A site to transform Pubmed publications into these bibliographic reference formats: ADS, BibTeX, EndNote, ISI used by the Web of Knowledge, RIS, MEDLINE, Microsoft's Word 2007 XML.

Ovarian cancer - Top 30 Publications

Targeted therapies: SOLO2 confirms olaparib maintenance in ovarian cancer.

Evaluating disease prediction models using a cohort whose covariate distribution differs from that of the target population.

Personal predictive models for disease development play important roles in chronic disease prevention. The performance of these models is evaluated by applying them to the baseline covariates of participants in external cohort studies, with model predictions compared to subjects' subsequent disease incidence. However, the covariate distribution among participants in a validation cohort may differ from that of the population for which the model will be used. Since estimates of predictive model performance depend on the distribution of covariates among the subjects to which it is applied, such differences can cause misleading estimates of model performance in the target population. We propose a method for addressing this problem by weighting the cohort subjects to make their covariate distribution better match that of the target population. Simulations show that the method provides accurate estimates of model performance in the target population, while un-weighted estimates may not. We illustrate the method by applying it to evaluate an ovarian cancer prediction model targeted to US women, using cohort data from participants in the California Teachers Study. The methods can be implemented using open-source code for public use as the R-package RMAP (Risk Model Assessment Package) available at .

pemetrexed + sildenafil, via autophagy-dependent HDAC down-regulation, enhances the immunotherapy response of NSCLC cells.

Pemetrexed is an approved therapeutic in NSCLC and ovarian cancer. Our studies focused on the ability of [pemetrexed + sildenafil] exposure to alter the immunogenicity of lung and ovarian cancer cells. Treatment of lung and ovarian cancer cells with [pemetrexed + sildenafil] in vitro rapidly reduced the expression of PD-L1, PD-L2 and ornithine decarboxylase (ODC), and increased the expression of Class I MHCA. In a cell-specific fashion, some cells also released the immunogenic nuclear protein HMGB1 into the extracellular environment. [Pemetrexed + sildenafil] reduced the expression of multiple histone deacetylases that was blocked by knock down of autophagy regulatory proteins. [Pemetrexed + sildenafil] lethality was enhanced by the histone deacetylase inhibitors AR42 and sodium valproate; AR42 and valproate as single agents also rapidly reduced the expression of PD-L1, PD-L2 and ODC, and increased expression of MHCA and CerS6. Nitric oxide and CerS6 signaling was required for drug-induced death receptor activation and tumor cell killing. In vivo, [pemetrexed + sildenafil] lethality against lung cancer cells was enhanced by sodium valproate. Using syngeneic mouse lung cancer cells [pemetrexed + sildenafil] enhanced the anti-tumor effects of antibodies directed to inhibit PD-1 or CTLA4. [Pemetrexed + sildenafil] interacted with the anti-PD-1 antibody to strongly enhance tumor infiltration by M1 macrophages; activated NK cells and activated T cells. Our data demonstrate that treatment of tumor cells with [pemetrexed + sildenafil] results in tumor cell killing and via autophagy-dependent down-regulation of HDACs, it opsonizes the remaining tumor cells to anti-tumor immunotherapy antibodies.

An ROR1 bi-specific T-cell engager provides effective targeting and cytotoxicity against a range of solid tumors.

We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), a cell surface antigen present on a range of malignancies and cancer-initiating cells. Focusing initially on pancreatic cancer, we demonstrated that our ROR1 BiTE results in T cell mediated and antigen-specific cytotoxicity against ROR1-expressing pancreatic cancer cell lines in vitro at exceedingly low concentrations (0.1 ng/mL) and low effector to target ratios. Our BiTE prevented engraftment of pancreatic tumor xenografts in murine models and reduced the size of established subcutaneous tumors by at least 3-fold. To validate its wider therapeutic potential, we next demonstrated significant cytotoxicity against ovarian cancer in an in vitro and in vivo setting and T-cell-mediated killing of a range of histologically distinct solid tumor cell lines. Overall, our ROR1 BiTE represents a promising immunotherapy approach, because of its ability to target a broad range of malignancies, many with significant unmet therapeutic needs.

The conceptual advances of carcinogenic sequence model in high-grade serous ovarian cancer.

The present review focuses on the current status of molecular pathology in high-grade serous cancer (HGSC) and preneoplastic conditions. This article reviews the English-language literature on HGSC, precursor, fallopian tubal epithelium, secretory cells, ciliated cells, secretory cell expansion, secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial carcinoma (STIC), DNA damage and immunohistochemistry in an effort to identify the precursor-carcinoma sequence in HGSC. The majority of HGSC originates from the fimbriated end of the fallopian tube secretory epithelial cells, while the small part of this disease may develop from ovarian cortical inclusion cyst (CIC). A series of morphological changes from normal fallopian epithelium to preneoplastic to neoplastic lesions were concomitant with the multistep accumulation of molecular and genetic alterations. Recent studies provide a stepwise progression of fallopian tubal epithelium to precursor lesions to carcinoma, with the aid of a 'secretory cell-SCE-SCOUT-p53 signature-STIC-HGSC sequence' model. Immunohistochemical markers, including p53, STMN1, EZH2, CCNE1, Ki67 and γ-H2AX, were gradually increased during the SCOUT-p53 signature-STIC-HGSC sequence. Conversely, PAX2 expression was decreased during the early phase of SCOUT development. Potential genes and proteins are involved in the evolutionary trajectory of the precursor-cancer lineage model. In the present review we examined detailed aspects of the molecular changes involved in malignant transformation from fallopian tube epithelium to HGSC. A precursor condition originating in 'field cancerization' may gain a growth advantage, leading to HGSC.

Evidence for the importance of post-transcriptional regulatory changes in ovarian cancer progression and the contribution of miRNAs.

High-throughput technologies have identified significant changes in patterns of mRNA expression over cancer development but the functional significance of these changes often rests upon the assumption that observed changes in levels of mRNA accurately reflect changes in levels of their encoded proteins. We systematically compared the expression of 4436 genes on the RNA and protein levels between discrete tumor samples collected from the ovary and from the omentum of the same OC patient. The overall correlation between global changes in levels of mRNA and their encoding proteins is low (r = 0.38). The majority of differences are on the protein level with no corresponding change on the mRNA level. Indirect and direct evidence indicates that a significant fraction of the differences may be mediated by microRNAs.

RGD delivery of truncated coagulase to tumor vasculature affords local thrombotic activity to induce infarction of tumors in mice.

Induction of thrombosis in tumor vasculature represents an appealing strategy for combating cancer. Herein, we combined unique intrinsic coagulation properties of staphylocoagulase with new acquired functional potentials introduced by genetic engineering, to generate a novel bi-functional fusion protein consisting of truncated coagulase (tCoa) bearing an RGD motif on its C-terminus for cancer therapy. We demonstrated that free coagulase failed to elicit any significant thrombotic activity. Conversely, RGD delivery of coagulase retained coagulase activity and afforded favorable interaction of fusion proteins with prothrombin and αvβ3 endothelial cell receptors, as verified by in silico, in vitro, and in vivo experiments. Although free coagulase elicited robust coagulase activity in vitro, only targeted coagulase (tCoa-RGD) was capable of producing extensive thrombosis, and subsequent infarction and massive necrosis of CT26 mouse colon, 4T1 mouse mammary and SKOV3 human ovarian tumors in mice. Additionally, systemic injections of lower doses of tCoa-RGD produced striking tumor growth inhibition of CT26, 4T1 and SKOV3 solid tumors in animals. Altogether, the nontoxic nature, unique shortcut mechanism, minimal effective dose, wide therapeutic window, efficient induction of thrombosis, local effects and susceptibility of human blood to coagulase suggest tCoa-RGD fusion proteins as a novel and promising anticancer therapy for human trials.

In vivo loss-of-function screens identify KPNB1 as a new druggable oncogene in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a deadly cancer, and its prognosis has not been changed significantly during several decades. To seek new therapeutic targets for EOC, we performed an in vivo dropout screen in human tumor xenografts using a pooled shRNA library targeting thousands of druggable genes. Then, in follow-up studies, we performed a second screen using a genome-wide CRISPR/Cas9 library. These screens identified 10 high-confidence drug targets that included well-known oncogenes such as ERBB2 and RAF1, and novel oncogenes, notably KPNB1, which we investigated further. Genetic and pharmacological inhibition showed that KPNB1 exerts its antitumor effects through multiphase cell cycle arrest and apoptosis induction. Mechanistically, proteomic studies revealed that KPNB1 acts as a master regulator of cell cycle-related proteins, including p21, p27, and APC/C. Clinically, EOC patients with higher expression levels of KPNB1 showed earlier recurrence and worse prognosis than those with lower expression levels of KPNB1. Interestingly, ivermectin, a Food and Drug Administration-approved antiparasitic drug, showed KPNB1-dependent antitumor effects on EOC, serving as an alternative therapeutic toward EOC patients through drug repositioning. Last, we found that the combination of ivermectin and paclitaxel produces a stronger antitumor effect on EOC both in vitro and in vivo than either drug alone. Our studies have thus identified a combinatorial therapy for EOC, in addition to a plethora of potential drug targets.

Stimulation of ovarian cell proliferation by tetrabromobisphenol A but not tetrachlorobisphenol A through G protein-coupled receptor 30.

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are bisphenol A (BPA) analogs, where the phenolic moieties are substituted with halogens (Br or Cl). Previous studies indicate that BPA has significant proliferative effects on in vitro cultured epithelial ovarian cancer (EOC) cells. Considering this, we analyzed the effects of both TBBPA and TCBPA at 1, 10, and 50nM on ovarian cancer cell proliferation. The majority of malignant ovarian tumors are epithelial in origin, but approximately 10% are classified as ovarian sex cord tumors, with the most common type being granulosa cell tumors (GCTs). OVCAR-3 and KGN cells were used as in vitro models to represent EOCs and GCTs, respectively. Here, we found that TBBPA, but not TCBPA, stimulated OVCAR-3 and KGN cell proliferation, with lower potency than BPA. The stimulatory effects of TBBPA and BPA on cell proliferation were reversed by pre-treatment with a G protein-coupled receptor 30 (GPR30) antagonist in both cell lines, which possess similar basal GPR30 expression levels. Taken together, our results show for the first time that TBBPA, which has lower potency than BPA, stimulates ovarian cancer cell proliferation through the GPR30 pathway.

Expression of Kruppel-like factor 8 and Ki67 in lung adenocarcinoma and prognosis.

Kruppel-like factor 8 (KLF8) belongs to the KLF family and has various roles in the regulation of the cell cycle, proliferation and tumor genesis. KLF8 is overexpressed in gastric, ovarian, breast and renal cancer. Additionally, KLF8 may affect invasion and metastasis of tumors. However, whether KLF8 also acts as an ontogeny in lung adenocarcinoma (LAC) remains unknown. The aim of the present study was to determine the association between KLF8 expression and various clinical and pathological parameters. Western blot assays and immune histochemistry analyses revealed that KLF8 level in LAC tissues was higher than that in the normal lung tissues and KLF8 expression was significantly associated with clinical variables (P<0.05). Kaplan-Meier curves revealed that high expression of KLF8 was related to poor prognosis in patients with LAC. The present study also demonstrated that KLF8 was involved in the progression of lung adenocarcinoma. This data suggested that KLF8 may act as a prognostic factor in lung adenocarcinoma progression.

Morphologic features of fallopian tubal epithelium in pelvic high-grade serous carcinoma.

Objective: To study the pathologic features of fallopian tubal epithelium in patients with pelvic high-grade serous carcinoma (HGSC), to investigate its role in pelvic serous carcinogenesis and to reclassify the primary site of HGSC based on recently proposed criteria. Methods: The fallopian tubes in 58 cases of pelvic HGSC (54 cases of ovarian primary, 3 cases of tubal primary, 1 case of peritoneum) and 25 cases of pelvic non-HGSC (5 cases of ovarian low-grade serous cancer, 9 cases of endometrioid cancer, and 11 cases of clear cell ovary carcinoma) were collected from June 2015 to December 2016, and serially examined under light microscope (SEE-FIM protocol). Immunostaining for p53 and Ki-67 was performed to evaluate the presence of p53 signature, serous tubal intraepithelial lesion (STIL), serous tubal intraepithelial carcinoma (STIC) and invasive carcinoma in these fallopian tubes. Meanwhile, primary site of HGSC based on the recently proposed diagnostic criteria were also reclassified. Results: Among the study group, the frequencies of p53 signature, STIL, STIC and invasive HGSC were 27.6% (16/58), 43.1% (25/58), 36.2% (21/58) and 67.2% (39/58), respectively, while in control group, the proportions were 24.0% (6/25), 0, 0 and 8.0% (2/25), respectively. The continuum of epithelial changes in the process of serous neoplasia including p53 signature, STIL, STIC and invasive carcinoma was identified in 8 cases of pelvic HGSC. The proportions of STIL, STIC and invasive carcinomas in HGSC group were higher than that in non-HGSC group (P<0.01). About 80.0% (20/25) of STIL and 85.7% (18/21) of STIC were present unilaterally. Diagnostically, the study group contained the 17 cases of ovarian HGSC, 40 cases of tubal HGSC, and 1 case of peritoneal HGSC after reclassification of the cancer primary. Conclusions: Continuous changes of tubal epithelium including p53 signature, STIL, STIC and invasive carcinomas are identified in patients with HGSC, supporting the current understanding that the fallopian tube is likely the cellular source of the majority HGSC. STIL and STIC may be specific to pelvic HGSC and may act as a target for future research on the early detection and prevention of this disease. The newly proposed diagnostic criteria for pelvic HGSC will lead us to more accurate classification of cancer primary sites. Correct classification of HGSC may have potential impacts for cancer prevention and improve our understanding of ovarian serous carcinogenesis.

Folate Receptor-Positive Gynecological Cancer Cells: In Vitro and In Vivo Characterization.

The folate receptor (FR) is expressed in a variety of gynecological cancer types. It has been widely used for tumor targeting with folic acid conjugates of diagnostic and therapeutic probes. The cervical KB tumor cells have evolved as the standard model for preclinical investigations of folate-based (radio) conjugates. In this study, a panel of FR-expressing human cancer cell lines-including cervical (HeLa, KB, KB-V1), ovarian (IGROV-1, SKOV-3, SKOV-3.ip), choriocarcinoma (JAR, BeWo) and endometrial (EFE-184) tumor cells-was investigated in vitro and for their ability to grow as xenografts in mice. FR-expression levels were compared in vitro and in vivo and the cell lines were characterized by determination of the sensitivity towards commonly-used chemotherapeutics and the expression of two additional, relevant tumor markers, HER2 and L1-CAM. It was found that, besides KB cells, its multiresistant KB-V1 subclone as well as the ovarian cancer cell lines, IGROV-1 and SKOV-3.ip, could be used as potentially more relevant preclinical models. They would allow addressing specific questions such as the therapeutic efficacy of FR-targeting agents in tumor (mouse) models of multi-resistance and in mouse models of metastases formation.

Fertility Preservation and Sexual Health After Cancer Therapy.

Recent developments in cancer diagnostics and treatments have considerably improved long-term survival rates. Despite improvements in chemotherapy regimens, more focused radiotherapy and diverse surgical options, cancer treatments often have gonadotoxic side-effects that can manifest as loss of fertility or sexual dysfunction, particularly in young cancer survivors. In this review, we focus on two pertinent quality-of-life issues in female cancer survivors of reproductive age-fertility preservation and sexual function. Fertility preservation encompasses all clinical and laboratory efforts to preserve a woman's chance to achieve future genetic motherhood. These efforts range from well-established protocols such as ovarian stimulation with cryopreservation of embryos or oocytes, to nascent clinical trials involving cryopreservation and re-implantation of ovarian tissue. Therefore, fertility preservation strategies are individualized to the cancer diagnosis, time interval until initiation of treatments must begin, prognosis, pubertal status, and maturity level of patient. Some patients choose not to pursue fertility preservation, and the conversation then centers around other quality of life issues. Not all cancer treatments cause loss of fertility; however, most treatments can directly impact the physical and psychosocial aspects of sexual function. Cancer treatment is also associated with fear, anxiety, and depression, which can further decrease sexual desire, function, and frequency. Sexual dysfunction after cancer treatment is generally ascertained by compassionate inquiry. Strategies to promote sexual function after cancer treatment include pelvic floor exercises, clitoral therapy devices, pharmacologic agents, as well as couples-based psychotherapeutic and psycho-educational interventions. Quality-of-life issues in young cancer survivors are often best addressed by utilizing a multidisciplinary team consisting of physicians, nurses, social workers, psychiatrists, sex educators, counselors, or therapists.

Preservation of Fertility and Ovarian Function: A Time-Sensitive Survivorship Need.

Changes in the use of erythropoiesis-stimulating agents (ESAs) and red blood cell transfusion in patients with cancer amidst regulatory and reimbursement changes.

Evaluate changes in use of erythropoiesis-stimulating agents (ESAs) and red blood cell transfusion in cancer patients receiving myelosuppressive chemotherapy following regulatory and reimbursement actions.

High expression of HO-1 predicts poor prognosis of ovarian cancer patients and promotes proliferation and aggressiveness of ovarian cancer cells.

HO-1 has been proved to be associated with tumor aggressivity and poor prognosis in various cancers. Our study provides the first study to demonstrate the relationship of HO-1 expression and clinical characteristics in ovarian cancer patients.

Red Snappers and Red Herrings: Pelvic Tuberculosis Causing Elevated CA 125 and Mimicking Advanced Ovarian Cancer. A Case Report and Literature Review.

Female genital tuberculosis (FGTB) is a form of extra-pulmonary tuberculosis that has been primarily described in developing countries, where it is an important cause of infertility, ectopic pregnancy, and miscarriage. FGTB is rare in the United States and because its clinical presentation is non-specific and often insidious, FGTB may be misdiagnosed as a gynecologic malignancy or endometriosis. The tendency of tuberculosis to dramatically increase serum CA 125 levels contributes to the potential for FGTB to be mistaken for ovarian cancer in particular. We describe the case of a young woman who presented with what was initially thought to be advanced ovarian cancer but who had tuberculosis of the peritoneum, uterus, and ovaries discovered at laparotomy. This case emphasizes the importance of considering tuberculosis in the differential of any patient presenting with an abdomino-pelvic mass and an elevated CA 125 level.

Inhibition of the mevalonate pathway augments the activity of pitavastatin against ovarian cancer cells.

Only 40% of patients with advanced ovarian cancer survive more than 5 years. We have previously shown that pitavastatin induces regression of ovarian cancer xenografts in mice. To evaluate whether the response of ovarian cancer cells to pitavastatin is potentiated by farnesyl diphosphate synthase inhibitors or geranylgeraniol transferase I inhibitors, we evaluated combinations of pitavastatin with zoledronic acid, risedronate and GGTI-2133 in a panel of ovarian cancer cells. Pitavastatin (IC50 = 0.6-14 μM), zoledronic acid (IC50 = 21-57 μM), risedronate (IC50 > 100 μM) or GGTI-2133 (IC50 > 25 μM) inhibited the growth of ovarian cancer cell cultures. Combinations of pitavastatin with zoledronic acid displayed additive or synergistic effects in cell growth assays in 10 of 11 cell lines evaluated as well as in trypan blue exclusion, cellular ATP or caspase 3/7, 8 and 9 assays. Pitavastatin reduced levels of GGT-IIβ and the membrane localization of several small GTPases and this was potentiated by zoledronic acid. siRNA to GGT-Iβ and GGT-IIβ used in combination, but not when used individually, significantly increased the sensitivity of cells to pitavastatin. These data suggest that zoledronic acid, a drug already in clinical use, may be usefully combined with pitavastatin in the treatment of ovarian cancer.

Antitumor properties of Coenzyme Q0 against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy.

Coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) has been reported to exert anticancer properties against human breast/lung cancer cells. This study investigated the in vitro and in vivo anticancer properties of CoQ0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ0 induced G2/M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ0-induced autophagy as a survival mechanism was evidenced by increased accumulation of LC3-II, GFP-LC3 puncta, AVOs formation and Beclin-1/Bcl-2 dysregulation. Increased TUNEL-positive cells and Annexin-V/PI stained cells indicated CoQ0-induced late apoptosis. Both mitochondrial (caspase-3, PARP and Bax/Bcl-2 dysregulation) and ER stress (caspase-12 and Hsp70) signals are involved in execution of apoptosis. Interestingly, CoQ0-induced apoptosis/autophagy is associated with suppression of HER-2/neu and PI3K/AKT signalling cascades. CoQ0 triggered intracellular ROS production, whereas antioxidant N-acetylcysteine prevented CoQ0-induced apoptosis, but not autophagy. Inhibition of apoptosis by Z-VAD-FMK suppressed CoQ0-induced autophagy (diminished LC3-II/AVOs), indicates CoQ0-induced apoptosis led to evoke autophagy. Contrary, inhibition of autophagy by 3-MA/CQ potentiated CoQ0-induced apoptosis (increased DNA fragmentation/PARP cleavage). Furthermore, CoQ0 treatment to SKOV-3 xenografted nude mice reduced tumor incidence and burden. Histopathological analyses confirmed that CoQ0 modulated xenografted tumor progression by apoptosis induction. Our findings emphasize that CoQ0 triggered ROS-mediated apoptosis and cytoprotective autophagy.

Cancer-associated pathways and biomarkers of venous thrombosis.

Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we will summarize common and cancer type-specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets and tissue factor-positive (TF+) microvesicles are all potential factors that alone or in combination increase cancer-associated thrombosis. Lung and colorectal cancer patients often exhibit leukocytosis. Neutrophils could increase VTE in cancer patients by releasing neutrophil extracellular traps whereas monocytes may express TF. Thrombocytosis is often observed in gastrointestinal, lung, breast and ovarian cancer and this could decrease the threshold required for VTE. Soluble P-selectin has been identified as a biomarker of cancer-associated thrombosis in a general cancer population, and may reflect activation of the endothelium. P-selectin expression by the endothelium may enhance VTE by increasing the recruitment of leukocytes. Studies with pancreatic and brain cancer patients suggest that elevated levels of PAI-1 may contribute to VTE. Although elevated levels of TF+ microvesicles have been observed in patients with different types of cancer, an association between TF+ microvesicles and VTE has only been observed in pancreatic cancer. Podoplanin expression is associated with VTE in brain cancer patients and may activate platelets. Future studies should measure multiple biomarkers in each cancer type to determine if combinations of biomarkers can be used as predictors of VTE. A better understanding of the pathways that increase VTE in cancer patients may lead to the development of new therapies to reduce the morbidity and mortality associated with thrombosis.

BRCA1/2 missense mutations and the value of in-silico analyses.

The clinical implications of genetic variants in BRCA1/2 in healthy and affected individuals are considerable. Variant interpretation, however, is especially challenging for missense variants. The majority of them are classified as variants of unknown clinical significance (VUS). Computational (in-silico) predictive programs are easy to access, but represent only one tool out of a wide range of complemental approaches to classify VUS. With this single-center study, we aimed to evaluate the impact of in-silico analyses in a spectrum of different BRCA1/2 missense variants.

An evaluation of progression free survival and overall survival of ovarian cancer patients with clear cell carcinoma versus serous carcinoma treated with platinum therapy: An NRG Oncology/Gynecologic Oncology Group experience.

We examined disparities in prognosis between patients with ovarian clear cell carcinoma (OCCC) and serous epithelial ovarian cancer (SOC).

Prospective screening with the validated Opioid Risk Tool demonstrates gynecologic oncology patients are at low risk for opioid misuse.

To characterize risk for opioid misuse among gynecologic oncology patients.

Ovarian cancer: Novel molecular aspects for clinical assessment.

Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients. The bulk of available scientific data and the high refinement of molecular classifications of ovarian cancers can today address the research towards innovative drugs with the adoption of targeted therapies tailored for single molecular profiles leading to a better prediction of therapeutic response. Here, we summarize the current state of knowledge on the molecular bases of ovarian cancer, from the description of its molecular subtypes derived from wide high-throughput analyses to the latest discoveries of the ovarian cancer stem cells. The latest personalized treatment options are also presented with recent advances in using PARP inhibitors, anti-angiogenic, anti-folate receptor and anti-cancer stem cells treatment approaches.

A prospective study to evaluate the risk malignancy index and its diagnostic implication in patients with suspected ovarian mass.

There is no universal screening method for discrimination between benign and malignant adnexal masses yet. Various authors have tried tumor markers, imaging studies, cytology but no one yet is a definite method for screening of cancer ovary, for which a combined diagnostic modality has come to practice in form of RMI. With this background we conducted our study "Evaluation of risk malignancy index and its diagnostic value in patients with adnexal masses".

Oncofertility in patients with stage I epithelial ovarian cancer: fertility-sparing surgery in young women of reproductive age.

Fertility-sparing surgery is indicated for patients with stage I epithelial ovarian cancers. We sought to evaluate the clinical outcomes and oncofertility in a cohort of patients of reproductive age with stage I epithelial ovarian cancer (EOC).

Network analysis identifies common genes associated with obesity in six obesity-related diseases.

Obesity has been reported to be associated with many diseases. However, common obesity-induced biological processes have not been evaluated across these diseases. We identified genes associated with obesity and obesity-related diseases, and used them to construct protein‒protein interaction networks. We also analyzed gene ontology (GO) in those genes overlapping between obesity and disease. Our work identifies gene modules common to obesity and obesity-related diseases, which can provide a basis for understanding the process of how obesity induces disease.

RAD6 promotes DNA repair and stem cell signaling in ovarian cancer and is a promising therapeutic target to prevent and treat acquired chemoresistance.

Ovarian cancer (OC) is the most deadly gynecological cancer and unlike most other neoplasms, survival rates for OC have not significantly improved in recent decades. We show that RAD6, an ubiquitin-conjugating enzyme, is significantly overexpressed in ovarian tumors and its expression increases in response to carboplatin chemotherapy. RAD6 expression correlated strongly with acquired chemoresistance and malignant behavior of OC cells, expression of stem cell genes and poor prognosis of OC patients, suggesting an important role for RAD6 in ovarian tumor progression. Upregulated RAD6 enhances DNA damage tolerance and repair efficiency of OC cells and promotes their survival. Increased RAD6 levels cause histone 2B ubiquitination-mediated epigenetic changes that stimulate transcription of stem cell genes, including ALDH1A1 and SOX2, leading to a cancer stem cell phenotype, which is implicated in disease recurrence and metastasis. Downregulation of RAD6 or its inhibition using a small molecule inhibitor attenuated DNA repair signaling and expression of cancer stem cells markers and sensitized chemoresistant OC cells to carboplatin. Together, these results suggest that RAD6 could be a therapeutic target to prevent and treat acquired chemoresistance and disease recurrence in OC and enhance the efficacy of standard chemotherapy.Oncogene advance online publication, 14 August 2017; doi:10.1038/onc.2017.279.

Benign metastasizing leiomyomas thought to be nodal metastases in a case of ovarian cancer.

A retrospective audit on usage of Diatrizoate Meglumine (Gastrografin(®)) for intestinal obstruction or constipation in patients with advanced neoplasms.

Intestinal obstruction and constipation are common conditions in patients with advanced neoplasms. Diatrizoate Meglumine has been used in the management of both these conditions without good quality evidence of its effectiveness and safety.