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Sample records for advanced ovarian carcinoma

  1. Study of consolidation chemotherapy in advanced epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Cheng Ning-hai; Huang Hui-fang; Pan Lin-ya; Shen Keng; Wu Ming; Yang Jia-xin

    2007-01-01

    Objective: A prospective randomized study was designed to evaluate the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.Methods: 50 patients with advanced epithelial ovarian carcinoma treated in our hospital during the period from March 2000 to October 2005 were enrolled in this study.All patients had achieved clinical complete remission by means of standard treatments, and were randomly divided into consolidation chemotherapy group and control group.Relapse rate, and disease-free survival(DFS) time were analyzed in both groups.Results: 24 patients were assigned in consolidation chemotherapy group, and 26 patients in control group.Tumor relapse interval in consolidation group was (26.5±7.4) months, vs.(16.8±7.0) months in control group respectively, P=0.001.Time to relapse(TTR) in consolidation group was (19.2±6.8) months, vs.(10.0±6.9)months in control group, P=0.002.Analysis of DFS time and overall survival time, Log Rank test:P=0.042 and P= 0.062, respectively.Conclusions: Consolidation chemotherapy could be the relevant factor that postpones tumor relapse interval and prolongs DFS time in advanced epithelial ovarian carcinoma patients who had achived chlinical complete remission.But so far the statistic result of our clinical study is beyond the conclusion that consolidation chemotherapy can decrease relapse rate or increase survival rate.Muhicenter randomized clinical trial should be performed to confirm the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.

  2. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Elshamy Maged R

    2005-08-01

    Full Text Available Abstract Background Patients with advanced ovarian cancer should be treated by radical debulking surgery aiming at complete tumor resection. Unfortunately about 70% of the patients present with advanced disease, when optimal debulking can not be obtained, and therefore these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT has been proposed as a novel therapeutic approach in such cases. In this study, we report our results with primary surgery or neoadjuvant chemotherapy as treatment modalities in the specific indication of operable patients with advanced ovarian carcinoma (no medical contraindication to debulking surgery. Patients and methods A total of 59 patients with stage III or IV epithelial ovarian carcinomas were evaluated between 1998 and 2003. All patients were submitted to surgical exploration aiming to evaluate tumor resectability. Neoadjuvant chemotherapy was given (in 27 patients where optimal cytoreduction was not feasible. Conversely primary debulking surgery was performed when we considered that optimal cytoreduction could be achieved by the standard surgery (32 patients. Results Optimal cytoreduction was higher in the NACT group (72.2% than the conventional group (62.4%, though not statistically significant (P = 0.5. More important was the finding that parameters of surgical aggressiveness (blood loss rates, ICU stay and total hospital stay were significantly lower in NACT group than the conventional group. The median overall survival time was 28 months in the conventional group and 25 months in NACT group with a P value of 0.5. The median disease free survival was 19 months in the conventional group and 21 months in NACT group (P = 0.4. In multivariate analysis, the pathologic type and degree of debulking were found to affect the disease free survival significantly. Overall survival was not affected by any of the study parameters. Conclusion Primary chemotherapy followed by interval debulking surgery

  3. Whole abdominal irradiation following chemotherapy in advanced ovarian carcinoma

    International Nuclear Information System (INIS)

    One hundred and sixteen patients with advanced ovarian carcinoma, who underwent primary cytoreductive surgery, received 6-11 courses of chemotherapy by cis-platin (50 mg/m2) and adriamycin (50 mg/m2) every 21 days. This was followed by second look laparotomy in 66 patients with no clinical evidence of disease. Consolidation abdominal irradiation was administered to 43 patients. Two techniques of irradiation were employed: between 1980-1983 whole abdominal irradiation was used and patients were to receive 3000 cGy in 4 weeks (Schedule I). Due to myelosuppression only 13 of 26 patients (50%) completed the planned dose of radiation. Between 1983-1985 the target volume was divided into upper and lower parts. First, the lower abdomen received 3000 cGy in 3 weeks, and then the upper abdomen received the same dose (Schedule II). Sixteen of seventeen patients (94%) thus treated, completed the planned dose of radiation. The actuarial survival for all 116 patients was 28% of 5 years. Irradiated patients with negative second look laparotomy had a survival probability of 100% at 24 months. Irradiated patients with microscopic disease at second look operation had an actuarial 5-year survival of 66%. Patients with minimal residual disease at second look laparotomy, receiving consolidation abdominal irradiation, had an actuarial survival of 5% only at 36 months. It is concluded that consolidation radiotherapy is effective in patients with negative or microscopic residual disease at second-look laparotomy. In regard to bone marrow tolerance, split field technique of irradiation is preferred

  4. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma

    OpenAIRE

    Elshamy Maged R; Setit Ahmed E; Elshafei Mohamed A; Hegazi Refaat AF; Hegazy Mohamed AF; Eltatoongy Mohamed; Halim Amal AF

    2005-01-01

    Abstract Background Patients with advanced ovarian cancer should be treated by radical debulking surgery aiming at complete tumor resection. Unfortunately about 70% of the patients present with advanced disease, when optimal debulking can not be obtained, and therefore these patients gain little benefit from surgery. Neoadjuvant chemotherapy (NACT) has been proposed as a novel therapeutic approach in such cases. In this study, we report our results with primary surgery or neoadjuvant chemothe...

  5. Neoadjuvant intraarterial chemotherapy and embolization in treatment of advanced ovarian epithelial carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘恩令; 糜若然

    2004-01-01

    Background The purpose of the study was to evaluate the role of neoadjuvant chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries in treating patients with advanced ovarian epithelial carcinoma.Methods Forty-two patients with advanced ovarian epithelial carcinoma (study group) were treated via the anterior branches of the bilateral internal iliac arteries after cytoreductive surgery and 7 courses of adjuvant platinum-based combination chemotherapy. Primary cytoreductive surgery was performed in 43 patients with advanced ovarian epithelial carcinoma (control group), and then followed by 8 courses of adjuvant platinum-based combination chemotherapy. The rate of optimal cytoreductive surgery, survival rate, blood loss during operation and operative time were investigated in the two groups. Statistical significance was asessed using Student's t test, the Chi-squre test and the log-rank test. Results In the study group, the rate of optimum debulking after platinum-based chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries was 71.43%(30/42) (χ2=10.06, P0.05).Conclusions Neoadjuvant platinum-based combination chemotherapy and embolization via the anterior branches of the bilateral internal iliac arteries is an alternative treatment for patients with advanced ovarian epithelial carcinoma, in whom the chance of optimal cytoreductive surgery is low. The treatment can reduce blood loss, decrease operative time, and increase the rate of optimal cytoreductive surgery; but the median survival can't be improved significantly.

  6. Advanced small-cell ovarian carcinoma, hypercalcemic type: a challenging therapeutic entity

    Directory of Open Access Journals (Sweden)

    Rafael Caparica Bitton

    2014-09-01

    Full Text Available Small-cell ovarian carcinoma (SCOC is a rare and aggressive neoplasia, predominantly affecting young women who are frequently first diagnosed with advanced stage disease. Platinum-based chemotherapy (ChT can provide high response rates and rapidly ameliorate symptoms in this scenario. However, progression after chemotherapy usually occurs quickly, leading to high mortality rates. In addition, ChT complications, such as tumor lysis syndrome (TLS can also occur, jeopardizing the patient’s outcome. We present a case of metastatic SCOC in a 47-year-old patient who achieved tumor response after platinum-based chemotherapy and developed TLS, from which she recovered with supportive treatment. After the second ChT cycle, she developed febrile neutropenia and died 8 weeks after the diagnosis of SCOC. Although SCOC is a chemo-sensitive tumor, short-lived responses and frequent chemotherapy complications lead to a dismal prognosis.

  7. Pathobiology of ovarian carcinomas

    OpenAIRE

    Mojgan Devouassoux-Shisheboran; Catherine Genestie

    2015-01-01

    Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular bas...

  8. WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study

    International Nuclear Information System (INIS)

    WT1 is a tumor suppressor gene responsible for Wilms' tumor. WT1 reactivity is limited to ovarian serous carcinomas. Recent studies have shown that WT1 plays an important role in the progression of disease and indicates a poorer prognosis of human malignancies such as acute myeloid leukemia and breast cancer. The aims of this study were to determine the survival and recurrence-free survival of women with advanced serous epithelial ovarian carcinoma in relation to WT1 gene expression. The study accrued women over an 18-year period, from 1987–2004. During the study period, 163 patients were diagnosed with advanced serous epithelial ovarian carcinoma and had undergone complete post-operative chemotherapy, but the final study group comprised 99 patients. The records of these women were reviewed and the paraffin-embedded tissue of these women stained with WT1 immunostaining. Survival analysis was performed using Kaplan-Meier and Cox regression methods. Fifty patients showed WT1 staining and forty-nine did not. Five-year survival of non-staining and staining groups were 39.4% and 10.7% (p < 0.00005); five-year recurrence-free survival of these groups were 29.8% and ≤ 7.5% (p < 0.00005), respectively. For survival the HR of WT1 staining, adjusted for residual tumor and chemotherapy response, was 1.98 (95% CI 1.28–3.79), and for recurrence-free survival the HR was 3.36 (95% CI 1.60–7.03). The HR for recurrence-free survival was not confounded by any other variables. This study suggests that expression of WT1 gene may be indicative of an unfavorable prognosis in patients with advanced serous epithelial ovarian carcinoma

  9. Hyperthermic intra-peritoneal chemotherapy using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma. Results of a phase II prospective multicentre trial. CHIPOVAC study

    OpenAIRE

    Pomel, Christophe; Ferron, Gwenaël; Lorimier, Gérard; Rey, Annie; Lhomme, Catherine; Classe, Jean Marc; Bereder, J.M.; Quenet, François; Meeus, Pierre; Marshall, Frederic; Morice, Philippe; Elias, Dominique

    2010-01-01

    Abstract Introduction The aim of the present study was to prospectively evaluate morbidity of intra-peritoneal hyper-thermic chemotherapy (HIPEC) using Oxaliplatin as consolidation therapy for advanced epithelial ovarian carcinoma and, secondly, to study peritoneal recurrence. Methods Between 2004 and 2007, 31 patients from 18 to 65 years with FIGO stage IIIC epithelial ovarian carcinoma were treated by surgery and a total of 6 cycles of platinum ba...

  10. Combination of radiotherapy and selective chemotherapy in the treatment of advanced ovarian carcinomas

    International Nuclear Information System (INIS)

    A report is given on 160 patients suffering from ovarian carcinomas the stages which were exactly determined by TNM classification. 32 patients had tumors of the stages T1-T3, 128 patients had tumors of the stage T4. All T3 subgroups showed favorable results after radical surgery and a postoperative combination of radiotherapy and selective cytostatic chemotherapy. The therapy plans including radiotherapy had more advantages than those without radiotherapy. Furthermore, the cytostatic treatment was more successful after a chemotherapy resistance test than after blind administration of cytostatic drugs. (orig.)

  11. Malnutrition Identified by the Nutritional Risk Index and Poor Prognosis in Advanced Epithelial Ovarian Carcinoma.

    Science.gov (United States)

    Yim, Ga Won; Eoh, Kyung Jin; Kim, Sang Wun; Nam, Eun Ji; Kim, Young Tae

    2016-07-01

    Ovarian cancer is a chronic disease with a risk of malnutrition. Nutritional Risk Index (NRI) has been reported as a simple and accurate tool to assess the nutritional status. We sought to explore the prevalence of malnutrition and its association with survival in ovarian cancer. A retrospective study was conducted in 213 advanced ovarian cancer patients. NRI was calculated before and at the end of treatment using patients' body weight and serum albumin level. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier method, and associations were assessed using a Cox proportional hazards analysis adjusted for known prognostic variables. Moderate to severely malnourished patients had lower 5-yr OS (45.3%) compared to normal to mild group (64.0%), respectively (P = 0.024). Adjusted for covariates, the relative risk of death was 5.8 times higher in moderate/severely malnourished group identified at the last course of chemotherapy (HR = 5.896, 95% CI = 2.723-12.764, P Malnutrition is prevalent among ovarian cancer patients and is found to be a significant predictor for mortality. PMID:27044606

  12. Genomic profile of ovarian carcinomas

    OpenAIRE

    Micci, Francesca; Haugom, Lisbeth; Vera M. Abeler; Davidson, Ben; Tropé, Claes G; Heim, Sverre

    2014-01-01

    Background It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. Methods We cytogenetically analyzed 110 new cases of ovarian carcinoma of different histologic...

  13. Peripartum disseminated extrapulmonary tuberculosis simulating ovarian carcinoma.

    Science.gov (United States)

    Sherer, David M; Osho, Joseph A; Zinn, Harry; Demetus, Spiro; Huang, Jennifer; Temkin, Sarah; Abulafia, Ovadia

    2005-10-01

    Disseminated extrapulmonary tuberculosis is an uncommon complication of pregnancy. We present a 26-year-old multiparous immigrant from Haiti who was admitted following an extramural preterm delivery. Marked ascites was confirmed by computerized tomography, which also revealed a thickened greater omentum. These findings were considered suggestive of advanced ovarian carcinoma, although extrapulmonary tuberculosis was also considered despite negative tuberculin skin test screening. Image-guided omental biopsy demonstrated caseating granulomas substantiating the diagnosis of abdominal tuberculosis, which was later confirmed by cultures. The patient responded well to antituberculosis medications. This case describes the unusual peripartum presentation of abdominal tuberculosis simulating advanced ovarian carcinoma, and demonstrates the importance of considering extrapulmonary tuberculosis when encountering ascites and omental thickening during pregnancy despite negative tuberculin skin test screening. PMID:16215926

  14. Genomic profile of ovarian carcinomas

    OpenAIRE

    Micci, Francesca; Haugom, Lisbeth; Vera M. Abeler; Davidson, Ben; Tropé, Claes G; Heim, Sverre

    2014-01-01

    Background It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. Methods ...

  15. Management of brain metastasis in a patient with advanced epithelial ovarian carcinoma by gamma-knife radiosurgery

    OpenAIRE

    Nikolaou Marinos; Stamenković Srđan; Stergiou Christos; Skarleas Christos; Torrens Michael

    2015-01-01

    Introduction. Brain metastases from epithelial ovarian cancer (EOC) are rare events. We present a rare case of single ovarian cancer metastasis to the brain treated with gamma-knife radiosurgery (GKRS). Case Outline. A 65-year-old woman with advanced EOC presented with severe neurologic symptoms. A single brain metastasis of 3.2 cm with surrounding edema in the left parietal lobe was detected by brain magnetic resonance imaging (MRI) scan during the work-up...

  16. [Cytostatic treatment of ovarian carcinoma].

    Science.gov (United States)

    Neijt, J P

    1999-10-30

    Shortly after treatment with the cytostatic combination of cisplatin and paclitaxel was generally accepted as the standard therapy for patients with epithelial ovarian carcinoma, many have come to regard the combination of carboplatin and paclitaxel as a better choice. The latter combination causes fewer side effects and may be used in the outpatient clinic. Conceivably, the carboplatin-paclitaxel scheme will shortly have to be adjusted again owing to results of current research. The intensive basic research of recent years, namely, is beginning to yield benefits for the therapeutic arsenal against ovarian carcinoma. Possibilities are inhibitors of the breakdown of extracellular matrix (such as marimastat) and inhibitors of signal transduction (such as trastuzumab). PMID:10578409

  17. Cost of illness of advanced ovarian carcinoma in Italy: results of an empirical, single-centre study

    Directory of Open Access Journals (Sweden)

    Carlo Lazzaro

    2015-09-01

    Full Text Available AIM: To perform an empirical, single-centre, retrospective and secondary cost of illness (COI study of advanced ovarian carcinoma (AOC in Italy. METHODS: Demographic, clinical, health care and non-health care resource consumption data concerning a convenience sample of subsequent patients in 1st line of treatment (100 patients, 2nd line of treatment A (surgery + chemotherapy; 30 patients and 2nd line of treatment B (chemotherapy only; 20 patients were obtained from a database created in 2011 by the Obstetrics and Ginecology Unit at Campus Biomedico teaching hospital, Rome. Patients were followed-up for 2 years. Resources were valued according to the above mentioned database and literature, following the societal viewpoint. Costs are expressed in Euro (€ 2014 and reported as mean and standard deviation (SD. RESULTS: One-year COI for 1st line of treatment reaches € 44,999.7 (SD: €28,757.3, € 55,410.8 (SD: € 32,454.6 and €46,895.6 (SD: € 28,407.4 for 2nd line of treatment A and B, respectively. Regardless the line of treatment, COI is mainly driven by cost borne by patient and her family. Due to the high costs of relapse the mean COI per patient after 2 years from the diagnosis of AOC equals € 81,869.4 (SD: € 30,660.9, or 182% of the COI for the 1st line of treatment. CONCLUSIONS: Despite some limitations, our results show that increasing progression-free survival could well reduce the COI for AOC in Italy.

  18. OVARIAN METASTASIS IN PATIENT WITH ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    ZHOU Feng-zhi; CHEN Yi-nan; ZHANG Guo-nan

    2005-01-01

    Objective: To study the clinical pathological characteristics of ovarian metastasis of endometrial carcinoma and the factors affecting prognosis. Methods: Retrospective analysis was made to the clinical pathological outcome of endometrial carcinoma patients receiving surgical treatment in our hospital from January 1990 to December 2002. Results:Among the 191 cases of endometrial carcinoma patients, 17 cases (8.9%) had ovarian metastasis and young patients were more likely to have ovarian metastasis. The multiple factor analysis showed that the independent risk factors of ovarian metastasis in endometrial carcinoma included the depth of myometrial invasion, lymph node metastasis and pathological types. Conclusion: Ovarian metastasis in patients with endometrial carcinoma is associated with poor prognosis, the depth of myometrial invasion, lymph node metastasis and histologic types are independent risk factors affecting the prognosis. For young patients at early stage of the disease, it should be prudent as to whether to retain the ovary.

  19. Axillary node metastasis from primary ovarian carcinoma

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    Trupti S Patel

    2014-01-01

    Full Text Available Metastasization and distinction from mammary carcinoma is of great clinical importance because of different treatment modalities. Here, we discuss a case of stage IIIC ovarian serous carcinoma, presenting with bilateral axillary nodes metastasis after 25 months interval of its initial presentation. Increased serum CA-125 level caused clinical suspicion. Computed tomography scan of abdomen and pelvis showed no residual disease or any abdominal lymphadenopathy. Mammography of both breast were normal. Bilateral axillary nodes were noted. Guided fine needle aspiration cytology (FNAC and biopsy of ovarian carcinoma to axillary node is a rare event. Its recogn done. Cytomorphology revealed poorly differentiated carcinoma, compatible to that of primary ovarian tumor. Thus, metastatic carcinoma to axillary node from ovary was confirmed. This case illustrates a rare metastatic presentation of ovarian carcinoma and unequivocal role of FNAC to provide rapid diagnosis and preferred to be first line diagnostic procedure.

  20. Human ovarian carcinomas detected by specific odor.

    Science.gov (United States)

    Horvath, György; Järverud, Gunvor Af Klinteberg; Järverud, Sven; Horváth, István

    2008-06-01

    The high mortality rate associated with ovarian carcinoma is mainly owing to late diagnosis. It is thus essential to develop inexpensive and simple methods for early diagnosis. Papers on canine scent detection of malignancies such as melanoma and bladder, lung, and breast cancer have recently been published in peer-reviewed journals, indicating a new diagnostic tool for malignancies. However, in these studies the dogs may have responded to odors associated with cancer, such as inflammation or metabolic products, rather than specifically to cancer itself. Therefore, it is important to ascertain whether or not human cancers are characterized by specific odors. We hypothesized that if ovarian carcinoma emits a specific odor, dogs may be trained to detect it. Using our training method, we taught a dog to distinguish different histopathological types and grades of ovarian carcinomas, including borderline tumors, from healthy control samples. Double-blind tests showed 100% sensitivity and 97.5% specificity. Moreover, the odor of ovarian carcinomas seems to differ from those of other gynecological malignances such cervical, endometrial, and vulvar carcinomas. Our study strongly suggests that the most common ovarian carcinomas are characterized by a single specific odor. PMID:18505901

  1. Potential targets for ovarian clear cell carcinoma: a review of updates and future perspectives

    OpenAIRE

    Matsuzaki, Shinya; Yoshino, Kiyoshi; Ueda, Yutaka; Matsuzaki, Satoko; Kakuda, Mamoru; Okazawa, Akiko; Egawa-Takata, Tomomi; Kobayashi, Eiji; Kimura, Tadashi

    2015-01-01

    Advances in surgical and medical treatments for ovarian cancer have improved prognoses. Platinum drugs in particular are pivotal for the medical treatment of ovarian cancer. However, previous studies have revealed that some histological subtypes, such as clear cell carcinoma, are resistant to medical treatment, including that with platinum drugs. Consequently, the clinical prognosis of advanced clear cell carcinoma is remarkably inferior, primarily because of its chemoresistant behavior. The ...

  2. Temsirolimus and Bevacizumab in Treating Patients With Advanced Endometrial, Ovarian, Liver, Carcinoid, or Islet Cell Cancer

    Science.gov (United States)

    2016-04-11

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; Endometrial Serous Adenocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Lung Carcinoid Tumor; Malignant Pancreatic Gastrinoma; Malignant Pancreatic Glucagonoma; Malignant Pancreatic Insulinoma; Malignant Pancreatic Somatostatinoma; Metastatic Digestive System Neuroendocrine Tumor G1; Ovarian Carcinosarcoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Pancreatic Alpha Cell Adenoma; Pancreatic Beta Cell Adenoma; Pancreatic Delta Cell Adenoma; Pancreatic G-Cell Adenoma; Pancreatic Polypeptide Tumor; Recurrent Adult Liver Carcinoma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Corpus Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma

  3. Clinical management of ovarian small-cell carcinoma of the hypercalcemic type: A proposal for conservative surgery in an advanced stage of disease

    NARCIS (Netherlands)

    R.H.M. Dykgraaf; D. de Jong (Diederick); M. van Veen (Mirjam); P.C. Ewing-Graham (Patricia); T.J.M. Helmerhorst (Theo); M. van der Burg (Mirjam)

    2009-01-01

    textabstractOvarian small-cell carcinoma of the hypercalcemic type is a rare and highly malignant tumor. In two thirds of the patients, the tumor is associated with asymptomatic paraneoplastic hypercalcemia. The diagnosis may be impeded; the tumor must be distinguished from other tumors with similar

  4. Oxidatively Modified Proteins in the Serous Subtype of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Sharifeh Mehrabi

    2014-01-01

    Full Text Available Serous subtype of ovarian cancer is considered to originate from fallopian epithelium mucosa that has been exposed to physiological changes resulting from ovulation. Ovulation influences an increased in inflammation of epithelial ovarian cells as results of constant exposure of cells to ROS. The imbalance between ROS and antioxidant capacities, as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids. This study applied spectrophotometric, dinitrophenylhydrazone (DNPH assay, two-dimensional gel electrophoresis, and Western blot analyses to assess the levels of oxidatively modified proteins in 100 primary serous epithelial ovarian carcinoma and normal/surrounding tissues. These samples were obtained from 56 Caucasian and 44 African-American patients within the age range of 61±10 years. Analyses showed that the levels of reactive protein carbonyl groups increased as stages progressed to malignancy. Additionally, the levels of protein carbonyls in serous ovarian carcinoma among African Americans are 40% (P<0.05 higher relative to Caucasian at similar advanced stages. Results suggest that oxidative stress is involved in the modification of carbonyl protein groups, leading to increased aggressiveness of epithelial ovarian tumors and may contribute to the disease's invasiveness among African Americans.

  5. Recent alcohol consumption and risk of incident ovarian carcinoma

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Bandera, Elisa V; Terry, Kathryn L;

    2013-01-01

    Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations.......Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations....

  6. Clinicopathologic and immunohistochemical profile of ovarian metastases from colorectal carcinoma

    OpenAIRE

    2010-01-01

    Metastasis of colorectal adenocarcinoma of the ovary is not an uncommon occurrence and ovarian metastases from colorectal carcinoma frequently mimic endometrioid and mucinous primary ovarian carcinoma. The clinical and pathologic features of metastatic colorectal adenocarcinoma involving the ovary is reviewed with particular focus on the diagnostic challenge of distinguishing these secondary ovarian tumors from primary ovarian neoplasm. Immunohistochemical stains that may be useful in the dif...

  7. A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma

    NARCIS (Netherlands)

    De Vos, F Y F L; Bos, A M E; Schaapveld, M; de Swart, C A M; de Graaf, H; van der Zee, A G J; Boezen, H M; de Vries, E G E; Willemse, P H B

    2005-01-01

    OBJECTIVE: Will amifostine (A) protect against chemotherapy-induced neuro- and myelotoxicity. PATIENTS AND METHODS: Ninety ovarian cancer patients were randomized to receive standard paclitaxel + carboplatin without (PC) or preceded by amifostine 740 mg/m(2) (PC + A). RESULTS: The mean baseline valu

  8. PHASE-II STUDY OF HIGH-DOSE MEGESTROL-ACETATE IN PATIENTS WITH ADVANCED OVARIAN-CARCINOMA

    NARCIS (Netherlands)

    VEENHOF, CHN; VANDERBURG, MEL; NOOY, M; AALDERS, JG; PECORELLI, S; OLIVEIRA, CF; ROTMENSZ, N; VERMORKEN, JB

    1994-01-01

    The EORTC Gynaecological Cancer Cooperative Group conducted a phase II study of high dose oral megestrol acetate: 800 mg/day for 1 month followed by 400 mg/day as maintenance treatment, in heavily pretreated patients with ovarian cancer. Of 72 patients included in this study, 54 were fully evaluable

  9. The Effect of Sortilin Silencing on Ovarian Carcinoma Cells

    OpenAIRE

    Ghaemimanesh, Fatemeh; Ahmadian, Gholamreza; Talebi, Saeed; Zarnani, Amir-Hassan; Behmanesh, Mehrdad; Hemmati, Shayda; Hadavi, Reza; Jeddi-Tehrani, Mahmood; Farzi, Maryam; Akhondi, Mohammad mehdi; Rabbani, Hodjattallah

    2014-01-01

    Background Our preliminary data on the protein expression of SORT1 in ovarian carcinoma tissues showed that sortilin was overexpressed in ovarian carcinoma patients and cell lines, while non-malignant ovaries expressed comparably lower amount of this protein. In spite of diverse ligands and also different putative functions of sortilin (NTR3), the function of overexpressed sortilin in ovarian carcinoma cells is an intriguing subject of inquiry. The aim of this study was, therefore, to investi...

  10. Postchemotherapy Histopathological Evaluation of Ovarian Carcinoma: A 40-Case Study

    OpenAIRE

    Kanwardeep Kaur Tiwana; Sarita Nibhoria; Manmeet Kaur; Tanvi Monga; Ratika Gupta

    2015-01-01

    Ovarian carcinomas are conventionally treated with primary debulking surgery followed by chemotherapy. Nowadays neoadjuvant chemotherapy followed by surgery is an upcoming treatment modality for ovarian carcinoma. This study highlights the histopathological changes observed after neoadjuvant chemotherapy. Present study is a 40-case study stressing five histological parameters: residual tumour, fibrosis, necrosis, inflammation, and psammoma bodies. All these parameters carry prognostic signifi...

  11. Genomic/Epigenomic Alterations in Ovarian Carcinoma: Translational Insight into Clinical Practice

    Science.gov (United States)

    Dong, Anliang; Lu, Yan; Lu, Bingjian

    2016-01-01

    Ovarian carcinoma is the most lethal gynecological malignancy worldwide. Recent advance in genomic/epigenomic researches will impact on our prevention, detection and intervention on ovarian carcinoma. Detection of germline mutations in BRCA1/BRCA2, mismatch repair genes, and other genes in the homologous recombination/DNA repair pathway propelled the genetic surveillance of most hereditary ovarian carcinomas. Germline or somatic mutations in SMARCA4 in familial and sporadic small cell carcinoma of the ovary, hypercalcemia type, lead to our recognition on this rare aggressive tumor as a new entity of the atypical teratoma/rhaboid tumor family. Genome-wide association studies have identified many genetic variants that will contribute to the evaluation of ovarian carcinoma risk and prognostic prediction. Whole exome sequencing and whole genome sequencing discovered rare mutations in other drive mutations except p53, but demonstrated the presence of high genomic heterogeneity and adaptability in the genetic evolution of high grade ovarian serous carcinomas that occurs in cancer progression and chemotherapy. Gene mutations, copy number aberrations and DNA methylations provided promising biomarkers for the detection, diagnosis, prognosis, therapy response and targets of ovarian cancer. These findings underscore the necessity to translate these potential biomarkers into clinical practice. PMID:27471560

  12. 节律化疗作为体力状况较差的晚期卵巢上皮癌患者的姑息治疗%Metronomic chemotherapy as a palliative treatment in poor performance status patients with advanced epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Eman I.Ismail; Mohamed A.Elgawad

    2011-01-01

    Objective: The aim of our study was to evaluate the clinical efficacy and tolerability of metronomic chemotherapy in patients with advanced ovarian carcinoma. Methods: Fifteen patients with advanced ovarian carcinoma and bad performance status were subjected to daily cyclophosphamide(CTX)after failure of 1st line chemotherapy which included paditaxel and carboplatin. Evaluation of the cases during treatment as regard treatment side effects and progression free survival. Results: Patients could tolerate low dose oral cyclophosphamide treatment without considerable side effects with improvement of performance status. The mean progression free survival was 12 months. Conclusion: Low dose oral cydophosphamide could be considered as a palliative treatment of pretreated ovarian carcinomas with poor performance status.

  13. Characteristic odour in the blood reveals ovarian carcinoma

    International Nuclear Information System (INIS)

    Ovarian carcinoma represents about 4% of all cancers diagnosed in women worldwide. Mortality rate is high, over 50%, mainly due to late diagnosis. Currently there are no acceptable screening techniques available, although ovarian cancer belongs to the group of malignancies for which mortality could be dramatically reduced by early diagnosis. In a recently published study, we clearly demonstrated that human ovarian carcinoma tissues can be characterized by a specific odour, detectable by a trained dog. Another recent study confirmed these results using an electronic nose. In the present work, we examined whether the cancer-specific odour can also be found in the blood. Two specially trained dogs were used. Both ovarian cancer tissues and blood from patients with ovarian carcinoma were tested. The tissue tests showed sensitivity of 100% and specificity of 95%, while the blood tests showed sensitivity of 100% and specificity of 98%. The present study strongly suggests that the characteristic odour emitted by ovarian cancer samples is also present in blood (plasma) taken from patients with the disease. This finding opens possibilities for future screening of healthy populations for early diagnosis of ovarian carcinoma. A future challenge is to develop a sensitive electronic nose for screening of ovarian carcinoma by testing the blood/plasma to detect the disease at a stage early enough for treatment to be effective

  14. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas

    OpenAIRE

    Crane, Erin K; Kwan, Suet-Yan; Daisy I Izaguirre; Tsang, Yvonne T. M.; Mullany, Lisa K.; Zu, Zhifei; Richards, JoAnne S.; Gershenson, David M.; Wong, Kwong-Kwok

    2015-01-01

    Epithelial ovarian cancer is a diverse molecular and clinical disease, yet standard treatment is the same for all subtypes. TP53 mutations represent a node of divergence in epithelial ovarian cancer histologic subtypes and may represent a therapeutic opportunity in subtypes expressing wild type, including most low-grade ovarian serous carcinomas, ovarian clear cell carcinomas and ovarian endometrioid carcinomas, which represent approximately 25% of all epithelial ovarian cancer. We therefore ...

  15. Treatment of advanced stage ovarian carcinoma with a combination of chemotherapy, radiotherapy, and radiosensitizer: report of a pilot study from the National Cancer Institute

    International Nuclear Information System (INIS)

    Twenty-eight patients with Stage III or IV ovarian carcinoma were treated with combined chemotherapy-radiotherapy employing a unique protocol. Four cycles of cyclophosphamide and hexamethylmelamine alternated with four cycles of concurrent cisplatin, whole abdominal radiotherapy, and intraperitoneal misonidazole. The entire treatment program lasted six months. Clinical complete responses were seen in 50% of the patients with an overall response rate of 61%. Pathologic complete response (PCR) confirmed at second look surgery occurred in 18% of the group (5 patients). Median survival of the entire group was 15.2 months with all PCR's alive NED. This outcome was no different than our previous experience with combination chemotherapy alone. Toxicities seen included leukopenia, thrombocytopenia, nausea, vomiting, and weight loss. However, these side effects were manageable. Two non-tumor deaths occurred. This study demonstrates the feasibility of combining drug and radiation therapy concurrently in the treatment of ovarian cancer; further research is needed to explore different sequencing and dose levels that could improve the outcome

  16. PET as a substitute for second-look surgery in patients with advnaced epithelia ovarian carcinomas

    International Nuclear Information System (INIS)

    To compare the prognostic value o PET with second look laparotomy(SLL) in patients with advanced ovarian carcinoma following primary chemotherapy. 55 patients undergone cytoreductive surgery and adjuvant chemotherapy for epithelial ovarian carcinoma were enrolled in this study. 30 patients underwent SLL after primary treatment. 25 patients underwent PET after primary treatment without SLL. We retrospectively reviewed the medical records of 55 patients for comparison of relapse-free interval. Ovarian carcinomas recurred in 12 of 55 patients. FDG PET detected the recurrence of ovarian carcinoma in 8 patients(sensitivity=66.7%; specificity=88.7%; p=0.003), and better than CT/MRI (sensitivity=41.7%; specificity=58.2%; p>0.05). The median duration of survival after SLL was 29.6 months and that after PET was 30.9 months(p>0.05). FDG PET can be a sustitute for SLL for following up patients who have had ovarian carcinoma, especially with high risk for recurrence

  17. Telomerase Activity in Human Ovarian Carcinoma

    Science.gov (United States)

    Counter, Christopher M.; Hirte, Hal W.; Bacchetti, Silvia; Harley, Calvin B.

    1994-04-01

    Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.

  18. Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

    International Nuclear Information System (INIS)

    Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. This study found significantly elevated Mucin-1 serum

  19. Expression and Function of CD44 in Epithelial Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Joelle D. Sacks

    2015-11-01

    Full Text Available CD44, a cell surface glycoprotein, has been increasingly implicated in the pathogenesis and progression of epithelial ovarian cancer, the deadliest gynecologic malignancy in women. Here, we review recent reports on the expression and function of CD44 in epithelial ovarian carcinoma. Further functional data for CD44 in peritoneal adhesion and metastatic progression and its association with stem cells is highlighted. Recent studies utilizing CD44 for therapeutic targeting are also discussed.

  20. Highly Metastatic Ovarian Yolk Sac Carcinoma in a Rat

    OpenAIRE

    Sakamoto, Akika; Yamaguchi, Yuko; Yamakawa, Seiki; Nagatani, Mariko; Tamura, Kazutoshi

    2011-01-01

    We investigated a highly metastatic ovarian yolk sac carcinoma in a 52-week-old female Crl:CD(SD) rat. Macroscopically, the present case had severe ascites, bilateral ovarian masses and numerous nodules in the abdominal and thoracic cavities. Histopathologically, these masses and nodules were generally composed of two types of cells mimicking a parietal and visceral yolk sac. The parietal cells were round to polygonal, contained eosinophilic droplets and were arranged in nests and cords in th...

  1. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yang; Pang, Xiaoyan; Dong, Mei; Wen, Fang, E-mail: wenfang64@hotmail.com; Zhang, Yi, E-mail: syzi960@yahoo.com

    2013-11-01

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients.

  2. Nesfatin-1 inhibits ovarian epithelial carcinoma cell proliferation in vitro

    International Nuclear Information System (INIS)

    Highlights: •Nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest. •Nesfatin-1 enhances HO-8910 cell apoptosis. •Nesfatin-1 inhibits HO-8910 cell proliferation via mTOR and RhoA/ROCK signaling pathway. •The first report of nesfatin-1-mediated proliferation in ovarian epithelial carcinoma. -- Abstract: Nesfatin-1, an 82-amino-acid peptide derived from a 396-amino-acid precursor protein nucleobindin 2 (NUCB2), was originally identified in hypothalamic nuclei involved in the regulation of food intake. It was recently reported that nesfatin-1 is a novel depot specific adipokine preferentially produced by subcutaneous tissue, with obesity- and food deprivation-regulated expression. Although a relation between ovarian cancer mortality and obesity has been previously established, a role of nesfatin-1 in ovarian epithelial carcinoma remains unknown. The aim of the present study is to examine the effect of nesfatin-1 on ovary carcinoma cells proliferation. We found that nesfatin-1 inhibits the proliferation and growth of HO-8910 cells by G1 phase arrest, this inhibition could be abolished by nesfatin-1 neutralizing antibody. Nesfatin-1 enhances HO-8910 cell apoptosis, activation of mammalian target of rapamycin (mTOR) and RhoA/ROCK signaling pathway block the effects of nesfatin-1-induced apoptosis, therefore reverses the inhibition of HO-8910 cell proliferation by nesfatin-1. In conclusion, the present study demonstrated that nesfatin-1 can inhibit the proliferation in human ovarian epithelial carcinoma cell line HO-8910 cells through inducing apoptosis via mTOR and RhoA/ROCK signaling pathway. This study provides a novel regulatory signaling pathway of nesfatin-1-regulated ovarian epithelial carcinoma growth and may contribute to ovarian cancer prevention and therapy, especially in obese patients

  3. Ovarian mucinous cystadenoma with mural nodule of anaplastic carcinoma.

    OpenAIRE

    Hong, S. R.; Chun, Y. K.; Kim, Y. J.; Lim, K. T.; Kim, H S

    1998-01-01

    The occurrence of malignant mural nodule in benign cystic common epithelial tumor of the ovary have been reported in only three cases; the case one was mucinous cystadenoma with a mural nodule of fibrosarcoma and the others were of carcinomas. Our case was another rare case of ovarian mucinous cystadenoma with mural nodule of anaplastic carcinoma in a 42-year-old woman. The cystadenoma had an unilocular cystic cavity and a mural nodule with thick multinodular solid wall. The internal cystic w...

  4. Quantitative autoradiography measurement of CA-MoV18 antigen concentration in ovarian carcinomas

    International Nuclear Information System (INIS)

    Concentrations of CA-MoV18 antigen in ovarian tumor and normal ovarian tissue samples were measured. Quantitative autoradiography was performed in 33 ovarian tissue samples with radiolabeled MoV18 monoclonal antibodies. Among them 22 samples were ovarian carcinomas, 7 samples were benign ovarian tumors and 4 samples were normal ovarian tissues. Among 19 serous ovarian carcinomas, 17 had MoV 18 antigen expression, ranging from 1.30 to 59.28 pmol/g tissue, 3 mutinous ovarian carcinomas and 11 nonmalignant ovaries (7 benign tumors and 4 normal tissues) were not detectable MoV 18 antigen. CA-MoV18 antigen was expressed in serous ovarian carcinomas. The concentration of CA-MoV 18 antigen was correlated with labelled antibodies (%ID/g) in tumor tissue

  5. Genome-wide significant risk associations for mucinous ovarian carcinoma

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Lawrenson, Kate; Tyrer, Jonathan;

    2015-01-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas but not for mucinous ovarian carcinomas (MOCs). Our analysis of 1,644 MOC cases and 21,693 controls with imputation identified 3 new risk associations: rs752590 at 2q13 (P = 3.3 × 10(-8)), rs711830 at 2......q31.1 (P = 7.5 × 10(-12)) and rs688187 at 19q13.2 (P = 6.8 × 10(-13)). We identified significant expression quantitative trait locus (eQTL) associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10(-4), false discovery rate (FDR) = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors and for PAX8 at...

  6. A meta-analysis: neoadjuvant chemotherapy versus primary surgery in ovarian carcinoma FIGO stageIII and IV

    OpenAIRE

    Dai-yuan, Ma; Bang-xian, Tan; Xian-fu, Li; Ye-qin, Zhou; Hong-Wei, Cai

    2013-01-01

    Background The purpose of the current study is to analyze the existing data comparing neoadjuvant chemotherapy with primary debulking surgery (PDS) in patients with advanced ovarian carcinoma. Methods Patients with stage IIIC and IV ovarian cancer were identified from articles in Medline, PubMed, Cochrane Library, and EMBASE database (1989 to February 2013). Two authors independently extracted the data. To assess the risk of bias of included literatures, Cochrane Collaboration’s risk of bias ...

  7. Estrogen receptor beta rs1271572 polymorphism and invasive ovarian carcinoma risk

    DEFF Research Database (Denmark)

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J;

    2011-01-01

    The association of ovarian carcinoma risk with the polymorphism rs1271572 in the estrogen receptor beta (ESR2) gene was examined in 4946 women with primary invasive ovarian carcinoma and 6582 controls in a pooled analysis of ten case-control studies within the Ovarian Cancer Association Consortium...

  8. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies.

    Directory of Open Access Journals (Sweden)

    Martin Köbel

    2008-12-01

    Full Text Available BACKGROUND: Although it has long been appreciated that ovarian carcinoma subtypes (serous, clear cell, endometrioid, and mucinous are associated with different natural histories, most ovarian carcinoma biomarker studies and current treatment protocols for women with this disease are not subtype specific. With the emergence of high-throughput molecular techniques, distinct pathogenetic pathways have been identified in these subtypes. We examined variation in biomarker expression rates between subtypes, and how this influences correlations between biomarker expression and stage at diagnosis or prognosis. METHODS AND FINDINGS: In this retrospective study we assessed the protein expression of 21 candidate tissue-based biomarkers (CA125, CRABP-II, EpCam, ER, F-Spondin, HE4, IGF2, K-Cadherin, Ki-67, KISS1, Matriptase, Mesothelin, MIF, MMP7, p21, p53, PAX8, PR, SLPI, TROP2, WT1 in a population-based cohort of 500 ovarian carcinomas that was collected over the period from 1984 to 2000. The expression of 20 of the 21 biomarkers differs significantly between subtypes, but does not vary across stage within each subtype. Survival analyses show that nine of the 21 biomarkers are prognostic indicators in the entire cohort but when analyzed by subtype only three remain prognostic indicators in the high-grade serous and none in the clear cell subtype. For example, tumor proliferation, as assessed by Ki-67 staining, varies markedly between different subtypes and is an unfavourable prognostic marker in the entire cohort (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.2%-2.4% but is not of prognostic significance within any subtype. Prognostic associations can even show an inverse correlation within the entire cohort, when compared to a specific subtype. For example, WT1 is more frequently expressed in high-grade serous carcinomas, an aggressive subtype, and is an unfavourable prognostic marker within the entire cohort of ovarian carcinomas (RR 1.7, 95% CI 1

  9. Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    Objective: To describe the experience at the National Cancer Institute (NCI) on the use of neoadjuvant chemotherapy as primary treatment for epithelial ovarian cancer among patients in stages IIIC and IV. Methods: We conducted a descriptive retrospective study (case series type) of patients diagnosed with epithelial ovarian cancer in stages IIIC and IV, treated at the NCI from January 1, 2003 to December 31,2006, who underwent neoadjuvant chemotherapy as primary treatment. Demographic characteristics and clinical outcomes are described. Results: Seventeen patients who fulfilled the above mentioned criteria were selected. Once neoadjuvant chemotherapy ended, 5 patients (29.4%) achieved complete or partial clinical response; 4 (23.8%) remained in stable condition, and 8 (47.6%) showed signs of progressive illness. Interval debulking surgery was performed on objective response patients. Maximum cytoreduction was achieved in 5 patients (100%); first relapse was reported at month 18 of follow-up; 2 disease-free survivors were identified in December, 2007; 8 (49%) reported some degree of non-severe chemotherapy-related toxicity. No mortality was related to chemotherapy, no post surgical complications were observed and no patient required advanced support management. Conclusions: Neoadjuvant chemotherapy, followed by optimal interval debulking surgery among selected patients, can be an alternative treatment for advanced epithelial ovarian cancer among women with irresecability or the critically ill. Further studies with improved design are required to confirm these findings.

  10. Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

    Directory of Open Access Journals (Sweden)

    Olsson Björn

    2009-10-01

    Full Text Available Abstract Background Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. Methods To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH, we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1 plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR to evaluate the impact of DNA alterations on the transcriptional level. Results We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. Conclusion In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate

  11. Potential predictive markers of chemotherapy resistance in stage III ovarian serous carcinomas

    International Nuclear Information System (INIS)

    Chemotherapy resistance remains a major obstacle in the treatment of women with ovarian cancer. Establishing predictive markers of chemoresponse would help to individualize therapy and improve survival of ovarian cancer patients. Chemotherapy resistance in ovarian cancer has been studied thoroughly and several non-overlapping single genes, gene profiles and copy number alterations have been suggested as potential markers. The objective of this study was to explore genetic alterations behind chemotherapy resistance in ovarian cancer with the ultimate aim to find potential predictive markers. To create the best opportunities for identifying genetic alterations of importance for resistance, we selected a homogenous tumor material concerning histology, stage and chemotherapy. Using high-resolution whole genome array comparative genomic hybridization (CGH), we analyzed the tumor genomes of 40 fresh-frozen stage III ovarian serous carcinomas, all uniformly treated with combination therapy paclitaxel/carboplatin. Fisher's exact test was used to identify significant differences. Subsequently, we examined four genes in the significant regions (EVI1, MDS1, SH3GL2, SH3KBP1) plus the ABCB1 gene with quantitative real-time polymerase chain reaction (QPCR) to evaluate the impact of DNA alterations on the transcriptional level. We identified gain in 3q26.2, and losses in 6q11.2-12, 9p22.3, 9p22.2-22.1, 9p22.1-21.3, Xp22.2-22.12, Xp22.11-11.3, and Xp11.23-11.1 to be significantly associated with chemotherapy resistance. In the gene expression analysis, EVI1 expression differed between samples with gain versus without gain, exhibiting higher expression in the gain group. In conclusion, we detected specific genetic alterations associated with resistance, of which some might be potential predictive markers of chemotherapy resistance in advanced ovarian serous carcinomas. Thus, further studies are required to validate these findings in an independent ovarian tumor series

  12. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    OpenAIRE

    Upasana Baruah; Debabrata Barmon; Amal Chandra Kataki; Pankaj Deka; Munlima Hazarika; Bhargab J Saikia

    2015-01-01

    Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with...

  13. Pure primary ovarian squamous cell carcinoma: A case report and review of the literature

    OpenAIRE

    Park, Jung-Woo; BAE, JONG WOON

    2014-01-01

    Pure primary ovarian squamous cell carcinoma (SCC) is a rare lesion that usually arises from the malignant transformation of an existing ovarian dermoid cyst. The de novo occurrence of an ovarian SCC in the absence of a prior ovarian dermoid cyst, Brenner tumor or endometriosis is extremely rare. At present, no effective therapy exists for treating pure primary ovarian SCC. The present case study describes a patient that presented with progressive coughing, who was diagnosed with an Internati...

  14. Postchemotherapy Histopathological Evaluation of Ovarian Carcinoma: A 40-Case Study

    Directory of Open Access Journals (Sweden)

    Kanwardeep Kaur Tiwana

    2015-01-01

    Full Text Available Ovarian carcinomas are conventionally treated with primary debulking surgery followed by chemotherapy. Nowadays neoadjuvant chemotherapy followed by surgery is an upcoming treatment modality for ovarian carcinoma. This study highlights the histopathological changes observed after neoadjuvant chemotherapy. Present study is a 40-case study stressing five histological parameters: residual tumour, fibrosis, necrosis, inflammation, and psammoma bodies. All these parameters carry prognostic significance and they are easily reproducible. Fleiss kappa statistics were used to measure intraobserver agreement between pathologists which was found to be substantial to almost perfect with κ ranging between 0.621 and 1.00. This study highlights easily reproducible parameters and their incorporation in histopathology report, thus helping in patient management.

  15. Genome-wide significant risk associations for mucinous ovarian carcinoma

    Science.gov (United States)

    Kelemen, Linda E.; Lawrenson, Kate; Tyrer, Jonathan; Li, Qiyuan; M. Lee, Janet; Seo, Ji-Heui; Phelan, Catherine M.; Beesley, Jonathan; Chen, Xiaoqin; Spindler, Tassja J.; Aben, Katja K.H.; Anton-Culver, Hoda; Antonenkova, Natalia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bruinsma, Fiona; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Chen, Y. Ann; Chen, Zhihua; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; Dennis, Joe; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; du Bois, Andreas; Dürst, Matthias; Eccles, Diana; Easton, Douglas T.; Edwards, Robert P.; Eilber, Ursula; Ekici, Arif B.; Engelholm, Svend Aage; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goode, Ellen L.; Goodman, Marc T.; Grownwald, Jacek; Harrington, Patricia; Harter, Philipp; Hasmad, Hanis Nazihah; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Estrid; Hogdall, Claus; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y; Kellar, Melissa; Kelley, Joseph L.; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Modugno, Francesmary; Moes-Sosnowska, Joanna; Moysich, Kirsten B.; Narod, Steven A.; Nedergaard, Lotte; Ness, Roberta B.; Nevanlinna, Heli; Azmi, Mat Adenan Noor; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste Leigh; Pejovic, Tanja; Pelttari, Liisa M.; Permuth-Wey, Jennifer; Pike, Malcolm C.; Poole, Elizabeth M.; Ramus, Susan J.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schildkraut, Joellen M.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Sucheston, Lara; Tangen, Ingvild L.; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J; Tworoger, Shelley S.; van Altena, Anne M.; Van Nieuwenhuysen, Els; Vergote, Ignace; Vierkant, Robert A.; Wang-Gohrke, Shan; Walsh, Christine; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wlodzimierz, Sawicki; Woo, Yin-Ling; Wu, Xifeng; Wu, Anna H.; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Sellers, Thomas A.; Freedman, Matthew L.; Chenevix-Trench, Georgia; Pharoah, Paul D.; Gayther, Simon A.; Berchuck, Andrew

    2015-01-01

    Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease. PMID:26075790

  16. Diagnosis of persistent ovarian carcinoma with three-step immunoscintigraphy

    OpenAIRE

    Magnani, P.; Fazio, F; C. Grana; Songini, C.; Frigerio, L; Pecorelli, S; Mangili, G; Colombo, N.; Mariani, C D A; Paganelli, G

    2000-01-01

    The diagnosis of recurrent ovarian carcinoma is usually determined at surgical re-exploration since the main non-invasive diagnostic tests have low accuracy. It would be desirable to have a high accuracy non-invasive diagnostic procedure. With this aim, we have assessed the utility of three-step immunoscintigraphy. Thirty patients were intravenously injected with biotinylated monoclonal antibodies MOv18 and B72.3, followed by avidin–streptavidin injection and finally by111In-biotin. Tumour re...

  17. Imaging of ovarian clear cell carcinoma

    International Nuclear Information System (INIS)

    The aim of this study is to examine the appearance of ovarian clear cell adenocarcinoma (OCCA) on MR, CT, US. In 39 cases with OCCA, the imaging characteristics of OCCA were evaluated morphologically and classified into three groups, that was, monomural nodule type, multi-mural nodule type and predominantly solid type. Forty-three percent of the patients had endometriosis. Contrast material-enhanced MRI was the most useful method for diagnosis of OCCA. (author)

  18. Imaging of ovarian clear cell carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Toshihiko; Sawano, Seishi; Yamada, Keiko [Japanese Foundation for Cancer Research, Tokyo (Japan). Hospital] (and others)

    1999-12-01

    The aim of this study is to examine the appearance of ovarian clear cell adenocarcinoma (OCCA) on MR, CT, US. In 39 cases with OCCA, the imaging characteristics of OCCA were evaluated morphologically and classified into three groups, that was, monomural nodule type, multi-mural nodule type and predominantly solid type. Forty-three percent of the patients had endometriosis. Contrast material-enhanced MRI was the most useful method for diagnosis of OCCA. (author)

  19. Endonucleases induced TRAIL-insensitive apoptosis in ovarian carcinoma cells

    International Nuclear Information System (INIS)

    TRAIL induced apoptosis of tumor cells is currently entering phase II clinical settings, despite the fact that not all tumor types are sensitive to TRAIL. TRAIL resistance in ovarian carcinomas can be caused by a blockade upstream of the caspase 3 signaling cascade. We explored the ability of restriction endonucleases to directly digest DNA in vivo, thereby circumventing the caspase cascade. For this purpose, we delivered enzymatically active endonucleases via the cationic amphiphilic lipid SAINT-18®:DOPE to both TRAIL-sensitive and insensitive ovarian carcinoma cells (OVCAR and SKOV-3, respectively). Functional nuclear localization after delivery of various endonucleases (BfiI, PvuII and NucA) was indicated by confocal microscopy and genomic cleavage analysis. For PvuII, analysis of mitochondrial damage demonstrated extensive apoptosis both in SKOV-3 and OVCAR. This study clearly demonstrates that cellular delivery of restriction endonucleases holds promise to serve as a novel therapeutic tool for the treatment of resistant ovarian carcinomas.

  20. MV-NIS Infected Mesenchymal Stem Cells in Treating Patients With Recurrent Ovarian Cancer

    Science.gov (United States)

    2016-02-18

    Malignant Ovarian Brenner Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  1. Novel biomarker candidates for the diagnosis of ovarian clear cell carcinoma

    OpenAIRE

    Kobayashi, Hiroshi; SUGIMOTO, HITOMI; ONISHI, SHUNSUKE; NAKANO, KAZUTOSHI

    2015-01-01

    Ovarian clear cell carcinoma can arise from endometriosis; however, it is distinct from other types of epithelial ovarian carcinoma in terms of its clinicopathological and molecular features. Cancer antigen 125 lacks the sensitivity and specificity required for accurate clinical diagnosis of clear cell carcinoma. Therefore, the aim of the current review was to identify novel biomarker candidates for the immunohistochemical and serological diagnosis of clear cell carcinoma. A search of the rel...

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

    Science.gov (United States)

    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

  3. CT diagnosis of intrasplenic metastasis from ovarian carcinoma

    International Nuclear Information System (INIS)

    Intrasplenic metastases from ovarian carcinoma cannot be always demonstrated intraoperatively. CT is the most important imaging modality of choice for staging and follow-up ovarian cancer; in this study we searched CT appearances of intrasplenic metastases from ovarian carcinoma. We retrospectively reviewed imaging histories of the patients with ovarian cancer from the radiology information system, and found 12 patients with intrasplenic metastasis. All patients underwent abdominal CT with 16-MDCT. We searched number, density and maximum diameters of splenic metastasis. The growing rate of three lesions, which were followed up by CT, was calculated. Serum cancer antigen (CA) 125 levels were noted. We also evaluated clinical history and pathology reports of all patients. Splenic metastases, solitary or multiple, were detected most frequently during the follow-up (1–14 years after initial diagnosis) and most were associated with other sites of recurrence. The diameters of lesions ranged from 4 to 85 mm. All lesions appeared hypodense except for one lesion with dense calcification. Densities of lesions ranged from 12 to 208 Hounsfield units (mean, 49 ± 51 HU). Most lesions appeared as solid well-defined nodules; however some lesions had lobulated and irregular contours with an infiltrative pattern. The growing rates of three lesions were 0.72 mm/month, 1.75 mm/month and 2.70 mm/month. Eight patients had elevated serum CA 125 levels (40–1256 U/mL). We concluded that CT can demonstrate intraparenchymal and infiltrative splenic metastasis in patients with ovarian cancer even in the absence of increased CA 125 levels.

  4. Pancreaticoduodenal Tuberculosis Simulating Metastatic Ovarian Carcinoma

    OpenAIRE

    1997-01-01

    A patient from Thailand presented with symptoms suggestive of peptic ulceration. Radiology showed an ulcerated duodenal stricture, a pancreaticoduodenal mass and extensive retroperitoneal lymphadenopathy suggestive of metastatic carcinoma. Tuberculosis was diagnosed only at laparotomy. The incidence of tuberculosis is increasing, and alimentary tuberculosis should be considered in patients from populations at risk presenting with obscure abdominal complaints or unexplained radiologic findings.

  5. Epithelial ovarian carcinoma in women aged below 30 years

    Institute of Scientific and Technical Information of China (English)

    Chen Rong; Shen Keng; Wu Ming; Pan Ling-ya; Huang Hui-fang; Yang Jia-xin; Lang Jing-he

    2005-01-01

    Objective: To study the manifestation, pathohistologic type, stage of disease, treatment and outcome of epithelial ovarian carcinoma in women under the age of 30 years.Methods: The 21 cases of epithelial ovarian carcinoma in women aged below 30 years between Jan, 1986 and Mar, 2002 were analyzed retrospectively.Results: The median age at the time of diagnosis was 24 years (range, 16-29 years). All carcinomas occurred after menarche. The most common symptoms were abdominal pain (50%), followed by tympanites (25%) and menstrual disorders (19%). The initial diagnosis was usually made by physical examination, ultrasonography and serum CA125. The mean maximal tumor diameter was 17.6 cm. Ten patients had Stage I disease (5 Ia, 5 Ic), five had Stage Ⅲ disease, and the other six were unknown during staging operation. There were nine mucinous tumors, six serous tumors. Most tumors were well-differentiated and classified as Grade1 in 11 cases, Grade2 in 2 cases, Grade3 in 2 cases, unknown in 6 cases. Optimal and suboptimal cytoreduction was achieved in 14 patients in primary treatment and 5 in recurrent treatment. 8 patients were treated with conservative surgery. 18 patients were treated with chemotherapy and 7 patients had experienced six or more than six courses of chemotherapy. The median follow-up was 50 months (range, 2-192 months). There were 6 deaths, 2 alive with tumor, 11 alive without the disease, 2 losing follow-up. The 3-year survival rate was 89%, and 5-year survival rate was 76%.Conclusion: Young patients with epithelial ovarian carcinoma appeared to have a less aggressive form of the disease and a more favorable prognosis.

  6. Surgical cytoreduction in recurrent ovarian carcinoma in patients with complete response to paclitaxel-platinum

    DEFF Research Database (Denmark)

    Gronlund, Bo; Lundvall, L; Christensen, Ib Jarle;

    2005-01-01

    AIM: The objective was to analyse the impact of secondary cytoreductive surgery in patients with recurrent ovarian carcinoma. METHODS: Retrospective review of 572 consecutive patients with primary ovarian carcinoma. Thirty-eight patients with intraabdominal/pelvic recurrence consisted the study g...

  7. Peritoneal and mediastinal highly differentiated follicular carcinoma of ovarian origin

    International Nuclear Information System (INIS)

    A 70-year-old female patient presented to her primary care doctor with persistent elevated alkaline phosphatase of suspected metastatic etiology. Computed tomography demonstrated epicardial and peritoneal nodules. Biopsy of one of the peritoneal nodules revealed thyroid tissue and extraovarian struma ovarii was considered. The patient had a history of remote total abdominal hysterectomy and bilateral salpingo-oophorectomy 31 years prior for endometriosis with no available pathology from that surgery. The patient recalls being told that she had a left ovarian cyst. A thyroid ultrasound was performed that demonstrated multiple nodules without concerning features; however, due to high clinical suspicion, a total thyroidectomy was performed. Upon full histological evaluation a 0.5 cm papillary microcarcinoma was found. Given the rarity of metastatic papillary cancer to the peritoneum and the small size and grade of the tumor, a diagnosis of highly differentiated follicular carcinoma of ovarian origin was favored. The patient was subsequently treated with radioiodine therapy

  8. Study of the Gene Expression Profile of Human Ovarian Carcinoma by a Gene Chip

    Institute of Scientific and Technical Information of China (English)

    Shenhua Xu; Hanzhou Mou; Chihong Zhu; Lijuan Qian; Zhengyan Yang; Ye Ying; Xianglin Liu

    2005-01-01

    OBJECTIVE To study the difference in gene expression between human ovarian carcinoma and normal ovarian tissues, and screen the novel associated genes by cDNA microarrays.METHODS Total RNA from 10 cases of ovarian cancer and from normal ovarian tissues were extracted by a single step method. The cDNA was retro-transcribed from an equal quantity of mRNA derived from the 10 cases of ovarian carcinoma and normal ovarian tissues, followed by labeling the cDNA strands with Cy5 and Cy3 fluorescence as probes. The mixed probes were hybridized with BiostarH 8464 dot human somatic cell genes.Fluorescence signals were assessed by a ScanArray 4000 laser scanner and the images analyzed by Gene Pix Pro 3.0 software with a digital computer.RESULTS By applying the cDNA microarray we found a total of 185 genes for which expression levels differed more than 5 times comparing human ovarian carcinoma with normal ovarian epithelium. Among these genes 86 were up-regulated >5 times and 99 were down regulated <0.2.CONCLUSION The cDNA microarray technique is effective in screening the differential gene expression between human ovarian cancers and normal ovarian epithelium. It is suggested that these genes identified are related to the genesis and development of ovarian carcinoma.

  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)

    Science.gov (United States)

    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. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome

    Directory of Open Access Journals (Sweden)

    Liu Jinsong

    2005-06-01

    Full Text Available Abstract Background The putative tumor suppressor WWOX gene spans the common chromosomal fragile site 16D (FRA16D at chromosome area 16q23.3-24.1. This region is a frequent target for loss of heterozygosity and chromosomal rearrangement in ovarian, breast, hepatocellular, prostate carcinomas and other neoplasias. The goal of these studies was to evaluate WWOX protein expression levels in ovarian carcinomas to determine if they correlated with clinico-pathological parameters, thus providing additional support for WWOX functioning as a tumor suppressor. Methods We performed WWOX protein expression analyses by means of immunobloting and immunohistochemistry on normal ovaries and specific human ovarian carcinoma Tissue Microarrays (n = 444. Univariate analysis of clinical-pathological parameters based on WWOX staining was determined by χ2 test with Yates' correction. The basic significance level was fixed at p Results Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels. The immunohistochemistry of normal human ovarian tissue sections confirmed strong WWOX expression in ovarian surface epithelial cells and in epithelial inclusion cysts within the cortex. Out of 444 ovarian carcinoma samples analyzed 30% of tumors showed lack of or barely detectable WWOX expression. The remaining ovarian carcinomas (70% stained moderately to strongly positive for this protein. The two histotypes showing significant loss of WWOX expression were of the Mucinous (70% and Clear Cell (42% types. Reduced WWOX expression demonstrated a significant association with clinical Stage IV (FIGO (p = 0.007, negative Progesterone Receptor (PR status (p = 0.008 and shorter overall survival (p = 0.03. Conclusion These data indicate that WWOX protein expression is highly variable among ovarian carcinoma histotypes. It was also observed that subsets

  11. WWOX protein expression varies among ovarian carcinoma histotypes and correlates with less favorable outcome

    International Nuclear Information System (INIS)

    The putative tumor suppressor WWOX gene spans the common chromosomal fragile site 16D (FRA16D) at chromosome area 16q23.3-24.1. This region is a frequent target for loss of heterozygosity and chromosomal rearrangement in ovarian, breast, hepatocellular, prostate carcinomas and other neoplasias. The goal of these studies was to evaluate WWOX protein expression levels in ovarian carcinomas to determine if they correlated with clinico-pathological parameters, thus providing additional support for WWOX functioning as a tumor suppressor. We performed WWOX protein expression analyses by means of immunobloting and immunohistochemistry on normal ovaries and specific human ovarian carcinoma Tissue Microarrays (n = 444). Univariate analysis of clinical-pathological parameters based on WWOX staining was determined by χ2 test with Yates' correction. The basic significance level was fixed at p < 0.05. Immunoblotting analysis from normal ovarian samples demonstrated consistently strong WWOX expression while 37% ovarian carcinomas showed reduced or undetectable WWOX protein expression levels. The immunohistochemistry of normal human ovarian tissue sections confirmed strong WWOX expression in ovarian surface epithelial cells and in epithelial inclusion cysts within the cortex. Out of 444 ovarian carcinoma samples analyzed 30% of tumors showed lack of or barely detectable WWOX expression. The remaining ovarian carcinomas (70%) stained moderately to strongly positive for this protein. The two histotypes showing significant loss of WWOX expression were of the Mucinous (70%) and Clear Cell (42%) types. Reduced WWOX expression demonstrated a significant association with clinical Stage IV (FIGO) (p = 0.007), negative Progesterone Receptor (PR) status (p = 0.008) and shorter overall survival (p = 0.03). These data indicate that WWOX protein expression is highly variable among ovarian carcinoma histotypes. It was also observed that subsets of ovarian tumors demonstrated loss of WWOX

  12. RELATIONSHIP AMONG COX-2 PROTEIN EXPRESSION, PGs LEVELS AND BIOLOGIC BEHAVIOR IN OVARIAN CARCINOMA TISSUES

    Institute of Scientific and Technical Information of China (English)

    王敏; 王欣彦; 唐丽霞; 高岩

    2004-01-01

    Objective: To study the relationship among cyclooxygenase-2 (COX-2) protein expression, prostaglandins levels and biologic behavior in ovarian carcinoma tissues. Methods: The expression of COX-2 protein, levels of prostaglandin (PG)E2, 6-keto-PGF1( and thromboxane (TX)B2 in 54 biopsy specimens from patients with ovarian serous tumors which included three groups: 33 samples of ovarian serous carcinoma; 10 samples of borderline ovarian serous tumors and 11 samples of benign ovarian serous tumors and 10 samples of normal ovarian tissues were detected by Western blot analysis and radioimmunoassay to investigate their clinical significance. Results: The expression of COX-2 protein (82%, 27/33) and its relative content (20.08±3.53) in ovarian serous carcinoma tissues were statistically higher than those in benign ovarian serous tumor tissues and normal ovary tissues i.e., 0 and (15.04(0.12), 0 and (15.33(0.60) (P0.05). The levels of PGE2, 6-keto-PGF1( and TXB2 showed no significant differences in ovarian carcinoma tissues with different clinical stages (I to II and III to IV), different histological grades, with or without ascites and lymph metastasis. COX-2 expression was correlated with the levels of PGE2, 6-KETO-PGF1( and TXB2 (P<0.01). Conclusion: Our data suggest that COX-2 overexpression leads to increased PGE2, 6-KETA-PGF1( and TXB2 biosynthesis, which may be mechanisms underlying the contribution of COX-2 to the development of ovarian serous carcinoma. BGF2, 6-keto-PGF1( and TXB2 may be helpful parameters of diagnosis and differentiate diagnosis in ovarian serous carcinoma.

  13. MAD2 Expression in Ovarian Carcinoma: Different Expression Patterns and Levels among Various Types of Ovarian Carcinoma and Its Prognostic Significance in High-Grade Serous Carcinoma

    OpenAIRE

    Park, Po Eun; Jeong, Ji Yun; Kim, Sun Zoo; Park, Ji Young

    2013-01-01

    Background Mitotic arrest deficiency protein 2 (MAD2) is a key component of spindle assembly checkpoint function, which mediates cell apoptosis through microtubule kinetics. Aberrant expression of MAD2 is believed to be associated with the development of chromosome instability. MAD2 also has a signihicant role in cellular drug resistance to taxane chemotherapeutic agents. Methods Expression of MAD2 and p53 was investigated using immunohistochemistry in 85 cases of ovarian carcinomas. Clinicop...

  14. Ovarian carcinoma histotype determination is highly reproducible, and is improved through the use of immunohistochemistry

    DEFF Research Database (Denmark)

    Köbel, Martin; Bak, Julia; Bertelsen, Björn I;

    2014-01-01

    AIMS: To assess the variation in ovarian carcinoma type diagnosis among gynaecological pathologists from Nordic countries, and whether a rationally designed panel of immunohistochemical markers could improve diagnostic reproducibility. METHODS AND RESULTS: Eight pathologists from four countries (...

  15. The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis

    OpenAIRE

    Nicole A. Hofmann; Yang, Jiang; Trauger, Sunia A.; Nakayama, Hironao; Huang, Lan; Strunk, Dirk; Moses, Marsha A.; Klagsbrun, Michael; Bischoff, Joyce; Graier, Wolfgang F

    2015-01-01

    Background and Purpose Highly vascularized ovarian carcinoma secretes the putative endocannabinoid and GPR55 agonist, L-α-lysophosphatidylinositol (LPI), into the circulation. We aimed to assess the involvement of this agonist and its receptor in ovarian cancer angiogenesis. Experimental Approach Secretion of LPI by three ovarian cancer cell lines (OVCAR-3, OVCAR-5 and COV-362) was tested by mass spectrometry. Involvement of cancer cell-derived LPI on angiogenesis was tested in the in vivo ch...

  16. Profile of olaparib in the treatment of advanced ovarian cancer

    Science.gov (United States)

    Chase, Dana M; Patel, Shreya; Shields, Kristin

    2016-01-01

    Olaparib is a poly(ADP-ribose) polymerase inhibitor that received accelerated approval from the US Food and Drug Administration as monotherapy for patients with germline BRCA mutations and ovarian cancer treated with three or more prior lines of chemotherapy. This article summarizes the mechanism of poly(ADP-ribose) polymerase inhibition, therapeutic profile and uses of olaparib, and current and ongoing literature pertaining to olaparib in advanced ovarian cancer. PMID:27186080

  17. Radiation improves gene transfer into human ovarian carcinoma cells

    International Nuclear Information System (INIS)

    Purpose/Objective: Poor gene transfer is the major stumbling block to successful gene therapy today. We hypothesized that ionizing radiation might activate cellular recombination, and so improve stable gene transfer. During studies to quantitate radiation activated recombination, we also found that both plasmid and adenoviral vector transduction could be increased by irradiation. The studies presented here describe the effects of irradiation on gene transduction efficiency (both transient and stable transduction) in several human ovarian carcinoma lines, as a prelude to in vivo animal studies. Materials and Methods: The effect of irradiation on stable gene transfer efficiency was determined in human ovarian carcinoma cell lines (SKOV3, CAOV3 and PA1). Either irradiated or unirradiated cells were transfected with pRSVZ plasmid (containing a LacZ expression cassette) in either the supercoiled and linearized (XmnI) forms and β-galactosidase expression followed with time. Transfection efficiency was measured by flow cytometry following FDG staining at 0, 48, and 96 hours after irradiation. FDG is converted to a fluorescent metabolite by LacZ, and thus reflects the transfection efficiency of the LacZ containing vector. Vector quantitation was also performed by southern hybridization. Stable transduction efficiency was measured 14 -35 days after irradiation. Optimization of the time of irradiation with respect to transfection was performed. Since cells demonstrated increased stable recombination for as long as 96 hours after irradiation, continuous low dose rate and multiple radiation fractions were also tested. These experiments were repeated using the Ad5CMVlacZ. Dividing cells were exposed to Ad5CMVlacZ at an MOI of 0.1,1,5,10 and 100 to determine optimum transfection concentration. Transduction efficiency was again measured at various intervals to determine the radiation dose and interval post transfection which provides the maximum increase in transfection

  18. Examestane in advanced or recurrent endometrial carcinoma

    DEFF Research Database (Denmark)

    Lindemann, Kristina; Malander, Susanne; Christensen, René dePont;

    2014-01-01

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.......We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma....

  19. Genetic variation in TYMS in the one-carbon transfer pathway is associated with ovarian carcinoma types in the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Goodman, Marc T; McGuire, Valerie;

    2010-01-01

    We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large...... sample of assembled cases to investigate associations by histologic type....

  20. Identification and characterization of a spontaneous ovarian carcinoma in Lewis rats

    OpenAIRE

    Sharrow, Allison C; Brigitte M Ronnett; Thoburn, Christopher J.; Barber, James P.; Giuntoli, Robert L.; Armstrong, Deborah K.; Jones, Richard J; Hess, Allan D.

    2010-01-01

    Background Ovarian carcinoma is the fourth most common cause of death from cancer in women. Limited progress has been made toward improving the survival rate of patients with this disease in part because of the lack of a good animal model. We present here a model of spontaneous ovarian carcinoma arising in a normal Lewis rat. Methods A spontaneously occurring tumor of the left ovary was found in a normal Lewis rat during necropsy, which was sectioned for histological examination and placed in...

  1. Intratumoral heterogeneity in a minority of ovarian low-grade serous carcinomas

    OpenAIRE

    Tone, Alicia A.; McConechy, Melissa K.; Yang, Winnie; Ding, Jiarui; Yip, Stephen; Kong, Esther; Wong, Kwong-Kwok; Gershenson, David M.; Mackay, Helen; Shah, Sohrab; Gilks, Blake; Tinker, Anna V.; Clarke, Blaise; Jessica N McAlpine; Huntsman, David

    2014-01-01

    Background Ovarian low-grade serous carcinoma (LGSC) has fewer mutations than ovarian high-grade serous carcinoma (HGSC) and a less aggressive clinical course. However, an overwhelming majority of LGSC patients do not respond to conventional chemotherapy resulting in a poor long-term prognosis comparable to women diagnosed with HGSC. KRAS and BRAF mutations are common in LGSC, leading to clinical trials targeting the MAPK pathway. We assessed the stability of targetable somatic mutations over...

  2. Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance

    OpenAIRE

    Swisher, Elizabeth M.; Sakai, Wataru; Karlan, Beth Y.; Wurz, Kaitlyn; Urban, Nicole; Taniguchi, Toshiyasu

    2008-01-01

    Although ovarian carcinomas with mutated BRCA1 or BRCA2 are sensitive to platinum compounds, such carcinomas eventually develop platinum resistance. Previously, we showed that acquired resistance to cisplatin in BRCA2-mutated tumors can be mediated by secondary intragenic mutations in BRCA2 that restore the wild-type BRCA2 reading frame. Here, we show that secondary mutations of BRCA1 also occur in BRCA1-mutated ovarian cancer with platinum resistance. We evaluated 9 recurrent BRCA1-mutated o...

  3. Preparation of humanized ovarian carcinoma anti-idiotypic minibody.

    Science.gov (United States)

    Chang, Xiaohong; Cui, Heng; Feng, Jie; Li, Yi; Liu, Bei; Cao, Shanjin; Cheng, Yexia; Qian, Henian

    2003-04-01

    Murine anti-idiotypic monoclonal antibody (MAb) 6B11 mimicking the tumor-associated antigen OC166-9 is used as a vaccine for the induction of an anti-tumoral immunity in experiments of in vitro and in vivo animal model with ovarian carcinoma. In this article, we have humanized 6B11 anti-idiotypic minibody using overlap polymerase chain reaction (PCR) and DNA recombinant technique, prokaryotic expression vector was produced by genetic fusion of 6B11V(L)-V(H) to human IgG1 hinge and CH3 region. Transformed E. coli BL21(DE3) were propagated and induced by isopropyl-beta D-thiogalactopyranoside (IPTG). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein band with molecular weight of 50kD appeared as the expected size after transformation. Molecular weight of 100 kDa may be examined by electrophoresis in nondenaturing systems. The fusion protein was analyzed with enzyme-linked immunosorbant assay (ELISA), inhibition ELISA tests and Western blot, respectively. The humanized anti-idiotype minibody showed capacity of bivalent binding to ovarian cancer MAb COC166-9 and goat anti-human immunoglobulin IgG1. It is useful reagents for clinical use. PMID:12831536

  4. Extracellular Vesicles from Ovarian Carcinoma Cells Display Specific Glycosignatures

    Directory of Open Access Journals (Sweden)

    Joana Gomes

    2015-08-01

    Full Text Available Cells release vesicles to the extracellular environment with characteristic nucleic acid, protein, lipid, and glycan composition. Here we have isolated and characterized extracellular vesicles (EVs and total cell membranes (MBs from ovarian carcinoma OVMz cells. EVs were enriched in specific markers, including Tsg101, CD63, CD9, annexin-I, and MBs contained markers of cellular membrane compartments, including calnexin, GRASP65, GS28, LAMP-1, and L1CAM. The glycoprotein galectin-3 binding protein (LGALS3BP was strongly enriched in EVs and it contained sialylated complex N-glycans. Lectin blotting with a panel of lectins showed that EVs had specific glycosignatures relative to MBs. Furthermore, the presence of glycoproteins bearing complex N-glycans with α2,3-linked sialic acid, fucose, bisecting-GlcNAc and LacdiNAc structures, and O-glycans with the T-antigen were detected. The inhibition of N-glycosylation processing from high mannose to complex glycans using kifunensine caused changes in the composition of EVs and induced a decrease of several glycoproteins. In conclusion, the results showed that glycosignatures of EVs were specific and altered glycosylation within the cell affected the composition and/or dynamics of EVs release. Furthermore, the identified glycosignatures of EVs could provide novel biomarkers for ovarian cancer.

  5. Abdominopelvic radiation therapy in the treatment of ovarian carcinoma

    International Nuclear Information System (INIS)

    From May 1981 through December 1990, 167 patients with ovarian carcinoma were treated with whole abdominal irradiation. All patients of the first group (n = 62) presented with no or minimal (< 2 cm) residual disease at the time of irradiation. They received whole abdominal irradiation after initial surgery. Residual disease was left after initial surgery for patients of the second group (n = 105). They underwent a cisplatin polychemotherapy regimen followed by second-look laparotomy and abdominopelvic irradiation. The irradiation was performed by a four orthogonal field's technique. Thirty grays were given with a 25 MV photon beam. Boosts were performed in 50 cases (mean dose of 15 Gy): 91% have completed irradiation at the prescribed dose level: 5% had severe intestinal toxicity requiring surgery. The median follow-up was 68 months. The 5-year actuarial survival rate was 50%, 67% group 1, 40% group 2. Five-year actuarial survival was 84% for T1, 61.5% for T2, 38% for T3. Five-year survival depended on tumor rest after initial surgery (residual disease 36.5%, no residual disease 70%). For patients in group 2, the size of residual disease at second-look laparotomy was a significant prognostic factor: five-year actuarial survival 76% with negative second-look, microscopic residual disease (positive cytology or random biopsies) 60% microscopic disease after cytoreductive surgery at second-look 22%, macroscopic residual disease (small nodules) 10%. These results indicate that abdominopelvic irradiation is valuable in the treatment of ovarian carcinoma when there is no macroscopic residual disease after initial surgery or second-look laparotomy. To assess the place of radiotherapy, randomized trials comparing whole abdominal irradiation with chemotherapy, watch policy for staged patients is warranted. 42 Refs

  6. Advances in Researches on the Relationship between P38MAPK Signaling Pathway and Ovarian Carcinoma%P38MAPK信号传导通路与卵巢癌关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈砚芬; 徐海帆

    2012-01-01

    丝裂原活化蛋白激酶(mitogen-activated proteinkinases,MAPKs)级联反应是细胞内重要的信号传导系统之一,参与细胞生长、发育、分化和凋亡等一系列生理、病理过程.P38 MAPK信号传导通路是MAPK通路的分支之一,介导了应激、炎性细胞因子、细菌产物等多种刺激引起的细胞反应,对细胞周期调控具有重要作用.但对不同的卵巢癌细胞系,或者不同的刺激,P38通路的作用不完全相同,甚至可能相反,提示对P38通路的功能仍需进一步的研究,他可能是肿瘤治疗的新靶点.本文就P38 MAPK信号传导通路与卵巢癌关系作一综述.%The cascade reaction of mitogen-activated protein kinases(MAPKs)is one of the vital intracellular signal transduction systems, participating in many physiological progressions, such as cell growth,proliferation,differentiation and apoptosis. P38 is a member of MAPKs, mediating many cell reactions induced by stress, inflammatory cytokines or bacterial products and playing a key role in the regulation of cell cycle. For different cell lines of ovarian carcinoma,P38 has different functions.The same phenomenon can be seen when the cells are presented under different stimulus.P38 pathway may be one candidate target of cancer therapy. This paper will review the relationship between P38MAPK signaling pathway and ovarian carcinoma.

  7. Neoadjuvant chemotherapy in advanced epithelial ovarian cancer: A survival study

    Directory of Open Access Journals (Sweden)

    Upasana Baruah

    2015-01-01

    Full Text Available Context: Patients with advanced ovarian cancer have a poor prognosis in spite of the best possible care. Primary debulking surgery has been the standard of care in advanced ovarian cancer; however, it is associated with high mortality and morbidity rates as shown in various studies. Several studies have discussed the benefit of neoadjuvant chemotherapy in patients with advanced ovarian cancer. Aims: This study aims to evaluate the survival statistics of the patients who have been managed with interval debulking surgery (IDS from January 2007 to December 2009. Materials and Methods: During the period from January 2007 to December 2009, a retrospective analysis of 104 patients who underwent IDS for stage IIIC or IV advanced epithelial ovarian cancer at our institute were selected for the study. IDS was attempted after three to five courses of chemotherapy with paclitaxal (175 mg/m 2 and carboplatin (5-6 of area under curve. Overall survival (OS and progression free survival (PFS were compared with results of primary debulking study from existing literature. OS and PFS rates were estimated by means of the Kaplan-Meier method. Results were statistically analyzed by IBM SPSS Statistics 19. Results: The median OS was 26 months and the median PFS was 18 months. In multivariate analysis it was found that both OS and PFS was affected by the stage, and extent of debulking. Conclusions: Neoadjuvant chemotherapy, followed by surgical cytoreduction is a promising treatment strategy for the management of advanced epithelial ovarian cancers.

  8. Genomic aberrations relate early and advanced stage ovarian cancer

    NARCIS (Netherlands)

    A. Zaal; W.J. Peyrot (Wouter ); P.M.J.J. Berns (Els); M.E.L. van der Burg (Maria); J.H.W. Veerbeek (Jan ); J.B. Trimbos; I. Cadron (Isabelle); P.J. van Diest (Paul); W.N. Wieringen (Wessel); O. Krijgsman (Oscar); G.A. Meijer (Gerrit); J.M.J. Piek (Jurgen ); P.J. Timmers (Petra); I. Vergote (Ignace); R.H.M. Verheijen (René); B. Ylstra (Bauke); R.P. Zweemer (Ronald )

    2012-01-01

    textabstractBackground Because of the distinct clinical presentation of early and advanced stage ovarian cancer, we aim to clarify whether these disease entities are solely separated by time of diagnosis or whether they arise from distinct molecular events. Methods Sixteen early and sixteen advanced

  9. Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

    International Nuclear Information System (INIS)

    The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

  10. Frequent POLE1 p.S297F mutation in Chinese patients with ovarian endometrioid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Yang; Liu, Fa-Ying; Liu, Huai; Wang, Feng [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Li, Wei [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Huang, Mei-Zhen [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Yan; Yuan, Xiao-Qun [Key Laboratory of Women' s Reproductive Health of Jiangxi Province, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, Jiangxi 330006 (China); Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Xu, Xiao-Yun [Graduate School of Nanchang University, Nanchang, Jiangxi 330031 (China); Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); Huang, Ou-Ping, E-mail: huangouping@gmail.com [Jiangxi Provincial Cancer Institute, Jiangxi Provincial Cancer Hospital, Nanchang, Jiangxi 330029 (China); He, Ming, E-mail: jxhm56@hotmail.com [Department of Pharmacology and Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang 330006 (China)

    2014-03-15

    The catalytic subunit of DNA polymerase epsilon (POLE1) functions primarily in nuclear DNA replication and repair. Recently, POLE1 mutations were detected frequently in colorectal and endometrial carcinomas while with lower frequency in several other types of cancer, and the p.P286R and p.V411L mutations were the potential mutation hotspots in human cancers. Nevertheless, the mutation frequency of POLE1 in ovarian cancer still remains largely unknown. Here, we screened a total of 251 Chinese samples with distinct subtypes of ovarian carcinoma for the presence of POLE1 hotspot mutations by direct sequencing. A heterozygous somatic POLE1 mutation, p.S297F (c.890C>T), but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was identified in 3 out of 37 (8.1%) patients with ovarian endometrioid carcinoma; this mutation was evolutionarily highly conserved from Homo sapiens to Schizosaccharomyces. Of note, the POLE1 mutation coexisted with mutation in the ovarian cancer-associated PPP2R1A (protein phosphatase 2, regulatory subunit A, α) gene in a 46-year-old patient, who was also diagnosed with ectopic endometriosis in the benign ovary. In addition, a 45-year-old POLE1-mutated ovarian endometrioid carcinoma patient was also diagnosed with uterine leiomyoma while the remaining 52-year-old POLE1-mutated patient showed no additional distinctive clinical manifestation. In contrast to high frequency of POLE1 mutations in ovarian endometrioid carcinoma, no POLE1 mutations were identified in patients with other subtypes of ovarian carcinoma. Our results showed for the first time that the POLE1 p.S297F mutation, but not p.P286R and p.V411L hotspot mutations observed in other cancer types, was frequent in Chinese ovarian endometrioid carcinoma, but absent in other subtypes of ovarian carcinoma. These results implicated that POLE1 p.S297F mutation might be actively involved in the pathogenesis of ovarian endometrioid carcinoma, but might not be actively

  11. Role of 18FDG-PET imaging in management of recurrent ovarian carcinoma

    International Nuclear Information System (INIS)

    Introduction: Serial assays of CA-125 have been established as a tumor marker for monitoring recurrent epithelial ovarian carcinoma following initial surgery and chemotherapy. The anatomical imaging is performed to localize the tumor site for possible resection. This retrospective study analyzed the efficacy of 18FDG-PET to detect suspected recurrent ovarian carcinoma. Materials and methods: Sixty consecutive patients, age range 40-83 years, mean age 55.8 years with known Ovarian Carcinoma underwent 76 PET-FDG studies. All patients were status post total abdominal Hysterectomy and bilateral salpingo- oopherectomy and were treated with chemo and/or radiation therapy. The imaging was performed at approximately 60 minutes following intravenous injection of average dose of 5.7 mCi 18FDG. Fifty concomitant CA-125 serum assays and 58 anatomical imaging (CT/MRI) were available for comparison. Thirty-eight combined PET, CA-125 and CT/MRI studies were available for evaluation. In addition to ovarian carcinoma in fifteen patients secondary tumors including lung, breast and colon carcinoma and lymphoma were diagnosed. The final diagnoses were based on clinical follow up and other relevant findings. Results: The comparison of the three studies including CA-125, 18FDG-PET and anatomical imaging Revealed. There was no significant difference among all three studies with regard to the diagnosis of recurrent ovarian carcinoma (p=ns). The combined studies improved the sensitivity to 0.98. Among 18 patients with normal CA-125 level, 5 had negative PET and 13 had positive PET studies. Conclusion: 18FDG-PET studies play a major role in detection of recurrent ovarian carcinoma. The Combination of all three studies improves the sensitivity. We recommend routine use of 18FDG- PET in the management of recurrent ovarian carcinoma especially when anatomical imaging is inconclusive. (authors)

  12. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas.

    Directory of Open Access Journals (Sweden)

    Erin K Crane

    Full Text Available Epithelial ovarian cancer is a diverse molecular and clinical disease, yet standard treatment is the same for all subtypes. TP53 mutations represent a node of divergence in epithelial ovarian cancer histologic subtypes and may represent a therapeutic opportunity in subtypes expressing wild type, including most low-grade ovarian serous carcinomas, ovarian clear cell carcinomas and ovarian endometrioid carcinomas, which represent approximately 25% of all epithelial ovarian cancer. We therefore sought to investigate Nutlin-3a--a therapeutic which inhibits MDM2, activates wild-type p53, and induces apoptosis--as a therapeutic compound for TP53 wild-type ovarian carcinomas. Fifteen epithelial ovarian cancer cell lines of varying histologic subtypes were treated with Nutlin-3a with determination of IC50 values. Western Blot (WB and quantitative real-time polymerase chain reaction (qRT-PCR analyses quantified MDM2, p53, and p21 expression after Nutlin-3a treatment. DNA from 15 cell lines was then sequenced for TP53 mutations in exons 2-11 including intron-exon boundaries. Responses to Nutlin-3a were dependent upon TP53 mutation status. By qRT-PCR and WB, levels of MDM2 and p21 were upregulated in wild-type TP53 sensitive cell lines, and p21 induction was reduced or absent in mutant cell lines. Annexin V assays demonstrated apoptosis in sensitive cell lines treated with Nutlin-3a. Thus, Nutlin-3a could be a potential therapeutic agent for ovarian carcinomas expressing wild-type TP53 and warrants further investigation.

  13. Nutlin-3a: A Potential Therapeutic Opportunity for TP53 Wild-Type Ovarian Carcinomas.

    Science.gov (United States)

    Crane, Erin K; Kwan, Suet-Yan; Izaguirre, Daisy I; Tsang, Yvonne T M; Mullany, Lisa K; Zu, Zhifei; Richards, JoAnne S; Gershenson, David M; Wong, Kwong-Kwok

    2015-01-01

    Epithelial ovarian cancer is a diverse molecular and clinical disease, yet standard treatment is the same for all subtypes. TP53 mutations represent a node of divergence in epithelial ovarian cancer histologic subtypes and may represent a therapeutic opportunity in subtypes expressing wild type, including most low-grade ovarian serous carcinomas, ovarian clear cell carcinomas and ovarian endometrioid carcinomas, which represent approximately 25% of all epithelial ovarian cancer. We therefore sought to investigate Nutlin-3a--a therapeutic which inhibits MDM2, activates wild-type p53, and induces apoptosis--as a therapeutic compound for TP53 wild-type ovarian carcinomas. Fifteen epithelial ovarian cancer cell lines of varying histologic subtypes were treated with Nutlin-3a with determination of IC50 values. Western Blot (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) analyses quantified MDM2, p53, and p21 expression after Nutlin-3a treatment. DNA from 15 cell lines was then sequenced for TP53 mutations in exons 2-11 including intron-exon boundaries. Responses to Nutlin-3a were dependent upon TP53 mutation status. By qRT-PCR and WB, levels of MDM2 and p21 were upregulated in wild-type TP53 sensitive cell lines, and p21 induction was reduced or absent in mutant cell lines. Annexin V assays demonstrated apoptosis in sensitive cell lines treated with Nutlin-3a. Thus, Nutlin-3a could be a potential therapeutic agent for ovarian carcinomas expressing wild-type TP53 and warrants further investigation. PMID:26248031

  14. CO-EXPRESSIONS OF SURVIVIN GENE,BCL-2 AND BAX PROTEINS IN OVARIAN CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    林蓓; 张淑兰; 赵长清

    2004-01-01

    Objective To characterize the cellular properties of ovarian cancer, we examined the correlation between the expression of apoptosis-related gene survivin and those of Bcl-2 and Bar proteins. Methods Expressions of survivin mRNA, and Bcl-2 and Bax proteins in 35 cases of ovarian carcinoma, 10 cases of borderline carcinoma, 10 cases of benign tumors and 10 cases of normal tissue were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry SABC method, respectively. Results Expression of survivin gene was detected in a significantly greater proportion in ovarian carcinoma and borderline carcinoma than those in benign tumors and normal tissues. Although there was no relationship between expression of survivin gene and FIGO stage, histologic grade, pathological type and lymphatic metastasis, expressions of Bcl-2 and Bar proteins were positively and negatively correlated with that of survivin gene, respectively. Conclusion Survivin may play an important role in pathogenesis of ovarian carcinoma, with a synergistic role of apoptosis-related gene Bcl-2protein and an antagonistic role of Bax protein in formation and progression of ovarian carcinoma.

  15. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    DEFF Research Database (Denmark)

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff;

    2015-01-01

    expressed by the patients' tumors and that the presence of these "neo-antigen" specific T-cells may be related to a high number of mutations in the tumor. In melanoma, treatment with autologous tumor-infiltrating lymphocytes (TILs) can mediate durable complete responses. Previous trials investigating TIL...... therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have...... stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe the...

  16. DNA methylation profiles of ovarian epithelial carcinoma tumors and cell lines.

    Directory of Open Access Journals (Sweden)

    Sahar Houshdaran

    Full Text Available BACKGROUND: Epithelial ovarian carcinoma is a significant cause of cancer mortality in women worldwide and in the United States. Epithelial ovarian cancer comprises several histological subtypes, each with distinct clinical and molecular characteristics. The natural history of this heterogeneous disease, including the cell types of origin, is poorly understood. This study applied recently developed methods for high-throughput DNA methylation profiling to characterize ovarian cancer cell lines and tumors, including representatives of three major histologies. METHODOLOGY/PRINCIPAL FINDINGS: We obtained DNA methylation profiles of 1,505 CpG sites (808 genes in 27 primary epithelial ovarian tumors and 15 ovarian cancer cell lines. We found that the DNA methylation profiles of ovarian cancer cell lines were markedly different from those of primary ovarian tumors. Aggregate DNA methylation levels of the assayed CpG sites tended to be higher in ovarian cancer cell lines relative to ovarian tumors. Within the primary tumors, those of the same histological type were more alike in their methylation profiles than those of different subtypes. Supervised analyses identified 90 CpG sites (68 genes that exhibited 'subtype-specific' DNA methylation patterns (FDR<1% among the tumors. In ovarian cancer cell lines, we estimated that for at least 27% of analyzed autosomal CpG sites, increases in methylation were accompanied by decreases in transcription of the associated gene. SIGNIFICANCE: The significant difference in DNA methylation profiles between ovarian cancer cell lines and tumors underscores the need to be cautious in using cell lines as tumor models for molecular studies of ovarian cancer and other cancers. Similarly, the distinct methylation profiles of the different histological types of ovarian tumors reinforces the need to treat the different histologies of ovarian cancer as different diseases, both clinically and in biomarker studies. These data

  17. Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

    Directory of Open Access Journals (Sweden)

    D. Ben Sellem

    2011-01-01

    Full Text Available Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii generate statistical models capable of classifying borderline tumors and (iii establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate and mucinous (N-acetyl-lysine carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.

  18. Quality of pathology reports for advanced ovarian cancer

    DEFF Research Database (Denmark)

    Verleye, Leen; Ottevanger, Petronella B; Kristensen, Gunnar B;

    2011-01-01

    To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant...

  19. Quality of pathology reports for advanced ovarian cancer

    DEFF Research Database (Denmark)

    Verleye, Leen; Ottevanger, Petronella B; Kristensen, Gunnar B; Ehlen, Tom; Johnson, Nick; van der Burg, Maria E L; Reed, Nick S; Verheijen, René H M; Gaarenstroom, Katja N; Mosgaard, Berit; Seoane, Jose Miguel; van der Velden, Jacobus; Lotocki, Robert; van der Graaf, Winette; Penninckx, Björn; Coens, Corneel; Stuart, Gavin; Vergote, Ignace

    2011-01-01

    To assess the quality of surgical pathology reports of advanced stage ovarian, fallopian tube and primary peritoneal cancer. This quality assurance project was performed within the EORTC-GCG 55971/NCIC-CTG OV13 study comparing primary debulking surgery followed by chemotherapy with neoadjuvant ch...

  20. Metastatic Renal Cell Carcinoma Masquerading as a Primary Ovarian Mass in a Post-Operative Case of Meningioma and Renal Cell Carcinoma

    OpenAIRE

    Sangita Bohara; Biswajit Dey; Swapnil Agarwal; Jyotsna Naresh Bharti; Nita Khurana; Poonam Sachdeva

    2015-01-01

    The clinical presentation of metastatic renal cell carcinoma to ovary is extremely rare as well as confusing due to its close resemblance to primary ovarian tumors, especially clear cell carcinoma. We present a case of metastatic renal cell carcinoma diagnosed in a 48-year-old female, who had renal cell carcinoma of the right kidney and right sphenoid wing meningioma of transitional type.

  1. ESTABLISHMENT OF INTRAPERITONEAL TRANSPLANTATION MODEL OF CISPLATIN-RESISTANT OVARIAN CARCINOMA CELL IN SCID MICE

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui; ZHAO Qun; ZUO Lian-fu; WANG Xiao-ling; WANG Yong-jun; JIA Jin-hua; KANG Shan

    2006-01-01

    Objective: to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics. Methods: Sixteen qualified C.B17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×107 cells (0.5 mL) per mouse. The behaviors of mice,tumor growth and morphology were analyzed. The expression of cancer antigen 125 (CA125), GST-π and Topo-Ⅱ were examined by immunohistochemical method. Results: In this experimental study, transplanted tumors are formed in 100%SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-Ⅱ gene in SKOV3/CDDP group were significantly higher (P<0.05). Conclusion: An intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.

  2. Expression of CD44v6 and Its Association with Prognosis in Epithelial Ovarian Carcinomas

    Directory of Open Access Journals (Sweden)

    Dang-xia Zhou

    2012-01-01

    Full Text Available The aim of this study was to evaluate CD44v6 protein expression and its prognostic value of CD44v6 in ovarian carcinoma. The expression of CD44v6 was analyzed in 62 patients with ovarian carcinoma by immunohistochemical method. The data obtained were analyzed by univariate and multivariate analyses. The present study clearly demonstrates that tumor tissues from 41 (66.1% patients showed positive expression with CD44v6. The expression of CD44v6 was significantly correlated with histological type, FIGO stage and histological grade of ovarian carcinomas. Concerning the prognosis, the survival period of patients with CD44v6 positive was shorter than that of patients with CD44v6 negative (36.6% versus 66.7%, 5-year survival, P<0.05. Univariate analysis showed that CD44v6 expression, histological type, FIGO stage and histological grade were associated with 5-year survival, and CD44v6 expression was associated with histological type, FIGO stage and histological grade and 5-year survival. In multivariate analysis, using the COX-regression model, CD44v6 expression was important prognostic factor. In conclusion, these results suggest that CD44v6 may be related to histological type, FIGO stage and histological grade of ovarian carcinomas, and CD44v6 may be an important molecular marker for poor prognosis in ovarian carcinomas.

  3. 31P NMR spectroscopy measurements of hum ovarian carcinoma xenografts

    International Nuclear Information System (INIS)

    /sup 31/P NMR spectroscopy was used to study lipid and energy metabolism as well as tumour pH in three human ovarian carcinoma xenograft lines with widely differing growth rate, necrotic fraction and differentiation status. Two of the liines showed decreasing PCr (phosphocreatine) and NTPbhta (nucleoside triphosphates bhta) resonances and an increasing P/sub i/ (inorganic phosphate) resonance with increasing tumour volume in the volume range 100-4000 mm/sup 3/. This decrease in bioenergetic status was accompanied by a decrease in tumour pH from about 7.15 to about 6.95. The volume-dependence of these spectral parametes probably reflected increased nutritional deprivation and development of hypoxia and necrosis during tumour growth. The third xenograft line did not show changes in the intensity of any of the resonances during tumour growth. The spectral parameters differed significantly among the xenograft lines at given tumour volumes, but no correlations with volume-doubling time, necrotic fraction of differentiation status were found

  4. 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

    Science.gov (United States)

    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

  5. Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

    International Nuclear Information System (INIS)

    Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

  6. Risk factors for lower limb lymphedema after lymph node dissection in patients with ovarian and uterine carcinoma

    OpenAIRE

    Tada, Harue; Teramukai, Satoshi; Fukushima, Masanori; Sasaki, Hiroshi

    2009-01-01

    Background Lymph node dissection has proven prognostic benefits for patients with ovarian or uterine carcinoma; however, one of the complications associated with this procedure is lymphedema. We aimed to identify the factors that are associated with the occurrence of lymphedema after lymph node dissection for the treatment of ovarian or uterine carcinoma. Methods A total of 694 patients with histologically confirmed ovarian (135 patients) or uterine cancer (258 with cervical cancer, 301 with ...

  7. Risk factors for lower limb lymphedema after lymph node dissection in patients with ovarian and uterine carcinoma.

    OpenAIRE

    Tada, Harue; Teramukai, Satoshi; Fukushima, Masanori; Sasaki, Hiroshi

    2009-01-01

    [Background]Lymph node dissection has proven prognostic benefits for patients with ovarian or uterine carcinoma; however, one of the complications associated with this procedure is lymphedema. We aimed to identify the factors that are associated with the occurrence of lymphedema after lymph node dissection for the treatment of ovarian or uterine carcinoma. [Methods]A total of 694 patients with histologically confirmed ovarian (135 patients) or uterine cancer (258 with cervical cancer, 301 wit...

  8. Risk factors for lower limb lymphedema after lymph node dissection in patients with ovarian and uterine carcinoma

    OpenAIRE

    Fukushima Masanori; Teramukai Satoshi; Tada Harue; Sasaki Hiroshi

    2009-01-01

    Abstract Background Lymph node dissection has proven prognostic benefits for patients with ovarian or uterine carcinoma; however, one of the complications associated with this procedure is lymphedema. We aimed to identify the factors that are associated with the occurrence of lymphedema after lymph node dissection for the treatment of ovarian or uterine carcinoma. Methods A total of 694 patients with histologically confirmed ovarian (135 patients) or uterine cancer (258 with cervical cancer, ...

  9. Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma

    International Nuclear Information System (INIS)

    Most patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis. The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups. A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such

  10. Low frequency of ESRRA-C11orf20 fusion gene in ovarian carcinomas.

    Directory of Open Access Journals (Sweden)

    Francesca Micci

    2014-02-01

    Full Text Available The identification of recurrent gene fusions in common epithelial cancers--for example, TMPRSS2/ERG in prostate cancer and EML4/ALK in nonsmall cell lung carcinomas--has raised the question of whether fusion genes are pathogenetically important also in ovarian carcinomas. The first recurrent fusion transcript in serous ovarian carcinomas was reported by Salzman et al. in 2011, who used deep paired-end sequencing to detect the fusion gene ESRRA-C11orf20 in 10 out of 67 (15% serous ovarian carcinomas examined, a finding that holds great promise for our understanding of ovarian tumorigenesis as well as, potentially, for new treatment strategies. We wanted to test how frequent the ESRRA/C11orf20 fusion is in ovarian carcinomas of all subtypes, and therefore examined a series of 230 ovarian carcinomas of which 197 were of the serous subtype and 163 of the 197 were of stages III and IV--that is, the very same carcinoma subset where the fusion transcript had been found. We performed PCR and high-throughput sequencing analyses in search of the fusion transcript. We used the same primers described previously for the detection of the fusion and the same primer combination, but found no ESRRA/C11orf20 fusion in our series. A synthetic DNA plasmid containing the reported ESRRA/C11orf20 fusion was included as a positive control for our PCR experiments. Data from high-throughput sequencing of 23 ovarian carcinomas were screened in search of alternative partner(s for the ESRRA and/or C11orf20 gene, but none was found. We conclude that the frequency of the ESRRA/C11orf20 gene fusion in serous ovarian carcinomas of stages III and IV must be considerable less than that reported previously (0/163 in our experience compared with 10/67 in the previous study. At the very least, it seems clear that the said fusion cannot be a common pathogenetic event in this tumor type.

  11. An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas

    OpenAIRE

    Braicu Elena I; Sehouli Jalid; Buckendahl Ann-Christin; Darb-Esfahani Silvia; Weichert Wilko; Schwabe Michael; Noske Aurelia; Budczies Jan; Dietel Manfred; Denkert Carsten

    2011-01-01

    Abstract Background In ovarian cancer, the reported rate of EGFR expression varies between 4-70% depending on assessment method and data on patient outcome are conflicting. Methods: In this study we investigated EGFR expression and its prognostic value in a cohort of 121 invasive ovarian carcinomas, using a novel antibody against the intracellular domain of the receptor. We further evaluated an association between EGFR, the nuclear transporter CRM1 as well as COX-2. Furthermore, we evaluated ...

  12. New advances in hepatocellular carcinoma

    Science.gov (United States)

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  13. New advances in hepatocellular carcinoma.

    Science.gov (United States)

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  14. Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma

    International Nuclear Information System (INIS)

    It has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear. The methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas. Intensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005). These findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients

  15. Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium

    OpenAIRE

    Kelemen Linda E; Bandera Elisa V; Terry Kathryn L; Rossing Mary Anne; Brinton Louise A; Doherty Jennifer A; Ness Roberta B; Kjær Susanne Krüger; Chang-Claude Jenny; Köbel Martin; Lurie Galina; Thompson Pamela J; Carney Michael E; Moysich Kirsten; Edwards Robert

    2013-01-01

    Abstract Background Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations. Methods We pooled data from 12 case-control studies in the Ovarian Cancer Association Consortium comprising 5,342 OC cases, 1,455 borderline tumors and 10,358 controls with quantitative information on recent alcoh...

  16. Struma ovarii mimicking ovarian carcinoma: a case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Landim, Fabio Machado [Hospital Geral Doutor Waldemar de Alcantara, Fortaleza, CE (Brazil)

    2008-07-01

    Struma Ovarii is a rare neoplasia. It is a monodermic mixed teratoma, with predominance of thyroid tissue and represents 3% of ovarian teratomas. This article reports a case of Struma Ovarii in a 66 years-old patient, with a progressive abdominal mass, ascites and high levels of CA-125. The findings were highly suggestive of ovarian carcinoma. The CT scan showed a complex ovarian lesion and the patient was submitted to an exploratory laparotomy. The pathology report showed a left ovary Struma Ovarii. (author)

  17. Mammary serine protease inhibitor and CD138 immunohistochemical expression in ovarian serous and clear cell carcinomas.

    Science.gov (United States)

    Hasby, Eiman Adel

    2016-04-01

    This study aims to investigate the immunohistochemical expression of mammary serine protease inhibitor (maspin) and CD138 in primary ovarian high-grade serous carcinomas (HGSC) as compared to low-grade serous carcinomas (LGSC) and clear cell carcinomas and investigate if the studied markers have a correlation to International Federation of Gynaecology and Obstetrics (FIGO) stage, Ki67 proliferation index, and to each other. Maspin cellular location varied significantly between studied groups with only nuclear expression seen in 46.7 % of LGSC group, mixed nuclear and cytoplasmic in 13.3, 28.6, and 20 % of LGSC, HGSC, and clear cell carcinoma, respectively, and was only cytoplasmic in 26.7, 71.4, and 80 % of LGSC, HGSC, and clear cell carcinoma, respectively. Mean maspin and CD138 counts were significantly higher in HGSC and clear cell carcinoma compared to LGSC. Both maspin and CD138 scores varied significantly between studied groups and were positively correlated with adverse prognostic factors in studied carcinomas including FIGO stage and Ki67 proliferation index. Besides, both maspin and CD138 had significant correlation to each other. These findings suggest that epithelial cytoplasmic expression of maspin and CD138 may have a significant role in tumorigenesis in ovarian high-grade serous carcinomas and clear cell carcinomas; these markers may regulate tumor cell proliferation, and their significant correlation to each other may suggest that CD138 probably induces maspin expression to protect tumor growth factors from being lysed by proteolytic enzymes. PMID:26526579

  18. 18F-fluorodeoxyglucose PET in ovarian carcinoma: methodology and preliminary results

    International Nuclear Information System (INIS)

    Aim of the present study was to evaluate 18FDG PET as a diagnostic tool in primary and recurrent ovarian cancer. Methods: PET of the abdomen and the pelvis was performed in 26 patients suspected for primary (n=17) or recurrent (n=9) ovarian cancer with an ECAT 953/15 scanner 45 min after intravenous administration of 245 MBq 18F-FDG (mean). PET findings were validated by surgery, histology and/or cytology. Results: Ovarian malignancies or recurrent ovarian cancer were demonstrated by PET in 16 out of 19 cases. Malignancy was excluded in six out of seven cases. False negative findings were obtained in two cases of low malignant potential tumors (LMP) and in one case of low grade serous/mucinous ovarian cystadenocarcinoma. PET yielded one false positive result in a case of salpingoophoritis. Quantitative analysis revealed a mean SUV of 6.8±2.3 in primary ovarian carcinoma vs. 2.6±1.2 in benign masses (p18FDG PET to be useful in diagnosis of recurrent ovarian cancer. PET is of limited use in differentiating LMP from benign tumors and ovarian cancer from inflammatory processes. Concerning this differentiation, quantitative analysis does not improve diagnostic accuracy. (orig.)

  19. Validity of computed tomography scan for the diagnosis of ovarian carcinoma and its stages

    International Nuclear Information System (INIS)

    Objective: To determine the validity of CT scan for the diagnosis of ovarian carcinoma and its stages taking histopathology as gold standard Study Design: Cross sectional validation study. Place and Duration of Study: The study was conducted in the Department of Radiology, DHQ Hospital Rawalpindi, RMC and Allied hospitals from October 2011 to March 2012. Patients and Methods: This study included one hundred thirty six consecutive subjects with symptoms of ovarian pelvic mass with an age range of 20 years to 70 years and pre-operative CA -125 level were enrolled in the study by the Principle Investigator (PI). All 136 patients were gone through CECT scan. Imaging findings of all patients were compared with results of histologic examination to determine the diagnostic accuracy of CECT scan in the evaluation of disease status. The Histopathological staging of ovarian carcinoma was obtained on the basis of FIGO Classification. Histopathological findings of each patient were obtained from laboratory were actually reported by consultant Pathologist Result: The mean age of the patient is 50.37 years. The sensitivity and specificity of CT in diagnosis of malignant ovarian carcinoma is 100% with the p value was 0.0001 and 84.85% respectively. The Positive Predictive Value (PPV) and Negative Predictive Value (NPV) is 95.37% and 100% respectively, taking histopathology as Gold Standard. The overall accuracy of CT in diagnosis and staging of ovarian carcinoma is 96% and 93% respectively. Conclusion: The beneficial effect of the study is to find a non-invasive, less time consuming and relatively easy modality for the diagnosis of ovarian carcinoma including its staging. Prompt diagnosis will lead to instant decision making for the management of this debilitating disease. (author)

  20. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    Directory of Open Access Journals (Sweden)

    Miller Dianne M

    2008-01-01

    Full Text Available Background Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH, and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. Methods A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Results Eighteen (37% of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5, clear cell (n = 4, or low grade serous (n = 2 carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. Conclusion High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic, BRCA1 loss (epigenetic, and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  1. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray, Joe; Huntsman, David G.

    2008-05-02

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  2. Ovarian carcinomas with genetic and epigenetic BRCA1 loss havedistinct molecular abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray,Joe; Huntsman, David G.

    2007-07-23

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.

  3. Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

    International Nuclear Information System (INIS)

    Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways

  4. Value of MRI with sliding multi-slice technique for staging ovarian carcinoma

    International Nuclear Information System (INIS)

    Objective: To analyze the technical characteristics of sliding multi-slice magnetic resonance imaging (SMS-MRI), and to evaluate the value of staging ovarian carcinoma by SMS-MRI. Methods: Pre-operative SMS-MRI of chest, abdomen and pelvis was performed on 15 patients with ovarian carcinoma. Sequences included TSE T2WI, SMS TIRM and fat-suppressed contrast-enhanced SMS FLASH. The SMS-MRI was analyzed and staged according to FIGO's classification by two radiologists. The location of tumor, local invasion of uterus and fallopian tube or other pelvic tissues, peritoneum metastasis, lymph node metastasis and distal metastasis were recorded. The results were compared with operative and pathological findings. Results: The pathological diagnosis was serous cystadenocarcinoma (9), mucinous cystadenocarcinoma (2), endometrioid carcinoma (2), clear cell carcinoma (1) and granular cell carcinoma (1) at stage II (2), stage III (10) and stage IV (3). The accuracy of SMS-MRI staging was 100% (15/15). The tumor location, involvement of uterus and fallopian tubes as well as distant metastasis were accurately demonstrated by SMS-MRI. Conclusion: SMS-MRI can be a faster one-stop examination with good image quality. SMS-MRI is an alternative imaging method of staging ovarian carcinoma. (authors)

  5. Radiation therapy for advanced laryngeal carcinoma

    International Nuclear Information System (INIS)

    From 1967 through 1985, 92 patients with T3 and T4 laryngeal carcinoma were treated with radiation at Osaka University Hospital. Of 92 patients, patients with 14 T3 and 29 T4 carcinoma were treated with a total dose of 60 Gy or more, and those with 14 T3 and 21 T4 carcinoma were treated with a total dose of 40 to 58 Gy and followed by total laryngectomy. Other 14 patients were palliatively treated with a total dose less than 60 Gy without surgery. The 5-year local control rates for T3 and T4 carcinoma treated with radical radiation were 48% and 24%, respectively. The 5-year cause-specific survival rates for T3 carcinoma treated with radical and preoperative radiotherapy were 48% and 71%, and corresponding figures for T4 carcinoma were 52% and 43%. There were no statistically significant differences between cause-specific survival rates of radical and preoperative groups. The 5-year cause-specific survival rates for T3N0 and T4N0 cases treated with radical radiation were 83% and 56%, and corresponding figures for T3N+ and T4N+ cases were 13% and 45%. Voice preservation rates of T3 and T4 patients treated with radical radiation were about 1/2 and 1/4, respectively. Considering the QOL of patients, radiotherapy for advanced carcinoma of larynx should be considered as a primary treatment especially for N0 cases. (author)

  6. Sequence alterations of the whole mitochondrial genome in primary and recurrent ovarian carcinomas

    Institute of Scientific and Technical Information of China (English)

    Shi Hong-hui; Song Tian; Pan Ling-ya

    2007-01-01

    Objective: To investigate mitochondrial DNA (mtDNA) alterations in primary and recurrent ovarian carcinomas to illuminate the impact of chemotherapy on mtDNA.Methods.Complete mtDNA genomes of tumor tissue from 7 pimary ovarian carcinoma patients without treatment and 9 recurrent ones with prior chemotherapies were sequenced as well as their matched normal tissue.MtDNA alterations, including somatic mutations and new polymorphisms and consequent amino-acid alterations were compared between the two groups.Results, A large number of mtDNA new polymorphisms (69) and somatic mutations (17) were found in 16 ovarian carcinoma samples.Chemotherapy might not lead to more, heteroplasmic mutations and consequent aminoacid alterations (P>0.05) in the recurrent ovarian carcinoma patients than in the untreated ones.Conclusions: MtDNA damage was not so certainly made by chemotherapies and some of the mtDNA defects might be part of the disease process rather than a consequence of treatment.

  7. Metastatic ovarian papillary serous carcinoma to the breast: Diagnosis and pitfalls

    OpenAIRE

    Mhawech-Fauceglia, Paulette; Kay, Brian; Li, Carrie J.; Lin, Yvonne G.

    2013-01-01

    ► The breast as a site of metastasis from primary ovarian carcinoma is uncommon. ► Distinguishing these metastases from primary breast tumors is important because the prognosis and therapeutic approach differ significantly. ► Immunohistochemical markers (e.g., PAX8) can be utilized when morphology and clinical history are insufficient to render the correct diagnosis.

  8. Can advanced-stage ovarian cancer be cured?

    Science.gov (United States)

    Narod, Steven

    2016-04-01

    Approximately 20% of women with advanced-stage ovarian cancer survive beyond 12 years after treatment and are effectively cured. Initial therapy for ovarian cancer comprises surgery and chemotherapy, and is given with the goal of eradicating as many cancer cells as possible. Indeed, the three phases of therapy are as follows: debulking surgery to remove as much of the cancer as possible, preferably to a state of no visible residual disease; chemotherapy to eradicate any microscopic disease that remains present after surgery; and second-line or maintenance therapy, which is given to delay disease progression among patients with tumour recurrence. If no cancer cells remain after initial therapy is completed, a cure is expected. By contrast, if residual cancer cells are present after initial treatment, then disease recurrence is likely. Thus, the probability of cure is contingent on the combination of surgery and chemotherapy effectively eliminating all cancer cells. In this Perspectives article, I present the case that the probability of achieving a cancer-free state is maximized through a combination of maximal debulking surgery and intraperitoneal chemotherapy. I discuss the evidence indicating that by taking this approach, cures could be achieved in up to 50% of women with advanced-stage ovarian cancer. PMID:26787282

  9. Bilateral ovarian squamous cell carcinoma with an antecedent dermoid cyst in the left ovary.

    Science.gov (United States)

    Prasad, Sruthi; Suguna, B V; Ravindra, Savithri

    2011-09-01

    Ovarian squamous cell carcinoma is a rare malignancy and its occurrence is commonly attributed to malignant transformation of a pre-existing mature cystic teratoma. The de novo occurrence of primary squamous cell carcinoma is extremely rare. Malignant transformation in a mature cystic teratoma is almost always unilateral; however, there have been isolated reports of an uncomplicated mature cystic teratoma in the contralateral ovary. We report here a case of a 40-year-old woman presenting with squamous cell carcinoma of both ovaries with antecedent dermoid cyst in the left ovary, along with involvement of the fallopian tubes, cervix and omentum. PMID:21518128

  10. MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

    Science.gov (United States)

    2016-06-24

    Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Ovarian Seromucinous Carcinoma; 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

  11. Advances in Tumor Screening, Imaging, and Avatar Technologies for High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Anders eOhman

    2014-11-01

    Full Text Available The majority of high-grade serous ovarian carcinoma cases are detected in advanced stages when treatment options are limited. Surgery is less effective at eradicating the disease when it is widespread, resulting in high rates of disease relapse and chemoresistance. Current screening techniques are ineffective for early tumor detection and consequently, BRCA mutations carriers, with an increased risk for developing high-grade serous ovarian cancer, elect to undergo risk-reducing surgery. While prophylactic surgery is associated with a significant reduction in the risk of cancer development, it also results in surgical menopause and significant adverse side effects. The development of efficient early-stage screening protocols and imaging technologies is critical to improving the outcome and quality of life for current patients and women at increased risk. In addition, more accurate animal models are necessary in order to provide relevant in vivo testing systems and advance our understanding of the disease origin and progression. Moreover, both genetically engineered and tumor xenograft animal models enable the preclinical testing of novel imaging techniques and molecularly targeted therapies as they become available. Recent advances in xenograft technologies have made possible the creation of avatar mice, personalized tumorgrafts, which can be used as therapy testing surrogates for individual patients prior to or during treatment. High-grade serous ovarian cancer may be an ideal candidate for use with avatar models based on key characteristics of the tumorgraft platform. This review explores multiple strategies, including novel imaging and screening technologies in both patients and animal models, aimed at detecting cancer in the early stages and improving the disease prognosis.

  12. Cancer stem cells, epithelial-mesenchymal transition, and drug resistance in high-grade ovarian serous carcinoma

    OpenAIRE

    Chen, Xiaoxiang; Zhang, Jing; Zhang, Zhihong; Li, Hongxia; CHENG, WENJUN; Liu, Jinsong

    2013-01-01

    Although epithelial ovarian cancer cells are eliminated by debulking surgery and chemotherapy during initial treatment, it is believed that only a subset of cancer cells, that is, cancer stem cells, may be an important source of tumor recurrence and drug resistance. This review highlights our current understanding of high-grade serous carcinoma, ovarian cancer stem cells, common methods for enrichment of ovarian cancer stem cells, mechanisms involved in drug resistance, and potential strategi...

  13. Consumption of vegetables and fruits and risk of ovarian carcinoma: Results from the Netherlands Cohort Study on Diet and Cancer

    NARCIS (Netherlands)

    Mommers, M.; Schouten, L.J.; Goldbohm, R.A.; Brandt, P.A. van den

    2005-01-01

    BACKGROUND. To the authors' knowledge, only a few prospective studies to date have investigated the correlation between vegetable and fruit consumption and the risk of ovarian carcinoma and their results have been inconclusive. METHODS. Vegetable and fruit intake was assessed in relation to ovarian

  14. PAPP-A proteolytic activity enhances IGF bioactivity in ascites from women with ovarian carcinoma

    DEFF Research Database (Denmark)

    Thomsen, Jacob; Hjortebjerg, Rikke; Espelund, Ulrick;

    2015-01-01

    serum and ascites from 22 women with ovarian carcinoma. We found that ascites contained 46-fold higher PAPP-A levels as compared to serum (P < 0.001). The majority (80%) of PAPP-A was enzymatically active. This is supported by the finding that ascites contained more cleaved than intact IGFBP-4 (P < 0......Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF) action through proteolysis of IGF-binding protein (IGFBP)-4. In experimental animals, PAPP-A accelerates ovarian tumor growth by this mechanism. To investigate the effect of PAPP-A in humans, we compared...

  15. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman

    OpenAIRE

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her ser...

  16. Ovarian carcinoma in two patients with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Mehlika Isildak; Gulay Sain Guven; Murat Kekilli; Yavuz Beyazit; Mustafa Erman

    2005-01-01

    Ascites is a common and debilitating complication of cirrhosis. However, patients with chronic liver disease are not spared from other causes of ascites and physicians should be careful not to miss an underlying malignancy.Ovarian cancer is an insidious disease, which is difficult to diagnose and it ranks first in mortality among all gynecological cancers. Here, we present two cases of patients with chronic liver disease that developed ascites not simply because of cirrhosis but as a manifestation of ovarian cancer. We would like to emphasize that the causes of ascites, other than the liver itself, should not be overlooked in patients with chronic liver disease.

  17. Sorafenib in advanced hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Køstner, Anne Helene; Sørensen, M; Olesen, René Krøjgaard;

    2013-01-01

    Advanced HCC is a clinical challenge with limited treatment options. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Furthermore we...

  18. Are there candidates for high-dose chemotherapy in ovarian carcinoma?

    Directory of Open Access Journals (Sweden)

    Sabatier Renaud

    2012-10-01

    Full Text Available Abstract Background Prognosis of advanced ovarian carcinomas (AOC remains poor with a 5-year survival of 30%. Benefit from high-dose chemotherapy (HDC in this disease has not been demonstrated to date. Methods To evaluate the value of HDC as consolidation treatment after surgery and platinum/taxane-based therapy, we designed a monocentric retrospective comparative study. We used a subset approach to identify parameters associated with HDC efficacy. Results One hundred and three AOC patients treated with conventional chemotherapy alone (CCA were compared to 60 patients receiving HDC plus hematopoietic stem cell support. After a median follow-up of 47.5 months there was no overall survival (OS advantage for the HDC group in the whole population (p=0.29. Nevertheless, HDC was associated to a better outcome in young patients (≤50 years, both in term of progression-free survival (p=0.02, log-rank test and OS (p=0.05, log-rank test. Median OS was 54.6 and 36 months in the HDC and CCA groups, respectively. Conclusions Although randomized trials failed to demonstrate any benefit for HDC in AOC patients, this study suggests that young patients may derive a substantial advantage from receiving it after the standard treatment. Further prospective studies are warranted to confirm this gain and to search for the biological processes associated with this improvement.

  19. miR-494 suppresses tumor growth of epithelial ovarian carcinoma by targeting IGF1R.

    Science.gov (United States)

    Li, Na; Zhao, Xiaosu; Wang, Lufei; Zhang, Shi; Cui, Manhua; He, Jin

    2016-06-01

    A growing body of evidence suggests that microRNA-494 (miR-494) could act as tumor-suppressive or oncogenic microRNAs (miRNAs) in different types of tumors. However, the biological roles and underlying mechanisms of miR-494 remain unknown in human epithelial ovarian carcinoma (EOC). Therefore, the aims of this study were to investigate the miR-494 expression and the significance of its clinical diagnosis in patients suffering EOC and to analyze its role and underlying molecular mechanism on the carcinogenesis of EOC. Here, we found that miR-494 was significantly decreased in EOC cell lines and tissues and its expression was negatively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, high pathological grade, and lymph node metastasis (all P system. Bioinformatic assay and dual-luciferase assay confirmed that insulin-like growth factor 1 receptor (IGF1R) was as a direct target of miR-494 in EOC cells. Western blot assay showed that overexpression of miR-494 inhibited IGF1R expression and its downstream signal protein expression. In addition, downregulation of IGF1R has similar effects with miR-494 overexpression on EOC cells and overexpression of IGF1R effectively rescued the inhibition of overexpressed miR-494 in EOC cells. These data suggested that miR-494 functions as a tumor suppressor in EOC by targeting IGF1R. PMID:26695144

  20. Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: pooled analysis in five studies within the Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J; Carney, Michael E; Palmieri, Rachel T; Pharoah, Paul D P; Song, Honglin; Hogdall, Estrid; Kjaer, Susanne Kruger; DiCioccio, Richard A; McGuire, Valerie; Whittemore, Alice S; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Goodman, Marc T

    2011-01-01

    The association of invasive ovarian carcinoma risk with the functional polymorphism rs2228570 (aka rs10735810; FokI polymorphism) in the vitamin D receptor (VDR) gene was examined in 1820 white non-Hispanic cases and 3479 controls in a pooled analysis of five population-based case-control studies...... analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility....

  1. Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy

    Science.gov (United States)

    2014-12-29

    Fatigue; Malignant Ovarian Mixed Epithelial Tumor; Neuropathy; Neurotoxicity Syndrome; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Pain; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  2. An intracellular targeted antibody detects EGFR as an independent prognostic factor in ovarian carcinomas

    International Nuclear Information System (INIS)

    In ovarian cancer, the reported rate of EGFR expression varies between 4-70% depending on assessment method and data on patient outcome are conflicting. Methods: In this study we investigated EGFR expression and its prognostic value in a cohort of 121 invasive ovarian carcinomas, using a novel antibody against the intracellular domain of the receptor. We further evaluated an association between EGFR, the nuclear transporter CRM1 as well as COX-2. Furthermore, we evaluated EGFR expression in ten ovarian cancer cell lines and incubated cancer cells with Leptomycin B, a CRM1 specific inhibitor. We observed a membranous and cytoplasmic EGFR expression in 36.4% and 64% of ovarian carcinomas, respectively. Membranous EGFR was an independent prognostic factor for poor overall survival in ovarian cancer patients (HR 2.7, CI 1.1-6.4, p = 0.02) which was also found in the serous subtype (HR 4.6, CI 1.6-13.4, p = 0.004). We further observed a significant association of EGFR with COX-2 and nuclear CRM1 expression (chi-square test for trends, p = 0.006 and p = 0.013, respectively). In addition, combined membranous EGFR/COX-2 expression was significantly related to unfavorable overall survival (HR 7.2, CI 2.3-22.1, p = 0.001). In cell culture, we observed a suppression of EGFR protein levels after exposure to Leptomycin B in OVCAR-3 and SKOV-3 cells. Our results suggest that the EGFR/COX-2/CRM1 interaction might be involved in progression of ovarian cancer and patient prognosis. Hence, it is an interesting anti-cancer target for a combination therapy. Further studies will also be needed to investigate whether EGFR is also predictive for benefit from EGFR targeted therapies

  3. Sialoglycoproteins and N-Glycans from Secreted Exosomes of Ovarian Carcinoma Cells

    OpenAIRE

    Escrevente, Cristina; Grammel, Nicolas; Kandzia, Sebastian; Zeiser, Johannes; Tranfield, Erin M; Conradt, Harald S.; Costa, Júlia

    2013-01-01

    Exosomes consist of vesicles that are secreted by several human cells, including tumor cells and neurons, and they are found in several biological fluids. Exosomes have characteristic protein and lipid composition, however, the results concerning glycoprotein composition and glycosylation are scarce. Here, protein glycosylation of exosomes from ovarian carcinoma SKOV3 cells has been studied by lectin blotting, NP-HPLC analysis of 2-aminobenzamide labeled glycans and mass spectrometry. An abun...

  4. [THE MODE OF CLARIFYING DIAGNOSTIC OF PROGRESSING FORMS OF OVARIAN CARCINOMA].

    Science.gov (United States)

    Dolgova, D R; Gening, T P; Abakumova, T V; Antoneeva, I I; Butov, A A; Korchagina, I A; Tuzeeva, A Yu; Fomina, A V

    2015-10-01

    The ovarian carcinoma is the most frequent cause of death because of malignant neoplasins in women. At that, there is no pathognomonic symptoms permitting diagnosing stage of process with sufficient degree of confidence. This is a determinative not only for choosing treatment regimen but also for correlation of expected results of treatments with economic factors with purpose to evaluate cost effectiveness under monitoring of these patients. The study was carried out to develop mode of clarifying diagnostic of progressing forms of ovarian carcinoma on the basis of evaluation of oxidative modification of proteins in blood plasma. In 100 female patients with primary ovarian carcinoma (stage III and IV according FIGO,) in blood plasma 21 indicators were determined in blood plasma using standardized techniques: absolute number of leukocytes, absolute and relative number of neutrophils, products of oxidative modification of proteins of basic and ketonic character (under wavelength of 356, 370, 430, 530 nm), Her-2/neu CA-125, matrix metalloproteinase 2 and 9 in blood serum and neutrophils, interleukin-6, interleukin-10, interleukin-1β, interferon-γ, tumor necrosis factor-α, malonic dialdehyde, catalase, glutaihione transferase, glutathione reductase. The least squares method was applied to every parameter to appmximnate relative rates by density of Rayleigh distribution. For every indicator likelihood ratio functions of likelihood ratio were constructed and intervals at every stage were determined. The reliability of approximation was proved under testing with Pirson criterion hypothesis of compliance of practical values of parameters to theoretical law of density of distribution. The results permit to assert that level of oxidative modification of proteins cab be used as a reliable indicator for differentiated diagnostic of stage III and IV of ovarian carcinoma. PMID:26841670

  5. The Patched gene is epigenetically regulated in ovarian dermoids and fibromas, but not in basocellular carcinomas

    OpenAIRE

    Čretnik, Maja; Musani, Vesna; Orešković, Slavko; Leović, Dinko; Levanat, Sonja

    2007-01-01

    The Hedgehog/Patched signaling pathway plays a prominent role during mammalian development but it is also involved in oncogenic transformation. We investigated the methylation status of the Patched promoter in a set of basocellular carcinomas of the skin and ovarian tumors as an alternative to mutational causes of the pathway deregulation. Our aim was to define a possible role of genetic and/or epigenetic mechanisms of Hedgehog/Patched signal transduction in the development of these tumors. B...

  6. Promoter methylation of IGFBP-3 and p53 expression in ovarian endometrioid carcinoma

    OpenAIRE

    Huang Su-Cheng; Yang Hui-Wen; Chan Michael WY; Lin Ching-Wei; Torng Pao-Ling; Lin Chin-Tarng

    2009-01-01

    Abstract Background Insulin-like growth factor binding protein (IGFBP-3) is an antiproliferative, pro-apoptotic and invasion suppressor protein which is transcriptionally regulated by p53. Promoter methylation has been linked to gene silencing and cancer progression. We studied the correlation between IGFBP-3 and p53 expression as well as IGFBP-3 promoter methylation in ovarian endometrioid carcinoma (OEC) by immunohistochemical staining and quantitative methylation-specific PCR (qMSP). Addit...

  7. New developments in treatment of ovarian carcinoma: focus on trabectedin

    Directory of Open Access Journals (Sweden)

    Philippe A Cassier

    2010-10-01

    Full Text Available Philippe A Cassier1, Aude Duret1*, Olivier Trédan1, Nicolas Carrabin2, Pierre Méeus2, Isabelle Treilleux3, Jean-Paul Guastalla1, Isabelle Ray-Coquard1,41Département de médecine, 2Département de chirurgie, and 3Département d’anatomopathologie, Centre Léon Bérard, 4EA 4129 SIS Lyon, France *DeceasedAbstract: Trabectedin is a new marine-derived compound that binds the DNA minor groove and interacts with proteins of the DNA repair machinery. Trabectedin has shown promising single-agent activity in pretreated patients with soft tissue sarcoma, and ovarian and breast cancer, and combination with various other chemotherapeutic drugs seems feasible. Toxicities are mainly hematologic and hepatic, with Grade 3–4 neutropenia and thrombocytopenia observed in approximately 50% and 20% of patients, respectively, and Grade 3–4 elevation of liver enzymes observed in 35%–50% of patients treated with trabectedin. The recently reported results of a large Phase III trial comparing pegylated liposomal doxorubicin (PLD alone with a combination of PLD and trabectedin in patients with recurrent ovarian cancer showed improved progression-free survival with the combination of trabectedin and PLD, albeit at the price of increased toxicity. Current research focuses on the identification of predictive factors for patients treated with trabectedin, as well as the development of other combinations.Keywords: chemotherapy, ovarian cancer, combination, drug development, DNA repair

  8. Maintenance Chemotherapy of Stage Ⅲ Epithelial Ovarian Carcinoma-Focusing on Individualized Maintenance Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Xiaodong Zhao; Yi Zhang; Qiao Zhang

    2005-01-01

    OBJECTIVE To investigate the role of maintenance chemotherapy on stage Ⅲ ovarian carcinoma.METHODS A retrospective analysis was conducted of 47 stage Ⅲ ovarian carcinoma patients with clinical complete remission after first-line chemotherapy. Among these patients, 21 cases were treated with maintenance chemotherapy, while the other 26 cases were free of treatment until progression. The 2 groups were compared with respect to progression-free survival (PFS) and overall survival(OS).RESULTS The median PFS and OS were not significantly different between the 2 groups. For those patients, in a subgroup of suboptimal surgery (residual disease >2 cm), the median PFS was 110 weeks and 56 weeks and the median OS was 223 weeks and 157 weeks for the maintenance and non-treated respectively. Both PFS and OS values favoured the maintenance group, P=0.004 and P=0.015 respectively. In a subgroup of optimal surgery (residual disease ≤2 cm), the differences were not significant.CONCLUSION Patients with stage Ⅲ ovarian carcinoma with clinical complete remission may benefit from maintenance chemotherapy, if the residual disease is >2 cm. To those with a residual disease ≤2 cm, the maintenance chemotherapy maybe of no value. So "individualized maintenance chemotherapy" should be conducted in the clinical setting.

  9. Prognostic significance of MyD88 expression by human epithelial ovarian carcinoma cells

    Directory of Open Access Journals (Sweden)

    Zhu Yi

    2012-04-01

    Full Text Available Abstract Background MyD88 is an adaptor protein for TLR-4 signaling known to mediate paclitaxel resistance in epithelial ovarian carcinoma (EOC. This study examined the clinical significance of MyD88 expression in EOC. Methods MyD88 and TLR-4 expression were examined by immunocytochemistry in 109 specimens of ovarian tissues, comprising EOC (N = 83, borderline tumors (N = 9, benign cysts (N = 9 and normal ovarian tissue (N = 8, and clinical data collected by a retrospective chart review. The correlations between MyD88 expression and clinicopathological factors and outcomes were analyzed. Results TLR-4 expression was detected frequently in all the ovarian tissues. Distinct MyD88 expression was showed in EOC (64 of 83, 77.1 %, in borderline tumors (5 of 9, 55.6 % and in benign cysts (3 of 9, 33.3 %, and normal ovarian tissue showed no MyD88 expression. Positive MyD88 expression significantly correlated with shorter disease-free and overall survival for EOC (P  Conclusion Our data indicate that MyD88 expression is a significantly poor prognostic factor for EOC. A better understanding of the role of MyD88 expression in disease progression and outcome may be helpful for development of novel chemotherapies for patients with EOC.

  10. α2β1 integrin affects metastatic potential of ovarian carcinoma spheroids by supporting disaggregation and proteolysis

    Directory of Open Access Journals (Sweden)

    Ackland Margaret

    2007-01-01

    /MMP9 with no such activation of MMP's observed in monolayer cells. Flow cytometric analysis demonstrated enhanced expression of α2 and diminution of α6 integrin subunits in spheroids versus monolayer cells. No change in the expression of α3, αv and β1 subunits was evident. Conversely, except for αv integrin, a 1.5–7.5-fold decrease in α2, α3, α6 and β1 integrin subunit expression was observed in IOSE29 cells within 2 days. Neutralizing antibodies against α2, β1 subunits and α2β1 integrin inhibited disaggregation as well as activation of MMPs in spheroids. Conclusion Our results suggest that enhanced expression of α2β1 integrin may influence spheroid disaggregation and proteolysis responsible for the peritoneal dissemination of ovarian carcinoma. This may indicate a new therapeutic target for the suppression of the peritoneal metastasis associated with advanced ovarian carcinomas.

  11. THE RELATIONSHIP BETWEEN mdrl GENE EXPRESSION AND DRUG-RESISTANCE IN OVARIAN CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    朱玲; 郎景和; 沈铿; 冷金花

    1998-01-01

    Objective. To investigate the relationship between mdrl gene expression and multidrug resistance in ovarian Carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug sensitivity of OC/mdr cell and OC/mdr4 cell in vitro, investigated the effect of cyclosporin A on reversing the multidrug resistance both in vitro and in the tumor bearing mice model,detected the mdrl gene expresion in human ovarian carcinoma specimens. Main outcome measures. Anticancer drug sensitivity of both OC/mdr-cell and OC/mdr+ cell is measured by the methods of MTT assays. mdrl gene expression is detected by the methods of RT-PCR. Results. Using MTT assay,OC/mdr+ cell is 4.1~15.5 times more resistant to VP-16,VCR,DNR,and DOX than OC/mdr- cell in vitro 2μg/ml cyclosporice A(CsA)reducod the resistance of OC/mdr+ cell to DOX,from 0. 324±0. 072μg/ml to 0. 088±0. 024μg/ml. To OC/mdr- cell,CsA did not significandy increase its sensitivity to DOX. Tumor-hearing mice with positive mdrl gene expression showed non-responsiveness to DOX chemotherapy. When combined with intraperitonesl injection of CsA, the growth rate of tumor cells decreased significantly (P<0. 01). Only 4 of 23(17.39%)tumors from patients who had not received chemotherapy exhibited pcsitive mdrl gene expreession,while 6 of 9 (66.67%)treated patients showed positive mdrl gene expression (Fisher exact test= P<0. 05). After cytoreductive surgery and chemotherapy, 14 of 19 untreated patients with negative mdrl gene expression had partial or complete response, while in patients with positive rndrl gene expression, 8 of 10 showed poor prognosis(Fisher exact test: P<0. 05). Conclusion. The expression of nadrl gene is associated with previous chemotherapy. CsA can reverse the resistance of mdr+ cells to indr-associated drs both in vitro and in vivo. For the patients with ovarian Carcinomas, the percentage of nonresponsiveness to the chemotherapy was found to he significantly higher among

  12. Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.

    Science.gov (United States)

    Yu, Xiu-Jie; Zhang, Lin; Liu, Zai-Ping; Shi, Yi-Quan; Liu, Yi-Xin

    2014-01-01

    Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels. PMID:25674278

  13. Late results of chemotherapy of the advanced ovarian cancer

    International Nuclear Information System (INIS)

    Out of 108 patients with advanced ovarian cancer treated by postoperative combined chemotherapy with cisplatin, 13% survived 5 years, 11% with NED and 1.8% with signs of the disease. 67.6% patients responded to treatment in 33.3% of them it was CR and in 34.3% - PR. There was a close relationship between the type of response and survival, as 2 years survived 63.8% patients with CR, 31.4% with PR and only 5.4% of non-responders. Ten out of 36 patients with CR survived 5 years with NED, but out of 4 patients with PR 2 patients survived without symptoms and 2 with signs of the disease. During further follow-up in 4 out of 12 patients who survived 5 years with NED progression of cancer was diagnosed. (author)

  14. Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.

    Science.gov (United States)

    Pina, Christian; Khattab, Ahmed; Katzman, Philip; Bruckner, Lauren; Andolina, Jeffrey; New, Maria; Yau, Mabel

    2015-05-01

    A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma. PMID:25427061

  15. GSTP1 expression and promoter methylation in epithelial ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    V Shilpa

    2014-01-01

    Full Text Available Context: GSTP1 is a subgroup of glutathione-S-transferase family, which provides cellular protection against free radical and carcinogenic compounds due to its detoxifying function. Altered GSTP1 activity due to down regulation of enzyme activity and DNA methylation has been reported in many tumors, although data for ovarian cancer are few. In this study, we aimed at determining the expression of GSTP1 in relation to the methylation of the GSTP1 promoter in epithelial ovarian cancer (EOC. Materials and Methods: GSTP1 mRNA expression and GSTP1 enzyme concentration were assessed by quantitative reverse transcriptase polymerase chain reaction (PCR and enzyme-linked immunosorbent assay, respectively, in 88 EOCs, 14 low malignant potential (LMP tumors, and 20 benign tumors. The promoter methylation of GSTP1 gene was evaluated by methylation-specific PCR. Results: Reduced GSTP1 mRNA expression was observed in 49% EOCs, 21.4% LMP, and 45% benign tumors. Significantly lower levels of plasma GSTP1 were observed in all tumor samples compared to normal. GSTP1 promoter methylation was detected in 10 (11.4% EOCs and 1 (7.3% LMP tumors. No methylation was observed in benign tumors and normal ovaries. Conclusions: Our results show that there is a significant down regulation of GSTP1 expression while hypermethylation of the GSTP1 gene promoter is not very frequent in EOC. Further studies are needed to study underlying mechanisms leading to decreased expression.

  16. Open field whole abdomen irradiation of ovarian and endometrial carcinomas - early clinical tolerance

    International Nuclear Information System (INIS)

    Whole abdomen irradiation (WAI) is broadly applied as a part of the complex treatment of ovarian and high risk endometrial carcinomas prone to development and dissemination in the abdominal cavity. The aim of the present study is to evaluate the early clinical tolerance of WAI open field technique in ovarian and endometrial tumors. During the period 1993 - 2007 56 patients received open field WAI treatment in the Radiotherapy department, The clinical material included 20 patients with ovarian carcinomas, 26 - with endometrial cancer, 6 - with lymphomas and 4 - with other localizations of malignant tumors. The median age of the patients from the more numerous groups was 44 years for these with ovarian tumors and 56 - for these with endometrial tumors, all of them having a Karnofsky index of 100. The patients with endometrial tumors were in the Hi clinical stage, while earlier clinical stages were predominant (80%) for the patients with ovarian tumors. The serous-papillary histological types were prevalent in the ovarian tumors - 6 (30%), and the adenocarcinomas prevailed in the endometrial cancer - 18 (69%). The distribution of the patients with ovarian tumors according to the differentiation grade was: G1:G2:G3 -50%:22%:28%, and of those with endometrial tumors - 21%:67%:12%. WAI was delivered to all patients using tele gamma therapeutic equipment. The planned target volume (PTV) included the peritoneal cavity and the retroperitoneum from the diaphragm domes to the pelvis bottom. The irradiation was achieved via 2 opposite fields with daily doses of 1.0 - 1-5 Gy and total dose of 20 - 30 Gy. Lead protection of kidneys was included after total dose 16-18 Gy, and liver protection was applied after total dose 16-20 Gy.The patients with endometrial and ovarian tumors were given pelvic boost and/or boost in para aortal lymphatic chains and the rest of the patients - in the residual formations. The early clinical tolerance was evaluated using the scale of CTCAE v.3NCI

  17. Preoperative chemoradiotherapy for advanced lower rectal carcinoma

    International Nuclear Information System (INIS)

    Preoperative chemoradiotherapy in combination with radiation of 30 Gy and chemotherapy with oral uracil-tegafur for 14 patients with advanced lower rectal carcinoma was performed. Tumors were located at RaRb in 5 cases, RbRa in 2, Rb in 3, and RbP in 4 with a mean diameter of 3.8 cm. Preoperative lymphnodes were diagnosed as cN0 in 8 cases, cN1 (metastases of perirectal nodes) in 4, cN1 (perirectal and along superior rectal artery nodes) in 1, and cN3 (perirectal and lateral nodes) in 1. Efficacy for primary carcinomas was evaluated as Partial Response in 9 cases, Stable Disease in 5 and perirectal nodes were down-sized in 4 without down-sizing of either along superior rectal artery nodes or lateral nodes. Margins of primary carcinomas to anal verge were prolonged in 7 cases with a mean prolongation of 0.81 cm. Autonomic nerve-preserving resections with lymphadenectomy of perirectal and along superior rectal artery nodes were performed. Histopathologically efficacy for primary tumors was diagnosed to as not effective in 9 cases, partially effective in 5, and all lymphnodes were combined with necroses and fibrosis. Preoperative chemoradiotherapy is safe for preserving autonomic nerves and serves to preserve the sphincter. A forthcoming study with more appropriate radiation, chemotherapy and lymphadenectomy is being considered. (author)

  18. Ovarian Yolk Sac Tumor With High-Grade Serous Carcinoma in a 62-Year-Old Woman.

    Science.gov (United States)

    McCarthy, Whitney A; Masand, Ramya P

    2016-06-01

    Ovarian yolk sac tumors are germ cell tumors that usually present in children and young women. Rarely, these tumors can arise in older women, usually in conjunction with surface epithelial tumors, suggesting divergent differentiation from the latter. The combination of mixed ovarian yolk sac tumor and high-grade serous carcinoma is rare, with only one case documented in the literature. We present a case of mixed ovarian yolk sac tumor and high-grade serous carcinoma in a postmenopausal woman, including a brief discussion of the immunohistochemical findings and differential diagnosis. Despite the rarity of mixed ovarian yolk sac tumor and surface epithelial tumors, it is important to recognize the biphasic nature of the tumor, which should prompt a thorough immunohistochemical evaluation. The therapeutic and prognostic implications of proper diagnosis cannot be overemphasized. PMID:26782153

  19. Elastography, a sensitive tool for the evaluation of neoadjuvant chemotherapy in patients with high-grade serous ovarian carcinoma

    OpenAIRE

    Xie, Meng; ZHANG, XUYIN; JIA, ZHAN; Ren, Yunyun; Wang, Wenping

    2014-01-01

    The aim of the present study was to evaluate tumor stiffness by ultrasound elastography, which has the potential to provide additional information that is useful in predicting the response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian carcinoma (HGSC) patients. In total, 32 patients with International Federation of Gynecology and Obstetrics stage III and IV epithelial ovarian cancer treated with NACT underwent transvaginal and transabdominal sonography, followed by elastogra...

  20. Comparison of abdominopelvic CT results and findings at second-look laparotomy in ovarian carcinoma patients

    International Nuclear Information System (INIS)

    Restaging in epithelial ovarian carcinoma after primary therapy has proven difficult by standard noninvasive methods and commonly requires second-look laparotomy. In the authors' study to date preoperative abdominopelvic CT (CBT) results and operative findings have been compared in 24 patients (25 studies) with ovarian adenocarcinoma currently clinically free of disease originally graded as FIGO stage III or IV, except for one patient with stage IC, undergoing second-look laparotomy to determine tumor status. There were ten true-negative, three false-negative, 12 true-positive, and no false-positive CBTs. Negative studies were associated with positive findings at laparotomy, including microscopic foci, in only 12% of all cases; thus, CBT in the series has shown a better correlation with surgery than in previous studies. Currently the authors are combining monoclonal antibody scanning with the CBT results with the goal of possibly avoiding second-look surgery in certain patients

  1. Radionuclide bone scan, radiographic bone survey, and alkaline phosphatase: studies of limited value in asymptomatic patients with ovarian carcinoma

    International Nuclear Information System (INIS)

    Bone scans or skeletal surveys were obtained in 104 patients with ovarian carcinoma. No metastases were identified at staging in the 43 patients with Stage I or II disease. Four patients in the entire series had osseous metastases. Three of the 40 patients with Stage III epithelian ovarian carcinoma has osseous metastases at the time of staging. All of these were Grade III lesions. One Stage I, Grade III patient demonstrated osseous metastases two years after initial diagnosis. None of the four patients with osseous metastases had an elevated alkaline phosphatase; three of the four had bone pain. Based on these results, it is suggested that radiographic bone survey and radionuclide bone scans are not indicated as screening procedures in asymptomatic patients with ovarian carcinoma

  2. Metaplastic carcinoma of the right breast and simultaneous giant ovarian teratoma: a case report

    Institute of Scientific and Technical Information of China (English)

    Shuang Li; Qing-Zhu Wei

    2012-01-01

    We describe here a female patient who presented with a breast mass and giant abdominal mass.Fine needle aspiration cytology of the breast mass and histological examination after modified radical mastectomy confirmed metaplastic carcinoma of the breast.The epithelial components were formed by infiltrating ductal carcinoma with poor differentiation,and the sarcomatous components were formed by fibrosarcoma and osteosarcoma.Histological examination of the abdominal mass confirmed ovarian teratoma.The patient underwent modified radical mastectomy of the right breast and laparoscopic excision of the abdominal mass in the lower right quadrant.Having underwent six courses of chemotherapy,the patient is now in her tenth month after surgery and under follow-up,and she has no relapsed disease.These two diseases have never seen in one patient before.The case we report here provides some new data for research and clinical experience and it may also provide a new insight into the relationship between metaplastic breast carcinoma and ovarian teratoma.

  3. Diagnostic value of dual detection of hepatocyte nuclear factor 1 beta (HNF-1β) and napsin A for diagnosing ovarian clear cell carcinoma

    OpenAIRE

    Li, Qing; Zeng, Xin; Cheng, Xue; Zhang, Jingmin; Ji, Jie; Wang, Jinsong; Xiong, Kemei; Qi, Qiong; Huang, Wenbin

    2015-01-01

    We evaluated the diagnostic value of hepatocyte nuclear factor 1 beta (HNF-1β) and napsin A for diagnosing ovarian clear cell carcinoma. Immunohistochemical EnVision was used to measure HNF-1β and napsin A expression in 38 cases of ovarian clear cell carcinoma, 30 cases of high-grade serous carcinoma, 22 cases of endometrioid adenocarcinoma, and 16 metastatic Krukenberg tumor cases. Then we found that HNF-1β appeared in all ovarian clear cell carcinoma and was less common in high-grade serous...

  4. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Hong Zheng; Jia-Yu Liu; Feng-Ju Song; Ke-Xin Chen

    2013-01-01

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70%of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30%because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer.

  5. Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

    International Nuclear Information System (INIS)

    Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70% of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30% because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer

  6. Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells

    OpenAIRE

    Mizutani Shigehiko; Nawa Akihiro; Ino Kazuhiko; Shibata Kiyosumi; Kajiyama Hiroaki; Terauchi Mikio; Kikkawa Fumitaka

    2007-01-01

    Abstract Background Aminopeptidase N (APN/CD13), a 150-kDa metalloprotease, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression of several human malignancies. In the current study, we investigated the role of APN/CD13 in ovarian carcinoma (OVCA) progression. Methods We first examined the expression of APN/CD13 at the protein level in a variety of OVCA cell lines and tissues. We su...

  7. Dasatinib in Treating Patients With Recurrent or Persistent Ovarian, Fallopian Tube, Endometrial or Peritoneal Cancer

    Science.gov (United States)

    2016-05-19

    Endometrial Clear Cell Adenocarcinoma; Estrogen Receptor Negative; Ovarian Clear Cell Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

  8. Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma

    DEFF Research Database (Denmark)

    Köbel, M; Madore, J; Ramus, S J;

    2014-01-01

    stage I/II tumours, patients with FOLR1-positive HGSC showed increased OS during the first 2 years only (hazard ratio=0.44, 95% confidence interval=0.20-0.96) and patients with FOLR1-positive clear cell carcinomas (CCC) showed decreased PFS independent of follow-up time (HR=1.89, 95% CI=1.10-3.25, N=259......BACKGROUND: Folate receptor 1 (FOLR1) is expressed in the majority of ovarian carcinomas (OvCa), making it an attractive target for therapy. However, clinical trials testing anti-FOLR1 therapies in OvCa show mixed results and require better understanding of the prognostic relevance of FOLR1...

  9. MAL2 and tumor protein D52 (TPD52 are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    Directory of Open Access Journals (Sweden)

    Fanayan Susan

    2010-09-01

    Full Text Available Abstract Background The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52, which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Methods Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. Results MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p Conclusions MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients.

  10. Study on the role of mitochondria in sodium butyrate-induced apoptosis of ovarian carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Liu Wei; Tang Chunsheng; Rong Fengnian

    2005-01-01

    Objective:To investigate the role of mitochondria in sodium butyrate-induced apoptosis of ovarian carcinoma cells in vitro.Methods:Human ovarian epithelial cancer 3AO cells were cultured in vitro and treated with sodium butyrate of different concentration for different time. The characters of apoptosis were assessed through light microscopy and DNA ladder analysis. The morphological changes of mitochondria were detected through electron and epifluorescence microscopy. The functional changes of mitochondria and the expression of Bcl-2/Bax protein were analyzed by flow cytometry.Results:As the concentration of sodium butyrate rose to 4mmol/L, the morphologic characters of apoptosis were found by light microscopy, DNA ladder was observed. Under epifluorescence microscope the fluorescence of the control group was stronger than that of the experimental group. Under electron microscope swelled mitochondria was detected. Flow cytometry analysis showed mitochondria transmembrane potentials decreased and there were down-regulate of Bcl-2 protein and up-regulate of the Bax protein(P<0.05).Conclusion:Sodium butyrate can induce apoptosis of 3AO cells in a time-dose dependent manner. Mitochondrion may play a key role in the procedure of apoptosis of ovarian cancer cells.

  11. Models of endometriosis and their utility in studying progression to ovarian clear cell carcinoma.

    Science.gov (United States)

    King, Claire M; Barbara, Cynthia; Prentice, Andrew; Brenton, James D; Charnock-Jones, D Stephen

    2016-01-01

    Endometriosis is a common benign gynaecological condition affecting at least 10% of women of childbearing age and is characterized by pain--frequently debilitating. Although the exact prevalence is unknown, the economic burden is substantial (∼$50 billion a year in the USA alone) and it is associated with considerable morbidity. The development of endometriosis is inextricably linked to the process of menstruation and thus the models that best recapitulate the human disease are in menstruating non-human primates. However, the use of these animals is ethically challenging and very expensive. A variety of models in laboratory animals have been developed and the most recent are based on generating menstrual-like endometrial tissue that can be transferred to a recipient animal. These models are genetically manipulable and facilitate precise mechanistic studies. In addition, these models can be used to study malignant transformation in epithelial ovarian carcinoma. Epidemiological and molecular evidence indicates that endometriosis is the most plausible precursor of both clear cell and endometrioid ovarian cancer (OCCA and OEA, respectively). While this progression is rare, understanding the underlying mechanisms of transformation may offer new strategies for prevention and therapy. Our ability to pursue this is highly dependent on improved animal models but the current transgenic models, which genetically modify the ovarian surface epithelium and oviduct, are poor models of ectopic endometrial tissue. In this review we describe the various models of endometriosis and discuss how they may be applicable to developing our mechanistic understanding of OCCA and OEA. PMID:26456077

  12. Treatment results and prognostic factors of clear cell ovarian carcinomas and ovarian carcinomas with clear cell component

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    M. D. Ahmedova

    2014-07-01

    Full Text Available The most important prognostic factors for clear cell carcinoma (CCC are clinical and morphological signs and clinical stage of the disease. Analyses of 5-year survival in patients with I stage of CCC is 69 %, in II stage – 55 %, in III stage – 14 % and in IV stage – 4 % patients. We analyzed distant results of treatment of 71 patients with CCC and of 25 patients with mixed malignant ovaries neoplasm with obligatory clear cell component taking into consideration main clinical and morphological sings of disease. On the base of performed reseal we revealed that morphological structure of the tumors and stage of the disease exerted heist influence on the exponent of survival of the patients with clear CCC ovaries neoplasm. Besides, there is a correlation between exponent of patients’ survival and radicalized of surgery, character of tumor growth, differentiation degree, cell anaplasia and mitotic activity of tumor cells.

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

    Science.gov (United States)

    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

  14. Expression of IL-18, IL-18 Binding Protein, and IL-18 Receptor by Normal and Cancerous Human Ovarian Tissues: Possible Implication of IL-18 in the Pathogenesis of Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Liat Medina

    2014-01-01

    Full Text Available Proinflammatory cytokine IL-18 has been shown to be elevated in the sera of ovarian carcinoma patients. The aim of the study was to examine the levels and cellular origin of IL-18, IL-18 binding protein, and IL-18 receptor in normal and cancerous ovarian tissues. Ovarian tissue samples were examined by immunohistochemical staining for IL-18, IL-18BP, and IL-18R and mRNA of these cytokines was analyzed with semiquantitative PT-PCR. IL-18 levels were significantly higher in cancerous ovarian tissues (P=0.0007, IL-18BP levels were significantly higher in normal ovarian tissues (P=0.04, and the ratio of IL-18/IL-18BP was significantly higher in cancerous ovarian tissues (P=0.036. Cancerous ovarian tissues expressed significantly higher IL-18 mRNA levels (P=0.025, while there was no difference in the expression of IL-18BP mRNA and IL-18R mRNA between cancerous and normal ovarian tissues. IL-18 and IL-18BP were expressed dominantly in the epithelial cells of both cancerous and normal ovarian tissues, while IL-18R was expressed dominantly in the epithelial cells of cancerous ovarian tissues but expressed similarly in the epithelial and stromal cells of normal cancerous tissues. This study indicates a possible role of IL-18, IL-18BP, and IL-18R in the pathogenesis of epithelial ovarian carcinoma.

  15. Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma

    DEFF Research Database (Denmark)

    Bergmann, Troels K; Filppula, Anne M; Launiainen, Terhi;

    2015-01-01

    AIM: The aim of this case report is to describe a novel pharmacokinetic drug-drug interaction between the antiplatelet agent clopidogrel and the antineoplastic agent paclitaxel. METHODS: The patient was identified in a previously described cohort of 93 patients with ovarian carcinoma treated with...

  16. New blocking antibodies impede adhesion, migration and survival of ovarian cancer cells, highlighting MFGE8 as a potential therapeutic target of human ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Lorenzo Tibaldi

    Full Text Available Milk Fat Globule--EGF--factor VIII (MFGE8, also called lactadherin, is a secreted protein, which binds extracellularly to phosphatidylserine and to αvβ3 and αvβ5 integrins. On human and mouse cells expressing these integrins, such as endothelial cells, phagocytes and some tumors, MFGE8/lactadherin has been shown to promote survival, epithelial to mesenchymal transition and phagocytosis. A protumoral function of MFGE8 has consequently been documented for a few types of human cancers, including melanoma, a subtype of breast cancers, and bladder carcinoma. Inhibiting the functions of MFGE8 could thus represent a new type of therapy for human cancers. Here, we show by immunohistochemistry on a collection of human ovarian cancers that MFGE8 is overexpressed in 45% of these tumors, and we confirm that it is specifically overexpressed in the triple-negative subtype of human breast cancers. We have established new in vitro assays to measure the effect of MFGE8 on survival, adhesion and migration of human ovarian and triple-negative breast cancer cell lines. Using these assays, we could identify new MFGE8-specific monoclonal antibodies, which efficiently blocked these three tumor-promoting effects of MFGE8. Our results suggest future use of MFGE8-blocking antibodies as new anti-cancer therapeutics in subgroups of ovarian carcinoma, and triple-negative breast carcinoma patients.

  17. Sociodemographic disparities in advanced ovarian cancer survival and adherence to treatment guidelines

    OpenAIRE

    Bristow, RE; Chang, J.; Ziogas, A.; Campos, B.; Chavez, LR; Anton-Culver, H.

    2015-01-01

    © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. Objective: To estimate whether race or ethnic and socioeconomic strata are independently associated with advanced-stage ovarian cancer-specific survival after adjusting for adherence to National Comprehensive Cancer Network treatment guidelines. Methods: The design was a retrospective population-based cohort study of patients with stage IIIC-IV epithelial ovarian ca...

  18. Recent Technological Advances in Using Mouse Models to Study Ovarian Cancer

    OpenAIRE

    House, Carrie Danielle; Hernandez, Lidia; Annunziata, Christina Messineo

    2014-01-01

    Serous epithelial ovarian cancer (SEOC) is the most lethal gynecological cancer in the United States with disease recurrence being the major cause of morbidity and mortality. Despite recent advances in our understanding of the molecular mechanisms responsible for the development of SEOC, the survival rate for women with this disease has remained relatively unchanged in the last two decades. Preclinical mouse models of ovarian cancer, including xenograft, syngeneic, and genetically engineered ...

  19. The next steps in improving the outcomes of advanced ovarian cancer.

    Science.gov (United States)

    Openshaw, Mark R; Fotopoulou, Christina; Blagden, Sarah; Gabra, Hani

    2015-06-01

    Worldwide ovarian cancer affects over 200,000 women per year. Overall survival rates are poor due to two predominate reasons. First, the majority of patients present with advanced disease creating significant difficulty with effecting disease eradication. Second, acquisition of chemotherapy resistance results in untreatable progressive disease. Advances in treatment of advanced ovarian cancer involve a spectrum of interventions including improvements in frontline debulking surgery and combination chemotherapy. Anti-angiogenic factors have been shown to have activity in frontline and recurrent disease while novel chemotherapeutic agents and targeted treatments are in development particularly for disease that is resistant to platinum-based chemotherapy. These developments aim to improve the progression-free and overall survival of women with advanced ovarian cancer. PMID:26102473

  20. [Endometrial adenocarcinoma and clear cell carcinoma in a young woman with polycystic ovarian syndrome: a case report].

    Science.gov (United States)

    Niu, Jing; Liu, Nan; Liu, Guo-Bing

    2016-05-20

    A 26-year-old unmarried woman with irregular menstruation for 4 years was admitted for an intrauterine space-occupying mass. Pathological examination before surgery showed moderately to poorly differentiated endometrial adenocarcinoma. The patient underwent laparoscopically assisted epifascial panhysterectomy with bilateral salpingo-oophorectomy. Pathological examination of the surgical specimens reported moderately to poorly differentiated endometrial adenocarcinoma and stage II clear cell carcinoma. The patient then received chemotherapy and remained alive without evidence of recurrence. Young women with polycystic ovarian syndrome are at high risk of developing endometrial carcinoma, but concurrent clear cell carcinoma is rare. Careful evaluation before and after treatment are essential to improve the patients prognosis. PMID:27222196

  1. VEGF-D-induced draining lymphatic enlargement and tumor lymphangiogenesis promote lymph node metastasis in a xenograft model of ovarian carcinoma

    OpenAIRE

    Du, Li-Cheng; Chen, Xian-Cheng; Wang, Dong; Wen, Yan-Jun; Wang, Chun-Ting; Wang, Xue-mei; Kan, Bing; WEI, YU-QUAN; Zhao, Xia

    2014-01-01

    Background Vascular endothelial growth factor (VEGF)-D has been shown to promote lymph node metastasis in several cancers. Although generally overexpressed in ovarian carcinoma, its role in nodal dissemination of this cancer is unclear. To clarify the role of VEGF-D and the underlying molecular mechanisms, we investigated the function of VEGF-D using a mouse xenograft model of ovarian cancer. Methods Human ovarian serous adenocarcinoma SKOV3 cells were transfected with VEGF-D recombinant plas...

  2. Intensity-Modulated Whole Abdominal Radiotherapy After Surgery and Carboplatin/Taxane Chemotherapy for Advanced Ovarian Cancer: Phase I Study

    International Nuclear Information System (INIS)

    Purpose: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. Methods and Materials: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. Results: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. Conclusions: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

  3. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F;

    2015-01-01

    %). CONCLUSIONS: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).......BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to...

  4. HER2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy

    Directory of Open Access Journals (Sweden)

    Swenerton Kenneth D

    2009-12-01

    Full Text Available Abstract Background The response rate of ovarian mucinous carcinomas to paclitaxel/carboplatin is low, prompting interest in targeted molecular therapies. We investigated HER2 expression and amplification, and the potential for trastuzumab therapy in this histologic subtype of ovarian cancer. Methods HER2 status was tested in 33 mucinous carcinomas and 16 mucinous borderline ovarian tumors (BOT. Five cases with documented recurrence and with tissue from the recurrence available for testing were analyzed to determine whether HER2 amplification status changed over time. Three prospectively identified recurrent mucinous ovarian carcinomas were assessed for HER2 amplification and patients received trastuzumab therapy with conventional chemotherapy. Results Amplification of HER2 was observed in 6/33 (18.2% mucinous carcinomas and 3/16 (18.8% BOT. HER2 amplification in primary mucinous carcinomas was not associated with an increased likelihood of recurrence. The prospectively identified recurrent mucinous carcinomas showed overexpression and amplification of HER2; one patient's tumor responded dramatically to trastuzumab in combination with conventional chemotherapy, while another patient experienced an isolated central nervous system recurrence after trastuzumab therapy. Conclusion HER2 amplification is relatively common in ovarian mucinous carcinomas (6/33, 18.2%, although not of prognostic significance. Trastuzumab therapy is a treatment option for patients with mucinous carcinoma when the tumor has HER2 amplification and overexpression.

  5. Computed tomography, primary laparotomy and 'second-look' operation for ovarian carcinoma

    International Nuclear Information System (INIS)

    The value of computed tomography for staging and for observing the course of ovarian carcinomas was analysed in 56 patients in whom the diagnosis has been verified by laparotomy. CT achieved correct staging in 85% of cases. The ability of CT to demonstrate a variety of abnormalities varies; ascites and pleural effusions were shown in 100%, lymph node metastases in 90%, infiltration of the recto-sigmoid and terminal ileum in 70-80%, subcapsular liver metastases in 70%, involvement of the omentum in 70%, of the peritoneum in 65% and of the mesentery in 35%. A ''second-look'' operation remains necessary in order to confirm complete remission after chemotherapy, since CT is only rarely able to show residual tumours smaller than 1.5-2 cm. (orig.)

  6. Ovarian carcinoma: improved survival following abdominopelvic irradiation in patients with a completed pelvic operation

    International Nuclear Information System (INIS)

    A prospective, stratified, randomized study of 190 postoperative ovarian carcinoma patients with Stages IB, II, and III (asymptomatic) presentations is reported. The median time of follow-up was 52 months. Patients in whom bilateral salpingo-oophorectomy and hysterectomy (BSOH) could not be completed because of extensive pelvic tumor had a poor prognosis which did not differ for any of the therapies tested. When BSOH was completed, pelvic plus abdominopelvic irradiation (P + AB) with no diaphragmatic shielding significantly improved patient survival rate and long-term control of occult upper abdominal disease in approximately 25% more patients than pelvic irradiation alone or followed by adjuvant daily chlorambucil therapy. The effectiveness of P + AB in BSOH-completed patients was independent of stage or tumor grade and was most clearly appreciated in patients with all gross tumor removed. Chlorambucil added to pelvic irradiation delayed the time to treatment failure without reducing the number of treatment failures

  7. Metastatic liver tumor from cystic ovarian carcinomas. CT and MRI appearance

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yi; Yamashita, Yasuyuki; Ogata, Ichiro; Namimoto, Tomohiro; Abe, Yasuko; Urata, Joji; Takahashi, Mutsumasa [Kumamoto Univ. (Japan). School of Medicine

    1999-08-01

    The initial and follow-up CT and MRI images of ten patients with hepatic metastases from ovarian tumors were retrospectively analyzed to establish their features and sequential changes in appearance. Ten patients with hepatic metastasis from ovarian tumors received initial and follow-up CT and MRI examinations. Six patients were followed up every two to three weeks before surgical tumor resection. Both CT and MR images were analyzed by two radiologists. A total of fourteen lesions were detected by CT and MRI in 10 patients. All 14 lesions were demonstrated as areas of marked hyperintensity on T2-weighted MRI. Eleven cyst-like tumors were demonstrated as round or oval low density lesions on CT and as areas of hypointensity on T1-weighted imaging. Three lesions were shown as solid masses with slightly low attenuation at the initial CT examination and slightly low or iso-intensity areas on T1-weighted imaging, and these lesions showed early peripheral globular enhancement and delayed enhancement on contrast-enhanced CT and MR imaging. Cystic formation was observed two to three weeks later after initial study in all the 3 solid lesions. Rapid subcapsular effusion, which showed obvious enhancement on delayed Gd-DTPA enhanced MR imaging, was observed in two patients. The hepatic metastatic tumor from cystic ovarian carcinoma may manifest as a well-defined cystic lesion or as a solid mass, and the solid mass shows delayed enhancement on contrast-enhanced CT and MR imaging. Furthermore, rapid cystic formation and rapid subcapsular extension is frequently seen. (author)

  8. Metastatic liver tumor from cystic ovarian carcinomas. CT and MRI appearance

    International Nuclear Information System (INIS)

    The initial and follow-up CT and MRI images of ten patients with hepatic metastases from ovarian tumors were retrospectively analyzed to establish their features and sequential changes in appearance. Ten patients with hepatic metastasis from ovarian tumors received initial and follow-up CT and MRI examinations. Six patients were followed up every two to three weeks before surgical tumor resection. Both CT and MR images were analyzed by two radiologists. A total of fourteen lesions were detected by CT and MRI in 10 patients. All 14 lesions were demonstrated as areas of marked hyperintensity on T2-weighted MRI. Eleven cyst-like tumors were demonstrated as round or oval low density lesions on CT and as areas of hypointensity on T1-weighted imaging. Three lesions were shown as solid masses with slightly low attenuation at the initial CT examination and slightly low or iso-intensity areas on T1-weighted imaging, and these lesions showed early peripheral globular enhancement and delayed enhancement on contrast-enhanced CT and MR imaging. Cystic formation was observed two to three weeks later after initial study in all the 3 solid lesions. Rapid subcapsular effusion, which showed obvious enhancement on delayed Gd-DTPA enhanced MR imaging, was observed in two patients. The hepatic metastatic tumor from cystic ovarian carcinoma may manifest as a well-defined cystic lesion or as a solid mass, and the solid mass shows delayed enhancement on contrast-enhanced CT and MR imaging. Furthermore, rapid cystic formation and rapid subcapsular extension is frequently seen. (author)

  9. Characterization of chemically induced ovarian carcinomas in an ethanol-preferring rat model: influence of long-term melatonin treatment.

    Directory of Open Access Journals (Sweden)

    Luiz Gustavo A Chuffa

    Full Text Available Ovarian cancer is the fourth most common cause of cancer deaths among women, and chronic alcoholism may exert co-carcinogenic effects. Because melatonin (mel has oncostatic properties, we aimed to investigate and characterize the chemical induction of ovarian tumors in a model of ethanol-preferring rats and to verify the influence of mel treatment on the overall features of these tumors. After rats were selected to receive ethanol (EtOH, they were surgically injected with 100 µg of 7,12-dimethyl-benz[a]anthracene (DMBA plus sesame oil directly under the left ovarian bursa. At 260 days old, half of the animals received i.p. injections of 200 µg mel/100 g b.w. for 60 days. Four experimental groups were established: Group C, rats bearing ovarian carcinomas (OC; Group C+EtOH, rats voluntarily consuming 10% (v/v EtOH and bearing OC; Group C+M, rats bearing OC and receiving mel; and Group C+EtOH+M, rats with OC consuming EtOH and receiving mel. Estrous cycle and nutritional parameters were evaluated, and anatomopathological analyses of the ovarian tumors were conducted. The incidence of ovarian tumors was higher in EtOH drinking animals 120 days post-DMBA administration, and mel efficiently reduced the prevalence of some aggressive tumors. Although mel promoted high EtOH consumption, it was effective in synchronizing the estrous cycle and reducing ovarian tumor mass by 20%. While rats in the C group displayed cysts containing serous fluid, C+EtOH rats showed solid tumor masses. After mel treatment, the ovaries of these rats presented as soft and mobile tissues. EtOH consumption increased the incidence of serous papillary carcinomas and sarcomas but not clear cell carcinomas. In contrast, mel reduced the incidence of sarcomas, endometrioid carcinomas and cystic teratomas. Combination of DMBA with EtOH intake potentiated the incidence of OC with malignant histologic subtypes. We concluded that mel reduces ovarian masses and the incidence of

  10. 111In-labeled KCCYSL peptide as an imaging probe for ErbB-2-expressing ovarian carcinomas

    OpenAIRE

    Deutscher, Susan L.; Figueroa, Said D.; Kumar, Senthil R.

    2009-01-01

    Aberrant expression of ErbB-2, a member of the epidermal growth factor family of receptors, has been implicated in the formation of various malignancies including ovarian cancer. The objective of this study was to determine if the bacteriophage (phage) display-selected ErbB-2 targeting peptide, KCCYSL, once radiolabeled with 111In would serve as a tumor targeting and Single Photon Emission Computed Tomography (SPECT/CT) imaging agent in a mouse model of human ovarian carcinoma expressing ErbB...

  11. Whole-abdomen radiation therapy in ovarian carcinoma: Its role as a salvage therapeutic modality

    International Nuclear Information System (INIS)

    A significant proportion of patients with epithelial ovarian carcinoma eventually fail after initial responses to chemotherapy. Further treatment with chemotherapy consisting of either the same combination or second-line regimens has been ineffective in producing durable responses. Thus, between June 1983 and June 1987, thirty patients with epithelial ovarian carcinoma who failed one or more chemotherapeutic regimens were treated with whole-abdominopelvic-cavity radiation therapy. Prior to the radiation the amount of residual disease after debulking was noted to be microscopic in 16 patients and macroscopic in 14 patients. Radiation was delivered with an open-field technique that extended from the domes of the diaphragm to the obturator foramina. Doses of 2500 cGy were planned to the whole abdomen, with a boost of another 2500 cGy to the pelvic and or paraaortic nodes when indicated. Higher doses were delivered to the areas of gross disease in the pelvis. Only 2 patients were unable to complete the planned therapy. Another 26% of the patients required interruption of the therapy secondary to hematologic toxicity but eventually completed the treatment. With an overall median follow-up of 14 months, 56% of the patients remain alive. Two-year actuarial survival and recurrence-free survival rates are 47 and 32%, respectively. The survival and recurrence-free survival rates for the group with microscopic residual disease--61 and 33%, respectively--are better than those for the patients with macroscopic residual disease--36 and 18%. The abdominopelvic cavity was the first site of failure in all but one of the 17 patients who have failed. In spite of the higher doses, pelvic failure alone or as a component occurred in 54% of the patients. Small bowel obstruction necessitating surgical intervention as a complication of therapy was seen in 13% of the patients

  12. Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells

    Directory of Open Access Journals (Sweden)

    Mizutani Shigehiko

    2007-07-01

    Full Text Available Abstract Background Aminopeptidase N (APN/CD13, a 150-kDa metalloprotease, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression of several human malignancies. In the current study, we investigated the role of APN/CD13 in ovarian carcinoma (OVCA progression. Methods We first examined the expression of APN/CD13 at the protein level in a variety of OVCA cell lines and tissues. We subsequently investigated whether there was a correlation between APN/CD13 expression and invasive potential of various OVCA cell lines. Moreover, we investigated the function of APN/CD13 in OVCA cells using bestatin, an APN/CD13 inhibitor, or transfection of siRNA for APN/CD13. Results We confirmed that APN/CD13 was expressed in OVCA tissues and cell lines to various extents. There was a positive correlation between APN/CD13 expression and migratory potential in various OVCA cell lines with accordingly enhanced secretion of endogenous MMP-2. Subsequently, we found a significant decrease in the proliferative and migratory abilities of OVCA cells after the addition of bestatin or the inhibition of APN/CD13 expression by siRNA. Furthermore, in an animal model, daily intraperitoneal administration of bestatin after inoculation of OVCA cells resulted in a decrease of peritoneal dissemination and in prolonged survival of nude mice. Conclusion The current data indicate the possible involvement of APN/CD13 in the development of OVCA, and suggest that clinical use of bestatin may contribute to better prognosis for ovarian carcinoma patients.

  13. Inhibition of APN/CD13 leads to suppressed progressive potential in ovarian carcinoma cells

    International Nuclear Information System (INIS)

    Aminopeptidase N (APN/CD13), a 150-kDa metalloprotease, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression of several human malignancies. In the current study, we investigated the role of APN/CD13 in ovarian carcinoma (OVCA) progression. We first examined the expression of APN/CD13 at the protein level in a variety of OVCA cell lines and tissues. We subsequently investigated whether there was a correlation between APN/CD13 expression and invasive potential of various OVCA cell lines. Moreover, we investigated the function of APN/CD13 in OVCA cells using bestatin, an APN/CD13 inhibitor, or transfection of siRNA for APN/CD13. We confirmed that APN/CD13 was expressed in OVCA tissues and cell lines to various extents. There was a positive correlation between APN/CD13 expression and migratory potential in various OVCA cell lines with accordingly enhanced secretion of endogenous MMP-2. Subsequently, we found a significant decrease in the proliferative and migratory abilities of OVCA cells after the addition of bestatin or the inhibition of APN/CD13 expression by siRNA. Furthermore, in an animal model, daily intraperitoneal administration of bestatin after inoculation of OVCA cells resulted in a decrease of peritoneal dissemination and in prolonged survival of nude mice. The current data indicate the possible involvement of APN/CD13 in the development of OVCA, and suggest that clinical use of bestatin may contribute to better prognosis for ovarian carcinoma patients

  14. Vascular endothelial growth factor expression in ovarian serous carcinomas and its effect on tumor proliferation

    Directory of Open Access Journals (Sweden)

    Gayatri Ravikumar

    2013-01-01

    Full Text Available Introduction: Vascular endothelial growth factor (VEGF, an endothelial mitogen, acts through VEGF receptors (VEGFRs on the endothelial cells. During neoplastic transformation, it is hypothesized that the tumor expresses VEGF and also acquire VEGF receptor, enabling VEGF action in an autocrine and paracrine manner with varied effects on the tumor growth and progression. This study on ovarian serous carcinomas (OSCs was done to determine the expression of VEGF and to correlate it with tumor proliferation. Material and Methods: Forty cases of OSCs were included. Immunohistochemistry was performed for VEGF and Ki-67. The VEGF slides were assigned an immunohistochemical score based on the staining intensity (a and the percentage of tumor cells staining (b. The sum of both (a and (b ranged from 0-6. VEGF was considered positive when the score was more than 2. For Ki-67, maximally immunostained areas were selected; 500 cells counted and positive fraction determined. Mann Whitney test was used to determine the difference in the median value of Ki-67 between VEGF positive tumors and VEGF negative tumors. Results: Of the 40 cases, 32 cases had a VEGF score of >2 (positive and 8 cases had VEGF score <2 (negative. The Ki-67 score ranged from 2-98%, with mean of 51%. The median Ki-67 index was much higher in VEGF positive cases as compared to VEGF negative tumors (57.5% vs. 40%. However, the difference in the two categories did not reach statistical significance (P = 0.45, Mann Whitney test. Conclusion: Ovarian serous carcinomas express VEGF in a significant number of cases (80% in the present study although its potential mitogenic effect on tumor cells was not confirmed.

  15. Pancreatic Metastasis of High-Grade Papillary Serous Ovarian Carcinoma Mimicking Primary Pancreas Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Yusuf Gunay

    2012-01-01

    Full Text Available Introduction. Reports of epithelial ovarian carcinomas metastatic to the pancreas are very rare. We herein present a metastasis of high grade papillary serous ovarian cancer to mid portion of pancreas. Case. A 42-year-old patient was admitted with a non-specified malignant cystic lesion in midportion of pancreas. She had a history of surgical treatment for papillary serous ovarian adenocarcinoma. A cystic lesion was revealed by an abdominal computerized tomography (CT performed in her follow up . It was considered as primary mid portion of pancreatic cancer and a distal pancreatectomy was performed. The final pathology showed high-grade papillary serous adenocarcinoma morphologically similar to the previously diagnosed ovarian cancer. Discussion. Metastatic pancreatic cancers should be considered in patients who present with a solitary pancreatic mass and had a previous non-pancreatic malignancy. Differential diagnosis of primary pancreatic neoplasm from metastatic malignancy may be very difficult. A biopsy for tissue confirmation is required to differentiate primary and secondary pancreatic tumors. Although, the value of surgical resection is poorly documented, resection may be considered in selected patients. Conclusion. Pancreatic metastasis of ovarian papillary serous adenocarcinoma has to be kept in mind when a patient with pancreatic mass has a history of ovarian malignancy.

  16. MAL2 and tumor protein D52 (TPD52) are frequently overexpressed in ovarian carcinoma, but differentially associated with histological subtype and patient outcome

    International Nuclear Information System (INIS)

    The four-transmembrane MAL2 protein is frequently overexpressed in breast carcinoma, and MAL2 overexpression is associated with gain of the corresponding locus at chromosome 8q24.12. Independent expression microarray studies predict MAL2 overexpression in ovarian carcinoma, but these had remained unconfirmed. MAL2 binds tumor protein D52 (TPD52), which is frequently overexpressed in ovarian carcinoma, but the clinical significance of MAL2 and TPD52 overexpression was unknown. Immunohistochemical analyses of MAL2 and TPD52 expression were performed using tissue microarray sections including benign, borderline and malignant epithelial ovarian tumours. Inmmunohistochemical staining intensity and distribution was assessed both visually and digitally. MAL2 and TPD52 were significantly overexpressed in high-grade serous carcinomas compared with serous borderline tumours. MAL2 expression was highest in serous carcinomas relative to other histological subtypes, whereas TPD52 expression was highest in clear cell carcinomas. MAL2 expression was not related to patient survival, however high-level TPD52 staining was significantly associated with improved overall survival in patients with stage III serous ovarian carcinoma (log-rank test, p < 0.001; n = 124) and was an independent predictor of survival in the overall carcinoma cohort (hazard ratio (HR), 0.498; 95% confidence interval (CI), 0.34-0.728; p < 0.001; n = 221), and in serous carcinomas (HR, 0.440; 95% CI, 0.294-0.658; p < 0.001; n = 182). MAL2 is frequently overexpressed in ovarian carcinoma, and TPD52 overexpression is a favourable independent prognostic marker of potential value in the management of ovarian carcinoma patients

  17. Papillary serous carcinoma of the peritoneal surface: matched-case comparison with papillary serous ovarian carcinoma.

    Science.gov (United States)

    Killackey, M A; Davis, A R

    1993-11-01

    Between 1984 and 1991, 199 patients underwent laparotomy for epithelial "ovarian" malignancy. In 29 cases (15%) normal-sized ovaries (PSOC). PSPS was also characterized by ascites (mean = 3036 cc), malignant washings (91%), and omental involvement with bulky infiltration and/or multiple tumor nodules (96%). Mean cytoreduction in the PSPS group was 65.5% compared to 79% in the PSOC group (P = 0.049). Patients received combination chemotherapy with platinum-based regimens. In general, there was a poor response to treatment with a disease-free interval of 3.4 and median survival time of 19 months in PSPS compared to 11.7 and 31 months in the PSOC patients. Patients with PSPS have more limited cytoreduction, shorter disease-free interval, and shorter overall survival time. Such differences prompt re-evaluation of treatment modalities for PSPS and recognition that this is a condition distinct from PSOC. PMID:8276289

  18. Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2016-07-29

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

  19. Acute non-ST elevation myocardial infarction following paclitaxel administration for ovarian carcinoma: A case report and review of literature

    OpenAIRE

    Kajal Shah; Sudeep Gupta; Jaya Ghosh; Jyoti Bajpai; Amita Maheshwari

    2012-01-01

    We report a case of an acute non-ST elevation myocardial infarction (AMI) induced by paclitaxel in a patient with ovarian cancer. A 45-year-old premenopausal lady without any co-morbidity was started on the first cycle of neoadjuvant chemotherapy with paclitaxel-based regimen for advanced stage ovarian cancer. The patient developed chest pain 3 h after paclitaxel infusion with characteristic electrocardiographic changes of antero-apical myocardial infarction. The patient recovered on conserva...

  20. Kinase inhibitors for advanced medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Martin Schlumberger

    2012-01-01

    Full Text Available The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.

  1. Genomic and sieroproteomic analysis for the identification of molecular tumor markers for diagnosis, therapy and follow-up of ovarian and endometrial carcinomas

    International Nuclear Information System (INIS)

    The aim of the study is the identification, through the analysis of genomic and proteomic expression profiles, of novel molecular bio markers correlated with pathogenesis, progression, diagnosis or therapy of ovarian cancer. Patients referring to the Division of Gynecologic Oncology at the University of Brescia have been enrolled in the study starting from April 2007. 66 patients with ovarian carcinoma were included (49 with primary ovarian cancer and 17 with relapse/progression). Controls included 134 patients with histologically proven benign pelvic masses (64 uterine fibromas, 36 benign ovarian cysts, 34 endometriosis). All patients signed an informed consent according to institutional guidelines. Clinico pathological features of patients were collected

  2. Metastatic dissemination of human ovarian epithelial carcinoma is promoted by alpha2beta1-integrin-mediated interaction with type I collagen.

    Science.gov (United States)

    Fishman, D A; Kearns, A; Chilukuri, K; Bafetti, L M; O'Toole, E A; Georgacopoulos, J; Ravosa, M J; Stack, M S

    1998-01-01

    Metastatic dissemination of epithelial ovarian carcinoma is thought to be mediated via tumor cell exfoliation into the peritoneal cavity, followed by adhesion to and invasion through the mesothelium which overlies the contents of the peritoneal cavity. In this study, we have utilized short-term primary cultures to analyze the effect of specific extracellular matrix proteins on properties of human ovarian epithelial carcinoma cells which contribute to the invasive phenotype. Analysis of cell:matrix adhesive profiles indicated that ovarian carcinoma cells adhere preferentially to type I collagen. Immunoprecipitation analyses demonstrated the presence of the collagen-binding alpha2beta1 integrin in biotin-labeled ovarian carcinoma cell membranes, and cellular adhesion was inhibited by blocking antibodies directed against the alpha2 and beta1 integrin subunits. The alpha2beta1-binding peptide Asp-Gly-Glu-Ala (DGEA) was also moderately effective at blocking adhesion to collagen relative to the control peptide Ala-Gly-Glu-Ala (AGEA). Analysis of cell motility on protein-coated colloidal gold coverslips demonstrated that ovarian carcinoma cells migrate preferentially on type I collagen coated surfaces. Type I collagen promoted migration in a concentration-dependent, saturable manner, with maximal migration observed at a collagen-coating concentration of 50 microg/ml. Migration on collagen was inhibited by antibodies directed against the alpha2 and beta1 integrin subunits and by DGEA peptide, providing evidence for the role of the alpha2beta1 integrin in ovarian carcinoma cell motility. Culturing ovarian carcinoma cells on type I collagen gels led to a significant increase in conversion of the matrix metalloproteinase 2 zymogen to the 66-kD form, suggesting that adhesion to collagen also influences matrix-degrading proteinases. These data suggest that alpha2beta1-integrin-mediated interaction of ovarian carcinoma cells with type I collagen, a protein prevalent both in the

  3. Systemic mastocytosis in a patient with ovarian germ cell carcinoma and mast cell leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Sun, G.; Hajianpour, M.J.; Hajianpour, A.K. [Alfigen/The Genetics Institute, Pasadena, CA (United States)] [and others

    1994-09-01

    We report a 12-year-old female with a history of mixed germ cell carcinoma of the right ovary who developed a generalized skin rash after oophorectomy and chemotherapy. She also presented with periodic episodes of flushing, anemia, tachycardia, shortness of breath, high fever, hepatosplenomegaly, nausea, abdominal cramping with diarrhea, and a papuloerythematous skin rash. There was no evidence of secondary carcinoma. Skin biopsy revealed nonspecific inflammatory cells with negative staining for mast cells. Peripheral blood smear showed an increased number of mast cells, thrombocytopenia and normal white cells count. Bone marrow showed hypercellularity with 38% of the nucleated cells being mast cells. Bone marrow chromosome analysis revealed hyperdiploidy in 30% of the cells: 58-64,XX, +1, +2, +5, +6, +7, +8, +14, +16, +18, +19, +19, +20, +21, +22. She expired two months after the occurrence of systemic mastocytosis. Systemic mastocytosis has been reported in association with hematopoietic disorders and with germ cell tumors. The association between mediastinal germ cell tumors and hematological malignancies has also been observed. To our knowledge, combination of most cell leukemia, systemic mastocytosis, and ovarian germ cell carcinoma has not been observed. It is know that mutations at the locus of either proto-oncogene c-kit receptor or its ligand, mast/stem cell factor (SCF) may impair the development of three stem cell populations: hematopoietic stem cells, germ cells and melanoblasts. There have been also extensive investigations on the expression and modulation of the SCF/c-kit interaction in various malignancies. Further molecular studies in patients with germ cell tumor/hematopoietic malignancy syndrome are required to delineate underlying mechanisms.

  4. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    OpenAIRE

    Ryuichi Kita; Toru Kimura; Hiroki Nishikawa; Yukio Osaki

    2012-01-01

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of ...

  5. In vivo SPECT/CT imaging of human orthotopic ovarian carcinoma xenografts with {sup 111}In-labeled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Huhtala, Tuulia [Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 (Finland); Laakkonen, Pirjo [Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 (Finland); Molecular Cancer Biology Research Program and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki (Finland); Sallinen, Hanna [Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 (Finland); Ylae-Herttuala, Seppo [Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 (Finland); Biocenter Kuopio, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio (Finland); Naervaenen, Ale, E-mail: ale.narvanen@uku.f [Department of Biotechnology and Molecular Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211 (Finland); Biocenter Kuopio, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio (Finland)

    2010-11-15

    Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 3 (VEGFR-3) are expressed in the tumor area during the progression of ovarian carcinoma. Monoclonal antibodies developed against these receptors are potential diagnostic molecules for in vivo imaging of ovarian carcinoma. Methods: Biodistribution of the monoclonal antibodies cetuximab against EGFR and mF4-31C1 against VEGFR-3 was studied in nude mice with orthotopic SKOV-3m human ovarian carcinoma xenografts. The biodistribution of {sup 111}Indium-labeled antibodies was followed up to 48 h postinjection using combined SPECT and CT imaging modality. Organ samples were collected postmortem and specific organ activity was measured. Accumulation of the intravenously injected antibodies in the tumor tissue and lymph nodes was verified using immunohistology. Results: Imaging studies with SPECT/CT showed clear accumulation of both antibodies into tumor area. The tumor uptake was 8.78{+-}0.74 %ID/g for cetuximab and 5.77{+-}0.62 %ID/g for mF4-31C1 after 48 h postinjection. Cetuximab had lower liver tropism and faster tumor homing rate. In addition, after 48 h two of five tumor-bearing mice showed a clear accumulation of the In-labeled mF4-31C1 at the left axillary area. Both intravenously administered antibodies could also be detected from the tumor sections by immunohistological staining but only mF4-31C1 forms in the lymph nodes. Conclusion: These results demonstrate the accumulation of EGFR- and VEGFR-3-specific antibodies in orthotopic ovarian carcinoma tumors. Systemically administered they had slow pharmacokinetics which is typical for antibodies. Accumulation of mF4-31C1 antibody in the lymph nodes suggests the remote activation of VEGFR-3 by the primary tumor.

  6. Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells

    International Nuclear Information System (INIS)

    Caveolin-1 (cav-1), a member of a protein family associated mainly with cell membrane microdomains in many cell types, acts as a tumor suppressor in ovarian carcinoma cells. Biochemical analyses demonstrated that cav-1 was also localized in the nuclei of ovarian carcinoma cells, endogenously (SKOV3) or ectopically (IGtC3) expressing cav-1. By confocal analyses, the same cell lines as well as IGROV1 and SKOV3 cells transiently transfected with green fluorescent protein-cav-1 fusion protein showed nuclear punctate speckled pattern. Subnuclear distribution analysis revealed cav-1 mainly associated with the nuclear matrix, but also slightly with chromatin. Cav-1 was found in nuclear high-molecular weight complexes and by confocal analysis was found to co-localized with the inner nuclear membrane protein emerin. Cyclin D1 and folate receptor promoters were modulated by cav-1 in SKOV3 cells as demonstrated by transient transfection with or silencing of cav-1. Chromatin immunoprecipitation and supershift assays indicated that nuclear cav-1 can bind in vitro and in vivo to promoter sequences of both cyclin D1 and folate receptor genes. These data suggest that in ovarian carcinoma cells cav-1, localized in transcriptionally inactive chromatin, exerts a functional activity mediated, at least in part, by directly binding to sequences of genes involved in proliferation

  7. THE ABERRANT PROMOTER HYPERMETHYLATION PATTERN OF THE ANTI - ANGIOGENIC TSP1 GENE IN EPITHELIAL OVARIAN CARCINOMA: AN INDIAN STUDY

    Directory of Open Access Journals (Sweden)

    Ramesh

    2015-06-01

    Full Text Available PURPOSE: The promoter hypermethylation patterns of Thrombospodin - 1 gene in 50 EOC patients were studied and the methylation pattern was correlated with various clinic pathological parameters. METHODS: The promoter hypermethylation pattern of the TSP - 1 gene was assessed using nested PCR and Methylation specific PCR. STATISTICAL ANALYSIS: All the available data was statistically analyzed using the Chi square test or Fisher Exact Test on the SPSS software version 22.0 and a value <0.0 5 was considered statistically significant. RESULTS: Forty of the fifty ovarian carcinoma samples reported positive for methylation corresponding to a methylation frequency of 80%. A methylation frequency of 89.2%, 83.3% and 42.8% was observed in malignant , Low malignant potential (borderline and benign sample cohorts. CONCLUSION: From the results drawn from this study, it clearly shows that the anti angiogenic protein TSP - 1 is extensively hypermethylated in ovarian carcinoma and that it accumulates over t he progression of the disease from benign to malignant. As previous reports suggest that there is no evidence of mutation of this gene, promoter hypermethylation may be a crucial factor for the down regulation of the gene. Further by clubbing together the promoter hypermethylation pattern of TSP - 1 gene with hypermethylation patterns of other TSG may provide a better insight into the application of using methylation profiles of TSG as a biomarker in the detection of ovarian carcinoma.

  8. Human carcinoma-associated mesenchymal stem cells promote ovarian cancer chemotherapy resistance via a BMP4/HH signaling loop

    Science.gov (United States)

    Coffman, Lan G.; Choi, Yun-Jung; McLean, Karen; Allen, Benjamin L.; di Magliano, Marina Pasca; Buckanovich, Ronald J.

    2016-01-01

    The tumor microenvironment is critical to cancer growth and therapy resistance. We previously characterized human ovarian carcinoma-associated mesenchymal stem cells (CA-MSCs). CA-MSCs are multi-potent cells that can differentiate into tumor microenvironment components including fibroblasts, myofibroblasts and adipocytes. We previously reported CA-MSCs, compared to normal MSCs, express high levels of BMP proteins and promote tumor growth by increasing numbers of cancer stem-like cells (CSCs). We demonstrate here that ovarian tumor cell-secreted Hedgehog (HH) induces CA-MSC BMP4 expression. CA-MSC-derived BMP4 reciprocally increases ovarian tumor cell HH expression indicating a positive feedback loop. Interruption of this loop with a HH pathway inhibitor or BMP4 blocking antibody decreases CA-MSC-derived BMP4 and tumor-derived HH preventing enrichment of CSCs and reversing chemotherapy resistance. The impact of HH inhibition was only seen in CA-MSC-containing tumors, indicating the importance of a humanized stroma. These results are reciprocal to findings in pancreatic and bladder cancer, suggesting HH signaling effects are tumor tissue specific warranting careful investigation in each tumor type. Collectively, we define a critical positive feedback loop between CA-MSC-derived BMP4 and ovarian tumor cell-secreted HH and present evidence for the further investigation of HH as a clinical target in ovarian cancer. PMID:26755648

  9. Nanoparticle Albumin-Bound Rapamycin in Treating Patients With Advanced Cancer With mTOR Mutations

    Science.gov (United States)

    2016-04-18

    Advanced Malignant Neoplasm; Cervical Squamous Cell Carcinoma; Endometrial Carcinoma; Malignant Uterine Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Cervical Carcinoma; Recurrent Head and Neck Carcinoma; Recurrent Malignant Neoplasm; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Solid Neoplasm; Stage III Bladder Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IV Breast Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Renal Cell Cancer; Stage IVA Bladder Cancer; Stage IVA Cervical Cancer; Stage IVB Bladder Cancer; Stage IVB Cervical Cancer

  10. Neoadjuvant chemotherapy in advanced ovarian cancer: latest results and place in therapy

    OpenAIRE

    Sato, Seiya; Itamochi, Hiroaki

    2014-01-01

    Approximately 70% of women with epithelial ovarian cancer (EOC) are diagnosed with advanced stage disease, which is associated with high morbidity and mortality. The standard approach to treating patients with advanced EOC remains primary debulking surgery (PDS) followed by chemotherapy. EOC is one of the most sensitive of all solid tumors to cytotoxic drugs, with over 80% of women showing a response to standard chemotherapy combined with taxane and platinum. Furthermore, residual disease is ...

  11. Ovarian Cancer

    OpenAIRE

    Yong Sang Song; Hee Seung Kim; Daisuke Aoki; Danny N. Dhanasekaran; Tsang, Benjamin K

    1986-01-01

    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 ver...

  12. Differential expression of alpha 2 macroglobulin in response to dietylstilbestrol and in ovarian carcinomas in chickens

    Directory of Open Access Journals (Sweden)

    Bazer Fuller W

    2011-10-01

    Full Text Available Abstract Background Alpha 2 macroglobulin (A2M; also known as ovostatin, a homotetrameric protein with four disulfide-linked subunits, has the unique feature of inactivating/inhibiting most known proteases including serine-, threonine-, cysteine-, aspartic- and metalloproteases. In chickens, A2M has been identified and characterized biochemically, but little is known of its functional role(s in the oviduct, hormonal regulation of expression or its expression in ovarian carcinomas in chickens. Therefore, we investigated estrogen regulation of A2M gene expression during development of the chicken oviduct, and its expression in normal and cancerous ovaries from chickens. Methods To determine tissue-specific expression of A2M in chickens, we collected various organs from male and female chickens and performed RT-PCR analyses. To examine A2M gene expression in the oviduct of 1-week-old female chicks that received a subcutaneous implant of 15 mg DES in the abdominal region for 20 days, we performed RT-PCR, qPCR and in situ hybridization analyses using cDNAs from control- (n = 5 and DES-treated oviducts (n = 5, and then each segment of the oviduct from DES-treated chicks. To determine if A2M is a biomarker of ovarian cancer in hens, we collected cancerous (n = 10 ovaries from a total of 136 chickens which had completely stopped egg-laying and performed RT-PCR and in situ hybridization analyses. Results We found that A2M is most abundant in the chicken oviduct, specifically luminal (LE and glandular epithelia (GE, but it was not detected in any other tissues of either sex. We then determined that DES (dietylstilbestrol, a synthetic nonsteroidal estrogen increased A2M mRNA only in LE and GE of the oviduct of chicks. Further, expression of A2M was most abundant in GE of endometrioid adenocarcinoma of cancerous, but not normal ovaries of hens. Conclusions Collectively, results of the present study indicate that A2M is novel estrogen-stimulated gene

  13. Advanced Upper Eyelid Sebaceous Gland Carcinoma with Deep Orbital Extension

    Directory of Open Access Journals (Sweden)

    Rizvi SAR

    2010-03-01

    Full Text Available Sebaceous gland carcinomas (SGC are highly malignant lid tumors which originate from meibomian glands and rarely from the gland of Zeis, sebaceous gland of caruncle, eyebrows and periocular skin. In many cases correct diagnosis of SGC is delayed because of its ability to masquerade as a variety of other ocular conditions.A forty year old male presented with a left upper eyelid swelling with an ulcerated wound on its nasal aspect. A differential diagnosis of sebaceous gland carcinoma or preseptal cellulitis was made. Contrast enhanced computed tomography showed an ill defined soft tissue density mass in the left orbit encasing the whole of the optic nerve. A total exentration was performed. A diagnosis of meibomian gland carcinoma was confirmed on histopathology.This is a report of an advanced sebaceous gland carcinoma with deep orbital extension. An early diagnosis and appropriate treatment may decrease the long term morbidity and extend the survival rate of such patients.

  14. Therapeutic potential of paclitaxel-radiation treatment of a murine ovarian carcinoma

    International Nuclear Information System (INIS)

    Background. Paclitaxel has been shown to radiosensitize tumor cells in culture by arresting them in the most radiosensitive G2 and M cell cycle phases. In vivo preclinical studies are now necessary to obtain full insight into the radiopotentiating potential of this drug and its ability to increase the therapeutic gain of radiotherapy. We tested its ability to enhance the tumor radioresponse of an ovarian carcinoma and to influence the normal tissue radioresponse of recipient mice. Methods. Mice bearing 8-mm isotransplants of a syngeneic ovarian carcinoma, designated OCA-I, in their legs were treated with 40 mg/kg paclitaxel i.v., 14-60 Gy single-dose local tumor irradiation, or both; radiation was given under ambient conditions 1-96 h after paclitaxel. Tumor growth delay, tumor cure rate (TCD50 assay), and delay in tumor recurrences were measured. Normal tissue radioresponse was determined using jejunal crypt cell survival at 3.5 days after exposure of mice to 9-14 Gy single dose of total body irradiation; the mice were untreated or treated with 40 mg/kg i.v. paclitaxel 4-96 h before irradiation. Results. Paclitaxel alone was effective against OCA-I, but its combination with irradiation produced supra-additive tumor growth delay. It also reduced TCD50 values and delayed tumor recurrences. The enhancement of tumor radioresponse ranged from 1.33 to 1.96; the value increased as the time between paclitaxel administration and tumor irradiation increased up to 48 h, but then decreased again at 96 h. In contrast, paclitaxel protected jejunum against radiation damage by factors of 1.03 to 1.07 when given 24-96 h before irradiation. It showed some potentiation of damage (by a factor of 1.07), but only when given 4 h before irradiation. Conclusions. Paclitaxel potentiated tumor radioresponse if given within 4 days before irradiation, whereas it caused radioprotection of normal tissue (jejunum) at that time. Therefore, paclitaxel significantly increased therapeutic gain and

  15. Accumulation and toxicity of antibody-targeted doxorubicin-loaded PEG-PE micelles in ovarian cancer cell spheroid model

    OpenAIRE

    Perche, Federico; Torchilin, Vladimir P.

    2012-01-01

    We describe the evaluation of doxorubicin-loaded PEG-PE micelles targeting using an ovarian cancer cell spheroid model. Most ovarian cancer patients present at an advanced clinical stage and develop resistance to standard of care platinum/taxane therapy. Doxorubicin is also approved for ovarian cancer but had limited benefits in refractory patients. In this study, we used drug-resistant spheroid cultures of ovarian carcinoma to evaluate the uptake and cytotoxicity of an antibody-targeted doxo...

  16. Distribution of p53 expression in tissue from 774 Danish ovarian tumour patients and its prognostic significance in ovarian carcinomas

    DEFF Research Database (Denmark)

    Hogdall, E.V.S.; Christensen, L.; Frederiksen, K.;

    2008-01-01

    The clinical roles played by normal and altered p53 in cancer are under intensive investigation, but larger studies describing the pattern as well as the prognostic value are still needed. The aim of this study was, using tissue array (TA), to examine the overexpression of p53 protein in 774...... epithelial ovarian tumour tissues from Danish women and to evaluate whether p53 tissue expression levels correlate with clinicopathological parameters and prognosis. The distribution of p53 expression levels at different stages of disease, in different histological subtypes, and the prognostic value of p53...... tissue expression were examined. Overall, p53 was expressed in 24/189 (13%) low malignant potential ovarian tumours (LMP) and in 278/585 (48%) ovarian cancers (OC). No significant difference in frequency of p53 tissue expression in LMP tissue was noted with increasing tumour stage (p=0.98). By contrast...

  17. Neurofibromin 1 (NF1 Defects Are Common in Human Ovarian Serous Carcinomas and Co-occur with TP53 Mutations

    Directory of Open Access Journals (Sweden)

    Navneet Sangha

    2008-12-01

    Full Text Available Ovarian serous carcinoma (OSC is the most common and lethal histologic type of ovarian epithelial malignancy. Mutations of TP53 and dysfunction of the Brca1 and/or Brca2 tumor-suppressor proteins have been implicated in the molecular pathogenesis of a large fraction of OSCs, but frequent somatic mutations in other well-established tumor-suppressor genes have not been identified. Using a genome-wide screen of DNA copy number alterations in 36 primary OSCs, we identified two tumors with apparent homozygous deletions of the NF1 gene. Subsequently, 18 ovarian carcinoma-derived cell lines and 41 primary OSCs were evaluated for NF1 alterations. Markedly reduced or absent expression of Nf1 protein was observed in 6 of the 18 cell lines, and using the protein truncation test and sequencing of cDNA and genomic DNA, NF1 mutations resulting in deletion of exons and/or aberrant splicing of NF1 transcripts were detected in 5 of the 6 cell lines with loss of NF1 expression. Similarly, NF1 alterations including homozygous deletions and splicing mutations were identified in 9 (22% of 41 primary OSCs. As expected, tumors and cell lines with NF1 defects lacked mutations in KRAS or BRAF but showed Ras pathway activation based on immunohistochemical detection of phosphorylated MAPK (primary tumors or increased levels of GTP-bound Ras (cell lines. The TP53 tumor-suppressor gene was mutated in all OSCs with documented NF1 mutation, suggesting that the pathways regulated by these two tumor-suppressor proteins often cooperate in the development of ovarian carcinomas with serous differentiation.

  18. Multidrug Resistance-Linked Gene Signature Predicts Overall Survival of Patients With Primary Ovarian Serous Carcinoma

    Science.gov (United States)

    Gillet, Jean-Pierre; Calcagno, Anna Maria; Varma, Sudhir; Davidson, Ben; Bunkholt Elstrand, Mari; Ganapathi, Ram; Kamat, Aparna A.; Sood, Anil K.; Ambudkar, Suresh V.; Seiden, Michael V.; Rueda, Bo R.; Gottesman, Michael M.

    2012-01-01

    Purpose This study assesses the ability of multidrug resistance (MDR)-associated gene expression patterns to predict survival in patients with newly diagnosed carcinoma of the ovary. The scope of this research differs substantially from that of previous reports, as a very large set of genes was evaluated whose expression has been shown to affect response to chemotherapy. Experimental Design We applied a customized TaqMan Low Density Array, a highly sensitive and specific assay, to study the expression profiles of 380 MDR-linked genes in 80 tumor specimens collected at initial surgery to debulk primary serous carcinoma. The RNA expression profiles of these drug resistance genes were correlated with clinical outcomes. Results Leave-one-out cross-validation was used to estimate the ability of MDR gene expression to predict survival. Although gene expression alone does not predict overall survival (P=0.06), four covariates (age, stage, CA125 level and surgical debulking) do (P=0.03). When gene expression was added to the covariates, we found an 11-gene signature that provides a major improvement in overall survival prediction (log-rank statistic P<0.003). The predictive power of this 11-gene signature was confirmed by dividing high and low risk patient groups, as defined by their clinical covariates, into four specific risk groups based on expression levels. Conclusion This study reveals an 11-gene signature that allows a more precise prognosis for patients with serous cancer of the ovary treated with carboplatin- and paclitaxel-based therapy. These 11 new targets offer opportunities for new therapies to improve clinical outcome in ovarian cancer. PMID:22492981

  19. High immunosuppressive burden in advanced hepatocellular carcinoma patients

    OpenAIRE

    Lugade, Amit A.; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

    2013-01-01

    The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

  20. Prevalence of Helicobacter pylori infection in advanced gastric carcinoma

    OpenAIRE

    Irami Araújo-Filho; José Brandão-Neto; Laíza Araújo Mohana Pinheiro; Ítalo Medeiros Azevedo; Flávio Henrique Miranda de Araújo Freire; Aldo Cunha Medeiros

    2006-01-01

    BACKGROUD: There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS: To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's c...

  1. Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age

    OpenAIRE

    Miyahara, Koji; Nouso, Kazuhiro; Yamamoto,Kazuhide

    2014-01-01

    The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma (HCC). After development of sorafenib and its introduction as a therapeutic agent used in the clinic, several critical questions have been raised. Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated. Although it is difficult to know the responders in advance using conven...

  2. Total abdominal and pelvic radiotherapy in the management of early stage ovarian carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Macbeth, F.R.; Macdonald, H.; Williams, C.J.

    1988-08-01

    In a prospective study, 57 women with early stage ovarian carcinoma received total abdominal and pelvic radiotherapy (TAPR) following radical surgery. The whole abdomen received 22.5 Gy m.p.d. by large opposed fields in 18 fractions over 4 1/2 weeks, with 8 MeV X rays, followed by a further 22.5 Gy in 10 fractions over 2 weeks to the pelvis alone, using a dosage and technique similar to that described from the Princess Margaret Hospital, Toronto. The actuarial 5-year relapse-free and overall survival figures were 49 and 57% respectively, which appear to be significantly worse than those reported from Toronto (73% and 75%). The incidence of severe bowel toxicity (7%) was higher. There was no correlation between survival and FIGO stage at laparotomy, but a significant correlation with histological grade. These data do not seem to support the idea of a curative role for post-operative irradiation at this dosage in these patients.

  3. Experimental comparison of three background subtraction agents for monoclonal antibody imaging of ovarian carcinoma xenografts

    International Nuclear Information System (INIS)

    Dual-isotope background subtraction imaging can be used to enhance lesion detection in imaging studies using monoclonal antibodies. The best agent for background subtraction has not been determined, however. The author compared Tc-99m human serum albumin, Tc-99m red blood cells, and I-123-labeled nonspecific murine myeloma immunoglobulin (UPC-10) for their ability to enhance imaging of ovarian carcinoma xenografts in groups of nude mice 24 hours after they were injected with I-131 5G6.4 tumor-specific intact immunoglobulin. Using dual-isotope dynamic background subtraction, tumor imaging was most clear with Tc-99m red blood cells, second best with Tc-99m human serum algumin, and least clear with I-123 UPC-10. while verification in humans will be essential, these animal findings suggest that dual-isotope monoclonal antibody imaging of tumors is enhanced most with Tc-99m red blood cells and least with an isotype-matched monoclonal antibody

  4. Exome profiling of primary, metastatic and recurrent ovarian carcinomas in a BRCA1-positive patient

    International Nuclear Information System (INIS)

    Ovarian carcinoma is a common, and often deadly, gynecological cancer. Mutations in BRCA1 and BRCA2 genes are present in at least a fifth of patients. Uncovering other genes that become mutated subsequent to BRCA1/BRCA2 inactivation during cancer development will be helpful for more effective treatments. We performed exome sequencing on the blood, primary tumor, omental metastasis and recurrence following therapy with carboplatin and paclitaxel, from a patient carrying a BRCA1 S1841R mutation. We observed loss of heterozygosity in the BRCA1 mutation in the primary and subsequent tumors, and somatic mutations in the TP53 and NF1 genes were identified, suggesting their role along with BRCA1 driving the tumor development. Notably, we show that exome sequencing is effective in detecting large chromosomal rearrangements such as deletions and amplifications in cancer. We found that a large deletion was present in the three tumors in the regions containing BRCA1, TP53, and NF1 mutations, and an amplification in the regions containing MYC. We did not observe the emergence of any new mutations among tumors from diagnosis to relapse after chemotherapy, suggesting that mutations already present in the primary tumor contributed to metastases and chemotherapy resistance. Our findings suggest that exome sequencing of matched samples from one patient is a powerful method of detecting somatic mutations and prioritizing their potential role in the development of the disease

  5. Effects of Dexamethasone on glucocorticoid receptor expression in a human ovarian carcinoma cell line 3AO

    Institute of Scientific and Technical Information of China (English)

    徐明娟; 宋亮年; 王昭梅

    2003-01-01

    Objective To observe the effects of Dexamethasone (Dex), a synthetic glucocorticoid, on glucocorticoid receptor expression in the human ovarian carcinoma cell line 3AO. The molecular mechanism of glucocorticoid (GC) on 3AO cells was also studied.Methods The expression and regulation of the glucocorticoid receptor in 3AO cells was studied by utilizing radioligand binding assay and quantitative RT-PCR. Results High affinity and low capacity GR existed in 3AO cells, in addition, GR binding activity was down-regulated by Dex in a time-dependent manner, to a level about 28.34% of control following 24 hours treatment, with a concomitant decrease in GR mRNA. The induction of alkaline phosphatase (AKP) activity by Dex was reversed by RU486, a potent glucocorticoid antagonist.Conclusion In 3AO cells, functional GR which can be down-regulated by Dex at the protein and mRNA level, exists suggesting that the regulating effects of Dex on GR occur at least partially at the GR mRNA level, and that the cellular effects of Dex on 3AO cells might be mediated by GR.

  6. Apoptosis of drug-resistant human ovarian carcinoma cell line COC1/DDP induced by survivin antisense oligonucleotides

    Institute of Scientific and Technical Information of China (English)

    ZHENG Fei; RUAN Fei; XIE Xian-kuan; LIU Shao-yang

    2006-01-01

    @@ Currently, surgery-oriented treatment plays a major role in the treatment of ovarian cancer patients. But 5-year survival rate of patients is still around 30%. One of the main reasons for the Iow survival rate is the drug resistance of tumor cells against chemotherapy.1,2 The function of antiapoptosis in the course of initiation and progress of cancer has a close relationship with drug resistance of tumor cells. Survivin is a new discovered anti-apoptosis gene, its expression levels correlating with more aggressive disease and poor clinical outcome in many of these tumors. It has been reported that survivin is expressed during fetal development and in cancer tissues.3 Furthermore,survivin overexpression, by disrupting the balance between cell proliferation/differentiation and apoptosis, may relate with the resistance to a variety of apoptotic stimuli, including chemotherapy.4,5 We designed antisense oligonucleotides of survivin to treat the drug-resistant human ovarian carcinoma cell line COC1/DDP, and studied its effects on inducing COC1/DDP apoptosis. The purpose of this study was to find a novel approach to improve the sensitivity of ovarian carcinoma chemotherapy.

  7. Aldesleukin in advanced renal cell carcinoma.

    Science.gov (United States)

    Schmidinger, Manuela; Hejna, Michael; Zielinski, Christoph C

    2004-12-01

    Renal cell carcinoma accounts for 2-3% of all malignancies. The most common subtype [85%] is the clear cell variant. A total of 30% of patients present with metastatic disease at diagnosis and another 30-40% will develop metastases during the course of the disease. Conventional cancer treatment is not effective, but cytokines including recombinant interleukin-2 (aldesleukin) have demonstrated clinical activity of various degrees. This drug profile provides a review of the literature on studies using aldesleukin in patients with metastatic renal cell carcinoma. Aldesleukin has been used in different dose schedules applying various administration routes, as either monotherapy or in combination with other cytokines, chemotherapy, endocrine treatment and adoptive cellular immunotherapy. Although a large number of randomized trials have been performed with different treatment strategies, it still remains uncertain whether the dose or combination of aldesleukin with other agents substantially influence treatment outcome. It appears that factors other than those that are treatment related are responsible for the course of the disease. PMID:15606326

  8. Phosphorylated Smad2 in Advanced Stage Gastric Carcinoma

    International Nuclear Information System (INIS)

    Transforming growth factor β (TGFβ) receptor signaling is closely associated with the invasion ability of gastric cancer cells. Although Smad signal is a critical integrator of TGFβ receptor signaling transduction systems, not much is known about the role of Smad2 expression in gastric carcinoma. The aim of the current study is to clarify the role of phosphorylated Smad2 (p-Smad2) in gastric adenocarcinomas at advanced stages. Immunohistochemical staining with anti-p-Smad2 was performed on paraffin-embedded specimens from 135 patients with advanced gastric adenocarcinomas. We also evaluated the relationship between the expression levels of p-Smad2 and clinicopathologic characteristics of patients with gastric adenocarcinomas. The p-Smad2 expression level was high in 63 (47%) of 135 gastric carcinomas. The p-Smad2 expression level was significantly higher in diffuse type carcinoma (p = 0.007), tumours with peritoneal metastasis (p = 0.017), and tumours with lymph node metastasis (p = 0.047). The prognosis for p-Smad2-high patients was significantly (p = 0.035, log-rank) poorer than that of p-Smad2-low patients, while a multivariate analysis revealed that p-Smad2 expression was not an independence prognostic factor. The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma

  9. Advances in ovarian cancer diagnosis: A journey from immunoassays to immunosensors.

    Science.gov (United States)

    Sharma, Shikha; Raghav, Ragini; O'Kennedy, Richard; Srivastava, Sudha

    2016-07-01

    This review focuses on the technological advancements, challenges and trends in immunoassay technologies for ovarian cancer diagnosis. Emphasis is placed on the principles of the technologies, their merits and limitations and on the evolution from laboratory-based methods to point-of-care devices. While the current market is predominantly associated with clinical immunoassay kits, over the last decade a major thrust in development of immunosensors is evident due to their potential in point-of-care devices. Technological advancements in immunosensors, extending from labeled to label-free detection, with and without mediators, for enhancing proficiencies and reliability have been dealt with in detail. Aspects of the utilisation of nanomaterials and immobilization strategies for enhancing sensitivity and altering the detection range have also been addressed. Finally, we have discussed some distinct characteristics and limitations associated with the recently commericalised technologies used for quantitation of relevant ovarian cancer markers. PMID:27233124

  10. Lipoic acid decreases Mcl-1, Bcl-xL and up regulates Bim on ovarian carcinoma cells leading to cell death.

    OpenAIRE

    Kafara, Perrine; Icard, Philippe; Guillamin, Marilyne; Schwartz, Laurent; Lincet, Hubert

    2014-01-01

    Background Ovarian carcinoma is the leading cause of death from gynecological cancer because there is risk of chemoresistance. As previously demonstrated in our laboratory, Alpha-lipoic acid (LA), a co-factor for metabolic enzymes, suppresses the tumor growth. In this study, we have researched the mechanisms that are responsible for the activity of LA. Methods We have studied the mechanisms of LA in two ovarian cancer cell lines, a cisplatin sensitive one, IGROV1 and its resistant counterpart...

  11. Case of pure ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin but responsive to monotherapy with weekly irinotecan.

    Science.gov (United States)

    Nakamura, Yasuhiko; Kamei, Toshiaki; Shinagawa, Masahiro; Sakamoto, Yuka; Miwa, Ichiro

    2015-05-01

    Primary ovarian squamous cell carcinoma is uncommon, and the optimal treatment strategy for this disease has not yet been established. A 71-year-old woman diagnosed with FIGO stage IIb pure ovarian squamous cell carcinoma underwent cytoreductive surgery followed by combination chemotherapy with paclitaxel and carboplatin. After the second treatment course, a recurrent mass grew rapidly, and serum tumor maker levels increased. Monotherapy with weekly irinotecan was then instituted. This second-line chemotherapy was remarkably effective, and the patient subsequently underwent complete interval debulking surgery with a pathological complete response after the third treatment course. Weekly irinotecan is an effective choice for primary ovarian squamous cell carcinoma resistant to combination chemotherapy with paclitaxel and carboplatin. PMID:25511544

  12. Adopting a Uniform Approach to Site Assignment in Tubo-Ovarian High-Grade Serous Carcinoma: The Time has Come.

    Science.gov (United States)

    Singh, Naveena; Gilks, C Blake; Hirshowitz, Lynn; Wilkinson, Nafisa; McCluggage, W Glenn

    2016-05-01

    There is currently sufficient evidence that nonuterine high-grade serous carcinoma (HGSC) originates in the fallopian tube in the majority of cases, but this is not uniformly reflected in our diagnostic terminology. This is because there remains wide variation in awareness and acceptance of this evidence, which conflicts with traditional views on origin. Accurate disease classification is fundamental to routine clinical practice and research, particularly at a time when exciting new approaches to therapy, early detection, and prevention are appearing on the horizon. We feel the time has come to minimize individual and institutional variations in practice, and agree on an evidence-based approach to uniform terminology and primary site assignment. In this paper we put forward a proposal for a unified approach based on published research evidence and discuss the reasons why it is vital to agree on a uniform protocol. We propose the term "Tubo-ovarian HGSC" in preference to "pelvic" or "Müllerian," as it accurately reflects the origin of this disease in the vast majority of cases, and is unambiguous, distinguishing it clearly from uterine serous carcinoma and ovarian low-grade serous carcinomas. A detailed protocol for primary site assignment is presented for different scenarios, which is easy to follow and has been developed with a view to promoting a uniform approach worldwide. PMID:26977579

  13. Primary Surgery or Neoadjuvant Chemotherapy in Advanced Ovarian Cancer: The Debate Continues….

    Science.gov (United States)

    Leary, Alexandra; Cowan, Renee; Chi, Dennis; Kehoe, Sean; Nankivell, Matthew

    2016-01-01

    Primary debulking surgery (PDS) followed by platinum-based chemotherapy has been the cornerstone of treatment for advanced ovarian cancer for decades. Primary debulking surgery has been repeatedly identified as one of the key factors in improving survival in patients with advanced ovarian cancer, especially when minimal or no residual disease is left behind. Achieving these results sometimes requires extensive abdominal and pelvic surgical procedures and consultation with other surgical teams. Some clinicians who propose a primary chemotherapy approach reported an increased likelihood of leaving no macroscopic disease after surgery and improved patient-reported outcomes and quality-of-life (QOL) measures. Given the ongoing debate regarding the relative benefit of PDS versus neoadjuvant chemotherapy (NACT), tumor biology may aid in patient selection for each approach. Neoadjuvant chemotherapy offers the opportunity for in vivo chemosensitivity testing. Studies are needed to determine the best way to evaluate the impact of NACT in each individual patient with advanced ovarian cancer. Indeed, the biggest utility of NACT may be in research, where this approach provides the opportunity for the investigation of predictive markers, mechanisms of resistance, and a forum to test novel therapies. PMID:27249696

  14. miR-29b regulates cell proliferation and invasion in human ovarian clear cell carcinoma by targeting Lysyl oxidase (LOX

    Directory of Open Access Journals (Sweden)

    Wang Xuan

    2016-01-01

    Full Text Available Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its chemoresistance and frequent late diagnosis, and suggesting that a more effective treatment approach is needed. Lysyl oxidase (LOX is involved in important biological processes such as gene regulation, cell signaling and cell motility, its deregulation contributing to tumor formation and development. Although it is known that LOX is involved in proliferation, migration and invasion in several types of tumors, studies of LOX in ovarian cancers are scarce. To explore the molecular regulation mechanisms in ovarian cancer tumorigenesis, the expression change and the function of LOX was confirmed in ovarian tissues and cells, which suggested that LOX is a tumor suppressor gene. To further understand how LOX expression is regulated in ovarian cancer, microRNAs(miRNAs were considered because of their role in post-transcriptional regulation of many genes. Recent work has described differential expression of mature miRNAs in human cancers. Bioinformatics prediction which was used to find the appropriate miRNA regulating LOX, revealed that miR-29b regulates LOX protein level via its binding site on the 3'UTR of LOX mRNAin ES-2 cells, a human ovarian clear cell carcinoma cell line. miR-29b knockdown inhibited proliferation and invasion in ES-2 cells. Taken together, these findings suggest that influencing LOX regulation bychanging the level of miR-29b expression could provide a novel potential approachfor treating human ovarian clear cell carcinoma.

  15. Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium

    International Nuclear Information System (INIS)

    Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations. We pooled data from 12 case-control studies in the Ovarian Cancer Association Consortium comprising 5,342 OC cases, 1,455 borderline tumors and 10,358 controls with quantitative information on recent alcohol intake to estimate odds ratios (OR) and 95% confidence intervals (CI) according to frequencies of average daily intakes of beer, wine, liquor and total alcohol. Total alcohol intake was not associated with all OC: consumption of >3 drinks per day compared to none, OR=0.92, 95% CI=0.76-1.10, P trend=0.27. Among beverage types, a statistically non-significant decreased risk was observed among women who consumed >8 oz/d of wine compared to none (OR=0.83, 95% CI=0.68-1.01, P trend=0.08). This association was more apparent among women with clear cell OC (OR, 0.43; 95% CI, 0.22-0.83; P trend=0.02), although based on only 10 cases and not statistically different from the other histologic types (P value for statistical heterogeneity between histologic types = 0.09). Statistical heterogeneity of the alcohol- and wine-OC associations was seen among three European studies, but not among eight North American studies. No statistically significant associations were observed in separate analyses evaluating risk with borderline tumors of serous or mucinous histology. Smoking status did not significantly modify any of the associations. We found no evidence that recent moderate alcohol drinking is associated with increased risk for overall OC, or that variation in risk is associated strongly with specific histologic types. Understanding modifiable causes of these elusive and deadly cancers remains a priority for the research community

  16. Recent alcohol consumption and risk of incident ovarian carcinoma: a pooled analysis of 5,342 cases and 10,358 controls from the Ovarian Cancer Association Consortium

    Directory of Open Access Journals (Sweden)

    Kelemen Linda E

    2013-01-01

    Full Text Available Abstract Background Studies evaluating the association between alcohol intake and ovarian carcinoma (OC are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations. Methods We pooled data from 12 case-control studies in the Ovarian Cancer Association Consortium comprising 5,342 OC cases, 1,455 borderline tumors and 10,358 controls with quantitative information on recent alcohol intake to estimate odds ratios (OR and 95% confidence intervals (CI according to frequencies of average daily intakes of beer, wine, liquor and total alcohol. Results Total alcohol intake was not associated with all OC: consumption of >3 drinks per day compared to none, OR=0.92, 95% CI=0.76-1.10, P trend=0.27. Among beverage types, a statistically non-significant decreased risk was observed among women who consumed >8 oz/d of wine compared to none (OR=0.83, 95% CI=0.68-1.01, P trend=0.08. This association was more apparent among women with clear cell OC (OR, 0.43; 95% CI, 0.22-0.83; P trend=0.02, although based on only 10 cases and not statistically different from the other histologic types (P value for statistical heterogeneity between histologic types = 0.09. Statistical heterogeneity of the alcohol- and wine-OC associations was seen among three European studies, but not among eight North American studies. No statistically significant associations were observed in separate analyses evaluating risk with borderline tumors of serous or mucinous histology. Smoking status did not significantly modify any of the associations. Conclusions We found no evidence that recent moderate alcohol drinking is associated with increased risk for overall OC, or that variation in risk is associated strongly with specific histologic types. Understanding modifiable causes of these elusive and deadly cancers remains a priority for the research community.

  17. A brief symptom index for advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Cella David

    2006-09-01

    Full Text Available Abstract Background Our objective was to test a brief, symptom index for advanced renal cell carcinoma, a disease affecting over 38,000 Americans each year and often diagnosed in late stages. Methods We conducted secondary data analyses on patient-reported outcomes of 209 metastatic renal cell carcinoma patients participating in a Phase III clinical trial. Patient-reported outcomes, obtained from the FACT-Biological Response Modifier (FACT-BRM scale, were available at baseline, 2, and 8 weeks. We analyzed data from eight FACT-BRM items previously identified by clinical experts to represent the most important symptoms of advanced renal cell carcinoma. Items comprising this index assess nausea, pain, appetite, perceived sickness, fatigue and weakness, with higher scores indicating fewer symptoms. We determined reliability and validity of the index and estimated a minimally important difference. Results The index had excellent internal reliability at all three time points (alphas ≥ 0.83. Baseline scores were able to discriminate patients across Karnofsky performance status, number of metastatic sites, and risk group categories (ps Conclusion The 8-item index of patient-reported symptoms of renal cell carcinoma appears to be a psychometrically sound measure. It is a brief, reliable, and valid measure that can easily be adapted for use in clinical trials and observational studies.

  18. Experience in immunoscintigraphy with 131I-labelled OC-125 F(ab')2 in patients with ovarian carcinoma

    International Nuclear Information System (INIS)

    In the specialized postoperative follow-up of patients with epithelial ovarian carcinoma, radioimmunoscintigraphy could usefully complete computed tomography and ultrasound results. Restrictions concerning the use of 131I labelled antibody fragments result, however, from radiation dosimetry and protection aspects: Although not more than 140 MBq of the 131I agent is administered because of the high thyroid and whole-body radiation exposure, for some days substantial excretion of 131I into urine occurs. This prevents us drastically from applying the method to the same extent as recommended in the literature. These limitations are expected to be overcome with 99mTc or 111In antibodies. (author)

  19. The co-occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome.

    Science.gov (United States)

    Durieux, Emeline; Descotes, Françoise; Mauduit, Claire; Decaussin, Myriam; Guyetant, Serge; Devouassoux-Shisheboran, Mojgan

    2016-05-01

    The DICER1 gene encodes an endoribonuclease involved in the production of mature microRNAs which regulates gene expression through several mechanisms. Carriers of germline DICER1 mutations are predisposed to a rare cancer syndrome, the DICER1 syndrome. Pleuropulmonary blastoma is the most frequent lesion seen in this syndrome. Thyroid abnormalities are also a common finding, essentially concerning multinodular goiter. However, differentiated thyroid carcinoma is infrequently seen in such pedigrees. In addition to germline DICER1 mutations, specific somatic mutations have been identified in the DICER1 RNase IIIb catalytic domain in several tumor types, including ovarian Sertoli-Leydig cell tumors. We report two cases of differentiated thyroid carcinoma associated with ovarian Sertoli-Leydig cell tumor and with a heterozygous DICER1 gene mutation, occurring in two unrelated young girls without pleuropulmonary blastoma. Both thyroid carcinomas showed an E1813 mutation in exon 25 while the ovarian tumors harboured a somatic mutation in E1705 in exon 24 and a D1709 mutation in exon 25. Our observations confirm that the occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome. We contend that the possibility of a relationship between sporadic thyroid carcinoma in young patients and somatic DICER1 gene mutation needs further investigation. PMID:26983701

  20. Cryotherapy for advanced carcinoma of the trachea and bronchi.

    OpenAIRE

    Maiwand, M O

    1986-01-01

    Cryotherapy was used to relieve symptoms in 75 patients suffering from advanced carcinoma of the trachea or bronchi. In all patients surgical resection, radiotherapy, or chemotherapy had been tried and been unsuccessful or had been thought to be unsuitable because of the patients' poor general condition. In cryotherapy the intraluminal tumour was frozen through a Stortz bronchoscope. Localised necrosis increased the patency of the lumen of the trachea or bronchi, resulting in relief of sympto...

  1. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    OpenAIRE

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic r...

  2. Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

    Directory of Open Access Journals (Sweden)

    Eichbaum Michael H

    2011-01-01

    a new promising option in the consolidation treatment of ovarian carcinoma in patients with a complete pathologic remission after adjuvant chemotherapy. Further consequent studies will be needed to enable firm conclusions regarding the value of consolidation radiotherapy within the multimodal treatment of advanced ovarian cancer. Trial registration Clinicaltrials.gov: NCT01180504

  3. Phase II study evaluating consolidation whole abdominal intensity-modulated radiotherapy (IMRT) in patients with advanced ovarian cancer stage FIGO III - The OVAR-IMRT-02 Study

    International Nuclear Information System (INIS)

    ovarian carcinoma in patients with a complete pathologic remission after adjuvant chemotherapy. Further consequent studies will be needed to enable firm conclusions regarding the value of consolidation radiotherapy within the multimodal treatment of advanced ovarian cancer. Clinicaltrials.gov: http://clinicaltrials.gov/ct2/show/NCT01180504

  4. Neoadjuvant chemotherapy and radiation therapy in advanced stage nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    To assess the feasibility and the toxicity of the neoadjuvant chemotherapy on the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. We analyzed 77 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with neoadjuvant chemotherapy followed by radiation therapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC stage 111-2, stage IV-75. Sixty-six patients received infusion of 5-FU (1000 mg/m2, on Day 1-5) and cisplatin (100 mg/m2, on Day 1), eleven patients received infusion of 5.FU (1000 mg/m2, on Day 1-5) and carboplatin (300 mg/m2, on Day 1) as neoadjuvant chemotherapy prior to radiation therapy. The median follow-up for surviving patients was 44 months. The overall chemotherapy response rates were 87%. The toxicities of chemotherapy were mild. Only 3 patients experienced Grade 3 toxicities (1 for cytopenia, 2 for nausea/vomiting). The degree of radiation induced mucositis was not severe, and ten patients developed Grade 2 mucositis. The 5-year overall survival rates were 68% and the 5-year disease free survival rates were 65%. The 5-year freedom from distant metastasis rates were 82% and 5-year locoregional control rates were 75%. This single institution experience suggests that neoadjuvant chemotherapy improves overall survival and disease free survival for patients with advanced stage nasopharyngeal carcinoma without increase of toxicity

  5. Primary Surgery or Interval Debulking for Advanced Epithelial Ovarian Cancer: Does It Matter?

    DEFF Research Database (Denmark)

    Markauskas, A.; Mogensen, O.; Christensen, R. D.;

    2014-01-01

    that NACT-IDS may be a better treatment alternative for the group of highly selected women not suitable for PDS, where expected suboptimal cytoreduction does not have any appreciable survival benefit and exposes them for unnecessary risks. A substantial number of women who receive either PDS or NACT......Objective: The aim of the present study was to investigate the surgical complexity, the postoperative morbidity, and the survival of the women after primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for advanced epithelial ovarian cancer....... Materials and Methods: We consecutively included all patients who underwent debulking surgery at our institution between January 2007 and December 2012 for stages IIIc and IV of epithelial ovarian cancer. Results: Of the 332 patients included, 165 (49.7%) underwent PDS, and 167 (50.3%) had NACT...

  6. MicroRNA-194 promotes the growth, migration, and invasion of ovarian carcinoma cells by targeting protein tyrosine phosphatase nonreceptor type 12

    Science.gov (United States)

    Liang, Tian; Li, Liru; Cheng, Yan; Ren, Chengcheng; Zhang, Guangmei

    2016-01-01

    Ovarian carcinoma is the most lethal gynecologic malignancy among women. Ovarian cancer metastasis is the main reason for poor prognosis. MicroRNAs (miRNAs) have been shown to play an important role in tumorigenesis and metastasis in various cancers by affecting the expression of their targets. In this study, we explored the role of miR-194 in ovarian cancer. Real-time polymerase chain reaction assays showed that miR-194 was significantly upregulated in ovarian cancer tissues. Overexpression of miR-194 in ovarian cancer cells promotes cell proliferation, migration, and invasion; in contrast, inhibition of the expression of miR-194 has the opposite effects. Meanwhile, bioinformatics tools were used to identify protein tyrosine phosphatase nonreceptor type 12 (PTPN12) as a potential target of miR-194. The luciferase assay showed that miR-194 directly binds to the 3′-untranslated region of PTPN12. Western blot analysis and quantitative real-time polymerase chain reaction assay revealed that PTPN12 expression was negatively associated with miR-194 expression in both ovarian cancer tissues and cells. Thus, we conclude that miR-194 targets PTPN12 and functions as an oncogene in ovarian cancer cells. This novel pathway may provide a new insight to explain ovarian cancer development and metastasis. PMID:27486333

  7. Overexpression of inhibitor of DNA-binding (ID)-1 protein related to angiogenesis in tumor advancement of ovarian cancers

    International Nuclear Information System (INIS)

    The inhibitor of DNA-binding (ID) has been involved in cell cycle regulation, apoptosis and angiogenesis. This prompted us to study ID functions in tumor advancement of ovarian cancers. Sixty patients underwent surgery for ovarian cancers. In ovarian cancers, the levels of ID-1, ID-2 and ID-3 mRNAs were determined by real-time reverse transcription-polymerase chain reaction. The histoscore with the localization of ID-1 was determined by immunohistochemistry. Patient prognosis was analyzed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD34 and factor VIII-related antigen. ID-1 histoscores and mRNA levels both significantly (p < 0.001) increased in ovarian cancers according to clinical stage, regardless of histopathological type. Furthermore, 30 patients with high ID-1 expression had a lower survival rate (53%) compared to patients with low ID-1 expression (80%). ID-1 histoscores and mRNA levels significantly (p < 0.0001) correlated with microvessel counts in ovarian cancers. ID-1 increased in ovarian cancer cells during tumor progression. Moreover, ID-1 expression levels correlated with microvessel counts. Therefore, ID-1 might work on tumor advancement via angiogenesis and is considered to be a candidate for a prognostic indicator in ovarian cancers

  8. ABERRANT PROMOTER HYPERMETHYLATION OF DEATH ASSOCIATED PROTEIN KINASE (DAPK) IN EPITHELIAL OVARIAN CARCINOMA

    OpenAIRE

    Ramesh; Shalini. N.; Sandeep Kumar; Premalata; Pallavi

    2015-01-01

    PURPOSE: The aim of the study was to assess the promoter hypermethylation status of the apoptotic gene Death Associated Protein Kinase (DAPK) in epithelial ovarian cancer and its association with various clinicopathological parameters. METHODS: 110 epithelial ovarian cancers samples were assessed to study the hypermethylation by nested and Methylatio...

  9. Burkitt’s Lymphoma Presented as Advanced Ovarian Cancer without Evidence of Lymphadenopathy: CT and MRI Findings

    OpenAIRE

    Lucia Manganaro; Silvia Bernardo; Maria Eleonora Sergi; Paolo Sollazzo; Valeria Vinci; Alessandra De Grazia; Anna Clerico; Maria Giovanna Mollace; Matteo Saldari

    2013-01-01

    Burkitt's lymphoma is a rare non-Hodgkin's lymphoma which can occasionally involve the ovary and may cause confusion for the clinician since its presentation might mimic other much more frequent tumors. We present a case of a 23-year-old woman with sporadic Burkitt’s lymphoma presented as advanced ovarian cancer with bilateral ovarian masses, peritoneal carcinomatosis, ascites, and marked elevation of CA-125. Liver involvement and atypical bone lesions, such as the cranial vault and the ili...

  10. Psychological Distress during Ovarian Cancer Treatment: Improving Quality by Examining Patient Problems and Advanced Practice Nursing Interventions

    OpenAIRE

    Cynthia Kline O'Sullivan; Bowles, Kathryn H.; Sangchoon Jeon; Elizabeth Ercolano; Ruth McCorkle

    2011-01-01

    Background/Significance. Ovarian cancer patients are prone to psychological distress. The clinical significance and best practices for distress among this population are poorly understood. Method. Secondary analysis of research records from a six month randomized control trial included 32 women with primary ovarian cancer. All received 18 advanced practice nurse (APN) visits over six months. Three sub-samples were determined by distress level (high/low) and mental health service consent for h...

  11. Synchronous ovarian and endometrial carcinomas in a patient with Rubinstein-Taybi syndrome: a case report and literature review.

    Science.gov (United States)

    Johannesen, Eric J; Williams, Todd; Miller, Douglas C; Tuller, Erin

    2015-03-01

    Rubinstein-Taybi syndrome is characterized by distinctive facial and limb features and is associated with several types of tumors. A 29-yr-old woman with this syndrome presented with a large, complex ovarian mass. She was subsequently diagnosed with a low-grade serous carcinoma of the ovary and an endometrioid adenocarcinoma of the uterus. Rubinstein-Taybi syndrome is an autosomal dominant, multiple congenital anomalies-mental retardation syndrome. Two genes, CREBBP and EP300, have been found to be associated with this disorder, although some cases do not have an identifiable cause. These genes code for proteins that acetylate histone tails, an epigenetic modification that serves to control transcription. They also serve as cofactors to several transcription factors and modulate p53. Although these patients have a predisposition to benign and malignant neoplasms, no malignant gynecologic neoplasm has been described thus far. Although no significant evidence linking CREBBP and EP300 to gynecologic malignancies has yet been found, some studies have suggested that hypoacetylation of histones may be involved in endometrial and ovarian carcinomas. PMID:25675181

  12. Overexpression of Elafin in Ovarian Carcinoma Is Driven by Genomic Gains and Activation of the Nuclear Factor κB Pathway and Is Associated with Poor Overall Survival

    Directory of Open Access Journals (Sweden)

    Adam Clauss

    2010-02-01

    Full Text Available Ovarian cancer is a leading cause of cancer mortality in women. The aim of this study was to elucidate whether whey acidic protein (WAP genes on chromosome 20q13.12, a region frequently amplified in this cancer, are expressed in serous carcinoma, the most common form of the disease. Herein, we report that a trio of WAP genes (HE4, SLPI, and Elafin is overexpressed and secreted by serous ovarian carcinomas. To our knowledge, this is the first report linking Elafin to ovarian cancer. Fluorescence in situ hybridization analysis of primary tumors demonstrates genomic gains of the Elafin locus in a majority of cases. In addition, a combination of peptidomimetics, RNA interference, and chromatin immunoprecipitation experiments shows that Elafin expression can be transcriptionally upregulated by inflammatory cytokines through activation of the nuclear factor κB pathway. Importantly, using a clinically annotated tissue microarray composed of late-stage, high-grade serous ovarian carcinomas, we show that Elafin expression correlates with poor overall survival. These results, combined with our observation that Elafin is secreted by ovarian tumors and is minimally expressed in normal tissues, suggest that Elafin may serve as a determinant of poor survival in this disease.

  13. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial: a multicentre randomized controlled study

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    Rutten Marianne J

    2012-01-01

    Full Text Available Abstract Background Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant chemotherapy (NACT in combination with interval debulking surgery (IDS is performed. Current methods of staging are not always accurate in predicting surgical outcome, since approximately 40% of patients will have more than 1 cm residual tumour after primary debulking surgery (PDS. In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer. Methods Multicentre randomized controlled trial, including all gynaecologic oncologic centres in the Netherlands and their affiliated hospitals. Patients are eligible when they are planned for PDS after conventional staging. Participants are randomized between direct PDS or additional diagnostic laparoscopy. Depending on the result of laparoscopy patients are treated by PDS within three weeks, followed by six courses of platinum based chemotherapy or with NACT and IDS 3-4 weeks after three courses of chemotherapy, followed by another three courses of chemotherapy. Primary outcome measure is the proportion of PDS's leaving more than one centimetre tumour residual in each arm. In total 200 patients will be randomized. Data will be analysed according to intention to treat. Discussion Patients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis. However, there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high. Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool

  14. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

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    Behl Susanne

    2008-03-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

  15. Patients with ovarian carcinoma excrete different altered levels of urine CD59, kininogen-1 and fragments of inter-alpha-trypsin inhibitor heavy chain H4 and albumin

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    Hashim Onn H

    2010-11-01

    Full Text Available Abstract Background Diagnosis of ovarian carcinoma is in urgent need for new complementary biomarkers for early stage detection. Proteins that are aberrantly excreted in the urine of cancer patients are excellent biomarker candidates for development of new noninvasive protocol for early diagnosis and screening purposes. In the present study, urine samples from patients with ovarian carcinoma were analysed by two-dimensional gel electrophoresis and the profiles generated were compared to those similarly obtained from age-matched cancer negative women. Results Significant reduced levels of CD59, kininogen-1 and a 39 kDa fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4, and enhanced excretion of a 19 kDa fragment of albumin, were detected in the urine of patients with ovarian carcinoma compared to the control subjects. The different altered levels of the proteins were confirmed by Western blotting using antisera and a lectin that bind to the respective proteins. Conclusion CD59, kininogen-1 and fragments of ITIH4 and albumin may be used as complementary biomarkers in the development of new noninvasive protocols for diagnosis and screening of ovarian carcinoma.

  16. Correction of coagulopathy associated with non-bacterial thrombotic endocarditis (NBTE) by surgical debulking in a case of ovarian clear cell carcinoma.

    Science.gov (United States)

    Albright, Benjamin B; Black, Jonathan D; Vilardo, Nicole; Schwartz, Peter E

    2016-08-01

    Ovarian cancer, particularly clear cell carcinoma, creates a hypercoagulable state.•This state can predispose to non-bacterial thrombotic endocarditis (NBTE).•NBTE can embolize and cause widespread arterial infarction.•NBTE is sometimes associated with a treatment refractory disseminated coagulopathy.•Surgical removal of the primary mass can sometimes reverse the coagulopathy. PMID:27354993

  17. Outcomes of advanced epithelial ovarian cancer with integration of metronomic chemotherapy: An Indian rural cancer centre experience

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    Avinash Pandey

    2016-01-01

    Full Text Available Background: Paclitaxel-platinum and optimal cytoreductive surgery are the standard of care for ovarian carcinoma. Poor socioeconomic profile and therapeutic constraints in rural India poses a therapeutic challenge. Aim: To evaluate outcomes of epithelial ovarian carcinoma. Objectives: To calculate disease-free survival (DFS, overall survival (OS, and factors affecting outcomes. Materials and Methods: Data of patients diagnosed as ovarian carcinoma registered between March 2009 and March 2014 were retrieved. Demographic profile, chemotherapy and response, surgery, and disease progression were collected. Patients who underwent surgery or completed three cycles of chemotherapy were selected. Kaplan-Meir survival was used to determine disease-free and OS. Log-rank test used to evaluate factors affecting outcome. Results: Median follow-up is 26 months. 93/102 patients (91% underwent cytoreductive surgery, of which 37 had primary cytoreduction (40% while 56 had interval cytoreduction. 21/93 (23%, 57/93 (61%, and 15/93 (16% patients were operated by local surgeons, surgeons of our hospital, and trained oncosurgeons, respectively. Induction paclitaxel-platinum was used in 35/63 (56% patients while 28/63 patients (44% received neoadjuvant metronomic chemotherapy. Median DFS and OS are 17 and 54 months respectively while 3 year OS of 66%. Median DFS of patients operated by oncosurgeons versus local surgeons were 22 months versus 15 months (P = 0.01, OS was 54 versus 26 months (P = 0.01.40/88 (45% patients received maintenance metronomic therapy after adjuvant chemotherapy with median of 6 months (range 2-18 months. Patients receiving metronomic maintenance had better DFS, 18 months versus 15 months (P = 0.69. Conclusion: Induction therapy in ovarian carcinoma helps in selecting patients for cytoreductive surgery. Outcomes are better if operated by trained oncosurgeons. Maintenance metronomic has potential to delay disease progression.

  18. A genomic and transcriptomic approach for a differential diagnosis between primary and secondary ovarian carcinomas in patients with a previous history of breast cancer

    International Nuclear Information System (INIS)

    The distinction between primary and secondary ovarian tumors may be challenging for pathologists. The purpose of the present work was to develop genomic and transcriptomic tools to further refine the pathological diagnosis of ovarian tumors after a previous history of breast cancer. Sixteen paired breast-ovary tumors from patients with a former diagnosis of breast cancer were collected. The genomic profiles of paired tumors were analyzed using the Affymetrix GeneChip® Mapping 50 K Xba Array or Genome-Wide Human SNP Array 6.0 (for one pair), and the data were normalized with ITALICS (ITerative and Alternative normaLIzation and Copy number calling for affymetrix Snp arrays) algorithm or Partek Genomic Suite, respectively. The transcriptome of paired samples was analyzed using Affymetrix GeneChip® Human Genome U133 Plus 2.0 Arrays, and the data were normalized with gc-Robust Multi-array Average (gcRMA) algorithm. A hierarchical clustering of these samples was performed, combined with a dataset of well-identified primary and secondary ovarian tumors. In 12 of the 16 paired tumors analyzed, the comparison of genomic profiles confirmed the pathological diagnosis of primary ovarian tumor (n = 5) or metastasis of breast cancer (n = 7). Among four cases with uncertain pathological diagnosis, genomic profiles were clearly distinct between the ovarian and breast tumors in two pairs, thus indicating primary ovarian carcinomas, and showed common patterns in the two others, indicating metastases from breast cancer. In all pairs, the result of the transcriptomic analysis was concordant with that of the genomic analysis. In patients with ovarian carcinoma and a previous history of breast cancer, SNP array analysis can be used to distinguish primary and secondary ovarian tumors. Transcriptomic analysis may be used when primary breast tissue specimen is not available

  19. Bilateral ovarian metastasis from distal common bile duct carcinoma developing after choledochal cyst excision

    OpenAIRE

    Lee, Seung Eun; Choi, Yoo Shin; Kim, Mi Kyung; Oh, Hyoung-Chul; Do, Jae Hyuk

    2015-01-01

    Ovarian metastases represent about 3-5% of all ovarian malignancies. Most of these tumors originate in the digestive tract and cholangiocarcinoma rarely involves the ovary. A 60-year-old woman was admitted for the investigation of abdominal distension that had lasted 1 week. One and a half years prior, the patient had undergone choledochal cyst excision, Roux-en Y hepaticojejunostomy and cholecystectomy. Computed tomography scans of the abdomen revealed a papillary mass in the remnant distal ...

  20. Social Isolation is associated with Elevated Tumor Norepinephrine in Ovarian Carcinoma Patients

    OpenAIRE

    Lutgendorf, Susan K.; DeGeest, Koen; Dahmoush, Laila; Farley, Donna; Penedo, Frank; Bender, David; Goodheart, Michael; Buekers, Thomas E.; Mendez, Luis; Krueger, Gina; Clevenger, Lauren; Lubaroff, David M.; Sood, Anil K.; Cole, Steve W.

    2010-01-01

    Noradrenergic pathways have been implicated in growth and progression of ovarian cancer. Intratumoral norepinephrine (NE) has been shown to increase with stress in an animal cancer model, but little is known regarding how tumor NE varies with disease stage and with biobehavioral factors in ovarian cancer patients. This study examined relationships between pre-surgical measures of social support, depressed mood, perceived stress, anxiety, tumor histology and tumor catecholamine (NE and epineph...

  1. Genetic Polymorphisms in the Paraoxonase 1 Gene and Risk of Ovarian Epithelial Carcinoma

    OpenAIRE

    Lurie, Galina; Wilkens, Lynne R.; Pamela J Thompson; McDuffie, Katharine E.; Carney, Michael E; Terada, Keith Y.; Goodman, Marc T.

    2008-01-01

    Oxidative stress during successive ovulations increases the opportunity for DNA damage to ovarian epithelial cells and the potential for malignant transformation. Paraoxonase 1 (PON1) is an endogenous free radical scavenger that reduces oxidative stress. The association of two common functional single nucleotide polymorphisms (SNP), rs854560 T>A and rs662 A>G, with the risk of epithelial ovarian cancer was examined in a population-based case-control study in Hawaii. A personal interview and b...

  2. Outcome in Advanced Ovarian Cancer following an Appropriate and Comprehensive Effort at Upfront Cytoreduction: A Twenty-Year Experience in a Single Cancer Institute

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    Anne Marszalek

    2010-01-01

    Full Text Available Objectives. The purpose of this retrospective evaluation of advanced-stage ovarian cancer patients was to compare outcome with published findings from other centers and to discuss future options for the management of advanced ovarian carcinoma patients. Methods. A retrospective series of 340 patients with a mean age of 58 years (range: 17–88 treated for FIGO stage III and IV ovarian cancer between January 1985 and January 2005 was reviewed. All patients had primary cytoreductive surgery, without extensive bowel, peritoneal, or systematic lymph node resection, thereby allowing initiation of chemotherapy without delay. Chemotherapy consisted of cisplatin-based chemotherapy in combination with alkylating agents before 2000, whereas carboplatin and paclitaxel regimes were generally used after 1999-2000. Overall survival and disease-free survival were analyzed by the Kaplan-Meier method and the log-rank test. Results. With a mean followup of 101 months (range: 5 to 203, 280 events (recurrence or death were observed and 245 patients (72% had died. The mortality and morbidity related to surgery were low. The main prognostic factor for overall survival was postoperative residual disease (P<.0002, while the main prognostic factor for disease-free survival was histological tumor type (P<.0007. Multivariate analysis identified three significant risk factors: optimal surgery (RR=2.2 for suboptimal surgery, menopausal status (RR=1.47 for postmenopausal women, and presence of a taxane in the chemotherapy combination (RR=0.72. Conclusion. These results confirm that optimal surgery defined by an appropriate and comprehensive effort at upfront cytoreduction limits morbidity related to the surgical procedure and allows initiation of chemotherapy without any negative impact on survival. The impact of neoadjuvant chemotherapy to improve resectability while lowering the morbidity of the surgical procedure is discussed.

  3. Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

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    Lamont Alan

    2003-07-01

    Full Text Available Abstract Background We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. Methods From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse Results The overall response rate was 59% (33/56 per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS was 6.6 months per course of chemotherapy; median overall survival (OAS for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9–12.8 months. Conclusion The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centres.

  4. Concomitant chemo radiation in the treatment of advanced cervical carcinoma

    International Nuclear Information System (INIS)

    The study results of non randomized radio chemotherapy in the cervix cancer treatment are cheering and clinically the answers are faster. However only some randomized studies using hydroxyurea showed a benefit in survival term. The association tolerance of 5 FU with cisplatin is generally acceptable but we don't know yet the long-range toxicity. Finally we'll have to determine in which quantity, the pelvis control improvement should be able to increase the survival rate, because the metastases are frequent in these carcinoma advanced forms. 59 refs., 2 tabs

  5. Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?

    Science.gov (United States)

    Vidal, Fabien; Guerby, Paul; Luyckx, Mathieu; Haddad, Pascale; Stoeckle, Eberhard; Morice, Philippe; Leblanc, Eric; Lecuru, Fabrice; Daraï, Emile; Classe, Jean Marc; Pomel, Christophe; Filleron, Thomas; Ferron, Gwenael; Querleu, Denis; Rafii, Arash

    2016-01-01

    Objective Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients. Study Design We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. Results The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758, p = 0.017 and HR = 8.641, p = 0.001 respectively). The relative risk of death within 12 months following relapse in ER patients was 1.61 according to RD status. However, RD did not affect DFS (HR = 0.889, p = 0.5). Conclusion ER in advanced-stage ovarian cancer does not inevitably portend a short-term poor prognosis. RD status after initial cytoreduction strongly modulates OS, that gives additional support to the concept of maximum surgical effort even in patients who will experience early recurrence. The heterogeneity in outcomes within the ER group suggests a role for tumor biology in addition to classical clinical parameters. PMID:26820579

  6. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    International Nuclear Information System (INIS)

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer

  7. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    Energy Technology Data Exchange (ETDEWEB)

    Nishikawa, Hiroki, E-mail: h-nishikawa@osaka-med.jrc.or.jp; Osaki, Yukio; Kita, Ryuichi; Kimura, Toru [Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027 (Japan)

    2012-02-21

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  8. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    Directory of Open Access Journals (Sweden)

    Ryuichi Kita

    2012-02-01

    Full Text Available Transcatheter methods such as transcatheter arterial chemoembolization (TACE and hepatic arterial infusion chemotherapy (HAIC have an important role in the treatment for advanced hepatocellular carcinoma (HCC. Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  9. Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway

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    Cong Jianping

    2009-12-01

    Full Text Available Abstract Background Lewis y antigen is difucosylated oligosaccharide and is carried by glycoconjugates at cell surface. Elevated expression of Lewis y has been found in 75% of ovarian tumor, and the high expression level is correlated to the tumor's pathological staging and prognosis. This study was to investigate the effect and the possible mechanism of Lewis y on the proliferation of human ovarian cancer cells. Methods We constructed a plasmid encoding α1,2-fucosyltransferase (α1,2-FT gene and then transfected it into ovarian carcinoma-derived RMG-I cells with lowest Lewis y antigen expression level. Effect of Lewis y on cell proliferation was assessed after transfection. Changes in cell survival and signal transduction were evaluated after α-L-fucosidase, anti-Lewis y antibody and phosphatidylinositol 3-kinase (PI3K inhibitor treatment. Results Our results showed that the levels of α1,2-FT gene and Lewis y increased significantly after transfection. The cell proliferation of ovarian carcinoma-derived RMG-I cells sped up as the Lewis y antigen was increased. Both of α-L-fucosidase and anti-Lewis y antibody inhibited the cell proliferation. The phosphorylation level of Akt was apparently elevated in Lewis y-overexpressing cells and the inhibitor of PI3K, LY294002, dramatically inhibited the growth of Lewis y-overexpressing cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of α1,2-FT were attenuated significantly by the monoantibody to Lewis y and by the PI3K inhibitor LY294002. Conclusions Increased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. Inhibition of Lewis y expression may provide a new therapeutic approach for Lewis y positive ovarian cancer.

  10. Platinum Sensitivity as an Independent Prognostic Factor in Patients with Brain Metastases from Ovarian Carcinoma

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    John Windara Green

    2011-10-01

    Full Text Available Background: The brain is a rare site of metastases from ovarian cancer. Limited data are available on prognostic factors, standard treatment, and survival. Knowledge of clinical prognostic factors would help the management of patients with brain metastases. The aim of this study is to evaluate the impact of clinical factors and treatment modalities on survival in patients with brain metastases from ovarian cancer. Methods: We performed a retrospective analysis of an electronic database of patients with brain metastases from ovarian primary treated at Clatterbridge Centre for Oncology. Results: A total of 20 patients with brain metastases from an ovarian primary were treated from April 2001-February 2011. Median age at occurrence of brain metastases was 55 years. The median time from primary diagnosis to occurrence of brain metastases was 23 months. Median overall survival from diagnosis of brain metastases was 9 months. Poor ECOG performance status, platinum resistance, andadvanced FIGO staging were the most significant adverse variables identified. Median survival was 13 months for platinum sensitive patients and 6 months for platinum resistant patients. Conclusion: Platinum sensitivity is an important prognostic factor in patients with brain metastases from an ovarian primary tumor. Multimodal therapy that consists of surgery, radiotherapy, and chemotherapy should be considered where feasible.

  11. Temsirolimus, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Tumors

    Science.gov (United States)

    2014-06-18

    Ovarian Sarcoma; Ovarian Stromal Cancer; Recurrent Endometrial Carcinoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Unspecified Adult Solid Tumor, Protocol Specific

  12. Different altered stage correlative expression of high abundance acute-phase proteins in sera of patients with epithelial ovarian carcinoma

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    Lim Boon-Kiong

    2009-08-01

    Full Text Available Abstract Background The general enhanced expression of α1-antichymotrypsin (ACT, clusterin (CLU, α1-antitrypsin (AAT, haptoglobin β-chain (HAP, and leucine rich glycoprotein (LRG in the sera of patients with epithelial ovarian carcinoma (EOCa was recently reported. In the present study, we compared the expression of the serum acute-phase proteins (APPs in the patients according to their stages of cancer. Results Different altered stage correlative expression of the high abundance serum APPs was demonstrated in sera of the patients studied. While the expression of ACT, HAP and AAT appeared to demonstrate positive correlation with the three initial stages of the cancer, inverse correlation was apparently detected in the expression of LRG and CLU. For patients who were diagnosed with stage IV of the cancer, expression of the serum APPs did not conform to the altered progression changes. Conclusion Our results highlight the potential prognostic significance of selective high abundance serum APPs in patients with EOCa.

  13. Consortium analysis of gene and gene–folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Terry, Kathryn L; Goodman, Marc T;

    2014-01-01

    SCOPE: We reevaluated previously reported associations between variants in pathways of one-carbon (1-C) (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. METHODS AND RESULTS: Odds......11587873 (OR = 0.92; p = 6 × 10(-5)) and rs828054 (OR = 1.06; p = 1 × 10(-4)). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 × 10(-6)) but collectively explained only 0.2% of OC risk....... Although no other associations were significant after multiple testing correction, variants in SHMT1 in 1-C transfer, previously reported with OC, suggested lower risk at higher folate (p(interaction) = 0.03-0.006). CONCLUSION: Variation in pyrimidine metabolism genes, particularly DPYD, which...

  14. Preclinical Evaluation on the Tumor Suppression Efficiency and Combination Drug Effects of Fermented Wheat Germ Extract in Human Ovarian Carcinoma Cells

    OpenAIRE

    Chia-Woei Wang; Chien-Kai Wang; Yu-Jia Chang; Chen-Yen Choong; Chi-Shian Lin; Cheng-Jeng Tai; Chen-Jei Tai

    2015-01-01

    Fermented wheat germ extract (FWGE) is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s) to be 643.76 μg/mL and 246.11 μg/mL after 48 h of FWGE treatment. FWGE treatment also induced program...

  15. DNA damage induced by cis- and carboplatin as indicator for in vitro sensitivity of ovarian carcinoma cells

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    de Wilde Rudy L

    2009-10-01

    Full Text Available Abstract Background The DNA damage by platinum cytostatics is thought to be the main cause of their cytotoxicity. Therefore the measurement of the DNA damage induced by cis- and carboplatin should reflect the sensitivity of cancer cells toward the platinum chemotherapeutics. Methods DNA damage induced by cis- and carboplatin in primary cells of ovarian carcinomas was determined by the alkaline comet assay. In parallel, the reduction of cell viability was measured by the fluorescein diacetate (FDA hydrolysis assay. Results While in the comet assay the isolated cells showed a high degree of DNA damage after a 24 h treatment, cell viability revealed no cytotoxicity after that incubation time. The individual sensitivities to DNA damage of 12 tumour biopsies differed up to a factor of about 3. DNA damage after a one day treatment with cis- or carboplatin correlated well with the cytotoxic effects after a 7 day treatment (r = 0,942 for cisplatin r = 0.971 for carboplatin. In contrast to the platinum compounds the correlation of DNA damage and cytotoxicity induced by adriamycin was low (r = 0,692, or did not exist for gemcitabine. Conclusion The measurement of DNA damage induced by cis- and carboplatin is an accurate method to determine the in vitro chemosensitivity of ovarian cancer cells towards these cytostatics, because of its quickness, sensitivity, and low cell number needed.

  16. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    Science.gov (United States)

    Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

    2016-05-13

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. PMID:27091429

  17. Prevalence of Helicobacter pylori infection in advanced gastric carcinoma

    Directory of Open Access Journals (Sweden)

    Irami Araújo-Filho

    2006-12-01

    Full Text Available BACKGROUD: There is substantial evidence that infection with Helicobacter pylori plays a role in the development of gastric cancer and that it is rarely found in gastric biopsy of atrophic gastritis and gastric cancer. On advanced gastric tumors, the bacteria can be lost from the stomach. AIMS: To analyze the hypothesis that the prevalence of H.pylori in operated advanced gastric carcinomas and adjacent non-tumor tissues is high, comparing intestinal and diffuse tumors according to Lauren's classification METHODS: A prospective controlled study enrolled 56 patients from "Hospital Universitário", Federal University of Rio Grande do Norte, Natal, RN, Brazil, with advanced gastric cancer, treated from February 2000 to March 2003. Immediately after partial gastrectomy, the resected stomach was opened and several mucosal biopsy samples were taken from the gastric tumor and from the adjacent mucosa within 4 cm distance from the tumor margin. Tissue sections were stained with hematoxylin and eosin. Lauren's classification for gastric cancer was used, to analyse the prevalence of H. pylori in intestinal or diffuse carcinomas assessed by the urease rapid test, IgG by ELISA and Giemsa staining. H. pylori infected patients were treated with omeprazole, clarithromycin and amoxicillin for 7 days. Follow-up endoscopy and serology were performed 6 months after treatment to determine successful eradication of H. pylori in non-tumor tissue. Thereafter, follow-up endoscopies were scheduled annually. Chi-square and MacNemar tests with 0.05 significance were used. RESULTS: Thirty-four tumors (60.7% were intestinal-type and 22 (39.3% diffuse type carcinomas. In adjacent non-tumor gastric mucosa, chronic gastritis were found in 53 cases (94.6% and atrophic mucosa in 36 patients (64.3%. All the patients with atrophic mucosa were H. pylori positive. When examined by Giemsa and urease test, H. pylori positive rate in tumor tissue of intestinal type carcinomas was

  18. Prognostic significance of specific anti-WT1 IgG antibody level in plasma in patients with ovarian carcinoma

    International Nuclear Information System (INIS)

    Ovarian carcinoma (OC) has a poor prognosis and lack early effective screening markers. Wilm's tumor gene 1 (WT1) is overexpressed in OCs. Therefore, it is of great interest to investigate whether WT1-specific antibody (Ab) measurements in plasma can serve as a biomarker of anti-OC response, and is of importance in relation to patient prognosis. Peripheral blood samples were obtained from a total of 103 women with ovarian tumors with median being 1 day (range 0–48 days) before operation. WT1 IgG Ab levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Immunohistochemical analysis of WT1 protein expression was performed on OC tissue samples. We found that low-WT1 Ab level in plasma was related to improved survival in patients diagnosed at stages III–IV and grade 3 carcinomas. Positive WT1 protein staining on OC tissue samples had a negative impact on survival in the entire cohort, both overall survival (OS) (P = 0.046) and progression-free survival (PFS) (P = 0.006), but not in the serous OC subtype. Combining WT1 IgG Ab levels and WT1 staining, patients with high-WT1 IgG Ab levels in plasma and positive WT1 protein staining in cancer tissues had shorter survival, with a significant association in PFS (P = 0.016). These results indicated that WT1 Ab measurements in plasma and WT1 staining in tissue specimens could be useful as biomarkers for patient outcome in the high-risk subtypes of OCs for postoperative individualized therapy

  19. The effects of selenium on tumor growth in epithelial ovarian carcinoma

    OpenAIRE

    Park, Jin Sun; Ryu, Ji Yoon; Jeon, Hye-Kyung; Cho, Young Jae; Park, Young Ae; Choi, Jung-Joo; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

    2012-01-01

    Objective Epidemiological studies suggest that selenium protects against the development of several cancers. Selenium (sodium selenite) has been reported to interfere with cell growth and proliferation, and to induce cell death. In this study, we tested whether selenium could have growth-inhibiting effect in ovarian cancer cells and an orthotopic animal model. Methods Cell growth in selenium-treated cells was determined in human ovarian cancer cells, A2780, HeyA8, and SKOV3ip1 using 3-(4,5-di...

  20. ESRRA-C11orf20 Is a Recurrent Gene Fusion in Serous Ovarian Carcinoma

    OpenAIRE

    Salzman, Julia; Marinelli, Robert J.; Wang, Peter L.; Green, Ann E.; Julie S Nielsen; Nelson, Brad H; Drescher, Charles W.; Brown, Patrick O.

    2011-01-01

    Every year, ovarian cancer kills approximately 14,000 women in the United States and more than 140,000 women worldwide. Most of these deaths are caused by tumors of the serous histological type, which is rarely diagnosed before it has disseminated. By deep paired-end sequencing of mRNA from serous ovarian cancers, followed by deep sequencing of the corresponding genomic region, we identified a recurrent fusion transcript. The fusion transcript joins the 5′ exons of ESRRA, encoding a ligand-in...

  1. Inhibition of RUNX2 transcriptional activity blocks the proliferation, migration and invasion of epithelial ovarian carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Zhi-Qiang Wang

    Full Text Available Previously, we have identified the RUNX2 gene as hypomethylated and overexpressed in post-chemotherapy (CT primary cultures derived from serous epithelial ovarian cancer (EOC patients, when compared to primary cultures derived from matched primary (prior to CT tumors. However, we found no differences in the RUNX2 methylation in primary EOC tumors and EOC omental metastases, suggesting that DNA methylation-based epigenetic mechanisms have no impact on RUNX2 expression in advanced (metastatic stage of the disease. Moreover, RUNX2 displayed significantly higher expression not only in metastatic tissue, but also in high-grade primary tumors and even in low malignant potential tumors. Knockdown of the RUNX2 expression in EOC cells led to a sharp decrease of cell proliferation and significantly inhibited EOC cell migration and invasion. Gene expression profiling and consecutive network and pathway analyses confirmed these findings, as various genes and pathways known previously to be implicated in ovarian tumorigenesis, including EOC tumor invasion and metastasis, were found to be downregulated upon RUNX2 suppression, while a number of pro-apoptotic genes and some EOC tumor suppressor genes were induced. Taken together, our data are indicative for a strong oncogenic potential of the RUNX2 gene in serous EOC progression and suggest that RUNX2 might be a novel EOC therapeutic target. Further studies are needed to more completely elucidate the functional implications of RUNX2 and other members of the RUNX gene family in ovarian tumorigenesis.

  2. Analysis of HLA class I-II haplotype frequency and segregation in a cohort of patients with advanced stage ovarian cancer.

    Science.gov (United States)

    Gamzatova, Z; Villabona, L; van der Zanden, H; Haasnoot, G W; Andersson, E; Kiessling, R; Seliger, B; Kanter, L; Dalianis, T; Bergfeldt, K; Masucci, G V

    2007-09-01

    In solid tumors, human leucocyte antigen (HLA)-A2 has been suggested to be a risk factor and a negative prognostic factor. The HLA-A2 allele in Scandinavia has a high prevalence; it decreases with latitude and also with ovarian cancer mortality in Europe. Furthermore, an association of the HLA-A2 allele with severe prognosis in serous adenocarcinoma of the ovary in stages III-IV was found. Thirty-two unrelated Swedish women with relapsing or progressive ovarian cancer were analysed for the genotypes at the HLA-A, HLA-B, HLA-Cw, and HLA-DRB1 loci by the polymerase chain reaction/sequence-specific primer method. The frequencies of HLA alleles of healthy Swedish bone marrow donors provided by the coordinating centre of the Bone Marrow Donors Worldwide Registries, Leiden, the Netherlands were used as controls. When this cohort of epithelial ovarian cancer patients was compared with healthy Swedish donors, the frequency of HLA-A1 and HLA-A2 gene/phenotype appears, although not statistically significant, to be increased in patients with ovarian carcinoma, while HLA-A3 was decreased. HLA-A2 homozygotes were twofold higher in patients. The A2-B8 haplotype was significantly increased (corrected P value). A2-B5, A2-B15, A2-DRB1*03, A2-DRB1*04, A2-B15-Cw3, and A2-B8-DRB1*03 had odds ratio as well as the level of the lower confidence interval above 1 and significant P value only when considered as single, non-corrected analysis. HLA-B15 and HLA-Cw3 were only present in HLA-A2-positive patients showing that the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes were segregated. In this selected cohort with advanced disease, there are indications of an unusual overrepresentation of HLA class I and II genes/haplotypes as well as segregation for the HLA-A2-HLA-Cw3 and HLA-B15 haplotypes. These findings are presented as a descriptive analysis and need further investigations on a larger series of ovarian cancer patients to establish prognostic associations. PMID:17661908

  3. Temsirolimus in the treatment of advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Bernard J. Escudier

    2011-12-01

    Full Text Available Temsirolimus is a novel inhibitor of mammalian target of rapamycin (mTOR, which is a central regulator of the response of tumour cells to growth and survival signals. When heavily pretreated patients with advanced solid tumours received intravenous (IV temsirolimus over a broad dose range, antitumour activity was observed in various tumour types, including advanced renal cell carcinoma (RCC. A study of singleagent temsirolimus in patients with cytokine-refractory metastatic RCC subsequently demonstrated antitumour activity and encouraging progression- free survival and overall survival. Temsirolimus was generally well tolerated over the 3 dose levels tested (25 mg, 75 mg or 250 mg weekly as a 30-minute IV infusion. The most frequent grade 3 or 4 treatment-related adverse events reported (n=110 were hyperglycemia (17%, hypophosphatemia (13%, anemia (9%, and hypertriglyceridemia (6%. Results from a randomized phase III study that enrolled previously untreated patients with advanced RCC and poor-prognostic features have recently demonstrated a significant increase in overall survival (p=0.0089 for patients who received temsirolimus 25 mg IV, 30-minute infusion once weekly compared with those who received interferon-alpha up to 18 million units subcutaneously thrice weekly. On the basis of improved survival, temsirolimus can be considered a first-line treatment for patients with advanced RCC.

  4. Primary peritoneal serous papillary carcinoma: a study of 25 cases and comparison with stage III-IV ovarian papillary serous carcinoma.

    Science.gov (United States)

    Ben-Baruch, G; Sivan, E; Moran, O; Rizel, S; Menczer, J; Seidman, D S

    1996-03-01

    The clinical characteristics and treatment outcome of patients with primary peritoneal serous papillary carcinoma (PPSC) (n = 22) was compared with stage III-IV papillary serous ovarian carcinoma (PSOC) patients (n = 63). There were no statistically significant differences between the PPSC and PSOC patients with regard to the mean age, menopausal status, parity, ascites fluid volume, proportion of stage IV disease, and the rate of optimal debulking achieved. The median disease-free interval was 15 and 18 months; the median survival was 21 and 26 months; and the 5-year survival was 18 and 24% for the PPSC and PSOC groups, respectively. The median survival time for patients with a residual tumor > or = 2 cm was 20.5 and 24 months, and for residual tumor > or = 2 cm was 46 and 41 months, in PPSC and PSOC patients, respectively. Survival was thus better, in both groups, when residual disease at the end of the operation was PSOC (P PSOC patients. Combining optimal debulking with a platinum-based chemotherapy may offer the patient the most effective treatment. PMID:8774644

  5. Ovarian cancer

    International Nuclear Information System (INIS)

    The radiosensitivity of 4 human ovarian cancer cell lines was investigated in vitro by a clonogenic assay and analyzed using the linear-quadratric model. 2 Cell lines were found to be highly radiosensitive (mean inactivation dose (D-bar) 0.82-0.92 Gy; surviving fraction 2 Gy (SF2)2 0.22-0.38). Although the use of external radiotherapy in ovarian cancer has been limited due to the pattern of metastatic spread of this cancer, the present data support the view that ovarian carcinomas are radiosensitive tumors. Investigations on the effects of new approaches, such as delivering radiation more specifically to intraperitoneal ovarian cancer cells, are warranted. (author). 24 refs.; 4 figs.; 2 tabs

  6. Bilateral ovarian metastasis from distal common bile duct carcinoma developing after choledochal cyst excision.

    Science.gov (United States)

    Lee, Seung Eun; Choi, Yoo Shin; Kim, Mi Kyung; Oh, Hyoung-Chul; Do, Jae Hyuk

    2015-05-01

    Ovarian metastases represent about 3-5% of all ovarian malignancies. Most of these tumors originate in the digestive tract and cholangiocarcinoma rarely involves the ovary. A 60-year-old woman was admitted for the investigation of abdominal distension that had lasted 1 week. One and a half years prior, the patient had undergone choledochal cyst excision, Roux-en Y hepaticojejunostomy and cholecystectomy. Computed tomography scans of the abdomen revealed a papillary mass in the remnant distal common bile duct and enlargement of both ovaries with a huge amount of ascites. An explorative laparotomy disclosed no peritoneal seeding with resectable cholangiocarcinoma and bilateral ovarian mass. Pylorus-preserving pancreatoduodenectomy and bilateral salphingo-oophorectomy with hysterectomy were performed. Histologically, it was a well-differentiated adenocarcinoma and all surgical margins were free of tumor. Both ovarian masses were consistent with metastatic adenocarcinoma from the common bile duct. The patient received six cycles of postoperative adjuvant systemic chemotherapy, dying after 10 months due to pulmonary embolism. PMID:26155281

  7. Vaccine Therapy in Treating Patients With Stage IIIC-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer Following Surgery and Chemotherapy

    Science.gov (United States)

    2016-01-07

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Tumor; Fallopian Tube Mucinous Neoplasm; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; 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 Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  8. Macrophage Capping Protein CapG Is a Putative Oncogene Involved in Migration and Invasiveness in Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    J. Glaser

    2014-01-01

    Full Text Available The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38% of ovarian carcinomas (OC analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF of SNP rs6886 (c.1004A/G was higher and the homozygous (A/A, His335 genotype was significantly more prevalent in patients with fallopian tube carcinomas (50% as in controls (10%. With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.

  9. Clinical experience with radiolabelled monoclonal antibodies in the detection of colorectal and ovarian carcinoma recurrence and review of the literature.

    Science.gov (United States)

    Pinkas, L; Robins, P D; Forstrom, L A; Mahoney, D W; Mullan, B P

    1999-08-01

    A retrospective study was carried out to determine the diagnostic value of OncoScint CR/OV immunoscintigraphy in assessing patients with suspected recurrence of carcinoma of the colon and ovary. The scintigraphic results of 31 patients were compared with surgical and histopathological findings, conventional radiological examinations and clinical disease outcome over an average 3-year follow-up. Detected lesions were divided by location into hepatic or extrahepatic and the latter group was classified as local recurrence at the resection site, pelvic or abdominal regional lymph node involvement and distant metastatic disease. The combined sensitivity and accuracy of immunoscintigraphy in the detection of extra-hepatic disease was significantly higher than that of cross-sectional radiological imaging (87% and 83% vs 44% and 53% respectively) with equal specificity of 74%. Scintigraphy identified 14 (36%) of 39 extra-hepatic malignant lesions not diagnosed by conventional radiological techniques and influenced therapeutic planning in 8 (26%) of 31 patients studied. In the liver, conventional imaging had a significantly higher detection rate than immunoscintigraphy (sensitivity 93% vs 28%). In conclusion, these results show that OncoScint scintigraphy is a sensitive method for the detection of local recurrence and extra-hepatic metastases in colorectal and ovarian carcinoma and has an important role in the therapeutic decision-making process. PMID:10451876

  10. Inhibitory Effects of Anti-sense PTTG on Malignant Phenotype of Human Ovarian Carcinoma Cell Line SK-OV-3

    Institute of Scientific and Technical Information of China (English)

    陈刚; 李静; 李辅军; 李箫; 周剑锋; 卢运萍; 马丁

    2004-01-01

    To construct eukaryotic expression vector expressing full length anti-sense pituitary tumor transforming gene (PTTG) mRNA and observe its blocking effect on the potential invasion of human ovarian carcinoma cell line SK-OV-3. PCR primers containing designed enzyme cut sites were used for cloning full-length PTTG gene fragment, and the resulting PCR product was inserted into the eukaryotic vector pcDNA3. 1 in the antisense direction. The recombinant vector was then transfected into SK-OV-3 by Lipofectamine. The positive cell clone was screened by G418, PTTG and bFGF at protein level expression were detected by Western blot. The biological behavior change of transfection positive cells was observed by colony formation in soft agar assay. Our results showed that SK-OV-3 clones stably expressing full-length recombinant pcDNA3. 1-PTTGas were obtained. The expressions of PTTG and bFGF protein in transfected cells were decreased by 61.5 % and 52.3%, respectively as compared with non-transfected ones. The number of colony formation was reduced significantly in transfected cells as compared with empty vector transfected and non-transfected cells. It is concluded that the recombinant vector pcDNA3. 1-PTTGas is a novel tool and provides an alternative anti-sense gene therapy targeted at PTTG in human carcinoma.

  11. Advanced supraglottic carcinoma: a comparative study of sequential treatment policies

    International Nuclear Information System (INIS)

    Data from 131 consecutive patients with operable stage III or IV (American Joint Committee) supraglottic carcinoma were analyzed. Based on existing treatment policies at the time of presentation, patients received either preoperative radiation therapy (RT) (48 patients), surgery alone (42 patients), or postoperative RT (41 patients). Preoperative RT dose levels were either 2000 rad in five fractions (33 patients) or 5000 rad in 25 fractions (15 patients). Postoperative RT dosages were 5000 to 6000 rad in 6 to 6 1/2 weeks. Surgical procedures included either subtotal or total laryngectomy and radical neck dissection. Tumor control was achieved in 21 of 42 patients (50%) treated with surgery alone, 23 of 48 patients (48%) treated with preoperative RT, and 29 of 41 patients (71%) treated with postoperative RT (P . 0.005). The actuarial, recurrence-free survival at 5 years was 36% and 35%, respectively, in the surgery alone or preoperative RT groups as compared to 55% in postoperatively irradiated patients. The authors conclude that advanced but resectable supraglottic carcinomas may be best treated with surgery followed by RT, rather than with surgery alone or with combined preoperative RT and surgery

  12. A prospective comparison of perioperative morbidity in advanced epithelial ovarian cancer: Primary versus interval cytoreduction - experience from India

    OpenAIRE

    Sheikh Zahoor Ahmad; Anupama Rajanbabu; Vijaykumar, D. K.; Altaf Gauhar Haji; Pavithran, K.

    2015-01-01

    Objectives: The objective was to compare perioperative morbidity and mortality of patients with advanced epithelial ovarian cancer (EOC) treated with either of the two treatment approaches; neoadjuvant chemotherapy (NACT) followed by interval debulking versus upfront surgery. Design: Prospective comparative observational study. Participants: In total, 51 patients were included in the study. All patients with diagnosed advanced EOC (International Federation of Gynecology and Obstetrics IIIC an...

  13. Comparison of prognoses according to non-positive and positive spectrin αII expression detected immunohistochemically in epithelial ovarian carcinoma: a retrospective study.

    Science.gov (United States)

    Maeda, Osamu; Miyata-Takata, Tomoko; Shibata, Kiyosumi; Kajiyama, Hiroaki; Mizuno, Mika; Tamakoshi, Koji; Shimoyama, Yoshie; Nakamura, Shigeo; Kikkawa, Fumitaka

    2016-06-01

    Anticancer drug sensitivity affects prognosis in ovarian carcinoma. Previously, we purified spectrin αII and βII tetramers from cisplatin-resistant ovarian serous adenocarcinoma cells and demonstrated that they contribute to platinum anticancer drug resistance. In this clinical study, we focused on the role of spectrin αII expression. It is our objective to demonstrate the potential of spectrin αII expression as a useful predictor of anticancer drug resistance and postoperative prognosis in epithelial ovarian carcinoma. Spectrin αII expression in the ovarian adenocarcinoma surgical specimens of 193 patients was examined by immunohistochemical staining. Staining strength was scored 3+, regarded as positive expression, and 2+, 1+, and 0, regarded as non-positive expression. Prognoses obtained from clinical records were evaluated by statistical analysis. In the 193 cases studied, positive spectrin αII expression was associated with worse overall survival when compared with non-positive expression (P spectrin αII expression was identified as an independent predictive factor of overall survival (hazard ratio[HR]: 3.77, 95% confidence interval[CI]: 1.77-8.00; P spectrin αII expression was not associated with prognoses. However, similar results as overall survival were obtained for survival after recurrence of the 92 recurrent cases (P = 0.0051 by log-rank test, HR: 4.49, 95% CI: 2.06-9.79; P Spectrin αII expression is a useful predictor of anticancer drug resistance and postoperative prognosis in epithelial ovarian carcinoma.. PMID:26993048

  14. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  15. Expression of α2,6-sialic acid-containing and Lewis-active glycolipids in several types of human ovarian carcinomas

    OpenAIRE

    Tanaka, Kyoko; Mikami, Mikio; Aoki, Daisuke; Kiguchi, Kazushige; Ishiwata, Isamu; IWAMORI, MASAO

    2010-01-01

    To identify glycolipid antigens associated with histologically defined types of ovarian carcinomas, we determined the amounts of α2,6-sialyl and Lewis-active glycolipids, the specific activities of the α2,3- and α2,6-sialyltransferases, and the gene expression of sugar transferases in mucinous and serous cystadenocarcinoma, clear cell adenocarcinoma and endometrioid carcinoma tissues and cell lines derived from them. α2,6-sialyl glycolipid IV6NeuAcα-nLc4Cer detected with a newly developed mon...

  16. Preclinical Evaluation on the Tumor Suppression Efficiency and Combination Drug Effects of Fermented Wheat Germ Extract in Human Ovarian Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chia-Woei Wang

    2015-01-01

    Full Text Available Fermented wheat germ extract (FWGE is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s to be 643.76 μg/mL and 246.11 μg/mL after 48 h of FWGE treatment. FWGE treatment also induced programmed cell death by activating the caspase-7 cleavage in both SKOV-3 and ES-2 cells, but only caspase-3 and poly(adenosine diphosphate-ribose polymerase cleavages were activated in SKOV-3 cells. Moreover, FWGE exhibited combination drug effects with cisplatin and docetaxel in SKOV-3 and ES-2 cells by enhancing the cytotoxicity of both drugs. In conclusion, we found that FWGE not only suppressed cell growth but also induced caspase-3-related and caspase-7-related cell death in human ovarian carcinoma cells. FWGE treatment further enhanced the cytotoxicity of cisplatin and docetaxel, suggesting that FWGE is a potential ingredient in the development of adjuvant chemotherapy with cisplatin or docetaxel for treating ovarian cancer patients.

  17. Activity- and schedule-dependent interactions of paclitaxel, etoposide and hydroperoxy-ifosfamide in cisplatin-sensitive and -refractory human ovarian carcinoma cell lines.

    OpenAIRE

    Klaassen, U; Harstrick, A.; Schleucher, N; Vanhoefer, U.; SchrÖder, J.; Wilke, H.; Seeber, S

    1996-01-01

    Paclitaxel has demonstrated broad clinical activity in a variety of malignancies both alone and in combination with other chemotherapeutic agents. The in vitro cytotoxicity of a 2 h exposure to paclitaxel, hydroperoxy-ifosfamide and etoposide alone, in combination and in sequence, was evaluated against established cisplatin-sensitive and cisplatin-refractory human ovarian carcinoma cell lines using isobologram analysis. The combinations of either paclitaxel-hydroperoxy-ifosfamide or paclitaxe...

  18. KPNA2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-Myc and downregulation of FOXO3a

    OpenAIRE

    Huang, L.; Wang, H-Y; Li, J-D; Wang, J-H; Zhou, Y.; Luo, R-Z; Yun, J-P; Zhang, Y.; Jia, W-H; Zheng, M.

    2013-01-01

    Karyopherin alpha 2 (KPNA2), a member of the karyopherin family, has a central role in nucleocytoplasmic transport and is overexpressed in many cancers. Our previous study identified KPNA2 as significantly upregulated in epithelial ovarian carcinoma (EOC), correlating with poor survival of patients. However, the precise mechanism of this effect remains unclear. The aim of the present study was to examine the role of KPNA2 in the proliferation and tumorigenicity of EOC cells, and its clinical ...

  19. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    International Nuclear Information System (INIS)

    Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. 44 patients (84 % male, median age 69 years) not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Median survival was 11.5 months (95% CI 7.9–15.0) with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01), a low score in the Okuda- and CLIP-classification (p < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8–12). Grade 1 local reactions following injection were the only side effects. Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage) in addition to response to thymostimulin

  20. Expression Compilation of Several Putative Cancer Stem Cell Markers by Primary Ovarian Carcinoma

    OpenAIRE

    Di Jiabo; Yigit Refika; G. Figdor Carl; Duiveman-de Boer Tjitske; Massuger Leon; Torensma Ruurd

    2010-01-01

    Cancer stem cells (CSCs) or tumor initiating cells are rare cells that are able to establish a tumor or metastasis. Identification of those CSCs is, however, cumbersome even in established cell lines. Several cancer stem cell markers were reported to be expressed by ovarian cancer. Those cancer stem cells are gifted with lower vulnerability to irradiation and cytostatic drugs explaining the high incidence of recurrence after treatment. A variety of different cancer stem cell markers were desc...

  1. MicroRNA expression and regulation in human ovarian carcinoma cells by luteinizing hormone.

    Directory of Open Access Journals (Sweden)

    Juan Cui

    Full Text Available BACKGROUND: MicroRNAs have been widely-studied with regard to their aberrant expression and high correlation with tumorigenesis and progression in various solid tumors. With the major goal of assessing gonadotropin (luteinizing hormone, LH contributions to LH receptor (LHR-positive ovarian cancer cells, we have conducted a genome-wide transcriptomic analysis on human epithelial ovarian cancer cells to identify the microRNA-associated cellular response to LH-mediated activation of LHR. METHODS: Human ovarian cancer cells (SKOV3 were chosen as negative control (LHR- and stably transfected to express functional LHR (LHR+, followed by incubation with LH (0-20 h. At different times of LH-mediated activation of LHR the cancer cells were analyzed by a high-density Ovarian Cancer Disease-Specific-Array (DSA, ALMAC™, which profiled ∼ 100,000 transcripts with ∼ 400 non-coding microRNAs. FINDINGS: In total, 65 microRNAs were identified to exhibit differential expression in either LHR expressing SKOV3 cells or LH-treated cells, a few of which have been found in the genomic fragile regions that are associated with abnormal deletion or amplification in cancer, such as miR-21, miR-101-1, miR-210 and miR-301a. By incorporating the dramatic expression changes observed in mRNAs, strong microRNA/mRNA regulatory pairs were predicted through statistical analyses coupled with collective computational prediction. The role of each microRNA was then determined through a functional analysis based on the highly-confident microRNA/mRNA pairs. CONCLUSION: The overall impact on the transcriptome-level expression indicates that LH may regulate apoptosis and cell growth of LHR+ SKOV3 cells, particularly by reducing cancer cell proliferation, with some microRNAs involved in regulatory roles.

  2. Systemic Chemotherapy for Advanced Hepatocellular Carcinoma: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Masafumi Ikeda

    2015-12-01

    Full Text Available Systemic chemotherapy is one of the most important treatment modalities for advanced hepatocellular carcinoma (HCC. Before the introduction of sorafenib, cytotoxic agents, hormonal therapies, or many combinations of these were the mainly used modalities for systemic chemotherapy of advanced HCC. However, such regimens were of only limited value in clinical practice, because some randomized controlled studies comparing promising regimens with no treatment or doxorubicin alone failed to show any overall survival advantage. In two pivotal phase III placebo-controlled studies, the SHARP trial and the Asia-Pacific trial, sorafenib was demonstrated to significantly delay the time to progression and the overall survival time in patients with advanced HCC. Therefore, sorafenib therapy has come to be acknowledged as a standard therapy for advanced HCC worldwide. After the introduction of sorafenib, a number of phase III trials of various molecular-targeted agents vs. sorafenib as first-line chemotherapy and of various molecular-targeted agents vs. placebo as second-line chemotherapy have been conducted to determine if any of these agents could offer a survival benefit, however, none of the agents examined so far has been demonstrated to provide any survival benefit over sorafenib or placebo. Recently, favorable treatment efficacies have been reported in some clinical trials of molecular-targeted agents in the biomarker-enriched population. Development of individualized cancer treatments using molecular-targeted agents based on the results of genome-sequencing is aggressively ongoing. Furthermore, immune-oncologic agents, such as anti-CTLA-4 antibody and anti-PD-1/PD-L1 antibody, have been reported to provide promising outcomes. Thus, various novel systemic chemotherapeutic agents are currently under development, and further improvements in the treatment outcomes are expected.

  3. Genetic polymorphisms in the Paraoxonase 1 gene and risk of ovarian epithelial carcinoma.

    Science.gov (United States)

    Lurie, Galina; Wilkens, Lynne R; Thompson, Pamela J; McDuffie, Katharine E; Carney, Michael E; Terada, Keith Y; Goodman, Marc T

    2008-08-01

    Oxidative stress during successive ovulations increases the opportunity for DNA damage to ovarian epithelial cells and the potential for malignant transformation. Paraoxonase 1 (PON1) is an endogenous free radical scavenger that reduces oxidative stress. The association of two common functional single nucleotide polymorphisms (SNP), rs854560 T>A and rs662 A>G, with the risk of epithelial ovarian cancer was examined in a population-based case-control study in Hawaii. A personal interview and blood specimens were collected from 274 women with histologically confirmed, primary ovarian cancer and 452 controls frequency matched on age and ethnicity. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. Both PON1 SNPs were significantly associated with ovarian cancer risk. The ORs were 0.53 (95% CI, 0.35-0.79; P for allele-dose effect = 0.01) for women carrying the rs854560 T allele compared with women with the AA genotype and 0.65 (95% CI, 0.44-0.95; P for allele-dose effect = 0.03) for women carrying the rs662 A allele compared with women with the GG genotype. The association of the rs854560 T genotype with risk was stronger among smokers (OR, 0.33; 95% CI, 0.17-0.64; P for allele-dose effect = 0.0007) than among nonsmokers (OR, 0.68; 95% CI, 0.40-1.18; P for allele-dose effect = 0.53). The decreased risk associated with the rs854560 T allele was also stronger among obese women (OR, 0.19; 95% CI, 0.06-0.55; P for allele-dose effect = 0.007) than among nonobese women (OR, 0.62; 95% CI, 0.40-0.98; P for allele-dose effect = 0.16). Our study provides evidence for an association of two PON1 SNPs with the risk of epithelial ovarian cancer. Possible effect modification of these associations by tobacco smoking and obesity needs confirmation in other studies. PMID:18708400

  4. Epithelial-mesenchymal transition-associated miRNAs in ovarian carcinoma, with highlight on the miR-200 family: prognostic value and prospective role in ovarian cancer therapeutics.

    Science.gov (United States)

    Koutsaki, Maria; Spandidos, Demetrios A; Zaravinos, Apostolos

    2014-09-01

    MicroRNAs (miRNAs) are a family of short ribonucleic acids found to play a pivotal role in cancer pathogenesis. MiRNAs are crucial in cellular differentiation, growth, stress response, cell death and other fundamental cellular processes, and their involvement in ovarian cancer has been recently shown. They can repress the expression of important cancer-related genes and they can also function both as oncogenes and tumour suppressor genes. During epithelial-mesenchymal transition (EMT), epithelial cells lose their cell polarity and cell-cell adhesion and gain migratory and invasive properties. In the ovarian surface epithelium, EMT is considered the key regulator of the post-ovulatory repair process and it can be triggered by a range of environmental stimuli. The aberrant expression of the miR-200 family (miR-200a, miR-200b, miR-200c, miR-141 and miR-429) in ovarian carcinoma and its involvement in ovarian cancer initiation and progression has been well-demonstrated. The miR-200 family members seem to be strongly associated with a pathologic EMT and to have a metastasis suppressive role. MiRNA signatures can accurately distinguish ovarian cancer from the normal ovary and can be used as diagnostic tools to predict the clinical response to chemotherapy. Recent evidence suggests a growing list of new miRNAs (miR-187, miR-34a, miR-506, miRNA-138, miR-30c, miR-30d, miR-30e-3p, miR-370 and miR-106a, among others) that are also implicated in ovarian carcinoma-associated EMT, either enhancing or suppressing it. MiRNA-based gene therapy provides a prospective anti-tumour approach for integrated cancer therapy. The aim of nanotechnology-based delivery approach for miRNA therapy is to overcome challenges in miRNA delivery and to effectively encourage the reprogramming of miRNA networks in cancer cells, which may lead to a clinically translatable miRNA-based therapy to benefit ovarian cancer patients. PMID:24952258

  5. Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    You-xin Ji; Lei Sun; Zong-chun Zhang; Zhong-fa Zhang; Ke-tao Lan; Ke-ke Nie; Chuan-xin Geng; Shi-chao Liu; Ling Zhang; Xing-jun Zhuang; Xiao Zou

    2014-01-01

    Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75;P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48;95%confidence interval, 0.35-0.68;P Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

  6. Predictive value of 18F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study

    International Nuclear Information System (INIS)

    Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. 18F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of 18F-FDG PET/CT performed in the restaging process in a multicentre study. We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging 18F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUVmax and SUVmean, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT. PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53 % vs 23 and 12 %, respectively; p < 0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25 % in negative and positive groups, respectively; p < 0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p = 0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I-II but with negative PET had a significantly better 4-year OS than patients with low FIGO stage but positive PET. This

  7. Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era

    Directory of Open Access Journals (Sweden)

    Berger JL

    2014-08-01

    responses to Lipo-Dox, raising the question as to whether it is an equivalent substitute for Doxil. Further evaluation is needed, but if confirmed, these findings raise concerns regarding the use of current stocks of Lipo-Dox, as well as the prudence of managing future drug shortages with pharmacologically similar, but clinically untested drugs. Keywords: recurrent ovarian carcinoma, liposomal doxorubicin, drug shortage

  8. Kisspeptin and GPR54 immunoreactivity in a cohort of 518 patients defines favourable prognosis and clear cell subtype in ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Mehl Erika

    2007-11-01

    Full Text Available Abstract Background Kisspeptins and their G-protein coupled receptor, GPR54 are required for GnRH release and have been associated with anti-metastatic tumour cell behaviour in model systems. The latter might suggest that their overexpression would be associated with a better prognosis in cancer. However, kisspeptin/GPR54 interactions (autocrine, paracrine, and/or endocrine could also impact tumour behaviour in a negative manner. Here, for the first time, we associate the immunoreactivity of the kisspeptin/GPR54 ligand-receptor pair with favourable prognosis in a large cohort of ovarian carcinomas. Methods Immunohistochemical analysis for kisspeptin and GPR54 was performed on a tissue microarray (TMA consisting of 518 early stage ovarian carcinomas, all with linked clinical outcome data. The TMA was scored using a staining intensity scale of 0 (negative, +1 (mild-moderate, and +2 (strong. Strong staining cases were considered either kisspeptin or GPR54 positive and designated as 1, while all other cases were considered negative and designated 0. All statistical analysis was conducted using two-sided tests and a p value equal to or less than 0.05 was considered significant. Results Kisspeptin and GPR54 immunoreactive cases show a favourable prognosis in univariable disease specific survival (p = 0.0023, p = 0.0092, as well as in overall survival (p = 0.0006, p = 0.0002. Furthermore, kisspeptin is an independent marker for favourable prognosis as determined by multivariable disease specific (p = 0.0046 and overall survival analysis (p = 0.0170, while GPR54 is an independent marker for overall survival only (p = 0.0303. Both kisspeptin positive and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p Conclusion Kisspeptin and GPR54 immunoreactivity are significantly associated with favourable prognosis in both disease specific and overall survival, as well as being significantly associated with the clear

  9. Ovarian Small Cell Carcinoma in a 12-year-old Girl: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang Hyun; Kim, Young Tong; Kim, Sang Won; Yang, Seung Ha [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2009-05-15

    Small cell carcinoma of the ovary occurs mainly in young women and is extremely rare in a patient younger than 16 years of age. Early distant metastases or recurrence of this type of tumor is common and the response to chemotherapy or radiotherapy has been disappointing. The prognosis of this type of tumor is very poor. We report the ultrasonography, PET/CT and MRI findings of a small cell carcinoma of the ovary with severe peritoneal metastases in a 12-year-old girl.

  10. Ovarian Small Cell Carcinoma in a 12-year-old Girl: A Case Report

    International Nuclear Information System (INIS)

    Small cell carcinoma of the ovary occurs mainly in young women and is extremely rare in a patient younger than 16 years of age. Early distant metastases or recurrence of this type of tumor is common and the response to chemotherapy or radiotherapy has been disappointing. The prognosis of this type of tumor is very poor. We report the ultrasonography, PET/CT and MRI findings of a small cell carcinoma of the ovary with severe peritoneal metastases in a 12-year-old girl

  11. Therapeutic considerations in the use of intraperitoneal radiolabelled monoclonal antibodies in ovarian carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Crowther, M.E.; Ward, B.G.; Granowska, M.; Mather, S.; Britton, K.E.; Shepherd, J.H.; Slevin, M.L.

    1989-03-01

    Eleven patients with ovarian cancer have been treated with a radiolabelled monoclonal antibody directed against human milk fat globule membrane (HMFG2). All patients had Stage III disease and had previously undergone debulking surgery followed by chemotherapy. Although 16 patients have been referred, 5 could not be treated. This paper discusses the criteria for patient selection and treatment, and describes the technical difficulties of this form of therapy and the complications sustained following the intraperitoneal instillation of up to 150 mCi iodine-131 labelled HMFG2. Significant complications included two ileo-cutaneous fistulae and peritonitis in one patient which prevented treatment from being given.

  12. Therapeutic considerations in the use of intraperitoneal radiolabelled monoclonal antibodies in ovarian carcinoma

    International Nuclear Information System (INIS)

    Eleven patients with ovarian cancer have been treated with a radiolabelled monoclonal antibody directed against human milk fat globule membrane (HMFG2). All patients had Stage III disease and had previously undergone debulking surgery followed by chemotherapy. Although 16 patients have been referred, 5 could not be treated. This paper discusses the criteria for patient selection and treatment, and describes the technical difficulties of this form of therapy and the complications sustained following the intraperitoneal instillation of up to 150 mCi iodine-131 labelled HMFG2. Significant complications included two ileo-cutaneous fistulae and peritonitis in one patient which prevented treatment from being given. (author)

  13. The Prognostic Value of BRCA1 and PARP Expression in Epithelial Ovarian Carcinoma

    DEFF Research Database (Denmark)

    Hjortkjær, Mette; Waldstrøm, Marianne; Jakobsen, Anders;

    2016-01-01

    BRCA1/2 mutation status in epithelial ovarian cancer (EOC) presently relies on genetic testing which is resource consuming. Immunohistochemistry is cheap, fairly reproducible, and may identify gene product alterations due to both germline and somatic mutations and other defects along the BRCA gene...... tissue from 170 patients with EOC was stained immunohistochemically with BRCA1 and PARP antibodies. Semiquantitative analyses were performed to determine loss of, equivocal, and retained BRCA1 and high versus low PARP protein expression. These parameters were analyzed for relation with patient and...

  14. Regular multivitamin supplement use, single nucleotide polymorphisms in ATIC, SHMT2 and SLC46A1 and risk of ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Linda E Kelemen

    2012-03-01

    Full Text Available ATIC, SHMT2 and SLC46A1 have essential roles in one-carbon (1-C transfer. The authors examined whether associations between ovarian carcinoma and 15 variants in these genes are modified by regular multivitamin use, a source of 1-C donors, among Caucasian participants from two U.S. case control studies. Using a phased study design, variant-by-multivitamin interactions were tested, and associations between variants and ovarian carcinoma were reported stratified by multivitamin supplement use. Per-allele risk associations were modified by multivitamin use at six variants among 655 cases and 920 controls (Phase 1. In a larger sample of 968 cases and 1,265 controls (Phases 1 and 2, interactions were significant (P≤0.03 for two variants, particularly among regular multivitamin users: ATIC rs7586969 (odds ratio [OR]=0.7, 95% confidence interval [CI]=0.6-0.9 and ATIC rs16853834 (OR=1.5, 95% CI=1.1-2.0. The two ATIC SNPs did not share the same haplotype; however, the haplotypes they comprised mirrored their SNP risk associations among regular multivitamin supplement users. A multi-variant analysis was also performed by comparing the observed likelihood ratio test statistic from adjusted models with and without the two ATIC variant-by-multivitamin interaction terms with a null distribution of test statistics generated by permuting case status 10,000 times. The corresponding observed P value of 0.001 was more extreme than the permutation-derived P value of 0.009, suggesting rejection of the null hypothesis of no association. In summary, there is little statistical evidence that the 15 variants are independently associated with risk of ovarian carcinoma. However, the statistical interaction of ATIC variants with regular multivitamin intake, when evaluated at both the SNP and gene level, may support these findings as relevant to ovarian health and disease processes.

  15. Evolution of surgery in advanced epithelial ovarian cancer in a dedicated gynaecologic oncology unit—seven year audit from a tertiary care centre in a developing country

    OpenAIRE

    Rajanbabu, Anupama; Kuriakose, Santhosh; Ahmad, Sheikh Zahoor; Khadakban, Tejal; Khadakban, Dhiraj; R. Venkatesan; Vijaykumar, D. K.

    2014-01-01

    Aims To audit our performance as a dedicated gynaecologic oncology unit and to analyse how it has evolved over the years. To retrospectively evaluate the outcome of advanced ovarian cancer treated with neoadjuvant chemotherapy (NACT) followed by interval surgery versus upfront surgery. Methods and results One hundred and ninety-eight patients with advanced epithelial ovarian cancer (EOC) who were treated from 2004 to 2010 were analysed. Eighty-two patients (41.4%) underwent primary surgery an...

  16. DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets

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    Tropé Claes G

    2007-07-01

    Full Text Available Abstract Background The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52 and their in vitro models (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3 by methylation-specific polymerase chain reaction (MSP. Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features. Results Eight out of the 13 genes were hypermethylated among the ovarian carcinomas, and altogether 40 of 52 tumours were methylated in one or more genes. Promoter hypermethylation of HOXA9, RASSF1A, APC, CDH13, HOXB5, SCGB3A1 (HIN-1, CRABP1, and MLH1 was found in 51% (26/51, 49% (23/47, 24% (12/51, 20% (10/51, 12% (6/52, 10% (5/52, 4% (2/48, and 2% (1/51 of the carcinomas, respectively, whereas ADAMTS1, MGMT, NR3C1, p14ARF, and p16INK4a were unmethylated in all samples. The methylation frequencies of HOXA9 and SCGB3A1 were higher among relatively early-stage carcinomas (FIGO I-II than among carcinomas of later stages (FIGO III-IV; P = 0.002, P = 0.020, respectively. The majority of the early-stage carcinomas were of the endometrioid histotype. Additionally, HOXA9 hypermethylation was more common in tumours from patients older than 60 years of age (15/21 than among those of younger age (11/30; P = 0.023. Finally, there was a significant difference in HOXA9 methylation frequency among the histological types (P = 0.007. Conclusion DNA hypermethylation of tumour suppressor genes seems to play an important role in ovarian carcinogenesis and HOXA9, HOXB5, SCGB3A1, and CRABP1 are identified as novel hypermethylated target genes in this tumour type.

  17. Effect of c-Met Inhibitor on HGF-induced Ovarian Carcinoma Cell Migration

    Science.gov (United States)

    Lo, Chun-Min; Lo, Jun-Chih; Yip, Kay-Pong

    2010-03-01

    The dysregulation of hepatocyte growth factor (HGF) and its receptor, c-Met, in cell migration contributes to tumor invasion and metastasis in numerous cancers including ovarian cancer. Specific inhibitors against HGF/c-Met signaling like SU11274, therefore, may have important therapeutic potential for the treatment of cancers. Here, we applied electric cell-substrate impedance sensing (ECIS) and traction force microscopy to evaluate the effect of SU11274 on HGF-treated SKOV-3 ovarian cancer cells. Our results showed that, compared with control cells, HGF-treated cell monolayer displayed lower junctional resistance between cells, larger cell-substrate separation, and higher cell micromotion. In addition, individual HGF-treated SKOV-3 cells demonstrated weaker traction forces on the collagen-coated polyacrylamide substrate than did control cells. These changes lead to faster directional movement of HGF-treated cells, as demonstrated with wound healing assay. Treatment of SKOV-3 cells with SU11274 indicated significant inhibition of HGF stimulation on all assays tested.

  18. ABERRANT PROMOTER HYPERMETHYLATION OF DEATH ASSOCIATED PROTEIN KINASE (DAPK IN EPITHELIAL OVARIAN CARCINOMA

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    Ramesh

    2015-05-01

    Full Text Available PURPOSE: The aim of the study was to assess the promoter hypermethylation status of the apoptotic gene Death Associated Protein Kinase (DAPK in epithelial ovarian cancer and its association with various clinicopathological parameters. METHODS: 110 epithelial ovarian cancers samples were assessed to study the hypermethylation by nested and Methylation Specific PCR. STATISTICAL ANALYSIS : All the available data was statistically analyzed using the Chi square test or Fisher Test on the SPSS software version 21.0 . RESULTS: 31.2% and 14.2% methylation frequencies were observed for malignant and low malignant potential tumors respectively. A zero percent methylation was noted in benig n and non - malignant samples. CONCLUSION: The observed promoter hypermethylation frequency for DAPK gene suggests that it plays a role in tumorogenesis. The methylation status along with biochemical parameters can aid in the early diagnosis of the disease and also serve as a prognostic tool. Due to Frequent hypermethylation of the DAPK promoter in several cancer types, studying the methylation pattern of the gene has been proposed as a diagnostic and follow - up test

  19. CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

    Institute of Scientific and Technical Information of China (English)

    苏勇; 张锦明; 夏云飞; 朱荣; 钱朝南; 莫浩元

    2002-01-01

    Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

  20. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    OpenAIRE

    Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    The safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced hepatocellular carcinoma were assessed. Bevacizumab was active and well tolerated. The clinical value of circulating endothelial cells and interleukin-6 and -8 warrants further investigation.

  1. Female genital tract tuberculosis presenting as ovarian cancer

    Directory of Open Access Journals (Sweden)

    Malihe Hasanzadeh

    2014-01-01

    Full Text Available Background: Tuberculosis (TB is still a major worldwide concern. There is no pathognomonic clinical feature or imaging findings for definite diagnosis of extra pulmonary TB. Therefore, TB involvement of Gastrointestinal or Genitourinary tract can be easily confused with peritoneal carcinomatosis and advanced ovarian carcinoma. Our aim is to emphasize the importance of considering the disease based upon the epidemiologic clues of the patients, while interpreting the positive results for a suspicious ovarian malignancy. Cases: This paper illustrates 8 cases of ovarian or peritoneal tuberculosis, whose initial diagnoses were malignant processes of the GU tract. Conclusion: Tuberculosis ( TB should be always being considered in the differential diagnosis of advanced ovarian cancer, especially in the regions that are endemic for the disease.

  2. Standardized FDG uptake as a prognostic variable and as a predictor of incomplete cytoreduction in primary advanced ovarian cancer

    International Nuclear Information System (INIS)

    Introduction. In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor). Material and methods. From September 2004 to August 2007, 201 consecutive patients with a pelvic tumor and a Risk of Malignancy Index (RMI) > 150 based on serum CA-125, ultrasound examinations and menopausal state, underwent PET/CT within two weeks prior to standard surgery/debulking of a pelvic tumor. At two-year follow-up (August 15, 2009) the association between SUV and overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients (58 stage III and two stage IV). Results. At inclusion median age was 62 years (range 35-85 years); 97% (58/60) had a performance status ≤2; 42% (25/60) underwent complete debulking (no macroscopic residual tumor); median SUVmax was 13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUVmax in patients alive was not statistically different from SUVmax in dead patients (p=0.69), and SUVmax was not correlated with the amount of residual tumor after surgery (p=0.19). Using univariate Cox regression analysis, residual tumor was a significant prognostic variable (p=0.001); SUVmax was not a statistically significant prognostic variable (p=0.86). Discussion. FDG uptake (SUVmax) in the primary tumor of patients with advanced ovarian cancer was not a prognostic variable and the FDG uptake did not predict complete cytoreduction after primary surgery. Future prospective clinical trials will need to clarify if other PET tracers can serve as prognostic variables in ovarian cancer

  3. Sorafenib in advanced hepatocellular carcinoma: current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Hsu CH

    2014-06-01

    Full Text Available Chih-Hung Hsu,1,4 Ying-Chun Shen,1,2 Yu-Yun Shao,1,4 Chiun Hsu,1,4 Ann-Lii Cheng,1,3,41Department of Oncology, 2Department of Medical Research, 3Department of Internal Medicine, National Taiwan University Hospital, 4Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, TaiwanAbstract: The approval of sorafenib, a multikinase inhibitor targeting primarily Raf kinase and the vascular endothelial growth factor receptor, in 2007 for treating advanced hepatocellular carcinoma (HCC has generated considerable enthusiasm in drug development for this difficult-to-treat disease. However, because several randomized Phase III studies testing new multikinase inhibitors failed, sorafenib remains the standard of first-line systemic therapy for patients with advanced HCC. Field practice studies worldwide have suggested that in daily practice, physicians are adopting either a preemptive dose modification or a ramp-up strategy to improve the compliance of their patients. In addition, accumulating data have suggested that patients with Child–Pugh class B liver function can tolerate sorafenib as well as patients with Child–Pugh class A liver function, although the actual benefit of sorafenib in patients with Child–Pugh class B liver function has yet to be confirmed. Whether sorafenib can be used as an adjunctive therapy to improve the outcomes of intermediate-stage HCC patients treated with transcatheter arterial chemoembolization or early-stage HCC patients after curative therapies is being investigated in several ongoing randomized Phase III studies. An increasing number of studies have reported that sorafenib exerts "off-target" effects, including the modulation of signaling pathways other than Raf/MEK/ERK pathway, nonapoptotic cell death mechanisms, and even immune modulation. Finally, although sorafenib in combination with chemotherapy or other targeted therapies has the potential to improve therapeutic efficacy in

  4. A case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma

    OpenAIRE

    Tsuji, Kunihiro; Takemura, Kenichi; Minami, Keisuke; Teramoto, Ryota; Nakashima, Keisuke; Yamada, Shinya; Doyama, Hisashi; Oiwake, Hisanori; Hasatani, Kenkou

    2013-01-01

    We report on a case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. A 70-year-old man was admitted to our hospital with fatigue, myalgia and an elevated creatine phosphokinase level. He was diagnosed as rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. After discontinuation of sorafenib, his fatigue and myalgia resolved and his creatine phosphokinase level returned to normal. Rhabdomyolysis related to sorafenib treatme...

  5. MicroRNA profile of paclitaxel-resistant serous ovarian carcinoma based on formalin-fixed paraffin-embedded samples

    International Nuclear Information System (INIS)

    To assess the feasibility of validating microRNA (miRNA) profile related to paclitaxel-sensitivity in formalin-fixed paraffin-embedded (FFPE) samples of serous ovarian carcinoma (OC) patients. Deregulated miRNAs identified by miRNA microarray were further detected in 45 FFPE OC samples using Realtime PCR. Correlations between paired FFPE and frozen tumor samples were analyzed. Survival times were compared between 6 high and low miRNAs groups. Western blot and luciferase reporter assay were used for validating the target of miRNA. Sixteen up-regulated miRNAs and twenty-three down-regulated miRNAs were revealed in pacilitaxel-resistant ST30 cells. The up-regulated miRNAs (miR-320a, 22 and 129-5p) and down-regulated miRNAs (miR-9, 155 and 640) were confirmed in paclitaxel-resistant FFPE tumor samples, compared with paclitaxel-sensitive samples. Higher miR-9 and miR-640 showed better survival time in OC patients. Expressions of miR-9, 155 and 22 in FFPE samples were closely mimicked by those in frozen tissues. RAB34 was validated as a direct target of miR-9. We validated miRNA profile in pacilitaxel-resistant OC using FFPE samples, which might enable treatment stratification and help us to predict outcomes in OC patients. FFPE samples are feasible materials for miRNA research

  6. EFFECTS OF RETINOIC ACID ON PROLIFERATION AND DIFFERENTIATION OF A HUMAN OVARIAN CARCINOMA CELL LINE: 3AO

    Institute of Scientific and Technical Information of China (English)

    Ming-Juan Xu; Ying Cui; Ning Hui; Yu-Jian Liu

    2005-01-01

    Objective To observe the effects ofretinoic acid (RA) on the proliferation and differentiation of a human ovarian carcinoma cell line: 3AO cells.Methods 3AO cell proliferation was evaluated by viable cell count, percentage of cells in each cycle phase were analyzed by flow cytometric analysis, alkaline phosphatase (AKP) activity was determined as described, and CA125 expression was measured by ELISA.Results RA could inhibit the proliferation of 3AO cells accompanied with morphological changes in a dose-dependent manner. Cell cycle analysis indicated that RA inhibition of 3AO cells growth occurred through induction of G1 arrest with a concomitant reduction in the proportion of cells in S phase, AKP activity increased significantly after treatment with RA (0. l μmol/L) for 1-5 days. Dose-response studies revealed that the AKP activity increased to a different extent as a function of RA concentrations. Furthermore, RA could suppress the expression of CA125 tumor marker in 3AO cells.Conclusion RA could markedly inhibit the proliferation and induce the differentiation of 3AO cells.

  7. The clinical significance of the expression of the metastasis suppressor gene KAI1 in epithelial ovarian carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhang Xiangning; Han Qiuyu; Li Xiaocui

    2005-01-01

    Objective:To investigate the potential role of KAI1 in epithelial ovarian carcinoma(EOC), and to determine whether the expression of the KAI1 gene is associated with EOC progression.The clinical significance in this tumor is also evaluated.Method: Immunohistochemistry SP method was performed to examine the expression level of KAI1 in EOC.Results: Thirty eight of 66 cancer specimens showed KAI1 protein positive (57.58%),which lower significantly than that in the patients with benign and borderline tumors(90.91%).The statistical evaluation showed that the expression of KAI1 had a correlation with FIGO stags as well as lymph node metastasis(or distant metastasis)(P<0.05).It also revealed an inverse relationship between histological grade and KAI1 expression (P<0.05).Conclusion: KAI1 protein expression is closely correlated with the malignent progression and metastasis of EOC; detecting the expression of KAI1 probably possesses clinical significance in evaluating the differentiation,tumor progression and predicting the prognosis of EOC.

  8. Ovarian small cell carcinoma of hypercalcemic type - evidence of germline origin and SMARCA4 gene inactivation. a pilot study.

    Science.gov (United States)

    Kupryjańczyk, J; Dansonka-Mieszkowska, A; Moes-Sosnowska, J; Plisiecka-Hałasa, J; Szafron, L; Podgórska, A; Rzepecka, I K; Konopka, B; Budziłowska, A; Rembiszewska, A; Grajkowska, W; Spiewankiewicz, B

    2013-12-01

    Ovarian tumors from two patients, compatible by histological and immunohistochemical criteria with small cell carcinoma of hypercalcemic type (SCCHT) (WT1+, EMA dispersed+, synaptophysin+ or dispersed+), were extensively sampled in order to find clues to their histogenesis. Subsequently, small foci of immature teratoma were found in both of them (in 1/122 and in 3/80 tumor sections). In one case, microfoci of yolk sac tumor were also present within the teratoma area as well as in the background of the small cell tumor population - in the primary tumor and in omental metastasis. We found a resemblance of the microscopic patterns of SCCHT and atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, and this prompted us to evaluate INI-1 and SMARCA4 immunohistochemical expression, because their alternative loss is regarded as a molecular hallmark of AT/RT. INI-1 expression was retained, while that of SMARCA4 was lost. We therefore analyzed tumor DNA by PCR amplification and sequencing for mutations in the SMARCA4 gene (NG_011556.1), which were identified in both tumors (c.2184_2206del; nonsense c.3277C>T - both in one tumor; nonsense c.3760G>T in another tumor). These data suggest that SCCHT is most likely an embryonal tumor originating from immature teratoma and related to malignant rhabdoid tumor. Further analyses are necessary to determine whether the tumors diagnosed as SCCHT constitute a homogeneous group or represent more than one entity. PMID:24375037

  9. Concomitant lung metastasis in patients with advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tian Yang; Jun-Hua Lu; Chuan Lin; Song Shi; Ting-Hao Chen; Rong-Hua Zhao; Yi Wang; Meng-Chao Wu

    2012-01-01

    AIM:To investigate the clinical features and prognostic factors of advanced hepatocellular carcinoma (HCC) patients presenting with lung metastasis at initial diagnosis.METHODS:Between 2001 and 2010,we recruited 76consecutive HCC patients initially presenting with lung metastasis,without co-existing metastasis from other sites.These patients were divided into three groups:untreated group (n =22),single treatment group (n =19),and combined treatment group (n =35).RESULTS:Metastasis of bilateral lung lobes was common and noted in 35 patients (46.1%),and most of patients (59/76,77.6%) presented with multiple lung metastatic nodules.Nineteen patients (25.0%)received single-method treatment,including hepatectomy in 4,transcatheter arterial chemoembolization in 6,radiotherapy in 5,and oral sorafenib in 4.Thirty-five patients (46.1%) received combined treatment modalities.The overall median survival of the all patients was 8.7 ± 0.6 mo; 4.1 ± 0.3,6.3 ± 2.5 and 18.6 ± 3.9 mo,respectively in the untreated group,single treatment group and combined treatment group,respectively,with a significant difference (log-rank test,P < 0.001).Multivariate analysis revealed that Child-Pugh score,the absence or presence of portal vein tumor thrombus,and treatment modality were three independent prognostic factors affecting survival of patients with advanced HCC and concomitant lung metastasis.CONCLUSION:Combined treatment modalities tend to result in a better survival as compared with the conservative treatment or single treatment modality for HCC patients initially presenting with lung metastasis.

  10. Recovery of CD8+ T-cell function during systemic chemotherapy in advanced ovarian cancer.

    Science.gov (United States)

    Coleman, Sharon; Clayton, Aled; Mason, Malcolm D; Jasani, Bharat; Adams, Malcolm; Tabi, Zsuzsanna

    2005-08-01

    Immunologic approaches are emerging as new treatment options in several types of cancer. However, whereas the ability of patients to develop potent CD8+ T-cell responses is crucial for efficient antitumor responses, immunocompetence and T-cell function are not tested routinely in patients entering immunotherapy. The objective of our study was to monitor T-cell function in advanced cancer and during chemotherapy. CD8+ T-cell function of 21 patients with advanced ovarian cancer (stages III-IV) was assessed by cytokine flow cytometry following stimulation of 42 PBMC samples with a panel of synthetic viral peptides in vitro, consisting of pan-Caucasian epitopes. CD8+ T-cell responses were significantly lower in patients with high levels (>200 units/mL) of Ca125 (marker of tumor load and progression) than in those with low Ca125 levels (P = 0.0013). In longitudinal studies of nine patients, chemotherapy was associated with decreasing Ca125 levels in seven cases and also with improvement or maintenance of CD8+ T-cell function in seven cases. After the full course of chemotherapy, five of nine patients in remission displayed potent CD8+ T-cell responses, whereas four of nine patients in progression displayed low or decreasing T-cell responses, pointing toward a correlation between T-cell function and clinical response. Our results show for the first time that CD8+ T-cell function is not permanently suppressed in advanced cancer and successful chemotherapy is associated with improved antigen-specific T-cell reactivity. We suggest that functional assays determining T-cell immunocompetence can be valuable tools for optimizing cancer immunotherapy for improved clinical success. PMID:16061686

  11. 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

    Science.gov (United States)

    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

  12. Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction: customization instead of conformity.

    Science.gov (United States)

    Reed, Beverly G; Babayev, Samir N; Bukulmez, Orhan

    2015-05-01

    As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols. PMID:26036898

  13. Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Høgdall, Claus; Kehlet, Henrik; Christensen, Ib J; Ottesen, Bent

    2011-01-01

    Denmark, involving a total of 1,160 patients with stage IIIC or IV ovarian cancer. Data were extracted for 2,024 patients with all stages of ovarian cancer recorded in the Danish Gynecological Cancer Database between 1 January 2005 and 31 December 2008. The main outcome measure was overall survival...

  14. Immunoassay for SKOV-3 human ovarian carcinoma cells using a graphene oxide-modified electrode

    International Nuclear Information System (INIS)

    We describe a highly sensitive electrochemical immunoassay for the tumor maker HER2 on the surface of SKOV-3 human ovarian cancer cells. Following the binding of the cancer cells, ssDNA-labeled anti-HER2 antibody (ssDNA-Ab; the detection antibody) was added to conjugate unbound antigen on the target cells. Following hybridization of ssDNA with its complementary DNA, daunorubicin was injected in order to intercalate into the duplex. This enables electron transfer between daunorubicin and electrode to take place. The GO film strongly amplifies the redox signal of daunorubicin. This new assay has a detection limit of 5.2 cells per mL and in our opinion holds great promise for clinical screening of cancer biomarkers and point-of-care diagnostics. (author)

  15. Neoadjuvant chemotherapy for advanced ovarian cancer: literature data and in vitro studies

    Directory of Open Access Journals (Sweden)

    S. A. Kuznetsov

    2015-01-01

    Full Text Available This paper analyzes large amounts of literature data on studies of the efficiency of neoadjuvant chemotherapy (NCT for advanced ovarian cancer (OC, which is performed prior to standard surgery. Clinical trials have demonstrated that a NCT regimen followed by cytoreductive surgery is less effective than primary cytoreductive one; however, evidence for the benefit of NCT is lacking so far. The authors conducted investigations using the intraoperative material obtained from 17 patients with T3a–cNxM0 OC, who were divided for a comparative examination into 2 groups. Group 1 included OC patents who received NCT; Group 2 comprised OC patients who did not. The tumor cells obtained from the intraoperative material of both groups were able to generate a well-proliferating culture in in vitro experiments. The cultured OC cells were characterized, by analyzing cytological specimens and the functional activity of these cells. It was ascertained that 35 % of the cultured tumor cells from OC retained their resistance to the cytotoxic action of effector cells (autologous lymphocytes at a target cell/effector cell ratio of 1:5. Thus, both the literature and the experiment provide no unambiguous evidence supporting the fact that NCT before cytoreductive surgery is a better approach than primary surgical treatment. The optimal regimen of NCT, which would be able to enhance its efficiency, remains important. 

  16. Comparative Study on Three Chemotherapeutic Regimens for the Treatment of Advanced Epithelial Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To investigate the best first-line chemotherapy regimen for the treatment of advanced epithelial ovarian cancer (AEOC), the efficacy of three chemotherapy regimens for treatment of the patients with AEOC in our hospital during Jan. 1992- Jan. 1999 was retrospectively analyzed. The therapeutic effects were compared with the supplement of Melphalan + Hexamethylme (PAM + HMM), cisplatin + adriamycin +cyclophosphamide or isofamide (PAC) or cisplatin + cyclophosphamide or isofamide (PC), Taxol+cisplatin (TP) combined chemotherapy after cytoreductive surgery. The results showed that the overall effective rate of TP was significantly higher than that of PAM+ HMM (P<0. 05); The complete remission rate of TP was significantly higher than that of PAM+ HMM and PAC or PC (all P<0.05);The 2-year survival rate free of tumor of TP was obviously higher than that of PAM+HMM and PAC or PC(all P<0. 05). It was concluded that the therapeutic effect of TP regimen in the treatment of AEOC was better than PAM +HMM and PAC or PC and TP regimen could be recommended currently as the preferred first-line one for the treatment of AEOC.

  17. Simultaneous suppression of epidermal growth factor receptor and c-erbB-2 reverses aneuploidy and malignant phenotype of a human ovarian carcinoma cell line.

    Science.gov (United States)

    Pack, Svetlana D; Alper, Ozgül M; Stromberg, Kurt; Augustus, Meena; Ozdemirli, Metin; Miermont, Anne M; Klus, Greg; Rusin, Marek; Slack, Rebecca; Hacker, Neville F; Ried, Thomas; Szallasi, Zoltan; Alper, Ozge

    2004-02-01

    Coexpression of epidermal growth factor receptor (EGFR) and c-erbB-2 in 47-68% of ovarian cancer cells indicate their strong association with tumor formation. We examined the effects of simultaneous antisense- or immunosuppression of EGFR and c-erbB-2 expression on the invasive phenotype, aneuploidy, and genotype of cultured human ovarian carcinoma cells (NIH:OVCAR-8). We report here that suppression of both EGFR and c-erbB-2 results in regression of aneuploidy and genomic imbalances in NIH:OVCAR-8 cells, restores a more normal phenotype, and results in a more normal gene expression profile. Combined with cytogenetic analysis, our data demonstrate that the regression of aneuploidy is due to the selective apoptosis of double antisense transfected cells with highly abnormal karyotype. PMID:14871800

  18. Quantification of activity by alpha-camera imaging and small-scale dosimetry within ovarian carcinoma micrometastases treated with targeted alpha therapy

    DEFF Research Database (Denmark)

    Chouin, N; Lindegren, S; Jensen, Holger;

    2012-01-01

    Targeted alpha therapy (TAT) a promising treatment for small, residual, and micrometastatic diseases has questionable efficacy against malignant lesions larger than the α-particle range, and likely requires favorable intratumoral activity distribution. Here, we characterized and quantified the...... activity distribution of an alpha-particle emitter radiolabelled antibody within >100-µm micrometastases in a murine ovarian carcinoma model. Nude mice bearing ovarian micrometastases were injected intra-peritoneally with 211At-MX35 (total injected activity 6 MBq, specific activity 650 MBq/mg). Animals......% IA/g at 4 h) in the outer tumor layer and a sharp drop beyond a depth of 50 µm. Small-scale dosimetry was performed on a multi-cellular micrometastasis model, using time-integrated activities derived from the experimental data. With injected activity of 400 kBq, tumors exhibiting uniform activity...

  19. {sup 18}F-fluorodeoxyglucose PET in ovarian carcinoma: methodology and preliminary results; {sup 18}F-Fluordeoxyglukose PET beim Ovarialkarzinom: Methodik und erste Ergebnisse

    Energy Technology Data Exchange (ETDEWEB)

    Zimny, M.; Cremerius, U.; Buell, U. [Technische Hochschule Aachen (Germany). Klinik fuer Nuklearmedizin; Schroeder, W.; Wolters, S.; Rath, W. [Technische Hochschule Aachen (Germany). Frauenklinik

    1997-10-01

    Aim of the present study was to evaluate {sup 18}FDG PET as a diagnostic tool in primary and recurrent ovarian cancer. Methods: PET of the abdomen and the pelvis was performed in 26 patients suspected for primary (n=17) or recurrent (n=9) ovarian cancer with an ECAT 953/15 scanner 45 min after intravenous administration of 245 MBq {sup 18}F-FDG (mean). PET findings were validated by surgery, histology and/or cytology. Results: Ovarian malignancies or recurrent ovarian cancer were demonstrated by PET in 16 out of 19 cases. Malignancy was excluded in six out of seven cases. False negative findings were obtained in two cases of low malignant potential tumors (LMP) and in one case of low grade serous/mucinous ovarian cystadenocarcinoma. PET yielded one false positive result in a case of salpingoophoritis. Quantitative analysis revealed a mean SUV of 6.8{+-}2.3 in primary ovarian carcinoma vs. 2.6{+-}1.2 in benign masses (p<0.05). Conclusion: These preliminary data show {sup 18}FDG PET to be useful in diagnosis of recurrent ovarian cancer. PET is of limited use in differentiating LMP from benign tumors and ovarian cancer from inflammatory processes. Concerning this differentiation, quantitative analysis does not improve diagnostic accuracy. (orig.) [Deutsch] Ziel der vorliegenden Studie war die Evaluierung der PET mit {sup 18}F-Fluordeoxyglukose in der Primaer- und Rezidivdiagnostik von Ovarialkarzinomen. Methoden: Untersucht wurden 26 Patientinnen mit Verdacht auf primaeres Ovarialkarzinom (n=17) bzw. Rezidivverdacht (n=9). Die PET-Untersuchung von Abdomen und Becken erfolgte mit einem ECAT 953/15-Scanner beginnend 45 min nach i.v. Applikation von im Mittel 245 MBq {sup 18}FDG. Die PET-Ergebnisse wurden anhand von intraoperativem Befund, Histologie und Zytologie validiert. Ergebnisse: Der richtige Nachweis eines primaeren, malignen Ovarialtumors bzw. eines Rezidivs gelang in 16 von 19 Faellen, der Malignomausschluss in sechs von sieben Faellen. Falsch negative PET

  20. Ovarian small cell carcinoma of pulmonary type appearing in ante-mortem ascites: An autopsy case and review of the literature

    Directory of Open Access Journals (Sweden)

    Hirotsugu Hashimoto, MD

    2015-09-01

    Full Text Available Ovarian small cell carcinoma of pulmonary type (OSCCPT is an extremely rare and aggressive disease. The diagnostic significance of cytology of ascites for OSCCPT, however, has not been shown so far. Here, we report the diagnosis of this carcinoma in an autopsy case with ante-mortem cytology of ascites. A 75 year-old woman was detected with bilateral ovarian cancer by radiological imaging. Although operation was planned, massive ascites was discovered a few weeks later. Ascites was removed with abdominocentesis, which cytologically diagnosed presence of carcinoma, suspicious of adenocarcinoma. A few days later, she died. From autopsy samples, we diagnosed this case as bilateral OSCCPT, showing neuroendocrine differentiation by immunohistochemistry. We reviewed ante-mortem cytology of ascites and found scattered small atypical cells. Immunocytochemical study of the cell block of the ascites showed neuroendocrine differentiation of the atypical cells in an identical manner as the autopsy specimens. Since small atypical cells of OSCCPT often exist with other histological tumor components, careful screening of all cells on the preparation is advisable to accurately diagnose OSCCPT by cytology of ascites.

  1. Expression and Significance of CD44, CD47 and c-met in Ovarian Clear Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Huimin Wang

    2015-02-01

    Full Text Available Aims: The aim of the present study is to investigate the differential expression of CD44, CD47 and c-met in ovarian clear cell carcinoma (OCCC, the correlation in their expression and their relationship with the biological behavior of OCCC. Methods: We used immunohistochemistry to examine the expression of CD44, CD47 and c-met in OCCC (86 cases and investigated the effects of the expression and interaction of these molecules on the development of OCCC. Results: CD44, CD47 and c-met expression was significantly high in OCCC. Expression of CD44 and CD47 correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05, and expression of c-met correlated with chemotherapy resistance and prognosis (all p < 0.05, but did not correlate with lymph node metastasis (all p > 0.05. The surgical stage, CD44, CD47 and c-met expression were independent risk factors for OCCC prognosis (all p < 0.05. Patients with low levels of CD44, CD47 and c-met showed better survival than those with high levels (all p < 0.05. There was a positive correlation between CD44 (or CD47 and c-met, as well as between CD44 and CD47 (the Spearman correlation coefficient rs was 0.783, 0.776 and 0.835, respectively, all p < 0.01. Additionally, pairwise correlation analysis of these three markers shows that the high expression of CD44/CD47, CD44/c-met and CD47/c-met were correlated with patient surgical stage, chemotherapy resistance and prognosis (all p < 0.05, but did not correlate with lymph node metastasis (all p > 0.05. Conclusions: Expression of CD44, CD47 and c-met was upregulated in OCCC and pairwise correlation. CD44, CD47 and c-met may have synergistic effects on the development of OCCC and are prognostic factors for ovarian cancer.

  2. Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database

    Directory of Open Access Journals (Sweden)

    Jian-Hua Sun

    2016-04-01

    Full Text Available BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC has been developed to treat peritoneal carcinomatosis (PC. This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A or recurrent EOC (group B were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS and overall survival (OS; the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2 for group B (P = .68. The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5 for group B (P = .034. Better median OS correlated with peritoneal cancer index (PCI 20 group, P = .01, complete cyroreduction (residual disease ≤ 2.5 mm [79.5 months for completeness of cytoreduction (CC score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05. Serious adverse events occurred in five patients (10.0%. Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

  3. Mixed ovarian germ cell tumor composed of immature teratoma, yolk sac tumor and embryonal carcinoma.

    Science.gov (United States)

    Wang, Ying; Zhou, Feng; Qian, Zhida; Qing, Jiale; Zhao, Mengdam; Huang, Lili

    2014-11-01

    We report the case of a 19-year-old woman experiencing lower abdominal distension and pain. Laboratory tests indicated elevated serum levels of Alpha-Fetoprotein (AFP) and human Chorionic Gonadotropin (hCG). A large mass was detected in the abdomen by physical examination and by transvaginal ultrasonography. Exploratory laparotomy was performed, and a smooth-surfaced, spherical, solid tumor was found on the left ovary, measuring 11.5 x 9.9 x 6.9 cm. Histological evaluation revealed that the tumor consisted of a combination of immature teratoma, Yolk Sac Tumor, and embryonal carcinoma; this is a very rare combination in mixed germ cell tumors. PMID:25518772

  4. Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma

    OpenAIRE

    Ming-Chun Ma; Yen-Yang Chen; Shau-Hsuan Li; Yu-Fan Cheng; Chih-Chi Wang; Tai-Jan Chiu; Sung-Nan Pei; Chien-Ting Liu; Tai-Lin Huang; Chen-Hua Huang; Yu-Li Su; Yen-Hao Chen; Sheng-Nan Lu; Kun-Ming Rau

    2014-01-01

    Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were r...

  5. Locally advanced cervix carcinoma - innovation in combined modality therapy

    International Nuclear Information System (INIS)

    Locally advanced cervical carcinoma continues to be a challenge to the clinician due to local failure as well as systemic metastases. Standard intracavitary and external beam techniques result in local control rates of only 35-65%, with long term survival rates of 25-60% in patients with state IIIA-IVA disease, indicating the need to identify new treatment strategies. Optimization programs for remote-afterloading interstitial brachytherapy allow the delivery of higher local doses of radiation to volumes that more closely approximate tumor target volumes as identified on MR scans, leading to improved therapeutic ratios. Identification of subsets of patients more likely to fail standard therapy, either locally or systemically, may be possible through such techniques as in vivo measurements of hypoxia with Eppendorf oxygen electrodes, interstitial fluid pressure measurements, the Comet assay, and nitroimidazole binding methods. Traditional chemotherapies, administered in either a neoadjuvant role or concomitantly with radiation have been disappointing in prospective trials. A variety of new agents are being investigated to determine if they can increase the frequency or duration of complete response. The taxanes, with response rates of 17-23% by themselves, are being assessed as potential radiosensitizers. The camptotheicin CRT-11 (Irinotecan) has demonstrated activity in platinum resistant cervix cancer, with response rates of 24%. Bioradiotherapeutic approaches, using 13-cis-retinoic acid and interferon-2a, are undergoing phase II studies. Neoangiogenesis inhibitors and vaccines against HPV are also being examined. The aggressive pursuit of techniques that help identify those patients most likely to fail, that allow the delivery of higher radiation doses more safely to the target volume, and that incorporate the use of more effective systemic therapies is necessary to improve the outcome for this disease

  6. Paclitaxel, Bevacizumab And Adjuvant Intraperitoneal Carboplatin in Treating Patients Who Had Initial Debulking Surgery for Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    Science.gov (United States)

    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; Stage II Ovarian Epithelial Cancer; Stage III Ovarian Epithelial Cancer; Stage IV Ovarian Epithelial Cancer

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

    Science.gov (United States)

    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

  8. Targeting of p38 Mitogen-activated Protein Kinases to Early Growth Response gene 1 (EGR-1) in the Human Paclitaxel-resistance Ovarian Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    Meisong LU; Lan XIAO; Jianli HU; Suo DENG; Yan XU

    2008-01-01

    To investigate the relationship between the expression of early growth response gene 1(EGR-1) and p38MAPK pathway in the paclitaxel resistance of ovarian carcinoma cells, the effect of p38MAPK inhibitor SB203580 on cell apoptosis was examined by using Hoechst 33258 staining.The intracellular Rh123 (Rhodamine 123) accumulation was detected by the flow cytometry (FCM).The 50% inhibition concentration (IC50) of paclitaxel for A2780/Taxol cells was determined by MTT method. Electrophoretic motility shift assay (EMSA) was employed to examine the EGR-1DNA binding activity. MDR1 and EGR-1 mRNA were assessed by RT-PCR. The expressed of p-gp, phosphorylated p53 and p38 were detected by Western blotting. SB203580 could remarkably promote the apoptosis of A2780/Taxol cells, and the cell apoptosis was in a time-dependent manner. Cellular Rh123 accumulation was increased, and the IC50 of paclitaxel for A2780/Taxol cells was decreased significantly. A2780/Taxol cell line after SB203580 treatment was shown to have a significantly higher level of EGR-1 DNA binding activity. SB203580 down-regulated the activity of p38MAPK pathway, but up-regulated EGR-1 expression. SB203580 significantly increased the level of cellular phosphorylated p53 protein, but decreased the p-gp protein level and MDR1 mRNA level in A2780/Taxol cells. There existed a close relationship between p38MAPK pathway and the paclitaxel resistance of ovarian carcinoma cells. The expression of EGR-1 mediated by p38MAPK pathway plays a critical role in paclitaxel resistance of ovarian carcinoma cells.

  9. Expression of the human fast-twitch skeletal muscle troponin I cDNA in a human ovarian carcinoma suppresses tumor growth

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    To explore the efficiency and mechanism of ovarian carcinoma gene therapy with the human fast-twitch skeletal muscle troponin I gene (TnI-fast), TnI-fast cDNA was transferred into human ovarian adeno-carcinoma cell-line SK-OV-3. In vitro, the cell growth and cell cycle of TnI-fast-, vector-, and mock-transfected cells were determined by MTT and flow cytometry assay, respectively. The condi-tioned media of TnI-fast-, vector-, and mock-transfected SK-OV-3 cells were collected, and the cell pro-liferation inhibiting rates of human umbilical cord venous endothelial cells (HUVECs) by the three conditioned media were assayed. All the three cell lines were implanted into node mice, and the tumor growth, cell apoptosis, angiogenesis, and expression of TnI-fast were observed or analyzed, respec-tively. In vitro, expression of TnI-fast protein had no inhibiting effect on the growth of the dominant and stable transfectant cells, but endothelium, when compared with vector-transfected cells and nontrans-fected parental SK-OV-3 cells. Implantation of stable clone expressing TnI-fast in the female BALB/c nude mice inhibits primary tumor growth by an average of 73%. The nude mice grafts expressing TnI-fast exhibit a significant decrease of microvascular density, a higher rate of tumor cells apoptosis and a comparable proliferation rate as control. Our study, to our knowledge, shows the slowed down growth of the primary ovarian carcinoma, suggested that grafts were self-inhibitory by halting angio-genesis. Our data might also provide a novel useful strategy for cancer therapy by antiangiogenic gene therapy with a specific angiogenesis inhibitor TnI-fast.

  10. G蛋白耦联雌激素受体-1与卵巢癌%G Protein-coupled Estrogen Receptor-1 and Ovarian Carcinoma

    Institute of Scientific and Technical Information of China (English)

    蒋雪莉; 闫彦; 刘国艺

    2013-01-01

    G protein-coupled estrogen receptor 1 (GPER-1) is a novel estrogen receptor,which has been found to mediate the non-genomic effects of estrogen.GPER-1 has a high affinity to natural and synthetic estrogens.It is capable of activating multiple second messengers and rapid signaling pathways,and indirectly regulates transcriptional activities of estrogens.A growing body of evidence has demonstrated that GPER-1 is involved in the tumorigenesis and progression of female reproductive malignancies.GPER-1 is overexpressed in ovarian carcinomas,and predicts the poor outcome of the disease.GPER-1 might serve as a therapeutic target in the treatment of ovarian carcinomas.In the present review,the structure,location and signaling transduction of GPER-1,and its biological functions in ovarian carcinomas were discussed,and its prospect as a new therapeutic target of ovarian carcinomas was also previewed.%G蛋白耦联雌激素受体-1(G protein-coupled estrogen receptor l,GPER-1)是一种新型的雌激素受体,能够介导雌激素的快速非基因组效应.GPER-1与雌激素具有高亲和力,能与天然雌激素和人工合成雌激素结合,快速激活细胞内第二信使或级联信号通路,间接调节转录活动,从而介导雌激素的生物学效应.GPER-1的亚细胞定位存在争议,因其亚细胞定位可能取决于不同的细胞类型.另外,性别、年龄等内在因素以及细胞外刺激、损伤等外在因素也影响GPER-1在质膜的相对丰度.近年来研究表明GPER-1的表达与女性生殖系统肿瘤的发生、发展密切相关,在卵巢癌组织中高表达,参与卵巢癌的发生发展,并可能作为评价卵巢癌患者预后的指标,有望成为卵巢癌重要的治疗靶点.

  11. Advanced Ovarian Dysgerminoma Infiltrating Both Ovaries and Uterus in a 7-Year-Old Girl

    OpenAIRE

    Nexhmi Hyseni; Sadik Llullaku; Hysni Jashari; Kaltrina Zahiti; Fjolla Hyseni; Fisnik Kurshumliu; Lumturije Luci; Fehim Muqolli; Antigona Hasani

    2014-01-01

    Introduction. Ovarian dysgerminoma is a rare malignant ovarian germ cell tumor with its peak incidence in young women. Abdominal pain, abdominal distention, and the presence of a palpable mass are common symptoms at presentation. Depending on the FIGO stage at presentation the prognosis of dysgerminomas after surgical treatment, adjuvant chemotherapy, and radiotherapy is promising. Case Presentation. A 7-year-old girl was presented at our clinic with abdominal pain in all abdominal quadrants....

  12. Alternative treatment of chemoresistant, recurrent or advanced ovarian cancer. Part II

    Directory of Open Access Journals (Sweden)

    Jacek R. Wilczyński

    2011-10-01

    Full Text Available Lack of satisfactory efficacy of classical chemotherapy in ovarian tumours led to attempts of treatmentbased on use of small molecules able to modulate or inhibit intracellular pathways engaged in cell growth,proliferation and apoptosis. The paper presents clinical trials in ovarian cancer patients using such drugs as:1 protein kinase inhibitors, 2 molecules interfering with DNA transcription and repair, 3 inhibitors oftranscription factors NF-κB and HIF-1.

  13. Potential for imaging ovarian carcinoma by radioiodinated 11. beta. methoxy 17. cap alpha. -iodovinylestradiol (MIVE/sub 2/)

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, R.E.; Holt, J.A.; Greene, G.L.; Jagoda, E.M.; Eckelman, W.C.; Rzeszotarski, W.J.; Francis, B.E.; Reba, R.C.

    1984-01-01

    I-125 labeled MIVE/sub 2/ provides the highest extent of receptor mediated localization and the highest uterus to blood ratio (immature rat) of any radioiodinated derivative of estradiol. The authors have determined that 48% of the activity which localizes in the uterus remains after 24 hrs. Nonetheless, in vivo the I-127 derivative is an agonist as demonstrated by the induction of progesterone synthesis by the ovaries of rabbit. In addition to estrogen dependent breast tumors, ovarian carcinoma (OVCA) has been shown to exhibit high concentrations of estrogen receptor. The receptor isolated from OVCA has been studied using I-125 labeled MIVE/sub 2/ as the receptor radiotracer. In addition to sucrose gradient profiles consistent with that of ER and competition studies (diethylstilbestrol and estradiol compete, testosterone, progesterone and cortisol do not) consistent with an ER drug profile, antibodies H222, H226 (Abbott Lab.) and D547, all raised against human breast cancer, interact with the receptor from OVCA. The affinities of MIVE/sub 2/ for ER from rat uterus and OVCA are the same (K/sub A/ = 6.5 x 10/sup 9/ M/sup -1/ and K/sub A/ = 9.1 x 10/sup 9/ M/sup -1/, respectively). These results are consistent with the receptor being ER. The longer retention time of MIVE/sub 2/ in ER rich tissue should provide time for clearance of radiotracer from background tissues to allow the imaging of OVCA primaries and metasteses. In addition, MIVE/sub 2/ labeled with I-131 or an analogue containing Br-80m or Br-77, may prove radiotoxic to the receptor rich OVCA.

  14. The Effects of Vandetanib on Paclitaxel Tumor Distribution and Antitumor Activity in a Xenograft Model of Human Ovarian Carcinoma

    Directory of Open Access Journals (Sweden)

    Marta Cesca

    2009-11-01

    Full Text Available This study was designed to determine the effects of vandetanib, a small-molecule receptor tyrosine kinase inhibitor of vascular endothelial growth factor and epidermal growth factor receptor, on paclitaxel (PTX tumor distribution and antitumor activity in xenograft models of human ovarian carcinoma. Nude mice bearing A2780-1A9 xenografts received daily (5, 10, or 15 days doses of vandetanib (50 mg/kg per os, combined with PTX (20 mg/kg intravenously. Morphologic and functional modifications associated with the tumor vasculature (CD31 and α-smooth muscle actin staining and Hoechst 33342 perfusion and PTX concentrations in plasma and tumor tissues were analyzed. Activity was evaluated as inhibition of tumor growth subcutaneously and spreading into the peritoneal cavity. Vandetanib treatment produced no significant change in tumor vessel density, although a reduced number of large vessels, an increased percentage of mature vessels, and diminished tumor perfusion were evident. Pretreatment with vandetanib led to decreased tumor PTX levels within 1 hour of PTX injection, although 24 hours later, tumor PTX levels were comparable with controls. In efficacy studies, the combination of vandetanib plus PTX improved antitumor activity compared with vandetanib or PTX alone, with greater effects being obtained when PTX was administered before vandetanib. The combination of PTX plus vandetanib reduced tumor burden in the peritoneal cavity of mice and significantly increased their survival. Analysis of vascular changes and PTX tumor uptake in vandetanib-treated tumors may help to guide the scheduling of vandetanib plus PTX combinations and may have implications for the design of clinical trials with these drugs.

  15. Apoptosis is triggered by melatonin in an in vivo model of ovarian carcinoma.

    Science.gov (United States)

    Chuffa, Luiz Gustavo A; Alves, Michelly S; Martinez, Marcelo; Camargo, Isabel Cristina C; Pinheiro, Patricia F F; Domeniconi, Raquel F; Júnior, Luiz Antonio L; Martinez, Francisco Eduardo

    2016-02-01

    Apoptosis plays an important role in the treatment of cancer, and targeting apoptosis-related molecules in ovarian cancer (OC) is of great therapeutic value. Melatonin (Mel) is an indoleamine displaying several anti-cancer properties and has been reported to modulate apoptosis signaling in multiple tumor subtypes. We investigated OC and the role of Mel therapy on the pro-apoptotic (p53, BAX, caspase-3, and cleaved caspase-3) and anti-apoptotic (Bcl-2 and survivin) proteins in an ethanol (EtOH)-preferring rat model. To induce OC, the left ovary was injected directly with a single dose of 100 μg 7,12-dimethylbenz(a)anthracene dissolved in 10 μl of sesame oil under the bursa. Right ovaries were used as sham-surgery controls. After developing OC, half of the animals received i.p. injections of Mel (200 μg/100 g BW per day) for 60 days. Body weight gain, EtOH consumption, and energy intake were unaffected by the treatments. Interestingly, absolute and relative OC masses showed a significant reduction after Mel therapy, regardless of EtOH consumption. To accomplish OC-related apoptosis, we first observed that p53, BAX, caspase-3, and cleaved caspase-3 were downregulated in OC tissue while Bcl-2 and survivin were overexpressed. Notably, Mel therapy and EtOH intake promoted apoptosis along with the upregulation of p53, BAX, and cleaved caspase-3. Fragmentation of DNA observed by TUNEL-positive nuclei was also enhanced following Mel treatment. In addition, Bcl-2 was downregulated by the EtOH intake and lower survivin levels were observed after Mel therapy. Taken together, these results suggest that Mel induce apoptosis in OC cells of EtOH-preferring animals. PMID:26555801

  16. Weekly dose-dense paclitaxel and carboplatin in recurrent ovarian carcinoma: A phase II trial

    International Nuclear Information System (INIS)

    Purpose: The aim of this study was to investigate efficacy and toxicity of the dose-dense weekly paclitaxel (T) and carboplatin (C) in the management of platinum-resistant/sensitive recurrent epithelial ovarian cancer (EOC) previously treated with 3 weekly paclitaxel/carboplatin. Methods: Thirty two patients with recurrent EOC who had received 3 weekly TC before were enrolled. Nine patients relapsed within 6 months (platinum-resistant), 13 patients relapsed after 12 months (platinum-sensitive) and in 10 patients recurrence occurred between 6 and 12 months (intermediate platinum-sensitive). Weekly (T) at a dose of 80 mg/m2, followed by weekly (C) AUC 2 on day 1, 8, and 15 of a 28-day cycle for 6 planned cycles were administrated. End-points were overall response rate (ORR), progression free survival (PFS), overall survival (OS) and toxicity. Results: The ORR was 62.5%. For the platinum-resistant, intermediate platinum-sensitive and platinum-sensitive patients the ORR was 44.4% (4/9), 60% (6/10) and 76.9% (10/13), respectively, and 1 (11.1%), 2 (20%) and 5 (38.46%) patients, respectively had CR. PFS was 9.1 months (6.13, 9.1 and 12.17 months, for the 3 groups, respectively) (P < 0.001). OS was 14 months (9.17, 15.2, and 19.23 months, for the 3 groups, respectively) (P < 0.001). Treatment-related adverse events were manageable with only 1 patient (3.1%) suffering from grade 4 neutropenia. Grade 3 hematological and non-hematological toxicities were neutropenia in 8 (25%), and peripheral neuropathy in 4 (12.5%) patients, respectively. Conclusion: Weekly TC is active and well-tolerated in platinum-resistant and platinum-sensitive patients with recurrent EOC previously treated with TC given every 3 weeks

  17. Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas.

    KAUST Repository

    Jain, Harsh Vardhan

    2014-01-06

    Platinum drug-resistance in ovarian cancers mediated by anti-apoptotic proteins such as Bcl-xL is a major factor contributing to the chemotherapeutic resistance of recurrent disease. Consequently, concurrent inhibition of Bcl-xL in combination with chemotherapy may improve treatment outcomes for patients. Here, we develop a mathematical model to investigate the potential of combination therapy with ABT-737, a small molecule inhibitor of Bcl-xL, and carboplatin, a platinum-based drug, on a simulated tumor xenograft. The model is calibrated against in vivo experimental data, wherein xenografts established in mice were treated with ABT-737 and/or carboplatin on a fixed periodic schedule. The validated model is used to predict the minimum drug load that will achieve a predetermined level of tumor growth inhibition, thereby maximizing the synergy between the two drugs. Our simulations suggest that the infusion-duration of each carboplatin dose is a critical parameter, with an 8-hour infusion of carboplatin given weekly combined with a daily bolus dose of ABT-737 predicted to minimize residual disease. The potential of combination therapy to prevent or delay the onset of carboplatin-resistance is also investigated. When resistance is acquired as a result of aberrant DNA-damage repair in cells treated with carboplatin, drug delivery schedules that induce tumor remission with even low doses of combination therapy can be identified. Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified. These results highlight the potential of our model to accelerate the development of novel therapeutics such as BH3 mimetics.

  18. Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

    OpenAIRE

    Sanambar Sadighi; Amanolah Keyhani; Iraj Harirchi; Ata Garajei; Mahdi Aghili; Ali Kazemian; Maziar Motiee Langroudi; Kazem Zendehdel; Nariman Nikparto

    2015-01-01

    To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF) induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SP...

  19. Standardized FDG uptake as a prognostic variable and as a predictor of incomplete cytoreduction in primary advanced ovarian cancer

    DEFF Research Database (Denmark)

    Risum, Signe; Jakobsen, Annika Loft; Høgdall, Claus;

    2011-01-01

    Abstract Introduction. In patients with advanced ovarian cancer undergoing preoperative PET/CT, we investigated the prognostic value of SUV in the primary tumor and we evaluated the value of SUV for predicting incomplete primary cytoreduction (macroscopic residual tumor). Material and methods. From...... 15, 2009) the association between SUV and overall survival/cytoreductive result were analyzed in 60 ovarian cancer patients (58 stage III and two stage IV). Results. At inclusion median age was 62 years (range 35-85 years); 97% (58/60) had a performance status =2; 42% (25/60) underwent complete...... debulking (no macroscopic residual tumor); median SUV(max) was 13.5 (range 2.5-39.0). Median follow-up was 30.2 months. At follow-up 57% (34/60) were alive and 43% (26/60) had died from ovarian cancer. SUV(max) in patients alive was not statistically different from SUV(max) in dead patients (p=0.69), and...

  20. Complete remission of advanced hepatocellular carcinoma by radiofrequency ablation after sorafenib therapy

    OpenAIRE

    Park, Jung Gil; Park, Soo Young; Lee, Hye Won

    2015-01-01

    Sorafenib, a potent multikinase inhibitor, lead to a significant improvement in progression free survival and overall survival in patients with advanced hepatocellular carcinoma (HCC). Though sorafenib has proven its efficacy in advanced stage HCC, there are limited reports on the role of sorafenib allowing for curative treatment by down-staging. We herein report a case of advanced HCC with vascular invasion, which showed treatment response by sorafenib therapy as to allow for radiofrequency ...

  1. Cryotherapy is associated with improved clinical outcomes of sorafenib for the treatment of advanced hepatocellular carcinoma

    OpenAIRE

    Yang, Yongping; LU, YINYING; Wang, Chunping; Bai, Wenlin; Qu, Jianhui; Chen, Yan; Chang, Xiujuan; An, Linjing; Zhou, Lin; Zeng, Zhen; Lou, Min; LV, JIYUN

    2011-01-01

    Sorafenib may prolong survival in patients with advanced hepatocellular carcinoma (HCC), but with limited efficacy. The present study aimed to assess the safety and efficacy of sorafenib combined with cryotherapy (cryoRx) for the treatment of advanced HCC. A total of 104 patients met the following criteria: advanced HCC without distant metastasis, presence of portal vein thrombosis, Child-Pugh class A or B and life expectancy of at least 12 weeks. All patients were randomly assigned to sorafe...

  2. Case analysis of complete remission of advanced hepatocellular carcinoma achieved with sorafenib

    OpenAIRE

    Liu, Daizhong; Liu, Aixiang; Peng, Junping; Hu, Yong; Feng, Xielin

    2015-01-01

    Background To evaluate the feasibility and security of complete remission (CR) of advanced hepatocellular carcinoma (HCC) achieved with sorafenib treatment, and investigate the previously described predictive factors in CR. Methods The case of a patient who achieved CR of advanced HCC with sorafenib treatment was analyzed. The case analysis was performed by a literature review of relevant reports retrieved from the PubMed database. Results A 58-year-old male patient achieved CR of advanced HC...

  3. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    Science.gov (United States)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  4. Case report from Mayo Clinic. Locally advanced Bartholin gland carcinoma

    International Nuclear Information System (INIS)

    Tumors of the Bartholin gland are rare, comprising less than 5% of all vulvar malignancies. Treatment is largely based on that of vulvar and anal squamous cell carcinomas. A case of invasive, grade 4, poorly differentiated squamous cell carcinoma of the Bartholin gland is presented. Our patient, a 47-year-old woman, had a history significant for cervical intraepithelial neoplasia treated with conization, type 2 diabetes mellitus, and tobacco use. The course of treatment included preoperative radiotherapy plus 5-fluorouracil and cisplatin chemotherapy, followed by restaging and posterior exenteration in combination with vaginal reconstruction. (author)

  5. Standard first-line chemotherapy with or without nintedanib for advanced ovarian cancer (AGO-OVAR 12)

    DEFF Research Database (Denmark)

    Bois, Andreas du; Kristensen, Gunnar; Ray-Coquard, Isabelle;

    2016-01-01

    combination of nintedanib with standard carboplatin and paclitaxel chemotherapy in patients with newly diagnosed advanced ovarian cancer. METHODS: In this double-blind phase 3 trial, chemotherapy-naive patients (aged 18 years or older) with International Federation of Gynecology and Obstetrics (FIGO) IIB...... endpoint was investigator-assessed progression-free survival analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01015118. FINDINGS: Between Dec 9, 2009, and July 27, 2011, 1503 patients were screened and 1366 randomly assigned by nine study groups in...

  6. Dys-psychological Stress Effect on Expressions of P53 and NFκBp65 in Human Ovarian Carcinoma In Vivo

    Institute of Scientific and Technical Information of China (English)

    Li-qun Yu; Guo-lan Gao; Fun-jun Liu; Qiong-jing Zeng

    2012-01-01

    Objective:To investigate the dys-psychological stress effect on the growth of subcutaneous xenotransplanted tumor in nude mice bearing human epithelium ovarian carcinoma,and the influence on P53 and NFκBp65 expressions.Methods:The subcutaneous tumor xenografts were established by implanting human epithelium ovarian carcinoma tissues into nude mice and the dys-psychological stress model was established with restraint.The mice were randomized into the following four treatment groups with each group six mice respectively:tumor group (group A),normal saline intraperitoneal injection; tumor with stress group (group B),normal saline intraperitoneal injection;tumor therapy group (group C),cisplatin intraperitoneal injection; and tumor therapy with stress group (group D),cisplatin intraperitoneal injection.The expressions of P53 and NFκBp65 in tumor tissues were determined by Western blotting.Results:The expressions of P53 and NFκBp65 in each restraint group were enhanced compared with the control groups (P<0.05).Conclusion:The dys-psychological stress may induce the high expressions of P53 and NFκBp65 proteins and further promote tumor growth.

  7. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Choueiri, Toni K; Escudier, Bernard; Powles, Thomas;

    2015-01-01

    antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. METHODS: We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily...

  8. Catamnestic studies of radiosurgical combination therapy of advanced carcinoma of the larynx

    International Nuclear Information System (INIS)

    The first part of the study summarizes the post-therapeutical course of development of 165 patients who have been treated for advanced internal and external carcinoma of the larynx with a combined, pre- or postoperative radiosurgical therapy, with particular attention being paid to the frequency of focal or lymph node recidivation, post-therapeutical apparent distant metastases and postoperative complications, and also to tumour-independent mortality. The second part of the study is concerned with the determination of survival rates of patients suffering from advanced carcinoma of the larynx or hypopharynx, following low-dose preoperative irradiation (119 patients) or postoperative irradiation (209 patients). (orig./MG)

  9. Expression of Hyaluronan Synthases (HAS1–3 and Hyaluronidases (HYAL1–2 in Serous Ovarian Carcinomas: Inverse Correlation between HYAL1 and Hyaluronan Content

    Directory of Open Access Journals (Sweden)

    Heikkinen Anna-Mari

    2009-05-01

    Full Text Available Abstract Background Hyaluronan, a tumor promoting extracellular matrix polysaccharide, is elevated in malignant epithelial ovarian tumors, and associates with an unfavorable prognosis. To explore possible contributors to the accumulation of hyaluronan, we examined the expression of hyaluronan synthases (HAS1, HAS2 and HAS3 and hyaluronidases (HYAL1 and HYAL2, correlated with hyaluronidase enzyme activity hyaluronan content and HAS1–3 immunoreactivity. Methods Normal ovaries (n = 5 and 34 serous epithelial ovarian tumors, divided into 4 groups: malignant grades 1+2 (n = 10; malignant grade 3 (n = 10; borderline (n = 4 and benign epithelial tumors (n = 10, were analyzed for mRNA by real-time RT-PCR and compared to hyaluronidase activity, hyaluronan staining, and HAS1–3 immunoreactivity in tissue sections of the same specimens. Results The levels of HAS2 and HAS3 mRNA (HAS1 was low or absent, were not consistently increased in the carcinomas, and were not significantly correlated with HAS protein or hyaluronan accumulation in individual samples. Instead, the median of HYAL1 mRNA level was 69% lower in grade 3 serous ovarian cancers compared to normal ovaries (P = 0.01. The expression of HYAL1, but not HYAL2, significantly correlated with the enzymatic activity of tissue hyaluronidases (r = 0.5; P = 0.006. An inverse correlation was noted between HYAL1 mRNA and the intensity of hyaluronan staining of the corresponding tissue sections (r = -0.4; P = 0.025. Conclusion The results indicate that in serous epithelial ovarian malignancies HAS expression is not consistently elevated but HYAL1 expression is significantly reduced and correlates with the accumulation of hyaluronan. (233 words

  10. Expression of the tumor suppressor gene PTEN is not altered in the progression of ovarian carcinomas and does not correlate with p27Kip1 expression.

    Science.gov (United States)

    Schöndorf, Thomas; Hoopmann, Markus; Eversheim, Barbara; Valter, Markus M; Becker, Martina; Wappenschmidt, Barbara; Göhring, Uwe-Jochen; Kübler, Tanja; Schmutzler, Rita K; Schäfer, Robert

    2003-01-01

    This study was designed to investigate the role of PTEN in the progression of ovarian cancer. We performed mutation analysis and determined PTEN gene expression in tissue from both primary and relapsed cancers and in the corresponding occult metastases. Furthermore, p27Kip1 staining was conducted in order to explore a putative functional link. The study group comprised 112 tumor tissue specimens from 37 ovarian cancer patients. Expression of both PTEN and p27Kip1 was determined by immunohistochemistry. The PTEN mutational spectrum was determined by PCR-based sequence analysis. Fifty-six per cent of the tumors were positive for PTEN expression and 75% were p27Kip1 positive. For both markers, tumor cells ranged from 0 to 90% positivity. In 55% (20/37) of the cases, PTEN expression in the primary tumor was consistent and in the corresponding advanced cancer tissues, whereas the remainder showed considerable variation. p27Kip1 was consistently expressed in 16 out of 37 cases (43%). No mutations were observed in the coding region of the PTEN gene. No correlation was observed between PTEN and p27Kip1 expression. Our data indicate that expression of PTEN, but not p27Kip1 (one of the major mediators of PTEN function) is unchanged during the progression of ovarian cancer. This study suggests that in ovarian cancer PTEN does not play a major role in disease progression and is not involved in the alteration of p27Kip1 expression. PMID:14534684

  11. Uptake of a nido-carboranylporphyrin by human glioma xenografts in athymic nude mice and by syngeneic ovarian carcinomas in immunocompetent mice

    International Nuclear Information System (INIS)

    A tetraphenylporphyrin bearing four dicarbollide ([B9C2H11]-) cages linked to the o-phenyl ring positions by anilide bonds, known as boronated tetraphenylporphyrin (BTPP), has been synthesized in excellent yield from tetra-(o-aminophenyl)porphyrin and carborane carbonyl chloride followed by base-assisted cage opening and ion exchange to give the highly water-soluble potassium salt. Preliminary studies showed that BTPP accumulates in liver and in a syngeneic ovarian carcinoma, but not in normal brain parenchyma, of mice infused with BTPP subcutaneously for 6 or 7 days via surgically implanted osmotic minipumps. In this study, the uptake of boron was measured in human gliomas xenografted subcutaneously to athymic nude mice in which BTPP was infused intraperitoneally or subcutaneously or both for 3 or 7 days by using similar minipumps. Immunocompetent mice bearing a syngeneic ovarian carcinoma were similarly infused to provide comparative data. Bulk concentrations of boron up to 18 μg/g of glioma and up to 45 μg/g of carcinoma were observed when up to 102 μg/g of tissue was present in the liver after 7 days of BTPP infusion. Glioma boron concentrations were increased by ∼80% on the average correspondingly greater amounts of BTPP were infused in only 3 days. Cell counts and chemical tests on blood samples from individual mice indicate that BTPP causes moderate hepatotoxicity and thromboxytopenia. This hepatohematic toxicity syndrome should be taken into account if BTPP or a similar agent is used for boron neutron-capture therapy (BNCT) of human malignancies

  12. Ovarian Cancer in Hereditary Cancer Susceptibility Syndromes.

    Science.gov (United States)

    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

  13. Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

    OpenAIRE

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-01-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was...

  14. Advanced Pyoderma Gangrenosum Previously Treated as Squamous Cell Carcinoma

    OpenAIRE

    Tamara Čuk Radović; Krešimir Kostović; Jaka Radoš; Zrinjka Paštar; Gordana Pavliša; Branka Marinović

    2015-01-01

    Pyoderma gangrenosum is a rare, neutrophilic ulcerative skin disease of unknown etiology often associated with an underlying systemic disease. We present a case of a pyoderma gangrenosum that was initially misdiagnosed and treated as squamous cell carcinoma in another hospital. Multiple surgical treatments triggered postoperative exacerbations and further rapid progression of the lesions. History of pathergy, clinical findings, and histopathological features examined at our Department indicat...

  15. Targeted treatments in advanced renal cell carcinoma: focus on axitinib

    Directory of Open Access Journals (Sweden)

    Verzoni E

    2014-03-01

    Full Text Available Elena Verzoni, Paolo Grassi, Isabella Testa, Roberto Iacovelli, Pamela Biondani, Enrico Garanzini , Filippo De Braud, Giuseppe ProcopioDepartment of Medical Oncology 1, Fondazione IRCCS Istituto Nazionale Tumori, Milan, ItalyAbstract: Antiangiogenesis options have evolved rapidly in the last few years, with an increasing number of agents currently approved by the US Food and Drug Administration and European Medicines Agency. Angiogenesis inhibitors have been shown to be very effective for the treatment of metastatic renal cancer cell. Axitinib is a third-generation inhibitor of vascular endothelial growth factor receptor and is currently being developed for the treatment of various malignancies. The pharmacokinetic properties of axitinib may have a selective therapeutic effect, with minimal adverse reactions and enhanced safety. In a large Phase III study of previously treated patients with metastatic renal cell carcinoma, axitinib achieved a longer progression-free survival than sorafenib with an acceptable safety profile and good quality of life. This review focuses on the pharmacology, pharmacokinetics, and clinical activity of axitinib in the current treatment of renal cell carcinoma. The role of axitinib in the adjuvant and/or neoadjuvant setting needs to be evaluated in further clinical trials.Keywords: axitinib, renal cell carcinoma, vascular endothelial growth factor receptor, angiogenesis

  16. Pelvic-peritoneal tuberculosis mimicking ovarian cancer

    International Nuclear Information System (INIS)

    Pelvic-peritoneal tuberculosis is a common extrapulmonary site in young females mimicking an advanced ovarian malignancy. We present 2 cases with the classical triad of advanced-stage ovarian carcinoma-ascites, abdominopelvic masses and elevated serum CA-125 levels. Laparoscopic examination revealed peritoneal nodules which on biopsy showed granulomatous inflammation and no malignant cells. Patients were started on anti-tuberculous therapy and on follow-up their symptoms as well as CA-125 levels normalized. Medical awareness of peritoneal tuberculosis is lacking and many young women with this disease undergo unnecessary extended surgery. Diagnostic laparoscopy combined with peritoneal biopsy seems to be a sufficient and safe method to provide a definitive diagnosis for this curable infection. If left untreated, the disease may disseminate and result in significant organ dysfunctions particularly infertility. (author)

  17. FXYD5 is a Marker for Poor Prognosis and a Potential Driver for Metastasis in Ovarian Carcinomas

    OpenAIRE

    Pichai Raman; Timothy Purwin; Richard Pestell; Aydin Tozeren

    2015-01-01

    Ovarian cancer (OC) is a leading cause of cancer mortality, but aside from a few well-studied mutations, very little is known about its underlying causes. As such, we performed survival analysis on ovarian copy number amplifications and gene expression datasets presented by The Cancer Genome Atlas in order to identify potential drivers and markers of aggressive OC. Additionally, two independent datasets from the Gene Expression Omnibus web platform were used to validate the identified markers...

  18. Trimodality Therapy for an Advanced Thymic Carcinoma With Both Aorta and Vena Cava Invasion.

    Science.gov (United States)

    Momozane, Tohru; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Okumura, Meinoshin

    2016-08-01

    A case of locally advanced thymic carcinoma that was successfully resected with the great vessels after chemoradiation therapy is reported. A 57-year-old man with Masaoka stage III thymic carcinoma received two cycles of cisplatin/docetaxel and 60 Gy irradiation. The response was stable disease with 19% size reduction, and a radical resection with the ascending aorta and superior vena cava with the patient under circulatory arrest with the use of cardiopulmonary bypass was performed. The postoperative course was uneventful, and the patient has been free of disease for 28 months. Trimodality therapy with use of a cardiovascular surgical procedure might be a valuable option in locally advanced thymic carcinoma. PMID:27449450

  19. A STUDY OF ENDOSCOPIC TREATMENT OF ADVANCED ESOPHAGEAL AND GASTRIC CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    Zhang Jichang; Zhang Lijian; Wang Yanmeng; Li Wei

    1998-01-01

    Objective: To investigate the effect of endoscopic treatment on advanced esophageal and gastric carcinoma.Methods: Twenty advanced gastric cancer patients and 25advanced esophageal cancer patients, who had recurrence after operation and radiotherapy were managed by endoscopic treatment. Results: 10 cases were treated to stop bleeding only, 35 cases were treated by microwave,dilation and local chemotherapy. The successful rate of hemostasis was about 67%, the remission rate of digestive obstruction was about 100% after dilation, 83% of the recurrence lesions were relieved by endoscopic chemotherapy. Conclusion: Endoscope treatment has certain therapeutic efficiency for the recurrence of advanced esophageal and gastric cancer.

  20. P53, MAPK, topoisomerase II alpha and Ki67 immunohistochemical expression and KRAS/BRAF mutation in ovarian serous carcinomas

    Directory of Open Access Journals (Sweden)

    Sundov Dinka

    2013-02-01

    Full Text Available Abstract Background We investigated the immunohistochemical expression of p53, MAPK, topoisomerase II alpha (topoII alpha and Ki67 in ovarian serous carcinomas (OSCs along with mutational analysis for KRAS and BRAF. Methods Eighty one cases of OSCs were reviewed and examined immunohistochemically using antibodies against p53, MAPK, topoII alpha and Ki67. Staining was evaluated as a percentage of immunopositive cells with cut-off levels at 10% for p53 and topoII alpha, and 5% for MAPK. The Ki67 immunoexpression was assessed by means of Olympus Image Analysis System as a percentage of immunopositive cells in 1000 tumor cells. KRAS and BRAF mutational analysis was performed on 73 available microdissected samples. Results Of 81 cases of OSCs 13.6% were of low-grade and 86.4% were of high-grade morphology. In the high-grade group there was a significantly higher immunoexpression of p53 (P P = 0.001, with Ki67 median 56.5 vs. 19 in low-grade group (P P = 0.003. MAPK positive immunostaining was detected in 63.6% of low-grade vs. 17.1% of high-grade OSCs. The frequency of KRAS mutation was significantly higher in low-grade as compared to high-grade group (P = 0.006. None of the samples had BRAF mutation. In addition, we detected positive MAPK immunoexpression in 13/59 samples with wild-type KRAS, suggesting that activation of MAPK pathway is not ultimately related either to KRAS or BRAF mutation. Seven morphologically high-grade samples (11.7% showed both KRAS mutation and p53 immunopositivity. Conclusions Although this study is limited by its humble number of low-grade samples, our data fit the proposed dualistic pathway of ovarian carcinogenesis. Mutational analysis for KRAS and BRAF discloses some possible interactions between different tumorigenic pathways of low- and high-grade carcinomas. Immunohistochemical staining for MAPK was not sufficiently sensitive, nor specific, to precisely predict the KRAS mutation. However, it appears

  1. Prognostic significance of mediastinal 18F-FDG uptake in PET/CT in advanced ovarian cancer

    International Nuclear Information System (INIS)

    To evaluate the prognostic significance of increased mediastinal 18F-FDG uptake in PET/CT for the staging of advanced ovarian cancer. We retrospectively evaluated patients managed for FIGO stage III/IV ovarian cancer between 1 January 2006 and 1 June 2009. Patients were included if they had undergone 18F-FDG PET/CT and surgery for initial staging. Exclusion criteria were age younger than 18 years, inability to undergo general anaesthesia, recurrent ovarian cancer, and borderline or nonepithelial malignancy. Whole-body PET/CT was performed after intravenous 18F-FDG injection. The location of abnormal hot spots and 18F-FDG maximal standard uptake values (SUVmax) were recorded. We compared the complete cytoreduction and survival rates in groups defined based on mediastinal 18F-FDG uptake and SUVmax values. Kaplan-Meier curves of overall survival and disease-free survival were compared using the log-rank test. Hazard ratios with their 95% confidence intervals were computed. Adjusted hazard ratios were obtained using a multivariate Cox model. We included 53 patients, of whom 17 (32%) had increased mediastinal 18F-FDG uptake. Complete cytoreduction was achieved in 14 (87.5%) of the 16 patients managed with primary surgery and in 21 (75%) of the 28 patients managed with interval surgery. Complete cytoreduction was achieved significantly more often among patients without increased mediastinal 18F-FDG uptake (80.6% vs. 35.3%; p = 0.001). Disease-free survival was comparable between the two groups. By univariate analysis, overall mortality was significantly higher among patients with increased mediastinal 18F-FDG uptake (hazard ratio 5.70, 95% confidence interval 1.74-18.6). The only factor significantly associated with overall survival by multivariate analysis was complete cytoreduction (adjusted hazard ratio 0.24, 95% confidence interval 0.07-0.89). Increased mediastinal 18F-FDG uptake was common in patients with advanced ovarian cancer. However, complete cytoreduction

  2. Prognostic significance of mediastinal {sup 18}F-FDG uptake in PET/CT in advanced ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bats, Anne-Sophie; Lecuru, Fabrice [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Universite Paris Descartes, Sorbonne Paris Cite, INSERM UMR-S 747, Paris (France); Hugonnet, Florent; Faraggi, Marc [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France); Huchon, Cyrille [Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, Paris (France); Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Bensaid, Cherazade [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Chirurgie Gynecologique et Cancerologique, Paris (France); Pierquet-Ghazzar, Nadia [Hopital Europeen Georges-Pompidou, Assistance Publique-Hopitaux de Paris, Service de Medecine Nucleaire, Paris (France)

    2012-03-15

    To evaluate the prognostic significance of increased mediastinal {sup 18}F-FDG uptake in PET/CT for the staging of advanced ovarian cancer. We retrospectively evaluated patients managed for FIGO stage III/IV ovarian cancer between 1 January 2006 and 1 June 2009. Patients were included if they had undergone {sup 18}F-FDG PET/CT and surgery for initial staging. Exclusion criteria were age younger than 18 years, inability to undergo general anaesthesia, recurrent ovarian cancer, and borderline or nonepithelial malignancy. Whole-body PET/CT was performed after intravenous {sup 18}F-FDG injection. The location of abnormal hot spots and {sup 18}F-FDG maximal standard uptake values (SUV{sub max}) were recorded. We compared the complete cytoreduction and survival rates in groups defined based on mediastinal {sup 18}F-FDG uptake and SUV{sub max} values. Kaplan-Meier curves of overall survival and disease-free survival were compared using the log-rank test. Hazard ratios with their 95% confidence intervals were computed. Adjusted hazard ratios were obtained using a multivariate Cox model. We included 53 patients, of whom 17 (32%) had increased mediastinal {sup 18}F-FDG uptake. Complete cytoreduction was achieved in 14 (87.5%) of the 16 patients managed with primary surgery and in 21 (75%) of the 28 patients managed with interval surgery. Complete cytoreduction was achieved significantly more often among patients without increased mediastinal {sup 18}F-FDG uptake (80.6% vs. 35.3%; p = 0.001). Disease-free survival was comparable between the two groups. By univariate analysis, overall mortality was significantly higher among patients with increased mediastinal {sup 18}F-FDG uptake (hazard ratio 5.70, 95% confidence interval 1.74-18.6). The only factor significantly associated with overall survival by multivariate analysis was complete cytoreduction (adjusted hazard ratio 0.24, 95% confidence interval 0.07-0.89). Increased mediastinal {sup 18}F-FDG uptake was common in patients

  3. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Knigge, Ulrich; Federspiel, Birgitte;

    2014-01-01

    BACKGROUND: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second...

  4. Sorafenib and hepatic arterial infusion chemotherapy for unresectable advanced hepatocellular carcinoma: A comparative study

    OpenAIRE

    Hiramine, Yasunari; Uto, Hirofumi; Imamura, Yasushi; Tabu, Kazuaki; BABA, YOSHIROU; HIWAKI, TAKUYA; SHO, YUKIHIKO; TAHARA, KENJI; HIGASHI, HIROFUMI; TAMAI, TUTOMU; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

    2011-01-01

    Sorafenib is a kinase-targeted drug that has high efficacy for advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine whether sorafenib is more effective than hepatic arterial infusion chemotherapy (HAIC) for HCC. Twenty patients treated with sorafenib (sorafenib group) initiated at 800 mg/day and 45 patients treated with HAIC (HAIC group) for unresectable Child-Pugh A advanced HCC were investigated retrospectively. The treatment effect was assessed using the R...

  5. Sorafenib-induced acute interstitial pneumonia in patients with advanced hepatocellular carcinoma: report of three cases

    OpenAIRE

    Takeda, Haruhiko; Nishikawa, Hiroki; Iguchi, Eriko; Matsuda, Fumihiro; Kita, Ryuichi; Kimura, Toru; Osaki, Yukio

    2012-01-01

    Little is known about acute interstitial pneumonia (AIP) induced by sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC). Here, we present three patients with advanced HCC who developed AIP during sorafenib therapy, with fatal complications in two cases. Case 1 was a 76-year-old man who developed dyspnea. Chest CT showed interstitial pneumonia. Sorafenib was discontinued immediately, and prednisolone was started. His pneumonia resolved. A drug-induced lymphocyte stimulat...

  6. Tamoxifen compared to best supportive care in advanced hepatocelluar carcinoma: A retrospective matched-cohort study

    OpenAIRE

    Ahmed Abdelmabood Zeeneldin; Salem Mohamed Eid; Amira Diaa Darweesh; Manar Mohamed Moneer; Mohamed Saadeldin

    2014-01-01

    Background: Hepatocelluar carcinoma (HCC) is a common cancer worldwide as well as in Egypt with hepatitis B and C, alcohol and aflatoxins being the commonest risk factors. Tamoxifen was initially reported to confer a marginal survival benefit in advanced HCC. However, later reports declined any benefit. Objective: To study the impact of tamoxifen on overall survival (OS) compared to best supportive care (BSC) in Egyptian patients with advanced HCC. Methods: This retrospective matched-co...

  7. The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer.

    Science.gov (United States)

    Adams, M; Navabi, H; Croston, D; Coleman, S; Tabi, Z; Clayton, A; Jasani, B; Mason, M D

    2005-03-18

    A clinical trial employing an immunotherapeutic approach based on the use of a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes carrying tumour-associated antigens is planned in advanced ovarian cancer in conjunction with conventional first line chemotherapy. Most patients with ovarian cancer present with advanced disease and despite high initial response rate to chemotherapy the majority will relapse within 2 years with poor overall survival. Tumour antigen-specific T cells are naturally occurring in ovarian cancer patients and T cell infiltration of the tumour is highly prognostic. Novel immunotherapy to expand and activate tumour antigen-specific T cells combined with adjuvant treatment to overcome tumour-induced immunosuppression is considered to be therapeutically beneficial. The rationale for adopting such a combined approach is discussed here. PMID:15755631

  8. Extrauterine Pelvic Serous Carcinomas: Current Update on Pathology and Cross-sectional Imaging Findings.

    Science.gov (United States)

    Katabathina, Venkata S; Amanullah, Farhan S; Menias, Christine O; Chen, Melissa M; Valente, Philip T; Chintapalli, Kedar N; Prasad, Srinivasa R

    2016-01-01

    The spectrum of extrauterine pelvic serous carcinomas includes ovarian serous carcinoma, primary peritoneal serous carcinoma, and primary fallopian tube carcinoma. Ovarian serous carcinoma, the most common ovarian malignant epithelial neoplasm, consists of two distinct entities: high-grade and low-grade serous carcinomas. Primary peritoneal serous carcinoma and primary fallopian tube carcinoma are rare malignancies that share many characteristics of high-grade serous carcinomas. Recent advances in the genetics and molecular biology of gynecologic cancers have suggested a common origin of many extrauterine pelvic serous carcinomas from fallopian tube epithelium. With the exception of low-grade serous carcinomas, which arise from cortical inclusion cysts lined by tubal epithelium, most extrauterine pelvic serous carcinomas are believed to originate from serous tubal intraepithelial carcinomas and show similar clinical-biologic behaviors and natural histories. Indeed, the International Federation of Gynecology and Obstetrics Committee on Gynecologic Oncology recently recognized that these cancers should be considered collectively, with a common system of staging and management strategies for ovarian, primary peritoneal, and fallopian tube cancers. A paradigm shift has occurred in our understanding of the pathogenesis of extrauterine pelvic serous carcinomas that has the potential to change current strategies for screening, prevention, diagnosis, and management. Ultrasonography (US), computed tomography (CT), magnetic resonance imaging, and combined positron emission tomography and CT are pivotal in screening, initial diagnosis, and treatment follow-up; however, because of this paradigm shift, new radiologic techniques, such as contrast material-enhanced US and molecular US imaging, and various optical imaging techniques are being investigated as important screening and diagnostic tools. Because of evolving knowledge of genetic and molecular changes underlying the

  9. Cross-sectional study on comorbidities and adverse events in patients with advanced and recurrent ovarian cancer in France

    Directory of Open Access Journals (Sweden)

    Le Saux O

    2015-10-01

    Full Text Available Olivia Le Saux,1 Aliki Taylor,2 Victoria Chia,3 Demetris Pillas,2 Moninder Kaur,2 Gilles Freyer11Department of Medical Oncology, Centre Hospitalier Lyon-Sud, Pierre-Bénite Cédex, France; 2Center for Observational Research, Amgen Ltd, Uxbridge, UK; 3Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Purpose: The purpose of this study was to evaluate the prevalence of comorbidities and adverse events (AEs, and determine the treatment patterns according to platinum-sensitivity status in patients with advanced (stage IIIB–IV or recurrent epithelial ovarian cancer (EOC. Methods: A cross-sectional study was carried out in France with patients over 18 years, diagnosed with advanced (stage IIIB–IV or recurrent EOC between 2009 and 2012. A total of 23 physicians (oncologists and gynecologists participated, contributing 127 patients. Data were abstracted by participating physicians into a case report form. Results: Of the 127 patients included, 92 (72.4% had advanced EOC and 35 (27.6% had recurrent EOC. A total of 73 comorbidities were reported in 44 patients (34.6%. Vascular (10.2%, metabolic (7.1%, respiratory (5.5%, and psychiatric disorders (5.5% were the most common types of comorbidities reported. Prevalence of AEs was 74.8%, of which 12.6% were classified as serious. The most common AEs were anemia (16.5%, hematologic events (12.6%, taste change (11.8%, and headache (7.1%. Throughout the follow-up period, twelve patient deaths were reported (six due to disease progression. Of 35 patients with recurrent disease, 16 were highly platinum sensitive (recurrence >12 months after stopping platinum-based therapy, eleven were partially platinum sensitive (recurrence 6–12 months after stopping platinum-based therapy, seven were platinum resistant (recurrence within 6 months of stopping platinum-based therapy or progression while receiving second- or later-line platinum-based therapy, and one was platinum refractory (recurrence

  10. BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma

    International Nuclear Information System (INIS)

    Fifty patients with inoperable squamous cell carcinoma of the bronchus were treated with radical radiotherapy. Afterwards, 16 patients received levamisole on 2 days per week and bacillus calmette guerin (B.C.G.) skin innoculations every two weeks;another 16 received the same dosage of levamisole but B.C.G. every 4 weeks; 18 patients were controls. Survival was better in the first group of patients only during the first two years of study (P = 0.02) but not later: metastases were fewer. Both B.C.G. and levamisole gave little discomfort when the dose was adjusted for each patient

  11. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    OpenAIRE

    Bukowski, Ronald M; Heng, Daniel Y.C.

    2011-01-01

    The treatment of metastatic renal cell carcinoma (RCC) has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Ma...

  12. Auto-Penectomy: A Devastating Complication of Advanced, Neglected Penile Carcinoma: Autopenectomy due to penile carcinoma

    OpenAIRE

    Kumar, Arvind; Goel, Apul; Sankhwar, Satya N.

    2013-01-01

    Auto-penectomy is a rare consequence of penile carcinoma (PC). Two men, 65 and 74 years of age, presented with total penile loss secondary to PC. Due to poor hygiene and negligence, the ulcer was infected with maggots. The management was by local debridement and suprapubic cystostomy. No further treatment was done as the patients did not come for follow-up.

  13. Advanced Ovarian Dysgerminoma Infiltrating Both Ovaries and Uterus in a 7-Year-Old Girl

    Directory of Open Access Journals (Sweden)

    Nexhmi Hyseni

    2014-01-01

    Full Text Available Introduction. Ovarian dysgerminoma is a rare malignant ovarian germ cell tumor with its peak incidence in young women. Abdominal pain, abdominal distention, and the presence of a palpable mass are common symptoms at presentation. Depending on the FIGO stage at presentation the prognosis of dysgerminomas after surgical treatment, adjuvant chemotherapy, and radiotherapy is promising. Case Presentation. A 7-year-old girl was presented at our clinic with abdominal pain in all abdominal quadrants. Later the pain localized in the region of her right ovary. CT scan revealed a massive formation which was connected to her right ovary. Conclusion. Although malignant ovarian germ cell tumours are rare in children, physicians must always consider the possibility of MOGT-occurrences. The clinical symptoms might not be specific: abdominal pain, abdominal distention, nausea, and vomiting. In order to make a correct diagnosis the patients should undergo a complete clinical examination including radiological scans. Initial management is frequently surgery, followed by adjuvant chemotherapy and radiotherapy. Although disgerminoma is malignant tumor, the prognosis is promising.

  14. Ovarian Cancer Pathogenesis: A Model in Evolution

    Directory of Open Access Journals (Sweden)

    Alison M. Karst

    2010-01-01

    Full Text Available Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease.

  15. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): A multicentre randomized controlled study

    NARCIS (Netherlands)

    M.J. Rutten (Marianne); K.N. Gaarenstroom (Katja); T. van Gorp (Toon); H.S. van Meurs (Hannah); H.J.G. Arts (Henriette); P.M.M. Bossuyt (Patrick); H.G. ter Brugge (Henk); R.H. Hermans (Ralph); B.C. Opmeer; J.M.A. Pijnenborg (Johanna); H.W.R. Schreuder (Henk); E.M. Schutter (Eltjo); A.M. Spijkerboer (Anje); C.W.M. Wensveen (C. W M); P.L.M. Zusterzeel (Petra); B.W.J. Mol (Ben); G.G. Kenter (Gemma ); M.R. Buist (Marrije)

    2012-01-01

    textabstractBackground: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, n

  16. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study.

    NARCIS (Netherlands)

    Rutten, M.J.; Gaarenstroom, K.N.; Gorp, T. Van; Meurs, H.S. van; Arts, H.J.; Bossuyt, P.M.; Brugge, H.G. ter; Hermans, R.H.; Opmeer, B.C.; Pijnenborg, J.M.A.; Schreuder, H.W.B.; Schutter, E.M.; Spijkerboer, A.M.; Wensveen, C.W.; Zusterzeel, P.L.; Mol, B.W.; Kenter, G.G.; Buist, M.R.

    2012-01-01

    BACKGROUND: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant c

  17. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial) : a multicentre randomized controlled study

    NARCIS (Netherlands)

    Rutten, Marianne J.; Gaarenstroom, Katja N.; Van Gorp, Toon; van Meurs, Hannah S.; Arts, Henriette J. G.; Bossuyt, Patrick M.; Ter Brugge, Henk G.; Hermans, Ralph H. M.; Opmeer, Brent C.; Pijnenborg, Johanna M. A.; Schreuder, Henk W. R.; Schutter, Eltjo M. J.; Spijkerboer, Anje M.; Wensveen, Celesta W. M.; Zusterzeel, Petra; Mol, Ben Willem J.; Kenter, Gemma G.; Buist, Marrije R.

    2012-01-01

    Background: Standard treatment of advanced ovarian cancer is surgery and chemotherapy. The goal of surgery is to remove all macroscopic tumour, as the amount of residual tumour is the most important prognostic factor for survival. When removal off all tumour is considered not feasible, neoadjuvant c

  18. [A CASE OF ADVANCED BLADDER NEUROENDOCRINE CARCINOMA (SMALL CELL CARCINOMA) SIGNIFICANTLY IMPROVED BY LOW DOSE OF ORAL TEGAFUR-URACIL].

    Science.gov (United States)

    Nomi, Hayahito; Takahara, Kiyoshi; Minami, Koichiro; Maenosono, Ryoichi; Matsunaga, Tomohisa; Yoshikawa, Yuki; Tsujino, Takuya; Hirano, Hajime; Inamoto, Teruo; Yamamoto, Ikuhisa; Tsuji, Motomu; Kiyama, Satoshi; Azuma, Haruhito

    2015-10-01

    A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years. PMID:26717786

  19. Advanced Hepatocellular Carcinoma with Subtotal Occlusion of the Inferior Vena Cava and a Right Atrial Mass

    Directory of Open Access Journals (Sweden)

    Christian Steinberg

    2013-01-01

    Full Text Available Hepatocellular carcinoma usually metastasizes to regional lymph nodes, lung, and bones but can rarely invade the inferior vena cava with intravascular extension to the right atrium. We present the case of a 75-year-old man who was admitted for generalized oedema and was found to have advanced HCC with invasion of the inferior vena cava and endovascular extension to the right atrium. In contrast to the great majority of hepatocellular carcinoma, which usually develops on the basis of liver cirrhosis due to identifiable risk factors, none of those factors were present in our patient.

  20. Should CA-125 response criteria be preferred to response evaluation criteria in solid tumors (RECIST) for prognostication during second-line chemotherapy of ovarian carcinoma?

    DEFF Research Database (Denmark)

    Gronlund, Bo; Høgdall, Claus; Hilden, Jørgen; Engelholm, Svend A; Høgdall, Estrid V S; Hansen, Heine H

    2004-01-01

    assessable disease by the CA-125 criteria (n = 68), the CA-125 criteria were 2.6 times better than the RECIST at disclosing survival. In a multivariate Cox analysis with inclusion of nine potential prognostic parameters, CA-125 response (responders v nonresponders; hazard ratio, 0.21; P < .001) and number of......PURPOSE: The aim of the study was to compare the prognostic value of a response by the Gynecologic Cancer Intergroup (GCIG) Cancer Antigen (CA) -125 response criteria and the Response Evaluation Criteria in Solid Tumors (RECIST) on survival in patients with ovarian carcinoma receiving second...... a platinum compound, refractory or recurrent disease, and second-line chemotherapy consisting of topotecan or paclitaxel plus carboplatin. Univariate and multivariate analyses of survival were performed using the landmark method. RESULTS: In patients with measurable disease by RECIST and with...

  1. The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yu; Wong, Nicholas; Guan, Yinghui; Salamanca, Clara M.; Cheng, Jung Chien; Lee, Jonathan M.; Gray, Joe W.; Auersperg, Nelly

    2008-04-25

    Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is a transcriptional repressor, enhanced expression of eEF1A2. In this study, array comparative genomic hybridization, single nucleotide polymorphism and Affymetrix analysis of ZNF217-overexpressing cell lines confirmed consistently increased expression of eEF1A2 but not of other oncogenes, and revealed early changes in EEF1A2 gene copy numbers and increased expression at crisis during immortalization. We defined the influence of eEF1A2 overexpression on immortalized ovarian surface epithelial cells, and investigated interrelationships between effects of ZNF217 and eEF1A2 on cellular phenotypes. Lentivirally induced eEF1A2 overexpression caused delayed crisis, apoptosis resistance and increases in serum-independence, saturation densities, and anchorage independence. siRNA to eEF1A2 reversed apoptosis resistance and reduced anchorage independence in eEF1A2-overexpressing lines. Remarkably, siRNA to eEF1A2 was equally efficient in inhibiting both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression. Our data define neoplastic properties that are caused by eEF1A2 in nontumorigenic ovarian cancer precursor cells, and suggest that eEF1A2 plays a role in mediating ZNF217-induced neoplastic progression.

  2. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

    International Nuclear Information System (INIS)

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells

  3. Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma

    OpenAIRE

    Joshi, P.; V Patil; Joshi, A; V Norohna; Chaturvedi, P.; Chaukar, D.; P Pai; D Nair; Juvekar, S; Agarwal, J. P.; A K D′cruz; Prabhash, K

    2013-01-01

    Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 w...

  4. Calibration and Optimization of p53, WT1, and Napsin A Immunohistochemistry Ancillary Tests for Histotyping of Ovarian Carcinoma: Canadian Immunohistochemistry Quality Control (CIQC) Experience.

    Science.gov (United States)

    Lee, Sandra; Piskorz, Anna M; Le Page, Cécile; Mes Masson, Anne-Marie; Provencher, Diane; Huntsman, David; Chen, Wenqian; Swanson, Paul E; Gilks, C Blake; Köbel, Martin

    2016-05-01

    The Canadian Immunohistochemistry Quality Control provides proficiency testing for immunohistochemistry in Canadian laboratories. Canadian Immunohistochemistry Quality Control Run 42 assessed WT1, Napsin A, and p53; commonly used markers for histotyping ovarian carcinomas. A 42-core tissue microarray, which included the 5 major histotypes of ovarian carcinomas with a subset having known TP53 mutational status, was used for this Canadian Immunohistochemistry Quality Control challenge. Participants included 43 laboratories for p53, 29 for WT1, and 26 for Napsin A. p53 was scored as aberrant if the staining was strong and diffuse or absent. Napsin A and WT1 were scored positive if any tumor cells stained. The reference p53 expression pattern was inferred by TP53 mutation type when available. For WT1, Napsin A, and cases lacking mutational data, the reference staining pattern was based on the majority staining result. The error rate for p53 was 8.8%. Most errors (84%) were due to weak staining. The sensitivity and specificity of aberrant p53 expression for an underlying TP53 mutation was 91.6% and 87.9%, respectively. The error rate for WT1 was 0.76% with all errors occurring in laboratories using the 6F-h2 clone. The average errors for laboratories using 6F-h2 were 2.4 compared with 0 for WT-49. The error rate for Napsin A was 4%. The average errors for laboratories using polyclonal Napsin A were 3 compared with 1.1 for monoclonal Napsin A. Weak p53 staining increases interpretative errors, primarily due to absence of staining in tumors with wild-type TP53. p53 immunohistochemistry correlates strongly with TP53 mutational status. Polyclonal Napsin A and 6F-h2 may lack specificity in comparison to monoclonal Napsin A and WT-49. PMID:26598982

  5. Unilateral follicular variant of papillary thyroid carcinoma with unique KRAS mutation in struma ovarii in bilateral ovarian teratoma: a rare case report

    Directory of Open Access Journals (Sweden)

    Stanojevic Boban

    2012-06-01

    Full Text Available Abstract Background Struma ovarii (SO is a rare form of ovarian mature teratoma in which thyroid tissue is the predominant element. Because of its rarity, the differential diagnosis between benign and malignant SO has not been clearly defined. It is believed that malignant transformation of SO has similar molecular features with and its prognosis corresponds to that of malignant tumors originating in the thyroid. Case presentation We report 35-year-old woman with bilateral ovarian cysts incidentally detected by ultrasound during the first trimester of pregnancy. Four months after delivery of a healthy child without complication she was admitted to the hospital for acute abdominal pain. Laparoscopic left adnexectomy was performed initially in a regional hospital; right cystectomy was done later in a specialized clinic. Intraoperative frozen section and a final pathology revealed that the cyst from the left ovary was composed of mature teratomatous elements, normal thyroid tissue (>50% and a non-encapsulated focus of follicular variant of papillary thyroid carcinoma (PTC. Normal and cancerous thyroid tissues were tested for BRAF and RAS mutations by direct sequencing, and for RET/PTC rearrangements by RT-PCR/Southern blotting. A KRAS codon 12 mutation, the GGT → GTT transversion, corresponding to the Gly → Val amino acid change was identified in the absence of other genetic alterations commonly found in PTC. Conclusion To the best of our knowledge, this is the first time this mutation is described in a papillary thyroid carcinoma arising in struma in the ovarii. This finding provides further evidence that even rare mutations specific for PTC may occur in such tumors. Molecular testing may be a useful adjunct to common differential diagnostic methods of thyroid malignancy in SO.

  6. Unilateral follicular variant of papillary thyroid carcinoma with unique KRAS mutation in struma ovarii in bilateral ovarian teratoma: a rare case report

    International Nuclear Information System (INIS)

    Struma ovarii (SO) is a rare form of ovarian mature teratoma in which thyroid tissue is the predominant element. Because of its rarity, the differential diagnosis between benign and malignant SO has not been clearly defined. It is believed that malignant transformation of SO has similar molecular features with and its prognosis corresponds to that of malignant tumors originating in the thyroid. We report 35-year-old woman with bilateral ovarian cysts incidentally detected by ultrasound during the first trimester of pregnancy. Four months after delivery of a healthy child without complication she was admitted to the hospital for acute abdominal pain. Laparoscopic left adnexectomy was performed initially in a regional hospital; right cystectomy was done later in a specialized clinic. Intraoperative frozen section and a final pathology revealed that the cyst from the left ovary was composed of mature teratomatous elements, normal thyroid tissue (>50%) and a non-encapsulated focus of follicular variant of papillary thyroid carcinoma (PTC). Normal and cancerous thyroid tissues were tested for BRAF and RAS mutations by direct sequencing, and for RET/PTC rearrangements by RT-PCR/Southern blotting. A KRAS codon 12 mutation, the GGT → GTT transversion, corresponding to the Gly → Val amino acid change was identified in the absence of other genetic alterations commonly found in PTC. To the best of our knowledge, this is the first time this mutation is described in a papillary thyroid carcinoma arising in struma in the ovarii. This finding provides further evidence that even rare mutations specific for PTC may occur in such tumors. Molecular testing may be a useful adjunct to common differential diagnostic methods of thyroid malignancy in SO

  7. Downregulation of miR-17~92 Expression Increase Paclitaxel Sensitivity in Human Ovarian Carcinoma SKOV3-TR30 Cells via BIM Instead of PTEN

    Directory of Open Access Journals (Sweden)

    Cui Hong Bai

    2013-02-01

    Full Text Available To better understand the molecular mechanisms of paclitaxel resistance in ovarian carcinoma, we evaluated the expression of miRNAs using miRNA microarray between human ovarian carcinoma SKOV3 cells and paclitaxel resistant SKOV3-TR30 cells. Results showed that 69 miRNAs were upregulated while 102 miRNAs were downregulated in SKOV3-TR30 cells. Using real-time PCR, we further clarified that miR-17~92 was overexpressed in SKOV3-TR30 cells compared with that in SKOV3 cells. We then established stable virally transduced SKOV3-TR30-m-PTIP-Sponge all SKOV3-TR30 cells and its vector-only control SKOV3-TR30-m-PTIP-GFP cells. Real time-PCR revealed that SKOV3-TR30-m-PTIP-Sponge all cells expressed approximately 6.18-fold lower levels of miR-17~92 compared with the control group. Decreased expression of miR-17~92 resulted in cell cycle arrest in the G2/M phase and growth inhibition. After the transduction, the BIM protein level was increased in SKOV3-TR30 cells and luciferase reporter assays revealed that miR-17~92 binds directly to the 3'-UTR of BIM. Results of luciferase reporter assays accompanied with Western Blot showed that although miR-17~92 binds directly to the 3'-UTR of PTEN, the PTEN protein expression level was upregulated slightly while the result is of no statistical significance. Our results showed that miR-17~92 could be a causal factor of the downregulation of BIM in SKOV3-TR30 cells and thus induce the paclitaxel resistance in SKOV3-TR30 cells.

  8. Recent advances in the prevention of hepatocellular carcinoma recurrence.

    Science.gov (United States)

    Lu, Li-Chun; Cheng, Ann-Lii; Poon, Ronnie T P

    2014-11-01

    Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Early-stage HCC can be curatively treated, but the recurrence rate remains high. To date, adjuvant treatments have not proven effective in preventing HCC recurrence after curative treatment. Although early studies explored the potential of vitamin K2, retinoid, chemotherapy, and recently, sorafenib, none of the studies reported successful outcomes. Several new lines of evidence have emerged to support the use of novel antiviral agents for preventing the recurrence of virus-related HCC after curative treatment. In this review, the authors provide a thorough overview of the various adjuvant treatments that have been attempted or are being considered for trial. PMID:25369304

  9. Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

    Science.gov (United States)

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-05-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery. PMID:26019766

  10. Increased cell survival by inhibition of BRCA1 using an antisense approach in an estrogen responsive ovarian carcinoma cell line

    OpenAIRE

    Annab, Lois A; Hawkins, Rebecca E; Solomon, Greg; Barrett, J Carl; Afshari, Cynthia A.

    2000-01-01

    Introduction: Germline mutations in the breast and ovarian cancer susceptibility gene BRCA1, which is located on chromosome 17q21, are associated with a predisposition to the development of cancer in these organs [1,2]. No mutations in the BRCA1 gene have been detected in sporadic breast cancer cases, but mutations have been detected in sporadic cases of ovarian cancer [3,4]. Although there is debate regarding the level of cancer risk associated with mutations in BRCA1 and the significance of...

  11. A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas

    OpenAIRE

    Ansari, M.; Omidvari, S; Mosalaei, A.; Ahmadloo, N; Mosleh-Shirazi, M. A.; Mohammadianpanah, M.

    2011-01-01

    Background The combination of cisplatin and 5-fluorouracil (PF) is currently considered a standard and effective regimen for the treatment of advanced head and neck carcinomas. The aim of this study was to evaluate the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with unresectable head and neck carcinomas. Methods Forty-six patients with previously untreated non-metastatic stage IV head and neck carcinomas were enrolled. All patients received three cycles o...

  12. Association of IL12B Polymorphisms with susceptibility to Ovarian Carcinoma%IL12B基因多态性与卵巢癌的相关性研究

    Institute of Scientific and Technical Information of China (English)

    胡月子; 张冉

    2012-01-01

    目的:探讨IL12B基因多态性与女性卵巢癌的关系.方法:采用PCR-RFLP技术检测92例卵巢癌患者与38例正常对照者IL12Brs3212227基因多态性.结果:IL12B基因型频率分布在病例组和对照组人群中的差异无统计学意义(p=0.086).非变异基因型IL12B rs3212227AA与变异基因型IL12B rs3212227AC/CC在两组人群中的分布差异具有显著性(P=0.036),而与AA基因型相比,AC/CC基因型能显著提高卵巢癌的患病风险(OR=2.47;95%可信区间为1.05-5.84).结论:本研究结果提示,IL12B rs3212227基因多态性与卵巢癌的患病风险有关,其变异提高卵巢癌的发病率,是卵巢癌的危险因子之一.%The aim of this study was to investigate whether IL12B polymorphisms might be associated with increased risk of ovarian carcinoma. Methods We genotyped IL12B rs3212227 by PCR-RFLP in a hospital -based study of 92 ovarian carcinoma cases and 38 cancer -free controls. Results No significant difference was found in frequency distribution of genotypes of IL12B rs 3212227 polymorphisms between cases and controls (P=0.086), while a significant difference was found in frequency distribution of the AA genotype and non-AA genotype between cases and controls (P<0.05), the IL12B rs3212227 AC/CC variant genotypes were associated with a significantly increased risk of ovarian carcinoma [odds ratio,2.47;95% confidence interval(CI), 1.05-5.84], compared with their corresponding wild-type homozygotes. Conclusion These findings suggest that IL12B rs3212227 polymorphisms may contribute to the risk of ovarian carcinoma, and variant genotypes may increase the incidence of ovarian carcinoma, as a risk factor for ovarian carcinoma.

  13. Combination of radiotherapy with chemotherapy using cisplatin of advanced esophageal carcinoma

    International Nuclear Information System (INIS)

    Of 38 patients with esophageal carcinoma who were treated at the Department of Radiology, Tokushima University Hospital between 1983 and 1987, 13 (34 %) received a combination of radiation and chemotherapy of cisplatin-based combination regimens. Twelve patients with squamous cell carcinoma and one with adenocarcinoma were treated by a 6 MV linear accelerater. They received a cummulative dose ranging from 18 to 68 Gy (average dose : 50.5 Gy), in 2 Gy fractions. The response rate was 62 % (CR 1, PR 7). Two of the six patients with Stage III survived more than three years. Median survival time was 11.4 months for patients with Stage III and 4.7 months for Stage IV. Chemotherapy improved median survival duration for patients with advanced esophageal carcinoma but did not produce a significant improvement in survival, as reported in other recent series. (author)

  14. Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

    Science.gov (United States)

    2016-03-16

    Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

  15. Photodynamic action of LED-activated pyropheophorbide-α methyl ester in cisplatin-resistant human ovarian carcinoma cells

    International Nuclear Information System (INIS)

    Cisplatin-resistance is a major obstacle for the successful therapy to ovarian cancer, and exploring novel approach to deactivate cisplatin-resistant ovarian cells will improve the clinical outcomes. Our present study showed that there was no dark cytotoxicity of MPPa in the COC1/DDP cells at the dose of 0.25 – 4 μM, and LED-activated MPPa resulted in drug dose- and light-dependent cytotoxicity. Apoptotic rate 6 h after LED-activated MPPa (2 μM) increased to 16.71% under the light energy of 1 J/cm2. Confocal laser scanning microscopy showed that MPPa mainly localized in the intracellular membrane system, namely the endoplasmic reticulum, Golgi apparatus, lysosomes and mitochondria in the COC1/DDP cells. Mitochondrial membrane potential (ΔΨm) was collapsed when COC1/DDP cells were exposed to 2 μM MPPa for 20 h and then 1 J/cm2 irradiation of LED source. These data demonstrated that LED-activated MPPa significantly deactivated cisplatin-resistant ovarian cell line COC1/DDP cells and enhanced apoptosis and decreased ΔΨm, which suggests LED is an efficient light source for PDT and LED-activated MPPa can be developed as new modality for treating cisplatin-resistant ovarian

  16. Effect of Procyanidin-rich Extract from Natural Cocoa Powder on Cellular Viability, Cell Cycle Progression, and Chemoresistance in Human Epithelial Ovarian Carcinoma Cell Lines

    Science.gov (United States)

    Taparia, Shruti; Khanna, Aparna

    2016-01-01

    cocoa powder is one of the richest sources of procyanidinsCocoa procyanidin-rich extract (CPRE) caused cytotoxicity and chemosensitization in ovarian carcinoma cell lines OAW42 and OVCAR3CPRE affected normal cell cycle progressionCPRE also downregulated P-glycoprotein, which mediates chemoresistance in multidrug-resistant OVCAR3 cell line. Abbreviations used: P-gp: P-glycoprotein, CPRE: Cocoa procyanidin rich extract, DMAC: 4-dimethylaminocinnamaldehyde, DPPH: Diphenylpicrylhydrazyl, ABTS: 2,2’;-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), PI: Propidium iodide, FITC: Fluorescein isothiocyanate, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, TLC: Thin layer chromatography, HPTLC: High-performance thin layer chromatography. PMID:27279694

  17. Perfusion CT in patients with advanced bronchial carcinomas: a novel chance for characterization and treatment monitoring?

    International Nuclear Information System (INIS)

    Advanced bronchial carcinomas by means of perfusion and peak enhancement using dynamic contrast-enhanced multislice CT are characterized. Twenty-four patients with advanced bronchial carcinoma were examined. During breathhold, after injection of a contrast-medium (CM), 25 scans were performed (1 scan/s) at a fixed table position. Density-time curves were evaluated from regions of interest of the whole tumor and high- and low-enhancing tumor areas. Perfusion and peak enhancement were calculated using the maximum-slope method of Miles and compared with size, localization (central or peripheral) and histology. Perfusion of large tumors (>50 cm3) averaged over both the whole tumor (P=0.001) and the highest enhancing area (P=0.003) was significantly lower than that of smaller ones. Independent of size, central carcinomas had a significantly (P=0.04) lower perfusion (mean 27.9 ml/min/100 g) than peripheral ones (mean 66.5 ml/min/100 g). In contrast, peak enhancement of central and peripheral carcinomas was not significantly different. Between non-small-cell lung cancers and small-cell lung cancers, no significant differences were observed in both parameters. In seven tumors, density increase after CM administration started earlier than in the aorta, indicating considerable blood supply from pulmonary vessels. Tumor perfusion was dependent on tumor size and localization, but not on histology. Furthermore, perfusion CT disclosed blood supply from both pulmonary and/or bronchial vessels in some tumors. (orig.)

  18. Advanced Urothelial Carcinoma: Overcoming treatment resistance through novel treatment approaches

    Directory of Open Access Journals (Sweden)

    RichardMBambury

    2013-02-01

    Full Text Available The current standard of care for metastatic urothelial carcinoma (UC is cisplatin-based chemotherapy but treatment is generally not curative. Mechanisms of resistance to conventional cytotoxic regimens include tumor cell drug efflux pumps, intracellular anti-oxidants and enhanced anti-apoptotic signaling. Blockade of signaling pathways with small molecule tyrosine kinase inhibitors has produced dramatic responses in subsets of other cancers. Multiple potential signaling pathway targets are altered in UC. Blockade of the PI3K/Akt/mTOR pathway may prove efficacious because 21% have activating PI3K mutations and another 30% have PTEN inactivation (which leads to activation of this pathway. The fibroblast growth factor receptor 3 protein may be overactive in 50-60% and agents which block this pathway are under active development. Blockade of multiple other pathways including HER2 and aurora kinase also have potential efficacy. Anti-angiogenic and immunotherapy strategies are also under development in UC and are discussed in this review. Novel therapeutic approaches are needed in UC. We review the various strategies under development in this disease and discuss how best to evaluate and optimize their efficacy.

  19. Advanced Gastric Neuroendocrine Carcinoma with an Adenocarcinoma Component

    Directory of Open Access Journals (Sweden)

    Masashi Miguchi

    2012-01-01

    Full Text Available In the present study, we observed that the adenocarcinoma component in the mucosa was continuous with neuroendocrine carcinoma (NEC in the deeper layers; this suggests the normal course of NEC carcinogenesis at the histological level. A 72-year-old man was admitted to our hospital with a chief complaint of tarry stools. Endoscopic examination of the upper gastrointestinal tract revealed a 2-cm tumor, with a deep central depression, surrounded by a smooth elevated area, in the middle of the stomach body. A biopsy showed that the tumor was a moderately differentiated gastric adenocarcinoma. The patient underwent total gastrectomy and standard lymph node dissection. The resected tumor was a 3.5 × 2.5 cm type 2 lesion. It comprised two elements at the histological level: (i a moderately differentiated adenocarcinoma in the superficial portion of the mucous membrane layer, and (ii NEC-like cells with dark, round nuclei and scant cytoplasm, presenting a solid and trabecular pattern, in the submucosal and muscularis propria layers. Immunohistochemical findings showed that the NEC-like cells were diffusely positive for chromogranin A, synaptophysin, neural cell adhesion molecule, and neuron-specific enolase, but were negative for carcinoembryonic antigen. The Ki-67 labeling index was 95%. The final pathological diagnosis was gastric NEC with an adenocarcinoma component and a high cellular proliferative potential.

  20. Current Advances in Epigenetic Modification and Alteration during Mammalian Ovarian Folliculogenesis

    Institute of Scientific and Technical Information of China (English)

    Zengxiang Pan; Jinbi Zhang; Qifa Li; Yinxia Li; Fangxiong Shi; Zhuang Xie; Honglin Liu

    2012-01-01

    During the growth and development of mammalian ovarian follicles,the activation and deactivation of mass genes are under the synergistic control of diverse modifiers through genetic and epigenetic events.Many factors regulate gene activity and functions through epigenetic modification without altering the DNA sequence,and the common mechanisms may include but arc not limited to: DNA methylation,histone modifications (e.g.,acetylation,deacetylation,phosphorylation,methylation,and ubiquitination),and RNA-associated silencing of gene expression by noncoding RNA.Over the past decade,substantial progress has been achieved in studies involving the epigenetic alterations during mammalian germ cell development.A number of candidate regulatory factors have been identified.This review focuses on the current available information of epigenetic alterations (e.g.,DNA methylation,histone modification,noncoding-RNA-mediated regulation) during mammalian folliculogenesis and recounts when and how epigenetic patterns are differentially established,maintained,or altered in this process.Based on different types of epigenetic regulation,our review follows the temporal progression of events during ovarian folliculogenesis and describes the epigenetic changes and their contributions to germ cell—specific functions at each stage (i.e.,primordial folliculogenesis (follicle formation),follicle maturation,and follicular atresia).

  1. Gene Set-Based Functionome Analysis of Pathogenesis in Epithelial Ovarian Serous Carcinoma and the Molecular Features in Different FIGO Stages.

    Science.gov (United States)

    Chang, Chia-Ming; Chuang, Chi-Mu; Wang, Mong-Lien; Yang, Ming-Jie; Chang, Cheng-Chang; Yen, Ming-Shyen; Chiou, Shih-Hwa

    2016-01-01

    Serous carcinoma (SC) is the most common subtype of epithelial ovarian carcinoma and is divided into four stages by the Federation of Gynecologists and Obstetrics (FIGO) staging system. Currently, the molecular functions and biological processes of SC at different FIGO stages have not been quantified. Here, we conducted a whole-genome integrative analysis to investigate the functions of SC at different stages. The function, as defined by the GO term or canonical pathway gene set, was quantified by measuring the changes in the gene expressional order between cancerous and normal control states. The quantified function, i.e., the gene set regularity (GSR) index, was utilized to investigate the pathogenesis and functional regulation of SC at different FIGO stages. We showed that the informativeness of the GSR indices was sufficient for accurate pattern recognition and classification for machine learning. The function regularity presented by the GSR indices showed stepwise deterioration during SC progression from FIGO stage I to stage IV. The pathogenesis of SC was centered on cell cycle deregulation and accompanied with multiple functional aberrations as well as their interactions. PMID:27275818

  2. Renal cell carcinoma: evolving approaches to advanced non-clear cell carcinoma

    Directory of Open Access Journals (Sweden)

    Daniel Y.C. Heng

    2011-12-01

    Full Text Available The treatment of metastatic renal cell carcinoma (RCC has changed dramatically with the introduction of targeted therapies including sunitinib, sorafenib, and temsirolimus. Because patients with conventional clear cell histology account for 75- 80% of all patients with RCC, there has been little accumulated evidence on the treatment of patients with non-clear cell histologies. Most clinical trials have excluded them from enrolment, except for randomized studies investigating temsirolimus. Many retrospective studies on the use of all three of these targeted therapies in patients with non-clear cell histology have demonstrated response rates ranging from 3.7%–16%. Although response rates may not be as high compared to patients with clear cell histologies, targeted therapy does provide a clinically meaningful response.

  3. Neoadjuvant treatment in advanced renal cell carcinoma: current situation and future perspectives.

    Science.gov (United States)

    Timsit, Marc-Olivier; Albiges, Laurence; Méjean, Arnaud; Escudier, Bernard

    2012-12-01

    Neoadjuvant approaches in renal cell carcinoma are currently under investigation, following the demonstration of targeted therapy efficacy in the metastatic setting. It raises the issues of downsizing locally advanced or nonresectable tumor and offering organ-sparing surgery, safety and its potential role in early micrometastatic disease. Relevant studies of the neoadjuvant setting in renal cell carcinoma with targeted therapies were identified from the literature, clinical trial databases and conference abstracts. To date, a neoadjuvant approach appears feasible in terms of safety. Currently available drugs do not achieve major tumor downsizing with primary tumor diameters response rate of 10%. Neoadjuvants should only be considered in clinical trials or as a litmus test in locally advanced patients. PMID:23253222

  4. The observation and nursing for advanced hepatocellular carcinoma patients treated with Sorafenib

    International Nuclear Information System (INIS)

    Objective: To summarize the author's experience which was obtained in observing and nursing the adverse reactions of advanced hepatocellular carcinoma patients who were treated with Sorafenib. Methods: The adverse reactions and their severity observed in 34 patients with advanced hepatocellular carcinoma who were treated with Sorafenib were retrospectively analyzed. Results: Side effects or toxic reaction were observed in all the patients, which included neutropenia, foot-hand syndrome (FHS), fatigue, diarrhea, hypertention, rash, etc. Five patients had to cut down the dose of Sorafenib in order to relieve the symptom, among them one patient had grade 4 FHS, 3 patients had grade 3 FHS and one patient had grade 3 neutropenia. Conclusion: Being familiar with sorafenib's adverse reaction, closely observing the patients condition and affording appropriate nursing measures, all the above items can definitely improve the therapeutic results and patient's living quality. (authors)

  5. Effective multimodality treatment for advanced epidermoid carcinoma of the female genital tract

    Energy Technology Data Exchange (ETDEWEB)

    Kalra, J.; Cortes, E.; Chen, S.; Krumholz, B.; Rovinsky, J.J.; Molho, L.; Seltzer, V.; Papantoniou, P.; Lee, J.Y.

    1985-07-01

    Fifteen patients with advanced or recurrent squamous-cell carcinoma of the cervix, vulva, vagina, and urethra were treated with simultaneous combination chemotherapy (5-fluorouracil infusion and mitomycin C) and radiotherapy (3,000 rad for a period of three weeks). Three to four weeks after completion of radiotherapy, 13 of 15 patients achieved partial or complete tumor shrinkage. Nine of 15 patients are alive, eight of whom (at a median follow-up time of 24 months) have no evidence of disease. The longest survival time was 45 + months. There was minimal toxicity associated with this therapy. The results of this pilot study suggest that the simultaneous administration of radiation and chemotherapy is an effective method of treatment of advanced female genital tract carcinoma.

  6. Selective arterial embolization for control of haematuria secondary to advanced or recurrent transitional cell carcinoma of the bladder.

    LENUS (Irish Health Repository)

    Halpenny, D

    2014-05-02

    Haematuria is a common symptom in patients with advanced transitional cell carcinoma of the bladder. We report our experience of selective pelvic embolization using gelfoam as an embolic agent to treat intractable haematuria in these patients.

  7. A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Xun He

    2015-01-01

    Conclusion: Neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve the 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in the patients with locally advanced nasopharyngeal carcinoma.

  8. Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

    Science.gov (United States)

    2016-02-15

    Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; 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

  9. The Role of Sorafenib in the Treatment of Advanced Hepatocellular Carcinoma: An Update

    OpenAIRE

    Gauthier, Angela; Ho, Mitchell

    2012-01-01

    Sorafenib is the first and only orally administered drug currently approved to treat advanced hepatocellular carcinoma (HCC). However, concerns have been raised about sorafenib therapy, including acquired drug resistance. This review provides an overview of sorafenib in the treatment of HCC on the basis of data obtained in the laboratory and in clinical studies. Three underlying mechanisms have been found to support sorafenib therapy. First, sorafenib blocks HCC cell proliferation by inhibiti...

  10. Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO’s guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan

  11. Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma

    OpenAIRE

    ISHIKAWA, TORU

    2008-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, including Japan. Although the development of imaging modalities has made the early diagnosis of HCC possible, surgically resectable cases are relatively uncommon because of hepatic function reserve and/or an advanced stage at presentation. Several modalities, such as transcatheter arterial chemoembolization, percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation are reportedly u...

  12. Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle; Carroll, William R.; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J. Scott [Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (United States); Rosenthal, Eben L., E-mail: oto@uab.edu [Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama (United States)

    2013-04-01

    Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

  13. Ovarian Cyst

    Science.gov (United States)

    MENU Return to Web version Ovarian Cyst Overview What is an ovarian cyst? An ovarian cyst is a fluid-filled sac in or on the ovary. There are several types of ovarian cysts. Many ovarian cysts are noncancerous cysts that ...

  14. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    Science.gov (United States)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  15. A CLINICAL STUDY OF LOCALLY ADVANCED CARCINOMA OF BREAST

    Directory of Open Access Journals (Sweden)

    Mrinalini

    2015-06-01

    Full Text Available BACKGROUND : In India it is observed that most of the patients of breast cancer clinically present in late stage due to their ignorance of disease despite so much advancement in its detection and management. Locally advanced breast cancer (LABC accounts for 30 - 35% of all cases of breast cancers in India. This study aims to evaluate C linical features, Investigations, various Treatment modalities and the Clinico - pathological correlation & outcome of various treatment modalities of LABC, with special emphasis on Neo - adjuvant chemotherapy (NACT in Indian setting. MATERIAL AND METHOD : This was a non - randomised prospective observational study. We analyzed 57 patients of LABC Stage IIIB & IIIC presenting at Government Medical College, Nagpur, Maharashtra, a tertiary care C entre from September 2012 to November 2014. RESULTS : Stage IIIB comprised 84.21% patients while remaining 15.79% were having Stage IIIC disease. Skin involvement was observed in 91.23% patients. 15.79% showed supraclavicular lymph node involvement. 32 patients received NACT (2 to 6 cycles. Out of these 32, complete clinical response (cCR was 12.5%, partial response (cPR was 68.75% and pathological CR (pCR was 6.25% with Total Objective response (cCR+cPR 81.25%. Feasibility of Breast Conserving Surgery (BCS was observed in 12.5% patients. 25 patients underwent primary surgery followed by adjuvant chemotherapy. Modified Radical Mastectomy was performed in 89.48% patients. CONCLUSIONS : With overall clinical response of 81.25%, n eoadjuvant chemotherapy is the best treatment option for patients with Locally Advanced Breast Cancer with added advantage of in vivo testing the sensitivity of chemotherapeutic agents, early management of micrometastasis and down staging the primary tumour with feasibility of BCS. Patients presenting LABC constitute a diverse group for whic h a variety of treatment modalities should be instituted with co o rdinated treatment planning among surgeons

  16. Renal cell carcinoma in long-term survivors of advanced stage neuroblastoma in early childhood

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is rare in children and comprises only 1-3% of all pediatric primary renal tumors. Recently, several case reports have described RCC developing in patients previously treated for advanced stage neuroblastoma (NB). Our experience with four patients treated for advanced stage NB during early childhood who developed RCC later in life are added to 14 others in the literature. These patients and our review of the literature suggest an association between RCC and NB that warrants further study. (orig.)

  17. Administering of I-125 preparation from blood of tortoise into organs of rats with experimental ovarian carcinoma

    International Nuclear Information System (INIS)

    Full text: Complexes of substances of the peptide nature, received mainly from lymphoid bodies that normalize immune processes, are offered. The preparation 'Tortesin' can be related to this group. Tortesin is a drug isolated from the blood cells of the Central Asian tortoise, an animal with a unique radioresistance (LD50 = 100 Gy). During a short spring the tissues of tortoises produce biogenetic stimulators that can positively affect the organisms of irradiated animals. Tortesin acts by stimulating haemo- and immunopoietic systems and aids in recovery from radiation exposure. Thus, at animals treated with Tortesin, DNA and RNA synthesis in the bone marrow was enhanced, both antibody forming cells number and spleenic size increased, and haemopoietic parameters normalized. The survival rate also increased. That is why the determination of the point of initial application of the preparation is an important scientific objective. The research with the use of 125I was carried out for this purpose. The labeling was conducted via reaction with chloramine T. The preparation 125I issued by 'Radiopreparat' (Tashkent) was used. After the purification by chromatography the activity of 1000 impulse/min by 1 μg of protein was got. The experiment was carried out in the Center of oncology and radiology Republic of Uzbekistan. The including of the marker was being determined in young rats at the age of 1 month with an experimental ovarian carcinoma in 15 min, 1 hour and 1 day after the injection. The preparation was injected into the tail vein. The following 22 organs were examined: blood, ascitic fluid with cells, ascitic fluid without cells, tumor, liver, spleen, stomach, bowels, lungs, heart, testicles, kidneys, cerebral, marrow, thymus, fat, muscles, skin, thyroid gland, thigh-bone, tail, excrements. The results can be classified into three groups. The first group of organs (heart, cerebral, cells from tumor, thigh-bone, marrow, thyroid gland, thymus,) do not include the

  18. Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    P Joshi

    2013-01-01

    Full Text Available Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane or three drug with (platinum, taxane with 5-flurouracil [5 FU] as 3 weekly regimen with cisplatin and docetaxel as 75 mg/m 2 each, 5-FU as 1000 mg/m 2 . NACT was either given with the intent of achieving: (1 surgical resection (extensive soft tissue disease, oropharyngeal involvement, extensive disease with cartilage erosion or (2 organ preservation (Bulky disease with inner cartilage erosion, exolaryngeal disease without cartilage erosion, large N3 nodes. Results: The mean age of this population was 55 years. Most (83% of the patients had pyriform sinus (PFS involvement. 69% patients had Stage IVa disease, 21% Stage IVb and 10% Stage III. The overall response rate was 66%, including 06% complete responses and 60% partial responses. Following NACT, resectability was achieved in 30% (10/33 and organ preservation protocol was planned after NACT in 73% (19/26 patients. The main toxicities were neutropenia (grade 3, 4, 04%; febrile neutropenia, 4%, mucositis 5%, diarrhea 5%. The median progression free survival was 20 months. Conclusions: NACT can be useful in patients with oropharyngeal involvement to achieve surgical resection and larynx preservation in patients with bulky T3 disease.

  19. FDG-PET/CT in advanced ovarian cancer staging: Value and pitfalls in detecting lesions in different abdominal and pelvic quadrants compared with laparoscopy

    Energy Technology Data Exchange (ETDEWEB)

    De Iaco, Pierandrea [Department of Gynaecology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Musto, Alessandra [Department of Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Orazi, Luca [Department of Gynaecology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Zamagni, Claudio; Rosati, Marta [Department of Medical Oncology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Allegri, Vincenzo [Department of Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Cacciari, Nicoletta [Department of Medical Oncology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Al-Nahhas, Adil [Department of Nuclear Medicine, Hammersmith Hospital, London (United Kingdom); Rubello, Domenico, E-mail: domenico.rubello@libero.it [Department of Nuclear Medicine, PET/CT Centre, Radiology, Medical Physics, ' Santa Maria della Misericordia' Hospital, Viale Tre Martiri 140, 45100 Rovigo (Italy); Venturoli, Stefano [Department of Gynaecology, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy); Fanti, Stefano [Department of Nuclear Medicine, Azienda Ospedaliero-Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Bologna (Italy)

    2011-11-15

    Introduction and aim: Ovarian carcinoma (OC) is a common cancer in the Western Countries, and an important cause of death in patients suffering with gynaecologic malignancies. The majority of patients present with advanced disease at the time of diagnosis. Treatment with debulking surgery followed by chemotherapy is the standard approach while chemotherapy is contemplated when surgery is not possible. A correct pre-operative staging is important to ensure a most appropriate management. Laparoscopy (LPS) is the standard diagnostic tool for the assessment of intraperitoneal infiltration but is invasive and requires general anaesthesia. FDG-PET/CT is increasingly used for staging different types of cancer, and the aim of this study is to assess the value of FDG-PET/CT in staging advanced OC and its sensitivity to detect lesions in different quadrants of the abdominal-pelvic area compared to laparoscopy. Materials and methods: From September 2004 till April 2008, 40 patients with high suspicion of OC were referred to our hospital for diagnostic LPS to explore the possibility of optimal debulking surgery. Those who were not suitable for surgery were referred for chemotherapy. Before chemotherapy, the patients underwent an FDG-PET/CT scan. The findings in 9 quadrants of abdominal-pelvic area (total 360 quadrants) for PET/CT and LPS were recorded and compared. Results: In 14/360 areas (3.8%), surgical evaluation was not possible because of presence of adhesions, thus the number of areas explored by laparoscopy was 346. Tumour was found in 308 quadrants (38 quadrants free of disease). PET/CT was positive in all 40 patients with true negative results in 26/346 quadrants (7.5%), and true positives results in 243/346 quadrants (70.2%). False positive and negative PET/CT results were found in 12/346 and 65/346 quadrants, respectively. False positive PET/CT findings were evenly present in all quadrants. False negative PET/CT findings were present in 31/109 (28.4%) upper

  20. FDG-PET/CT in advanced ovarian cancer staging: Value and pitfalls in detecting lesions in different abdominal and pelvic quadrants compared with laparoscopy

    International Nuclear Information System (INIS)

    Introduction and aim: Ovarian carcinoma (OC) is a common cancer in the Western Countries, and an important cause of death in patients suffering with gynaecologic malignancies. The majority of patients present with advanced disease at the time of diagnosis. Treatment with debulking surgery followed by chemotherapy is the standard approach while chemotherapy is contemplated when surgery is not possible. A correct pre-operative staging is important to ensure a most appropriate management. Laparoscopy (LPS) is the standard diagnostic tool for the assessment of intraperitoneal infiltration but is invasive and requires general anaesthesia. FDG-PET/CT is increasingly used for staging different types of cancer, and the aim of this study is to assess the value of FDG-PET/CT in staging advanced OC and its sensitivity to detect lesions in different quadrants of the abdominal-pelvic area compared to laparoscopy. Materials and methods: From September 2004 till April 2008, 40 patients with high suspicion of OC were referred to our hospital for diagnostic LPS to explore the possibility of optimal debulking surgery. Those who were not suitable for surgery were referred for chemotherapy. Before chemotherapy, the patients underwent an FDG-PET/CT scan. The findings in 9 quadrants of abdominal-pelvic area (total 360 quadrants) for PET/CT and LPS were recorded and compared. Results: In 14/360 areas (3.8%), surgical evaluation was not possible because of presence of adhesions, thus the number of areas explored by laparoscopy was 346. Tumour was found in 308 quadrants (38 quadrants free of disease). PET/CT was positive in all 40 patients with true negative results in 26/346 quadrants (7.5%), and true positives results in 243/346 quadrants (70.2%). False positive and negative PET/CT results were found in 12/346 and 65/346 quadrants, respectively. False positive PET/CT findings were evenly present in all quadrants. False negative PET/CT findings were present in 31/109 (28.4%) upper

  1. Could tumor characteristics identified by colonoscopy predict the locally advanced rectal carcinoma?

    Institute of Scientific and Technical Information of China (English)

    WANG Hao; CAO Fu-ao; GONG Hai-feng; ZHENG Jian-ming; FU Chuan-gang

    2010-01-01

    Background Neoadjuvant chemoradiation is now considered the standard care for locally advanced rectal carcinoma (T3-4 or/and N1-2 lesions), but the accuracy of staging examinations including endorectal ultrasonography (ERUS) and MRI is far from excellent. In addition, the above staging equipment or professionals who perform the examinations may not be available in some hospitals, while preoperative colonoscopy and biopsy are usually obtainable in most hospitals.The objective of the present study was to investigate the clinical and pathological characteristics of locally advanced rectal carcinoma and identify candidates for neoadjuvant chemoradiation.Methods This was a retrospective study. Patients who were treated for rectal cancer at Changhai Hospital from January 1999 to July 2008 were identified from our prospectively collected database. Statistical analysis was performed using SPSS Software System (version 15.0). The Mann-Whitney test, chi-square test and multivariate Logistic regression analysis were performed,Results A total of 1005 cases were included in this research, of which 761 cases were identified as locally advanced rectal carcinoma depending on postoperative TNM staging. The results of multivariate Logistic regression analysis indicated seven independent risk factors that could be used to predict a locally advanced rectal carcinoma independently: a high grade (including poor differentiation and undifferentiation) (OR: 3.856; 95% CI: 2.064 to 7.204;P=0.000); large tumor size (OR: 2.455; 95% CI: 1.755 to 3.436; P=0.000); elevated preoperative serum CEA level (OR:1.823; 95% CI: 1.309 to 2.537; P=0.000); non-polypoid tumor type (OR: 1.758; 95% CI: 1.273 to 2.427; P=0.001); the absence of synchronous polyps (OR: 1.602; 95% CI: 1.103 to 2.327; P=0.013); the absence of blood in stool (OR: 1.659;95% CI: 1.049 to 2.624; P=0.030); and a greater circumferential tumor extent (OR: 1.813; 95% CI: 1.055 to 3,113;P=0.031). Based on these findings, a Logistic

  2. A prospective comparison of perioperative morbidity in advanced epithelial ovarian cancer: Primary versus interval cytoreduction - experience from India

    Directory of Open Access Journals (Sweden)

    Sheikh Zahoor Ahmad

    2015-01-01

    Full Text Available Objectives: The objective was to compare perioperative morbidity and mortality of patients with advanced epithelial ovarian cancer (EOC treated with either of the two treatment approaches; neoadjuvant chemotherapy (NACT followed by interval debulking versus upfront surgery. Design: Prospective comparative observational study. Participants: In total, 51 patients were included in the study. All patients with diagnosed advanced EOC (International Federation of Gynecology and Obstetrics IIIC and IV presenting for the 1st time were included in the study. Interventions: Patients were either operated upfront (n = 19 if deemed operable or were subjected to NACT followed by interval debulking (n = 32. Primary and Secondary Outcomes: Intra- and postoperative morbidity and mortality were the primary outcome measures. Results: Patients with interval cytoreduction were noted to have significantly lesser operative time, blood loss, and extent of surgery. Their discharge time was also significantly earlier. However, they did not differ from the other group vis. a vis. postoperative complications or mortality. Conclusions: Neoadjuvant chemotherapy although has a positive impact on various intraoperative adverse events, fails to show any impact on immediate postoperative negative outcomes.

  3. Increased intragenic IGF2 methylation is associated with repression of insulator activity and elevated expression in serous ovarian carcinoma

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    Zhiqing eHuang

    2013-05-01

    Full Text Available Overexpression of insulin-like growth factor-II (IGF2 is a prominent characteristic of many epithelial ovarian malignancies. IGF2 imprinting and transcription are regulated in part through DNA methylation, which in turn regulates binding of the insulator protein, CTCF, within the IGF2/H19 imprint center. We have shown that IGF2 overexpression in ovarian cancer is associated with hypermethylation of CTCF binding sites within the IGF2/H19 imprint center. The aim of this study was to investigate the methylation and binding capacity of a novel putative CTCF binding motif located intragenic to IGF2 and determine how this relates to IGF2 expression. In 35 primary serous epithelial ovarian cancer specimens, methylation of two CpGs, including one within the core binding motif and another adjacent to this motif, was higher in the 18 cancers with elevated IGF2 expression versus 10 with low expression (avg. 68.2% vs. 38.5%; p<0.0001. We also found that the CpG site within the CTCF binding motif is hypermethylated in male gametes (>92%; avg. 93.2%; N=16. We confirmed binding of CTCF to this region in ovarian cancer cells, as well as the paralog of CTCF, BORIS, which is frequently overexpressed in cancers. The unmethylated CTCF binding motif has insulator activity in cells that express CTCF or BORIS, but not in cells that express both CTCF and BORIS. These intragenic CpG dinucleotides comprise a novel paternal germline imprint mark and are located in a binding motif for the insulator protein CTCF. Methylation of the CpG dinucleotides is positively correlated with IGF2 transcription, supporting that increased methylation represses insulator function. These combined results suggest that methylation and CTCF binding at this region play important roles in regulating the level of IGF2 transcription. Our data have revealed a novel epigenetic regulatory element within the IGF2/H19 imprinted domain that is highly relevant to aberrant IGF2 expression in ovarian

  4. Ovarian Cancer

    Science.gov (United States)

    ... 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 ...

  5. Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva

    Energy Technology Data Exchange (ETDEWEB)

    Scheistroeen, M. (Norwegian Radium Hospital, Oslo (Norway)); Trope, C. (Norwegian Radium Hospital, Oslo (Norway))

    1993-01-01

    Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.).

  6. Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva

    International Nuclear Information System (INIS)

    Forty-two patients with advanced squamous cell carcinoma of the vulva were treated with a combination regimen of bleomycin 180 mg and external irradiation 30-45 Gy. Twenty patients had primary lesions, and 22 patients had recurrent disease. Fifteen (75%) of the patients with primary disease showed objective response (five complete and ten partial response). Four underwent surgery. Of these, one is alive after 60 months with no evidence of disease. Two have died of unrelated causes without signs of recurrence. Seventeen relapsed and died of carcinoma of the vulva. Median survival for patients treated for primary disease was 8.0 months. Thirteen (59%) of 22 patients treated for recurrence showed objective response (two complete and eleven partial responses). None underwent surgery. All these patients died of carcinoma of the vulva. Median survival was 6.4 months. Toxicity was acceptable, and there were no treatment-related deaths. Even taking into account that our patients had very advanced disease, the results are disappointing. An increase of the radiation dose beyond the maximum of 45 Gy given, and more aggressive surgery, might have improved the results. (orig.)

  7. Induction Chemotherapy in Technically Unresectable Locally Advanced Carcinoma of Maxillary Sinus

    Directory of Open Access Journals (Sweden)

    Vanita Noronha

    2014-01-01

    Full Text Available Background. Locally advanced carcinoma of maxillary sinus has been historically reported to have poor prognosis. We evaluated the role of NACT in improving the outcome in these patients. Methods. 41 patients with locally advanced technically unresectable (stage IVa or unresectable maxillary carcinoma (stage IVb were treated with induction chemotherapy between 2008 and 2011. The demographic profile, response and toxicity of chemotherapy, definitive treatment received, progression free survival (PFS, and overall survival (OS were analyzed. Univariate and multivariate analysis were performed to determine factors associated with PFS and OS. Results. The chemotherapy included two drugs (platinum and taxane in 34 patients (82.9% and three drugs (platinum, taxane, and 5 FU in 7 (17.1%. There was no complete response seen in any of the patients, stable disease in 18 (43.9%, partial response in 16 (39%, and progression in 7 (17.1% patients. After induction, the treatment planned included surgery in 12 (29.3%, CT-RT in 24 (58.5%, radical RT in 1 (2.4%, palliative RT in 1 (2.4%, and palliative chemotherapy in 3 (7.3% patients. Overall, the median PFS was 10.0 months. The OS at 24 months and 36 months was 41% and 35%, respectively. Conclusion. In unresectable maxillary carcinoma, induction chemotherapy has clinically significant benefit with acceptable toxicity.

  8. Usefulness of C-arm CT during superselective infusion chemotherapy for advanced head and neck carcinoma

    International Nuclear Information System (INIS)

    To evaluate the usefulness of C-arm computed tomography (CT) during superselective intra-arterial infusion chemotherapy for advanced head and neck carcinoma. C-arm CT was performed during superselective intra-arterial infusion chemotherapy for 11 patients with advanced head and neck carcinoma located in the hypopharynx (n = 3), maxillary sinus (n = 3), oropharynx (n = 1), larynx (n = 1), extra-auditory canal (n = 1), tonsil (n = 1) and tongue (n = 1). The usefulness of C-arm CT during superselective catheterisation was evaluated. On arteriography, nine tumours showed tumour stains and two in the oropharynx or tonsil showed no obvious tumour stains. C-arm CT was performed one to four times (mean ± standard deviation, 2.5 ± 0.8) in each patient during a single procedure. C-arm CT clearly showed not only the vascular territory of the selected branch but also the tumour itself in all patients. Intra-arterial infusion chemotherapy was performed through one to three branches (mean, 1.7 ± 0.9) according to C-arm CT findings without any complications. C-arm CT during superselective intra-arterial infusion chemotherapy was useful to determine the arterial supply of head and neck carcinoma. C-arm CT may replace conventional CT during superselective arteriography in this procedure.

  9. Increased cell survival by inhibition of BRCA1 using an antisense approach in an estrogen responsive ovarian carcinoma cell line

    International Nuclear Information System (INIS)

    We tested the hypothesis that BRCA1 may play a role in the regulation of ovarian tumor cell death as well as the inhibition of ovarian cell proliferation. Introduction of BRCA1 antisense retroviral constructs into BG-1 estrogen-dependent ovarian adenocarcinoma cells resulted in reduced BRCA1 expression. BRCA1 antisense pooled populations and derived subclones were able to proliferate in monolayer culture without estrogen, whereas control cells began to die after 10 days of estrogen deprivation. In addition, both populations and subclones of BRCA1 antisense infected cells demonstrated a growth advantage in monolayer culture in the presence of estrogen and were able to proliferate in monolayer culture without estrogen, while control cells did not. Furthermore, clonal studies demonstrated that reduced levels of BRCA1 protein correlated with growth in soft agar and greater tumor formation in nude mice in the absence of estrogen. These data suggest that reduction of BRCA1 protein in BG-1 ovarian adenocarcinoma cells may have an effect on cell survival during estrogen deprivation both in vitro and in vivo. Germline mutations in the breast and ovarian cancer susceptibility gene BRCA1, which is located on chromosome 17q21, are associated with a predisposition to the development of cancer in these organs [1,2]. No mutations in the BRCA1 gene have been detected in sporadic breast cancer cases, but mutations have been detected in sporadic cases of ovarian cancer [3,4]. Although there is debate regarding the level of cancer risk associated with mutations in BRCA1 and the significance of the lack of mutations in sporadic tumors, it is possible that alterations in the function of BRCA1 may occur by mechanisms other than mutation, leading to an underestimation of risk when it is calculated solely on the basis of mutational analysis. Such alterations cannot be identified until the function and regulation of BRCA1 are better understood. The BRCA1 gene encodes a 220-kDa nuclear

  10. Emerging new therapeutic applications of capecitabine as a first-line chemotherapeutic agent in the management of advanced carcinomas other than colorectal carcinoma

    Directory of Open Access Journals (Sweden)

    Kapoor S

    2012-05-01

    Full Text Available Shailendra KapoorRichmond, VA, USAI read with great interest the recent article by Hameed et al in a recent issue of your journal.1 The article is very interesting. Interestingly, the past few years have seen the emergence of capecitabine as a highly potent first-line chemotherapeutic agent against advanced systemic carcinomas other than colorectal carcinoma. For instance, capecitabine has recently been used successfully as a first-line monotherapeutic agent for HER-2-negative metastatic breast cancer.2 Cotherapy with agents such as sorafenib and paclitaxel for HER-2-negative metastatic breast cancer has also been recently used first-line, and significantly improves progressionfree survival, in addition to being very safe.3,4 Similarly, in patients with advanced gastric carcinoma, capecitabine has been used successfully as first-line therapy in combination with agents such as cisplatin.5 The XELOX regimen comprising capecitabine in conjunction with oxaliplatin is another recent highly effective alternative for gastric carcinoma.6 The modified XELIRI regimen compromising capecitabine and irinotecan is a further option for advanced and unresectable gastric carcinoma.7View original paper by Hameed and colleagues.

  11. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

    OpenAIRE

    Park, Jung Gil

    2015-01-01

    Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A su...

  12. Rationale for targeted therapies and potential role of pazopanib in advanced renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Peter E Clark

    2010-06-01

    Full Text Available Peter E ClarkVanderbilt University Medical Center, Nashville, Tennessee, USAAbstract: Advanced renal cell carcinoma (RCC remains a challenging, major health problem. Recent advances in understanding the fundamental biology underlying one form of RCC, ie, clear cell (or conventional RCC, have opened the door to a series of targeted agents, such as the tyrosine kinase inhibitors (TKIs, which have become the standard of care in managing advanced clear cell RCC. Among the newest of these agents to receive Food and Drug Administration approval in this disease is pazopanib. This review will summarize what is known about the fundamental biology that underlies clear cell RCC, the data surrounding the previously approved targeted agents for this disease, including not only the TKIs but also the mTOR inhibitors and the vascular endothelial growth factor-specific agent, bevacizumab, and the newest TKI, pazopanib. It will also explore the potential role for pazopanib relative to the other available agents and where it may fit into the armamentarium for treatment of advanced/metastatic RCC.Keywords: pazopanib, targeted therapy, tyrosine kinase inhibitor, clear cell renal cell carcinoma

  13. Predictive value of {sup 18}F-FDG PET/CT in restaging patients affected by ovarian carcinoma: a multicentre study

    Energy Technology Data Exchange (ETDEWEB)

    Caobelli, Federico [Medizinische Hochschule Hannover, Klinik fuer Nuklearmedizin, Hanover (Germany); Alongi, Pierpaolo [University of Milano-Bicocca, Nuclear Medicine Unit, Milan (Italy); IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Evangelista, Laura; Saladini, Giorgio [Veneto Institute of Oncology IOV - IRCCS, Radiotherapy and Nuclear Medicine Unit, Padua (Italy); Picchio, Maria [IRCSS San Raffaele Scientific Institute, Nuclear Medicine Department, Milan (Italy); Rensi, Marco; Geatti, Onelio [Hospital of Udine, Nuclear Medicine Department, Udine (Italy); Castello, Angelo; Laghai, Iashar [University of Florence, Nuclear Medicine Department, Florence (Italy); Popescu, Cristina E. [Niguarda Ca' Granda Hospital, Nuclear Medicine Department, Milan (Italy); Dolci, Carlotta; Crivellaro, Cinzia [University of Milan-Bicocca, Nuclear Medicine Department, San Gerardo Hospital, Tecnomed Foundation, Milan (Italy); Seghezzi, Silvia [Hospital of Treviglio, Nuclear Medicine Department, Treviglio, Bergamo (Italy); Kirienko, Margarita [University of Milano-Bicocca, Nuclear Medicine Unit, Milan (Italy); De Biasi, Vincenzo [Nuclear Medicine Department, Arcispedale Santa Maria Nuova, Reggio Emilia (Italy); Cocciolillo, Fabrizio [Catholic University of the Sacred Heart, Nuclear Medicine Department, Rome (Italy); Quartuccio, Natale [University of Messina, Nuclear Medicine Unit, Department of Biomedical Sciences and of Morphological and Functional Images, Messina (Italy); Collaboration: Young AIMN Working Group

    2016-03-15

    Ovarian cancer is the eighth most common malignancy among women and has a high mortality rate. Prognostic factors able to drive an effective therapy are essential. {sup 18}F-Fluoro-2-deoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) has been investigated in patients with epithelial ovarian cancer and showed promise in diagnosing, staging, detecting recurrent lesions and monitoring treatment response. Conversely, its prognostic role remains unclear. We aimed at assessing the prognostic value of {sup 18}F-FDG PET/CT performed in the restaging process in a multicentre study. We evaluated 168 patients affected by ovarian carcinoma, who underwent a restaging {sup 18}F-FDG PET/CT. The presence of local recurrences, lymph node involvement and distant metastasis was recorded as well as lesion dimensions, maximum and mean standardized uptake values (SUV{sub max} and SUV{sub mean}, respectively). Progression-free survival (PFS) and overall survival (OS) at 3 and 4 years were computed by using Kaplan-Meier curves. Increased odds ratio was assessed using Cox regression analysis testing all lesion parameters measured by PET/CT. PFS was significantly longer in patients with a negative than a positive restaging PET/CT study (3- and 4-year PFS 64 and 53 % vs 23 and 12 %, respectively; p < 0.001). Similarly, a negative study was associated with a significantly higher OS rate after 4 years of follow-up (67 vs 25 % in negative and positive groups, respectively; p < 0.001). Lymph node or distant involvement were also independently associated with an increased risk of disease progression [hazard ratio (HR) 1.6 and 2.2, respectively; p = 0.003]. Moreover, PET/CT showed an incremental prognostic value compared to the International Federation of Gynecology and Obstetrics (FIGO) staging system. In the analysis of patient subsets, individuals with the same FIGO stage I-II but with negative PET had a significantly better 4-year OS than patients with low

  14. Analysis of Founder Mutations in Rare Tumors Associated With Hereditary Breast/Ovarian Cancer Reveals a Novel Association of BRCA2 Mutations with Ampulla of Vater Carcinomas.

    Science.gov (United States)

    Pinto, Pedro; Peixoto, Ana; Santos, Catarina; Rocha, Patrícia; Pinto, Carla; Pinheiro, Manuela; Leça, Luís; Martins, Ana Teresa; Ferreira, Verónica; Bartosch, Carla; Teixeira, Manuel R

    2016-01-01

    BRCA1 and BRCA2 mutations are responsible for hereditary breast and ovarian cancer, but they also confer an increased risk for the development of rarer cancers associated with this syndrome, namely, cancer of the pancreas, male breast, peritoneum, and fallopian tube. The objective of this work was to quantify the contribution of the founder mutations BRCA2 c.156_157insAlu and BRCA1 c.3331_3334del for cancer etiology in unselected hospital-based cohorts of Portuguese patients diagnosed with these rarer cancers, by using a strategy that included testing of archival tumor tissue. A total of 102 male breast, 68 pancreatic and 33 peritoneal/fallopian tube carcinoma cases were included in the study. The BRCA2 c.156_157insAlu mutation was observed with a frequency of 7.8% in male breast cancers, 3.0% in peritoneal/fallopian tube cancers, and 1.6% in pancreatic cancers, with estimated total contributions of germline BRCA2 mutations of 14.3%, 5.5%, and 2.8%, respectively. No carriers of the BRCA1 c.3331_3334del mutation were identified. During our study, a patient with an ampulla of Vater carcinoma was incidentally found to carry the BRCA2 c.156_157insAlu mutation, so we decided to test a consecutive series of additional 15 ampullary carcinomas for BRCA1/BRCA2 mutations using a combination of direct founder mutation testing and full gene analysis with next generation sequencing. BRCA2 mutations were observed with a frequency of 14.3% in ampulla of Vater carcinomas. In conclusion, taking into account the implications for both the individuals and their family members, we recommend that patients with these neoplasias should be offered BRCA1/BRCA2 genetic testing and we here show that it is feasible to test for founder mutations in archival tumor tissue. Furthermore, we identified for the first time a high frequency of germline BRCA2 mutations in ampullary cancers. PMID:27532258

  15. Tolerance of weekly metronomic paclitaxel and carboplatin as neoadjuvant chemotherapy in advanced ovarian cancer patients who are unlikely to tolerate 3 weekly paclitaxel and carboplatin

    OpenAIRE

    Dessai, S. B.; Chakraborty, S; Babu, T. V. S.; Nayanar, S.; A Bhattacharjee; Jones, J.; S Balasubramanian; Patil, Vijay M.

    2016-01-01

    Objective: There are little data regarding safety and effectiveness of neoadjuvant chemotherapy (NACT) in patients who are considered unfit for receiving 3 weekly paclitaxel and carboplatin. The aim of this study was to examine the toxicity and response rates of weekly paclitaxel and carboplatin as NACT in such cohort of patients. Methods: Study population included advanced ovarian cancer patients who were unlikely to tolerate 3 weekly paclitaxel and carboplatin and hence received weekly pacl...

  16. Circulating epidermal growth factor (EGF) and insulin - like growth factor - I (IGF-I) in patients with epithelial ovarian carcinoma

    International Nuclear Information System (INIS)

    Circulating epidermal growth factor (EGF) and insulin - like growth factor - I (EGF-I) were estimated in 58 patients with epithelial ovarian cancer and were correlated with clinically and biochemically important prognosticators. EGF-I levels were significantly low in patients as compared to controls. The relation of growth factors with clinically important prognosticators was non - significant. Moreover, the levels of EGF and IGF - I in ER+/PR+ and ER-/PR- groups and in the low and high EGFR + tumors did not differ significantly. Patients with EGF1.0 ng/ml. (author)

  17. Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Toru Ishikawa

    2008-05-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common malignancies worldwide, including Japan. Although the development of imaging modalities has made the early diagnosis of HCC possible, surgically resectable cases are relatively uncommon because of hepatic function reserve and/or an advanced stage at presentation. Several modalities, such as transcatheter arterial chemoembolization, percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation are reportedly useful in treating patients with non-resectable disease. However, unfortunately, many HCC patients have tumor recurrence. The overall prognosis of patients with HCC is very poor, and treatment of the advanced form is still problematic. In this article, we review the clinical efficacy and toxicity of enteric-coated tegafur/uracil in the treatment of patients with advanced non-resectable HCC.

  18. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3)

    DEFF Research Database (Denmark)

    Sorbye, H; Welin, S; Langer, S W;

    2013-01-01

    Background As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Patients and methods Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively...

  19. Primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Hong Zheng; Yu-Nong Gao

    2012-01-01

    Objectives:To compare the survival and perioperative morbidity between primary debulking surgery (PDS) and neoadjuvant chemotherapy followed by interval debulking surgery (NAC/IDS) in treating patients with advanced epithelial ovarian cancer (EOC).Methods:We retrospectively reviewed 67 patients with stage ⅢC or Ⅳ EOC treated at Peking University Cancer Hospital from January 2006 to June 2009.Wherein,37 and 30 patients underwent PDS and NAC/IDS,respectively.Results:No difference in overall survival (OS) or progression-free survival (PFS) was observed between NAC/IDS group and PDS group (OS:41.2 vs.39.1 months,P=0.23; PFS:27.1 vs.24.3 months,P=0.37).The optimal debulking rate was 60% in the NAC/IDS group,which was significantly higher than that in the PDS group (32.4%) (P=0.024).The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion,lower nasogastric intubation rate,and earlier ambulation and recovery of intestinal function than the PDS group (P<0.05).Conclusions:NAC/IDS is less invasive than PDS,and offers the advantages regarding optimal cytoreduction rate,intraoperative blood loss,and postoperative recovery,without significantly impairing the survival compared with PDS in treating patients with stage ⅢC or Ⅳ EOC.Therefore,NAC/IDS may be a valuable treatment alternative for EOC patients.

  20. Induction chemotherapy and radiotherapy in loco-regionally advanced epidermoid carcinoma of the anal canal

    International Nuclear Information System (INIS)

    Purpose: To evaluate the efficacy of induction chemotherapy in combination with radiotherapy for treatment of loco-regionally advanced epidermoid anal carcinoma. Methods and Materials: Thirty-one patients diagnosed during the period 1989-1994 with loco-regionally advanced cancer of the anal canal (PHITmax ≥ 4 cm or T4 or N+) were treated with induction chemotherapy consisting of one to three courses of carboplatin (300-375 mg/m2 i.v.) and 5-fluorouracil [5,000 mg/(m2 x 120 h) i.v.] followed by external beam irradiation ± surgery. Results: The toxicity of the chemotherapy was low. Twenty-nine patients were tumor free after the primary therapy. Kaplan-Meier analyses were made for overall survival, tumor-specific survival, freedom from recurrence, preservation of sphincter, and event-free survival. For these end points the 5-year data were 67, 85, 80, 69, and 51%, respectively. Conclusion: The results are promising but a well-designed randomized trial is needed to further elucidate the role of induction chemotherapy in the treatment of loco-regionally advanced anal carcinoma

  1. Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone

    International Nuclear Information System (INIS)

    Purpose: To identify prognostic factors for local and distant relapse and perform risk stratification for patients with advanced cervical cancer treated with radiotherapy (RT) alone. Methods and Materials: A total of 1031 patients with Stage IB-IVA squamous cell carcinoma of the cervix treated with full-course RT but without any chemotherapy were included for analysis. Of these, 311 patients with nonbulky Stage IB-IIA disease were designated the reference group and the other 720 patients were the study group. The associations of stage, squamous cell carcinoma antigen (SCC-ag) level, hemoglobin level, age, cell differentiation, and pelvic lymph node status with treatment failure were evaluated. The independent prognostic factors were identified by multivariate analysis. The study group was further stratified into subgroups using combinations of these risk factors. Results: In the study group, independent risk factors for local relapse were advanced stage and age 2, and positive pelvic lymph nodes. The 5-year distant relapse-free survival rate was 83% for patients with bulky Stage IB-IIA and IIB disease, SCC-ag level 2, and positive lymph nodes. Conclusion: The risk of treatment failure in advanced-stage cervical cancer patients treated by RT alone can be more precisely predicted by risk stratification. A certain subgroup of patients had better control than the others. The benefit of treating these relatively low-risk patients with additional treatment such as concurrent chemotherapy should be further evaluated in prospective studies or meta-analyses

  2. Prognostic factors in the treatment of locally advanced hepatocellular carcinoma with radiotherapy and arterial infusion

    International Nuclear Information System (INIS)

    Prognostic factors in the treatment of local advanced hepatocellular carcinoma with radiotherapy, transcatheter arterial embolization and arterial infusion. The treatment effects of radiotherapy and combination modality therapy for the local advanced hepatocellular carcinoma (HCC) were retrospectively reviewed. Three hundred and fifty-six patients of HCC (187 recurrent cases after surgical resection) were treated by: radiotherapy only ; bi-therapeutic method: hepatic artery ligation (HAL) and/or hepatic artery embolization (HAE) plus radiotherapy; and tri-therapeutic method (bi-therapeutic method plus hepatic artery infusion) from 1975 to 1996. Kaplan-Meier method has been used to evaluate the survival rates. There were no significant differences among these three treatment groups in the symptom relied rate, but the mean relief time period was much shorter in radiotherapy alone group (2.5 vs 44 months, P 0.05). There were evident differences in five-year survivals among these three treatment groups: 0 % for radiotherapy alone, 22.8 % for bi-therapeutic method and 38.8 % for tri-therapeutic method (P < 0.01). The prognosis was influenced by Okuda classification. Non-resectable local advanced HCC can be treated by the combination modality therapy, including radiotherapy, with a quite high cure rate. Radiotherapy alone can relief the symptoms. (authors)

  3. Results of three-dimensional conformal radiotherapy and thalidomide for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the effectiveness of three-dimensional conformal radiotherapy and thalidomide in the treatment of advanced hepatocellular carcinoma. Between 1999 and 2003, 121 patients (mean age, 54.4±12.4 years; range, 20-81 years) with advanced hepatocellular carcinoma received three-dimensional conformal radiotherapy and thalidomide. Radiation was delivered in 1.5 Gy fractions twice daily for 5 days a week, for a total dose of 45-75 Gy. Mean treatment volume was 429.52±408.50 cm3 (range, 26.89-2284.82 cm3). Thalidomide was given concomitantly: 200 mg/day in 109 patients, 300 mg/day in 8 patients and 400 mg/day in 4 patients. Treatment responses, survival rates and factors affecting survival were analyzed. Treatment responses were observed in 61% of the patients. Liver cirrhosis (P=0.001) and tumor size (P=0.001) significantly affected the tumor responses. Overall survival at 6, 12 and 24 months was 84.8, 60.0 and 44.6%, respectively. On univariate analysis, liver cirrhosis (P=0.003), Karnofsky performance status (P=0.007), tumor size (P<0.001), portal vein tumor thrombosis (P<0.001) and alpha-fetoprotein level (P=0.003) were shown to significantly affect survival. On multivariate analysis, only thrombosis (P=0.039) and alpha-fetoprotein level (P=0.006) were shown to be factors affecting survival. Three-dimensional conformal radiotherapy with thalidomide seems to be effective in the treatment of advanced hepatocellular carcinoma. (author)

  4. Chronic thyroiditis in patients with advanced breast carcinoma: metabolic and morphologic changes on PET-CT

    Energy Technology Data Exchange (ETDEWEB)

    Tateishi, Ukihide [University of Texas, MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Yokohama City University Graduate School of Medicine, Department of Radiology, Yokohama (Japan); University of Texas MD Anderson Cancer Center, Division of Diagnostic Imaging, Houston, TX (United States); Gamez, Cristina; Yeung, Henry W.D.; Macapinlac, Homer A. [University of Texas, MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Dawood, Shaheenah; Cristofanilli, Massimo [University of Texas, MD Anderson Cancer Center, Division of Breast Medical Oncology, Houston, TX (United States); Inoue, Tomio [Yokohama City University Graduate School of Medicine, Department of Radiology, Yokohama (Japan)

    2009-06-15

    To investigate clinical implications of FDG uptake in the thyroid glands in patients with advanced breast carcinoma by comparing metabolic and morphologic patterns on positron emission tomography (PET)/computed tomography (CT). The institutional review board waived the requirement for informed consent. A retrospective analysis was performed in 146 women (mean age 54 years) with advanced breast carcinoma who received systemic treatment. All patients underwent PET-CT before and after treatment. All PET-CT studies were reviewed in consensus by two reviewers. Morphologic changes including volume and mean parenchymal density of the thyroid glands were evaluated. Maximum standardized uptake value (SUVmax) and total lesion glycolysis (TLG) were determined to evaluate metabolic changes. These parameters were compared between patients with chronic thyroiditis who received thyroid hormone replacement therapy and those who did not. Of the 146 patients, 29 (20%) showed bilaterally diffuse uptake in the thyroid glands on the baseline PET-CT scan. The SUVmax showed a linear relationship with volume (r = 0.428, p = 0.021) and the mean parenchymal density (r = -0.385, p = 0.039) of the thyroid glands. In 21 of the 29 patients (72%) with hypothyroidism who received thyroid hormone replacement therapy, the volume, mean parenchymal density, SUVmax, and TLG of the thyroid glands showed no significant changes. In contrast, 8 of the 29 patients (28%) who did not receive thyroid hormone replacement therapy showed marked decreases in SUVmax and TLG. Diffuse thyroid uptake on PET-CT represents active inflammation caused by chronic thyroiditis in patients with advanced breast carcinoma. Diffuse thyroid uptake may also address the concern about subclinical hypothyroidism which develops into overt disease during follow-up. (orig.)

  5. Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. Methods and Materials: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. Results: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) Conclusion: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma

  6. A comparison of androgen deprivation therapy versus surgical castration for patients with advanced prostatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu-hsiang LIN; Chien-lun CHEN; Chen-pang HOU; Phei-lang CHANG; Ke-hung TSUI

    2011-01-01

    Airn:To examine the outcomes of patients with advanced prostate carcinoma who underwent medical or surgical castration.Methods:A hundred twenty one consecutive cases of patients with advanced prostate carcinoma who underwent medicaI or surgical castration between 2001 and 2006 were retrospectively reviewed.Associations between clinicaI outcomes and prognostic scoring factors were determined based on the Reijke study.In the surgical and medical castration groups.the impact on the prostate-specific antigen(PSA)normalization rate,the rebound rate and the disease-free survivaI rate were evaluated.The mean foIlow-up was 36.1months.Results:In the initial 12 months.there were no statisticaI differences in the PSA normalization rate and the PSA rebound rate between the two groups.However,the PSA rebound rate after the 12th month(20.90%vs 40.74%.P=-0.0175)and the 18th month PSA normalization rate(59.70%vs 37.04%.P=0.0217)differed significantly between the two groups,and these differences were maintained to the end of the study.When comparing patients grouped according to Reijke prognosis scores.there was no difference between medical and surgical castration for the good prognosis group.However, among the patients given a poor prognosis,surgical castration was superior in terms of the PSA normalization rate,the PSA rebound rate.the tumor progression-free survival rate(P<0.001)and the overalI survivaI rate (P<0.001).Conclusion:Advanced prostate carcinoma patients with poor pretreatment prognosis scores should undergo surgical castration rather than medical castration for better PSA rebound rates and overaII survival.

  7. Ovarian follicle development in vitro and oocyte competence: advances and challenges for farm animals.

    Science.gov (United States)

    Silva, J R V; van den Hurk, R; Figueiredo, J R

    2016-04-01

    During the last 2 decades, research on in vitro preantral follicle growth and oocyte maturation has delivered fascinating advances concerning the knowledge of processes regulating follicle growth and the developmental competence of oocytes. These advances include (1) information about the role of several hormones and growth factors on in vitro activation of primordial follicles; (2) increased understanding of the intracellular pathway involved in the initiation of primordial follicle growth; (3) the growth of primary and secondary follicles up to antral stages; and (4) production of embryos from oocytes from in vitro grown preantral follicles. This review article describes these advances, especially in regard farm animals, and discusses the reasons that limit embryo production from oocytes derived from preantral follicles cultured in vitro. PMID:26836404

  8. Gigantoxin-4-4D5 scFv is a novel recombinant immunotoxin with specific toxicity against HER2/neu-positive ovarian carcinoma cells.

    Science.gov (United States)

    Lv, Xinxin; Zhang, Jian; Xu, Rui; Dong, Yuguo; Sun, Aiyou; Shen, Yaling; Wei, Dongzhi

    2016-07-01

    Immunotoxins are a new class of antibody-targeted therapy in clinical development. Traditional immunotoxins that are constructed from the toxins of plants or bacteria need to be internalized to the cytoplasm and thus have limited antitumor efficacy. In the present study, we combined a recently reported sea anemone cytolysin Gigantoxin-4 with an anti-HER2/neu single-chain variable fragment 4D5 scFv to construct a novel immunotoxin. We fused a SUMO tag to the N-terminus of Gigantoxin-4-4D5 scFv and it was successfully expressed in Escherichia coli strain BL21 (DE3) in a soluble form. After purification, the purity of Gigantoxin-4-4D5 scFv reached 96 % and the yield was 14.3 mg/L. Our results demonstrated that Gigantoxin-4-4D5 scFv exerted a highly cytotoxic effect on the HER2/neu-positive ovarian carcinoma SK-OV-3 cell line. And the hemolytic activity was weaker, making it safe for normal cells. The results of immunofluorescence analysis showed that this novel immunotoxin could specifically bind to SK-OV-3 cells with no recognition of human embryonic kidney 293 cells. Scanning electron microscope observations and extracellular lactate dehydrogenase activity indicated that it could induce necrosis in SK-OV-3 cells by disrupting the cell membrane. Moreover, it could also mediate apoptosis of SK-OV-3 cells. PMID:27063011

  9. Aquaporin 3 is regulated by estrogen in the chicken oviduct and is involved in progression of epithelial cell-derived ovarian carcinomas.

    Science.gov (United States)

    Yang, C; Lim, W; Bae, H; Song, G

    2016-04-01

    Aquaporins (AQPs) are membrane proteins that passively deliver water across the plasma membrane to play an important role in maintaining cell shape. Members of the AQP family are distributed in most of the tissues in the human body and perform a variety of functions based on the water homeostasis suitable for each organ. However, there is little known about the expression and regulation of AQP family members in chickens. Therefore, we determined the expression of AQPs in various tissues of chickens. Among 13 isotypes, AQP3 was highly expressed in the chicken oviduct. Expression of AQP3 messenger RNA (mRNA) increased in the magnum (P laying hens. In conclusion, AQP3 does not simply function to transport water into and out of cells but also appears to be closely involved in development of the chicken oviduct, which is regulated by estrogens. Furthermore, our results suggest AQP3 as a new diagnostic for early detection and treatment of epithelial cell-derived ovarian carcinomas. PMID:26808975

  10. Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era [Corrigendum

    Directory of Open Access Journals (Sweden)

    Berger JL

    2015-03-01

    Full Text Available Berger JL, Smith A, Zorn KK, et al. Onco Targets Ther. 2014;7:1409–1413.It has been brought to our attention that there are two pharmaceutical companies that market drugs with the name ‘lipodox’ and we erroneously refer to the product used in our current study-Outcomes analysis of an alternative formulation of PEGylated liposomal doxorubicin in recurrent epithelial ovarian carcinoma during the drug shortage era. by the trade name Lipo-dox®, a drug produced by TTY Biopharm Co. Ltd, when the Sun Pharma product is Lipodox. Lipo-Dox® utilizes a different liposomal particle than Doxil®, DSCP versus HSCP. Due to the similarity of the drug names, we were under the mistaken impression that Sun Pharma’s Lipodox utilized the DSCP liposome. We postulated that this might be related to the poor clinical outcomes seen in our population. It is now clear that Lipodox utilizes the same liposome as Doxil® and this is not a relevant point of discussion. The authors would like to let the readers know that Lipodox uses HSCP as the liposome and this should be corrected in the manuscript. The patients in our current study were all treated with Lipodox, and this drug uses HSCP as the liposome.

  11. Sorafenib Prevents Escape from Host Immunity in Liver Cirrhosis Patients with Advanced Hepatocellular Carcinoma

    OpenAIRE

    Yasukiyo Sumino; Takanori Mukozu; Hidenari Nagai; Yoshinori Igarashi; Koji Ishii; Kouichi Momiyama; Mie Shinohara; Noritaka Wakui; Masahiro Kanayama; Takenori Kanekawa; Kazunari Iida; Daigo Matsui

    2012-01-01

    Purpose. It has been reported that Th2 cytokines downregulate antitumor immunity, while activation of type T cells promotes antitumor immunity. The aim of this paper was to evaluate host immunity in liver cirrhosis (LC) patients with advanced hepatocellular carcinoma (aHCC) receiving sorafenib therapy. Methods. Forty-five adult Japanese LC patients received sorafenib for aHCC between 2009 and 2011 at our hospital. Sorafenib was administered at a dose of 200–800 mg/day for 4 weeks. Blood sampl...

  12. Sorafenib induced tumor lysis syndrome in an advanced hepatocellular carcinoma patient

    Institute of Scientific and Technical Information of China (English)

    Wu-Shiung Huang; Chang-Hsu Yang

    2009-01-01

    A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to have advanced hepatocellular carcinoma. His AFP was initially 9828 mg/L and rapidly dropped to 5597 mg/L in ten days after oral sorafenib treatment. However, he developed acute renal failure, hyperkalemia, and hyperuricemia 30 d after receiving the sorafenib treatment. Tumor lysis syndrome was suspected and intensive hemodialysis was performed. Despite intensive hemodialysis and other supportive therapy, he developed multiple organ failure (liver, renal, and respiratory failure) and metabolic acidosis. The patient expired 13 d after admission.

  13. Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Ye Liu; Yong-Hong Li; Zhuo-Wei Liu; Zhi-Ling Zhang; Yun-Lin Ye; Kai Yao; Hui Han; Zi-Ke Qin; Fang-Jian Zhou

    2013-01-01

    The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on local y advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregional y advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overal survival for the patients was 24 months (range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potential y curative in locoregional y advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

  14. Combined therapy with thrombospondin-1 type I repeats (3TSR) and chemotherapy induces regression and significantly improves survival in a preclinical model of advanced stage epithelial ovarian cancer

    OpenAIRE

    Russell, Samantha; Duquette, Mark; Liu, Joyce; Drapkin, Ronny; Lawler, Jack; Petrik, Jim

    2014-01-01

    Most women are diagnosed with epithelial ovarian cancer (EOC) at advanced stage, where therapies have limited effectiveness and the long-term survival rate is low. We evaluated the effects of combined antiangiogenic and chemotherapy treatments on advanced stage EOC. Treatment of EOC cells with a recombinant version of the thrombospondin-1 type I repeats (3TSR) induced more apoptotic cell death (36.5 ± 9.6%) in vitro compared to untreated controls (4.1 ± 1.4). In vivo, tumors were induced in a...

  15. Radiation therapy for the treatment of feline advanced cutaneous squamous cell carcinoma

    International Nuclear Information System (INIS)

    The efficacy of radiation therapy for feline advanced cutaneous squamous cell carcinoma was evaluated. A full course radiation therapy protocol was applied to six cats showing single or multiple facial squamous cell carcinomas, in a total of seven histologically confirmed neoplastic lesions. Of the lesions, one was staged as T1, and six as T4 according to WHO staging system of epidermal tumors. The animals were submitted to twelve radiation fractions of 4 Gy each, on a Monday-Wednesday-Friday schedule, and the equipment used was an orthovoltage unit. Energy used was 120 kV, 15 mA and 2 mm aluminum filter. The cats were evaluated during the treatment and 30 and 60 days after the end of the radiation therapy. In this study, 87% of the lesions had complete remission and 13% partial remission to the treatment. Side effects were considered mild according to Veterinary Radiation Therapy Oncology Group Toxicity criteria, and included erythema, epilation and rhinitis. Radiation Therapy was considered safe for feline cutaneous squamous cell carcinoma, leading to mild side effects and can represent a good therapeutic option. (author)

  16. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    Science.gov (United States)

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  17. Diagnostic accuracy of FDG PET in the follow-up of platinum-sensitive epithelial ovarian carcinoma

    International Nuclear Information System (INIS)

    This study was designed to retrospectively evaluate the diagnostic yield of FDG PET for the diagnosis of recurrent ovarian cancer. Eighty FDG PET scans were performed on 55 patients owing to suspicion of relapse, and 45 FDG PET scans were performed on 31 patients who were clinically disease free. PET results were compared with the results of conventional radiological imaging (CIM) and serum CA 125 levels, and related to pathological findings in 54 cases or clinical follow-up in 71 cases. CIM correctly identified 49 cases with recurrence [sensitivity (SE) 53.3%],and there were 27 true negatives [specificity (SP) 81.8%] However, 43 cases were false negative and six were false positive. The positive predictive value (PPV), negative predictive value (NPV) and accuracy (ACC) of CIM were 89%, 38.6% and 60.8%, respectively. FDG PET correctly detected recurrent disease in 80/92 cases (SE 86.9%, p < 0.05) and ruled out relapse in 26/33 cases (SP = 78.8%). The PPV, NPV and ACC of PET were 91.9%, 68.4% and 84.8%, respectively. Standardised uptake values did not provide additional diagnostic accuracy compared with visual analysis. The CA 125 results showed an SE of 57.6%, an SP of 93.9% and an ACC of 67.2%. In 23 patients with positive serum CA 125 levels, but negative CIM, FDG PET was positive and relapse was confirmed. Furthermore, FDG PET was positive and relapse was confirmed in 11 patients with negative serum CA 125 levels and CIM. FDG PET may detect recurrent ovarian cancer earlier than CIM, with higher sensitivity and even higher diagnostic accuracy. (orig.)

  18. Markers of T cell infiltration and function associate with favorable outcome in vascularized high-grade serous ovarian carcinoma.

    Directory of Open Access Journals (Sweden)

    Katelin N Townsend

    Full Text Available BACKGROUND: When T cells infiltrate the tumor environment they encounter a myriad of metabolic stressors including hypoxia. Overcoming the limitations imposed by an inadequate tumor vasculature that contributes to these stressors may be a crucial step to immune cells mounting an effective anti-tumor response. We sought to determine whether the functional capacity of tumor infiltrating lymphocytes (TIL could be influenced by the tumor vasculature and correlated this with survival in patients with ovarian cancer. METHODOLOGY AND PRINCIPAL FINDINGS: In 196 high-grade serous ovarian tumors, we confirmed that the tumor vascularity as measured by the marker CD31 was associated with improved patient disease-specific survival. We also found that tumors positive for markers of TIL (CD8, CD4 and forkhead box P3 (FoxP3 and T cell function (granzyme B and T-cell restricted intracellular antigen-1 (TIA-1 correlated significantly with elevated vascularity. In vitro, hypoxic CD8 T cells showed reduced cytolytic activity, secreted less effector cytokines and upregulated autophagy. Survival analysis revealed that patients had a significant improvement in disease-specific survival when FoxP3 expressing cells were present in CD31-high tumors compared to patients with FoxP3 expressing cells in CD31-low tumors [HR: 2.314 (95% CI 1.049-5.106; p = 0.0377]. Patients with high vascular endothelial growth factor (VEGF expressing tumors containing granzyme B positive cells had improved survival compared to patients with granzyme B positive cells in VEGF-low tumors [HR: 2.522 (95% CI 1.097-5.799; p = 0.0294]. SIGNIFICANCE: Overall, this data provides a rationale for developing strategies aimed at improving the adaptability and function of TIL to hypoxic tumor conditions.

  19. FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings

    International Nuclear Information System (INIS)

    Gastric cancer carries a poor prognosis and is the second most frequent cause of cancer-related death worldwide. In spite of the clinical importance of this tumour entity, only a few fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) studies have been published on gastric carcinomas. The aim of this study was to characterise the FDG uptake of gastric carcinomas by relating it to the histopathological properties of the tumours. Within this context, we focussed particularly on the microscopic growth type according to Lauren since our preliminary observations indicated low FDG accumulation in the non-intestinal growth type compared with the intestinal type. Forty patients with locally advanced gastric carcinomas and ten control subjects were studied by FDG PET (300 MBq i.v., emission scan: 40 min p.i., one bed position, measured transmission, filtered back-projection). Detectability of the tumours was qualitatively assessed by two independent observers. For quantitative analysis the regional tumour uptake was measured by standardised uptake values (SUV normalised to the body surface area) using a region of interest technique. Qualitative and quantitative analyses were performed with respect to the microscopic growth type according to Lauren (intestinal type vs non-intestinal type). Other histopathological characteristics were also assessed: mucus content, grading, tumour extension and tumour location. In 36 patients the survival rates were compared for detectable vs non-detectable tumours and for tumour FDG uptake above and below the median. Only 24 of the 40 locally advanced gastric carcinomas (60%) were detected by FDG PET. The detection rate for tumours of the intestinal type was significantly higher than that for tumours of the non-intestinal type (83% vs 41%, P=0.01). Only 2/18 intestinal type tumours contained extracellular or intracellular mucus whereas 17/22 non-intestinal tumours did so (P<0.01). The mean SUV was significantly different

  20. Differences in Regional Diagnostic Strategies and in Intended Versus Actual First-Line Treatment of Patients With Advanced Ovarian Cancer in Denmark

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten Lindberg; Ottesen, Bent; Kehlet, Henrik;

    2014-01-01

    BACKGROUND: Triage of patients with ovarian cancer to primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT) is challenging. In Denmark, the use of NACT has increased, but substantial differences in the use of NACT or PDS exist among centers. We aimed to characterize the differences...... and 4% never had debulking surgery. Of the 288 patients (53%) referred to NACT, 44% were never debulked. Fourteen patients (3%) were referred to palliative treatment. The use of different imaging modalities, diagnostic laparoscopy, and laparotomy varied significantly among the centers. Diagnostic......-line treatments as well as in the diagnostic process and use of NACT, calling for further discussion on diagnostic strategy and therapeutically approach for patients with advanced ovarian cancer....

  1. Electrochemotherapy as a new therapeutic strategy in advanced Merkel cell carcinoma of head and neck region

    International Nuclear Information System (INIS)

    Merkel Cell Carcinoma (MCC) is a rare and aggressive tumour, arising from a cutaneous mechanoceptor cell located in the basal layer of epidermis, with poor prognosis. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. We report a case of 84 years old woman with a recurrent MCC of the chin treated with electrochemotherapy (ECT). During the period of 20 months, four sessions of ECT were employed, which resulted in an objective response of the tumour and good quality of residual life. Our case shows the effectiveness of ECT in the treatment of locally advanced MCC of the head and neck region in a patient not suitable for standard therapeutic options

  2. Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma using the dorsal approach: a case report.

    Science.gov (United States)

    Scheffer, Hester J; Melenhorst, Marleen C A M; Vogel, Jantien A; van Tilborg, Aukje A J M; Nielsen, Karin; Kazemier, Geert; Meijerink, Martijn R

    2015-06-01

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively. PMID:25288173

  3. Percutaneous Irreversible Electroporation of Locally Advanced Pancreatic Carcinoma Using the Dorsal Approach: A Case Report

    International Nuclear Information System (INIS)

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively

  4. Percutaneous Irreversible Electroporation of Locally Advanced Pancreatic Carcinoma Using the Dorsal Approach: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Scheffer, Hester J., E-mail: hj.scheffer@vumc.nl; Melenhorst, Marleen C. A. M., E-mail: m.melenhorst@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands); Vogel, Jantien A., E-mail: j.a.vogel@amc.uva.nl [Academic Medical Center, Department of Surgery (Netherlands); Tilborg, Aukje A. J. M. van, E-mail: a.vantilborg@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands); Nielsen, Karin, E-mail: k.nielsen@vumc.nl; Kazemier, Geert, E-mail: g.kazemier@vumc.nl [VU University Medical Center, Department of Surgery (Netherlands); Meijerink, Martijn R., E-mail: mr.meijerink@vumc.nl [VU University Medical Center, Department of Radiology and Nuclear Medicine (Netherlands)

    2015-06-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively.

  5. Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras.

    Science.gov (United States)

    Li, Pengxiang; Wong, Yu-Ning; Armstrong, Katrina; Haas, Naomi; Subedi, Prasun; Davis-Cerone, Margaret; Doshi, Jalpa A

    2016-02-01

    Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real-world setting. Utilizing the 2000-2010 SEER Research files, a pre-post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000-2005) and the targeted therapy era (2006-2010). RCC patients diagnosed in the targeted therapy era (N = 6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N = 7231, hazard ratio (HR) for all-cause death: 0.86, P < 0.01), while the change between the pre-post periods was not significant for advanced prostate cancer patients (HR: 0.97, P = 0.08). Advanced RCC patients had significantly larger improvements in overall survival compared to advanced prostate cancer patients (z = 4.31; P < 0.01). More detailed year-to-year analysis revealed greater survival improvements for RCC in the later years of the posttargeted period. Similar results were seen for cause-specific survival. Subgroup analyses by nephrectomy status, age, and gender showed consistent findings. Patients diagnosed with advanced RCC during the targeted therapy era had better survival outcomes than those diagnosed during the pretargeted therapy era. Future studies should examine the real-world survival improvements directly associated with targeted therapies. PMID:26645975

  6. [A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma].

    Science.gov (United States)

    Shinmura, Kazuyasu; Kaiho, Takashi; Yanagisawa, Shinji; Okamoto, Ryo; Nishimura, Masaki; Kobayashi, Soichi; Okaniwa, Akira; Mun, Yangi; Tsuchiya, Shunichi; Chiba, Ryoji

    2015-11-01

    A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma. PMID:26805152

  7. Cryotherapy combined with chemoembolization for the treatment of advanced hepatic carcinoma: a clinical study

    International Nuclear Information System (INIS)

    Objective: To discuss the technique, efficacy and clinical significance of cryoablation combined with transcatheter arterial chemoembolization(TACE) for the treatment of advanced hepatic carcinoma. Methods: One hundred and ninety-two patients, who accorded with the selected criterion, were divided into TACE group (n=100) and combination group (cryotherapy combined with TACE, n=92). Pre-and post-treatment AFP level, recurrence rate and life span between two groups were compared. Results: The complete necrosis rate of the tumor and the recurrence rate in TACE group were 29% and 42%, which were 88.04% and 24% in combination group, respectively. The serum AFP level was significantly decreased after treatment in both groups (P<0.05), and the reduction in AFP level was significantly greater in combination group than that in TACE group (P<0.05). During a follow-up of 30 months the survival rate at each evaluation period of combination group was higher than that of TACE group without exception. Conclusion: As an effective and safe technique, cryoablation combined with chemoembolization is far superior to simple TACE in treating advanced hepatic carcinoma. (authors)

  8. Preoperative radiotherapy followed by radical vulvectomy with inguinal lymphadenectomy for advanced vulvar carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Rotmensch, J.; Rubin, S.J.; Sutton, H.G.; Javaheri, G.; Halpern, H.J.; Schwartz, J.L.; Stewart, M.; Weichselbaum, R.R.; Herbst, A.L. (Univ. of Chicago, IL (USA))

    1990-02-01

    A therapeutic alternative to exenteration for large locally advanced vulvar carcinoma involving the rectum, anus, or vagina is the use of preoperative radiation followed by radical surgery. Between 1980 and 1988, 13 patients with Stage III and 3 with Stage IV vulvar carcinoma involving the rectum/anus, urethra, or vagina were treated with 4000 rad to the vulva and 4500 rad to the inguinal and pelvic nodes followed by a radical vulvectomy and inguinal lymphadenectomy 4 weeks later. The overall 5 year cumulative survival was 45%. Twelve tumors regressed after radiation with 62.5% of the patients having visceral preservation while in 4 patients there was no major response to radiation and urinary or fecal diversion was required. Of the 6 recurrences 4 were central and 2 distant. Three patients with central recurrences had tumor within 1 cm of the vulvectomy margin. Complications included wet desquamation, inguinal wound separation, lymphedema, and urethral strictures. There were no operative deaths. It is concluded that the use of preoperative radiation followed by radical vulvectomy may be an alternative to pelvic exenteration in selected patients with advanced vulvar lesions.

  9. Hemoglobin as an important prognostic factor in concurrent chemoradiotherapy for locally advanced carcinoma of the cervix

    International Nuclear Information System (INIS)

    The objective of this study was to examine a possible association of hemoglobin with clinical outcome in patients with locally advanced squamous cell carcinoma of the cervix who were treated with concurrent chemoradiotherapy (CCRT). Seventy-five patients with Stage IB to IVA disease who were treated with CCRT were reviewed retrospectively. The mean age was 49.8 years. In the treatment, standard radiotherapy was performed accompanied by concomitant chemotherapy using cisplatin. Pre-treatment hemoglobin was defined as the earliest hemoglobin level prior to the initiation of treatment. Weekly nadir hemoglobin levels throughout treatment were averaged and used as average weekly nadir hemoglobin during treatment (AWNHg). The mean follow-up time was 28.6 months. The mean pre-treatment hemoglobin of 11.6 g/dL was significantly reduced to the mean AWNHg of 9.9 g/dL. The levels of pre-treatment hemoglobin and AWNHg were significantly associated with tumor response to treatment. The 5-year cumulative disease-free survival and overall survival rates for all 75 patients were 67.8% and 75.3%, respectively. Multivariate statistical analysis revealed that AWNHg (≥9.0 versus <9.0 g/dL) was an independent prognostic factor for overall survival (p=0.038), but pre-treatment hemoglobin was not a significant factor. AWNHg was one of the most powerful independent predictors of overall survival in patients undergoing CCRT for locally advanced squamous cell carcinoma of the cervix. (author)

  10. Advanced basal cell carcinoma, the hedgehog pathway, and treatment options – role of smoothened inhibitors

    Directory of Open Access Journals (Sweden)

    Fecher LA

    2015-11-01

    Full Text Available Leslie A Fecher,1,3 William H Sharfman2 1Department of Internal Medicine and Dermatology, Indiana University Health Simon Cancer Center, Indianapolis, IN, USA; 2The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA, 3Department of Internal Medicine and Dermatology, University of Michigan, MI, USA Abstract: Cutaneous basal cell carcinoma (BCC is the most common human cancer and its incidence is rising worldwide. Ultraviolet radiation exposure, including tanning bed use, as well as host factors play a role in its development. The majority of cases are treated and cured with local therapies including surgery. Yet, the health care costs of diagnosis and treatment of BCCs in the US is substantial. In the United States, the cost of nonmelanoma skin cancer care in the Medicare population is estimated to be US$426 million per year. While rare, locally advanced BCCs that can no longer be controlled with surgery and/or radiation, and metastatic BCCs do occur and can be associated with significant morbidity and mortality. Vismodegib (GDC-0449, a smoothened inhibitor targeted at the hedgehog pathway, is the first US Food and Drug Association (FDA-approved agent in the treatment of locally advanced, unresectable, and metastatic BCCs. This class of agents appears to be changing the survival rates in advanced BCC patients, but appropriate patient selection and monitoring are important. Multidisciplinary assessments are essential for the optimal care and management of these patients. For some patients with locally advanced BCC, treatment with a hedgehog inhibitor may eliminate the need for an excessively disfiguring or morbid surgery. Keywords: basal cell carcinoma, hedgehog, smoothened, vismodegib, Gorlin, basal cell nevus syndrome

  11. A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium

    Directory of Open Access Journals (Sweden)

    Qian Jiong

    2007-06-01

    Full Text Available Abstract Background Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium. Methods Patients with advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and carboplatin area under the concentration-time curve(AUC 5 on day 1 every 21 days. Results Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1–6 was administered. Overall response rate was 46.2% (95% confidence interval: 32–65% including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6–8.4 months and 13.6 months (95% confidence interval: 10.2–17.0 months, respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4% patients. Conclusion The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens. Trial registration ISRCTN88259320

  12. A phase II trial of gemcitabine plus carboplatin in advanced transitional cell carcinoma of the urothelium

    International Nuclear Information System (INIS)

    Recent studies have demonstrated the effectiveness of cisplatin-based combinations in patients with advanced transitional cell carcinoma(TCC) of the urothelium. Concern over cisplatin toxicity instigated a search for alternative regimens. The aim of the study was to evaluate the activity and tolerability of gemcitabine plus carboplatin combination as first-line treatment in patients with advanced transitional cell carcinoma of the urothelium. Patients with advanced TCC were treated with gemcitabine 1200 mg/m2 on days 1 and 8 and carboplatin area under the concentration-time curve(AUC) 5 on day 1 every 21 days. Out of 41 patients, thirty-nine were evaluable for efficacy and 41 for toxicity. A median of 5 cycles (range 1–6) was administered. Overall response rate was 46.2% (95% confidence interval: 32–65%) including 10.3% complete responses and 35.9% partial responses. The median time to progression and median overall survival were 7.5 months (95% confidence interval: 6.6–8.4 months) and 13.6 months (95% confidence interval: 10.2–17.0 months), respectively. Grade 3/4 neutropenia, anemia and thrombocytopenia were observed in 36.6%, 26.8, and 24.4% of patients, respectively. Non-hematological toxicity was generally mild. Grade 3 vomiting occurred in 1 (2.4%) patients. The gemcitabine plus carboplatin combination is active in advanced TCC with acceptable toxicity and needs to be evaluated further and compared with other non-cisplatin-containing regimens. ISRCTN88259320

  13. Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

    Science.gov (United States)

    2016-03-17

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; 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 Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  14. C-kit:PDGFRα的表达与卵巢浆液性癌顺铂耐药的临床研究%Expression of C-Kit & PDGFRα and correlation with chemotherapy resistance in ovarian serous carcinomas: a clinical study

    Institute of Scientific and Technical Information of China (English)

    Cunjian Yi; Li Li; Ding Ma

    2009-01-01

    Objective: To investigate the expression of C-Kit and PDGFRα and their correlation with chemotherapy resis-tance in ovarian serous carcinoma. Methods: We undertook SP immunohistochemical technique to examine the expression of C-Kit and PDGFRα in 59 cases with ovarian serous carcinomas, using archival paraffin-embedded specimens. Then we observed the correlation with chemotherapy resistance. Results: C-Kit and PDGFRα immunostainings were observed posi-tively expressed in 57.63% and 66.10% cases. C-Kit expression was statistically correlated with the progression of disease after first-line chemotherapy (P 0.05). There were great difference between of C-Kit and PDGFRa expressions in samples of different differentiated and clinical stages of ovarian serous carci-nomas (P<0.01 or P<0.05). Conclusion: C-Kit is statistically correlated with chemotherapy resistance, while PDGFRα is not correlated.

  15. TP53 mutations in ovarian carcinomas from sporadic cases and carriers of two distinct BRCA1 founder mutations; relation to age at diagnosis and survival

    International Nuclear Information System (INIS)

    Ovarian carcinomas from 30 BRCA1 germ-line carriers of two distinct high penetrant founder mutations, 20 carrying the 1675delA and 10 the 1135insA, and 100 sporadic cases were characterized for somatic mutations in the TP53 gene. We analyzed differences in relation to BRCA1 germline status, TP53 status, survival and age at diagnosis, as previous studies have not been conclusive. DNA was extracted from paraffin embedded formalin fixed tissues for the familial cases, and from fresh frozen specimen from the sporadic cases. All cases were treated at our hospital according to protocol. Mutation analyses of exon 2 – 11 were performed using TTGE, followed by sequencing. Survival rates for BRCA1-familial cases with TP53 mutations were not significantly lower than for familial cases without TP53 mutations (p = 0.25, RR = 1.64, 95% CI [0.71–3.78]). Median age at diagnosis for sporadic (59 years) and familial (49 years) cases differed significantly (p < 0.001) with or without TP53 mutations. Age at diagnosis between the two types of familial carriers were not significantly different, with median age of 47 for 1675delA and 52.5 for 1135insA carriers (p = 0.245). For cases ≥50 years at diagnosis, a trend toward longer survival for sporadic over familial cases was observed (p = 0.08). The opposite trend was observed for cases <50 years at diagnosis. There do not seem to be a protective advantage for familial BRCA1 carriers without TP53 mutations over familial cases with TP53 mutations. However, there seem to be a trend towards initial advantage in survival for familial cases compared to sporadic cases diagnosed before the age of 50 both with and without TP53 mutations. However, this trend diminishes over time and for cases diagnosed ≥50 years the sporadic cases show a trend towards an advantage in survival over familial cases. Although this data set is small, if confirmed, this may be a link in the evidence that the differences in ovarian cancer survival reported, are

  16. The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

    Science.gov (United States)

    Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

    2015-10-13

    Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease. PMID:26267317

  17. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    Science.gov (United States)

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (pPIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  18. Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial

    Science.gov (United States)

    Stark, Dan; Nankivell, Matthew; Pujade-Lauraine, Eric; Kristensen, Gunnar; Elit, Lorraine; Stockler, Martin; Hilpert, Felix; Cervantes, Andrés; Brown, Julia; Lanceley, Anne; Velikova, Galina; Sabate, Eduardo; Pfisterer, Jacobus; Carey, Mark S; Beale, Philip; Qian, Wendi; Swart, Ann Marie; Oza, Amit; Perren, Tim

    2013-01-01

    Summary Background In the Gynecologic Cancer Intergroup International Collaboration on Ovarian Neoplasms 7 (ICON7) trial, bevacizumab improved progression-free survival in patients with ovarian cancer when used in combination with first-line chemotherapy and as a single-drug continuation treatment for 18 cycles. In a preliminary analysis of a high-risk subset of patients, there was also an improvement in overall survival. This study aims to describe the health-related quality-of-life (QoL) outcomes from ICON7. Methods ICON7 is a randomised, multicentre, open-label phase 3 trial. Between Dec 18, 2006, and Feb 16, 2009, after a surgical procedure aiming to debulk the disease, women with International Federation of Gynecology and Obstetrics (FIGO) high-risk stage I–IV epithelial ovarian cancer were randomly allocated (1:1) by computer program and block randomisation to receive either six cycles of standard chemotherapy (total 18 weeks) with carboplatin (area under the curve 5 or 6) and paclitaxel (175 mg/m2) alone or with bevacizumab (7·5 mg/kg) given intravenously with chemotherapy and continued as a single drug thereafter (total 54 weeks). The primary QoL endpoint was global QoL from the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire–core 30 at week 54, analysed by ANOVA and adjusted for baseline score. Analyses were by intention to treat. The ICON7 trial has completed recruitment and remains in follow-up. This study is registered, number ISRCTN91273375. Findings 764 women were randomly assigned to the standard chemotherapy group and 764 to the bevacizumab group. At baseline, 684 (90%) of women in the standard chemotherapy group and 691 (90%) of those in the bevacizumab group had completed QoL questionnaires. At week 54, 502 (66%) women in the bevacizumab group and 388 (51%) women in the standard chemotherapy group provided QoL data. Overall, the mean global QoL score improved during chemotherapy by 7·2 points (SD 24

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

    Science.gov (United States)

    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

  20. Prognostic impact of programmed cell death-1 (PD-1) and PD-ligand 1 (PD-L1) expression in cancer cells and tumor-infiltrating lymphocytes in ovarian high grade serous carcinoma

    OpenAIRE

    Darb-Esfahani, Silvia; Kunze, Catarina Alisa; Kulbe, Hagen; Sehouli, Jalid; Wienert, Stephan; Lindner, Judith; Budczies, Jan; Bockmayr, Michael; Dietel, Manfred; Denkert, Carsten; Braicu, Ioana; Jöhrens, Korinna

    2015-01-01

    Aims Antibodies targeting the checkpoint molecules programmed cell death 1 (PD-1) and its ligand PD-L1 are emerging cancer therapeutics. We systematically investigated PD-1 and PD-L1 expression patterns in the poor-prognosis tumor entity high-grade serous ovarian carcinoma. Methods PD-1 and PD-L1 protein expression was determined by immunohistochemistry on tissue microarrays from 215 primary cancers both in cancer cells and in tumor-infiltrating lymphocytes (TILs). mRNA expression was measure...