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Sample records for platinum-resistant ovarian cancer

  1. Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives

    PubMed Central

    McClung, E Clair; Wenham, Robert M

    2016-01-01

    Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3–4 months and a median overall survival of 9–12 months. Bevacizumab (Avastin), a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer. PMID:27051317

  2. Profile of bevacizumab in the treatment of platinum-resistant ovarian cancer: current perspectives.

    PubMed

    McClung, E Clair; Wenham, Robert M

    2016-01-01

    Patients with platinum-resistant ovarian cancer have progression of disease within 6 months of completing platinum-based chemotherapy. While several chemotherapeutic options exist for the treatment of platinum-resistant ovarian cancer, the overall response to any of these therapies is ~10%, with a median progression-free survival of 3-4 months and a median overall survival of 9-12 months. Bevacizumab (Avastin), a humanized, monoclonal antivascular endothelial growth factor antibody, has demonstrated antitumor activity in the platinum-resistant setting and was recently approved by US Food and Drug Administration for combination therapy with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan. This review summarizes key clinical trials investigating bevacizumab for recurrent, platinum-resistant ovarian cancer and provides an overview of efficacy, safety, and quality of life data relevant in this setting. While bevacizumab is currently the most studied and clinically available antiangiogenic therapy, we summarize recent studies highlighting novel alternatives, including vascular endothelial growth factor-trap, tyrosine kinase inhibitors, and angiopoietin inhibitor trebananib, and discuss their application for the treatment of platinum-resistant ovarian cancer. PMID:27051317

  3. Targeting c-MYC in Platinum-Resistant Ovarian Cancer.

    PubMed

    Reyes-González, Jeyshka M; Armaiz-Peña, Guillermo N; Mangala, Lingegowda S; Valiyeva, Fatma; Ivan, Cristina; Pradeep, Sunila; Echevarría-Vargas, Ileabett M; Rivera-Reyes, Adrian; Sood, Anil K; Vivas-Mejía, Pablo E

    2015-10-01

    The purpose of this study was to investigate the molecular and therapeutic effects of siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer. Statistical analysis of patient's data extracted from The Cancer Genome Atlas (TCGA) portal showed that the disease-free (DFS) and the overall (OS) survival were decreased in ovarian cancer patients with high c-MYC mRNA levels. Furthermore, analysis of a panel of ovarian cancer cell lines showed that c-MYC protein levels were higher in cisplatin-resistant cells when compared with their cisplatin-sensitive counterparts. In vitro cell viability, growth, cell-cycle progression, and apoptosis, as well as in vivo therapeutic effectiveness in murine xenograft models, were also assessed following siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer cells. Significant inhibition of cell growth and viability, cell-cycle arrest, and activation of apoptosis were observed upon siRNA-mediated c-MYC depletion. In addition, single weekly doses of c-MYC-siRNA incorporated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000)-based nanoliposomes resulted in significant reduction in tumor growth. These findings identify c-MYC as a potential therapeutic target for ovarian cancers expressing high levels of this oncoprotein. PMID:26227489

  4. Effect of neoadjuvant chemotherapy on platinum resistance in stage IIIC and IV epithelial ovarian cancer.

    PubMed

    Luo, Yanlin; Lee, Maria; Kim, Hee Seung; Chung, Hyun Hoon; Song, Yong Sang

    2016-09-01

    It remains controversial whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) induces chemoresistance in advanced epithelial ovarian cancer (EOC) compared with primary debulking surgery (PDS). The aim of this study was to compare platinum-resistant recurrence following treatment with NACT-IDS or PDS in patients with stage IIIC and IV EOC.We retrospectively reviewed the records of 341 patients who underwent PDS or NACT-IDS for Federation of Gynecology and Obstetrics stage IIIC or IV EOC between March 1990 and December 2010. Risk factors of platinum resistance, including NACT, postoperative residual tumor size, and various clinicopathological factors, were evaluated by univariate and multivariate logistic regression analyses. Survival analysis was performed by the Kaplan-Meier method and Cox regression modeling to measure overall survival (OS).Of 341 patients, 58 (17.0%) underwent NACT-IDS and 283 (83.0%) were treated with PDS. Twenty-nine (50.0%) patients developed platinum-resistant disease at first relapse after NACT-IDS and 99 (35.0%) patients recurred after PDS (P = 0.033). In the multivariate logistic regression analyses, NACT-IDS and postoperative residual tumor mass >1 cm were risk factors for platinum-resistant recurrence (adjusted odds ratios 2.950 and 2.915; 95% confidence intervals [CIs] 1.572-5.537 and 1.780-4.771, P = 0.001 and 0.000, respectively). Postoperative residual tumor mass >1 cm and platinum-resistant disease were significantly correlated with shorter OS (adjusted hazard ratios 1.579 and 4.078; 95% CI 1.193-2.089 and 3.074-5.412, P = 0.001 and 0.000, respectively), whereas NACT-IDS did not extend OS.NACT-IDS increases the risk of platinum-resistant recurrence in patients with stage IIIC and IV EOC. PMID:27603388

  5. HDAC4-regulated STAT1 activation mediates platinum resistance in ovarian cancer.

    PubMed

    Stronach, Euan A; Alfraidi, Albandri; Rama, Nona; Datler, Christoph; Studd, James B; Agarwal, Roshan; Guney, Tankut G; Gourley, Charlie; Hennessy, Bryan T; Mills, Gordon B; Mai, Antonello; Brown, Robert; Dina, Roberto; Gabra, Hani

    2011-07-01

    Ovarian cancer frequently acquires resistance to platinum chemotherapy, representing a major challenge for improving patient survival. Recent work suggests that resistant clones exist within a larger drug-sensitive cell population prior to chemotherapy, implying that resistance is selected for rather than generated by treatment. We sought to compare clinically derived, intrapatient paired models of initial platinum response and subsequent resistant relapse to define molecular determinants of evolved resistance. Transcriptional analysis of a matched cell line series from three patients with high-grade serous ovarian cancer before and after development of clinical platinum resistance (PEO1/PEO4/PEO6, PEA1/PEA2, PEO14/PEO23) identified 91 up- and 126 downregulated genes common to acquired resistance. Significantly enhanced apoptotic response to platinum treatment in resistant cells was observed following knockdown of histone deacetylase (HDAC) 4, FOLR2, PIK3R1, or STAT1 (P < 0.05). Interestingly, HDAC4 and STAT1 were found to physically interact. Acetyl-STAT1 was detected in platinum-sensitive cells but not in HDAC4 overexpressing platinum-resistant cells from the same patient. In resistant cells, STAT1 phosphorylation/nuclear translocation was seen following platinum exposure, whereas silencing of HDAC4 increased acetyl-STAT1 levels, prevented platinum-induced STAT1 activation, and restored cisplatin sensitivity. Conversely, matched sensitive cells were refractory to STAT1 phosphorylation on platinum treatment. Analysis of 16 paired tumor biopsies taken before and after development of clinical platinum resistance showed significantly increased HDAC4 expression in resistant tumors [n = 7 of 16 (44%); P = 0.04]. Therefore, clinical selection of HDAC4-overexpressing tumor cells upon exposure to chemotherapy promotes STAT1 deacetylation and cancer cell survival. Together, our findings identify HDAC4 as a novel, therapeutically tractable target to counter platinum

  6. HDAC4-regulated STAT1 activation mediates platinum resistance in ovarian cancer

    PubMed Central

    Stronach, Euan A; Alfraidi, Albandri; Rama, Nona; Datler, Christoph; Studd, Jamie; Agarwal, Roshan; Guney, Tankut G; Gourley, Charlie; Hennessy, Bryan T; Mills, Gordon B; Mai, Antonello; Brown, Robert; Dina, Roberto; Gabra, Hani

    2011-01-01

    Ovarian cancer frequently acquires resistance to platinum chemotherapy, representing a major challenge for improving patient survival. Recent work suggests resistant clones exist within a larger drug sensitive cell-population prior to chemotherapy, implying that resistance is selected for rather than generated by treatment. We sought to compare clinically-derived, intra-patient paired models of initial platinum response and subsequent resistant relapse to define molecular determinants of evolved resistance. Transcriptional analysis of a matched cell-line series from three patients with high-grade serous ovarian cancer before and after development of clinical platinum resistance (PEO1/PEO4/PEO6, PEA1/PEA2, PEO14/PEO23) identified 91 up- and 126 down-regulated genes common to acquired resistance. Significantly enhanced apoptotic response to platinum treatment in resistant cells was observed following knockdown of HDAC4, FOLR2, PIK3R1 or STAT1 (p<0.05). Interestingly, HDAC4 and STAT1 were found to physically interact. Acetyl-STAT1 was detected in platinum sensitive but not HDAC4 over-expressing platinum resistant cells from the same patient. In resistant cells, STAT1 phosphorylation/nuclear translocation was seen following platinum exposure, whereas silencing of HDAC4 increased acetyl-STAT1 levels, prevented platinum induced STAT1 activation and restored cisplatin sensitivity. Conversely, matched sensitive cells were refractory to STAT1 phosphorylation on platinum treatment. Analysis of 16 paired tumor biopsies taken before and after development of clinical platinum resistance showed significantly increased HDAC4 expression in resistant tumors (n=7/16[44%]; p=0.04). Therefore, clinical selection of HDAC4 overexpressing tumor cells upon exposure to chemotherapy promotes STAT1 deacetylation and cancer cell survival. Together, our findings identify HDAC4 as a novel, therapeutically tractable target to counter platinum resistance in ovarian cancer. PMID:21571862

  7. Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance.

    PubMed

    Nagaraj, Anil Belur; Joseph, Peronne; Kovalenko, Olga; Singh, Sareena; Armstrong, Amy; Redline, Raymond; Resnick, Kimberly; Zanotti, Kristine; Waggoner, Steven; DiFeo, Analisa

    2015-09-15

    Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/β-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/β-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/β-catenin signaling is activated in ovarian CICs, and targeted inhibition of β-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/β-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/β-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option. PMID:26125441

  8. Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance

    PubMed Central

    Nagaraj, Anil Belur; Joseph, Peronne; Kovalenko, Olga; Singh, Sareena; Armstrong, Amy; Redline, Raymond; Resnick, Kimberly; Zanotti, Kristine; Waggoner, Steven; DiFeo, Analisa

    2015-01-01

    Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/β-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/β-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/β-catenin signaling is activated in ovarian CICs, and targeted inhibition of β-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/β-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/β-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option. PMID:26125441

  9. Phase Ib-IIa study to reverse platinum resistance by the use of a hypomethylating agent azacitidine in platinum-resistant or refractory epithelial ovarian cancer

    PubMed Central

    Fu, Siqing; Hu, Wei; Iyer, Revathy; Kavanagh, John J.; Coleman, Robert L.; Levenback, Charles F.; Sood, Anil K.; Wolf, Judith K.; Gershenson, David M.; Markman, Maurie; Hennessy, Bryan T.; Kurzrock, Razelle; Bast, Robert C.

    2010-01-01

    Background Sequential treatment with azacitidine can induce re-expression of epigenetically silenced genes through genomic DNA hypomethylation and reverse carboplatin resistance of epithelial ovarian cancer cells. We initiated a phase Ib-IIa clinical trial of this sequential combination of azacitidine and carboplatin in platinum-resistant or refractory epithelial ovarian cancer. Methods Patients with pathologically confirmed intermediate- or high-grade epithelial ovarian cancer who had disease progression within 6 months (resistant, n = 18) or during a platinum-based therapy (refractory, n = 12) were eligible. All patients had measurable disease. Results Thirty patients received a total of 163 cycles of treatment. This regimen produced 1 CR, 3 PR (ORR: 13.8%), and 10 SD among 29 evaluable patients. For those who achieved clinical benefits, the median duration of the treatment was 7.5 months. The median PFS and OS for all patients were 3.7 months and 14 months, respectively. Patients with platinum resistant disease achieved an ORR of 22%, with a median PFS of 5.6 months and a median OS of 23 months. The predominant toxicities were fatigue and myelosuppression. Correlative studies showed that DR4 methylation in peripheral blood leukocytes was decreased during treatment in 3 of 4 objective responders (75%), but in only 5 of 13 non-responders (38%). Conclusions To our knowledge, this study provides the first clinical evidence that a hypomethylating agent may partially reverse platinum resistance in ovarian cancer. Further clinical evaluation of hypomethylating agents in combination with carboplatin is warranted. PMID:21472713

  10. Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

    PubMed Central

    Sayal, Karen; Gounaris, Ioannis; Basu, Bristi; Freeman, Sue; Moyle, Penny; Hosking, Karen; Iddawela, Mahesh; Jimenez-Linan, Mercedes; Abraham, Jean; Brenton, James; Hatcher, Helen; Earl, Helena; Parkinson, Christine

    2015-01-01

    Objective Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. Methods Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. Results Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. Conclusions Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after

  11. Evolving concepts in the management of drug resistant ovarian cancer: dose dense chemotherapy and the reversal of clinical platinum resistance.

    PubMed

    Pinato, David J; Graham, Janet; Gabra, Hani; Sharma, Rohini

    2013-04-01

    Despite the initially high response rate to standard front-line debulking surgery followed by platinum-based chemotherapy, the relapse rate in ovarian cancer is high and many patients will recur within 6 months of completing platinum based treatment. These patients may still require further chemotherapy despite being considered "platinum resistant". In this setting, response rates to conventionally scheduled second line platinum and non-platinum agents is low, ranging between 5% and 15%. There is an emerging body of evidence that in this scenario, chemotherapeutic activity can be enhanced using unconventionally scheduled "dose-dense" platinum and non-platinum based regimens with improved response rates of up to 65%. Randomised studies to evaluate the impact of this approach on survival in recurrent, platinum resistant disease are urgently required to confirm the promising phase II findings if there is to be a change in the standard of care of patients with platinum resistant disease. In this review we discuss the evolving strategies to overcome resistance in patients with platinum resistant ovarian cancer with a particular focus on alterations in dose schedule as a means of reversing platinum resistance. PMID:22595680

  12. Profile of vintafolide (EC145) and its use in the treatment of platinum-resistant ovarian cancer

    PubMed Central

    Luyckx, Mathieu; Votino, Raffaella; Squifflet, Jean-Luc; Baurain, Jean-François

    2014-01-01

    Objective Our aim was to review the profile of vintafolide (EC145) and its rationale for use in platinum-resistant ovarian cancer. First we investigated the folate receptors (FRs), folate’s pathway into cells, and its expression in normal and cancerous cells, before detailing the mechanism of action of vintafolide, its clinical applications, and the results of different study phases. Materials and methods A literature search was conducted through PubMed/Medline, Google, ClinicalTrials.gov and websites of pharmaceutical companies. Only articles in English were selected. All articles investigating folate receptor expression in ovarian cancer were selected first, than articles reviewing platinum resistance. Papers about vintafolide were collected, while those talking about synthesis and biochemistry concerns were excluded. The different Phase I and II studies were read, and an update on the website of pharmaceuticals companies were added. Results FR is a bundle-membrane receptor that is expressed normally in some normal tissues on the apical surface of cells, but highly expressed in ovarian cancer cells (>80%). It collects folate through endocytosis. Chemotherapy does not modify its expression in ovarian cancer cells, and its expression appears to be mostly associated with a poor prognosis and platinum resistance. Vintafolide is a folate-desacetylvinblastine monohydrazide conjugate, allowing a liberation of the drug into the cytoplasm of cancerous cells via the FR-α (FRα) and endocytosis, with high specificity. Phase I studies showed a 2.5 mg bolus dose to be nontoxic, with moderately adverse events. Phase II clinical trials for the first time demonstrated a statistically significant improvement in disease-free survival in patients with platinum-resistant ovarian cancer, and in those with a very poor prognosis who had already received three to four lines of systemic chemotherapy. The greater benefits were observed in patients with highly expressed FRα. Conclusion

  13. Annexin A3 Is a Potential Predictor of Platinum Resistance in Epithelial Ovarian Cancer Patients in a Prospective Cohort

    PubMed Central

    Jin, Ying; Feng, Li-ping; Jiang, Xiang; Wang, Yong-xue; Yin, Jie; Yang, Zi-ping; Li, Yan; Pan, Ling-ya

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies and is rarely cured in the recurrent setting, mainly because of progressive chemoresistance, especially platinum resistance. In our previous studies, the platinum-resistance-related protein, annexin A3, was selected by comparative proteomics. In this study, we detected serum annexin A3 levels using a self-developed chemiluminescence immunoassay kit in a prospective EOC patient cohort. We also evaluated the capacity of serum annexin A3 levels to predict platinum resistance. Serum annexin A3 levels in healthy women exhibited a similar normal distribution (Z=0.723, P=0.673), allowing determination of a normal cutoff level of 0.11-1.45 ng/mL. Of the 89 EOC patients, 21 were platinum resistant and 68 were platinum sensitive. Residual disease after primary surgery (p=0.004) and serum annexin A3 levels (p=0.036) were both independent factors associated with platinum resistance. The AUC was 0.733 (95% confidence interval (CI), 0.627-0.823). The optimal cutoff value for serum annexin A3 levels was 2.05 ng/mL. Multivariate logistic analysis showed that expression of annexin A3 as assessed by immunohistochemistry (P=0.005) and residual tumor size (P=0.000) had a significant influence on platinum resistance. The AUC of ROC curve of annexin A3 expression by immunohistochemistry was 0.664 (95% CI, 0.554-0.763) and the cut off value was “>=moderate scores”. In conclusion, we demonstrate that annexin A3 is a secreted protein that may be measured in the peripheral blood using a self-developed, chemiluminescence immunoassay kit. Serum annexin A3 levels may be a potential predictor of platinum resistance in epithelial ovarian cancer patients. PMID:26078799

  14. Oral etoposide (VP16) in platinum-resistant epithelial ovarian cancer (EOC).

    PubMed

    Alici, Süleyman; Saip, Pinar; Eralp, Yeşim; Aydiner, Adnan; Topuz, Erkan

    2003-08-01

    This phase II study evaluates the efficacy and toxicity of a prolonged schedule second-line and third-line treatment of oral VP16 in patients with measurable advanced ovarian cancer resistant to, or relapsed following, platinum-based chemotherapy. Twenty-two eligible women with progressive or relapsed ovarian cancer resistant to platinum-based therapy were included in this study. All the patients had received more than one prior treatment, and had evidence of disease progression within 6 months of the previous chemotherapy. Eleven patients had received more than two different chemotherapy regimens. Fifteen patients had received consolidation therapy with intraperitoneal cisplatin after an initial treatment course with six cycles of a platinum-based combination regimen. All patients with measurable disease observed in abdominal computed tomography scans were given oral VP16 at a daily dose of 50 mg/m2 for 14 consecutive days with 4 weekly intervals. Among 22 assessable patients, there were one complete response (CR) and three partial responses (PR), so the objective response rate, which is the addition of CR and PR rates, was 18%. Seven patients (32%) had stable disease. Median duration of response and stable disease was 2.5 months (range: 1-10 months). Overall median survival was 11 months from study entry (range: 3-36 months). Toxicity for most patients was mild, but a few severe myelotoxicities occurred, and there were no treatment-related deaths. According to World Health Organization toxicity criteria grade III/IV thrombocytopenia was seen in 4 of 22 patients, grade III/IV neutropenia in 6 of 22 patients, and grade III anemia was observed in 3 of 22 patients. Nonhematologic toxicity was mild, and mucositis was the most frequently observed nonhematologic toxicity. Oral etoposide has considerable activity with a tolerable toxicity profile for the treatment of platinum-resistant epithelial ovarian cancer. PMID:12902885

  15. Docetaxel in combination with irinotecan (CPT-11) in platinum-resistant paclitaxel-pretreated ovarian cancer.

    PubMed

    Polyzos, Aristides; Kosmas, Christos; Toufexi, Helen; Malamos, Nicholas; Lagadas, Antonios; Kosmidis, Christos; Ginopoulos, Panagiotis; Ziras, Nicholas; Kandilis, Kostas; Georgoulias, Vassilis

    2005-01-01

    The role of combination chemotherapy regimens in the management of ovarian cancer patients with tumors resistant to platinum compounds has not yet been defined. This multicenter prospective phase II study evaluated the activity and toxicity of the docetaxel-plus-irinotecan combination in ovarian cancer patients whose tumors were resistant to platinum compounds and who had been exposed to paclitaxel. Treatment consisted of docetaxel 60 mg/m2 i.v. followed by irinotecan 200 mg/m2 i.v. both on day 1 followed by prophylactic recombinant human granulocyte-colony stimulating factor (rhG-CSF) support from days 2 to 6, every 3 weeks. Thirty-one patients were enrolled in the study. The median age was 60 years, and the median performance status (ECOG) was 1. Eight (26%) patients had primary tumors resistant to platinum, while the rest of the population had tumor recurrence within 6 months from the last cisplatin treatment. Four chemotherapy cycles per patient were administered, with the delivered dose intensity at 75% of the planned dose for both agents. Among 30 patients evaluable for response, there were 2 (7%) complete and 4 (14%) partial responses (overall response rate 20%; (95% confidence interval, CI, 11%-33%). Stable disease was recorded in 8 (28%) patients and progressive disease in 15 (51%). The median response duration was 4.5 months (range, 3-12), the median time to progression 5 months (range, 2-17) and the median survival 11 months (range, 1-40); the 1-year survival was almost 50%. Myelotoxicity was moderate, with grade 3 and 4 neutropenia occurring in 23% of the patients, grade 3-4 thrombocytopenia in 6% and febrile neutropenia in 13%. Grade 3 diarrhea was observed in 2% of the patients. There was one treatment-related death due to sepsis. In conclusion, the combination of docetaxel plus irinotecan with rhG-CSF support, appears to be a moderately effective regimen with acceptable toxicity for platinum-resistant, paclitaxel-pretreated ovarian cancer patients

  16. Mechanistic Nanotherapeutic Approach Based on siRNA-Mediated DJ-1 Protein Suppression for Platinum-Resistant Ovarian Cancer.

    PubMed

    Schumann, Canan; Chan, Stephanie; Khalimonchuk, Oleh; Khal, Shannon; Moskal, Vitaliya; Shah, Vidhi; Alani, Adam W G; Taratula, Olena; Taratula, Oleh

    2016-06-01

    We report an efficient therapeutic modality for platinum resistant ovarian cancer based on siRNA-mediated suppression of a multifunctional DJ-1 protein that is responsible for the proliferation, growth, invasion, oxidative stress, and overall survival of various cancers. The developed therapeutic strategy can work alone or in concert with a low dose of the first line chemotherapeutic agent cisplatin, to elicit a maximal therapeutic response. To achieve an efficient DJ-1 knockdown, we constructed the polypropylenimine dendrimer-based nanoplatform targeted to LHRH receptors overexpressed on ovarian cancer cells. The quantitative PCR and Western immunoblotting analysis revealed that the delivered DJ-1 siRNA downregulated the expression of targeted mRNA and corresponding protein by more than 80% in various ovarian cancer cells. It was further demonstrated that siRNA-mediated DJ-1 suppression dramatically impaired proliferation, viability, and migration of the employed ovarian cancer cells. Finally, the combinatorial approach led to the most pronounced therapeutic response in all the studied cell lines, outperforming both siRNA-mediated DJ-1 knockdown and cisplatin treatment alone. It is noteworthy that the platinum-resistant cancer cells (A2780/CDDP) with the highest basal level of DJ-1 protein are most susceptible to the developed therapy and this susceptibility declines with decreasing basal levels of DJ-1. Finally, we interrogate the molecular underpinnings of the DJ-1 knockdown effects in the treatment of the ovarian cancer cells. By using various experimental techniques, it was revealed that DJ-1 depletion (1) decreases the activity of the Akt pathway, thereby reducing cellular proliferation and migration and increasing the antiproliferative effect of cisplatin on ovarian cancer cells; (2) enhances the activity of p53 tumor suppressor protein therefore restoring cell cycle arrest functionality and upregulating the Bax-caspase pathway, triggering cell death; and (3

  17. Cranberry Proanthocyanidins are Cytotoxic to Human Cancer Cells and Sensitize Platinum-Resistant Ovarian Cancer Cells to Paraplatin

    PubMed Central

    Singh, Ajay P.; Singh, Rakesh K.; Kim, Kyu Kwang; Satyan, K. S.; Nussbaum, Roger; Torres, Monica; Brard, Laurent; Vorsa, Nicholi

    2010-01-01

    Polyphenolic extracts of the principal flavonoid classes present in cranberry were screened in vitro for cytotoxicity against solid tumor cells lines, identifying two fractions composed principally of proanthocyanidins (PACs) with potential anticancer activity. Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-MS) analysis of the proanthocyanidins (PACs) fractions indicated the presence of A-type PACs with 1–4 linkages containing between 2–8 epicatechin units with a maximum of 1 epigallocatechin unit. PACs exhibited in vitro cytotoxicity against platinum-resistant human ovarian, neuroblastoma and prostate cancer cell lines (IC50 = 79–479 μg/mL) but were non-cytotoxic to lung fibroblast cells (IC50 > 1000 μg/ml). SKOV-3 ovarian cancer cells treated with PACs exhibited classic apoptotic changes. PACs acted synergistically with paraplatin in SKOV-3 cells. Pretreatment of SKOV-3 cells with PACs (106 μg/ ml) resulted in a significant reduction of the paraplatin IC50 value. Similarly, in a BrdU incorporation assay, co-treatment of SKOV-3 cells with PACs and paraplatin revealed reduced cell proliferation at lower concentrations than with either individually. In SKOV-3 cell cultures co-treated with PAC-1 and paraplatin, an HPLC analysis indicated differential quantitative presence of various PAC oligomers such as DP-8, -9, -11 and -14 indicating either selective binding or uptake. Cranberry proanthocyanidins exhibit cell-line specific cytotoxicity, induce apoptotic markers and augment cytotoxicity of paraplatin in platinum-resistant SKOV-3 ovarian cancer cells. PMID:19172579

  18. Eribulin mesylate (halichondrin B Analog E7389) in platinum-resistant and platinum-sensitive ovarian cancer: a two-cohort, phase II study

    PubMed Central

    Hensley, Martee L.; Kravetz, Sara; Jia, Xiaoyu; Iasonos, Alexia; Tew, William; Pereira, Lauren; Sabbatini, Paul; Whalen, Christin; Aghajanian, Carol A.; Zarwan, Corinne; Berlin, Suzanne

    2011-01-01

    Background Eribulin mesylate is a tubulin inhibitor with activity superior to paclitaxel in NIH:OVCAR-3 human epithelial ovarian cancer xenograft models. We sought to assess the efficacy of eribulin in platinum-resistant and platinum-sensitive recurrent ovarian cancer. Methods Patients with recurrent measurable epithelial ovarian cancer, ≤2 prior cytotoxic regimens, and adequate organ function were enrolled into two separate cohorts: 1) Platinum resistant (progression-free interval from last platinum-based therapy <6 months); and 2) Platinum sensitive (progression-free interval from last platinum-based therapy ≥6 months). Treatment: Eribulin 1.4 mg/m2 over 15 minutes by vein on days 1 and 8, every 21 days. Efficacy was determined by objective response by computed tomography. Results Platinum-resistant cohort: Thirty-seven patients enrolled. Thirty-six patients were evaluable for response and toxicity. Two patients achieved partial response (PR, 5.5%). Sixteen (44%) had a best response of stable disease. Median progression-free survival was 1.8 months (95% confidence interval, 1.4–2.8 months). Platinum-sensitive cohort: Thirty-seven patients enrolled, and all were evaluable for response. Seven patients achieved partial response (PR, 19%). Median progression-free survival was 4.1 months (95% confidence interval, 2.8–5.8 months). The major toxicity was grade 3 or 4 neutropenia (42% in platinum-resistant patients; 54% in platinum-sensitive patients). Conclusions Eribulin achieved objective response in 5.5% of women with platinum-resistant recurrent ovarian cancer and in 19% of women with platinum-sensitive disease. Median progression-free survival was 1.8 months in the platinum-resistant group and 4.1 months in the platinum-sensitive group. PMID:21935916

  19. Weekly Paclitaxel Versus Three-Weekly Paclitaxel in Recurrent Platinum-Resistant Epithelial Ovarian and Peritoneal Cancers: A Phase III Study

    PubMed Central

    Osman, Mohammed A.; Elkady, Mohammad S.; Nasr, Khalid E.

    2016-01-01

    INTRODUCTION Treatment of recurrent platinum-resistant ovarian and peritoneal cancers represents a therapeutic challenge. The aim of this Phase III prospective study was to compare the survival benefits, objective response rate, and toxicities among patients treated by weekly paclitaxel with those who underwent three-weekly paclitaxel in recurrent platinum-resistant ovarian and peritoneal cancers. METHOD Patients with recurrent platinum-resistant ovarian and peritoneal cancer were allocated to receive either weekly paclitaxel (arm 1) at 80 m/m2 or three-weekly paclitaxel (arm 2) at 175 mg/m2. RESULTS Fifty-five patients were enrolled (30 arm 1, 25 arm 2). The mean age was 56.7 years, and the median performance status was 0 (Eastern Cooperative Oncology Group [ECOG]). For arms 1 and 2, the objective response rates were 27% and 16%, the median progression-free survival were 7 and 4.5 months, and the median overall survival were 15.5 and 12.5 months, respectively. Treatments also significantly improved the quality of life. Treatment was associated with mild toxicities, and while neuropathy was slightly higher for weekly paclitaxel over three-weekly paclitaxel, hematological toxicities were significantly lower for the former than the latter. CONCLUSION Paclitaxel rechallenge showed antitumor activity in recurrent platinum-resistant ovarian and peritoneal cancers. Weekly paclitaxel achieved better results than three-weekly paclitaxel in terms of survival benefits, quality of life, and toxicities. PMID:27147900

  20. Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer

    PubMed Central

    ZHAO, YA-NAN; HE, DONG-NING; WANG, YA-DI; LI, JUN-JIE; HA, MIN-WEN

    2016-01-01

    The human major vault protein (MVP) has been linked to the development of multidrug resistance in cancer cells, and overexpression of MVP has been observed in ovarian cancer tissues. The aim of the present study was to investigate the association between single nucleotide polymorphisms (SNPs) in the MVP gene and the tumor response to platinum-based chemotherapy and survival of patients affected by epithelial ovarian cancer (EOC), in addition to confirm whether tetra-primer amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) is an accurate genotyping method. For this purpose, two polymorphisms in the MVP gene, namely reference SNP (rs)1057451 and rs4788186, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra-primer ARMS-PCR. Upon validation by DNA sequencing, the association of these polymorphisms with platinum resistance, progression-free survival (PFS) and overall survival (OS) in patients with EOC was assessed. The results of tetra-primer ARMS-PCR were in agreement with those derived from DNA sequencing. No significant differences were observed between platinum-sensitive and platinum-resistant cohorts in terms of allele and genotype distribution of these two polymorphisms in the MVP gene, which were not associated with PFS or OS. However, a trend toward prolonged PFS was observed in patients carrying the heterozygous AG allele at the rs4788186 locus. These results suggest that rs1057451 and rs4788186 variants in the MVP gene are not associated with favorable therapeutic response to platinum or longer survival in Chinese Han patients affected by EOC. In addition, the data of the present study confirm that tetra-primer ARMS-PCR is a trustworthy and economical genotyping method. PMID:27073578

  1. Microbeam PIXE analysis of platinum resistant and sensitive ovarian cancer cells

    NASA Astrophysics Data System (ADS)

    Jeynes, J. C. G.; Bailey, M. J.; Coley, H.; Kirkby, K. J.; Jeynes, C.

    2010-06-01

    Microbeam PIXE was used to analyse platinum in single ovarian cancer cells. Carboplatin sensitive and resistant cells were grown as a monolayer on polypropylene and treated with either carboplatin or cisplatin. Pt from the carboplatin could not be detected. The Pt from cisplatin in the cells could be detected, and significantly more Zn was found in the resistant cells compared to the sensitive cells. The sensitive cells probably accumulated more cisplatin than the resistant ones.

  2. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer.

    PubMed

    Matassa, D S; Amoroso, M R; Lu, H; Avolio, R; Arzeni, D; Procaccini, C; Faicchia, D; Maddalena, F; Simeon, V; Agliarulo, I; Zanini, E; Mazzoccoli, C; Recchi, C; Stronach, E; Marone, G; Gabra, H; Matarese, G; Landriscina, M; Esposito, F

    2016-09-01

    Tumour cells have long been considered defective in mitochondrial respiration and mostly dependent on glycolytic metabolism. However, this assumption is currently challenged by several lines of evidence in a growing number of tumours. Ovarian cancer (OC) is one of the most lethal cancers worldwide, but it continues to be a poorly understood disease and its metabolic features are far to be elucidated. In this context, we investigated the role of tumour necrosis factor receptor-associated protein 1 (TRAP1), which is found upregulated in several cancer types and is a key modulator of tumour cell metabolism. Surprisingly, we found that TRAP1 expression inversely correlated with grade, stage and lower survival in a large cohort of OC patients. Accordingly, TRAP1 silencing induced resistance to cisplatin, resistant cells showed increased oxidative metabolism compared with their sensitive counterpart, and the bioenergetics cellular index of higher grade tumours indicated increased mitochondrial respiration. Strikingly, cisplatin resistance was reversible upon pharmacological inhibition of mitochondrial oxidative phosphorylation by metformin/oligomycin. At molecular level, increased oxidative metabolism in low TRAP1-expressing OC cells and tissues enhanced production of inflammatory mediators such as interleukin (IL)-6 and IL-8. Mechanistically, we identified members of the multidrug resistance complex (MDR) as key mediators of such metabolism-driven, inflammation-induced process. Indeed, treatment of OC cell lines with TNFα and IL6 induced a selective increase in the expression of TAP1 and multidrug resistance protein 1, whereas TAP1 silencing sensitized cells to cisplatin-induced apoptosis. Our results unveil a novel role for TRAP1 and oxidative metabolism in cancer progression and suggest the targeting of mitochondrial bioenergetics to increase cisplatin efficacy in human OC. PMID:27206315

  3. Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

    PubMed Central

    2011-01-01

    Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation. PMID:21745358

  4. Dual mTORC1/2 Inhibition as a Novel Strategy for the Resensitization and Treatment of Platinum-Resistant Ovarian Cancer.

    PubMed

    Musa, Fernanda; Alard, Amandine; David-West, Gizelka; Curtin, John P; Blank, Stephanie V; Schneider, Robert J

    2016-07-01

    There is considerable interest in the clinical development of inhibitors of mTOR complexes mTORC1 and 2. Because mTORC1 and its downstream mRNA translation effectors may protect against genotoxic DNA damage, we investigated the inhibition of mTORC1 and mTORC1/2 in the ability to reverse platinum resistance in tissue culture and in animal tumor models of serous ovarian cancer. Cell survival, tumor growth, PI3K-AKT-mTOR pathway signaling, DNA damage and repair response (DDR) gene expression, and translational control were all investigated. We show that platinum-resistant OVCAR-3 ovarian cancer cells are resensitized to low levels of carboplatin in culture by mTOR inhibition, demonstrating reduced survival after treatment with either mTORC1 inhibitor everolimus or mTORC1/2 inhibitor PP242. Platinum resistance is shown to be associated with activating phosphorylation of AKT and CHK1, inactivating phosphorylation of 4E-BP1, the negative regulator of eIF4E, which promotes increased cap-dependent mRNA translation and increased levels of CHK1 and BRCA1 proteins. Animals with platinum-resistant OVCAR-3 tumors treated with carboplatin plus mTORC1/2 inhibition had significantly longer median survival and strikingly reduced metastasis compared with animals treated with carboplatin plus everolimus, which inhibits only mTORC1. Reduced tumor growth, metastasis, and increased survival by mTORC1/2 inhibition with carboplatin treatment was associated with reduced AKT-activating phosphorylation and increased 4E-BP1 hypophosphorylation (activation). We conclude that mTORC1/2 inhibition is superior to mTORC1 inhibition in reversing platinum resistance in tumors and strongly impairs AKT activation, DNA repair responses, and translation, promoting improved survival in the background of platinum resistance. Mol Cancer Ther; 15(7); 1557-67. ©2016 AACR. PMID:27196780

  5. High ERCC1 expression is associated with platinum-resistance, but not survival in patients with epithelial ovarian cancer

    PubMed Central

    Du, Pei; Wang, Yifeng; Chen, Liquan; Gan, Yaping; Wu, Qinian

    2016-01-01

    The present study aimed to investigate the association between excision repair cross-complementation group 1 (ERCC1) expression and clinical resistance to platinum-based chemotherapy or clinical characteristics, including survival time, in patients with epithelial ovarian cancer (EOC). ERCC1 expression was determined by immunohistochemical staining in 92 tumor specimens from patients with EOC. The effect of ERCC1 expression on progression-free survival time (PFS) or overall survival time (OS), and its association with clinical resistance to platinum-based chemotherapy was investigated by Kaplan-Meier survival analysis, Cox regression analysis and the χ2 test. Of 92 patients with EOC, 89.13% (82/92) had ERCC1-positive tumors. The positive rate was significantly higher in platinum-resistant patients compared with those who were platinum-responding (P<0.05). The PFS and median OS were 12 and 30 months, respectively, in ERCC1 high expression patients, and 17 and 39 months, respectively, in ERCC1 low expression patients. However, there was no statistically significant difference in PFS (P=0.099) or OS (P=0.103) between the high and low expression groups. Furthermore, it was identified that ERCC1 was not an independent factor affecting the prognosis of patients with EOC based on Cox proportional hazards regression analysis. These results demonstrate that high ERCC1 expression is associated with resistance to platinum-based chemotherapy, but not with survival time, and ERCC1 protein expression is not an independent factor or the only factor affecting the prognosis of patients with EOC. PMID:27446360

  6. Hope, quality of life, and benefit from treatment in women having chemotherapy for platinum-resistant/refractory recurrent ovarian cancer: the gynecologic cancer intergroup symptom benefit study.

    PubMed

    Sjoquist, Katrin M; Friedlander, Michael L; O'Connell, Rachel L; Voysey, Merryn; King, Madeleine T; Stockler, Martin R; Oza, Amit M; Gillies, Kim; Martyn, Julie K; Butow, Phyllis N

    2013-01-01

    Chemotherapy for platinum-resistant/refractory ovarian cancer is motivated by the hope of benefit. We sought to determine the relationships between: (a) trait hope, expectation of symptom benefit from chemotherapy, and anxiety and depression; (b) hope and perceived efficacy of chemotherapy; and (c) unfulfilled hope (where expectations for benefit are not fulfilled) and depression. Methods. Adult patients enrolled within stage 1 of the Gynecologic Cancer Intergroup Symptom Benefit Study were included. Patient. Reported outcomes were collected from 126 women with predominantly platinum-resistant ovarian cancer at baseline, prior to the first four treatment cycles (12-16 weeks), and four weeks after completing chemotherapy or at disease progression, whichever came first. Associations were assessed with Spearman rank correlation coefficient (r) and odds ratio. Results. Trait hope and expectation of symptom benefit from chemotherapy were weakly correlated with each other (r = 0.25). Trait hope, but not expectation of symptom benefit, was negatively correlated with anxiety (r = -0.43) and depression (r = -0.50). The smaller the discrepancy between perceived and expected symptom benefit, the less likely the patient was to have scores indicative of depression (odds ratio: 0.68; 95% confidence interval: 0.49-0.96; p = .026). Conclusion. Trait hope and expectation of symptom benefit from chemotherapy appear to be distinct and independent of the aspects of quality of life and scores for depression. Hope did not appear to affect perceived efficacy of chemotherapy in alleviating symptoms, but women whose expectation of symptom benefit from chemotherapy was not fulfilled were more likely to have scores indicative of depression. It may be preferable to encourage hope toward achievable goals rather than toward benefits from chemotherapy. PMID:24107972

  7. Patient-Reported Outcome Results From the Open-Label Phase III AURELIA Trial Evaluating Bevacizumab-Containing Therapy for Platinum-Resistant Ovarian Cancer

    PubMed Central

    Stockler, Martin R.; Hilpert, Felix; Friedlander, Michael; King, Madeleine T.; Wenzel, Lari; Lee, Chee Khoon; Joly, Florence; de Gregorio, Nikolaus; Arranz, José Angel; Mirza, Mansoor Raza; Sorio, Roberto; Freudensprung, Ulrich; Sneller, Vesna; Hales, Gill; Pujade-Lauraine, Eric

    2014-01-01

    Purpose To determine the effects of bevacizumab on patient-reported outcomes (PROs; secondary end point) in the AURELIA trial. Patients and Methods Patients with platinum-resistant ovarian cancer were randomly assigned to chemotherapy alone (CT) or with bevacizumab (BEV-CT). PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Ovarian Cancer Module 28 (EORTC QLQ-OV28) and Functional Assessment of Cancer Therapy–Ovarian Cancer symptom index (FOSI) at baseline and every two or three cycles (8/9 weeks) until disease progression. The primary PRO hypothesis was that more patients receiving BEV-CT than CT would achieve at least a 15% (≥ 15-point) absolute improvement on the QLQ-OV28 abdominal/GI symptom subscale (items 31-36) at week 8/9. Patients with missing week 8/9 questionnaires were included as unimproved. Questionnaires from all assessments until disease progression were analyzed using mixed-model repeated-measures (MMRM) analysis. Sensitivity analyses were used to determine the effects of differing assumptions and methods for missing data. Results Baseline questionnaires were available from 89% of 361 randomly assigned patients. More BEV-CT than CT patients achieved a ≥ 15% improvement in abdominal/GI symptoms at week 8/9 (primary PRO end point, 21.9% v 9.3%; difference, 12.7%; 95% CI, 4.4 to 20.9; P = .002). MMRM analysis covering all time points also favored BEV-CT (difference, 6.4 points; 95% CI, 1.3 to 11.6; P = .015). More BEV-CT than CT patients achieved ≥ 15% improvement in FOSI at week 8/9 (12.2% v 3.1%; difference, 9.0%; 95% CI, 2.9% to 15.2%; P = .003). Sensitivity analyses gave similar results and conclusions. Conclusion Bevacizumab increased the proportion of patients achieving a 15% improvement in patient-reported abdominal/GI symptoms during chemotherapy for platinum-resistant ovarian cancer. PMID:24687829

  8. Pre-Treatment of platinum resistant ovarian cancer cells with an MMP-9/MMP-2 inhibitor prior to cisplatin enhances cytotoxicity as determined by high content screening.

    PubMed

    Laios, Alexandros; Mohamed, Bashir M; Kelly, Lynn; Flavin, Richard; Finn, Stephen; McEvoy, Lynda; Gallagher, Michael; Martin, Cara; Sheils, Orla; Ring, Martina; Davies, Anthony; Lawson, Margaret; Gleeson, Noreen; D'Arcy, Tom; d'Adhemar, Charles; Norris, Lucy; Langhe, Ream; Saadeh, Feras Abu; O'Leary, John J; O'Toole, Sharon A

    2013-01-01

    Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated. PMID:23340649

  9. Iron(III)-Salophene: An Organometallic Compound with Selective Cytotoxic and Anti-Proliferative Properties in Platinum-Resistant Ovarian Cancer Cells

    PubMed Central

    Singh, Rakesh K.; Strongin, Robert M.; McCourt, Carolyn K.; Brard, Laurent

    2008-01-01

    Background In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovarian cancer cell lines were investigated. Methodology/Principal Findings Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 µM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed chromatin and chromatin fragmentation. Fe-SP treatment led to the activation of markers of the extrinsic (Caspase-8) and intrinsic (Caspase-9) pathway of apoptosis as well as of executioner Caspase-3 while PARP-1 was deactivated. Fe-SP exerted effects as an anti-proliferative agent with an IC50 value of 300 nM and caused delayed progression of cells through S-phase phase of the cell cycle resulting in a complete S-phase arrest. When intra-peritoneally applied to rats Fe-SP did not show any systemic toxicity at concentrations that in preliminary trials were determined to be chemotherapeutic relevant doses in a rat ovarian cancer cell model. Conclusion/Significance The present report suggests that Fe-SP is a potent growth-suppressing agent in vitro for cell lines derived from ovarian cancer and a potential therapeutic drug to treat such tumors in vivo. PMID:18509533

  10. Randomized Multicenter Phase II Trial Comparing Two Schedules of Etirinotecan Pegol (NKTR-102) in Women With Recurrent Platinum-Resistant/Refractory Epithelial Ovarian Cancer

    PubMed Central

    Vergote, Ignace B.; Garcia, Agustin; Micha, John; Pippitt, Charles; Bendell, Johanna; Spitz, Daniel; Reed, Nicholas; Dark, Graham; Fracasso, Paula M.; Ibrahim, Emad N.; Armenio, Vincent A.; Duska, Linda; Poole, Chris; Gennigens, Christine; Dirix, Luc Y.; Leung, Abraham C.F.; Zhao, Carol; Soufi-Mahjoubi, Raoudha; Rustin, Gordon

    2013-01-01

    Purpose Etirinotecan pegol (NKTR-102) is a unique, long-acting topoisomerase-I inhibitor with prolonged systemic exposure to SN38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan. This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma. Patients and Methods A total of 71 eligible patients were randomly assigned to receive etirinotecan pegol 145 mg/m2 every 14 or 21 days until progression or unacceptable adverse events (AEs). The primary end point was objective response rate (ORR) by RECIST (version 1.0). Secondary end points included response by Gynecologic Cancer Intergroup criteria, duration of ORR, progression-free survival (PFS), and overall survival (OS). Results The overall confirmed ORR was 20% (95% CI, 10% to 30%): 20% for once every 14 days, and 19% for once every 21 days. Median response duration was 4.1 months for once every 14 days and 4.0 months for once every 21 days. Median PFS for every 14 and every 21 days was 4.1 and 5.3 months, respectively, and median OS was 10.0 and 11.7 months, respectively. Etirinotecan pegol was well tolerated, with the most common grade 3 to 4 AEs being dehydration (24%) and diarrhea (23%). Diarrhea, dehydration, nausea, and neutropenia were less frequent with the schedule of once every 21 days than with that of once every 14 days. Conclusion Both schedules of etirinotecan pegol showed activity in patients with heavily pretreated ovarian cancer, with encouraging ORR and PFS rates. The schedule of once every 21 days was better tolerated and had slightly longer PFS and OS rates. The treatment schedule of etirinotecan pegol 145 mg/m2 once every 21 days was selected for the expanded phase II study and is preferred for future phase III studies. These findings provide support to directly compare etirinotecan pegol versus one of the approved drugs (eg, pegylated liposomal doxorubicin or topotecan) in platinum-resistant

  11. Emodin augments cisplatin cytotoxicity in platinum-resistant ovarian cancer cells via ROS-dependent MRP1 downregulation.

    PubMed

    Ma, Jun; Yang, Jie; Wang, Chao; Zhang, Nan; Dong, Ying; Wang, Chengjie; Wang, Yu; Lin, Xinjian

    2014-01-01

    The intracellular level of reactive oxygen species (ROS) is closely associated with chemosensitivity of cancer cells. Overexpression of ATP binding cassette transporter MRP1 is correlated with resistance to platinum drugs. In this study, we tested the hypothesis that emodin, a potent ROS generator, may increase sensitivity of cisplatin-(cDDP-) resistant ovarian carcinoma cells to cDDP cytotoxicity via ROS-mediated suppression of MRP1 expression. Using the isogenic pair of the human ovarian carcinoma cell line COC1 and its cDDP resistant variant COC1/DDP, we found that ROS level in the cDDP-sensitive ovarian cancer cells was significantly higher than that in the cDDP-resistant cells. Emodin enhanced ROS production in COC1/DDP cells and consequently sensitized them to cDDP-induced apoptosis. These effects were reversed by addition of the antioxidant N-acetyl-L-cysteine (NAC). Cotreatment with emodin and cDDP inhibited the tumor growth in vivo by increasing tumor cell apoptosis. The emodin-enhanced cDDP cytotoxicity was attributable to downregulation of multidrug resistance-related protein 1 (MRP1) expression. Together, these results suggest that emodin could act as an adjunct to enhance the anticancer effect of cDDP likely through ROS-related downregulation of MRP1 expression, and may be of therapeutic potential in cDDP-refractory ovarian carcinomas. PMID:25580427

  12. An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer

    PubMed Central

    Janzen, D. M.; Tiourin, E.; Salehi, J. A.; Paik, D. Y.; Lu, J.; Pellegrini, M.; Memarzadeh, S.

    2015-01-01

    High-grade serous ovarian cancers (HGSCs) are deadly malignancies that relapse despite carboplatin chemotherapy. Here we show that 16 independent primary HGSC samples contain a CA125-negative population enriched for carboplatin-resistant cancer initiating cells. Transcriptome analysis reveals upregulation of homologous recombination DNA repair and anti-apoptotic signals in this population. While treatment with carboplatin enriches for CA125-negative cells, co-treatment with carboplatin and birinapant eliminates these cells in HGSCs expressing high levels of the inhibitor of apoptosis protein cIAP in the CA125-negative population. Birinapant sensitizes CA125-negative cells to carboplatin by mediating degradation of cIAP causing cleavage of caspase 8 and restoration of apoptosis. This co-therapy significantly improves disease-free survival in vivo compared with either therapy alone in tumour-bearing mice. These findings suggest that therapeutic strategies that target CA125-negative cells may be useful in the treatment of HGSC. PMID:26234182

  13. Cediranib Maleate and Olaparib or Standard Chemotherapy in Treating Patients With Recurrent Platinum-Resistant or -Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-09-13

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  14. Phase I Study of DMOT4039A, an Antibody-Drug Conjugate Targeting Mesothelin, in Patients with Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer.

    PubMed

    Weekes, Colin D; Lamberts, Laetitia E; Borad, Mitesh J; Voortman, Johannes; McWilliams, Robert R; Diamond, Jennifer R; de Vries, Elisabeth G E; Verheul, Henk M; Lieu, Christopher H; Kim, George P; Wang, Yulei; Scales, Suzie J; Samineni, Divya; Brunstein, Flavia; Choi, YounJeong; Maslyar, Daniel J; Colon-Otero, Gerardo

    2016-03-01

    DMOT4039A, a humanized anti-mesothelin mAb conjugated to the antimitotic agent monomethyl auristatin E (MMAE), was given to patients with pancreatic and ovarian cancer every 3 weeks (0.2-2.8 mg/kg; q3w) or weekly (0.8-1.2 mg/kg). A 3+3 design was used for dose escalation followed by expansion at the recommended phase II dose (RP2D) to evaluate safety and pharmacokinetics. Antitumor response was evaluated per RECIST 1.1 and serum CA19-9 or CA125 declines. Tumor mesothelin expression was determined by IHC. Seventy-one patients (40 pancreatic cancer; 31 ovarian cancer) were treated with DMOT4039A. For the q3w schedule (n = 54), the MTD and RP2D was 2.4 mg/kg, with dose-limiting toxicities of grade 3 hyperglycemia and grade 3 hypophosphatemia at 2.8 mg/kg. For the weekly schedule (n = 17), the maximum assessed dose was 1.2 mg/kg, with further dose escalations deferred because of toxicities limiting scheduled retreatment in later cycles, and therefore the RP2D level for the weekly regimen was determined to be 1 mg/kg. Across both schedules, the most common toxicities were gastrointestinal and constitutional. Treatment-related serious adverse events occurred in 6 patients; 4 patients continued treatment following dose reductions. Drug exposure as measured by antibody-conjugated MMAE and total antibody was generally dose proportional over all dose levels on both schedules. A total of 6 patients had confirmed partial responses (4 ovarian; 2 pancreatic) with DMOT4039A at 2.4 to 2.8 mg/kg i.v. q3w. DMOT4039A administered at doses up to 2.4 mg/kg q3w and 1.0 mg/kg weekly has a tolerable safety profile and antitumor activity in both pancreatic and ovarian cancer. PMID:26823490

  15. Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma

    PubMed Central

    Sung, Pi-Lin; Jan, Yi-Hua; Lin, Shih-Chieh; Huang, Chao-Cheng; Lin, Hao; Wen, Kuo-Chang; Chao, Kuan-Chong; Lai, Chiung-Ru; Wang, Peng-Hui; Chuang, Chi-Mu; Wu, Hua-Hsi; Twu, Nae-Fang; Yen, Ming-Shyen; Hsiao, Michael; Huang, Chi-Ying F.

    2016-01-01

    The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics. PMID:26716408

  16. Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma.

    PubMed

    Sung, Pi-Lin; Jan, Yi-Hua; Lin, Shih-Chieh; Huang, Chao-Cheng; Lin, Hao; Wen, Kuo-Chang; Chao, Kuan-Chong; Lai, Chiung-Ru; Wang, Peng-Hui; Chuang, Chi-Mu; Wu, Hua-Hsi; Twu, Nae-Fang; Yen, Ming-Shyen; Hsiao, Michael; Huang, Chi-Ying F

    2016-01-26

    The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics. PMID:26716408

  17. Ovarian cancer.

    PubMed

    Matulonis, Ursula A; Sood, Anil K; Fallowfield, Lesley; Howitt, Brooke E; Sehouli, Jalid; Karlan, Beth Y

    2016-01-01

    Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies. PMID:27558151

  18. Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

    PubMed

    Mignogna, Chiara; Staropoli, Nicoletta; Botta, Cirino; De Marco, Carmela; Rizzuto, Antonia; Morelli, Michele; Di Cello, Annalisa; Franco, Renato; Camastra, Caterina; Presta, Ivan; Malara, Natalia; Salvino, Angela; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Barni, Tullio; Donato, Giuseppe; Di Vito, Anna

    2016-01-01

    High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment. PMID:27209210

  19. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines

    PubMed Central

    Ishiguro, Kimiko; Zhu, Yong-Lian; Lin, Z. Ping; Penketh, Philip G.; Shyam, Krishnamurthy; Zhu, Rui; Baumann, Raymond P.; Sartorelli, Alan C.; Rutherford, Thomas J.; Ratner, Elena S.

    2016-01-01

    Although epithelial ovarian cancers (EOCs) are initially treated with platinum-based chemotherapy, EOCs vary in platinum responsiveness. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive EOC cell lines is valuable for development of therapeutic strategies to avoid platinum inefficacy and to exploit platinum sensitivity. TOV-21G devoid of FANCF expression, OV-90 and SKOV-3 were employed as examples of platinum-sensitive, platinum-intermediate and platinum-resistant cell lines, respectively. Antineoplastic agents examined included mitomycin C, doxorubicin, etoposide, gemcitabine, chlorambucil, paclitaxel, triapine and X-rays. Their effectiveness against cell lines was analyzed by clonogenic assays. Cytotoxic profiles of mitomycin C and carboplatin were similar, with mitomycin C exhibiting greater potency and selectivity against TOV-21G than carboplatin. Cytotoxic profiles of doxorubicin, etoposide and X-rays overlapped with that of carboplatin, while OV-90 overexpressing Rad51 was more resistant to chlorambucil than SKOV-3. The efficacy of paclitaxel and triapine was independent of platinum sensitivity or resistance. Consistent with these cytotoxic profiles, cisplatin/mitomycin C, triapine, and paclitaxel differed in the capacity to induce phosphorylation of H2AX, and produced unique inhibitory patterns of DNA/RNA syntheses in HL-60 human leukemia cells. Paclitaxel and triapine in combination produced additive antitumor effects in M109 murine lung carcinoma. In conclusion, mitomycin C is potentially more effective against Fanconi anemia pathway-deficient EOCs than carboplatin. Doxorubicin and etoposide, because of their overlapping cytotoxic properties with carboplatin, are unlikely to be efficacious against platinum-refractory EOCs. Paclitaxel and triapine are effective regardless of platinum sensitivity status, and promising in combination for both platinum-sensitive and platinum-refractory EOCs

  20. Ovarian Cancer

    MedlinePlus

    Ovarian Cancer There are five main types of cancer that affect a woman’s reproductive organs: cervical, ovarian, uterine, ... rare fallopian tube cancer.) This fact sheet about ovarian cancer is part of the Centers for Disease Control ...

  1. Ovarian Cancer

    MedlinePlus

    ... deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian ...

  2. Ovarian cancer

    MedlinePlus

    Cancer - ovaries ... Ovarian cancer is the fifth most common cancer among women. It causes more deaths than any other type of female reproductive organ cancer. The cause of ovarian cancer is unknown. Risk ...

  3. Ovarian cancer

    MedlinePlus

    ... of ovarian cancer Already been diagnosed with ovarian cancer to determine how well treatment is working Other tests that may be done include: Complete blood count and blood chemistry Pregnancy test (serum HCG) CT or MRI of ...

  4. OVARIAN CANCER

    PubMed Central

    Cho, Kathleen R.; Shih, Ie-Ming

    2009-01-01

    Ovarian carcinomas are a heterogeneous group of neoplasms traditionally sub-classified based on type and degree of differentiation. Although current clinical management of ovarian carcinoma largely fails to take this heterogeneity into account, it is becoming evident that each major histological type has characteristic genetic defects that deregulate specific signaling pathways in the tumor cells. Moreover, within the most common histological types, the molecular pathogenesis of low-grade versus high-grade tumors appears to be largely distinct. Mouse models of ovarian carcinoma have been developed that recapitulate many of the morphological features, biological behavior, and gene expression patterns of selected subtypes of ovarian cancer. Such models will likely prove useful for studying ovarian cancer biology and for pre-clinical testing of molecularly targeted therapeutics, which may ultimately lead to better clinical outcomes for women with ovarian cancer. PMID:18842102

  5. The prognostic significance of specific HOX gene expression patterns in ovarian cancer.

    PubMed

    Kelly, Zoe; Moller-Levet, Carla; McGrath, Sophie; Butler-Manuel, Simon; Kavitha Madhuri, Thumuluru; Kierzek, Andrzej M; Pandha, Hardev; Morgan, Richard; Michael, Agnieszka

    2016-10-01

    HOX genes are vital for all aspects of mammalian growth and differentiation, and their dysregulated expression is related to ovarian carcinogenesis. The aim of the current study was to establish the prognostic value of HOX dysregulation as well as its role in platinum resistance. The potential to target HOX proteins through the HOX/PBX interaction was also explored in the context of platinum resistance. HOX gene expression was determined in ovarian cancer cell lines and primary EOCs by QPCR, and compared to expression in normal ovarian epithelium and fallopian tube tissue samples. Statistical analysis included one-way ANOVA and t-tests, using statistical software R and GraphPad. The analysis identified 36 of the 39 HOX genes as being overexpressed in high grade serous EOC compared to normal tissue. We detected a molecular HOX gene-signature that predicted poor outcome. Overexpression of HOXB4 and HOXB9 was identified in high grade serous cell lines after platinum resistance developed. Targeting the HOX/PBX dimer with the HXR9 peptide enhanced the cytotoxicity of cisplatin in platinum-resistant ovarian cancer. In conclusion, this study has shown the HOX genes are highly dysregulated in ovarian cancer with high expression of HOXA13, B6, C13, D1 and D13 being predictive of poor clinical outcome. Targeting the HOX/PBX dimer in platinum-resistant cancer represents a potentially new therapeutic option that should be further developed and tested in clinical trials. PMID:27225067

  6. Ovarian Cancer FAQ

    MedlinePlus

    ... Ovarian Cancer Patient Education FAQs Ovarian Cancer Patient Education Pamphlets - Spanish Ovarian Cancer FAQ096, April 2015 PDF Format Ovarian ... Your Practice Patient Safety & Quality Payment Reform (MACRA) Education & Events Annual ... Pamphlets Teen Health About ACOG About Us Leadership & ...

  7. What Is Ovarian Cancer?

    MedlinePlus

    ... the key statistics about ovarian cancer? What is ovarian cancer? Cancer starts when cells in the body begin ... section . Other cancers that are similar to epithelial ovarian cancer Primary peritoneal carcinoma Primary peritoneal carcinoma (PPC) is ...

  8. Targeting Aldehyde Dehydrogenase Cancer Stem Cells in Ovarian Cancer

    PubMed Central

    Landen, Charles N.; Goodman, Blake; Katre, Ashwini A.; Steg, Adam D.; Nick, Alpa M.; Stone, Rebecca L.; Miller, Lance D.; Mejia, Pablo Vivas; Jennings, Nicolas B.; Gershenson, David M.; Bast, Robert C.; Coleman, Robert L.; Lopez-Berestein, Gabriel; Sood, Anil K.

    2010-01-01

    Aldehyde dehydrogenase-1A1 (ALDH1A1) expression characterizes a subpopulation of cells with tumor initiating or cancer stem cell properties in several malignancies. Our goal was to characterize the phenotype of ALDH1A1-positive ovarian cancer cells and examine the biological effects of ALDH1A1 gene silencing. In our analysis of multiple ovarian cancer cell lines, we found that ALDH1A1 expression and activity was significantly higher in taxane and platinum-resistant cell lines. In patient samples, 72.9% of ovarian cancers had ALDH1A1 expression, in whom the percent of ALDH1A1-positive cells correlated negatively with progression-free survival (6.05 v 13.81 months, p<0.035). Subpopulations of A2780cp20 cells with ALDH1A1 activity were isolated for orthotopic tumor initiating studies, where tumorigenicity was approximately 50-fold higher with ALDH1A1-positive cells. Interestingly, tumors derived from ALDH1A1-positive cells gave rise to both ALDH1A1-positive and ALDH1A1-negative populations, but ALDH1A1-negative cells could not generate ALDH1A1-positive cells. In an in vivo orthotopic mouse model of ovarian cancer, ALDH1A1 silencing using nanoliposomal siRNA sensitized both taxane- and platinum-resistant cell lines to chemotherapy, significantly reducing tumor growth in mice compared to chemotherapy alone (a 74–90% reduction, p<0.015). These data demonstrate that the ALDH1A1 subpopulation is associated with chemoresistance and outcome in ovarian cancer patients, and targeting ALDH1A1 sensitizes resistant cells to chemotherapy. ALDH1A1-positive cells have enhanced, but not absolute, tumorigenicity, but do have differentiation capacity lacking in ALDH1A1-negative cells. This enzyme may be important for identification and targeting of chemoresistant cell populations in ovarian cancer. PMID:20889728

  9. Symptoms of Ovarian Cancer

    MedlinePlus

    ... Informed Cancer Home What Are the Symptoms of Ovarian Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Gynecologic cancer symptoms diaries Ovarian cancer may cause one or more of these signs ...

  10. ALDH1A1 Maintains Ovarian Cancer Stem Cell-Like Properties by Altered Regulation of Cell Cycle Checkpoint and DNA Repair Network Signaling

    PubMed Central

    Meng, Erhong; Mitra, Aparna; Tripathi, Kaushlendra; Finan, Michael A.; Scalici, Jennifer; McClellan, Steve; da Silva, Luciana Madeira; Reed, Eddie; Shevde, Lalita A.; Palle, Komaraiah; Rocconi, Rodney P.

    2014-01-01

    Objective Aldehyde dehydrogenase (ALDH) expressing cells have been characterized as possessing stem cell-like properties. We evaluated ALDH+ ovarian cancer stem cell-like properties and their role in platinum resistance. Methods Isogenic ovarian cancer cell lines for platinum sensitivity (A2780) and platinum resistant (A2780/CP70) as well as ascites from ovarian cancer patients were analyzed for ALDH+ by flow cytometry to determine its association to platinum resistance, recurrence and survival. A stable shRNA knockdown model for ALDH1A1 was utilized to determine its effect on cancer stem cell-like properties, cell cycle checkpoints, and DNA repair mediators. Results ALDH status directly correlated to platinum resistance in primary ovarian cancer samples obtained from ascites. Patients with ALDHHIGH displayed significantly lower progression free survival than the patients with ALDHLOW cells (9 vs. 3 months, respectively p<0.01). ALDH1A1-knockdown significantly attenuated clonogenic potential, PARP-1 protein levels, and reversed inherent platinum resistance. ALDH1A1-knockdown resulted in dramatic decrease of KLF4 and p21 protein levels thereby leading to S and G2 phase accumulation of cells. Increases in S and G2 cells demonstrated increased expression of replication stress associated Fanconi Anemia DNA repair proteins (FANCD2, FANCJ) and replication checkpoint (pS317 Chk1) were affected. ALDH1A1-knockdown induced DNA damage, evidenced by robust induction of γ-H2AX and BAX mediated apoptosis, with significant increases in BRCA1 expression, suggesting ALDH1A1-dependent regulation of cell cycle checkpoints and DNA repair networks in ovarian cancer stem-like cells. Conclusion This data suggests that ovarian cancer cells expressing ALDH1A1 may maintain platinum resistance by altered regulation of cell cycle checkpoint and DNA repair network signaling. PMID:25216266

  11. Ovarian Cancer Fact Sheet

    MedlinePlus

    ... States, ovarian cancer is the eighth most common cancer and the fifth leading cause of cancer death. Around one in every 60 ... States, ovarian cancer is the eighth most common cancer and the fifth leading cause of cancer death. Are some women more at ...

  12. Up-regulation of stromal versican expression in advanced stage serous ovarian cancer

    PubMed Central

    Ghosh, Sue; Albitar, Lina; LeBaron, Richard; Welch, William R.; Samimi, Goli; Birrer, Michael J.; Berkowitz, Ross S.; Mok, Samuel C.

    2010-01-01

    Objective The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. Methods Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n=111) and CD31 (n= 56) were done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. Results Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. Conclusions VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression free survival and platinum resistance. PMID:20619446

  13. Gemcitabine in patients with ovarian cancer.

    PubMed

    Poveda, Andres

    2005-01-01

    Standard first-line treatment of ovarian cancer (OC) consists of platinum-taxane combined chemotherapy. However, this regimen only cures about 25% of women with OC. Phase II studies have shown that platinum-gemcitabine doublet and platinum-taxane-gemcitabine triplet regimens are active first-line chemotherapy in advanced OC, with overall response rates (ORR) above 55%. Several phase III studies of gemcitabine-based doublet and triplet chemotherapy in OC are currently underway. Preliminary data show that these regimens are well-tolerated, with manageable haematological toxicity, and the efficacy results are eagerly awaited. Gemcitabine is also active as second-line monotherapy in women with recurrent OC, and studies combining gemcitabine with paclitaxel, docetaxel, liposomal doxorubicin or topotecan resulted in higher ORR than gemcitabine alone. Gemcitabine-cisplatin and gemcitabine-carboplatin are active in women with platinum-resistant recurrent OC suggesting in vivo synergy between these two classes of drug. These studies show that gemcitabine-based chemotherapy may have an important role as second-line treatment in women with platinum-resistant OC. Gemcitabine combinations are also highly recommended as they avoid the problems of neurotoxicity and alopecia seen with other regimens. In order to respect the quality of life of women with recurrent OC, assessment of prognostic factors is recommended so that the most appropriate chemotherapy can be administered. PMID:16360545

  14. Claudin and ovarian cancer

    PubMed Central

    Bose, Chinmoy K.; Mukhopadhyay, Ashis

    2010-01-01

    Claudins are a family of proteins and the most important component of the tight junction. They constitute a paracellular barrier that controls the flow of molecules in the intercellular space of an epithelium. Although it seems that claudin should be down regulated in cancer cell, some claudins are, in fact highly elevated in various human cancers, including ovarian cancer. Whereas the functional significance of claudin overexpression in ovarian carcinoma is unclear, these proteins are important for migration, invasion, and survival of ovarian cancer cells. They clearly represent a general pathway in tumorigenesis, are a novel marker for ovarian cancer and may become a target for therapy or diagnosis of this disease. PMID:24591894

  15. Claudin and ovarian cancer.

    PubMed

    Bose, Chinmoy K; Mukhopadhyay, Ashis

    2010-01-01

    Claudins are a family of proteins and the most important component of the tight junction. They constitute a paracellular barrier that controls the flow of molecules in the intercellular space of an epithelium. Although it seems that claudin should be down regulated in cancer cell, some claudins are, in fact highly elevated in various human cancers, including ovarian cancer. Whereas the functional significance of claudin overexpression in ovarian carcinoma is unclear, these proteins are important for migration, invasion, and survival of ovarian cancer cells. They clearly represent a general pathway in tumorigenesis, are a novel marker for ovarian cancer and may become a target for therapy or diagnosis of this disease. PMID:24591894

  16. Ovarian Cancer Stage IV

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IV Add to My Pictures View /Download : ... 1200x1335 View Download Large: 2400x2670 View Download Title: Ovarian Cancer Stage IV Description: Drawing of stage IV shows ...

  17. Ovarian Cancer Stage IIIC

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage IIIC Add to My Pictures View /Download : ... 1530x1350 View Download Large: 3060x2700 View Download Title: Ovarian Cancer Stage IIIC Description: Drawing of stage IIIC shows ...

  18. Ovarian Cancer Stage II

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage II Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage II Description: Three-panel drawing of stage ...

  19. Ovarian Cancer Stage I

    MedlinePlus

    ... hyphen, e.g. -historical Searches are case-insensitive Ovarian Cancer Stage I Add to My Pictures View /Download : ... 1650x675 View Download Large: 3300x1350 View Download Title: Ovarian Cancer Stage I Description: Three-panel drawing of stage ...

  20. T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin.

    PubMed

    Dziegielewska, Barbara; Casarez, Eli V; Yang, Wesley Z; Gray, Lloyd S; Dziegielewski, Jaroslaw; Slack-Davis, Jill K

    2016-03-01

    Ovarian cancer is the deadliest gynecologic cancer, due in large part to the diagnosis of advanced stage disease, the development of platinum resistance, and inadequate treatment alternatives. Recent studies by our group and others have shown that T-type calcium (Ca(2+)) channels play a reinforcing role in cancer cell proliferation, cell-cycle progression, and apoptosis evasion. Therefore, we investigated whether T-type Ca(2+) channels affect ovarian tumor growth and response to platinum agents. Inhibition of T-type Ca(2+) channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer cells with a simultaneous increase in apoptosis, which was accompanied by decreased expression of the antiapoptotic gene survivin (BIRC5). Analysis of intracellular signaling revealed mibefradil reduced AKT phosphorylation, increased the levels and nuclear retention of FOXO transcription factors that repress BIRC5 expression, and decreased the expression of FOXM1, which promotes BIRC5 expression. Combining carboplatin with mibefradil synergistically increased apoptosis in vitro. Importantly, mibefradil rendered platinum-resistant ovarian tumors sensitive to carboplatin in a mouse model of peritoneal metastasis. Together, the data provide rationale for future use of T-type channel antagonists together with platinum agents for the treatment of ovarian cancer. Mol Cancer Ther; 15(3); 460-70. ©2016 AACR. PMID:26832797

  1. Can Ovarian Cancer Be Found Early?

    MedlinePlus

    ... Topic Signs and symptoms of ovarian cancer Can ovarian cancer be found early? About 20% of ovarian cancers ... cancer in its earliest stage. Ways to find ovarian cancer early Regular women's health exams During a pelvic ...

  2. Epithelial ovarian cancer: An overview

    PubMed Central

    Desai, Arpita; Xu, Jingyao; Aysola, Kartik; Qin, Yunlong; Okoli, Chika; Hariprasad, Ravipati; Chinemerem, Ugorji; Gates, Candace; Reddy, Avinash; Danner, Omar; Franklin, Geary; Ngozi, Anachebe; Cantuaria, Guilherme; Singh, Karan; Grizzle, William; Landen, Charles; Partridge, Edward E; Rice, Valerie Montgomery; Reddy, E Shyam P; Rao, Veena N

    2014-01-01

    Ovarian cancer is the second most common gynecological cancer and the leading cause of death in the United States. In this article we review the diagnosis and current management of epithelial ovarian cancer which accounts for over 95 percent of the ovarian malignancies. We will present various theories about the potential origin of ovarian malignancies. We will discuss the genetic anomalies and syndromes that may cause ovarian cancers with emphasis on Breast cancer type 1/2 mutations. The pathology and pathogenesis of ovarian carcinoma will also be presented. Lastly, we provide a comprehensive overview of treatment strategies and staging of ovarian cancer, conclusions and future directions. PMID:25525571

  3. Ovarian Cancer Statistics

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 22,280 % of All New Cancer Cases 1.3% Estimated Deaths in 2016 14,240 % of All Cancer ... of This Cancer : In 2013, there were an estimated 195,767 women living with ovarian cancer in ...

  4. National Ovarian Cancer Coalition

    MedlinePlus

    ... ovarian cancer Read More View More News Upcoming Events Fabric Extravaganza! September 09, 2016 @ 12:00PM Hosted ... Roxy and Dukes Roadhouse View All Our Upcoming Events Latest from the Blog: Hailey's Story How her ...

  5. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance.

    PubMed

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-11-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  6. DNA-PK Mediates AKT Activation and Apoptosis Inhibition in Clinically Acquired Platinum Resistance12

    PubMed Central

    Stronach, Euan A; Chen, Michelle; Maginn, Elaina N; Agarwal, Roshan; Mills, Gordon B; Wasan, Harpreet; Gabra, Hani

    2011-01-01

    Clinical resistance to chemotherapy is a frequent event in cancer treatment and is closely linked to poor outcome. High-grade serous (HGS) ovarian cancer is characterized by p53 mutation and high levels of genomic instability. Treatment includes platinum-based chemotherapy and initial response rates are high; however, resistance is frequently acquired, at which point treatment options are largely palliative. Recent data indicate that platinum-resistant clones exist within the sensitive primary tumor at presentation, implying resistant cell selection after treatment with platinum chemotherapy. The AKT pathway is central to cell survival and has been implicated in platinum resistance. Here, we show that platinum exposure induces an AKT-dependent, prosurvival, DNA damage response in clinically platinum-resistant but not platinum-sensitive cells. AKT relocates to the nucleus of resistant cells where it is phosphorylated specifically on S473 by DNA-dependent protein kinase (DNA-PK), and this activation inhibits cisplatin-mediated apoptosis. Inhibition of DNA-PK or AKT, but not mTORC2, restores platinum sensitivity in a panel of clinically resistant HGS ovarian cancer cell lines: we also demonstrate these effects in other tumor types. Resensitization is associated with prevention of AKT-mediated BAD phosphorylation. Strikingly, in patient-matched sensitive cells, we do not see enhanced apoptosis on combining cisplatin with AKT or DNA-PK inhibition. Insulin-mediated activation of AKT is unaffected by DNA-PK inhibitor treatment, suggesting that this effect is restricted to DNA damage-mediated activation of AKT and that, clinically, DNA-PK inhibition might prevent platinum-induced AKT activation without interfering with normal glucose homeostasis, an unwanted toxicity of direct AKT inhibitors. PMID:22131882

  7. Cystathionine Beta-Synthase (CBS) Contributes to Advanced Ovarian Cancer Progression and Drug Resistance

    PubMed Central

    Giri, Karuna; Lanza, Ian R.; Nair, K. Sreekumar; Jennings, Nicholas B.; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Basal, Eati; Weaver, Amy L.; Visscher, Daniel W.; Cliby, William; Sood, Anil K.; Bhattacharya, Resham; Mukherjee, Priyabrata

    2013-01-01

    Background Epithelial ovarian cancer is the leading cause of gynecologic cancer deaths. Most patients respond initially to platinum-based chemotherapy after surgical debulking, however relapse is very common and ultimately platinum resistance emerges. Understanding the mechanism of tumor growth, metastasis and drug resistant relapse will profoundly impact the therapeutic management of ovarian cancer. Methods/Principal Findings Using patient tissue microarray (TMA), in vitro and in vivo studies we report a role of of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme in ovarian carcinoma. We report here that the expression of cystathionine-beta-synthase (CBS), a sulfur metabolism enzyme, is common in primary serous ovarian carcinoma. The in vitro effects of CBS silencing can be reversed by exogenous supplementation with the GSH and H2S producing chemical Na2S. Silencing CBS in a cisplatin resistant orthotopic model in vivo by nanoliposomal delivery of CBS siRNA inhibits tumor growth, reduces nodule formation and sensitizes ovarian cancer cells to cisplatin. The effects were further corroborated by immunohistochemistry that demonstrates a reduction of H&E, Ki-67 and CD31 positive cells in si-RNA treated as compared to scrambled-RNA treated animals. Furthermore, CBS also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial ROS production, oxygen consumption and ATP generation. This study reports an important role of CBS in promoting ovarian tumor growth and maintaining drug resistant phenotype by controlling cellular redox behavior and regulating mitochondrial bioenergetics. Conclusion The present investigation highlights CBS as a potential therapeutic target in relapsed and platinum resistant ovarian cancer. PMID:24236104

  8. Ixabepilone and Liposomal Doxorubicin in Advanced Ovarian Cancer

    ClinicalTrials.gov

    2016-02-11

    Fallopian Tube Cancer; Female Reproductive Cancer; Recurrent Breast Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer

  9. Immunotherapy in ovarian cancer

    PubMed Central

    Mantia-Smaldone, Gina M.; Corr, Bradley; Chu, Christina S.

    2012-01-01

    Ovarian cancer is the most deadly gynecologic malignancy, with more than 15,000 deaths anticipated in 2012.1 While approximately 80% of patients will respond to frontline chemotherapy, more than 60% of patients will experience disease recurrence and only 44% will be alive at 5 years.1,2 Host anti-tumor immune responses are associated with a significant improvement in overall survival for women with ovarian cancer.3,4 By bolstering these responses, it may therefore be possible to significantly influence the prognosis of women with this lethal disease. In this review, we will focus on innovative immune-based strategies which are currently being investigated in the treatment of ovarian cancer. PMID:22906947

  10. The E3 ubiquitin ligase EDD is an adverse prognostic factor for serous epithelial ovarian cancer and modulates cisplatin resistance in vitro.

    PubMed

    O'Brien, P M; Davies, M J; Scurry, J P; Smith, A N; Barton, C A; Henderson, M J; Saunders, D N; Gloss, B S; Patterson, K I; Clancy, J L; Heinzelmann-Schwarz, V A; Murali, Rajmohan; Scolyer, R A; Zeng, Y; Williams, E D; Scurr, L; Defazio, A; Quinn, D I; Watts, C K W; Hacker, N F; Henshall, S M; Sutherland, R L

    2008-03-25

    Despite a high initial response rate to first-line platinum/paclitaxel chemotherapy, most women with epithelial ovarian cancer relapse with recurrent disease that becomes refractory to further cytotoxic treatment. We have previously shown that the E3 ubiquitin ligase, EDD, a regulator of DNA damage responses, is amplified and overexpressed in serous ovarian carcinoma. Given that DNA damage pathways are linked to platinum resistance, the aim of this study was to determine if EDD expression was associated with disease recurrence and platinum sensitivity in serous ovarian cancer. High nuclear EDD expression, as determined by immunohistochemistry in a cohort of 151 women with serous ovarian carcinoma, was associated with an approximately two-fold increased risk of disease recurrence and death in patients who initially responded to first-line chemotherapy, independently of disease stage and suboptimal debulking. Although EDD expression was not directly correlated with relative cisplatin sensitivity of ovarian cancer cell lines, sensitivity to cisplatin was partially restored in platinum-resistant A2780-cp70 ovarian cancer cells following siRNA-mediated knockdown of EDD expression. These results identify EDD as a new independent prognostic marker for outcome in serous ovarian cancer, and suggest that pathways involving EDD, including DNA damage responses, may represent new therapeutic targets for chemoresistant ovarian cancer. PMID:18349819

  11. [ERCC1 as a Marker of Ovarian Cancer Resistance to Platinum Drugs].

    PubMed

    Bogush, T A; Popova, A S; Dudko, E A; Bogush, E A; Tyulyandina, A S; Tyulyandin, S A; Davydov, M I

    2015-01-01

    The review is concerned with the crucial marker of nucleotide excision repair ERCC1 and its contribution to platinum resistance of ovarian cancer. All the variants of the laboratory and clinical ERCC1 assessment in the ovarian cancer tissue (single nucleotide polymorphisms of the ERCC1 gene, levels of mRNA or protein) are considered. Data on the prognostic and predictive value of ERCC1 as a marker of the response to platinum-based therapy in ovarian cancer are systematized. The authors discuss the possible causes of heterogeneity of the results and emphasize the necessity of a unified and integrated approach to evaluation of ERCC1 in the tumor. The publications cited in the Search Engine Pub Med up to January 2015 were analyzed. PMID:26415382

  12. Denileukin Diftitox Used in Treating Patients With Advanced Refractory Ovarian Cancer, Primary Peritoneal Carcinoma, or Epithelial Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-05-02

    Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  13. [Individualized treatment for ovarian cancer may become possible].

    PubMed

    Kjölhede, Preben; Dahm-Kähler, Pernilla; Tholander, Bengt; Åvall Lundqvist, Elisabeth

    2015-01-01

    Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy in developed countries. Several promising steps toward individualized therapy have been taken recently due to increased knowledge of molecular biology. Multidisciplinary conferences for treatment planning and the centralization to tertiary surgical centers improve quality of surgery and survival. The primary treatment of EOC is radical surgery followed by adjuvant chemotherapy with carboplatin and paclitaxel. Bevacizumab added to the chemotherapy and used as maintenance treatment is standard in the primary treatment of patients with residual tumor or inoperable patients. The PARP inhibitor olaparib is recommended as maintenance treatment of women with platinum sensitive relapsed BRCA mutated high-grade serous EOC who have responded to platinum-based chemotherapy. BRCA testing should be offered to women with EOC. In platinum-resistant recurrence addition of bevacizumab to chemotherapy should be considered. PMID:26646960

  14. Pharmacotherapy for recurrent ovarian cancer: current status and future perspectives.

    PubMed

    Matsumoto, Koji; Onda, Takashi; Yaegashi, Nobuo

    2015-05-01

    Several 'lines of therapy' that utilize cytotoxic agents and are driven by platinum-free intervals are the current standard of care for patients with recurrent ovarian cancer. For patients with platinum-resistant disease, single agent chemotherapy (pegylated liposomal doxorubicin, topotecan, gemcitabine or weekly paclitaxel) is the standard of care. For patients with platinum-sensitive disease, combination chemotherapy (carboplatin plus paclitaxel, pegylated liposomal doxorubicin or gemcitabine) is the standard of care. In addition, antiangiogenic therapy using bevacizumab is an established option. Future directions could include 'lines of therapy' with biologic agents driven by specific biologic targets. Data from antiangiogenic agents (trebananib, pazopanib and cediranib), antifolate drugs (farletuzumab and vintafolide), poly(ADP-ribose) polymerase inhibitors (olaparib and veliparib), mTOR inhibitors (everolimus and temsirolimus) and immune editing agents (nivolumab) have been summarized in this review. PMID:25765457

  15. Do We Know What Causes Ovarian Cancer?

    MedlinePlus

    ... ovarian cancer be prevented? Do we know what causes ovarian cancer? We don’t yet know exactly what causes ... Another theory is that male hormones (androgens) can cause ovarian cancer. Researchers have made great progress in understanding how ...

  16. Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer

    PubMed Central

    Wang, Sisi; Zhang, Hongyong; Scharadin, Tiffany M.; Zimmermann, Maike; Hu, Bin; Pan, Amy Wang; Vinall, Ruth; Lin, Tzu-yin; Cimino, George; Chain, Patrick; Vuyisich, Momchilo; Gleasner, Cheryl; Mcmurry, Kim; Malfatti, Michael; Turteltaub, Kenneth; de Vere White, Ralph; Pan, Chong-xian; Henderson, Paul T.

    2016-01-01

    We report herein the development, functional and molecular characterization of an isogenic, paired bladder cancer cell culture model system for studying platinum drug resistance. The 5637 human bladder cancer cell line was cultured over ten months with stepwise increases in oxaliplatin concentration to generate a drug resistant 5637R sub cell line. The MTT assay was used to measure the cytotoxicity of several bladder cancer drugs. Liquid scintillation counting allowed quantification of cellular drug uptake and efflux of radiolabeled oxaliplatin and carboplatin. The impact of intracellular drug inactivation was assessed by chemical modulation of glutathione levels. Oxaliplatin- and carboplatin-DNA adduct formation and repair was measured using accelerator mass spectrometry. Resistance factors including apoptosis, growth factor signaling and others were assessed with RNAseq of both cell lines and included confirmation of selected transcripts by RT-PCR. Oxaliplatin, carboplatin, cisplatin and gemcitabine were significantly less cytotoxic to 5637R cells compared to the 5637 cells. In contrast, doxorubicin, methotrexate and vinblastine had no cell line dependent difference in cytotoxicity. Upon exposure to therapeutically relevant doses of oxaliplatin, 5637R cells had lower drug-DNA adduct levels than 5637 cells. This difference was partially accounted for by pre-DNA damage mechanisms such as drug uptake and intracellular inactivation by glutathione, as well as faster oxaliplatin-DNA adduct repair. In contrast, both cell lines had no significant differences in carboplatin cell uptake, efflux and drug-DNA adduct formation and repair, suggesting distinct resistance mechanisms for these two closely related drugs. The functional studies were augmented by RNAseq analysis, which demonstrated a significant change in expression of 83 transcripts, including 50 known genes and 22 novel transcripts. Most of the transcripts were not previously associated with bladder cancer

  17. Molecular Dissection of Induced Platinum Resistance through Functional and Gene Expression Analysis in a Cell Culture Model of Bladder Cancer

    DOE PAGESBeta

    Wang, Sisi; Zhang, Hongyong; Scharadin, Tiffany M.; Zimmermann, Maike; Hu, Bin; Pan, Amy Wang; Vinall, Ruth; Lin, Tzu-yin; Cimino, George; Chain, Patrick; et al

    2016-01-22

    Here, we report the development, functional and molecular characterization of an isogenic, paired bladder cancer cell culture model system for studying platinum drug resistance. The 5637 human bladder cancer cell line was cultured over ten months with stepwise increases in oxaliplatin concentration to generate a drug resistant 5637R sub cell line. The MTT assay was used to measure the cytotoxicity of several bladder cancer drugs. Liquid scintillation counting allowed quantification of cellular drug uptake and efflux of radiolabeled oxaliplatin and carboplatin. The impact of intracellular drug inactivation was assessed by chemical modulation of glutathione levels. Oxaliplatin- and carboplatin-DNA adduct formationmore » and repair was measured using accelerator mass spectrometry. Resistance factors including apoptosis, growth factor signaling and others were assessed with RNAseq of both cell lines and included confirmation of selected transcripts by RT-PCR. Oxaliplatin, carboplatin, cisplatin and gemcitabine were significantly less cytotoxic to 5637R cells compared to the 5637 cells. In contrast, doxorubicin, methotrexate and vinblastine had no cell line dependent difference in cytotoxicity. Upon exposure to therapeutically relevant doses of oxaliplatin, 5637R cells had lower drug-DNA adduct levels than 5637 cells. This difference was partially accounted for by pre-DNA damage mechanisms such as drug uptake and intracellular inactivation by glutathione, as well as faster oxaliplatin-DNA adduct repair. In contrast, both cell lines had no significant differences in carboplatin cell uptake, efflux and drug-DNA adduct formation and repair, suggesting distinct resistance mechanisms for these two closely related drugs. The functional studies were augmented by RNAseq analysis, which demonstrated a significant change in expression of 83 transcripts, including 50 known genes and 22 novel transcripts. Most of the transcripts were not previously associated with bladder cancer

  18. Introduction to managing patients with recurrent ovarian cancer

    PubMed Central

    Gabra, Hani

    2015-01-01

    Ovarian cancer is the 5th most common cancer found in women in the UK. It is the leading cause of death from gynaecological cancer, and is the 4th most common cause of cancer death among UK women. Similar to the majority of other cancers, relative survival rates for ovarian cancer are improving, although 5-year mortality rates remain stubbornly low. The stage of the disease at diagnosis is the single most important determinant of ovarian cancer survival, as many patients first present with advanced disease. Treatment of ovarian cancer involves a combination of ‘upfront’ primary surgery followed by chemotherapy. Platinum/taxane-based chemotherapy is the recommended standard-of-care first-line chemotherapy, but the majority of patients will relapse with drug-resistant disease within 3-5 years. However, not all patients can continue with platinum combination therapies due to loss of activity or toxicity-related issues, including hypersensitivity, neurotoxicity, alopecia and ototoxicity. Therefore the choice of second-line chemotherapy must take into account factors such as platinum-free treatment interval (PFI); patient's performance status; current symptoms; history of and likely future toxicities while on chemotherapy; dosing schedule requirement; and cost of treatment. A consensus in 2010 established 4 distinct subgroups within the ROC patient population based on the PFI: (platinum sensitive <12 months, partially platinum sensitive 6-12 months, platinum resistant <6 months, and refractory disease ≤4 weeks). Within patients with platinum sensitive disease, those with partially platinum sensitive disease remain the most clinically challenging to manage effectively. Non-platinum based combination therapies, in particular trabectedin with pegylated liposomal doxorubicin (PLD), offers new options together with a significant survival advantage relative to PLD alone for these patients. PMID:26759525

  19. Introduction to managing patients with recurrent ovarian cancer.

    PubMed

    Gabra, Hani

    2014-12-01

    Ovarian cancer is the 5th most common cancer found in women in the UK. It is the leading cause of death from gynaecological cancer, and is the 4th most common cause of cancer death among UK women. Similar to the majority of other cancers, relative survival rates for ovarian cancer are improving, although 5-year mortality rates remain stubbornly low. The stage of the disease at diagnosis is the single most important determinant of ovarian cancer survival, as many patients first present with advanced disease. Treatment of ovarian cancer involves a combination of 'upfront' primary surgery followed by chemotherapy. Platinum/taxane-based chemotherapy is the recommended standard-of-care first-line chemotherapy, but the majority of patients will relapse with drug-resistant disease within 3-5 years. However, not all patients can continue with platinum combination therapies due to loss of activity or toxicity-related issues, including hypersensitivity, neurotoxicity, alopecia and ototoxicity. Therefore the choice of second-line chemotherapy must take into account factors such as platinum-free treatment interval (PFI); patient's performance status; current symptoms; history of and likely future toxicities while on chemotherapy; dosing schedule requirement; and cost of treatment. A consensus in 2010 established 4 distinct subgroups within the ROC patient population based on the PFI: (platinum sensitive <12 months, partially platinum sensitive 6-12 months, platinum resistant <6 months, and refractory disease ≤4 weeks). Within patients with platinum sensitive disease, those with partially platinum sensitive disease remain the most clinically challenging to manage effectively. Non-platinum based combination therapies, in particular trabectedin with pegylated liposomal doxorubicin (PLD), offers new options together with a significant survival advantage relative to PLD alone for these patients. PMID:26759525

  20. Potential Application of Curcumin and Its Analogues in the Treatment Strategy of Patients with Primary Epithelial Ovarian Cancer

    PubMed Central

    Terlikowska, Katarzyna M.; Witkowska, Anna M.; Zujko, Malgorzata E.; Dobrzycka, Bozena; Terlikowski, Slawomir J.

    2014-01-01

    Recent findings on the molecular basis of ovarian cancer development and progression create new opportunities to develop anticancer medications that would affect specific metabolic pathways and decrease side systemic toxicity of conventional treatment. Among new possibilities for cancer chemoprevention, much attention is paid to curcumin—A broad-spectrum anticancer polyphenolic derivative extracted from the rhizome of Curcuma longa L. According to ClinicalTrials.gov at present there are no running pilot studies, which could assess possible therapeutic benefits from curcumin supplementation to patients with primary epithelial ovarian cancer. Therefore, the goal of this review was to evaluate potential preclinical properties of curcumin and its new analogues on the basis of in vivo and in vitro ovarian cancer studies. Curcumin and its different formulations have been shown to display multifunctional mechanisms of anticancer activity, not only in platinum-resistant primary epithelial ovarian cancer, but also in multidrug resistant cancer cells/xenografts models. Curcumin administered together with platinum-taxane chemotherapeutics have been reported to demonstrate synergistic effects, sensitize resistant cells to drugs, and decrease their biologically effective doses. An accumulating body of evidence suggests that curcumin, due to its long-term safety and an excellent profile of side effects should be considered as a beneficial support in ovarian cancer treatment strategies, especially in patients with platinum-resistant primary epithelial recurrent ovarian cancer or multidrug resistant disease. Although the prospect of curcumin and its formulations as anticancer agents in ovarian cancer treatment strategy appears to be challenging, and at the same time promising, there is a further need to evaluate its effectiveness in clinical studies. PMID:25429431

  1. The Cancer Genome Atlas ovarian cancer analysis

    Cancer.gov

    An analysis of genomic changes in ovarian cancer has provided the most comprehensive and integrated view of cancer genes for any cancer type to date. Ovarian serous adenocarcinoma tumors from 500 patients were examined by The Cancer Genome Atlas (TCGA) Re

  2. Can Ovarian Cancer Be Prevented?

    MedlinePlus

    ... ovaries removed with your doctor. Prevention strategies for women with a family history of ovarian cancer or BRCA mutation If your ... what the results mean to you. For some women with a strong family history of ovarian cancer, knowing they do not have ...

  3. Oncolytic virotherapy for ovarian cancer

    PubMed Central

    Li, Shoudong; Tong, Jessica; Rahman, Masmudur M; Shepherd, Trevor G; McFadden, Grant

    2012-01-01

    In the past two decades, more than 20 viruses with selective tropism for tumor cells have been developed as oncolytic viruses (OVs) for treatments of a variety of malignancies. Of these viruses, eleven have been tested in human ovarian cancer models in preclinical studies. So far, nine phase I or II clinical trials have been conducted or initiated using four different types of OVs in patients with recurrent ovarian cancers. In this article, we summarize the different OVs that are being assessed as therapeutics for ovarian cancer. We also present an overview of recent advances in identification of key genetic or immune-response pathways involved in tumorigenesis of ovarian cancer, which provides a better understanding of the tumor specificities and oncolytic properties of OVs. In addition, we discuss how next-generation OVs could be genetically modified or integrated into multimodality regimens to improve clinical outcomes based on recent advances in ovarian cancer biology. PMID:25977900

  4. Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage III Ovarian Cancer

    ClinicalTrials.gov

    2016-03-17

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  5. Calibration of platinum resistance thermometers.

    NASA Technical Reports Server (NTRS)

    Sinclair, D. H.; Terbeek, H. G.; Malone, J. H.

    1972-01-01

    Results of five years experience in calibrating about 1000 commercial platinum resistance thermometers (PRT) are reported. These PRT were relatively small and rugged, with ice-point resistances from 200 to 5000 ohms. Calibrations normalized in terms of resistance-difference ratios (Cragoe Z function) were found to be remarkably uniform for five of six different types of PRT tested, and to agree very closely with normalized calibrations of the primary reference standard type PRT. The Z function normalization cancels residual resistances which are not temperature dependent and simplifies interpolation between calibration points when the quality of a given type of PRT has been established in terms of uniform values of the Z function. Measurements at five or six well spaced base-point temperatures with Z interpolation will suffice to calibrate a PRT accurately from 4 to 900 K.

  6. Evaluation of platinum resistance thermometers

    NASA Technical Reports Server (NTRS)

    Daryabeigi, Kamran; Dillon-Townes, Lawrence A.

    1988-01-01

    An evaluation procedure for the characterization of industrial platinum resistance thermometers (PRTs) for use in the temperature range -120 to 160 C was investigated. This evaluation procedure consisted of calibration, thermal stability and hysteresis testing of four surface measuring PRTs. Five different calibration schemes were investigated for these sensors. The IPTS-68 formulation produced the most accurate result, yielding average sensor systematic error of 0.02 C and random error of 0.1 C. The sensors were checked for thermal stability by successive and thermal cycling between room temperature, 160 C, and boiling point of nitrogen. All the PRTs suffered from instability and hysteresis. The applicability of the self-heating technique as an in situ method for checking the calibration of PRTs located inside wind tunnels was investigated.

  7. "Incessant ovulation" and ovarian cancer.

    PubMed

    Casagrande, J T; Louie, E W; Pike, M C; Roy, S; Ross, R K; Henderson, B E

    1979-07-28

    A case-control study of 150 ovarian cancer patients under the age of 50 and individually matched controls was done to study the influence of fertility and oral contraceptive use on the risk of ovarian cancer. The risk decreased with increasing numbers of live births, with increasing numbers of incomplete pregnancies, and with the use of oral contraceptives. These three factors can be amalgamated into a single index of protection--"protected time"--by considering them all as periods of anovulation. The complement of protected time--viz., "ovulatory age", the period between menarche and diagnosis of ovarian cancer (or cessation of menses) minus "protected time"--was strongly related to risk of ovarian cancer. Other factors found to be associated with increased ovarian cancer risk were obesity, cervical polyps, and gallbladder disease. Women who had an "immediate" intolerance to oral contraceptive use had a fourfold increased risk of ovarian cancer. 7 patients, but no controls, could recall a family history of ovarian cancer. PMID:89281

  8. Polyglutamate Paclitaxel and Carboplatin in Treating Patients With Ovarian Epithelial, Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-05-07

    Fallopian Tube Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  9. Enzyme-Regulated Supramolecular Assemblies of Cholesterol Conjugates against Drug-Resistant Ovarian Cancer Cells.

    PubMed

    Wang, Huaimin; Feng, Zhaoqianqi; Wu, Dongdong; Fritzsching, Keith J; Rigney, Mike; Zhou, Jie; Jiang, Yujie; Schmidt-Rohr, Klaus; Xu, Bing

    2016-08-31

    We report that phosphotyrosine-cholesterol conjugates effectively and selectively kill cancer cells, including platinum-resistant ovarian cancer cells. The conjugate increases the degree of noncovalent oligomerization upon enzymatic dephosphorylation in aqueous buffer. This enzymatic conversion also results in the assembly of the cholesterol conjugates inside and outside cells and leads to cell death. Preliminary mechanistic studies suggest that the formed assemblies of the conjugates not only interact with actin filaments and microtubules but also affect lipid rafts. As the first report of multifaceted supramolecular assemblies of cholesterol conjugates against cancer cells, this work illustrates the integration of enzyme catalysis and self-assembly of essential biological small molecules on and inside cancer cells as a promising strategy for developing multifunctional therapeutics to treat drug-resistant cancers. PMID:27529637

  10. What Are the Key Statistics about Ovarian Cancer?

    MedlinePlus

    ... factors for ovarian cancer? What are the key statistics about ovarian cancer? The American Cancer Society estimates ... ovarian cancer is about 1 in 100. (These statistics don’t count low malignant potential ovarian tumors.) ...

  11. Involved-Field Radiation Therapy for Locoregionally Recurrent Ovarian Cancer

    PubMed Central

    Brown, Aaron P.; Jhingran, Anuja; Klopp, Ann H.; Schmeler, Kathleen M.; Ramirez, Pedro T.; Eifel, Patricia J.

    2015-01-01

    Objective To evaluate the effectiveness of definitive involved-field radiation therapy (IFRT) for selected patients with locoregionally-recurrent ovarian cancer. Methods We retrospectively reviewed records of 102 epithelial ovarian cancer patients treated with definitive IFRT (≥45 Gy). IFRT was directed to localized nodal (49%) and extranodal (51%) recurrences. Results The median time from diagnosis to IFRT was 36 months (range, 1–311), and the median follow-up after IFRT was 37 months (range, 1–123). Patients received a median of three chemotherapy courses before IFRT (range, 0–9). Five-year overall (OS) and progression-free survival (PFS) rates after IFRT were 40% and 24% respectively; the 5-year in-field disease control rate was 71%. Thirty-five patients (35%) had no evidence of disease at a median of 38 months after IFRT (range, 7–122), including 25 continuously without disease for a median of 61 months (range, 17–122) and 10 with salvage treatment following disease recurrence, disease-free for a median of 39 months after salvage treatment (range, 7–92). Eight clear cell carcinoma patients had higher 5-year OS (88% versus 37%; p=0.05) and PFS (75% versus 20%; p=0.01) rates than other patients. Patients sensitive to initial platinum chemotherapy had a higher 5-year OS rate than platinum-resistant patients (43% versus 27%, p=0.03). Patients who required chemotherapy for recurrence after IFRT often benefitted from longer chemotherapy-free intervals after than before IFRT. Conclusions Definitive IFRT can yield excellent local control, protracted disease-free intervals, and even cures in carefully selected patients. RT should be considered a tool in the curative management of locoregionally-recurrent ovarian cancer. PMID:23648467

  12. Survivorship Care Planning in Improving Quality of Life in Survivors of Ovarian Cancer

    ClinicalTrials.gov

    2016-08-19

    Cancer Survivor; Stage IA Ovarian Epithelial Cancer; Stage IB Ovarian Epithelial Cancer; Stage IC Ovarian Epithelial Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer

  13. Treatment options in recurrent ovarian cancer: latest evidence and clinical potential

    PubMed Central

    Luvero, Daniela; Milani, Andrea

    2014-01-01

    Ovarian cancer (OC) is the fifth most common cause of cancer death in women. Although significant progress has been made in the treatment of OC, the majority of patients experience disease recurrence and receive second-line and sometimes several lines of treatment. Here we review the options available for the treatment of recurrent disease and discuss how different agents are selected, combined and offered in a rationale sequence in the context of multidisciplinary care. We reviewed published work between 1990 and 2013 and meeting abstracts related to the use of chemotherapy and surgery in patients with recurrent ovarian cancer. We discuss treatment regimens, efficacy endpoints and safety profiles of the different therapies. Platinum-based drugs are the most active agents and are selected on the basis of a probability of response to retreatment. Nonplatinum-based chemotherapy regimens are usually given in the ‘platinum-resistant’ setting and have a modest effect on outcome. Molecular targeted therapy of ovarian cancer given alone or integrated with chemotherapy is showing promising results. Many patients are now receiving more than one line of therapy for recurrent disease, usually platinum based until platinum resistance emerges. The sequential use of chemotherapy regimens and the incorporation of molecularly targeted treatments, either alone or in combination with chemotherapy, have over the last decade significantly extended the median survival of patients with ovarian cancer. PMID:25342990

  14. Ovarian Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Ovarian Cancer in Hereditary Cancer Susceptibility Syndromes.

    PubMed

    Nakonechny, Quentin B; Gilks, C Blake

    2016-06-01

    Hereditary breast and ovarian cancer (HBOC) syndrome and Lynch syndrome (LS) are associated with increased risk of developing ovarian carcinoma. Patients with HBOC have a lifetime risk of up to 50% of developing high-grade serous carcinoma of tube or ovary; patients with LS have a 10% lifetime risk of developing endometrioid or clear cell carcinoma of the ovary. Testing all patients with tubo-ovarian high-grade serous carcinoma for mutations associated with HBOC syndrome, and all patients presenting with endometrioid or clear cell carcinoma of the ovary for mutations associated with LS can identify patients with undiagnosed underlying hereditary cancer susceptibility syndromes. PMID:27241103

  16. Inflammatory Breast Cancer from Metastatic Ovarian Cancer

    PubMed Central

    Achariyapota, Vuthinun; Chuangsuwanich, Tuenjai

    2016-01-01

    Metastases to the breast from tumors other than breast carcinomas are extremely rare and represent only 0.2–1.3% of all diagnosed malignant breast tumors. Furthermore, while the most common sites for advanced ovarian cancer metastases are the liver, lung, and pleura, metastasis to the breast from a primary ovarian cancer is uncommon and has only been reported in 0.03–0.6% of all breast cancers. Here we describe a case report of a 50-year-old female patient with a rare case of breast metastases from an advanced ovarian cancer, presenting as inflammatory breast cancer. Our observations emphasize the clinical importance of distinguishing between primary and metastatic breast cancer during diagnosis for the purpose of appropriate prognosis and treatment. PMID:27047697

  17. Combinations of platinums and selected phytochemicals as a means of overcoming resistance in ovarian cancer.

    PubMed

    Huq, Fazlul; Yu, Jun Q; Beale, Philip; Chan, Charles; Arzuman, Lalia; Nessa, Meher U; Mazumder, Mohammed E H

    2014-01-01

    Cancer sufferers are often found to use herbal products along with targeted therapy although not much information (whether beneficial or harmful) is available about the effects of such combinations. In this study, we investigated synergism from the combination of platinum drugs and a number of tumour-active phytochemicals including curcumin, epigallocatechin-3-gallate, thymoquinone, genistein, resveratrol, betulinic acid and ursolic acid in three human ovarian cancer cell lines A2780, A2780(cisR) and A2780(ZD0473R), as a function of concentration and the sequence of administration. Both the dose-effect curves and combination indices show that the binary combinations of platinum drugs with the phytochemicals exert concentration- and sequence-dependent synergism in the cell lines. Generally the degree of synergism is found to be greater in sequenced administration such as 0/2 h, 2/0 h, 0/4 h and 4/0 h than the bolus. The variation in the nature of the combined drug action from being highly synergistic to antagonistic with the change in sequence of administration clearly indicates that the action of one drug modulates that of the other (towards the induction or inhibition of apoptosis). We have also used sequenced combinations of platinum drugs and bortezomib (a proteasome inhibitor that prevents cisplatin-induced proteasomal degration of copper transporter CTR1) to enhance cellular platinum accumulation and the level of platinum-DNA binding especially in the resistant human ovarian tumour models. Proteomic studies to identify the key proteins associated with platinum resistance are ongoing. We have identified 59 proteins associated with platinum resistance in ovarian tumor models. PMID:24403514

  18. 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian Past Issues / Spring 2007 ... of this page please turn Javascript on. Gynecologic Cancers Cervical, Endometrial, and Ovarian NCI estimates that endometrial, ...

  19. Molecular imaging in ovarian cancer.

    PubMed

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  20. Exercise May Help Thwart Ovarian Cancer

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_159486.html Exercise May Help Thwart Ovarian Cancer Chronic inactivity linked ... TUESDAY, June 21, 2016 (HealthDay News) -- Lack of exercise is associated with an increased risk of ovarian ...

  1. Exercise May Help Thwart Ovarian Cancer

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_159486.html Exercise May Help Thwart Ovarian Cancer Chronic inactivity linked ... TUESDAY, June 21, 2016 (HealthDay News) -- Lack of exercise is associated with an increased risk of ovarian ...

  2. Ovarian cancer treatment in mutation carriers/BRCAness.

    PubMed

    Lorusso, Domenica; Perotto, Stefania

    2016-10-01

    Epithelial ovarian cancer remains the most lethal gynecologic malignancy. During the last 15 years, there has been only marginal improvement in 5-year overall survival. These daunting statistics are compounded by the fact that despite all subtypes exhibiting striking heterogeneity, their systemic management remains identical. Retrospective studies have shown an improved prognosis, higher response rates to platinum-containing regimens, and longer treatment-free intervals between relapses in patients with BRCA 1 and BRCA 2 (BRCA1/2)-mutated ovarian cancer (BMOC) compared with patients who are not carriers of this mutation. These features of BMOC are attributed to homologous-recombination repair deficiency in the absence of BRCA1/2 function, which results in an impaired ability of tumor cells to repair platinum-induced double-strand breaks, thereby conferring increased chemosensitivity and increased sensitivity to poly(ADP-ribose) polymerase enzyme inhibition and other DNA-damaging chemotherapeutic agents such as pegylated liposomal doxorubicin (PLD). Therefore, the chemotherapeutic approach for patients with BMOC should focus on treatment with platinum-based chemotherapy at first-line and recurrent-disease settings and measures to increase the platinum-free interval following early platinum-resistant relapse by using non-platinum cytotoxic agents, with the aim of reintroducing platinum again at a later date. The role of first-line intraperitoneal platinum-based therapy in the specific context of BMOC also merits further analysis. Other than platinum, alternative DNA-damaging agents (including PLD and trabectedin) also may have a therapeutic role in patients with recurrent BMOC. The approval of olaparib for clinical use in Europe and the United States will also affect chemotherapeutic strategies for these patients. Further work to clarify the precise relationship between BRCA1/2 mutation genotype and clinical phenotype is crucial to delineating the optimal therapeutic

  3. Evaluation of industrial platinum resistance thermometers

    NASA Technical Reports Server (NTRS)

    Daryabeigi, Kamran; Dillontownes, Lawrence A.; Alderfer, David W.

    1987-01-01

    The calibration and stability of four surface temperature measuring industrial platinum resistance thermometers for use in the temperature range -120 C to 160 C was investigated. It was found that the calibration formulation of the International Practical Temperature Scale of 1968 provided the most accurate calibration. It was also found that all the resistance thermometers suffered from varying degrees of instability and hysteresis.

  4. Genital Cancers in Women: Ovarian Cancer.

    PubMed

    Kuznia, Angela L; Roett, Michelle A

    2015-11-01

    More than 20,000 US women are diagnosed with ovarian cancer each year. The average lifetime risk is 1.3%, but risk increases with BRCA1 or BRCA2 gene mutations (40% and 18% risk, respectively, by age 70 years) or hereditary nonpolyposis colorectal cancer syndrome (12% lifetime risk). Other risk factors include smoking, possibly past clomiphene use, and more years of ovulation. Symptoms are nonspecific. Abdominal pain is most common; others include pelvic pain, bloating, and early satiety. When ovarian cancer is suspected, evaluation should begin with transvaginal ultrasonography with Doppler studies. Cancer antigen 125 testing can be obtained, but levels are not elevated in all patients. Other biomarkers (eg, OVA1) and scoring systems can be used to help determine if cancer is present. When diagnosed early (stage I), the 5-year survival rate is 90% for epithelial ovarian cancer. However, most patients with epithelial ovarian cancer are diagnosed in stage III or later, with a 5-year survival rate of 17% to 39%. Treatment involves total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without chemotherapy. Fertility-preserving options can be considered in some early-stage cancers, followed by more definitive surgical procedures. There is no evidence that routine screening is beneficial and it is associated with significant harms from unnecessary procedures. Women with genetic syndromes that increase risk should be considered for prophylactic bilateral salpingo-oophorectomy. PMID:26569048

  5. Ovarian stimulation in cancer patients.

    PubMed

    Cakmak, Hakan; Rosen, Mitchell P

    2013-05-01

    The patients referred for fertility preservation owing to a malignant disease do not represent the typical population of subfertile patients treated in IVF units. Cancer may affect multiple tissues throughout the body and can result in a variety of complications during controlled ovarian stimulation. Determination of the controlled ovarian stimulation protocol and gonadotropin dose for oocyte/embryo cryopreservation requires an individualized assessment. This review highlights the new protocols that are emerging to reduce time constraints and emphasizes management considerations to decrease complications. PMID:23635348

  6. Drug discovery in ovarian cancer.

    PubMed

    Chase, Dana M; Mathur, Nidhee; Tewari, Krishnansu S

    2010-11-01

    Drug discovery in the ovarian cancer arena has led to the activation of several important clinical trials. Many biologic agents have come down the pipeline and are being studied in phase II trials for recurrent disease. These agents include antivascular compounds that disrupt angiogenesis through a variety of mechanisms (e.g., prevention of ligand-binding to the vascular endothelial growth factor receptor-2 (VEGF-R2), high-affinity VEGF blockade, oral inhibitors of tyrosine kinases stimulated by VEGF, inhibition of alpha5beta1 integrin, neutralization of angioproteins, etc.). Other novel drugs include oral platinum compounds as well as those that antagonize the tumor proliferation genes in the Hedgehog pathway, and that target folic acid receptors which are expressed by ovarian cancer cells. In addition, studies are underway with oral agents that inhibit the tyrosine kinase activity associated with two oncogenes (epidermal growth factor receptor (EGFR) and HER-2/neu). Finally, emerging technologies in clinical trials include nanotechnology to enhance delivery of chemotherapy to ovarian tumors, drug resistance/sensitivity assays to guide therapy, and agents that mobilize and induce proliferation of hematopoetic progenitor cells to aid in red blood cell, white blood cell, and platelet recovery following chemotherapy. The relevant patents in drug discovery of ovarian cancer are discussed. PMID:20524931

  7. [Epidemiologic factors in ovarian cancer].

    PubMed

    Curie, P; Sussmann, M; Treisser, A; Renaud, R

    1985-05-01

    Ovarian carcinoma is the most severe gynecological cancer with an overall incidence of 12 per 1000 Americans or Europeans developing it over 40 years of age. Only 3 of the 12 cases will receive efficient care because the diagnosis will be made too late. This study reveals the principal risk factors i.e. upper socioeconomic echelon, ovarian function uninterrupted by a pregnancy or usage of oral contraceptives, anamnestic evidence of ovarian carcinoma in the family, some hereditary disorders, external insults (talcum powder). The synthesis of these various risk factors permits a comprehensive review of the hypotheses of pathogenesis concerning recurrence of tumors. But corollary epidemiologic studies are still needed to try to define better the high risk groups whose follow-up systematic detection and testing is a priority. PMID:4023542

  8. Ovarian metastasis from colorectal cancer.

    PubMed

    Birnkrant, A; Sampson, J; Sugarbaker, P H

    1986-11-01

    Controversies exist regarding the surgical treatment of the ovaries in women with primary colorectal cancer. A review of the authors' experience and the surgical literature reveals an incidence of ovarian metastases from colorectal cancer of approximately 6 percent. This problem may occur somewhat more frequently in premenopausal women. Resection of the ovaries at the time of colectomy is unlikely to affect survival. Removal of the ovaries at the time of bowel resection will prevent repeat laparotomy to resect an ovarian mass in approximately 2 percent of women with large bowel cancer. Oophorectomy should be performed in all postmenopausal females at the time of primary resection. Oophorectomy should be performed in premenopausal women if any gross abnormality of the ovary is detected or if peritoneal implants are seen at the time of primary resection. PMID:3533472

  9. Antivascular Therapy for Epithelial Ovarian Cancer

    PubMed Central

    Duhoux, Francois P.; Machiels, Jean-Pascal

    2010-01-01

    Ovarian cancer is the fifth largest cancer killer in women. Improved understanding of the molecular pathways implicated in the pathogenesis of ovarian cancer has led to the investigation of novel targeted therapies. Ovarian cancer is characterized by an imbalance between pro- and antiangiogenic factors in favor of angiogenesis activation. Various antivascular strategies are currently under investigation in ovarian cancer. They can schematically be divided into antiangiogenic and vascular-disrupting therapies. This paper provides a comprehensive review of these new treatments targeting the tumor vasculature in this disease. Promising activities have been detected in phase II trials, and results of phase III clinical trials are awaited eagerly. PMID:20072701

  10. Oncolytic Measles Virus Expressing the Sodium Iodide Symporter to Treat Drug-Resistant Ovarian Cancer

    PubMed Central

    Galanis, Evanthia; Atherton, Pamela J.; Maurer, Matthew J.; Knutson, Keith L.; Dowdy, Sean C.; Cliby, William A.; Haluska, Paul; Long, Harry J.; Oberg, Ann; Aderca, Ileana; Block, Matthew S.; Bakkum-Gamez, Jamie; Federspiel, Mark J.; Russell, Stephen J.; Kalli, Kimberly R.; Keeney, Gary; Peng, Kah Whye; Hartmann, Lynn C.

    2015-01-01

    Edmonston vaccine strains of measles virus (MV) have significant antitumor activity in mouse xenograft models of ovarian cancer. MV engineered to express the sodium iodide symporter gene (MV-NIS) facilitates localization of viral gene expression and offers a tool for tumor radiovirotherapy. Here, we report results from a clinical evaluation of MV-NIS in patients with taxol- and platinum-resistant ovarian cancer. MV-NIS was given intraperitoneally every 4 weeks for up to 6 cycles. Treatment was well tolerated and associated with promising median overall survival in these patients with heavily pretreated ovarian cancer; no dose-limiting toxicity was observed in 16 patients treated at high-dose levels (108–109 TCID50), and their median overall survival of 26.5 months compared favorably with other contemporary series. MV receptor CD46 and nectin-4 expression was confirmed by immunohistochemistry in patient tumors. Sodium iodide symporter expression in patient tumors after treatment was confirmed in three patients by 123I uptake on SPECT/CTs and was associated with long progression-free survival. Immune monitoring posttreatment showed an increase in effector T cells recognizing the tumor antigens IGFBP2 and FRα, indicating that MV-NIS treatment triggered cellular immunity against the patients' tumor and suggesting that an immune mechanism mediating the observed antitumor effect. Our findings support further clinical evaluation of MV-NIS as an effective immunovirotherapy. PMID:25398436

  11. PARP Inhibitors in Epithelial Ovarian Cancer: State of Art and Perspectives of Clinical Research.

    PubMed

    Gadducci, Angiolo; Guerrieri, Maria Elena

    2016-05-01

    Homologous recombination (HR) and base excision repair (BER) are two of the major DNA-repair pathways. The proteins encoded by breast-related cancer antigen (BRCA) and poly(adenosine diphosphate-ribose) polymerases (PARP) are involved in HR and BER, respectively. Tumors with HR deficiency, including those in BRCA mutation carriers, are sensitive to BER blockade via PARP inhibitors. These represent novel therapeutic tools for HR-deficient ovarian cancer, able to improve progression-free survival of women with recurrent, platinum-sensitive disease in response to recent platinum-based chemotherapy. More research is needed to assesses whether inhibitors of PARP have any role as maintenance treatment after first-line chemotherapy and as palliative treatment of platinum-resistant disease. Germline BRCA testing should be offered to all patients with ovarian cancer, regardless of age and family history. HR deficiency has been observed not only in germline BRCA mutation carriers, but also in patients with somatic mutations or epigenetic silencing of BRCA, and with loss of function of other genes. Half of all high-grade ovarian carcinomas are HR-deficient, and additional biological and clinical investigations are strongly warranted to identify patients with this subset of tumors. PMID:27127105

  12. Belinostat and Carboplatin in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Carboplatin or Cisplatin

    ClinicalTrials.gov

    2014-06-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer

  13. Ovulation and extra-ovarian origin of ovarian cancer.

    PubMed

    Yang-Hartwich, Yang; Gurrea-Soteras, Marta; Sumi, Natalia; Joo, Won Duk; Holmberg, Jennie C; Craveiro, Vinicius; Alvero, Ayesha B; Mor, Gil

    2014-01-01

    The mortality rate of ovarian cancer remains high due to late diagnosis and recurrence. A fundamental step toward improving detection and treatment of this lethal disease is to understand its origin. A growing number of studies have revealed that ovarian cancer can develop from multiple extra-ovarian origins, including fallopian tube, gastrointestinal tract, cervix and endometriosis. However, the mechanism leading to their ovarian localization is not understood. We utilized in vitro, ex vivo, and in vivo models to recapitulate the process of extra-ovarian malignant cells migrating to the ovaries and forming tumors. We provided experimental evidence to support that ovulation, by disrupting the ovarian surface epithelium and releasing chemokines/cytokines, promotes the migration and adhesion of malignant cells to the ovary. We identified the granulosa cell-secreted SDF-1 as a main chemoattractant that recruits malignant cells towards the ovary. Our findings revealed a potential molecular mechanism of how the extra-ovarian cells can be attracted by the ovary, migrate to and form tumors in the ovary. Our data also supports the association between increased ovulation and the risk of ovarian cancer. Understanding this association will lead us to the development of more specific markers for early detection and better prevention strategies. PMID:25135607

  14. Early Preinvasive Lesions in Ovarian Cancer

    PubMed Central

    Chene, Gautier; Lamblin, Gery; Le Bail-Carval, Karine; Chabert, Philippe; Bakrin, Naoual; Mellier, Georges

    2014-01-01

    Faced with the catastrophic prognosis for ovarian cancer due to the fact that it is most often diagnosed late at the peritoneal carcinomatosis stage, screening and early detection could probably reduce the mortality rate. A better understanding of the molecular characteristics of the different ovarian cancer subtypes and their specific molecular signatures is indispensable prior to development of new screening strategies. We discuss here the early natural history of ovarian cancer and its origins. PMID:24804229

  15. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    ClinicalTrials.gov

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  16. Surgical management of recurrent ovarian cancer.

    PubMed

    Leitao, Mario M; Chi, Dennis S

    2009-04-01

    Surgery is the cornerstone of treatment for patients with advanced ovarian cancer. The majority of patients with advanced ovarian cancer who experience a clinical remission after initial surgery will develop a recurrence. The optimal management for patients with recurrent ovarian cancer remains to be defined. Chemotherapy is frequently used with varying response rates. Repeat surgical cytoreduction appears to offer a survival benefit for select patients with recurrent ovarian cancer and should be considered. Surgery also plays a role in the palliation of certain patients. Continued investigations, especially randomized trials, are needed to further define the optimal treatment modalities for these patients. PMID:19332245

  17. Belinostat in Treating Patients With Advanced Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer or Ovarian Low Malignant Potential Tumors

    ClinicalTrials.gov

    2013-04-11

    Fallopian Tube Cancer; Primary Peritoneal Cavity Cancer; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Ovarian Epithelial Cancer; Stage III Borderline Ovarian Surface Epithelial-stromal Tumor; Stage III Ovarian Epithelial Cancer; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Ovarian Epithelial Cancer

  18. Defective hCNT1 Transport Contributes to Gemcitabine Chemoresistance in Ovarian Cancer Subtypes: Overcoming Transport Defects Using a Nanoparticle Approach

    PubMed Central

    Hung, Sau Wai; Marrache, Sean; Cummins, Shannon; Bhutia, Yangzom D.; Mody, Hardik; Hooks, Shelley B.; Dhar, Shanta; Govindarajan, Rajgopal

    2015-01-01

    Nucleoside analogs are used as chemotherapeutic options for the treatment of platinum-resistant ovarian cancers. Human concentrative nucleoside transporter 1 (hCNT1) is implicated in sensitizing solid tumors to nucleoside analogs although its role in determining drug efficacy in ovarian cancers remains unclear. Here we examined the functional expression of hCNT1 and compared its contributions towards gemcitabine efficacy in histological subtypes of ovarian cancer. Radioactivity analysis identified hCNT1-mediated 3H-gemcitabine transport in ovarian cancer cells to be significantly reduced compared with that of normal ovarian surface epithelial cells. Biochemical and immunocytochemical analysis identified that unlike normal ovarian cells which expressed high levels of hCNT1 at the apical cell surface, the transporter was either diminished in expression and/or mislocalized in cell lines of various subtypes of ovarian cancer. Retroviral expression of hCNT1 selectively rescued gemcitabine transport in cell lines representing serous, teratocarcinoma, and endometrioid subtypes, but not clear cell carcinoma (CCC). In addition, exogenous hCNT1 predominantly accumulated in intracytoplasmic vesicles in CCC suggesting defective cellular trafficking of hCNT1 as a contributing factor to transport deficiency. Despite diminution of hCNT1 transport in the majority of ovarian cancers and apparent trafficking defects with CCC, the chemotherapeutic efficacy of gemcitabine was broadly enhanced in all subtypes when delivered via engineered nanoparticles (NPs). Additionally, by bypassing the transport requirement, the delivery of a gemcitabine-cisplatin combination in NP formulation increased their synergistic interactions. These findings uncover hCNT1 as a putative determinant for nucleoside analog chemoresistance in ovarian cancer and may help rationalize drug selection and delivery strategies for various histological subtypes of ovarian cancer. PMID:25600708

  19. Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

    PubMed Central

    Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schröder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kübler, Kirsten

    2015-01-01

    Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes. PMID:25999351

  20. Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer.

    PubMed

    Ayub, Tiyasha H; Keyver-Paik, Mignon-Denise; Debald, Manuel; Rostamzadeh, Babak; Thiesler, Thore; Schröder, Lars; Barchet, Winfried; Abramian, Alina; Kaiser, Christina; Kristiansen, Glen; Kuhn, Walther; Kübler, Kirsten

    2015-06-30

    Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes. PMID:25999351

  1. OVARIAN CANCER: INVOLVEMENT OF THE MATRIX METALLOPROTEINASES

    PubMed Central

    Al-Alem, Linah; Curry, Thomas E.

    2016-01-01

    Ovarian cancer is the leading cause of death from gynecologic malignancies. Reasons for the high mortality rate associated with ovarian cancer include a late diagnosis at which time the cancer has metastasized throughout the peritoneal cavity. Cancer metastasis is facilitated by the remodeling of the extracellular tumor matrix by a family of proteolytic enzymes known as the matrix metalloproteinases (MMPs). There are 23 members in the MMP family, many of which have been reported to be associated with ovarian cancer. In the current paradigm, ovarian tumor cells and the surrounding stromal cells stimulate the synthesis and/or activation of various MMPs to aid in tumor growth, invasion, and eventual metastasis. This review sheds light on the different MMPs in the various types of ovarian cancer and their impact on the progression of this gynecologic malignancy. PMID:25918438

  2. Targeted Therapies in Epithelial Ovarian Cancer

    PubMed Central

    Dean, Emma; El-Helw, Loaie; Hasan, Jurjees

    2010-01-01

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer. PMID:24281034

  3. Rethinking Ovarian Cancer: Recommendations for Improving Outcomes

    PubMed Central

    Vaughan, Sebastian; Coward, Jermaine I.; Bast Jr., Robert C.; Berchuck, Andy; Berek, Jonathan S.; Brenton, James D.; Coukos, George; Crum, Christopher C.; Drapkin, Ronny; Etemadmoghadam, Dariush; Friedlander, Michael; Gabra, Hani; Kaye, Stan B.; Lord, Chris J.; Lengyel, Ernst; Levine, Douglas A.; McNeish, Iain A.; Menon, Usha; Mills, Gordon B.; Nephew, Kenneth P.; Oza, Amit M.; Sood, Anil K.; Stronach, Euan A.; Walczak, Henning; Bowtell, David D.; Balkwill, Frances R.

    2012-01-01

    There have been major advances in our understanding of the cellular and molecular biology of the human malignancies collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Perspective. PMID:21941283

  4. Ovarian cancer mortality and industrial pollution.

    PubMed

    García-Pérez, Javier; Lope, Virginia; López-Abente, Gonzalo; González-Sánchez, Mario; Fernández-Navarro, Pablo

    2015-10-01

    We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997-2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. PMID:26046426

  5. Role of PAR-4 in ovarian cancer.

    PubMed

    Meynier, Sonia; Kramer, Marianne; Ribaux, Pascale; Tille, Jean-Christophe; Delie, Florence; Petignat, Patrick; Cohen, Marie

    2015-09-01

    Prostate apoptosis response-4 (PAR-4) is considered as a tumour suppressor due to its ability to selectively induce cell apoptosis in most cancer cells. However little is known about the role of PAR-4 in ovarian cancer. In this study, we investigated for the first time the role of PAR-4 in ovarian carcinogenesis. We showed that PAR-4 mRNA level is not significantly different between healthy and cancer ovarian cells. Immunohistochemistry on ovarian tissue showed that ovarian cancer cells are positive for PAR-4 nuclear and cytoplasmic staining whereas ovarian healthy cells are negative for PAR-4 nuclear staining. We then studied the role of PAR-4 in cell apoptosis. We determined that PAR-4 induces cell apoptosis in response to stimuli, in vitro, but is also involved in the relocation of GRP78 from endoplasmic reticulum to the cell surface of ovarian cancer cell line (SKOV-3 cells). In ovo, PAR-4 decreases ovarian tumour development and increases the response to taxol treatment. These observations suggest that PAR-4 is a very interesting therapeutic target against ovarian carcinogenesis. PMID:26246468

  6. Role of PAR-4 in ovarian cancer

    PubMed Central

    Meynier, Sonia; Kramer, Marianne; Ribaux, Pascale; Tille, Jean-Christophe; Delie, Florence; Petignat, Patrick; Cohen, Marie

    2015-01-01

    Prostate apoptosis response-4 (PAR-4) is considered as a tumour suppressor due to its ability to selectively induce cell apoptosis in most cancer cells. However little is known about the role of PAR-4 in ovarian cancer. In this study, we investigated for the first time the role of PAR-4 in ovarian carcinogenesis. We showed that PAR-4 mRNA level is not significantly different between healthy and cancer ovarian cells. Immunohistochemistry on ovarian tissue showed that ovarian cancer cells are positive for PAR-4 nuclear and cytoplasmic staining whereas ovarian healthy cells are negative for PAR-4 nuclear staining. We then studied the role of PAR-4 in cell apoptosis. We determined that PAR-4 induces cell apoptosis in response to stimuli, in vitro, but is also involved in the relocation of GRP78 from endoplasmic reticulum to the cell surface of ovarian cancer cell line (SKOV-3 cells). In ovo, PAR-4 decreases ovarian tumour development and increases the response to taxol treatment. These observations suggest that PAR-4 is a very interesting therapeutic target against ovarian carcinogenesis. PMID:26246468

  7. Predictive and therapeutic markers in ovarian cancer

    DOEpatents

    Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

    2013-03-26

    Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

  8. EGEN-001 and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-08-11

    Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer

  9. What Should You Ask Your Doctor about Ovarian Cancer?

    MedlinePlus

    ... cancer? What should you ask your doctor about ovarian cancer? It is important for you to have honest, ... are some questions to consider: What type of ovarian cancer do I have? Has my cancer spread beyond ...

  10. Response time correlations for platinum resistance thermometers

    NASA Technical Reports Server (NTRS)

    Pandey, D. K.; Ash, R. L.; Dillon-Townes, L. A.

    1985-01-01

    The 'plunge method' recommended by ASTM has been used to determine the time constant of 100-ohm platinum resistance thermometers (PRT) considered for use in the National Transonic Facility. It is shown that the response time of ventilated PRT can be correlated with the reciprocal of the heat transfer coefficient in a given field. Universal correlations are established for the 100- and 1000-ohm PRT with uncertainties of 20 and 30 percent, respectively. The correlations are found to be consistent with the uncertainty involved in heat transfer correlations available in the literature and are recommended for use in flowing liquids and gases.

  11. Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells

    PubMed Central

    Hearn, Jessica M.; Romero-Canelón, Isolda; Munro, Alison F.; Fu, Ying; Pizarro, Ana M.; Garnett, Mathew J.; McDermott, Ultan; Carragher, Neil O.; Sadler, Peter J.

    2015-01-01

    The organometallic “half-sandwich” compound [Os(η6-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up-regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance. PMID:26162681

  12. Potent organo-osmium compound shifts metabolism in epithelial ovarian cancer cells.

    PubMed

    Hearn, Jessica M; Romero-Canelón, Isolda; Munro, Alison F; Fu, Ying; Pizarro, Ana M; Garnett, Mathew J; McDermott, Ultan; Carragher, Neil O; Sadler, Peter J

    2015-07-21

    The organometallic "half-sandwich" compound [Os(η(6)-p-cymene)(4-(2-pyridylazo)-N,N-dimethylaniline)I]PF6 is 49× more potent than the clinical drug cisplatin in the 809 cancer cell lines that we screened and is a candidate drug for cancer therapy. We investigate the mechanism of action of compound 1 in A2780 epithelial ovarian cancer cells. Whole-transcriptome sequencing identified three missense mutations in the mitochondrial genome of this cell line, coding for ND5, a subunit of complex I (NADH dehydrogenase) in the electron transport chain. ND5 is a proton pump, helping to maintain the coupling gradient in mitochondria. The identified mutations correspond to known protein variants (p.I257V, p.N447S, and p.L517P), not reported previously in epithelial ovarian cancer. Time-series RNA sequencing suggested that osmium-exposed A2780 cells undergo a metabolic shunt from glycolysis to oxidative phosphorylation, where defective machinery, associated with mutations in complex I, could enhance activity. Downstream events, measured by time-series reverse-phase protein microarrays, high-content imaging, and flow cytometry, showed a dramatic increase in mitochondrially produced reactive oxygen species (ROS) and subsequent DNA damage with up-regulation of ATM, p53, and p21 proteins. In contrast to platinum drugs, exposure to this organo-osmium compound does not cause significant apoptosis within a 72-h period, highlighting a different mechanism of action. Superoxide production in ovarian, lung, colon, breast, and prostate cancer cells exposed to three other structurally related organo-Os(II) compounds correlated with their antiproliferative activity. DNA damage caused indirectly, through selective ROS generation, may provide a more targeted approach to cancer therapy and a concept for next-generation metal-based anticancer drugs that combat platinum resistance. PMID:26162681

  13. Therapeutic advances in ovarian cancer.

    PubMed

    Rader, J S

    1992-02-01

    The propensity of ovarian cancer to recur--even after initial chemotherapeutic responses--is a problem that has been given a great deal of attention during the past year in the literature dealing with the treatment of ovarian cancer. Most of the articles address techniques to improve the percent of initial and secondary treatment responses. Several studies have described cytoreductive techniques to decrease the remaining tumor size for improved chemotherapeutic response. Cross-resistance between platinum analogues has been reconfirmed. However, improved secondary responses were seen when repeat treatment with platinum agents were preceded by a longer interval from initial platinum agent therapy. Radiation therapy has been shown to offer little solution to recurrent disease except possibly in a select group of patients with microscopic disease at second-look laparotomy. Reports on the use of carboplatin continue to demonstrate good initial responses, with decreased toxicity compared with cisplatin. Granisetron has been shown to significantly decrease the nausea and vomiting caused by emetogenic chemotherapy like cisplatin. PMID:1543823

  14. Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-05-01

    Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer

  15. Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-07-05

    Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  16. Oncolytic reovirus against ovarian and colon cancer.

    PubMed

    Hirasawa, Kensuke; Nishikawa, Sandra G; Norman, Kara L; Alain, Tommy; Kossakowska, Anna; Lee, Patrick W K

    2002-03-15

    Reovirus selectively replicates in and destroys cancer cells with an activated Ras signaling pathway. In this study, we evaluated the feasibility of using reovirus (serotype 3, strain Dearing) as an antihuman colon and ovarian cancer agent. In in vitro studies, reovirus infection in human colon and ovarian cell lines was assessed by cytopathic effect as detected by light microscopy, [(35)S]Methionine labeling of infected cells for viral protein synthesis and progeny virus production by plaque assay. We observed that reovirus efficiently infected all five human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48) and four human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626) which were tested, but not a normal colon cell line (CCD-18Co) or a normal ovarian cell line (NOV-31). We also observed that the Ras activity in the human colon and ovarian cancer cell lines was elevated compared with that in normal colon and ovarian cell lines. In animal models, intraneoplastic as well as i.v. inoculation of reovirus resulted in significant regression of established s.c. human colon and ovarian tumors implanted at the hind flank. Histological studies revealed that reovirus infection in vivo was restricted to tumor cells, whereas the surrounding normal tissue remained uninfected. Additionally, in an i.p. human ovarian cancer xenograft model, inhibition of ascites tumor formation and the survival of animals treated with live reovirus was significantly greater than of control mice treated with UV-inactivated reovirus. Reovirus infection in ex vivo primary human ovarian tumor surgical samples was also confirmed, further demonstrating the potential of reovirus therapy. These results suggest that reovirus holds promise as a novel agent for human colon and ovarian cancer therapy. PMID:11912142

  17. OPT-821 With or Without Vaccine Therapy in Treating Patients With Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer in Second or Third Complete Remission

    ClinicalTrials.gov

    2016-03-16

    Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  18. [Which patients with ovarian cancer shows the combination of trabectedin with pegylated liposomal doxorubicin].

    PubMed

    Khokhlova, S V; Cherkasova, M V; Orel, N F; Limareva, S V; Bazaeva, I Ia; Gorbunova, V A

    2013-01-01

    Given the high rate of recurrence of ovarian cancer, the search for new therapeutic strategies are topical issue. According to various studies the effectiveness of drug treatment relapse depends on the platinum-free interval, increasing in proportion to its duration. If therapy is platinum-resistant recurrent ovarian cancer is a standard approach, the treatment of platinum-sensitive recurrent algorithm is not fully defined. Comparison of platinum and non-platinum combinations revealed the advantage of combined platinum- treatment for patients with platinum-free interval of more than 6 months without an increase in life expectancy. Non-platinum combination of trabected in with pegylated liposomal doxorubicin has shown comparable efficacy with an advantage in overall survival in patients with platinum-free interval of 6-12 months. A platinum-free interval prolongation by the use of non-platinum mode increases the efficiency of subsequent platinum-based therapy, increasing the life expectancy of patients. Currently under study molecular markers and prognostic factors allowing to define a group of patients who have the greatest benefit from the use trabectedin with pegylated liposomal doxorubicin as second-line chemotherapy. PMID:24640740

  19. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer.

    PubMed

    Bowtell, David D; Böhm, Steffen; Ahmed, Ahmed A; Aspuria, Paul-Joseph; Bast, Robert C; Beral, Valerie; Berek, Jonathan S; Birrer, Michael J; Blagden, Sarah; Bookman, Michael A; Brenton, James D; Chiappinelli, Katherine B; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G; Iwanicki, Marcin; Karlan, Beth Y; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A; Lu, Karen H; McNeish, Iain A; Menon, Usha; Narod, Steven A; Nelson, Brad H; Nephew, Kenneth P; Pharoah, Paul; Powell, Daniel J; Ramos, Pilar; Romero, Iris L; Scott, Clare L; Sood, Anil K; Stronach, Euan A; Balkwill, Frances R

    2015-11-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  20. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer

    PubMed Central

    Bowtell, David D.; Böhm, Steffen; Ahmed, Ahmed A.; Aspuria, Paul-Joseph; Bast, Robert C.; Beral, Valerie; Berek, Jonathan S.; Birrer, Michael J.; Blagden, Sarah; Bookman, Michael A.; Brenton, James; Chiappinelli, Katherine B.; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G.; Iwanicki, Marcin; Karlan, Beth Y.; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A.; Lu, Karen H.; McNeish, Iain A.; Menon, Usha; Narod, Steve A.; Nelson, Brad H.; Nephew, Kenneth P.; Pharoah, Paul; Powell, Daniel J.; Ramos, Pilar; Romero, Iris L.; Scott, Clare L.; Sood, Anil K.; Stronach, Euan A.; Balkwill, Frances R.

    2016-01-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This ‘roadmap’ for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  1. Epidemiological characteristics of ovarian cancer in Korea

    PubMed Central

    Park, Boyoung; Park, Sohee; Kim, Tae-Joong; Ma, Seung Hyun; Kim, Byoung-Gie; Kim, Yong-Man; Kim, Jae Weon; Kang, Sokbom; Kim, Jaehoon; Kim, Tae Jin; Yoo, Keun-Young

    2010-01-01

    Objective This study was conducted to examine recent trends in ovarian cancer incidence and mortality and secular trends in demographic factors in Korea. Methods With the data from Korea Central Cancer Registry, International Agency for Research on Cancer, Korean Death Registry, and World Health Organization's Statistical Information System, we calculated age-standardized incidence and mortality rates for ovarian cancer. Also we estimated future incidence of ovarian and cervical cancer using linear regression model. To assess the demographic trend, data from national surveys in Korea or results from published papers were searched. Results Ovarian cancer incidence rate was similar to that in women worldwide but lower than those in Western countries, and the trend has been increased steadily. Ovarian cancer-related mortality rates have been increasing in Korea, even though those in western and some Asian countries, such as China, have been decreasing. Age-specific incidence rate and mortality rate showed steep increases with advancing age. The incidence rate of ovarian cancer was estimated to surpass that of uterine cervix cancer in 2015. Korea showed rapid changes in nutritional, reproductive, and anthropometric factors. Conclusion These recent trends in ovarian cancer incidence and mortality may be partly attributed to gradual westernizing of life styles and to changes in socio-demographic behavior factors. In particular, the increasing trend in ovarian cancer mortality in Korea may be attributed to a real rise in mortality as well as, in part, a decline in misclassification bias related to an increase in the proportion of deaths confirmed by physician diagnosis. PMID:21278886

  2. Ovarian cancer: emerging molecular-targeted therapies

    PubMed Central

    Sourbier, Carole

    2012-01-01

    With about 22,000 new cases estimated in 2012 in the US and 15,500 related deaths, ovarian cancer is a heterogeneous and aggressive disease. Even though most of patients are sensitive to chemotherapy treatment following surgery, recurring disease is almost always lethal, and only about 30% of the women affected will be cured. Thanks to a better understanding of the molecular mechanisms underlying ovarian cancer malignancy, new therapeutic options with molecular-targeted agents have become available. This review discusses the rationale behind molecular-targeted therapies and examines how newly identified molecular targets may enhance personalized therapies for ovarian cancer patients. PMID:22807625

  3. Olaparib for the treatment of ovarian cancer.

    PubMed

    Bornstein, E; Jimeno, A

    2016-01-01

    Olaparib, an oral poly(ADP-ribose) polymerase (PARP) inhibitor, is the first FDA-approved drug in its class for patients with ovarian cancer, specifically in a subset of patients with BRCA mutations and prior chemotherapy treatments. PARP inhibitors have had other implications in different solid tumor types including breast, gastric and pancreatic malignancies. In light of the recent FDA approval of olaparib for the treatment of ovarian cancer, this article aims to outline the mechanisms and implications of the drug. With a favorable adverse event profile and improved outcomes, including progression-free survival, olaparib has demonstrated augmentation to therapeutic options in the treatment of ovarian cancer. PMID:26937492

  4. Genomic similarities between breast and ovarian cancers

    Cancer.gov

    One subtype of breast cancer shares many genetic features with high-grade serous ovarian cancer, a cancer that is very difficult to treat, according to researchers supported by the National Institutes of Health. The findings suggest that the two cancers a

  5. Ormeloxifene efficiently inhibits ovarian cancer growth

    PubMed Central

    Maher, Diane M.; Khan, Sheema; Nordquist, Jordan; Ebeling, Mara C.; Bauer, Nichole A.; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C.; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer. PMID:25306892

  6. HOXB13 promotes ovarian cancer progression

    PubMed Central

    Miao, Jiangyong; Wang, Zuncai; Provencher, Heather; Muir, Beth; Dahiya, Sonika; Carney, Erin; Leong, Chee-Onn; Sgroi, Dennis C.; Orsulic, Sandra

    2007-01-01

    Deregulated expression of HOXB13 in a subset of estrogen receptor-positive breast cancer patients treated with tamoxifen monotherapy is associated with an aggressive clinical course and poor outcome. Because the ovary is another hormone-responsive organ, we investigated whether HOXB13 plays a role in ovarian cancer progression. We show that HOXB13 is expressed in multiple human ovarian cancer cell lines and tumors and that knockdown of endogenous HOXB13 by RNA interference in human ovarian cancer cell lines is associated with reduced cell proliferation. Ectopic expression of HOXB13 is capable of transforming p53−/− mouse embryonic fibroblasts and promotes cell proliferation and anchorage-independent growth in mouse ovarian cancer cell lines that contain genetic alterations in p53, myc, and ras. In this genetically defined cell line model of ovarian cancer, we demonstrate that HOXB13 collaborates with activated ras to markedly promote tumor growth in vivo and that HOXB13 confers resistance to tamoxifen-mediated apoptosis. Taken together, our results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer. PMID:17942676

  7. General Information about Ovarian Epithelial Cancer

    MedlinePlus

    ... Primary Peritoneal Cancer Treatment (PDQ®)–Patient Version General Information About Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  8. Genetic and molecular changes in ovarian cancer

    PubMed Central

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research. PMID:27458531

  9. Cytogenetic studies in ovarian cancer.

    PubMed

    Whang-Peng, J; Knutsen, T; Douglass, E C; Chu, E; Ozols, R F; Hogan, W M; Young, R C

    1984-01-01

    Cytogenetic studies of ovarian cancer have been conducted in the Medicine Branch, NCI, National Institutes of Health for 5 years. A total of 72 patients were studied by direct preparation and/or 1- to 3-day short-term culture of ascites (86 samples), pleural fluid (4 samples), and tumor (2 samples). Repeat examinations (1-24 months later) were performed in 7 of the 72 patients. Forty-four patients (62%) were successfully analyzed with banding techniques: 6 patients had adenocarcinoma, 7 had serous adenocarcinoma, 13 had serous papillary adenocarcinoma, 7 had serous papillary cystadenocarcinoma, 2 had mucinous adenocarcinoma, 6 had undifferentiated or poorly differentiated adenocarcinoma, 1 had clear cell adenocarcinoma, and 2 were not classified. Of these 44 patients, 29 had received prior chemotherapy, 14 were untreated, and in 1 patient the treatment status was unknown. Aneuploidy was observed in all patients and there was considerable variation in the chromosome numbers (even within single samples), often ranging from diploidy to triploidy to tetraploidy. All 44 patients had numerical abnormalities and 39 had structural abnormalities. The chromosomes most frequently involved in structural abnormalities (in decreasing order according to the number of patients involved) were #1, #3, #2, #4, #9, #10, #15, #19, #6, and #11; the least involved chromosomes were #21 and #5. Clone formation and the number of chromosomes involved in structural abnormalities increased with duration of disease and were more extensive in patients treated with chemotherapy than in patients treated with surgery alone. Our data did not show a deletion of chromosome #6 (6q-) to be specific for ovarian cancer. PMID:6690026

  10. Pharmacoprevention for hereditary breast and ovarian cancer.

    PubMed

    Cazzaniga, Massimiliano; Bonanni, Bernardo

    2016-10-01

    Hereditary breast and ovarian cancer (HBOC) syndrome is an important women's health condition characterized by an increased susceptibility to the development of cancer, in particular breast and ovarian neoplasms, and is caused by an inherited germline genetic mutation in one or both tumor suppressor genes named BRCA1 and BRCA2. This monographic issue provides an update on our knowledge of this syndrome with particular emphasis on the risk reduction strategies through a pharmacopreventive approach. PMID:26928419

  11. Surgical management of epithelial ovarian cancer.

    PubMed

    Salani, Ritu; Bristow, Robert E

    2012-03-01

    Ovarian cancer affects approximately 21,880 women and accounts for over 13,000 deaths annually in the United States. Although survival rates have improved over the past several decades, directly as a result of advances in chemotherapy and surgery, ovarian cancer continues to have high mortality rates. Understanding the multiple roles of surgery throughout the disease course is the focus of this review. PMID:22343231

  12. Rethinking ovarian cancer: recommendations for improving outcomes.

    PubMed

    Vaughan, Sebastian; Coward, Jermaine I; Bast, Robert C; Berchuck, Andy; Berek, Jonathan S; Brenton, James D; Coukos, George; Crum, Christopher C; Drapkin, Ronny; Etemadmoghadam, Dariush; Friedlander, Michael; Gabra, Hani; Kaye, Stan B; Lord, Chris J; Lengyel, Ernst; Levine, Douglas A; McNeish, Iain A; Menon, Usha; Mills, Gordon B; Nephew, Kenneth P; Oza, Amit M; Sood, Anil K; Stronach, Euan A; Walczak, Henning; Bowtell, David D; Balkwill, Frances R

    2011-10-01

    There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article. PMID:21941283

  13. The treatment of early stage ovarian cancer.

    PubMed

    Young, R C

    1995-10-01

    Approximately one third of women with ovarian cancer present with localized disease. A series of recent studies have identified a population of patients who require only comprehensive surgical staging for optimal results and another group that may benefit from adjuvant therapy. A series of national and international studies are evaluating a variety of adjuvant treatments in prospective randomized trials that may enhance long-term survival in poor-prognosis early ovarian cancer. PMID:7481865

  14. [The molecular biology of epithelial ovarian cancer].

    PubMed

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research. PMID:23238064

  15. Unbalanced estrogen metabolism in ovarian cancer.

    PubMed

    Zahid, Muhammad; Beseler, Cheryl L; Hall, James B; LeVan, Tricia; Cavalieri, Ercole L; Rogan, Eleanor G

    2014-05-15

    Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p < 0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes. Women with two low-activity alleles of catechol-O-methyltransferase plus one or two high-activity alleles of cytochrome P450 1B1 had higher levels of estrogen-DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen-DNA adducts plays a critical role in the initiation of ovarian cancer. PMID:24170413

  16. Homologous recombination deficiency and ovarian cancer.

    PubMed

    Ledermann, Jonathan A; Drew, Yvette; Kristeleit, Rebecca S

    2016-06-01

    The discovery that PARP inhibitors block an essential pathway of DNA repair in cells harbouring a BRCA mutation has opened up a new therapeutic avenue for high-grade ovarian cancers. BRCA1 and BRCA2 proteins are essential for high-fidelity repair of double-strand breaks of DNA through the homologous recombination repair (HRR) pathway. Deficiency in HRR (HRD) is a target for PARP inhibitors. The first PARP inhibitor, olaparib, has now been licensed for BRCA-mutated ovarian cancers. While mutated BRCA genes are individually most commonly associated with HRD other essential HRR proteins may be mutated or functionally deficient potentially widening the therapeutic opportunities for PARP inhibitors. HRD is the first phenotypically defined predictive marker for therapy with PARP inhibitors in ovarian cancer. Several different PARP inhibitors are being trialled in ovarian cancer and this class of drugs has been shown to be a new selective therapy for high-grade ovarian cancer. Around 20% of high-grade serous ovarian cancers harbour germline or somatic BRCA mutations and testing for BRCA mutations should be incorporated into routine clinical practice. The expanded use of PARP inhibitors in HRD deficient (non-BRCA mutant) tumours using a signature of HRD in clinical practice requires validation. PMID:27065456

  17. Diagnosis and Management of Ovarian Cancer.

    PubMed

    Doubeni, Chyke A; Doubeni, Anna R; Myers, Allison E

    2016-06-01

    Ovarian cancer is the most lethal gynecologic cancer. Less than one-half of patients survive for more than five years after diagnosis. Ovarian cancer affects women of all ages but is most commonly diagnosed after menopause. More than 75% of affected women are diagnosed at an advanced stage because early-stage disease is usually asymptomatic and symptoms of late-stage disease are nonspecific. The strongest risk factors are advancing age and family history of ovarian and breast cancer. Women who have symptoms concerning for ovarian cancer should undergo a physical examination, transvaginal ultrasonography, and measurement of biomarkers such as cancer antigen 125. If results are suspicious for ovarian cancer, the patient should be referred to a gynecologic oncologist. Despite the low rate of early diagnosis, guidelines recommend against routine screening for ovarian cancer in average-risk women because screening, including routine pelvic examinations, is ineffective and associated with harm. However, a recent trial found a potential benefit of annual screening using an algorithm based on serial cancer antigen 125 measurements followed by transvaginal ultrasonography for women at increased risk, as determined by the algorithm. Women with an increased-risk family history should be referred for genetic counseling and, if genetic mutations (e.g., BRCA mutations) are identified, bilateral salpingo-oophorectomy can be considered for risk reduction. In both average- and high-risk women, long-term hormonal contraceptive use reduces risk by about 50%. The treatment of ovarian cancer usually involves surgery, with or without intraperitoneal and intravenous chemotherapy. Primary care physicians have important roles in posttreatment surveillance and end-of-life care. PMID:27281838

  18. Features of ovarian cancer in Lynch syndrome (Review)

    PubMed Central

    NAKAMURA, KANAKO; BANNO, KOUJI; YANOKURA, MEGUMI; IIDA, MIHO; ADACHI, MASATAKA; MASUDA, KENTA; UEKI, ARISA; KOBAYASHI, YUSUKE; NOMURA, HIROYUKI; HIRASAWA, AKIRA; TOMINAGA, EIICHIRO; AOKI, DAISUKE

    2014-01-01

    Lynch syndrome is a hereditary ovarian cancer with a prevalence of 0.9–2.7%. Lynch syndrome accounts for 10–15% of hereditary ovarian cancers, while hereditary breast and ovarian cancer syndrome accounts for 65–75% of these cancers. The lifetime risk for ovarian cancer in families with Lynch syndrome is ~8%, which is lower than colorectal and endometrial cancers, and ovarian cancer is not listed in the Amsterdam Criteria II. More than half of sporadic ovarian cancers are diagnosed in stage III or IV, but ≥80% of ovarian cancers in Lynch syndrome are diagnosed in stage I or II. Ovarian cancers in Lynch syndrome mostly have non-serous histology and different properties from those of sporadic ovarian cancers. A screening method for ovarian cancers in Lynch syndrome has yet to be established and clinical studies of prophylactic administration of oral contraceptives are not available. However, molecular profiles at the genetic level indicate that ovarian cancer in Lynch syndrome has a more favorable prognosis than sporadic ovarian cancer. Inhibitors of the phosphatidylinositol 3-kinase/mammalian target of the rapamycin pathway and anti-epidermal growth factor antibodies may have efficacy for the disease. To the best of our knowledge, this is the first review focusing on ovarian cancer in Lynch syndrome. PMID:25279173

  19. Lost expression of DCC gene in ovarian cancer and its inhibition in ovarian cancer cells.

    PubMed

    Meimei, Liu; Peiling, Li; Baoxin, Li; Changmin, Li; Rujin, Zhuang; Chunjie, Hu

    2011-03-01

    Ovarian cancer is a leading cause of cancer-related women mortality in China. In recent years, the molecular mechanisms involved in ovarian carcinoma development and/or progression have been intensely studied, and several genes have been identified. Deleted in Colorectal Carcinoma (DCC), is an important tumor suppressor gene, which is inactivated in many kinds of tumors, and its function(s) is not clarified. Even though the lost expression of DCC occurred in later stages of multistep colorectal carcinogenesis, its contribution to the onset or progression of ovarian cancer is not fully understood. To investigate DCC expression in ovarian cancer, we studied 254 clinical samples by RT-PCR. Our results revealed that 52% malignant ovarian cancer did not express DCC gene. By contrast, DCC expression was observed in all normal ovary tissues and 80% benign ovarian tumors. Obviously, there was a significant correlation between DCC expression and ovarian cancer, especially in the epithelial ovarian cancer. The present study also suggested that the loss expression of DCC occurred more frequently in the cases of later clinical stage, higher pathological grade, and poorer prognosis. In the other part of this study, we further explored DCC expression after transfection in two kinds of ovarian cancer cell lines, namely SKOV3 cell and HO-8910 cell, using RT-PCR and immunocytochemistry. The results indicated that DCC expressed in SKOV3-DCC and HO-8910-DCC cells, and ultrastructural analysis showed the appearance of apoptotic features in them. Furthermore, cell growth was markedly down-regulated in above groups of cells, indicating that transfection with the DCC constructs can suppress the growth of tumor cells. In conclusion, our results suggest an association of lost expression of DCC with the ovarian cancer, and DCC gene may inhibit the growth of ovarian carcinoma cells. However, this result needs further trials with a larger sample. PMID:20054719

  20. Three-dimensional modeling of ovarian cancer

    PubMed Central

    Erin, White; Hilary, Kenny; Ernst, Lengyel

    2015-01-01

    New models for epithelial ovarian cancer initiation and metastasis are required to obtain a mechanistic understanding of the disease and to develop new therapeutics. Modeling ovarian cancer however is challenging as a result of the genetic heterogeneity of the malignancy, the diverse pathology, the limited availability of human tissue for research, the atypical mechanisms of metastasis, and because the origin is unclear. Insights into the origin of high-grade serous ovarian carcinomas and mechanisms of metastasis have resulted in the generation of novel three-dimensional (3D) culture models that better approximate the behavior of the tumor cells in vivo than prior two-dimensional models. The 3D models aim to recapitulate the tumor microenvironment, which has a critical role in the pathogenesis of ovarian cancer. Ultimately, findings using models that accurately reflect human ovarian cancer biology are likely to translate into improved clinical outcomes. In this review we discuss the design of new 3D culture models of ovarian cancer primarily using human cells, key studies in which these models have been applied, current limitations, and future applications. PMID:25034878

  1. Cisplatin and Paclitaxel in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-29

    Chemotherapeutic Agent Toxicity; Endometrial Adenocarcinoma; Fallopian Tube Carcinoma; Gastrointestinal Complication; Malignant Ovarian Mixed Epithelial Tumor; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Primary Peritoneal Carcinoma; Stage II Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; Undifferentiated Ovarian Carcinoma

  2. Genetic heterogeneity of breast-ovarian cancer revisited

    SciTech Connect

    Narod, S.; Ford, D.; Easton, D.

    1995-10-01

    We have recently reported the results of a linkage analysis of 145 breast-ovarian cancer families. Each family has three or more cases of early-onset breast cancer (age {le}60) or of ovarian cancer, and all families have at least one case of ovarian cancer (there were nine site-specific ovarian cancer families). Overall, we estimated that 76% of the families were linked to the BRCA1 locus. 5 refs., 1 tab.

  3. Adoptive immunotherapy against ovarian cancer.

    PubMed

    Mittica, Gloria; Capellero, Sonia; Genta, Sofia; Cagnazzo, Celeste; Aglietta, Massimo; Sangiolo, Dario; Valabrega, Giorgio

    2016-01-01

    The standard front-line therapy for epithelial ovarian cancer (EOC) is combination of debulking surgery and platinum-based chemotherapy. Nevertheless, the majority of patients experience disease recurrence. Although extensive efforts to find new therapeutic options, cancer cells invariably develop drug resistance and disease progression. New therapeutic strategies are needed to improve prognosis of patients with advanced EOC.Recently, several preclinical and clinical studies investigated feasibility and activity of adoptive immunotherapy in EOC. Our aim is to highlight prospective of adoptive immunotherapy in EOC, focusing on HLA-restricted Tumor Infiltrating Lymphocytes (TILs), and MHC-independent immune effectors such as natural killer (NK), and cytokine-induced killer (CIK). Adoptive cell therapy (ACT) has shown activity in several pre-clinical models. Available preclinical and clinical data suggest that adoptive cell therapy may provide the best benefit in settings of low tumor burden, minimal residual disease, or maintenance therapy. Further studies are needed to better define the optimal clinical setting. PMID:27188274

  4. Ovarian stimulation in patients with breast cancer

    PubMed Central

    Muñoz, Elkin; González, Naira; Muñoz, Luis; Aguilar, Jesús; Velasco, Juan A García

    2015-01-01

    Breast cancer is the most prevalent malignancy among women under 50. Improvements in diagnosis and treatment have yielded an important decrease in mortality in the last 20 years. In many cases, chemotherapy and radiotherapy develop side effects on the reproductive function. Therefore, before the anti-cancer treatment impairs fertility, clinicians should offer some techniques for fertility preservation for women planning motherhood in the future. In order to obtain more available oocytes for IVF, the ovary must be stimulated. New protocols which prevent exposure to increased estrogen during gonadotropin stimulation, measurements to avoid the delay in starting anti-cancer treatment or the outcome of ovarian stimulation have been addressed in this review. There is no evidence of association between ovarian stimulation and breast cancer. It seems that there are more relevant other confluent factors than ovarian stimulation. Factors that can modify the risk of breast cancer include: parity, age at full-term birth, age of menarche, and family history. There is an association between breast cancer and exogenous estrogen. Therefore, specific protocols to stimulate patients with breast cancer include anti-estrogen agents such as letrozole. By using letrozole plus recombinant follicular stimulating hormone, patients develop a multifollicular growth with only a mild increase in estradiol serum levels. Controlled ovarian stimulation (COS) takes around 10 days, and we discuss new strategies to start COS as soon as possible. Protocols starting during the luteal phase or after inducing the menses currently prevent a delay in starting ovarian stimulation. Patients with breast cancer have a poorer response to COS compared with patients without cancer who are stimulated with conventional protocols of gonadotropins. Although many centres offer fertility preservation and many patients undergo ovarian stimulation, there are not enough studies to evaluate the recurrence, breast cancer

  5. Paclitaxel, Cisplatin, and Topotecan With or Without Filgrastim in Treating Patients With Newly Diagnosed Stage III or Stage IV Epithelial Ovarian Cancer

    ClinicalTrials.gov

    2013-01-23

    Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  6. Studying platinum sensitivity and resistance in high-grade serous ovarian cancer: Different models for different questions.

    PubMed

    Alkema, Nicolette G; Wisman, G Bea A; van der Zee, Ate G J; van Vugt, Marcel A T M; de Jong, Steven

    2016-01-01

    High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among all gynecological cancers. Patients are generally diagnosed in an advanced stage with the majority of cases displaying platinum resistant relapses. Recent genomic interrogation of large numbers of HGSOC patient samples indicated high complexity in terms of genetic aberrations, intra- and intertumor heterogeneity and underscored their lack of targetable oncogenic mutations. Sub-classifications of HGSOC based on expression profiles, termed 'differentiated', 'immunoreactive', 'mesenchymal' and 'proliferative', were shown to have prognostic value. In addition, in almost half of all HGSOC patients, a deficiency in homologous recombination (HR) was found that potentially can be targeted using PARP inhibitors. Developing precision medicine requires advanced experimental models. In the current review, we discuss experimental HGSOC models in which resistance to platinum therapy and the use of novel therapeutics can be carefully studied. Panels of better-defined primary cell lines need to be established to capture the full spectrum of HGSOC subtypes. Further refinement of cell lines is obtained with a 3-dimensional culture model mimicking the tumor microenvironment. Alternatively, ex vivo ovarian tumor tissue slices are used. For in vivo studies, larger panels of ovarian cancer patient-derived xenografts (PDXs) are being established, encompassing all expression subtypes. Ovarian cancer PDXs grossly retain tumor heterogeneity and clinical response to platinum therapy is preserved. PDXs are currently used in drug screens and as avatars for patient response. The role of the immune system in tumor responses can be assessed using humanized PDXs and immunocompetent genetically engineered mouse models. Dynamic tracking of genetic alterations in PDXs as well as patients during treatment and after relapse is feasible by sequencing circulating cell-free tumor DNA and analyzing circulating tumor cells. We

  7. Two-Pronged Chemo Helps Some with Advanced Ovarian Cancer

    MedlinePlus

    ... html Two-Pronged Chemo Helps Some With Advanced Ovarian Cancer Study found using both abdomen drip and ... 4, 2016 (HealthDay News) -- Some women with advanced ovarian cancer may fare better if chemotherapy is dripped ...

  8. Breast and Ovarian Cancer and Family History Risk Categories

    MedlinePlus

    ... Diseases Genomic Resources Breast and Ovarian Cancer and Family History Risk Categories Recommend on Facebook Tweet Share ... Screening. U.S. Preventive Services Task Force. February 2016. Family Health History, Breast and Ovarian Cancer Risk, and ...

  9. Does Breast or Ovarian Cancer Run in Your Family?

    MedlinePlus

    ... Does Breast or Ovarian Cancer Run in Your Family? Language: English Español (Spanish) Recommend on Facebook Tweet ... get ovarian cancer by age 70. Does Your Family Health History Put You At Risk? Tell your ...

  10. Epigenetic targeting of ovarian cancer stem cells.

    PubMed

    Wang, Yinu; Cardenas, Horacio; Fang, Fang; Condello, Salvatore; Taverna, Pietro; Segar, Matthew; Liu, Yunlong; Nephew, Kenneth P; Matei, Daniela

    2014-09-01

    Emerging results indicate that cancer stem-like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem-like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem-like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem-like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH(+) ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH(+) cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem-like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. PMID:25035395

  11. Mucinous ovarian cancer: A therapeutic review.

    PubMed

    Xu, Wen; Rush, Jack; Rickett, Kirsty; Coward, Jermaine I G

    2016-06-01

    Mucinous ovarian cancer represents approximately 3% of epithelial ovarian cancers (EOC). Despite this seemingly low prevalence, it remains a diagnostic and therapeutic conundrum that has resulted in numerous attempts to adopt novel strategies in managing this disease. Anecdotally, there has been a prevailing notion that established gold standard systemic regimens should be substituted for those utilised in cancers such as gastrointestinal (GI) malignancies; tumours that share more biological similarities than other EOC subtypes. This review summarises the plethora of small studies which have adopted this philosophy and influenced the design of the multinational GOG142 study, which was ultimately terminated due to poor accrual. To date, there is a paucity of evidence to support delivering 'GI style' chemotherapy for mucinous ovarian cancer over and above carboplatin-paclitaxel doublet therapy. Hence there is an urge to develop studies focused on targeted therapeutic agents driven by refined mutational analysis and conducted within the context of harmonised international collaborations. PMID:27083591

  12. Olaparib in the management of ovarian cancer

    PubMed Central

    Bixel, Kristin; Hays, John L

    2015-01-01

    Alterations in the homologous repair pathway are thought to occur in 30%–50% of epithelial ovarian cancers. Cells deficient in homologous recombination rely on alternative pathways for DNA repair in order to survive, thereby providing a potential target for therapy. Olaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, capitalizes on this concept and is the first drug in its class approved for patients with ovarian cancer. This review article will provide an overview of the BRCA genes and homologous recombination, the role of PARP in DNA repair and the biological rationale for the use of PARP inhibitors as cancer therapy, and ultimately will focus on the use of olaparib in the management of ovarian cancer. PMID:26309417

  13. Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-01-15

    Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

  14. CA125 in Ovarian Cancer

    PubMed Central

    Urban, Nicole

    2009-01-01

    Summary Twenty five years after its discovery, circulating CA125 antigen is recommended for clinical use in the US for ovarian cancer (OC) screening of high risk women with ovaries despite its limited sensitivity and specificity. Recent findings suggest that CA125 might also serve as a predictive marker for pre-invasive OC. Methods to quantify circulating CA125 evolved towards sensitive and reliable double determinant ELISA assays. The CA125 gene, MUC16, was cloned 20 years after the protein discovery and revealed a very complex and unusual glycoprotein structure suggesting an immunological role. Recent evidence points toward CA125 function in the induction of materno-fetal tolerance through the alteration of NK phenotype. Two receptors for CA125 have been described: mesothelin and galectin-1. The specific location and functional proprieties of CA125 make it a therapeutic target of choice; clinical trials have demonstrated that anti-CA125 injections are well tolerated and suggest a potential survival benefit. PMID:20477371

  15. Tumor infiltrating lymphocytes in ovarian cancer

    PubMed Central

    Santoiemma, Phillip P; Powell, Daniel J

    2015-01-01

    The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment. PMID:25894333

  16. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    ClinicalTrials.gov

    2016-02-09

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  17. ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC.

    PubMed

    Cheng, Qijian; Zhou, Ling; Zhou, Jianping; Wan, Huanying; Li, Qingyun; Feng, Yun

    2016-09-01

    Angiotensin II (AngII) is a multifunctional bioactive peptide in the renin-angiotensin system (RAS). Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS. We previously reported that ACE2 overexpression may inhibit cell growth and vascular endothelial growth factor (VEGF) production in vitro and in vivo. In the present study, we investigated the effect of ACE2 on tumor-associated angiogen-esis after the development of acquired platinum resistance in non-small cell lung cancer (NSCLC). Four NSCLC cell lines, A549, LLC, A549-DDP and LLC-DDP, were used in vitro, while A549 and A549-DDP cells were used in vivo. A549-DDP and LLC-DDP cells were newly established at our institution as acquired platinum-resistant sublines by culturing the former parent cells in cisplatin (CDDP)-containing conditioned medium for 6 months. These platinum-resistant cells showed significantly higher angiotensin II type 1 receptor (AT1R), ACE and VEGF production and lower ACE2 expression than their corresponding parent cells. We showed that ACE2 overexpression inhibited the production of VEGF in vitro and in vivo compared to their corresponding parent cells. We also found that ACE2 overexpression reduced the expression of AT1R and ACE. Additionally, we confirmed that ACE2 overexpres-sion inhibited cell growth and VEGF production while simultaneously suppressing ACE and AT1R expression in human lung cancer xenografts. Our findings indicate that ACE2 overexpression may potentially suppress angiogenesis in NSCLC after the development of acquired platinum resistance. PMID:27460845

  18. Theaflavin-3, 3'-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells.

    PubMed

    Tu, Youying; Kim, Eunhye; Gao, Ying; Rankin, Gary O; Li, Bo; Chen, Yi Charlie

    2016-06-01

    Ovarian cancer is the most lethal gynecological cancer among women worldwide. Adverse side effects and acquired resistance to conventional platinum based chemotherapy are major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs that target cancer-specific defects. In this study, theaflavin-3, 3'-digallate (TF3), the major theaflavin monomer in black tea, exhibited a potent growth inhibitory effect on the cisplatin-resistant ovarian cancer A2780/CP70 cells (IC50, 23.81 µM), and was less cytotoxic to a normal ovarian IOSE‑364 cells (IC50, 59.58 µM) than to the cancer cells. Flow cytometry analysis indicated that TF3 induced preferential apoptosis and G2 cell cycle arrest in A2780/CP70 cells with respect to IOSE‑364 cells. TF3 induced apoptosis through both the intrinsic and extrinsic apoptotic pathways, and caused G2 cell cycle arrest via cyclin B1 in A2780/CP70 cells. The p53 protein played an important role in TF3-induced apoptosis and G2 cell cycle arrest. TF3 might upregulate the p53 expression via the Akt/MDM2 pathway. Our findings help elucidate the mechanisms by which TF3 may contribute to the prevention and treatment of platinum-resistant ovarian cancer. PMID:27082635

  19. Theaflavin-3, 3′-digallate induces apoptosis and G2 cell cycle arrest through the Akt/MDM2/p53 pathway in cisplatin-resistant ovarian cancer A2780/CP70 cells

    PubMed Central

    TU, YOUYING; KIM, EUNHYE; GAO, YING; RANKIN, GARY O.; LI, BO; CHEN, YI CHARLIE

    2016-01-01

    Ovarian cancer is the most lethal gynecological cancer among women worldwide. Adverse side effects and acquired resistance to conventional platinum based chemotherapy are major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs that target cancer-specific defects. In this study, theaflavin-3, 3′-digallate (TF3), the major theaflavin monomer in black tea, exhibited a potent growth inhibitory effect on the cisplatin-resistant ovarian cancer A2780/CP70 cells (IC50, 23.81 μM), and was less cytotoxic to a normal ovarian IOSE-364 cells (IC50, 59.58 μM) than to the cancer cells. Flow cytometry analysis indicated that TF3 induced preferential apoptosis and G2 cell cycle arrest in A2780/CP70 cells with respect to IOSE-364 cells. TF3 induced apoptosis through both the intrinsic and extrinsic apoptotic pathways, and caused G2 cell cycle arrest via cyclin B1 in A2780/CP70 cells. The p53 protein played an important role in TF3-induced apoptosis and G2 cell cycle arrest. TF3 might upregulate the p53 expression via the Akt/MDM2 pathway. Our findings help elucidate the mechanisms by which TF3 may contribute to the prevention and treatment of platinum-resistant ovarian cancer. PMID:27082635

  20. Ovarian cancer treatment: The end of empiricism?

    PubMed

    Lheureux, Stephanie; Karakasis, Katherine; Kohn, Elise C; Oza, Amit M

    2015-09-15

    The diagnosis, investigation, and management of ovarian cancer are in a state of flux-balancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence-informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer. PMID:26096019

  1. Paclitaxel and Carboplatin With or Without Bevacizumab in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2015-12-21

    Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinofibroma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  2. Ovarian Cancer Biomarker Performance in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Specimens

    PubMed Central

    Cramer, Daniel W.; Bast, Robert C.; Berg, Christine D.; Diamandis, Eleftherios P.; Godwin, Andrew K.; Hartge, Patricia; Lokshin, Anna E.; Lu, Karen H.; McIntosh, Martin W.; Mor, Gil; Patriotis, Christos; Pinsky, Paul F.; Thornquist, Mark D.; Scholler, Nathalie; Skates, Steven J.; Sluss, Patrick M.; Srivastava, Sudhir; Ward, David C.; Zhang, Zhen; Zhu, Claire S.; Urban, Nicole

    2011-01-01

    Establishing a cancer screening biomarker’s intended performance requires “phase III” specimens obtained in asymptomatic individuals before clinical diagnosis rather than “phase II” specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network (EDRN) or Ovarian Cancer Specialized Program of Research Excellence (SPORE) sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within six months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study. PMID:21372036

  3. Hypodontia and ovarian cancer: A systematic review

    PubMed Central

    Iavazzo, Christos; Papakiritsis, Matthaios; Gkegkes, Ioannis D.

    2016-01-01

    Hypodontia can be defined as the non-formation of one or more teeth during the developmental period. Mutation in several genes related to tooth formation has previously been correlated with cancer. Regarding the ovarian cancer, there are few studies that associate the presence of hypodontia with ovarian cancer. A systematic literature search was performed in PubMed and Scopus. In total, 385 patients were included in this study. Control group was present in 3 out of 4 studies (340 patients). Hypodontia was present in 56 out of 290 patients (incidence of 19.3%). Only in 2 out of 4 studies, the number of missing teeth was mentioned (47 teeth), while the majority of them were either maxillary second premolars or maxillary lateral incisors. Unilateral distribution of the missing teeth was present in 28 out of 46 patients, while bilateral distribution of the missing teeth was present in 18 out of 46 patients. The presence of ovarian cancer in the family medical history occurred in 12 out of 33 patients. Only 1 out of 4 studies examined the presence of genes with mutations in the included patients. Based on our findings, the lack of clinical studies was the principal obstacle to clarify the possible predictive value of hypodontia in the early prediction of patients with higher risk of ovarian cancer. PMID:27026778

  4. [Immunological analogies between ovarian cancer and pregnancy].

    PubMed

    Hanssen, S; Collinet, P; Leblanc, E; Salzet, M; Vinatier, D

    2013-05-01

    During pregnancy an environment allowing installation of tolerance toward the fetus is set up locally at the materno-fetal interface. Numerous effectors of immunity are involved in this tolerance (NK cell, T cell, Macrophages, dendritic cell). Specific mechanisms during pregnancy attract locally these immunological cells. In the decidua, they are educated toward tolerance. These mechanisms evolve during the pregnancy because at the end of the pregnancy, tolerance is broken to prepare and activate the labor. Ovarian tumors, after having surmounted the immunosurveillance, like trophoblast, chair the installation of a tolerance of their host facilitating the development of the disease. The blocking of these mechanisms of tolerance coupled with activation of mechanisms of defenses offer new perspectives in the treatment of the ovarian cancer. The authors suggest showing the analogies of the tolerance observed during ovarian cancer and pregnancy. The knowledge of the orchestration of the physiological mechanisms observed during pregnancy will offer new therapeutic targets. PMID:23182791

  5. Quality of Life and Care Needs of Patients With Persistent or Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

    ClinicalTrials.gov

    2016-03-17

    Anxiety; Fatigue; Nausea and Vomiting; Neurotoxicity Syndrome; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IB Fallopian Tube Cancer; Stage IC Fallopian Tube Cancer; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIB Fallopian Tube Cancer; Stage IIC Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIC Fallopian Tube Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  6. Targeting the EGF Receptor for Ovarian Cancer Therapy

    PubMed Central

    Zeineldin, Reema; Muller, Carolyn Y.; Stack, M. Sharon; Hudson, Laurie G.

    2010-01-01

    Ovarian carcinoma is the leading cause of death from gynecologic malignancy in the US. Factors such as the molecular heterogeneity of ovarian tumors and frequent diagnosis at advanced stages hamper effective disease treatment. There is growing emphasis on the identification and development of targeted therapies to disrupt molecular pathways in cancer. The epidermal growth factor (EGF) receptor is one such protein target with potential utility in the management of ovarian cancer. This paper will discuss contributions of EGF receptor activation to ovarian cancer pathogenesis and the status of EGF receptor inhibitors and EGF receptor targeted therapies in ovarian cancer treatment. PMID:20066160

  7. Targeted Immune Therapy of Ovarian Cancer

    PubMed Central

    Knutson, Keith L.; Karyampudi, Lavakumar; Lamichhane, Purushottam; Preston, Claudia

    2014-01-01

    Clinical outcomes, such as recurrence free survival and overall survival, in ovarian cancer are quite variable, independent of common characteristics such as stage, response to therapy and grade. This disparity in outcomes warrants further exploration and therapeutic targeting into the interaction between the tumor and host. One compelling host characteristic that contributes both to the initiation and progression of ovarian cancer is the immune system. Hundreds of studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease. Recent studies also show that anti-tumor immunity is often negated by immune regulatory cells present in the tumor microenvironment. Regulatory immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, in the future, research into immunotherapy targeting ovarian cancer will probably become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression. In this article, we summarize important immunological targets that influence ovarian cancer outcome as well as include an update on newer immunotherapeutic strategies. PMID:25544369

  8. Microvesicles as Potential Ovarian Cancer Biomarkers

    PubMed Central

    Giusti, Ilaria; D'Ascenzo, Sandra; Dolo, Vincenza

    2013-01-01

    Although the incidence of ovarian cancer is low (i.e., less than 5% in European countries), it is the most lethal gynecologic malignancy and typically has a poor prognosis. To ensure optimal survival, it is important to diagnose this condition when the pathology is confined to the ovary. However, this is difficult to achieve because the first specific symptoms appear only during advanced disease stages. To date, the biomarker mainly used for the diagnosis and prognosis of ovarian cancer is CA125; however, this marker has a low sensitivity and specificity and is associated with several other physiological and pathological conditions. No other serum ovarian cancer markers appear to be able to replace or complement CA125, and the current challenge is therefore to identify novel markers for the early diagnosis of this disease. For this purpose, studies have focused on the microvesicles (MVs) released from tumor cells. MVs may represent an ideal biomarker because they can be easily isolated from blood, and they have particular features (mainly regarding microRNA profiles) that strongly correlate with ovarian cancer stage and may be effective for early diagnosis. PMID:23484144

  9. Surgical management of recurrent ovarian cancer.

    PubMed

    Suh, Dong Hoon; Kim, Hee Seung; Chang, Suk-Joon; Bristow, Robert E

    2016-08-01

    Most patients with advanced-stage epithelial ovarian cancer will experience a relapse of disease despite a complete response after surgical cytoreduction and platinum-based chemotherapy. Treatment of recurrent ovarian cancer mainly comprises various combinations of systemic chemotherapy with or without targeted agents. The role of cytoreductive surgery for recurrent ovarian cancer is not well established. Although the literature on survival benefit of cytoreductive surgery for recurrent disease has expanded steadily over the past decade, most studies were retrospective, single-institution series with small numbers of patients. Given the balance between survival benefit and surgery-related morbidity during maximum cytoreductive surgical effort, it is essential to establish the optimal selection criteria for identifying appropriate candidates who will benefit from surgery without worsening quality of life. Three phase III randomized trials for this issue are currently underway. Herein, we present contemporary evidence supporting the positive role of cytoreductive surgery and offer selection criteria for optimal candidates for surgery in the treatment of recurrent ovarian cancer. PMID:27130407

  10. Ovarian Cancer Rates by Race and Ethnicity

    MedlinePlus

    ... any other group, followed by black, Hispanic, American Indian/Alaska Native, and Asian/Pacific Islander women. Ovarian Cancer Death Rates* by Race and Ethnicity, U.S., 1999–2012 Mortality source: U.S. Mortality Files, National Center for Health ...

  11. Use of ChemoFx® for Identification of Effective Treatments in Epithelial Ovarian Cancer

    PubMed Central

    Richard, Scott; Wells, Alan; Connor, Joseph; Price, Fredric

    2015-01-01

    Selection of appropriate chemotherapy, including identification of platinum resistance, is critical to effective management of advanced epithelial ovarian cancer (EOC). ChemoFx®, a multiple treatment marker (chemoresponse assay), has been developed to address this challenge and to improve outcomes in patients with advanced EOC. While much work has been done that has demonstrated the analytical validity of this assay, more recent studies have highlighted the unique clinical benefits offered by the assay. A prospective, multicenter trial has shown an increase in overall survival (OS) of 14 months and an increase in progression-free survival (PFS) by 3 months in patients with recurrent EOS treated by a “sensitive” therapy based on ChemoFx results. Along with other studies showing similar gains in OS and PFS, ChemoFx has been shown to be both a prognostic and predictive marker in patients with recurrent EOC where current treatment options are sorely lacking. In addition to these clinical benefits, economic analyses have shown that ChemoFx is a cost-effective intervention. Current guidelines and technology assessments relating to ChemoFx are largely outdated and refer primarily to metrics of analytical validity. Thus, in addition to analytical validity, the clinical validity, clinical utility and economic impact of ChemoFx are reviewed herein, including published literature, technology assessments by independent parties, and regulatory approvals of this marker. PMID:26213638

  12. Drugs Approved for Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Ovarian, Fallopian Tube, or Primary Peritoneal ... primary peritoneal cancer that are not listed here. Drugs Approved for Ovarian, Fallopian Tube, or Primary Peritoneal ...

  13. Ovarian cancer treatment: The end of empiricism?

    PubMed Central

    Lheureux, Stephanie; Karakasis, Katherine; Kohn, Elise C.

    2015-01-01

    The diagnosis, investigation, and management of ovarian cancer are in a state of flux—balancing ever rapid advances in our understanding of its biology with 3 decades of clinical trials. Clinical trials that started with empirically driven selections have evolved in an evidence‐informed manner to gradually improve outcome. Has this improved understanding of the biology and associated calls to action led to appropriate changes in therapy? In this review, the authors discuss incorporating emerging data on biology, combinations, dose, and scheduling of new and existing agents with patient preferences in the management of women with ovarian cancer. Cancer 2015;121:3203–3211. © 2015 American Cancer Society. PMID:26096019

  14. Identification of genes associated with platinum drug sensitivity and resistance in human ovarian cancer cells

    PubMed Central

    Roberts, D; Schick, J; Conway, S; Biade, S; Laub, P B; Stevenson, J P; Hamilton, T C; O'Dwyer, P J; Johnson, S W

    2005-01-01

    Platinum-based chemotherapeutic regimens are ultimately unsuccessful due to intrinsic or acquired drug resistance. Understanding the molecular basis for platinum drug sensitivity/resistance is necessary for the development of new drugs and therapeutic regimens. In an effort to identify such determinants, we evaluated the expression of approximately 4000 genes using cDNA microarray screening in a panel of 14 unrelated human ovarian cancer cell lines derived from patients who were either untreated or treated with platinum-based chemotherapy. These data were analysed relative to the sensitivities of the cells to four platinum drugs (cis-diamminedichloroplatinum (cisplatin), carboplatin, DACH-(oxalato)platinum (II) (oxaliplatin) and cis-diamminedichloro (2-methylpyridine) platinum (II) (AMD473)) as well as the proliferation rate of the cells. Correlation analysis of the microarray data with respect to drug sensitivity and resistance revealed a significant association of Stat1 expression with decreased sensitivity to cisplatin (r=0.65) and AMD473 (r=0.76). These results were confirmed by quantitative RT–PCR and Western blot analyses. To study the functional significance of these findings, the full-length Stat1 cDNA was transfected into drug-sensitive A2780 human ovarian cancer cells. The resulting clones that exhibited increased Stat1 expression were three- to five-fold resistant to cisplatin and AMD473 as compared to the parental cells. The effect of inhibiting Jak/Stat signalling on platinum drug sensitivity was investigated using the Janus kinase inhibitor, AG490. Pretreatment of platinum-resistant cells with AG490 resulted in significant increased sensitivity to AMD473, but not to cisplatin or oxaliplatin. Overall, the results indicate that cDNA microarray analysis may be used successfully to identify determinants of drug sensitivity/resistance and future functional studies of other candidate genes from this database may lead to an increased understanding of the

  15. Targeting CD133 in an in vivo ovarian cancer model reduces ovarian cancer progression

    PubMed Central

    Skubitz, Amy P.N.; Taras, Elizabeth P.; Boylan, Kristin L.M.; Waldron, Nate N.; Oh, Seunguk; Panoskaltsis-Mortari, Angela; Vallera, Daniel A.

    2013-01-01

    Objectives While most women with ovarian cancer will achieve complete remission after treatment, the majority will relapse within two years, highlighting the need for novel therapies. Cancer stem cells (CSC) have been identified in ovarian cancer and most other carcinomas as a small population of cells that can self-renew. CSC are more chemoresistant and radio-resistant than the bulk tumor cells; it is likely that CSC are responsible for relapse, the major problem in cancer treatment. CD133 has emerged as one of the most promising markers for CSC in ovarian cancer. The hypothesis driving this study is that despite their low numbers in ovarian cancer tumors, CSC can be eradicated using CD133 targeted therapy and tumor growth can be inhibited. Methods Ovarian cancer cell lines were evaluated using flow cytometry for expression of CD133. In vitro viability studies with an anti-CD133 targeted toxin were performed on one of the cell lines, NIH:OVCAR5. The drug was tested in vivo using a stably transfected luciferase-expressing NIH:OVCAR5 subline in nude mice, so that tumor growth could be monitored by digital imaging in real time. Results Ovarian cancer cell lines showed 5.6% to 16.0% CD133 expression. dCD133KDEL inhibited the in vitro growth of NIH:OVCAR5 cells. Despite low numbers of CD133-expressing cells in the tumor population, intraperitoneal drug therapy caused a selective decrease in tumor progression in intraperitoneal NIH: OVCAR5-luc tumors. Conclusions Directly targeting CSC that are a major cause of drug resistant tumor relapse with an anti-CD133 targeted toxin shows promise for ovarian cancer therapy. PMID:23721800

  16. Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-05-22

    Chemotherapeutic Agent Toxicity; Neuropathy; Neurotoxicity Syndrome; Pain; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  17. Cisplatin induces stemness in ovarian cancer.

    PubMed

    Wiechert, Andrew; Saygin, Caner; Thiagarajan, Praveena S; Rao, Vinay S; Hale, James S; Gupta, Nikhil; Hitomi, Masahiro; Nagaraj, Anil Belur; DiFeo, Analisa; Lathia, Justin D; Reizes, Ofer

    2016-05-24

    The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility. PMID:27105520

  18. Gene expression profiling analysis of ovarian cancer

    PubMed Central

    YIN, JI-GANG; LIU, XIAN-YING; WANG, BIN; WANG, DAN-YANG; WEI, MAN; FANG, HUA; XIANG, MEI

    2016-01-01

    As a gynecological oncology, ovarian cancer has high incidence and mortality. To study the mechanisms of ovarian cancer, the present study analyzed the GSE37582 microarray. GSE37582 was downloaded from Gene Expression Omnibus and included data from 74 ovarian cancer cases and 47 healthy controls. The differentially-expressed genes (DEGs) were screened using linear models for microarray data package in R and were further screened for functional annotation. Next, Gene Ontology and pathway enrichment analysis of the DEGs was conducted. The interaction associations of the proteins encoded by the DEGs were searched using the Search Tool for the Retrieval of Interacting Genes, and the protein-protein interaction (PPI) network was visualized by Cytoscape. Moreover, module analysis of the PPI network was performed using the BioNet analysis tool in R. A total of 284 DEGs were screened, consisting of 145 upregulated genes and 139 downregulated genes. In particular, downregulated FBJ murine osteosarcoma viral oncogene homolog (FOS) was an oncogene, while downregulated cyclin-dependent kinase inhibitor 1A (CDKN1A) was a tumor suppressor gene and upregulated cluster of differentiation 44 (CD44) was classed as an ‘other’ gene. The enriched functions included collagen catabolic process, stress-activated mitogen-activated protein kinases cascade and insulin receptor signaling pathway. Meanwhile, FOS (degree, 15), CD44 (degree, 9), B-cell CLL/lymphoma 2 (BCL2; degree, 7), CDKN1A (degree, 7) and matrix metallopeptidase 3 (MMP3; degree, 6) had higher connectivity degrees in the PPI network for the DEGs. These genes may be involved in ovarian cancer by interacting with other genes in the module of the PPI network (e.g., BCL2-FOS, BCL2-CDKN1A, FOS-CDKN1A, FOS-CD44, MMP3-MMP7 and MMP7-CD44). Overall, BCL2, FOS, CDKN1A, CD44, MMP3 and MMP7 may be correlated with ovarian cancer. PMID:27347159

  19. Familial ovarian cancer: a study of 11 families.

    PubMed

    Villani, C; Ficorella, C; Tomao, S

    1989-01-01

    In a group of 152 ovarian cancer patients, 11 cases with familial recurrence were investigated (7.23%). Of the families evaluated we found 26 patients with ovarian cancer and twenty two with different cancers in other sites. In ovarian cancer the familial aspect, despite its relatively low frequency, is one of the few factors for identifying "high risk" patients, thus allowing effective secondary prevention. PMID:2776785

  20. [Treatment of brain metastasis from ovarian cancer].

    PubMed

    Bondiau, P-Y; Largillier, R; Foa, C; Rasendrarijao, D; Frenay, M; Gérard, J-P

    2003-06-01

    Systemic metastases from ovarian carcinoma are frequent, but they seldom affect the central nervous system. We present here the case of a patient treated for an ovarian cancer by surgery and chemotherapy. Three months after the end of chemotherapy, the patient developed cerebral metastases from ovarian carcinoma (CMOC) treated by iterative surgery and and whole brain irradiation. As the frequency of solitary cerebral metastasis of ovarian cancer is higher than with other cancers, it is likely that they behave slightly differently. Literature analysis reveals an increase in the incidence of CMOC since the middle of the nineties. CMOC can occur during or after adjuvant chemotherapy and the best management strategies to better define determinants of survival for patients are not well known. It appears that a better outcome of CMOC may be obtained by an aggressive treatment, if possible, including surgery, radiotherapy, and chemotherapy. Taking into account the increase in the incidence of the CMOC and their early occurrence, some authors have proposed a prophylactic brain radiotherapy in patients who receive adjuvant chemotherapy. PMID:12834774

  1. Sargramostim and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With Advanced Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer That Did Not Respond to Previous Chemotherapy

    ClinicalTrials.gov

    2014-01-15

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Peritoneal Cavity Cancer; Recurrent Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  2. Second-look laparoscopy in ovarian cancer.

    PubMed

    Xygakis, A M; Politis, G S; Michalas, S P; Kaskarelis, D B

    1984-08-01

    Forty-six patients with epithelial ovarian cancer previously treated with surgery, chemotherapy or external radiation underwent second-look laparoscopy to evaluate management. Twenty of the patients had positive laparoscopic findings and were not subjected to further laparotomy. The frequency of positive findings was related to the stage of the disease. Laparoscopic examination revealed no evidence of cancer in the remaining 26 patients. Three of the patients in this group were found to have additional disease at subsequent laparotomy. The laparoscopic procedures were not associated with major complications. Although second-look laparoscopy cannot replace repeat laparotomy, it does have a role in the follow-up of patients with ovarian cancer. PMID:6237197

  3. Clinical Efficacy of Ovarian Cancer Screening

    PubMed Central

    Koshiyama, Masafumi; Matsumura, Noriomi; Konishi, Ikuo

    2016-01-01

    Various trials of ovarian cancer screening programs have been reported worldwide. In 2011, one of the most famous papers indicated that annual screening using CA125/transvaginal sonography (TVS) did not reduce ovarian cancer mortality in the United States of America (USA). To investigate the validity of ovarian cancer screening, we verified the analyses of previous reports. At first, we obtained the USA datasets that were used for the analyses and identified many patients in whom cancers were accidentally detected several years after the screening period. We thus performed a new prognostic comparison between the screening group (cancers that were detected through screening or within one year after screening) and the control group (cancers that were found more than one year after screening, without screening, or in the original control group). The results showed that the prognoses of the screening group were significantly better than those of the control group (p=0.0017). In addition, the screening group contained significantly fewer stage IV cases than the control group (p=0.005). In another screening in the United Kingdom, ovarian cancer was detected at a relatively earlier stage (stage I/II: 44%), while the rate of stage IV detection was low (4%). Very recently, this team showed significant difference in the rates with and without screening (p=0.021) when prevalent cases were excluded and indicated the delayed effect of screening. These results contrasted with the USA data. In other studies in the USA and Japan, annual screening was also associated with a decreased stage at detection. New histopathological, molecular and genetic studies have recently provided two categories of ovarian carcinogenesis. Type I carcinomas are slow-growing neoplasms that often develop from benign ovarian cysts. Type II carcinomas are high-grade clinically aggressive neoplasms. The rate of type II carcinomas is significantly higher in Europe and the USA than in Asia (p<0

  4. Ovarian cancer proteomics: Many technologies one goal.

    PubMed

    Narasimhan, Kothandaraman; Changqing, Zhao; Choolani, Mahesh

    2008-02-01

    The last decade has seen major changes in the technologies used to identify markers for diagnosing cancer. This review focuses on recent developments on the evolving field of biomarker discovery, and validation techniques using proteomics platforms for ovarian cancer. It is possible now to diagnose various disease conditions using microliter quantities of body fluids. Currently the major developments were made in three distinct areas: (i) protein profiling, (ii) high-throughput validation techniques, and (iii) solid and liquid phase protein microarray platforms for analyzing candidate markers across subclasses and stages of cancers. The recent addition to the long list of technologies is metabolomics using metabolite profiling and informatics-based filtering of information for biomarker discovery of ovarian cancer. Emerging technologies need to address ways to eliminate the limitations posed by the complex dynamic nature of body fluids as well as ways to enrich low-abundance tumor markers if they were to become a successful biomarker discovery tool. These new technologies hold significant promise in identifying more robust markers for ovarian cancer. Since the prevalence of this disease in the population is low, the test must have a high specificity. PMID:21136825

  5. Ovarian Cancer Rates by State

    MedlinePlus

    ... Controls Search The CDC Cancel Submit Search The CDC Gynecologic Cancers Note: Javascript is disabled or is not supported ... about this message, please visit this page: About CDC.gov . Gynecologic Cancers Basic Information What Is Gynecologic Cancer? What Are ...

  6. ARHGAP10, downregulated in ovarian cancer, suppresses tumorigenicity of ovarian cancer cells

    PubMed Central

    Luo, N; Guo, J; Chen, L; Yang, W; Qu, X; Cheng, Z

    2016-01-01

    Rho GTPase-activating proteins (RhoGAPs) are implicated in the development and progression of ovarian cancer. ARHGAP10 is a member of RhoGAP proteins and inactivates Cdc42 by converting GTP-bound form to GDP-bound form. Here, we aimed to evaluate ARHGAP10 expression profile and functions in ovarian cancer. The decreased expression of ARHGAP10 was found in 77.3% (58/75) of ovarian cancer tissues, compared with their non-tumorous counterparts. Furthermore, overall survival in ovarian cancer patients with higher expression of ARHGAP10 was longer than those with lower expression. Ectopic expression of ARHGAP10 in two ovarian cancer cell lines with lower expression of ARHGAP10 (A2780 and HO-8910) dramatically suppressed cell proliferation in vitro. In nude mice, its stable overexpression significantly inhibited the tumorigenicity of A2780 cells. We further demonstrated that overexpression of ARHGAP10 significantly inhibited cell adhesion, migration and invasion, resulted in cell arrest in G1 phase of cell cycle and a significant increase of apoptosis. Moreover, ARHGAP10 interacted with Cdc42 and overexpression of ARHGAP10 inhibited the activity of Cdc42 in A2780 cells. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that KEGG cell cycle, replication and base excision repair (BER) pathways were correlatively with the ARHGAP10 expression, which was further confirmed in ovarian cancer cells by western blotting. Hence, ARHGAP10 may serve as a tumor suppressor through inactivating Cdc42, as well as inhibiting cell cycle, replication and BER pathways. Our data suggest an important role of ARHGAP10 in the molecular etiology of cancer and implicate the potential application of ARHGAP10 in cancer therapy. PMID:27010858

  7. MicroRNAs in Ovarian Cancer.

    PubMed

    Katz, Betina; Tropé, Claes G; Reich, Reuven; Davidson, Ben

    2015-09-01

    Ovarian cancer, consisting predominantly of ovarian carcinoma, is the eighth most common cancer in women and the most lethal gynecologic malignancy. Efforts focus on identifying biomarkers which may aid in early diagnosis and reduce mortality, as well as on characterizing therapeutic targets with the aim of circumventing chemoresistance and prolonging survival at advanced-stage disease. MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression, and have been found to play an important role in ovarian carcinoma. Recent research has identified multiple miRNAs involved in the biology and progression of the disease, and supports a role for miRNAs as potential biomarkers, predictive markers and prognostic factors. Many of the studies published to date nevertheless suffer from critical weaknesses which affect data quality and reproducibility, including the comparison of normal ovaries to tumor tissue without compensation for the highly discrepant target cell fraction in these two specimen types and the inclusion of carcinomas of different histotypes, non-epithelial tumors or tumors of non-specified histology. These shortcomings highlight the critical role of pathologists as part of the team in the setting of such research. This review summarizes current knowledge in this area and discusses the potential clinical relevance of miRNAs in ovarian carcinoma, with focus on studies of clinical specimens in which tissue selection has been deemed adequate. PMID:26216350

  8. Hormone Therapy and Ovarian Cancer: Incidence and Survival

    PubMed Central

    Wernli, Karen J.; Newcomb, Polly A.; Hampton, John; Trentham-Dietz, Amy; Egan, Kathleen M.

    2009-01-01

    Objective We conducted a population-based case-control study to investigate the association between hormone therapy (HT) and ovarian cancer incidence, and followed all these cancer cases to determine the association of HT use with ovarian cancer mortality. Methods Seven hundred fifty-one incident cases of invasive epithelial ovarian cancer aged 40–79 years were diagnosed in Wisconsin and Massachusetts between 1993–1995 and 1998–2001 and matched to similarly-aged controls (n=5808). Study subjects were interviewed by telephone, which ascertained information on HT use and specific preparation, estrogen alone (E-alone) or estrogen plus progestin (EP). Ovarian cancer cases were followed-up for mortality through December 2005. Multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals (CI) for ovarian cancer incidence, and Cox proportional hazards modeling was used to estimate hazard ratios and corresponding confidence intervals for ovarian cancer mortality. Results Ever use of HT was significantly associated with an increased risk of ovarian cancer (odds ratio 1.57, 95% CI 1.31–1.87). The excess risk was confined to women who used E-alone preparations (OR 2.33, 95% CI 1.85–2.95). No significant associations were detected between pre-diagnosis HT use and ovarian cancer survival. Conclusions Hormone therapy increases risk of ovarian cancer among E-alone users, but there is no substantial impact on survival after diagnosis. PMID:18264784

  9. Mathematical models of breast and ovarian cancers.

    PubMed

    Botesteanu, Dana-Adriana; Lipkowitz, Stanley; Lee, Jung-Min; Levy, Doron

    2016-07-01

    Women constitute the majority of the aging United States (US) population, and this has substantial implications on cancer population patterns and management practices. Breast cancer is the most common women's malignancy, while ovarian cancer is the most fatal gynecological malignancy in the US. In this review, we focus on these subsets of women's cancers, seen more commonly in postmenopausal and elderly women. In order to systematically investigate the complexity of cancer progression and response to treatment in breast and ovarian malignancies, we assert that integrated mathematical modeling frameworks viewed from a systems biology perspective are needed. Such integrated frameworks could offer innovative contributions to the clinical women's cancers community, as answers to clinical questions cannot always be reached with contemporary clinical and experimental tools. Here, we recapitulate clinically known data regarding the progression and treatment of the breast and ovarian cancers. We compare and contrast the two malignancies whenever possible in order to emphasize areas where substantial contributions could be made by clinically inspired and validated mathematical modeling. We show how current paradigms in the mathematical oncology community focusing on the two malignancies do not make comprehensive use of, nor substantially reflect existing clinical data, and we highlight the modeling areas in most critical need of clinical data integration. We emphasize that the primary goal of any mathematical study of women's cancers should be to address clinically relevant questions. WIREs Syst Biol Med 2016, 8:337-362. doi: 10.1002/wsbm.1343 For further resources related to this article, please visit the WIREs website. PMID:27259061

  10. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer Prevention

    MedlinePlus

    ... lifestyle or eating habits. Avoiding things known to cause cancer. Taking medicines to treat a precancerous condition or ... called the endometrium. Ovarian cancer is the leading cause of death from cancer of the female reproductive system. In recent years, ...

  11. NMDA receptors are expressed in human ovarian cancer tissues and human ovarian cancer cell lines.

    PubMed

    North, William G; Liu, Fuli; Tian, Ruiyang; Abbasi, Hamza; Akerman, Bonnie

    2015-01-01

    We have earlier demonstrated that breast cancer and small-cell lung cancer express functional NMDA receptors that can be targeted to promote cancer cell death. Human ovarian cancer tissues and human ovarian cancer cell lines (SKOV3, A2008, and A2780) have now been shown to also express NMDA-receptor subunit 1 (GluN1) and subunit 2B (GluN2B). Seventeen ovarian cancers in two arrays were screened by immunohistochemistry using polyclonal antibodies that recognize an extracellular moiety on GluN1 and on GluN2B. These specimens comprised malignant tissue with pathology diagnoses of serous papillary cystadenocarcinoma, endometrioid adenocarcinoma, and clear-cell carcinoma. Additionally, archival tissues defined as ovarian adenocarcinoma from ten patients treated at this institute were also evaluated. All of the cancerous tissues demonstrated positive staining patterns with the NMDA-receptor antibodies, while no staining was found for tumor-adjacent normal tissues or sections of normal ovarian tissue. Human ovarian adenocarcinoma cell lines (A2008, A2780, SKOV3) were demonstrated to express GluN1 by Western blotting, but displayed different levels of expression. Through immunocytochemistry utilizing GluN1 antibodies and imaging using a confocal microscope, we were able to demonstrate that GluN1 protein is expressed on the surface of these cells. In addition to these findings, GluN2B protein was demonstrated to be expressed using polyclonal antibodies against this protein. Treatment of all ovarian cell lines with antibodies against GluN1 was found to result in decreased cell viability (P<0.001), with decreases to 10%-25% that of untreated cells. Treatment of control HEK293 cells with various dilutions of GluN1 antibodies had no effect on cell viability. The GluN1 antagonist MK-801 (dizocilpine maleate) and the GluN2B antagonist ifenprodil, like antibodies, dramatically decreased the viability of A2780 ovarian tumor cells (P<0.01). Treatment of A2780 tumor xenografts with

  12. NMDA receptors are expressed in human ovarian cancer tissues and human ovarian cancer cell lines

    PubMed Central

    North, William G; Liu, Fuli; Tian, Ruiyang; Abbasi, Hamza; Akerman, Bonnie

    2015-01-01

    We have earlier demonstrated that breast cancer and small-cell lung cancer express functional NMDA receptors that can be targeted to promote cancer cell death. Human ovarian cancer tissues and human ovarian cancer cell lines (SKOV3, A2008, and A2780) have now been shown to also express NMDA-receptor subunit 1 (GluN1) and subunit 2B (GluN2B). Seventeen ovarian cancers in two arrays were screened by immunohistochemistry using polyclonal antibodies that recognize an extracellular moiety on GluN1 and on GluN2B. These specimens comprised malignant tissue with pathology diagnoses of serous papillary cystadenocarcinoma, endometrioid adenocarcinoma, and clear-cell carcinoma. Additionally, archival tissues defined as ovarian adenocarcinoma from ten patients treated at this institute were also evaluated. All of the cancerous tissues demonstrated positive staining patterns with the NMDA-receptor antibodies, while no staining was found for tumor-adjacent normal tissues or sections of normal ovarian tissue. Human ovarian adenocarcinoma cell lines (A2008, A2780, SKOV3) were demonstrated to express GluN1 by Western blotting, but displayed different levels of expression. Through immunocytochemistry utilizing GluN1 antibodies and imaging using a confocal microscope, we were able to demonstrate that GluN1 protein is expressed on the surface of these cells. In addition to these findings, GluN2B protein was demonstrated to be expressed using polyclonal antibodies against this protein. Treatment of all ovarian cell lines with antibodies against GluN1 was found to result in decreased cell viability (P<0.001), with decreases to 10%–25% that of untreated cells. Treatment of control HEK293 cells with various dilutions of GluN1 antibodies had no effect on cell viability. The GluN1 antagonist MK-801 (dizocilpine maleate) and the GluN2B antagonist ifenprodil, like antibodies, dramatically decreased the viability of A2780 ovarian tumor cells (P<0.01). Treatment of A2780 tumor xenografts with

  13. Targeting the tumour microenvironment in ovarian cancer.

    PubMed

    Hansen, Jean M; Coleman, Robert L; Sood, Anil K

    2016-03-01

    The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy. PMID:26849037

  14. Ovarian cysts and cancer in pregnancy.

    PubMed

    Mukhopadhyay, Asima; Shinde, Aditi; Naik, Raj

    2016-05-01

    Adnexal masses are diagnosed in 5% pregnancies and pose diagnostic and management challenges. Ultrasound and magnetic resonance imaging (MRI) are the mainstay as an evaluation procedure; surgery is warranted for persistent masses with a diameter of >5 cm and sonographic signs of possible malignancy. Optimal timing for a planned surgery is the second trimester and does not adversely affect neonatal outcome. Laparoscopy is safe in pregnancy. Management for ovarian cancer during pregnancy should be individualised and formulated by a multidisciplinary team in a specialised centre while also considering the patients' wishes to preserve pregnancy. The following options can be considered: (i) induced abortion followed by standard management of ovarian cancer, (ii) pregnancy-preserving surgery followed by chemotherapy, planned delivery and secondary surgical completion or (iii) neoadjuvant chemotherapy followed by surgery during the postpartum period. Standard chemotherapy administered in non-pregnant population can only be used during the first trimester of pregnancy. PMID:26707193

  15. Knockdown of cathepsin L sensitizes ovarian cancer cells to chemotherapy

    PubMed Central

    ZHANG, HONGMEI; ZHANG, LUOSHENG; WEI, LIXIA; GAO, XINGWANG; TANG, LI; GONG, WEI; MIN, NA; ZHANG, LI; YUAN, YAWEI

    2016-01-01

    Ovarian cancer is a leading gynecological malignancy associated with high mortality. The development of acquired drug resistance is the primary cause of chemotherapy failure in the treatment of ovarian cancer. To examine the mechanism underlying paclitaxel resistance in ovarian cancer and attempt to reverse it, the present study induced a TAX-resistant ovarian cancer cell line, SKOV3/TAX. Cathepsin L (CTSL) has been found to be overexpressed in ovarian cancer. The aim of the present study was to investigate the possible involvement of CTSL in the development of TAX resistance in ovarian cancer. CTSL expression was knocked down in SKOV3 ovarian cancer cells and their phenotypic changes were analyzed. The effects of silenced CTSL on the resistant cell line were investigated by proliferation and apoptosis analysis compared with control SKOV3 cells. CTSL was more highly expressed in SKOV3/TAX cells compared with SKOV3 cells. Paclitaxel treatment downregulated the expression of CTSL in SKOV-3 but not in the paclitaxel-resistant SKOV3/TAX cells. CTSL small hairpin RNA (shRNA) knockdown significantly potentiated apoptosis induced by paclitaxel compared with SKOV3/TAX cells transfected with control shRNA, suggesting that CTSL contributes to paclitaxel resistance in ovarian cancer cells and that CTSL silencing can enhance paclitaxel-mediated cell apoptosis. Thus, CTSL should be explored as a candidate of therapeutic target for modulating paclitaxel sensitivity in ovarian cancer. PMID:27313771

  16. Transcriptional regulation of chemokine expression in ovarian cancer.

    PubMed

    Singha, Bipradeb; Gatla, Himavanth R; Vancurova, Ivana

    2015-01-01

    The increased expression of pro-inflammatory and pro-angiogenic chemokines contributes to ovarian cancer progression through the induction of tumor cell proliferation, survival, angiogenesis, and metastasis. The substantial potential of these chemokines to facilitate the progression and metastasis of ovarian cancer underscores the need for their stringent transcriptional regulation. In this Review, we highlight the key mechanisms that regulate the transcription of pro-inflammatory chemokines in ovarian cancer cells, and that have important roles in controlling ovarian cancer progression. We further discuss the potential mechanisms underlying the increased chemokine expression in drug resistance, along with our perspective for future studies. PMID:25790431

  17. Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-08-15

    Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  18. Three-photon imaging of ovarian cancer

    NASA Astrophysics Data System (ADS)

    Barton, Jennifer K.; Amirsolaimani, Babak; Rice, Photini; Hatch, Kenneth; Kieu, Khanh

    2016-02-01

    Optical imaging methods have the potential to detect ovarian cancer at an early, curable stage. Optical imaging has the disadvantage that high resolution techniques require access to the tissue of interest, but miniature endoscopes that traverse the natural orifice of the reproductive tract, or access the ovaries and fallopian tubes through a small incision in the vagina wall, can provide a minimally-invasive solution. We have imaged both rodent and human ovaries and fallopian tubes with a variety of endoscope-compatible modalities. The recent development of fiber-coupled femtosecond lasers will enable endoscopic multiphoton microscopy (MPM). We demonstrated two- and three-photon excited fluorescence (2PEF, 3PEF), and second- and third-harmonic generation microscopy (SHG, THG) in human ovarian and fallopian tube tissue. A study was undertaken to understand the mechanisms of contrast in these images. Six patients (normal, cystadenoma, and ovarian adenocarcinoma) provided ovarian and fallopian tube biopsies. The tissue was imaged with three-dimensional optical coherence tomography, multiphoton microscopy, and frozen for histological sectioning. Tissue sections were stained with hematoxylin and eosin, Masson's trichrome, and Sudan black. Approximately 1 μm resolution images were obtained with an excitation source at 1550 nm. 2PEF signal was absent. SHG signal was mainly from collagen. 3PEF and THG signal came from a variety of sources, including a strong signal from fatty connective tissue and red blood cells. Adenocarcinoma was characterized by loss of SHG signal, whereas cystic abnormalities showed strong SHG. There was limited overlap of two- and three- photon signals, suggesting that three-photon imaging can provide additional information for early diagnosis of ovarian cancer.

  19. Salpingectomy as a Means to Reduce Ovarian Cancer Risk

    PubMed Central

    Daly, Mary B.; Dresher, Charles W.; Yates, Melinda S.; Jeter, Joanne M.; Karlan, Beth Y.; Alberts, David S.; Lu, Karen H.

    2015-01-01

    Bilateral salpingo-oophorectomy (BSO) has become the standard of care for risk reduction in women at hereditary risk of ovarian cancer. While this procedure significantly decreases both the incidence of and mortality from ovarian cancer, it impacts quality of life, and the premature cessation of ovarian function may have long term health hazards. Recent advances in our understanding of the molecular pathways of ovarian cancer point to the fallopian tube epithelium as the origin of most high grade serous cancers (HGSC). This evolving appreciation of the role of the fallopian tube in HGSC has led to the consideration of salpingectomy alone as an option for risk management, especially in premenopausal women. In addition, it is postulated that bilateral salpingectomy with ovarian retention (BSOR), may have a public health benefit for women undergoing benign gynecologic surgery. In this review we provide the rationale for salpingectomy as an ovarian cancer risk reduction strategy. PMID:25586903

  20. Ovarian Cancer Biomarker Discovery Based on Genomic Approaches

    PubMed Central

    Lee, Jung-Yun; Kim, Hee Seung; Suh, Dong Hoon; Kim, Mi-Kyung; Chung, Hyun Hoon; Song, Yong-Sang

    2013-01-01

    Ovarian cancer presents at an advanced stage in more than 75% of patients. Early detection has great promise to improve clinical outcomes. Although the advancing proteomic technologies led to the discovery of numerous ovarian cancer biomarkers, no screening method has been recommended for early detection of ovarian cancer. Complexity and heterogeneity of ovarian carcinogenesis is a major obstacle to discover biomarkers. As cancer arises due to accumulation of genetic change, understanding the close connection between genetic changes and ovarian carcinogenesis would provide the opportunity to find novel gene-level ovarian cancer biomarkers. In this review, we summarize the various gene-based biomarkers by genomic technologies, including inherited gene mutations, epigenetic changes, and differential gene expression. In addition, we suggest the strategy to discover novel gene-based biomarkers with recently introduced next generation sequencing. PMID:25337559

  1. MicroRNAs and Recent Insights into Pediatric Ovarian Cancers

    PubMed Central

    Francis, Jessica C.; Kolomeyevskaya, Nonna; Mach, Claire M.; Dietrich, Jennifer E.; Anderson, Matthew L.

    2013-01-01

    Ovarian cancer is the most common pediatric gynecologic malignancy. When diagnosed in children, ovarian cancers present unique challenges that differ dramatically from those faced by adults. Here, we review the spectrum of ovarian cancers found in young women and girls and discuss the biology of these diseases. A number of advances have recently shed significant new understanding on the potential causes of ovarian cancer in this unique population. Particular emphasis is placed on understanding how altered expression of non-coding RNA transcripts known as microRNAs play a key role in the etiology of ovarian germ cell and sex cord-stromal tumors. Emerging transgenic models for these diseases are also reviewed. Lastly, future challenges and opportunities for understanding pediatric ovarian cancers, delineating clinically useful biomarkers, and developing targeted therapies are discussed. PMID:23641362

  2. Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-05-18

    Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

  3. Clinical tumour markers in ovarian cancer.

    PubMed

    Mazurek, A; Nikliński, J; Laudański, T; Pluygers, E

    1998-02-01

    Within past few years, the measurement of serological, histochemical and molecular genetic markers has had an increasing influence on clinical decisions about initial treatment and follow-up. This review presents data concerning the most studied and interesting markers in ovarian cancer. CA 125, CA 19.9, TATI, CASA, CEA, TPA, TPS and CYFRA21-1 are now the most widely used serological tumour markers for management of ovarian cancer patients. Ras oncogenes, C-erb2 proto-oncogene, p53 suppressor gene and Bcl-2 oncogene are examples of currently used molecular genetic markers. As histochemical markers-proliferation markers, flow cytometric analysis, thymidine labelling index, Ki-67 nuclear antigen or differentiation markers are nowadays the ones most often determined. Some of these markers might be useful adjuncts for monitoring response to therapy, including early detection of tumour reactivation to allow curative therapy and rapid detection of treatment failure. The study of these markers may also lead to a better understanding of the biological characteristics of ovarian cancer. Numerous tumour markers characterized in this paper have been recognized as promising prognostic factors. The information derived from studies of these markers also represents the most promising avenue towards new treatment strategies; nevertheless to validate these factors, prospective studies of a large patient population are needed. PMID:9511849

  4. [Hope for improvement of survival in ovarian cancer].

    PubMed

    Högberg, Thomas; Bergfeldt, Kjell; Borgfeldt, Christer; Holmberg, Erik; Åvall Lundqvist, Elisabeth

    2015-01-01

    Ovarian cancer is the most common cause of death from a gynecologic cancer. Every year around 700 women contracts ovarian cancer in Sweden. The overall survival is among the highest in Europe, but still long term relative survival is only 46%. It is a long-held myth that ovarian cancer is a disease without symptoms. Almost 90% of women have symptoms, even in the early stages. Symptoms that should arise suspicion of ovarian cancer and initiate diagnostic work-up are continuous abdominal extension, early feeling of satiety, pelvic or abdominal pain, urinary urge and postmenopausal bleeding. Women's awareness of symptoms and willingness to seek medical advice and the organization of the health care system are important factors determining cancer survival. Ovarian cancer is a heterogeneous group of diseases with different tumor traits and prognosis. Personalized medicine and preventive measures recognizing recent knowledge about tumor biology will positively affect survival. PMID:26646961

  5. Management of relapsed ovarian cancer: a review.

    PubMed

    Giornelli, Gonzalo H

    2016-01-01

    Around 70 % of ovarian cancer patients relapse after primary cytoreductive surgery and standard first-line chemotherapy. The biology of relapse remains unclear, but cancer stem cells seem to play an important role. There are still some areas of controversy on how to manage these relapses and or progressions that occur almost unavoidably in the course of this disease with shorter intervals between them as the natural history of this disease develops. The goal of treatments investigated in this neoplasm has shifted to maintenance therapy, trying to extend the progression free intervals in a disease that is becoming more and more protracted. PMID:27516935

  6. Noncontraceptive estrogen use and epithelial ovarian cancer.

    PubMed

    Kaufman, D W; Kelly, J P; Welch, W R; Rosenberg, L; Stolley, P D; Warshauer, M E; Lewis, J; Woodruff, J; Shapiro, S

    1989-12-01

    The relation of noncontraceptive estrogen use to epithelial ovarian cancer was evaluated in a case-control study conducted in hospitals mainly in the northeastern United States. There were 377 cases diagnosed within the year before hospital admission and 2,030 hospital controls; data were collected by interview in the hospital. Compared with women who never took noncontraceptive estrogens, the overall relative risk estimate for women whose estrogen use lasted at least one year and was not combined with progestogens or testosterone was 1.2 (95% confidence interval (CI) 0.8-1.9), after taking into account risk factors for ovarian cancer. There were 55 cases of the endometrioid, clear cell, or malignant mixed mesodermal cell type; the corresponding relative risk estimate was 0.9 (95% CI 0.3-3.0). There were 26 cases of undifferentiated cell type, with a relative risk estimate of 3.6 (95% CI 1.2-11). Relative risk estimates were similar in a subset of the cases (57%) for which pathology slides were reviewed. For estrogen use of long duration, use of high-dose preparations, or use in the distant past, the relative risk estimates were not significantly different from 1.0. The estimates were elevated for some categories of use, but not consistently--for example, for an interval of 5-9 years since estrogen use began (relative risk (RR) = 2.7), but not after shorter or longer intervals, and for use of conjugated estrogens with a dose of 0.3 mg (RR = 3.2) or 1.25 mg (RR = 2.4), but not for doses of 0.625 mg or 2.5 mg. The relative risk estimate was also elevated for use by nulliparous women (RR = 2.4). The results suggest that, overall, noncontraceptive estrogen use is not associated with the risk of epithelial ovarian cancer. Furthermore, our data do not support the hypothesis that estrogens increase the risk of endometrioid ovarian cancer. The elevated estimates could be due to multiple stratification of the data, but they should be explored in further studies, given the

  7. Tumor microenvironment: The culprit for ovarian cancer metastasis?

    PubMed

    Luo, Zhongyue; Wang, Qiu; Lau, Wayne Bond; Lau, Bonnie; Xu, Lian; Zhao, Linjie; Yang, Huiliang; Feng, Min; Xuan, Yu; Yang, Yanfei; Lei, Lingzi; Wang, Chenlu; Yi, Tao; Zhao, Xia; Wei, Yuquan; Zhou, Shengtao

    2016-07-28

    Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently, with poor prognosis. However, the molecular mechanisms underlying ovarian cancer metastasis still remain unelucidated. The tumor microenvironment, consisting of stromal cells (including fibroblasts, macrophages, regulatory T cells, myeloid-derived suppressor cells, endothelial cells, pericytes and platelets), the extracellular matrix component (EMC) (including inflammatory cytokines, chemokines, matrix metalloproteinases, integrins, and other secreted molecules) and exosomes (small extracellular vesicles loaded with molecules), establishes an autocrine-paracrine communication circuit that reinforces invasion and cancer cell metastasis via reciprocal signaling. Recent evidences have unraveled the significant contribution of tumor microenvironment to ovarian cancer metastasis. In this review, we provide a comprehensive landscape of the reciprocity between tumor stroma and ovarian cancer cells upon metastasis, aiming to offer novel clues on the development of novel diagnostic biomarkers and therapeutic targets for ovarian cancer in future clinical practice. PMID:27131957

  8. Development of a Mouse Model of Menopausal Ovarian Cancer

    PubMed Central

    Smith, Elizabeth R.; Wang, Ying; Xu, Xiang-Xi

    2014-01-01

    Despite significant understanding of the genetic mutations involved in ovarian epithelial cancer and advances in genomic approaches for expression and mutation profiling of tumor tissues, several key questions in ovarian cancer biology remain enigmatic: the mechanism for the well-established impact of reproductive factors on ovarian cancer risk remains obscure; cell of origin of ovarian cancer continue to be debated; and the precursor lesion, sequence, or events in progression remain to be defined. Suitable mouse models should complement the analysis of human tumor tissues and may provide clues to these questions currently perplexing ovarian cancer biology. A potentially useful model is the germ cell-deficient Wv (white spotting variant) mutant mouse line, which may be used to study the impact of menopausal physiology on the increased risk of ovarian cancer. The Wv mice harbor a point mutation in c-Kit that reduces the receptor tyrosine kinase activity to about 1–5% (it is not a null mutation). Homozygous Wv mutant females have a reduced ovarian germ cell reservoir at birth and the follicles are rapidly depleted upon reaching reproductive maturity, but other biological phenotypes are minimal and the mice have a normal life span. The loss of ovarian function precipitates changes in hormonal and metabolic activity that model features of menopause in humans. As a consequence of follicle depletion, the Wv ovaries develop ovarian tubular adenomas, a benign epithelial tumor corresponding to surface epithelial invaginations and papillomatosis that mark human ovarian aging. Ongoing work will test the possibility of converting the benign epithelial tubular adenomas into neoplastic tumors by addition of an oncogenic mutation, such as of Tp53, to model the genotype and biology of serous ovarian cancer. Model based on the Wv mice may have the potential to gain biological and etiological insights into ovarian cancer development and prevention. PMID:24616881

  9. Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

    PubMed Central

    Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

    2011-01-01

    Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

  10. 78 FR 54741 - National Ovarian Cancer Awareness Month, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ... America the two hundred and thirty- eighth. (Presidential Sig.) [FR Doc. 2013-21821 Filed 9-5-13; 8:45 am... Documents#0;#0; ] Proclamation 9008 of August 30, 2013 National Ovarian Cancer Awareness Month, 2013 By the... ovarian cancer, and more than half that number of women will die of this disease. During National...

  11. 77 FR 55095 - National Ovarian Cancer Awareness Month, 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-06

    .... (Presidential Sig.) [FR Doc. 2012-22148 Filed 9-5-12; 11:15 am] Billing code 3295-F2-P ... Documents#0;#0; ] Proclamation 8853 of August 31, 2012 National Ovarian Cancer Awareness Month, 2012 By the... their lives to ovarian cancer. They are mothers and daughters, sisters and grandmothers,...

  12. [Tardive cecal metastasis from ovarian cancer: a case report].

    PubMed

    Talarico, C; Casella, C; Gambarotti, M

    2004-01-01

    Intestinal insolvement is a frequent sequela of metastatic ovarian cancer may be syncronous or following ovaric resection, after several years of disease free condition. The authors herein describe a clinical report of a case of cecal metastatic neoplasm due to ovarian cancer treated with surgical resection 24 years before. PMID:15960367

  13. Recreational Physical Activity and Ovarian Cancer Risk and Survival

    PubMed Central

    Moorman, Patricia G.; Jones, Lee W.; Akushevich, Lucy; Schildkraut, Joellen M.

    2010-01-01

    Purpose Physical activity may influence ovarian cancer risk and outcomes through effects on ovulation, inflammatory markers and other processes. We examined associations between self-reported physical activity and ovarian cancer risk and survival in a population-based, case-control study in North Carolina. Methods The analyses involved 638 epithelial ovarian cancer cases and 683 controls recruited between 1999-2008. Logistic regression analyses were used to assess ovarian cancer risk in relation to reported average physical activity at various time periods. Kaplan-Meier analyses and proportional hazards modeling were used to assess associations between physical activity and survival among ovarian cancer cases. Results Modestly reduced risks for ovarian cancer were observed in some categories of physical activity, but there were no consistent patterns of greater reductions in risk with higher activity levels. Physical activity prior to diagnosis was not significantly related to ovarian cancer survival overall, but survival was better for women who reported >2 hours of activity/week as compared to those reporting <1 hour/week among women who were non-obese (multivariable hazard ratio=0.69, 95% CI 0.47 – 1.00) Conclusions Our data provide weak evidence in support of beneficial effects of physical activity on ovarian cancer risk and survival, but results should be interpreted cautiously because of the lack of a clear dose response relation with higher levels of exercise and the likely misclassification of self-reported activity. PMID:21296269

  14. 75 FR 54451 - National Ovarian Cancer Awareness Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    .... (Presidential Sig.) [FR Doc. 2010-22427 Filed 9-3-10; 11:15 am] Billing code 3195-W0-P ... Documents#0;#0; ] Proclamation 8551 of August 31, 2010 National Ovarian Cancer Awareness Month, 2010 By the... against ovarian cancer, this disease continues to claim more lives than any other gynecologic...

  15. Risk of Ovarian Cancer Relapse Score

    PubMed Central

    Rizzuto, Ivana; Stavraka, Chara; Chatterjee, Jayanta; Borley, Jane; Hopkins, Thomas Glass; Gabra, Hani; Ghaem-Maghami, Sadaf; Huson, Les; Blagden, Sarah P.

    2015-01-01

    Objective The aim of this study was to construct a prognostic index that predicts risk of relapse in women who have completed first-line treatment for ovarian cancer (OC). Methods A database of OC cases from 2000 to 2010 was interrogated for International Federation of Gynecology and Obstetrics stage, grade and histological subtype of cancer, preoperative and posttreatment CA-125 level, presence or absence of residual disease after cytoreductive surgery and on postchemotherapy computed tomography scan, and time to progression and death. The strongest predictors of relapse were included into an algorithm, the Risk of Ovarian Cancer Relapse (ROVAR) score. Results Three hundred fifty-four cases of OC were analyzed to generate the ROVAR score. Factors selected were preoperative serum CA-125, International Federation of Gynecology and Obstetrics stage and grade of cancer, and presence of residual disease at posttreatment computed tomography scan. In the validation data set, the ROVAR score had a sensitivity and specificity of 94% and 61%, respectively. The concordance index for the validation data set was 0.91 (95% confidence interval, 0.85-0.96). The score allows patient stratification into low (<0.33), intermediate (0.34–0.67), and high (>0.67) probability of relapse. Conclusions The ROVAR score stratifies patients according to their risk of relapse following first-line treatment for OC. This can broadly facilitate the appropriate tailoring of posttreatment care and support. PMID:25647256

  16. General Information About Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

    MedlinePlus

    ... condition or to keep cancer from starting. General Information About Ovarian, Fallopian Tube, and Primary Peritoneal Cancer ... PDQ Screening and Prevention Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  17. [Individualized therapy of synchronous ovarian and colon cancers with lymph].

    PubMed

    Deme, Dániel; Bishr, Abdulfatah M; Nizar, Jamool; Telekes, András

    2015-06-01

    A 71-year-old female patient underwent urgent laparotomy due to severe right lower quadrant abdominal pain and fever. Macroscopically duplex coecal and transverse colon cancer as well as a sigmoid or left ovarian cancer were suspected. Pathological findings revealed synchronous left ovarian and transverse colonic neoplasms. Both primaries metastatized to their regional lymph nodes. Furthermore, the ovarian cancer infiltrating the sigmoid colon gave distant metastasis in the coecum, too. Ovarian cancer histology showed papillary adenocarcinoma, and transverse colon cancer was a tubular adenocarcinoma. The affected lymph nodes were clearly distinguished by immunohistochemistry staining: ovarian metastases were CK7 positive, and colonic metastases were CK20 and CEA positive. The patient was treated with combinated chemotherapy: FOLFOX-4 two weekly and paclitaxel monotherapy every other week. The patient tolerated this combined treatment well. The authors conclude that multiple synchronous neoplasms can be treated with individualized chemotherapeutic protocol with good efficacy and few adverse reactions. PMID:26027602

  18. DNA methylation changes in epithelial ovarian cancer histotypes

    PubMed Central

    Earp, Madalene A.; Cunningham, Julie M.

    2016-01-01

    Survival after a diagnosis of ovarian cancer has not improved, and despite histological differences, treatment is similar for all cases. Understanding the molecular basis for ovarian cancer risk and prognosis is fundamental, and to this end much has been gleaned about genetic changes contributing to risk, and to a lesser extent, survival. There’s considerable evidence for genetic differences between the four pathologically defined histological subtypes; however, the contribution of epigenetics is less well documented. In this report, we review alterations in DNA methylation in ovarian cancer, focusing on histological subtypes, and studies examining the roles of methylation in determining therapy response. As epigenetics is making its way into clinical care, we review the application of cell free DNA methylation to ovarian cancer diagnosis and care. Finally, we comment on recurrent limitations in the DNA methylation literature for ovarian cancer, which can and should be addressed to mature this field. PMID:26363302

  19. Emerging and Evolving Ovarian Cancer Animal Models

    PubMed Central

    Bobbs, Alexander S; Cole, Jennifer M; Cowden Dahl, Karen D

    2015-01-01

    Ovarian cancer (OC) is the leading cause of death from a gynecological malignancy in the United States. By the time a woman is diagnosed with OC, the tumor has usually metastasized. Mouse models that are used to recapitulate different aspects of human OC have been evolving for nearly 40 years. Xenograft studies in immunocompromised and immunocompetent mice have enhanced our knowledge of metastasis and immune cell involvement in cancer. Patient-derived xenografts (PDXs) can accurately reflect metastasis, response to therapy, and diverse genetics found in patients. Additionally, multiple genetically engineered mouse models have increased our understanding of possible tissues of origin for OC and what role individual mutations play in establishing ovarian tumors. Many of these models are used to test novel therapeutics. As no single model perfectly copies the human disease, we can use a variety of OC animal models in hypothesis testing that will lead to novel treatment options. The goal of this review is to provide an overview of the utility of different mouse models in the study of OC and their suitability for cancer research. PMID:26380555

  20. Safety of Ovarian Tissue Autotransplantation for Cancer Patients

    PubMed Central

    Bockstaele, Laurence; Tsepelidis, Sophie; Dechene, Julie; Englert, Yvon; Demeestere, Isabelle

    2012-01-01

    Cancer treatments can induce premature ovarian failure in almost half of young women suffering from invasive neoplasia. Cryopreservation of ovarian cortex and subsequent autotransplantation of frozen-thawed tissue have emerged as promising alternatives to conventional fertility preservation technologies. However, human ovarian tissue is generally harvested before the administration of gonadotoxic treatment and could be contaminated with malignant cells. The safety of autotransplantation of ovarian cortex remains a major concern for fertility preservation units worldwide. This paper discusses the main tools for detecting disseminated cancer cells currently available, their limitations, and clinical relevance. PMID:22253631

  1. Inhibitory Effect of Baicalin and Baicalein on Ovarian Cancer Cells

    PubMed Central

    Chen, Jianchu; Li, Zhaoliang; Chen, Allen Y.; Ye, Xingqian; Luo, Haitao; Rankin, Gary O.; Chen, Yi Charlie

    2013-01-01

    Ovarian cancer is one of the primary causes of death for women all through the Western world. Baicalin and baicalein are naturally occurring flavonoids that are found in the roots and leaves of some Chinese medicinal plants and are thought to have antioxidant activity and possible anti-angiogenic, anti-cancer, anxiolytic, anti-inflammatory and neuroprotective activities. Two kinds of ovarian cancer (OVCAR-3 and CP-70) cell lines and a normal ovarian cell line (IOSE-364) were selected to be investigated in the inhibitory effect of baicalin and baicalein on cancer cells. Largely, baicalin and baicalein inhibited ovarian cancer cell viability in both ovarian cancer cell lines with LD50 values in the range of 45–55 μM for baicalin and 25–40 μM for baicalein. On the other hand, both compounds had fewer inhibitory effects on normal ovarian cells viability with LD50 values of 177 μM for baicalin and 68 μM for baicalein. Baicalin decreased expression of VEGF (20 μM), cMyc (80 μM), and NFkB (20 μM); baicalein decreased expression of VEGF (10 μM), HIF-1α (20 μM), cMyc (20 μM), and NFkB (40 μM). Therefore baicalein is more effective in inhibiting cancer cell viability and expression of VEGF, HIF-1α, cMyc, and NFκB in both ovarian cancer cell lines. It seems that baicalein inhibited cancer cell viability through the inhibition of cancer promoting genes expression including VEGF, HIF-1α, cMyc, and NFκB. Overall, this study showed that baicalein and baicalin significantly inhibited the viability of ovarian cancer cells, while generally exerting less of an effect on normal cells. They have potential for chemoprevention and treatment of ovarian cancers. PMID:23502466

  2. Chromosome abnormalities in primary ovarian cancer

    SciTech Connect

    Yonescu, R.; Currie, J.; Griffin, C.A.

    1994-09-01

    Chromosome abnormalities that are specific and recurrent may occur in regions of the genome that are involved in the conversion of normal cells to those with tumorigenic potential. Ovarian cancer is the primary cause of death among patients with gynecological malignancies. We have performed cytogenetic analysis of 16 ovarian tumors from women age 28-82. Three tumors of low malignant potential and three granulosa cell tumors had normal karyotypes. To look for the presence of trisomy 12, which has been suggested to be a common aberration in this group of tumors, interphase fluorescence in situ hybridization was performed on direct preparations from three of these tumors using a probe for alpha satellite sequences of chromosome 12. In the 3 preparations, 92-98 percent of the cells contained two copies of chromosome 12, indicating that trisomy 12 is not a universal finding in low grade ovarian tumors. Endometrioid carcinoma of the ovary is histologically indistinguishable from endometial carcinoma of the uterus. We studied 10 endometrioid tumors to determine the degree of genetic similarity between these two carcinomas. Six out of ten endometrioid tumors showed a near-triploid modal number, and one presented with a tetraploid modal number. Eight of the ten contained structural chromosome abnormalities, of which the most frequent were 1p- (5 tumors), 19q+ (3 tumors), 6q- or ins(6) (4 tumors), 3q- or 3q+ (4 tumors). These cytogenetic results resemble those reported for papillary ovarian tumors and differ from those of endometrial carcinoma of the uterus. We conclude that despite the histologic similarities between the endometrioid and endometrial carcinomas, the genetic abnormalities in the genesis of these tumors differ significantly.

  3. The Development of an Angiogenic Protein "Signature" in Ovarian Cancer Ascites as a Tool for Biologic and Prognostic Profiling.

    PubMed

    Trachana, Sofia-Paraskevi; Pilalis, Eleftherios; Gavalas, Nikos G; Tzannis, Kimon; Papadodima, Olga; Liontos, Michalis; Rodolakis, Alexandros; Vlachos, Georgios; Thomakos, Nikolaos; Haidopoulos, Dimitrios; Lykka, Maria; Koutsoukos, Konstantinos; Kostouros, Efthimios; Terpos, Evagelos; Chatziioannou, Aristotelis; Dimopoulos, Meletios-Athanasios; Bamias, Aristotelis

    2016-01-01

    Advanced ovarian cancer (AOC) is one of the leading lethal gynecological cancers in developed countries. Based on the important role of angiogenesis in ovarian cancer oncogenesis and expansion, we hypothesized that the development of an "angiogenic signature" might be helpful in prediction of prognosis and efficacy of anti-angiogenic therapies in this disease. Sixty-nine samples of ascitic fluid- 35 from platinum sensitive and 34 from platinum resistant patients managed with cytoreductive surgery and 1st-line carboplatin-based chemotherapy- were analyzed using the Proteome ProfilerTM Human Angiogenesis Array Kit, screening for the presence of 55 soluble angiogenesis-related factors. A protein profile based on the expression of a subset of 25 factors could accurately separate resistant from sensitive patients with a success rate of approximately 90%. The protein profile corresponding to the "sensitive" subset was associated with significantly longer PFS (8 [95% Confidence Interval {CI}: 8-9] vs. 20 months [95% CI: 15-28]; Hazard ratio {HR}: 8.3, p<0.001) and OS (20.5 months [95% CI: 13.5-30] vs. 74 months [95% CI: 36-not reached]; HR: 5.6 [95% CI: 2.8-11.2]; p<0.001). This prognostic performance was superior to that of stage, histology and residual disease after cytoreductive surgery and the levels of vascular endothelial growth factor (VEGF) in ascites. In conclusion, we developed an "angiogenic signature" for patients with AOC, which can be used, after appropriate validation, as a prognostic marker and a tool for selection for anti-angiogenic therapies. PMID:27258020

  4. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

    PubMed Central

    Pearce, C L; Near, A M; Van Den Berg, D J; Ramus, S J; Gentry-Maharaj, A; Menon, U; Gayther, S A; Anderson, A R; Edlund, C K; Wu, A H; Chen, X; Beesley, J; Webb, P M; Holt, S K; Chen, C; Doherty, J A; Rossing, M A; Whittemore, A S; McGuire, V; DiCioccio, R A; Goodman, M T; Lurie, G; Carney, M E; Wilkens, L R; Ness, R B; Moysich, K B; Edwards, R; Jennison, E; Kjaer, S K; Hogdall, E; Hogdall, C K; Goode, E L; Sellers, T A; Vierkant, R A; Cunningham, J C; Schildkraut, J M; Berchuck, A; Moorman, P G; Iversen, E S; Cramer, D W; Terry, K L; Vitonis, A F; Titus-Ernstoff, L; Song, H; Pharoah, P D P; Spurdle, A B; Anton-Culver, H; Ziogas, A; Brewster, W; Galitovskiy, V; Chenevix-Trench, G

    2009-01-01

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P⩽0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: ORhomozygous(hom)=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20–6.56, P=0.017, phet across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted. PMID:19127255

  5. Why have ovarian cancer mortality rates declined? Part I. Incidence.

    PubMed

    Sopik, Victoria; Iqbal, Javaid; Rosen, Barry; Narod, Steven A

    2015-09-01

    The age-adjusted mortality rate from ovarian cancer in the United States has declined over the past several decades. The decline in mortality might be the consequence of a reduced number of cases (incidence) or a reduction in the proportion of patients who die from their cancer (case-fatality). In part I of this three-part series, we examine rates of ovarian cancer incidence and mortality from the Surveillance Epidemiology and End Results (SEER) registry database and we explore to what extent the observed decline in mortality can be explained by a downward shift in the stage distribution of ovarian cancer (i.e. due to early detection) or by fewer cases of ovarian cancer (i.e. due to a change in risk factors). The proportion of localized ovarian cancers did not increase, suggesting that a stage-shift did not contribute to the decline in mortality. The observed decline in mortality paralleled a decline in incidence. The trends in ovarian cancer incidence coincided with temporal changes in the exposure of women from different birth cohorts to various reproductive risk factors, in particular, to changes in the use of the oral contraceptive pill and to declining parity. Based on recent changes in risk factor propensity, we predict that the trend of the declining age-adjusted incidence rate of ovarian cancer in the United States will reverse and rates will increase in coming years. PMID:26080287

  6. Chemotherapy for Patients with BRCA1 and BRCA2-Mutated Ovarian Cancer: Same or Different?

    PubMed

    Tan, David S P; Kaye, Stanley B

    2015-01-01

    Retrospective studies have shown an improved prognosis, higher response rates to platinum-containing regimens, and longer treatment-free intervals between relapses in patients with BRCA 1 and BRCA 2 (BRCA1/2)-mutated ovarian cancer (BMOC) compared with patients who are not carriers of this mutation. These features of BMOC are attributed to homologous-recombination repair (HR) deficiency in the absence of BRCA1/2 function, which results in an impaired ability of tumor cells to repair platinum-induced double-strand breaks (DSBs), thereby conferring increased chemosensitivity and increased sensitivity to poly(ADP-ribose) polymerase (PARP) enzyme inhibition and other DNA-damaging chemotherapeutic agents such as pegylated liposomal doxorubicin (PLD). Therefore, the chemotherapeutic approach for patients with BMOC should focus on treatment with platinum-based chemotherapy at first-line and recurrent-disease settings and measures to increase the platinum-free interval following early platinum-resistant relapse (i.e., progression-free survival of less than 6 months from last platinum-based chemotherapy) by using nonplatinum cytotoxic agents, with the aim of reintroducing platinum again at a later date. The role of first-line intraperitoneal platinum-based therapy in the specific context of BMOC also merits further analysis. Other than platinum, alternative DNA-damaging agents (including PLD and trabectedin) also may have a therapeutic role in patients with recurrent BMOC. The recent approval of olaparib for clinical use in Europe and the United States will also affect chemotherapeutic strategies for these patients. Further work to clarify the precise relationship between BRCA1/2 mutation genotype and clinical phenotype is crucial to delineating the optimal therapeutic choices in the future for patients with BMOC. PMID:25993149

  7. Carboplatin and Paclitaxel or Oxaliplatin and Capecitabine With or Without Bevacizumab as First-Line Therapy in Treating Patients With Newly Diagnosed Stage II-IV or Recurrent Stage I Epithelial Ovarian or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-06-29

    Borderline Ovarian Mucinous Tumor; Ovarian Mucinous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer

  8. Intraoperative radiation therapy in recurrent ovarian cancer

    SciTech Connect

    Yap, O.W. Stephanie . E-mail: stbeast@stanford.edu; Kapp, Daniel S.; Teng, Nelson N.H.; Husain, Amreen

    2005-11-15

    Purpose: To evaluate disease outcomes and complications in patients with recurrent ovarian cancer treated with cytoreductive surgery and intraoperative radiation therapy (IORT). Methods and Materials: A retrospective study of 24 consecutive patients with ovarian carcinoma who underwent secondary cytoreduction and intraoperative radiation therapy at our institution between 1994 and 2002 was conducted. After optimal cytoreductive surgery, IORT was delivered with orthovoltage X-rays (200 kVp) using individually sized and beveled cone applications. Outcomes measures were local control of disease, progression-free interval, overall survival, and treatment-related complications. Results: Of these 24 patients, 22 were available for follow-up analysis. Additional treatment at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and paracaval lymph node beds, inguinal region, or porta hepatitis. At a median follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients have recurred, of whom 4 are alive with disease and 13 died from disease. Five patients recurred within the radiation fields for a locoregional relapse rate of 32% and 12 patients recurred at distant sites with a median time to recurrence of 13.7 months. Five-year overall survival was 22% with a median survival of 26 months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from their treatments. Conclusion: In carefully selected patients with locally recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably tolerated and may contribute to achieving local control and disease palliation.

  9. Carboplatin and Paclitaxel With or Without Bevacizumab Compared to Docetaxel, Carboplatin, and Paclitaxel in Treating Patients With Stage II, Stage III, or Stage IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Carcinoma (Cancer)

    ClinicalTrials.gov

    2013-03-18

    Brenner Tumor; Fallopian Tube Cancer; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Primary Peritoneal Cavity Cancer; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

  10. Value of Symptom-Triggered Diagnostic Evaluation for Ovarian Cancer

    PubMed Central

    Andersen, M. Robyn; Lowe, Kimberly A.; Goff, Barbara A.

    2014-01-01

    Objective To evaluate the potential harms and ovarian cancer outcomes associated with symptom-triggered diagnostic evaluation of all women with symptoms of ovarian cancer. Methods Five thousand-twelve women over age 40 were prospectively enrolled in a cohort study of proactive symptom-triggered diagnostic evaluation. Women who tested positive on a Symptom Index were offered testing with CA125 and transvaginal ultrasound. Results of these tests and any subsequent procedures were recorded. Assessment of ovarian cancer outcomes for all participants through Surveillance, Epidemiology, and End Results (SEER) was performed a year after enrollment was complete. Results A positive Symptom Index was found in 241 (4.8%) of participating patients and 211 (88%) participated in CA125, transvaginal ultrasound, or both CA125 and transvaginal ultrasound. Twenty surgical procedures (laparoscopy, laparotomy, vaginal) were performed in the study population (0.4% of participating women). However, only six (0.12%) were performed for a suspicious ovarian mass and only 4 (0.08%) were performed solely due to study participation. A total of eight ovarian cancers were diagnosed, 31–843days after symptom assessment (50% distant, 50% local or regional). Of the two cancers diagnosed within 6 months, one was Symptom Index-positive. Conclusions Proactive symptom-triggered diagnostic evaluation for ovarian cancer results in minimal unindicated surgery. A small number of ovarian cancers were identified solely on the basis of symptom-triggered diagnostic testing. PMID:24463666