until August 31, 2020.ResultsA total of 1566 papers utilizing the SEER database that were authored by investigators in mainland China were identified. Over the past years, significant growth in studies based on the SEER database was observed (P<.001). The top 5 research topics were breast cancer (213/1566, 13.6%), followed by colorectal cancer (185/1566, 11.8%), lung cancer (179/1566, 11.4%), gastrointestinal cancer (excluding colorectal cancer; 149/1566, 9.5%), and genital system cancer (93/1566, 5.9%). Approximately 75.2% (1178/1566) of papers were published from the eastern coastal region of China, and Fudan University Shanghai Cancer Center (Shanghai, China) was the most active organization. Overall, 267 journals were analyzed in this study, of which Oncotarget was the most contributing journal (136/267, 50.9%). Of the 1566 papers studied, 585 (37.4%) were published in the second quartile, 489 (31.2%) in the third quartile, 312 (19.9%) in the first quartile, and 80 (5.1%) in the fourth quartile, with 100 (6.4%) having an unknown Journal Citation Reports ranking.ConclusionsClinical cancer research based on the SEER database in mainland China underwent constant and rapid growth during recent years. High-quality and comprehensive cancer databases based on Chinese demographic data are urgently needed.

CD24, A Review of its Role in Tumor Diagnosis, Progression and Therapy.

CD24, is a mucin-like GPI-anchored molecules. By immunohistochemistry, it is widely detected in many solid tumors, such as breast cancers, genital system cancers, digestive system cancers, neural system cancers and so on. The functional roles of CD24 are either fulfilled by combination with ligands or participate in signal transduction, which mediate the initiation and progression of neoplasms. However, the character of CD24 remains to be intriguing because there are still opposite voices about the impact of CD24 on tumors. In preclinical studies, CD24 target therapies, including monoclonal antibodies, target silencing by RNA interference and immunotherapy, have shown us brighten futures on the anti-tumor application. Nevertheless, evidences based on clinical studies are urgently needed. Here, with expectancy to spark new ideas, we summarize the relevant studies about CD24 from a tumor perspective.

Insulin Resistance and Endometrial Cancer: Emerging Role for microRNA.

Simple SummaryInsulin resistance is one of the risk factors of endometrial cancer. Hyperinsulinemia can trigger many physiological effects that drive carcinogenesis, which is also modulated by epigenetic dysregulation including miRNAs expression. Our working hypothesis was that there must be a more pronounced relationship between insulin resistance and alterations in miRNA profiles of endometrial cancer patients. Consequently, this work was undertaken to better clarify this assumption. Our careful literature search indicated that miRNA could represent a potential molecular link between the metabolic alterations related to insulin resistance and endometrial cancer. Additionally, by reporting the known relationships between miRNA and both insulin resistance and endometrial cancer, we highlighted their potential role as predictive factors of future endometrial cancer in insulin resistant patients.Endometrial cancer (EC) remains one of the most common cancers of the female reproductive system. Epidemiological and clinical data implicate insulin resistance (IR) and its accompanying hyperinsulinemia as key factors in the development of EC. MicroRNAs (miRNAs) are short molecules of non-coding endogenous RNA that function as post-transcriptional regulators. Accumulating evidence has shown that the miRNA expression pattern is also likely to be associated with EC risk factors. The aim of this work was the verification of the relationships between IR, EC, and miRNA, and, as based on the literature data, elucidation of miRNA’s potential utility for EC prevention in IR patients. The pathways affected in IR relate to the insulin receptors, insulin-like growth factors and their receptors, insulin-like growth factor binding proteins, sex hormone-binding globulin, and estrogens. Herein, we present and discuss arguments for miRNAs as a plausible molecular link between IR and EC development. Specifically, our careful literature search indicated that dysregulation of at least 13 miRNAs has been ascribed to both conditions. We conclude that there is a reasonable possibility for miRNAs to become a predictive factor of future EC in IR patients.

Association of the Expression Level of miR-16 with Prognosis of Solid Cancer Patients: A Meta-Analysis and Bioinformatic Analysis.

Objective To assess the association between the expression level of miR-16 and prognosis of solid cancer patients by meta-analysis and bioinformatic analysis. Methods PubMed, Web of Science, and Embase databases were searched until October 31, 2019, to identify eligible studies reporting the association of the miR-16 status with the prognosis of solid cancer patients. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled, and a heterogeneity test was conducted. Sensitivity analysis and a publication bias test were also carried out. Furthermore, the miRpower database was used to validate the association. Results Thirteen articles with 2303 solid cancer patients were included in the meta-analysis. Solid cancer patients with low expression level of miR-16 had shorter survival time (I2 = 84.0%, HR = 1.47, 95% CI: 1.13-1.91, P = 0.004). In the subgroup analyses of cancer sites, low miR-16 expression level was associated with poor prognosis in the reproductive system cancers (I2 = 33.3%, HR = 1.24, 95% CI: 1.06-1.45, P = 0.008). Sensitivity analysis suggested that the pooled HR was stable and omitting a single study did not change the significance of the pooled HR. Begg's test and Egger's test revealed no publication bias in the meta-analysis. In bioinformatic analysis, the significant association between miR-16 level and prognosis of patients with reproductive system cancers was further confirmed (HR = 1.21, 95% CI: 1.03-1.42, P = 0.017). Conclusion Low expression level of miR-16 is an indicator for poor prognosis of solid cancer patients, particularly in reproductive system cancers.

Inhibiting Importin 4-mediated nuclear import of CEBPD enhances chemosensitivity by repression of PRKDC-driven DNA damage repair in cervical cancer

Cervical cancer (CC) remains highest in the mortality of female reproductive system cancers, while cisplatin (CDDP) resistance is the one of main reasons for the lethality. Preceding evidence has supported that karyopherins are associated with chemoresistance. In this study, we simultaneously compared CDDP-incomplete responders with CDDP-complete responders of CC patients and CDDP‐insensitive CC cell lines with CDDP‐sensitive group. We finally identified that DNA-PKcs (PRKDC) was related to CDDP sensitivity after overlapping in CC sample tissues and CC cell lines. Further functional assay revealed that targeting PRKDC by shRNA and NU7026 (specific PRKDC inhibitor) could enhance CDDP sensitivity in vitro and in vivo, which was mediated by impairing DNA damage repair pathway in CC. Mechanistically, we found that PRKDC was transcriptionally upregulated by CCAAT/enhancer-binding protein delta (CEBPD), while intriguingly, CDDP treatment strengthened the transcriptional activity of CEBPD to PRKDC. We further disclosed that Importin 4 (IPO4) augmented the nuclear translocation of CEBPD through nuclear localization signals (NLS) to activate PRKDC-mediated DNA damage repair in response to CDDP. Moreover, we demonstrated that IPO4 and CEBPD knockdown improved CDDP-induced cytotoxicity in vitro and in vivo. Together, we shed the novel insight into the role of IPO4 in chemosensitivity and provide a clinical translational potential to enhance CC chemosensitivity since the IPO4-CEBPD-PRKDC axis is actionable via NU7026 (PRKDC inhibitor) or targeting IPO4 in combination with CDDP.

A Molecularly Targeted Intraoperative Near-Infrared Fluorescence Imaging Agent for High-Grade Serous Ovarian Cancer.

Ovarian cancer is the fifth leading cause of cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. The foundation of its management consists of cytoreductive surgery (CRS) followed by systemic chemotherapy, with the completeness of surgical resection consistently identified as one of the most important prognostic factors for the disease. The goal of our investigation is the development of a near-infrared fluorescence (NIRF) imaging agent for the intraoperative imaging of high-grade serous ovarian cancer (HGSOC). As surgeons are currently limited to the visual and manual assessment of tumor tissue during CRS, this technology could facilitate more complete resections as well as serve important functions at other points in the surgical management of the disease. Elevated levels of cancer antigen 125 (CA125) have proven a useful biomarker of HGSOC, and the CA125-targeting antibody B43.13 has shown potential as a platform for immunoPET imaging in murine models of ovarian cancer. Herein, we report the development of a NIRF imaging agent based on B43.13: ssB43.13-IR800. We site-specifically modified the heavy chain glycans of B43.13 with the near-infrared dye IRDye 800CW using a chemoenzymatic approach developed in our laboratories. SDS-PAGE analysis confirmed the specificity of the conjugation reaction, and flow cytometry, immunostaining, and fluorescence microscopy verified the specific binding of ssB43.13-IR800 to CA125-expressing OVCAR3 human ovarian cancer cells. NIRF imaging studies demonstrated that ssB43.13-IR800 can be used to image CA125-expressing HGSOC tumors in subcutaneous, orthotopic, and patient-derived xenograft mouse models. Finally, ex vivo analyses confirmed that ssB43.13-IR800 can bind and identify CA125-expressing cells in primary tumor and metastatic lymph node samples from human patients with HGSOC.

CANCER OF THE FEMALE REPRODUCTIVE SYSTEM IN THE FAR EASTERN FEDERAL DISTRICT

The aim of the study was to assess the incidence and mortality rates of female reproductive system cancer in the Far Eastern Federal District over the last ten years (2008–2017).Material and Methods. In our study we used statistical reports on the female reproductive system cancer incidence and mortality rates and 10-year follow-up data.Results. In 2017, 25155 new cases of female reproductive system cancer were diagnosed in the Far Eastern Federal District (26.6 % higher than in 2008). A total of 128776 patients (2.1 % of the population of the region) were followed up. Over the study period, there has been increase in the number of patients with stage I–II breast cancer (+4.8 %), cervical cancer (+6.3 %), uterine body (+3.9 %) and ovarian cancer (+5.7 %), with simultaneous reduction in the number of patients with advanced stages, except ovarian cancer (+5.0 %). For the past 10 years, cancer incidence rates have been steadily increasing, while cancer mortality rates have been decreasing with the exception of cervical cancer (+13.7 %). Morphological confirmation of the diagnosis (over 90 %) exceeded the national average ones. The number of patients followed-up for 5 or more years appeared to be lower than the average values in Russia; however the 1-year mortality rates after diagnosis improved. Ovarian cancer remains the most deadly of the gynecological cancers (22.9–27.9 %).Conclusion. Over the last ten years in the Far Eastern Federal District, in contrast to the overall decline in the mortality rates, there has been a steady increase in the incidence rates of female reproductive system cancer, except for cervical cancer.

Nuclear-Translocation of ACLY Induced by Obesity Related Factors Enhances Pyrimidine Metabolism Through Regulating Histone Acetylation in Endometrial Cancer

Background: Endometrial cancer (EC) is a common female reproductive system cancer, and obesity is a major risk factor for the disease. ATP-citrate lyase (ACLY), a vital enzyme linking both glycolytic and lipid metabolism, plays important roles in cancer progression. However, there is little evidence of ACLY involvement in EC development. Methods: The ACLY expression in EC was evaluated by using TCGA and GEO databases and verified it using clinical samples by IHC and RT-PCR methods. The functions of ACLY was determined by both the vitro and vivo studies. Gene expression array, co-immunoprecipitation, TUNEL assay, EdU assay, chromatin immunoprecipitation and luciferase reporter assay were applied for mechanism dissection. Findings: ACLY was significantly upregulated in EC patients, particularly in the nucleus. Upregulated ACLY promoted EC cell proliferation and colony formation, and attenuated apoptosis. Mechanistically, cotreatment with obesity-related factors (estradiol, insulin and leptin) promoted nuclear translocation of ACLY through Akt-mediated phosphorylation of ACLY at Ser455 . Nuclear-localized ACLY increased histone acetylation levels, thus resulting in upregulation of pyrimidine metabolism genes, such as DHODH. Moreover, STAT3 altered the ACLY expression at the transcriptional level via directly binding to its promoter region. Interpretation: ACLY nuclear-translocation induced by obesity-related factors promotes EC progression by modulating histone acetylation levels, The ACLY axis could be served as potential therapeutic targets for the treatment of EC. Funding Statement: This research was supported by The National Natural Science Foundation of China (Grant number: 81974406) and The Sailing Program Foundation of Hunan Cancer Hospital. Declaration of Interests: The authors declare that they have no competing interests with the contents of this article. Ethics Approval Statement: The study was approved by the Research Ethics Committee of the Sixth People's Hospital, and informed consent was provided by all patients before this study.

Structure and expression of the long noncoding RNA gene MIR503 in humans and non-human primates

Recent technical and other advances in genomics provide unique opportunities to improve our understanding of human physiology and disease predisposition through a detailed analysis of gene structure and expression by examining data in public genome and gene-expression repositories. Yet, the vast majority of human genes remain understudied. This is particularly true of genes for long noncoding RNAs (lncRNAs). Here, we describe the detailed characterization of MIR503HG, a lncRNA gene found on the X chromosome in humans. Using information extracted from public databases, we show that human MIR503HG is a 5-exon gene, and that it is highly conserved among 5 non-human primates spanning over 85 million years ago of evolutionary diversification. MIR503HG is transcribed and processed into multiple distinct RNAs in each of these species through differential exon use and alternative RNA splicing, with a higher abundance of transcripts being found in reproductive tissues, especially during the early stages of ovary and testis development, indicating a possible role in reproductive biology. Furthermore, in select reproductive system cancers, MIR503HG transcripts are downregulated, with higher levels of RNA expression being associated with clinical outcomes. Collectively, these investigations show how the use of genomic, gene expression, and other genetic resources can lead to new insights about human biology and disease, and argue that MIR503HG is worthy of additional study.

Claudins: New Players in Human Fertility and Reproductive System Cancers.

Claudins are major integral proteins of tight junctions (TJs), the apical cell–cell adhesions that enable maintaining polarity of epithelial cells, their differentiation, and cell signaling. A number of studies have indicated that claudins might play a crucial role in both physiology and pathogenesis. Their tissue-specific expression was originally linked to the development of different types of cancer and triggered a hope to use them as diagnostic or prognostic markers. However, it seems that their expression is more complex than that, and undoubtedly, claudins participate in one of the most important molecular events in cells. This review summarizes the recent research evaluating the role of claudins in fertility and the most common endocrine-dependent cancers in the reproductive system and highlights the crucial role of claudins both in human fertility and the most common cancers.

A New World of Biomarkers and Therapeutics for Female Reproductive System and Breast Cancers: Circular RNAs.

As one of the most recently (re)discovered types of non-coding RNAs (ncRNA), circular RNAs (circRNAs) differentiate from other ncRNAs by a specific biogenesis, high stability, and distinct functions. The biogenesis of circRNAs can be categorized into three mechanisms that permit the back-splicing reaction: exon-skipping, pairing of neighboring introns, and dimerization of RNA-binding proteins. Regarding their stability, circRNAs have no free ends, specific to linear RNA molecules, prompting a longer half-life and resistance to exonuclease-mediated activity by RNase R, bypassing the common RNA turnover process. Regarding their functions, circular transcripts can be categorized into four broad roles: miRNA sponging, protein binding, regulation of transcription, and coding for proteins and peptides. Female reproductive system (including mainly ovarian, corpus, and cervix uteri cancers) and breast cancers are the primary causes of death in women worldwide, accounting for over 1,212,772 deaths in 2018. We consider that a better understanding of the molecular pathophysiology through the study of coding and non-coding RNA regulators could improve the diagnosis and therapeutics of these cancers. Developments in the field of circRNA in regard to breast or gynecological cancers are recent, with most circRNA-related discoveries having been made in the last 2 years. Therefore, in this review we summarize the newly detected roles of circRNAs in female reproductive system (cervical cancer, ovarian cancer, and endometrial cancer) and breast cancers. We argue that circRNAs can become essential elements of the diagnostic and therapeutic tools for female reproductive system cancers in the future.

Clinicopathological features and prognosis of patients with esophageal cancer as the second primary cancer: a large population-based analysis using the SEER program [2000-2015

BackgroundThis study used the Surveillance, Epidemiology, and End Results (SEER) data to investigate clinicopathological characteristics and prognoses of patients with esophageal cancer as a second primary cancer from 2000 to 2015.MethodsEsophageal cancer as the second primary cancer (SEPC) patient information collected from the SEER database were extracted, evaluated, and compared with only primary esophageal cancer (OPEC) patient data. Overall survival (OS) was evaluated by the Kaplan-Meier method. Univariate analysis (UVA) and multivariate analysis (MVA) by the Cox proportional hazards regression identified risk factors that predicted OS and the results were used to construct a nomogram to predict OS in SEPC patients.ResultsA total of 7,161 esophageal cancer patients were identified from the SEER registry, which included 813 patients (11.4%) with SEPC in the patient history. The most common cancer for the first primary cancer prior to esophageal cancer (FPC) was genital system cancer (43.5%). The median OS was 7 (95% CI: 6.69–11.31) months and was not significantly different from that of patients with OPEC. The patients with SEPC appeared with unique clinical pathological features compared with OPEC, including older age, more squamous cell carcinoma, and early stage esophageal cancer, and less lower third of esophageal cancer (P<0.001). UVA and MVA identified M stage, surgery, and chemotherapy as independent risk factors. The nomogram had a calibration index of 0.682.ConclusionsSEPC had unique clinicopathological characteristics. M stage, surgery, and chemotherapy were independently associated with OS. The nomogram accurately predicted OS.

Gestational Trophoblastic Neoplasia

Introduction: Gestational trophoblastic neoplasia (GTN) account for less than 1% of cancers of the female reproductive system. Nearly 50% of gestational choriocarcinomas are seen after molar pregnancies. About 25% after abortions or ectopic pregnancy and another 25% after a normal pregnancy. FIGO staging and prognostic scoring index of modified WHO classification is used. Serum β-HCG assay is an important factor in the diagnosis and management of GTN. It is a sensitive tumour marker for GTN and its level is directly related to the number of viable tumour cells. Serial measurement of β-hCG levels is useful for follow-up of women diagnosed with complete or partial mole. An increasing level or plateauing of serum β-hCG is diagnostic of invasive disease which can be invasive mole or choriocarcinoma. Case Report: Patient A-was a 22 year old lady, para1, two year old child which was a normal delivery. She was asymptomatic and reported to the hospital for missed periods. Urine pregnancy test was positive. Ultrasound scan did not find any pregnancy. Beta HCG levels were very high. Then MRI was done which showed no abnormality, other than a bulky uterus. Curettage was done and the report came as trophoblastic tissue seen with possibility of choriocarcinoma. This patient was given 2 cycles of methotrexate with folinic acid after which the patient was lost to follow up. Patient B-was a 27 year old lady, para1, three year old child delivered by caesarean section. She also gave history of two subsequent abortions. She presented with menorrhagia and on examination a cervical polyp was detected. The polyp was resected and sent for histo-pathology and the report suggested choriocarcinoma. Her beta HCG was 30,000. This patient was given three cycles of multi-agent chemotherapy, MAC (Methotrexate, Actinomycin-D and Cyclophosphamide) regime and responded to treatment. Discussion: The main stay of treatment is chemotherapy. Mostly single agent chemotherapy is used methotrexate being the drug of choice. Methotrexate in the dose of 0.4 mg/kg IM or IV daily for 5 days, appears to be the most effective treatment protocol. Another widely used regimen is using folinic acid along with methotrexate. Some of the more commonly used multiagent chemotherapy combinations are – MAC, EMA-CO, EMA-EP, VBP and BEP. Conclusion: GTN can be treated with appropriate chemotherapy and supportive management, after correct staging and scoring of the disease. They are also the most curable of all cancers in women.

Assessment of peritoneal microbial features and tumor marker levels as potential diagnostic tools for ovarian cancer.

Epithelial ovarian cancer (OC) is the most deadly cancer of the female reproductive system. To date, there is no effective screening method for early detection of OC and current diagnostic armamentarium may include sonographic grading of the tumor and analyzing serum levels of tumor markers, Cancer Antigen 125 (CA-125) and Human epididymis protein 4 (HE4). Microorganisms (bacterial, archaeal, and fungal cells) residing in mucosal tissues including the gastrointestinal and urogenital tracts can be altered by different disease states, and these shifts in microbial dynamics may help to diagnose disease states. We hypothesized that the peritoneal microbial environment was altered in patients with OC and that inclusion of selected peritoneal microbial features with current clinical features into prediction analyses will improve detection accuracy of patients with OC. Blood and peritoneal fluid were collected from consented patients that had sonography confirmed adnexal masses and were being seen at SIU School of Medicine Simmons Cancer Institute. Blood was processed and serum HE4 and CA-125 were measured. Peritoneal fluid was collected at the time of surgery and processed for Next Generation Sequencing (NGS) using 16S V4 exon bacterial primers and bioinformatics analyses. We found that patients with OC had a unique peritoneal microbial profile compared to patients with a benign mass. Using ensemble modeling and machine learning pathways, we identified 18 microbial features that were highly specific to OC pathology. Prediction analyses confirmed that inclusion of microbial features with serum tumor marker levels and control features (patient age and BMI) improved diagnostic accuracy compared to currently used models. We conclude that OC pathogenesis alters the peritoneal microbial environment and that these unique microbial features are important for accurate diagnosis of OC. Our study warrants further analyses of the importance of microbial features in regards to oncological diagnostics and possible prognostic and interventional medicine.