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Sample records for primary malignant ovarian

  1. Increased risk of concurrent primary malignancies in patients diagnosed with a primary malignant epithelial ovarian tumor.

    PubMed

    van Niekerk, Catharina C; Vooijs, G Peter; Bulten, Johan; van Dijck, Jos A A M; Verbeek, Andre L M

    2007-03-01

    Ovarian cancer and second malignant neoplasms are found to occur rather frequently in the same patient. From a clinical perspective, it is important to have quantitative information on concurrent malignancies in the same year of diagnosis of the epithelial ovarian cancer. In this population-based study, we used data from the Netherlands Nationwide Network for Registry of histo- and cytopathology (PALGA) and the Netherlands Cancer Registry (NCR). Data of the ovarian cancer as well as data on previous or later cancers were obtained. Age-specific cancer rates from the NCR were used to calculate expected numbers of cancer. Between 1987 and 1993, histopathology reports were identified of 4577 patients with primary epithelial malignant or primary borderline malignant ovarian cancers and its longitudinal data. As the database may lack detailed information on histopathology, a recent sample of 789 patients diagnosed with ovarian cancer in 1996-2003 was comprehensively studied as well. In the eventual data analysis of 5366 patients, 244 cases (4.5%) of concurrent primary malignancy were reported in the same year that the malignant epithelial ovarian tumor had been diagnosed against 51 expected. The observed vs expected ratio was 4.8 and the 95% confidence interval (CI) (4.3-5.5). For cancer of the uterus/endometrium the observed vs expected ratio was 62.3 (95% CI 52.5-73.5). For skin, breast, colorectal, urinary bladder, renal and cervical cancer the ratio was also larger than unity. The elevated risk of concurrent cancer may lead to clinical screening protocols. The findings on endometrial cancer may prompt research on common etiologies and biomarkers.

  2. Osteopathic Approach to the Diagnosis of Appendiceal Mucinous Cystadenocarcinoma Mimicking Primary Ovarian Malignant Neoplasm.

    PubMed

    Martingano, Daniel; Gurm, Hashroop; Oliff, Andrew; Martingano, Francis X; Aglialoro, George

    2016-07-01

    The fifth leading cause of cancer-related deaths among women in the United States is ovarian cancer. An estimated 21,980 new cases and 14,270 estimated deaths occurred nationwide in 2014. More than two-thirds of cases of ovarian cancer are diagnosed at stage III or IV when the peritoneal cavity or other organs are affected. Primary appendiceal malignant neoplasms may mimic advanced-stage ovarian cancer and can be misdiagnosed because of its presentation as a palpable adnexal mass. The authors describe a 42-year-old woman who was admitted to the department of obstetrics and gynecology to receive treatment for presumed advanced-stage ovarian cancer. She subsequently received a diagnosis of primary pseudomyxoma peritonei metastatic to the ovaries, mimicking a primary ovarian cancer by osteopathic structural examination findings, serum tumor markers, surgical exploration, and histopathologic confirmation. PMID:27367953

  3. Secondary Primary Malignancy Risk in Patients With Ovarian Cancer in Taiwan

    PubMed Central

    Hung, Yi-Ping; Liu, Chia-Jen; Hu, Yu-Wen; Chen, Min-Huang; Li, Chun-Pin; Yeh, Chiu-Mei; Chiou, Tzeon-Jye; Chen, Tzeng-Ji; Yang, Muh-Hwa; Chao, Yee

    2015-01-01

    Abstract To evaluate the incidence of secondary primary malignancy (SPM) in patients with ovarian cancer using a nationwide retrospective population-based dataset. Patients newly diagnosed with ovarian cancer between 1997 and 2010 were identified using Taiwan's National Health Insurance database. Patients with antecedent malignancies were excluded. Standardized incidence ratios (SIRs) for SPM were calculated and compared with the cancer incidence in the general population. Risk factors for cancer development were analyzed using Cox proportional hazard models. Effects of surgery, chemotherapy, and radiotherapy after ovarian cancer diagnosis were regarded as time-dependent variables to prevent immortal time bias. During the 14-year study period (follow-up of 56,214 person-years), 707 cancers developed in 12,127 patients with ovarian cancer. The SIR for all cancers was 2.78 (95% confidence interval 2.58–3.00). SIRs for follow-up periods of >5, 1–5, and <1 year were 1.87, 2.04, and 6.40, respectively. After the exclusion of SPM occurring within 1 year of ovarian cancer diagnosis, SIRs were significantly higher for cancers of the colon, rectum, and anus (2.14); lung and mediastinum (1.58); breast (1.68); cervix (1.65); uterus (7.96); bladder (3.17), and thyroid (2.23); as well as for leukemia (3.98) and others (3.83). Multivariate analysis showed that age ≥ 50 years was a significant SPM risk factor (hazard ratio [HR] 1.60). Different treatments for ovarian cancer, including radiotherapy (HR 2.07) and chemotherapy (HR 1.27), had different impacts on SPM risk. Patients with ovarian cancer are at increased risk of SPM development. Age ≥ 50 years, radiotherapy, and chemotherapy are independent risk factors. Close surveillance of patients at high risk should be considered for the early detection of SPM. PMID:26402833

  4. A6 in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2015-02-27

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

  5. Elesclomol Sodium and Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-12-23

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

  6. 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

    ClinicalTrials.gov

    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

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

    ClinicalTrials.gov

    2016-03-17

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

  8. YKL-40 in Serum Samples From Patients With Newly Diagnosed Stage III-IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer Receiving Chemotherapy

    ClinicalTrials.gov

    2016-02-19

    Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Mixed Epithelial Tumor; Malignant Ovarian Mucinous Tumor; Malignant Ovarian Neoplasm; Malignant Ovarian Serous Tumor; Malignant Ovarian Transitional Cell Tumor; Ovarian Adenocarcinoma; 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

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

    ClinicalTrials.gov

    2014-12-29

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

  10. Primary Ovarian Insufficiency.

    PubMed

    Laven, Joop S E

    2016-07-01

    Primary ovarian insufficiency (POI), also known as premature ovarian failure or premature menopause, is defined as cessation of menstruation before the expected age of menopause. Potential etiologies for POI can be divided into genetic, autoimmune, and iatrogenic categories. This review will try to summarize the genetic basis of POI focusing on recent data that are available using newer genetic techniques such as genome-wide association studies, whole-exome sequencing (WES), or next-generation sequencing techniques. By using these techniques, many genes have arisen that play some role in the pathophysiology of POI. Some of them have been replicated in other studies; however, the majority has not been proven yet to be unequivocally causative through functional validation studies. Elucidating the genetic and molecular basis of POI is of paramount importance not only in understanding ovarian physiology but also in providing genetic counseling and fertility guidance. Once additional variants are detected, it might become possible to predict the age of (premature) menopause in women at risk for POI. Women having certain perturbations of POI can be offered the option of oocyte cryopreservation, with later thawing and use in assisted reproductive technology at an appropriate age. PMID:27513024

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

    ClinicalTrials.gov

    2015-05-07

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

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

    ClinicalTrials.gov

    2016-07-08

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

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

    ClinicalTrials.gov

    2016-05-18

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

  14. Pathology of primary and metastatic mucinous ovarian neoplasms.

    PubMed

    Leen, Sarah Lam Shang; Singh, Naveena

    2012-07-01

    Recent years have seen a dramatic change in the pathological approach to ovarian mucinous neoplasms. A substantial proportion of tumours previously considered to be ovarian primaries actually represent secondary ovarian involvement by tumours elsewhere in the body. Two major categories of tumour have completely disappeared from the diagnostic spectrum: ovarian 'borderline' mucinous tumour associated with pseudomyxoma peritonei, and widely disseminated mucinous carcinomas. The emergent picture of true ovarian primary carcinoma of pure mucinous morphology is that this is a rare malignancy that is low grade and low stage at presentation in the vast majority of cases, with a very low likelihood of aggressive clinical behaviour. A large volume of literature has appeared concerning the pathological distinction of primary from metastatic ovarian mucinous neoplasms in view of the dramatically different prognosis and treacherously similar morphology. Clinicopathological parameters useful in the distinction of primary from metastatic mucinous ovarian carcinomas are reviewed. Major features favouring metastases are bilaterality, size <10 cm, surface involvement, extensive intra-abdominal spread and an extensive infiltrative pattern with desmoplasia. Two morphological patterns essentially exclude ovarian origin: colloid and signet ring carcinomas. Features favouring primary ovarian origin are unilaterality, large size >12 cm, smooth external surface and association with other ovarian pathology. An admixture of benign, borderline and malignant patterns in the same tumour favour primary origin, but can be misleading as a 'maturation' pattern in metastases can result in the same appearance.

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

    ClinicalTrials.gov

    2016-10-26

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian 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 Seromucinous Carcinoma; 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

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

    ClinicalTrials.gov

    2016-07-05

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

  17. General Information about Ovarian Low Malignant Potential Tumors

    MedlinePlus

    ... Malignant Potential Tumors Treatment (PDQ®)–Patient Version General Information About Ovarian Low Malignant Potential Tumors Go to ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  18. Primary pineal malignant melanoma

    PubMed Central

    Cedeño Diaz, Oderay Mabel; Leal, Roberto García; La Cruz Pelea, Cesar

    2011-01-01

    Primary pineal malignant melanoma is a rare entity, with only thirteen cases reported in the world literature to date. We report a case of a 70-year-old man, who consulted with gait disturbance of six months duration, associated in the last month with dizziness, visual abnormalities and diplopia. No other additional melanocytic lesions were found elsewhere. The magnetic resonance showed a 25 mm expansive mass in the pineal gland that was associated with hydrocephaly, ventricular and transependimary oedema. The lesion was partially excised by a supracerebellar infratentorial approach. The histological examination revealed a melanoma. The patient received radiation therapy, but died of disease 16 weeks later. We herein review the literature on this rare tumour and comment on its clinical, radiological and histopathological features and differential diagnosis. PMID:24765293

  19. 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

    ClinicalTrials.gov

    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

  20. Primary malignant melanoma

    PubMed Central

    Mısır, A. Ferhat; Durmuşlar, Mustafa C.; Zerener, Tamer; Gün, Banu D.

    2016-01-01

    Malignant melanomas (MM) of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period. PMID:27052289

  1. TLR8 Agonist VTX-2337 and Pegylated Liposomal Doxorubicin Hydrochloride or Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer

    ClinicalTrials.gov

    2014-12-23

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

  2. Chromosome abnormalities in primary ovarian cancer

    SciTech Connect

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

    1994-09-01

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

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

    ClinicalTrials.gov

    2015-12-21

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

  4. PAX2 Expression in Low Malignant Potential Ovarian Tumors and Low-Grade Ovarian Serous Carcinomas

    PubMed Central

    Tung, Celestine S.; Mok, Samuel C.; Tsang, Yvonne T.M.; Zu, Zhifei; Song, Huijuan; Liu, Jinsong; Deavers, Michael; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.; Wong, Kwong-Kwok

    2009-01-01

    Ovarian tumors of low-malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on 3 normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes up-regulated and 232 genes down-regulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most up-regulated genes in low-grade ovarian serous carcinoma. The up-regulation of PAX2 was validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analyses. Real-time RT-PCR demonstrated a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low-malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low-malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low-malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with previous immunohistochemical findings, PAX2 expression was found to be expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low-malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. Additionally, the absence of PAX2 expression in normal

  5. Osteosarcoma as Malignant Mural Nodule in Ovarian Mucinous Neoplasms of Intestinal Type: Report of 2 Cases.

    PubMed

    McFarland, Marie; Dina, Roberto; Fisher, Cyril; McCluggage, W Glenn

    2015-07-01

    Mural nodules, which may be benign or malignant, are well recognized in ovarian mucinous neoplasms, especially of borderline type. Malignant mural nodules most commonly comprise anaplastic carcinoma but sarcomas of various types have been reported. We report 2 cases of osteosarcoma occurring in young women (aged 18 and 34) as malignant mural nodules in a Grade 1 ovarian mucinous carcinoma of intestinal type and a borderline mucinous tumor of intestinal type. Primary osteosarcomas of the ovary have been described either arising within a teratoma or as a pure neoplasm but, to the best of our knowledge, osteosarcoma occurring as a mural nodule in an ovarian mucinous neoplasm has not been reported. In both our cases, the tumor was Stage 1 at presentation and the patients were treated with surgery without adjuvant chemotherapy. Both patients are free of disease with follow-up of 12 and 18 mo.

  6. Update on Primary Ovarian Insufficiency

    PubMed Central

    Hewlett, Meghan; Mahalingaiah, Shruthi

    2016-01-01

    Purpose of Review Despite an incidence of one percent among women under the age of forty, primary ovarian insufficiency (POI) is still poorly understood. As the variable etiology and presentation of POI complicate its management, a standard regimen for treatment remains to be established. However, emerging research has provided new insight on current mainstays of treatment as well as novel management approaches and therapeutic interventions. Recent findings Recent clinical trials in women with POI indicate that the widely-used regimen of transdermal estradiol and medroxyprogesterone acetate restores bone mineral density (BMD) to a level equal to women with normal ovarian function. Further research verifies that compounded bioidentical hormones and androgen supplementation are inadequate in treating POI and lowering risk for long-term sequelae. Additionally, assessing changes in bone turnover markers may be useful for monitoring BMD. Alternative therapies such as acupuncture, DHEA, and buproprion may be effective in treating the effects of estrogen deficiency at some level, but require further investigation. Summary Recent updates show promise in improving management methods and reducing risk of long-term sequelae. Additional research that expands upon the most current literature is critical in order to achieve an evidence-based standard of best practice. PMID:26512773

  7. Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-02-09

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

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

    ClinicalTrials.gov

    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

  9. Primary Malignant Tumours of Bone Following Previous Malignancy

    PubMed Central

    Patton, J. T.; Sommerville, S. M. M.; Grimer, R. J.

    2008-01-01

    Destructive bone lesions occurring in patients who have previously had a malignancy are generally assumed to be a metastasis from that malignancy. We reviewed 60 patients with a previous history of malignancy, who presented with a solitary bone lesion that was subsequently found to be a new and different primary sarcoma of bone. These second malignancies occurred in three distinct groups of patients: (1) patients with original tumours well known to be associated with second malignancies (5%); (2) patients whose second malignancies were likely to be due to the previous treatment of their primary malignancy (40%); (3) patients in whom there was no clearly defined association between malignancies (55%). The purpose of this study is to emphasise the necessity for caution in assuming the diagnosis of a metastasis when a solitary bone lesion is identified following a prior malignancy. Inappropriate biopsy and treatment of primary bone sarcomas compromises limb salvage surgery and can affect patient mortality. PMID:18414590

  10. Management of bilateral malignant ovarian germ cell tumors: Experience of a single institute

    PubMed Central

    Zhao, Ting; Liu, Yan; Jiang, Hongyuan; Zhang, Hao; Lu, Yuan

    2016-01-01

    Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls and young women who may wish to preserve their fertility. In order to review the prevalence, clinical characteristics, treatment and outcome of bilateral MOGCTs, we performed a retrospective review of patients who were diagnosed with bilateral MOGCTs and underwent primary surgery at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China) between January, 2001 and December, 2014. Of the 130 patients investigated, 8 were diagnosed with bilateral disease, most of whom were International Federation of Gynecology and Obstetrics stage I. There was no significant difference in overall and disease-free survival between patients with unilateral and those with bilateral disease. Cases with dysgerminoma, dysgerminoma coexisting with gonadoblastoma, yolk sac tumor and ovarian primary choriocarcinoma were included in this study. Fertility was spared in 2 patients (1 with dysgerminoma and 1 with ovarian primary choriocarcinoma). The patient with ovarian choriocarcinoma experienced relapse and was finally salvaged by radical surgery and adjuvant chemotherapy. According to our results and the published data, patients affected by bilateral MOGCTs have a satisfactory prognosis. The treatment modalities largely depend on the histological type of the tumor. Fertility-sparing surgery may be safe for patients affected by dysgerminoma, but should be considered with caution in patients with ovarian primary choriocarcinoma. PMID:27446585

  11. [Positron emission tomography (PET) in malignant ovarian tumors].

    PubMed

    Fularz, Maciej; Adamiak, Paulina; Czepczyński, Rafał; Jarzabek-Bielecka, Grazyna; Kedzia, Witold; Ruchała, Marek

    2013-08-01

    Accessibility of positron emission tomography integrated with computed tomography (PET/CT) has improved significantly in recent years. PET/CT with the use of 18F-deoxyglucose (FDG) is widely used in patients with ovarian malignancies at different stages of the management. FDG PET/CT shows high diagnostic accuracy in the differentiation of benign and malignant ovarian lesions with the exception of borderline tumors that may cause false negative results. Moreover FDG PET/CT is used in some centers for preoperative staging and determining the prognosis of ovarian cancer However further studies including larger groups of patients are needed to confirm the applicability of FDG PET/CT in case of the two abovementioned indications. Until now, the best documented indication for FDG PET/ CT in patients with ovarian cancer has been the detection of recurrence, especially in subjects with elevated CA 125 marker and negative results of other imaging techniques. This review focuses on the applicability of PET with the use of FDG in ovarian malignancies and points out to the limitations of this method.

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

    ClinicalTrials.gov

    2015-08-18

    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

  13. Barr body in fine needle aspiration cytology of ovarian malignancies.

    PubMed

    Agrawal, Pallavi; Dey, Pranab

    2012-11-01

    The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. The aim of this study is to evaluate the significance of Barr body count in malignant ovarian tumors on fine needle aspiration cytology (FNAC) smears. In this retrospective study, Barr body was counted in FNAC smears of 20 successive malignant ovarian lesions and expressed as percentage. Mean (±SD) Barr body score was 2.4 ± 2.58. Minimum Barr body count was 1 and maximum was 9. The gross reduction of Barr body in ovarian neoplasms is an interesting cytomorphologic finding.

  14. Primary malignant myelomatous pleural effusion.

    PubMed

    Mangla, Ankit; Agarwal, Nikki; Kim, George J; Catchatourian, Rosalind

    2016-08-01

    Primary malignant myelomatous pleural effusion (PMMPE) occurs in less than 1% of patients with multiple myeloma and is diagnosed either by visualization of plasma cells on cytology or by positive flow cytometry. The presence of immature plasma cells characterized by high nucleus to cytoplasm ratio, visible nucleolus and presence of Mott cells and Russell bodies are independent poor prognostic factors. The clinician should differentiate PMMPE from secondary pleural effusion as it is associated with a significantly worse prognosis and poor overall survival. PMID:27525090

  15. [Pure form of primary ovarian choriocarcinoma. Report of a case].

    PubMed

    Trigueros Velázquez, M; Sereno Coló, J A; Villagrán Urive, J

    1995-08-01

    Ovarian choriocarcinoma from the germ cells is a very rare malignant neoplasia. About the pure form, very few cases have been reported in medical literature. Ovarian choriocarcinoma may originate in three modalities. As primary choriocarcinoma associated to ovarian pregnancy, 2. As a metastatic ovarian carcinoma, from other organs, mainly the uterus, 3. As a primary tumour of germ cells with differentiation to trophoblastic structures. The latter grows in girls or in adult woman, generally young, where necessarily pregnancy has to be excluded. A case is presented of a 21 years old woman, treated at Hospital General "Dr. Miguel Silva", Morelia, Mich. single, without sexual life, with an abdomino-pelvic tumor of 24 cm, from the right ovary and adhered to ascending colon. Beta subunity of chorionic gonadotrophin was 200,000 mUI/ml of blood plasma. At laparotomy a right ovarian tumour, with infiltration to ascending colon, was found; this required total hysterectomy with bilateral salpingo-oophorectomy and right hemicolectomy. After surgery the patient received chemotherapy with cisplatin, bleomicin and vinblastine. After the third treatment cycle and at three months, chorionic gonadotropin became negative; and at four years follow up residual tumoural activity is absent. Largest mortality with these tumors appears during early post-operative stage and it is atributed to the tumour itself or to post-operative complications. If the patient survives this stage and with a good chemotherapeutic program, survival and even complete cure, occurs.

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

    MedlinePlus

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

  17. Ovarian mucinous tumor with malignant mural nodules: dedifferentiation or collision?

    PubMed

    Desouki, Mohamed M; Khabele, Dineo; Crispens, Marta A; Fadare, Oluwole

    2015-01-01

    Ovarian mucinous tumors with mural nodules are rare surface epithelial-stromal tumors. The mural nodules are divergent neoplasms that may be benign or malignant. The latter may be in the form of a sarcoma, carcinosarcoma, anaplastic carcinoma, or a variety of other recognized histotypes of carcinoma, which raises the question of whether malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors or whether they represent collision tumors. We recently reported the K-RAS gene mutation status in a case of ovarian mucinous adenocarcinoma with mural nodule of high-grade sarcoma. The mucinous and sarcomatous components revealed a mutation in codon 12 of the K-RAS gene of a different nucleotide substitution, indicating that these 2 tumor components were different clones of the same tumor. Herein, we are reporting another case of a 20-yr-old woman who presented with 22 cm pelvic mass, omental caking, and ascites. A diagnosis of invasive mucinous carcinoma with mural nodules of anaplastic carcinoma was rendered. K-RAS gene mutation studies revealed p.G12V, c.35G>T mutation in the 2 components of the tumor, which is the most common mutation reported in mucinous tumors of the ovary. The fact that sarcomatous or anaplastic carcinomatous mural nodules in ovarian mucinous tumors display the same K-RAS mutations as their underlying mucinous neoplasms provides supportive evidence that at least some malignant mural nodules represent a form of dedifferentiation in ovarian mucinous tumors, rather than a collision of 2 divergent tumor types.

  18. Genetics of primary ovarian insufficiency: a review.

    PubMed

    Fortuño, Cristina; Labarta, Elena

    2014-12-01

    Primary ovarian insufficiency is one of the main causes of female infertility owing to an abnormal ovarian reserve. Its relevance has increased in more recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less chances of pregnancy when women consider the option of having their first baby. Several exogenous factors can lead to this event, such us viral infections, metabolomic dysfunction, autoimmune diseases, and environmental or iatrogenic factors, although in most cases the mechanism that leads to the disorder is unknown. Genetic factors represent the most commonly identified cause and the impact of sex chromosome abnormalities (e.g., Turner syndrome or X structural abnormalities), autosomal and X-linked mutations on the genesis of primary ovarian insufficiency has also been well described. Yet in most cases, the genetic origin remains unknown and there are multiple candidate genes. This review aims to collect all the genetic abnormalities and genes associated with syndromic and non syndromic primary ovarian insufficiency that have been published in the literature to date using the candidate-gene approach and a genome-wide analysis.

  19. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-10-10

    Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  20. Ultrastructural study of benign, low-malignant potential (LMP), and malignant ovarian tumors.

    PubMed

    Ishioka, Shin-ichi; Sagae, Satoru; Ito, Eiki; Kudo, Ryuichi

    2004-03-01

    Ultrastructural characteristics of benign, low-malignant potential (LMP), and malignant ovarian tumors were investigated, considering the aspects of histologic subtypes and histologic grading. In addition, the histogenesis of ovarian cancer was histologically investigated in an attempt to elucidate whether malignant tumor was generated from benign or LMP tumor, or whether it was generated de novo from normal tissues. Although all the benign, LMP, and malignant tumors appeared to be derived from Mullerian duct in serous tumors, the origin of endometrioid or mucinous tumor could not be ultrastructurally clarified. However, there was ultrastructural similarity between benign and malignant tumors among serous, endometrioid, and mucinous tumors, and it was suggested that benign adenoma may be the developmental origin of malignant tumors regardless of the histologic subtype. In addition, the investigation of endometrioid tumors revealed that the differences of histologic grading in malignant tumors reflected the ultrastructural differences, and that G1 tumor had an ultrastructure that was more similar to that of benign and LMP tumors than to that of G2 tumor.

  1. Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency.

    PubMed

    Visser, Jenny A; Schipper, Izaäk; Laven, Joop S E; Themmen, Axel P N

    2012-06-01

    Primary ovarian insufficiency (POI), also known as premature ovarian failure, is a disorder of infertility characterized by amenorrhoea, low estrogen levels and increased gonadotropin levels in women aged <40 years. POI is the result of premature exhaustion of the follicle pool or can be attributed to follicular dysfunction, for example, owing to mutations in the follicle-stimulating hormone receptor or steroidogenic cell autoimmunity. Moreover, advances in cancer therapeutics over the past decades have led to increasing survival rates for both paediatric and adult malignancies. Given the gonadotoxic effect of many cancer treatments, more women develop POI. A marker that predicts whether women are at risk of POI would, therefore, aid in early diagnosis and fertility counselling. Anti-Müllerian hormone (AMH), a growth factor produced solely by small, growing follicles in the ovary, might constitute such a marker, as serum levels of this hormone correlate strongly with the number of growing follicles. In addition, AMH could potentially help assess the progression of ovarian senescence, as serum AMH levels are independent of hypothalamic-pituitary-gonadal axis function and decrease to undetectable levels at menopause. In cancer survivors, serum AMH levels correlate with the extent of gonadal damage. In this Review, we provide an overview of the current studies that have measured AMH in women with POI of various aetiologies and discuss its possible application as a marker to determine ovarian reserve.

  2. Cardiovascular Disease and Primary Ovarian Insufficiency

    PubMed Central

    Wellons, Melissa

    2012-01-01

    Cardiovascular disease (CVD) is the number-one killer of women. Women with primary ovarian insufficiency (POI) may be more burdened by cardiovascular disease, such as myocardial infarction and stroke, as compared with women with normal menopause. The increased burden may be mediated by a worsening of cardiovascular risk factors, such as lipids, corresponding with the loss of ovarian function. In contrast, the increased burden may be caused by factors that precede and potentially contribute to both CVD events and ovarian decline, such as X-chromosome abnormalities and smoking. Regardless of the cause, women with POI may serve as an important population to target for CVD screening and prevention strategies. These strategies should include the use of CVD risk stratification tools to identify women that may benefit from lifestyle modification and pharmacological therapy to prevent CVD. Sex steroid therapy for the sole purpose of CVD prevention in women with POI cannot be recommended, based on a lack of evidence. PMID:21969267

  3. Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours.

    PubMed

    Szala, Agnieszka; Sawicki, Sambor; Swierzko, Anna St; Szemraj, Janusz; Sniadecki, Marcin; Michalski, Mateusz; Kaluzynski, Andrzej; Lukasiewicz, Jolanta; Maciejewska, Anna; Wydra, Dariusz; Kilpatrick, David C; Matsushita, Misao; Cedzynski, Maciej

    2013-08-01

    Ficolins are serum pattern recognition molecules. They have opsonic properties and are able to activate complement via the lectin pathway. This paper reports investigations concerning ficolin-2 and ficolin-3 in ovarian cancer (OC). Their serum levels, single nucleotide polymorphisms of the corresponding FCN2 and FCN3 genes and specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary OC and 197 controls operated on for reasons other than malignancies. The latter consisted of two reference groups: those with benign tumours (n = 123) and those with normal ovaries (NO) (n = 74). Serum ficolin-2 and ficolin-3 concentrations were higher among patients with malignant disease when compared with either of the reference groups. A significant correlation between ficolin-2 and ficolin-3 concentrations was found, while no correlations with CA125 antigen or CRP were observed. No differences in the frequency of single nucleotide polymorphisms at sites -64, -4 (promoter), +6359, or +6424 (exon 8) (FCN2 gene) nor in the frame-shift mutation 1637delC (FCN3 gene) were found between investigated groups. In contrast to serum concentrations, the expression of FCN2 gene (reported for the first time in ovarian sections) was significantly lower in women with OC in comparison with patients with NO but not with benign ovarian tumours. In case of FCN3 gene, its expression levels in OC group inversely correlated with serum ficolin-3 and were lower in comparison with controls.

  4. Pegylated Liposomal Doxorubicin Hydrochloride, Carboplatin, Veliparib, and Bevacizumab in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-09-26

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

  5. Functional Expression of TWEAK and the Receptor Fn14 in Human Malignant Ovarian Tumors: Possible Implication for Ovarian Tumor Intervention

    PubMed Central

    Zhu, Jing; Ding, Chuanwei; Xu, Hai-bo; Qiu, Lihua; Di, Wen

    2013-01-01

    The aim of this current study was to investigate the expression of the tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) in human malignant ovarian tumors, and test TWEAK’s potential role on tumor progression in cell models in-vitro. Using immunohistochemistry (IHC), we found that TWEAK and its receptor Fn14 were expressed in human malignant ovarian tumors, but not in normal ovarian tissues or in borderline/benign epithelial ovarian tumors. High levels of TWEAK expression was detected in the majority of malignant tumors (36 out of 41, 87.80%). Similarly, 35 out of 41 (85.37%) malignant ovarian tumors were Fn14 positive. In these malignant ovarian tumors, however, TWEAK/Fn14 expression was not corrected with patients’ clinical subtype/stages or pathological features. In vitro, we demonstrated that TWEAK only inhibited ovarian cancer HO-8910PM cell proliferation in combination with tumor necrosis factor-α (TNF-α), whereas either TWEAK or TNF-α alone didn’t affect HO-8910PM cell growth. TWEAK promoted TNF-α production in cultured THP-1 macrophages. Meanwhile, conditioned media from TWEAK-activated macrophages inhibited cultured HO-8910PM cell proliferation and invasion. Further, TWEAK increased monocyte chemoattractant protein-1 (MCP-1) production in cultured HO-8910PM cells to possibly recruit macrophages. Our results suggest that TWEAK/Fn14, by activating macrophages, could be ovarian tumor suppressors. The unique expression of TWEAK/Fn14 in malignant tumors indicates that it might be detected as a malignant ovarian tumor marker. PMID:23469193

  6. A pathology study of malignant and benign ovarian tumors among atomic-bomb survivors--case series report.

    PubMed

    Inai, Kouki; Shimizu, Yukiko; Kawai, Kioko; Tokunaga, Masayoshi; Soda, Midori; Mabuchi, Kiyohiko; Land, Charles E; Tokuoka, Shoji

    2006-03-01

    The present article describes the series of incident primary ovarian tumors in the Life Span Study (LSS) cohort of the Radiation Effects Research Foundation, with particular emphasis on case ascertainment and characterization of histological features of the tumors. We identified 723 ovarian tumors (260 malignant, 463 benign) in 648 individuals of about 70,000 female LSS subjects; 71 cases had more than one ovarian tumor. We histologically confirmed 601 tumors (182 malignant, 419 benign tumors). The most frequent histological type was common epithelial tumor (90.7% for malignant and 59.7% for benign tumors). The distributions of ovarian tumors by histological type were similar to those from other studies. Among malignancies, the frequency of common epithelial types relative to other tumor types increased with radiation dose (p = 0.02). Among benign tumors, the relative frequency of sex-cord stromal tumors increased with radiation dose (p = 0.04). The women with mucinous cancer had better survival than those with serous cancers (p = 0.03). Within tumor types, there was no consistent pattern of survival by radiation dose. Variations in histological types of ovarian tumors in response to radiation dose, suggested by the case series data need to be followed up by population-based incidence analysis.

  7. Primary aldosteronism and malignant adrenocortical neoplasia.

    PubMed Central

    Salassa, T. M.; Weeks, R. E.; Northcutt, R. C.; Carney, J. A.

    1975-01-01

    Our experience indicates that although adrenal carcinoma is not a common cause of primary aldosteronism, 4 to 5% of patients in a single large series may have a malignant adrenocortical tumor. The magnitude of the hypokalemia and the hyperaldosteronuria tends to be greater in patients with malignant tumors, but these patients cannot be clearly separated from those with benign tumors or hyperplasia on this basis. Patients who have malignant tumors may have no chemical evidence of adrenocortical dysfunction other than excessive aldosterone secretion. Finally, a good response to spironolactone for months does not exclude adrenal carcinoma as the cause of primary aldosteronism. Images Fig. 1 PMID:1179589

  8. Response to microtubule-interacting agents in primary epithelial ovarian cancer cells

    PubMed Central

    2013-01-01

    Background Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. Methods Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated. Results All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients. Conclusions The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients’ specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings. PMID:23574945

  9. Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels

    PubMed Central

    Lanitis, Evripidis; Dangaj, Denarda; Hagemann, Ian S.; Song, De-Gang; Best, Andrew; Sandaltzopoulos, Raphael; Coukos, George; Powell, Daniel J.

    2012-01-01

    The breadth of HER2 expression by primary human ovarian cancers remains controversial, which questions its suitability as a universal antigen in this malignancy. To address these issues, we performed extensive HER2 expression analysis on a wide panel of primary tumors as well as established and short-term human ovarian cancer cell lines. Conventional immunohistochemical (IHC) analysis of multiple tumor sites in 50 cases of high-grade ovarian serous carcinomas revealed HER2 overexpression in 29% of evaluated sites. However, more sensitive detection methods including flow cytometry, western blot analysis and q-PCR revealed HER2 expression in all fresh tumor cells derived from primary ascites or solid tumors as well as all established and short-term cultured cancer cell lines. Cancer cells generally expressed HER2 at higher levels than that found in normal ovarian surface epithelial (OSE) cells. Accordingly, genetically-engineered human T cells expressing an HER2-specific chimeric antigen receptor (CAR) recognized and reacted against all established or primary ovarian cancer cells tested with minimal or no reactivity against normal OSE cells. In conclusion, all human ovarian cancers express immunologically-detectable levels of HER2, indicating that IHC measurement underestimates the true frequency of HER2-expressing ovarian cancers and may limit patient access to otherwise clinically meaningful HER2-targeted therapies. PMID:23189165

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

    ClinicalTrials.gov

    2015-05-01

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

  11. Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2014-05-06

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

  12. Ovarian, Fallopian Tube, and Primary Peritoneal Cancer—Patient Version

    Cancer.gov

    Information about ovarian, fallopian tube, and primary peritoneal cancer treatment, prevention, genetics, causes, screening, clinical trials, research and statistics from the National Cancer Institute.

  13. Blood clotting activation analysis for preoperative differentiation of benign versus malignant ovarian masses.

    PubMed

    Amirkhosravi, Ali; Bigsby, Glenn; Desai, Hina; Rivera-Amaya, Mildred; Coll, Enriqueta; Robles-Carrillo, Liza; Faust, Patricia; Waters, Alane; Meyer, Todd; Reyes, Enriquo; Langer, Florian; Francis, John L

    2013-07-01

    Preoperative evaluation of patients presenting with ovarian masses is challenging, partly due to shortcomings with the commonly used marker, CA-125. Ovarian cancer is associated with systemic coagulation activation. Measurement of D-dimer, serum tissue factor (TF), and the coagulation process as a whole are considered candidates for improving discrimination between benign and malignant ovarian masses. We therefore sought to identify possible benefits by analyzing preoperative coagulation status in conjunction with CA-125 in patients with ovarian masses. Preoperative blood from 95 patients with ovarian masses (75 benign, 20 malignant) and 30 controls was analyzed, prospectively. Thromboelastography served for global hemostatic assessment. Plasma TF antigen and D-dimer were measured by ELISA and microparticle-associated TF activity by thrombin generation assay. TF microparticles were enumerated by flow cytometry. Time to clot formation by thromboelastography was similar between patients having either benign or malignant ovarian tumors. Clot formation rate, clot strength, and coagulation index were significantly increased in patients having malignant versus benign tumors, indicating that thromboelastography differentiated malignant from benign tumors. D-dimer alone differentiated malignant from benign ovarian tumors and also improved differentiation when combined with CA-125. Circulating TF antigen, activity, and TF microparticle numbers, however, failed to differentiate benign from malignant tumors. Significant coagulation activation occurs in women with ovarian malignancies. Plasma D-dimer may help discriminate between patients with benign and malignant tumors. Thromboelastography may also contribute meaningfully when combined with CA-125 in the preoperative evaluation of ovarian masses. Larger studies are needed to assess these possibilities.

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

    ClinicalTrials.gov

    2016-09-02

    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

  15. Primary malignancy, secondary malignancy and semimalignancy of bone tumors.

    PubMed

    Uehlinger, E

    1976-01-01

    1. Bone tumors in contrast to tumors in soft tissue, show a wide variety of clinical behavior qualified by the expressions semimalignancy, low grade of malignancy, sarcomatous degeneration and primarily benign bone tumors and bone lesions. 2. The term semimalignancy is characterized by local invasive and destructive tumor growth with a tendency to recur locally but no hematogeneous spreading. Semimalignancy requires wide en-bloc resection of amputation. 3. The term low grade malignancy is used to describe a tumor of very slow growth and with very late metastasis. Low-grade malignancy requires resection with careful preservation of functional structures. 4. The term secondary malignancy means the sarcomatous degeneration of a primarily benign lesion or bone tumor. This transformation is enhanced by irradiation and probably by acceleration of the normal turnover of bone tissue. In Paget's disease sarcomatous degeneration is to be expected in 2 percent of cases and in fibrous dysplasia in 0.5 percent of cases. 5. Sarcomatous degeneration of bone infarcts is rare, but an increase is to be expected due to an increased frequency of bone infarcts caused by long-term treatment with cortisone. 6. Primary bone tumors and recurrences show the same structure and cytology. In a minority of cases the recurrences are less differentiated; in a very few cases the recurrences are more highly differentiated and have a better prognosis than the initial lesion. PMID:1070716

  16. Prior appendectomy does not protect against subsequent development of malignant or borderline mucinous ovarian neoplasms

    PubMed Central

    Elias, Kevin M.; Labidi-Galy, S. Intidhar; Vitonis, Allison F.; Hornick, Jason L.; Doyle, Leona A.; Hirsch, Michelle S.; Cramer, Daniel W.; Drapkin, Ronny

    2014-01-01

    Background Due to concern that mucinous malignant or borderline ovarian neoplasms (MON) may represent metastatic deposits from appendiceal primaries, gynecologic oncologists routinely perform appendectomy in these cases. However, a multidisciplinary critique of this practice is lacking. Methods The New England Case-Control study database was utilized to compare the effect of prior appendectomy against known risk factors for MON. Pathology and operative reports of local cases of MON were reviewed to estimate the frequency of microscopic mucinous lesions in the appendix. Protein expression patterns among mucinous ovarian, colorectal, and appendiceal cancers were compared by immunohistochemistry. Results From the New England Case-Control study, 287 cases of MON were compared against 2,339 age-matched controls. Prior appendectomy did not reduce the risk of MON (OR 1.28, 95% CI 0.83–1.92, p=0.23), while prior tubal ligation, parity, and breastfeeding were each protective against MON. Active smoking (OR 2.04, 95% CI 1.48–2.80, p<0.001) was associated with an increased risk of MON. Among 196 mucinous adnexal tumors, appendectomy did not reclassify any MON as appendiceal in origin. By immunohistochemistry, mucinous ovarian carcinomas tended to be CK7+/CK20-/MUC2-/CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were typically CK7-/CK20+/MUC2+/CDX2+, although with some overlap in immunophenotype. Additionally, PAX8 was positive in a subset of MOC and negative in all appendiceal carcinomas. Conclusion Prior appendectomy is not protective against development of malignant or borderline MON. Routine appendectomy during surgery for MON seldom reveals an unsuspected GI primary in early stage tumors but may aid in final diagnosis in advanced stage cases. PMID:24342438

  17. [Primary malignant melanoma of the vagina].

    PubMed

    Lomeo, A M; Iacobellis, G; Martoccia, G; Manzione, L; De Sanctis, D; Maglietta, R; Vita, G

    1993-03-01

    We report two cases of primary malignant melanoma of the vagina explaining the essential clinical pathological and therapeutic features. They themselves, added those represented in literature, might constitute a further contribution to best definition of the unusual genital pathology, especially as regards prognostic and therapeutic aspects.

  18. Validity of Cancer Antigen-125 (CA-125) and Risk of Malignancy Index (RMI) in the Diagnosis of Ovarian Cancer

    PubMed Central

    Al-Musalhi, Khawla; Al-Kindi, Manal; Ramadhan, Fatma; Al-Rawahi, Thuraya; Al-Hatali, Khalsa; Mula-Abed, Waad-Allah

    2015-01-01

    Objective We sought to determine the validity of cancer antigen 125 (CA-125) and the risk of malignancy index (RMI) in the diagnosis of ovarian cancer in women presenting with adnexal lesions of various histopathology types. Methods This retrospective cross- sectional study included all women with adnexal lesions who were evaluated at the Royal Hospital, Oman, between January 2012 and December 2014. The inclusion criteria included women who underwent surgical intervention and who had preoperative CA-125 testing and pelvic ultrasound in the work-up plan of their management. The surgical intervention was usually followed by a histopathological diagnosis of the nature of the lesion, which was used as the gold standard for the evaluation of both CA-125 and RMI. Results The cohort included 361 women who had serum CA-125 and pelvic ultrasound prior to the surgical intervention of the adnexal lesion. Of these women, 61 (17%) had malignant ovarian lesions. Using the proposed cut-off 35 U/ml for CA-125 and 200 for RMI, the CA-125 test was more sensitive for detecting the majority of malignant ovarian tumors compared to the RMI (69% vs. 57%). Both tests were more sensitive in detecting epithelial ovarian cancer compared to other ovarian cancers. However, RMI was more specific in excluding benign ovarian lesions compared to CA-125 (81% vs. 68%). Additionally, RMI had a better area under the curve compared to CA-125 (0.771 vs. 0.745; p<0.005). Lowering the RMI cut-off to 150 resulted in a better sensitivity (62% vs. 57%) and had an acceptable specificity (78% vs. 81%) compared to a cut-off of 200. Conclusion Both CA-125 and RMI have good validity in the diagnosis of ovarian tumors. CA-125 has higher sensitivity; however, RMI has higher specificity. In combination, CA-125 might be more valid for the diagnosis of malignant ovarian cancer while RMI is more valid for excluding the diagnosis of these tumors. Differential use of these two tools will improve the triage of women with

  19. Malignant mixed müllerian tumor of primary peritoneal origin☆

    PubMed Central

    Kanis, Margaux; Kesterson, Joshua P.; Shroff, Stuti; Lele, Shashikant; Mhawech-Fauceglia, Paulette

    2016-01-01

    The aim of this study was to describe 2 cases of primary peritoneal malignant mixed müllerian tumor (MMMT). Two patients with primary peritoneal MMMT were examined for their clinical and pathologic features. We describe 2 cases of primary peritoneal MMMT in which the carcinomatous and mesenchymal components were readily identifiable, predominantly involving the peritoneum, with no ovarian involvement. The peritoneum and ovaries, with their common embryologic origin, likely account for the peritoneum’s ability to undergo a similar malignant transformation, with the resultant genesis of an MMMT of peritoneal origin. PMID:20952288

  20. Analysis of falsely elevated risk of ovarian malignancy algorithm in women with ovarian endometrioma

    PubMed Central

    Shin, Jae Jun; Lee, Ye Ji; Kim, Ranah; Lee, Da Yong; Won, Kyu-Hee

    2016-01-01

    Objective To estimate the incidence of falsely elevated risk of ovarian malignancy algorithm (ROMA) in a group of women with pathologically confirmed endometrioma and to investigate the associated factors. Methods One hundred premenopausal women surgically diagnosed with ovarian endometrioma were selected. Preoperative clinical, laboratory, and surgical characteristics were compared between the elevated-risk group (ROMA-premenopausal value, ≥7.4%) and normal-risk group (ROMA-premenopausal value, <7.4%). Results Elevated ROMA was observed in 15 women (false positive rate, 15%). Excluding one woman with known chronic renal failure, we compared the characteristics of 99 women between the elevated-risk group (n=14) and the normalrisk group (n=85). None of the clinical and surgical variables distinguished the two groups. Serum level of CA 125 >82.3 U/mL and serum level of human epididymis protein 4 (HE4) >46 pmol/L could predict an elevated ROMA test with a statistical significance. When serum level of HE4 ≤46 pmol/L, none of the women showed an elevated ROMA test, regardless of serum level of CA 125; however, 55.6% of the women showed an elevated ROMA test when serum level of HE4 >46 pmol/L and CA 125 ≤82.3 U/mL and all women showed an elevated ROMA test when serum level of HE4 >46 pmol/L and CA 125 >82.3 U/mL. Conclusion The incidence of falsely elevated ROMA was 15% in the group of women with pathologically confirmed endometrioma. Interpretation of the ROMA results should be cautious when serum level of HE4 >46 pmol/L and CA 125 >82.3 U/mL in women with suspicious ovarian endometrioma. PMID:27462596

  1. Nonbreast Second Malignancies After Treatment of Primary Breast Cancer

    SciTech Connect

    Yadav, Budhi S. Sharma, Suresh C.; Patel, Firuza D.; Ghoshal, Sushmita; Kapoor, Rakesh; Kumar, Rajinder

    2009-04-01

    Purpose: To determine the incidence and risk factors for nonbreast second malignancies (NBSMs) in women after treatment for primary breast cancer. Methods and Materials: Between January 1985 and December 1995, a total of 1,084 breast cancer patients were analyzed for NBSMs. Detailed analysis was carried out for age, family history, disease stage, radiation therapy, chemotherapy, hormone therapy, other clinical/pathologic characteristics, and site of NBSMs. The Cox proportional hazard regression model was used to estimate the relative risk of NBSMs. Results: Median follow-up was 12 years. In total, 33 cases of NBSMs were noted in 29 patients. The overall incidence of NBSM was 3%, and the median time for NBSMs was 7 years. The most common NBSMs were gynecologic (22 patients), gastrointestinal (4 patients), head and neck (3 patients), hematologic (2 patients), lung (1 patient), and thyroid (1 patient). The NBSMs rate at 12 years was 2.4% for both mastectomy and radiation therapy groups. In the subset of patients less than 45 years of age at the time of treatment, the NBSMs rate was 0.7% as compared with 4.6% in patients more than 45 years of age (p = 0.001). Statistically significant higher incidences of endometrial and ovarian cancer were seen in patients with hormonal therapy (5.2%) as compared with patients without hormonal therapy (1.8%, p = 0.002). Women with a family history of breast cancer had a higher incidence (6%) of endometrial and ovarian malignancy compared with women without such a history (2.1%, p = 0.003). Chemotherapy did not affect the risk of second malignancy. Conclusion: The most common NBSMs in this study were gynecologic. Family history of breast cancer was a high risk factor for NBSMs. No risk of NBSMs with radiotherapy was observed.

  2. Protein levels and gene expressions of the epidermal growth factor receptors, HER1, HER2, HER3 and HER4 in benign and malignant ovarian tumors.

    PubMed

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Andersen, Rikke Fredslund; Olsen, Dorte Aalund; Jeppesen, Ulla; Knudsen, Hans Jørgen; Brandslund, Ivan; Jakobsen, Anders

    2008-07-01

    The epidermal growth factor receptors, HER1, HER2, HER3 and HER4 play a key role in the growth of malignant tumors. The receptors of the EGF receptor family are not cancer-specific proteins since these receptors are expressed to some extent in both normal and benign tissue, but this is not elucidated in detail in ovarian tissue. High tumor-to-normal-tissue concentration ratios would be favorable for molecular targeted anti-cancer treatment. The primary aim of the study was to analyze the potential differential protein content and gene expression of the four receptors in benign and malignant ovarian tumors. Tissue from 207 patients (101 malignant, 19 borderline, 64 benign ovarian tumors and 23 normal ovaries) were analyzed by quantitative ELISA for HER1-HER4 protein concentrations and by real-time PCR for HER1-HER4 gene expression. HER2 was also analyzed by immunohistochemistry. The HER2-4 receptor protein content and the median gene expression level was significantly higher in ovarian cancer patients compared to patients with benign ovarian tumors and normal ovaries (p<0.0000001). The protein content of the HER1 receptor was significantly lower in ovarian cancer compared to borderline tumors (p=0.012), benign ovarian tumors (p=0.049) and to normal ovaries (p=0.000069). A sound correlation between the protein levels and gene expressions was documented. In conclusion, decreased concentration of HER1 protein and increased HER2, HER3 and HER4 protein concentration were observed, as also elevated HER2-HER4 gene expression levels in ovarian cancer patients with barely any overlap of the HER3 and HER4 expression in malignant ovarian tumors compared to benign ovarian tissues.

  3. Olaparib and Cediranib Maleate in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-08-24

    BRCA1 Gene Mutation; BRCA2 Gene Mutation; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

  4. Hemodynamic Consequences of Malignant Ascites in Epithelial Ovarian Cancer Surgery∗

    PubMed Central

    Hunsicker, Oliver; Fotopoulou, Christina; Pietzner, Klaus; Koch, Mandy; Krannich, Alexander; Sehouli, Jalid; Spies, Claudia; Feldheiser, Aarne

    2015-01-01

    Abstract Malignant ascites (MA) is most commonly observed in patients scheduled for epithelial ovarian cancer (EOC) surgery and is supposed as a major risk factor promoting perioperative hemodynamic deterioration. We aimed to assess the hemodynamic consequences of MA on systemic circulation in patients undergoing cytoreductive EOC surgery. This study is a predefined post-hoc analysis of a randomized controlled pilot trial comparing intravenous solutions within a goal-directed algorithm to optimize hemodynamic therapy in patients undergoing cytoreductive EOC surgery. Ascites was used to stratify the EOC patients prior to randomization in the main study. We analyzed 2 groups according to the amount of ascites (NLAS: none or low ascites [<500 mL] vs HAS: high ascites group [>500 mL]). Differences in hemodynamic variables with respect to time were analyzed using nonparametric analysis for longitudinal data and multivariate generalized estimating equation adjusting the analysis for the randomized study groups of the main study. A total of 31 patients in the NLAS and 16 patients in the HAS group were analyzed. Although cardiac output was not different between groups suggesting a similar circulatory blood flow, the HAS group revealed higher heart rates and lower stroke volumes during surgery. There were no differences in pressure-based hemodynamic variables. In the HAS group, fluid demands, reflected by the time to reindication of a fluid challenge after preload optimization, increased steadily, whereas stroke volume could not be maintained at baseline resulting in hemodynamic instability after 1.5 h of surgery. In contrast, in the NLAS group fluid demands were stable and stroke volume could be maintained during surgery. Clinically relevant associations of the type of fluid replacement with hemodynamic consequences were particularly observed in the HAS group, in which transfusion of fresh frozen plasma (FFP) was associated to an improved circulatory flow and reduced

  5. A novel biomarker ARMc8 promotes the malignant progression of ovarian cancer.

    PubMed

    Jiang, Guiyang; Yang, Dalei; Wang, Liang; Zhang, Xiupeng; Xu, Hongtao; Miao, Yuan; Wang, Enhua; Zhang, Yong

    2015-10-01

    Ovarian cancer is the most lethal gynecologic malignancy worldwide, and the survival rates have remained low in spite of medical advancements. More research is dedicated to the identification of novel biomarkers for this deadly disease. The association between ARMc8 and ovarian cancer remained unraveled. In this study, immunohistochemical staining was used to examine ARMc8 expression in 247 cases of ovarian cancer, 19 cases of borderline ovarian tumors, 41 cases of benign ovarian tumors, and 9 cases of normal ovarian tissues. It was shown that ARMc8 was predominantly located in the cytoplasm of tumor cells, and its expression was up-regulated in the ovarian cancer (61.9%) and the borderline ovarian tumor tissues (57.9%), in comparison with the benign ovarian tumors (12.2%; P < .05) and the normal ovarian tissues (11.1%; P < .05). In ovarian cancer, ARMc8 expression was closely related to International Federation of Gynecology and Obstetrics stages (P = .002), histology grade (P < .001), lymph node metastasis (P = .008), and poor prognosis (P < .001). Univariate and multivariate Cox analyses revealed that ARMc8 expression was an independent prognostic factor for ovarian cancer (P = .039 and P = .005). In addition, ARMc8 could promote the invasion and migration of ovarian cancer cells. Overexpressing ARMc8 enhanced the invasion and metastasis capacity of ARMc8-low Cavo-3 cells (P < .001), whereas interfering ARMc8 significantly reduced cell invasion and metastasis in ARMc8-high SK-OV-3 cells (P < .001). Furthermore, ARMc8 could up-regulate matrix metalloproteinase-7 and snail and down-regulate α-catenin, p120ctn, and E-cadherin. Collectively, ARMc8 may enhance the invasion and metastasis of ovarian cancer cells and likely to become a potential therapeutic target for ovarian cancer. PMID:26232863

  6. Primary Malignant Melanoma in the Pineal Region

    PubMed Central

    Hong, Yong-Kil

    2014-01-01

    A 59-year-old male patient had 5-month history of gait disturbance and memory impairment. His initial brain computed tomography scan showed 3.5×2.8 cm sized mass with high density in the pineal region. The tumor was hypointense on T2 weighted magnetic resonance images and hyperintense on T1 weighted magnetic resonance images with heterogenous enhancement of central portion. The tumor was totally removed via the occipital transtentorial approach. Black mass was observed in the operation field, and after surgery, histopathological examination confirmed the diagnosis of malignant melanoma. Whole spine magnetic resonance images and whole body 18-fluoro-deoxyglucose positron emission tomography could not demonstrate the primary site of this melanoma. Scrupulous physical examination of his skin and mucosa was done and dark pigmented lesion on his left leg was found, but additional studies including magnetic resonance images and skin biopsy showed negative finding. As a result, final diagnosis of primary pineal malignant melanoma was made. He underwent treatment with the whole brain radiotherapy and extended local boost irradiation without chemotherapy. His preoperative symptoms were disappeared, and no other specific neurological deficits were founded. His follow-up image studies showed no recurrence or distant metastasis until 26 weeks after surgery. Primary pineal malignant melanomas are extremely rare intracranial tumors, and only 17 cases have been reported since 1899. The most recent case report showed favorable outcome by subtotal tumor resection followed by whole brain and extended local irradiation without chemotherapy. Our case is another result to prove that total tumor resection with radiotherapy can be the current optimal treatment for primary malignant melanoma in the pineal region. PMID:25628812

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

    ClinicalTrials.gov

    2014-06-18

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

  8. Synchronous primary malignancies of the appendix and ovary causing carcinomatosis in one patient.

    PubMed

    Redondo, Raquel Elisa; Giannotti, Giovanni; Thomas, Korathu; Ruiz, Ofelia S

    2015-01-01

    Associated tumors of the ovary and the appendix are commonly found in cases of pseudomyxoma peritonei (PP); the origin of these tumors are a continually debated topic. Outside of the setting of PP, this finding is exceedingly rare and there are no documented reports of two primary processes causing carcinomatosis in the absence of PP. Here, we present a patient who underwent cytoreductive surgery for peritoneal carcinomatosis presumptively secondary to ovarian carcinoma and who on pathological examination was found to have synchronous primary malignant processes of both the appendix and the ovary. This represents the first documented case of carcinomatosis resulting from two separate malignant processes in the absence of PP. PMID:25832462

  9. Synchronous primary malignancies of the appendix and ovary causing carcinomatosis in one patient

    PubMed Central

    Redondo, Raquel Elisa; Giannotti, Giovanni; Thomas, Korathu; Ruiz, Ofelia S.

    2015-01-01

    Associated tumors of the ovary and the appendix are commonly found in cases of pseudomyxoma peritonei (PP); the origin of these tumors are a continually debated topic. Outside of the setting of PP, this finding is exceedingly rare and there are no documented reports of two primary processes causing carcinomatosis in the absence of PP. Here, we present a patient who underwent cytoreductive surgery for peritoneal carcinomatosis presumptively secondary to ovarian carcinoma and who on pathological examination was found to have synchronous primary malignant processes of both the appendix and the ovary. This represents the first documented case of carcinomatosis resulting from two separate malignant processes in the absence of PP. PMID:25832462

  10. Osteoprotegerin (OPG) protects ovarian cancer cells from TRAIL-induced apoptosis but does not contribute to malignant ascites-mediated attenuation of TRAIL-induced apoptosis

    PubMed Central

    2012-01-01

    Background Resistance to apoptosis is a major problem in ovarian cancer and correlates with poor prognosis. Osteoprotegerin (OPG) is a secreted factor in malignant ascites and acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). TRAIL promotes apoptosis in ovarian cancer cells. Ovarian cancer ascites attenuate TRAIL-induced apoptosis raising the possibility that OPG contained in ascites may abrogate the anti-tumor activity of TRAIL. Methods Determination of OPG levels in ascites was measured by ELISA. Effect of OPG on TRAIL-induced cell death was determined by XTT and colony forming assays in ovarian cancer cell lines and primary tumor cells. Apoptosis was assessed by ELISA. Results We found that recombinant OPG and malignant ascites attenuates TRAIL-induced cell death and apoptosis in a dose-dependent manner in ovarian cancer cell lines and primary ovarian tumor cells. OPG is present at high levels in the ascites of patients with ovarian cancer. We found a positive correlation between the levels of OPG in ascites and the ability of the ascites to attenuate TRAIL-induced cell death. The anti-apoptotic effect of ascites was not reversed by co-incubation with an OPG blocking antibody. Conclusions OPG and malignant ascites protect ovarian cancer cells from TRAIL-induced apoptosis. Although malignant ascites contain high levels of OPG, OPG is not a critical component that contributes to ascites-mediated attenuation of TRAIL-induced apoptosis. PMID:23153223

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

    MedlinePlus

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

  12. Cytochrome P450 CYP1B1 over-expression in primary and metastatic ovarian cancer

    PubMed Central

    McFadyen, M C E; Cruickshank, M E; Miller, I D; McLeod, H L; Melvin, W T; Haites, N E; Parkin, D; Murray, G I

    2001-01-01

    Ovarian cancer is the most frequent cause of death from gynaecological malignancies world wide. Little improvement has been made in the long-term outcome of this disease, with the 5-year survival of patients only 30%. This poor prognosis is due to the late presentation of the disease and to the unpredictable response of ovarian cancer to chemotherapy. The cytochrome P450 enzymes are a superfamily of haemoproteins, known to be involved in the metabolic activation and/or detoxification of a number of anti-cancer drugs. CYP1B1 is a tumour-related form of cytochrome P450 which is over expressed in a wide variety of primary tumours of different histological type. The presence of CYP1B1 may be of importance in the modulation of these tumours to anti-cancer drugs. We have conducted a comprehensive immunohistochemical investigation, into the presence of cytochrome P450 CYP1B1 in primary and metastatic ovarian cancer. The key findings of this study are the increased expression of CYP1B1 in the majority of ovarian cancers investigated (92%), with a strong correlation demonstrated between CYP1B1 expression in both primary and metastatic ovarian cancer (P= 0.005 Spearman's rank correlation test). In contrast no detectable CYP1B1 was found in normal ovary. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11461084

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

    ClinicalTrials.gov

    2015-01-15

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

  14. Primary malignant lymphomas of the salivary glands.

    PubMed

    Nime, F A; Cooper, H S; Eggleston, J C

    1976-02-01

    Primary malignant lymphomas of the salivary glands are rare, and only 43 possible cases have been reported. Four new cases from the Johns Hopkins Hospital are described, including clinical presentation, histologic findings, and subsequent course. The literature on this subject is reviewed, including cases arising in preexisting benign lymphoepithelial lesion with or without Sjögren's syndrome. Although the number of reported cases with complete documentation and follow-up information is too small for significant statistical analysis, these patients appear to have a better prognosis than the usual lymphoma patient. The possible reasons for this are discussed.

  15. DNA Cytometry and Nuclear Morphometry in Ovarian Benign, Borderline and Malignant Tumors

    PubMed Central

    el Din, Amina A. Gamal; Badawi, Manal A.; Aal, Shereen E. Abdel; Ibrahim, Nihad A.; Morsy, Fatma A.; Shaffie, Nermeen M.

    2015-01-01

    BACKDROUND: Ovarian carcinoma is a leading cause of death in gynecological malignancy. Ovarian surface epithelial serous and mucinous tumours are classified as benign, borderline, and malignant. The identification of borderline tumours most likely to act aggressively remains an important clinical issue. AIM: This work aimed to study DNA ploidy and nuclear area in ovarian serous and mucinous; benign, borderline and malignant tumours. MATERIAL AND METHODS: This study included forty ovarian (23 serous and 17 mucinous) tumours. Paraffin blocks were sectioned; stained with haematoxylin and eosin for histopathologic and morphometric studies and with blue feulgen for DNA analysis. RESULTS: All four serous and six out of nine mucinous benign tumours were diploid. All eight serous and five mucinous malignant tumours were aneuploid. Nine of eleven (81.8%) serous and all three mucinous borderline tumours were aneuploid. There were highly significant differences in mean aneuploid cells percentage between serous benign (1.5%), borderline (45.6%) and malignant (74.5%) (p = 0.0001) and between mucinous benign (13.2%) and both borderline (63.7%) and malignant (68.4%) groups (p = 0.0001). There were significant differences in nuclear area between serous benign (26.191%), borderline (45.619%) and malignant (67.634 %) and a significant positive correlation between mean percentage aneuploid value and mean nuclear area in all serous and mucinous groups. CONCLUSION: We suggest that DNA ploidy and nuclear area combined, may be adjuncts to histopathology; in ovarian serous and mucinous benign, borderline and malignant neoplasms; identifying the aggressive borderline tumours. PMID:27275284

  16. BRCA1 mutations in primary breast and ovarian carcinomas

    SciTech Connect

    Futreal, P.A.; Cochran, C.; Bennett, L.M.; Haugen-Strano, A.; Terry, L.; Barrett, J.C.; Wiseman, R.; Liu, Q.; Shattuck-Eidens, D.; Harshman, K.

    1994-10-07

    Loss of heterozygosity data from familial tumors suggested that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele.

  17. Primary malignant lymphomas of the breast.

    PubMed

    Mambo, N C; Burke, J S; Butler, J J

    1977-05-01

    Fourteen cases of primary malignant lymphomas of the breast were found in the pathology files of the M. D. Anderson Hospital and Tumor Institute from 1944 to 1975. The lymphomas represented only 0.12% of 11,277 primary malignant breast tumors seen during the same period. There were no definite clinical features to distinguish the patients with lymphoma from those with breast carcinoma. All of the lymphomas had a diffuse pattern. Eight cases were classified as undifferentiated lymphoma, five as histiocytic, and one as poorly differentiated lymphocytic, convoluted cell type. Four patients had mastectomies and the remainder biopsies as their sole surgical procedure. Eight patients received post-surgical radiotherapy and all eventually had chemotherapy. The five-year survival rate for the 13 patients with follow-up was 49%. Patients with histiocytic lymphoma appeared to have a more favorable prognosis than those with the undifferentiated type. Six of the latter patients are dead with a median survival of seven months, comparable to the reported survival of patients with American Burkitt's lymphoma. The patient with the convoluted cell type has developed acute blastic leukemia and is currently under therapy.

  18. Unexpected Malignant Diagnosis in Colonic Biopsies: Malignant Transformation of Ovarian Mature Teratomas—Two Case Reports and Review of the Literature

    PubMed Central

    Rojas, Claudia P.; Ganjei-Azar, Parvin; Garcia-Buitrago, Monica T.

    2015-01-01

    Colorectal adenocarcinoma is the second cause of cancer-related deaths in the United States. The occurrence of squamous cell carcinoma in the colorectum is extremely unusual. Malignant transformation from mature cystic teratoma of the ovary is a rare event. The most common transformation is squamous cell carcinoma, followed by adenocarcinoma. It occurs more often in elderly patients, who usually present with advance disease. We report two unusual cases of postmenopausal women diagnosed with squamous cell carcinoma in colon biopsies. After surgical resections, the carcinoma was proven to be the result of malignant transformation of ovarian mature cystic teratomas. Since squamous cell carcinoma of the colorectum is extremely rare, the presence of squamous cell carcinoma in a colonic biopsy in a female patient should alert the clinicians to other possible primary sites, as seen in these cases. PMID:26881165

  19. Epidemiologic and molecular characteristics of borderline and malignant epithelial ovarian tumors

    NASA Astrophysics Data System (ADS)

    Bastos, Eugenia Maria Chaves De Moraes

    Data from the Cancer and Steroid Hormone Study, a multicenter, population-based, case-control study were used to identify risk factors for epithelial ovarian cancer according to tumor behavior, histologic types, as well as p53 expression. Cases were women between 20 to 54 years old diagnosed with epithelial ovarian cancer from 1980 to 1982. Controls were women selected by random digit dialing. Tumor samples were analyzed for p53 overexpression using immunohistochemistry. Case-case and case-control conditional logistic regression models matched on age and diagnosing centers were used to calculate odds ratios (OR's) and 95% confidence intervals (CI's) for borderline, malignant, mucinous, and nonmucinous tumors, and p53 positive and p53 negative cases. The OR's for high number of lifetime ovulatory cycles (376-533 compared with less than 234) were 3.1 (95% CI 1.6-6.1) for malignant and 1.4 (95% CI 0.5-3.7) for borderline cases. The high number of ovulatory cycles was also a strong risk factor among nonmucinous cases. OR's for current and recent ex-smokers compared with never smokers were 2.8 (95% CI 1.7-4.8) for mucinous and 0.9 (95% CI 0.7-1.1) for nonmucinous types. Infertility showed a positive association with borderline ovarian cancer. Family history of ovarian or breast cancer was positively associated with malignant and nonmucinous cases. Parity had an inverse association with malignant ovarian cancer cases. When cases were subdivided by p53 results, the OR for tobacco smoking and p53 positive ovarian cancer was elevated for mucinous (OR = 3.9; 95% CI 0.8-18) at localized stage. Alcohol use showed a positive association with p53 positive malignant cases at advanced stage (OR = 2.0; 95% CI 1.2-3.2) and with p53 positive nonmucinous cases at advanced stage (OR = 2.1; 95% CI 1.2-3.4). A positive association between high number of ovulatory cycles and p53 positive malignant cases was observed in cases with localized stage (OR = 6.6; 95% CI 1.0-45) and advanced

  20. Induction of ovarian function by using short-term human menopausal gonadotrophin in patients with ovarian failure following cytotoxic chemotherapy for haematological malignancy.

    PubMed

    Chatterjee, R; Mills, W; Katz, M; McGarrigle, H H; Goldstone, A H

    1993-07-01

    Currently no treatment has proved successful in inducing ovarian steroidogenic and/or gametogenic recovery in patients with haematological malignancies treated by cytotoxic chemotherapy once biochemical failure becomes manifest i.e., when FSH levels exceed 40 IU/L. This paper reports two such cases with classical biochemical ovarian failure in which ovarian function was induced by brief stimulation with Human Menopausal Gonadotrophin (HMG). PMID:7693105

  1. Primary malignant melanoma of cervix and vagina.

    PubMed

    Lee, Jae Hoon; Yun, Jisun; Seo, Jung-Won; Bae, Go-Eun; Lee, Jeong-Won; Kim, Sang Wun

    2016-09-01

    Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains. PMID:27668208

  2. Primary malignant melanoma of cervix and vagina

    PubMed Central

    Lee, Jae Hoon; Yun, Jisun; Seo, Jung-Won; Bae, Go-Eun; Lee, Jeong-Won

    2016-01-01

    Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains. PMID:27668208

  3. Primary malignant melanoma of cervix and vagina

    PubMed Central

    Lee, Jae Hoon; Yun, Jisun; Seo, Jung-Won; Bae, Go-Eun; Lee, Jeong-Won

    2016-01-01

    Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains.

  4. The prognostic value of epidermal growth factor receptor mRNA expression in primary ovarian cancer.

    PubMed Central

    Bartlett, J. M.; Langdon, S. P.; Simpson, B. J.; Stewart, M.; Katsaros, D.; Sismondi, P.; Love, S.; Scott, W. N.; Williams, A. R.; Lessells, A. M.; Macleod, K. G.; Smyth, J. F.; Miller, W. R.

    1996-01-01

    The expression of mRNA for the epidermal growth factor (EGF) receptor, EGF and transforming growth factor alpha (TGF-alpha) was determined in 76 malignant, six borderline and 15 benign primary ovarian tumours using the reverse transcriptase-polymerase chain reaction and related to clinical and pathological parameters. Of the malignant tumours, 70% (53/76) expressed EGF receptor mRNA, 31% (23/75) expressed EGF mRNA and 35% (26/75) expressed TGF-alpha mRNA. For the borderline tumours, four of six (67%) expressed EGF receptor mRNA, 1/6 (17%) expressed TGF-alpha mRNA and none expressed EGF mRNA. Finally, 33% (5/15) of the benign tumours expressed EGF receptor mRNA, whereas 40% (6/15) expressed EGF mRNA and 7% (1/15) expressed TGF-alpha mRNA. The presence of the EGF receptor in malignant tumours was associated with that of TGF-alpha (P = 0.0015) but not with EGF (P = 1.00), whereas there was no relationship between the presence of EGF and TGF-alpha (P = 1.00). EGF receptor mRNA expression was significantly and positively associated with serous histology (P = 0.006) but not with stage or grade. Neither EGF nor TGF-alpha showed any link with histological subtype or stage. The survival of patients with malignant tumours possessing EGF receptor mRNA was significantly reduced compared with that of patients whose tumours were negative (P = 0.030 for all malignant tumours; P = 0.007 for malignant epithelial tumours only). In contrast, neither the expression of TGF-alpha nor EGF was related to survival. These data suggest that the presence of EGF receptor mRNA is associated with poor prognosis in primary ovarian cancer. Images Figure 1 PMID:8562334

  5. Isolation of alpha 1-protease inhibitor from human normal and malignant ovarian tissue.

    PubMed Central

    Bagdasarian, A; Wheeler, J; Stewart, G J; Ahmed, S S; Colman, R W

    1981-01-01

    Proteolytic enzymes are associated with normal and neoplastic tissues. Therefore protease inhibitors might also be involved in the control of cell function. alpha 1-protease antigen and antitryptic activity have been found in normal and neoplastic human ovarian homogenate. The inhibitor has been localized to ovarian stromal cells or tumor cells by immunoperoxidase staining. The protein was purified to apparent homogeneity as judged by alkaline gel and sodium dodecyl sulfate (SDS) gel electrophoresis. Immunochemical studies revealed antigenic similarity of plasma alpha 1-protease inhibitor by double immunodiffusion and similar mobility on immunoelectrophoresis and two-dimensional electroimmunodiffusion. The molecular weight was similar to that described for plasma alpha 1-protease inhibitor: 60,000 by gel filtration and 53,500 by SDS electrophoresis. Furthermore, the phenotypic pattern as determined by acid starch gel electrophoresis and immunoprecipitation was PiMM, which is the predominant genetic variant in normal plasma alpha 1-protease inhibitor. An inhibitor ws isolated and purified from an ovarian carcinoma that exhibited functional, immunochemical, and physical similarity to the normal ovarian alpha 1-protease inhibitor. alpha 1-protease inhibitor from normal and malignant ovaries competitively inhibited bovine pancreatic trypsin at incubation times of 5 min at 30 degrees C. Inhibition constant (Ki) values were calculated at 0.67 and 0.51 inhibitory units, respectively. The alpha 1-protease inhibitor in malignant cells may be a factor in the control of proliferation in this tissue. Since ovulation is in part a proteolytic event, the alpha 1-protease inhibitor in ovarian cells may play a role in the control of this specialized tissue. Persistance of this protein in malignant ovarian tissue may be a vestige of its differentiated origin. Images PMID:6161137

  6. Metastatic Malignant Ovarian Steroid Cell Tumor: A Case Report and Review of the Literature

    PubMed Central

    Lee, Jessica; John, Veena S.; Liang, Sharon X.; D'Agostino, Catherine A.; Menzin, Andrew W.

    2016-01-01

    We report a case of malignant ovarian steroid cell tumor not otherwise specified (NOS) in a 47-year-old female who presented with hirsutism, virilization, and amenorrhea. At the time of laparotomy, the tumor had already spread to the pelvic cul-de-sac. She underwent a total hysterectomy, bilateral salpingo-oophorectomy, and tumor resection with no residual disease. She received three cycles of bleomycin, etoposide, and cisplatin (BEP) and is now free of disease 24 months after surgery. Literature review of ovarian steroid cell tumors NOS including clinicopathological features and clinical management was performed. PMID:27375912

  7. Primary Spindle Cell Malignant Melanoma of Esophagus: An Unusual Finding.

    PubMed

    Rawandale, Nirmalkumar A; Suryawanshi, Kishor H

    2016-02-01

    Malignant melanoma of esophagus is usually a metastatic tumour rather than a primary tumour. Primary malignant melanoma accounts for less than 0.2% of all esophageal neoplasm. We report a case of primary spindle cell malignant melanoma of esophagus in a 69-year-old male who presented with history of dysphagia since 1 month. Radiological examinations revealed polypoidal growth at lateral aspect of esophagus. Biopsy was reported as grade III squamous cell carcinoma. Video assisted thoracoscopic esophagectomy was performed. Histopathological examination along with immunohistochemistry gave confirmed diagnosis of primary spindle cell malignant melanoma of esophagus. Though a rare entity, due to its aggressive nature and poor prognosis primary malignant melanoma should be one of the differential diagnoses in a patient with polypoidal esophageal mass lesion. Despite radical surgical treatment prognosis is extremely poor. PMID:27042502

  8. Intraperitoneal Bortezomib and Carboplatin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-06-21

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

  9. Metallothionein expression and nuclear size in benign, borderline, and malignant serous ovarian tumours.

    PubMed

    Tan, Y; Sinniah, R; Bay, B H; Singh, G

    1999-09-01

    Metallothioneins (MTs) are low-molecular-weight proteins involved in metalloregulatory functions such as cell proliferation, growth, and differentiation. In recent years, MT expression has been linked with carcinogenesis, resistance to cancer therapy, and tumour progression. However, the significance of MT expression in ovarian cancers is at present inadequately documented. In this study, MT immunohistochemistry was performed in 12 benign, 14 borderline, and eight malignant serous tumours of the ovary. The intensity of the immunostaining was evaluated by image analysis. There was a significantly higher number of MT-immunopositive cells in the multilayered epithelial cells of borderline serous tumours (atypical proliferative serous tumours) than in the single layered epithelial cells within the same tumour, and in the single cell layer of benign serous tumours. There was no difference in the expression of MTs in the single layered tumour cells of benign and borderline serous tumours. Significantly higher numbers of MT-immunopositive cells were observed in both the single and the multilayered epithelial cells of serous carcinomas, the highest number being observed in the multiple layers of serous carcinomas. The positively stained malignant tumour cells in both single and multiple layers were larger than the negatively stained cells in benign, borderline, and malignant serous ovarian tumours. There was moderate to intense staining. These findings indicate that there is increased expression of MTs in the progression of malignancy, which could be used as a marker in grading the three groups of ovarian serous tumours and for determining prognosis.

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

    ClinicalTrials.gov

    2016-11-02

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

  11. Recent progress in the treatment of epithelial ovarian malignancy.

    PubMed

    Berek, J S; Hacker, N F; Lagasse, L D

    1982-10-01

    Improved surgical and chemotherapeutic management has ensured that more than half the patients with advanced ovarian cancer will be clinically free of disease shortly after treatment begins. Aggressive cytoreductive surgical treatment and combination cytotoxic chemotherapy have appreciably prolonged survival and have induced cures in some women with metastatic disease. An increasing number of women are being seen with small residual disease at second-look laparotomy, and intraperitoneal administration of chemotherapeutic and immunotherapeutic agents is being investigated for these patients. Specific immunotherapies, including monoclonal antibodies raised against patients' own tumor cells, are also being investigated. During the next five years we may see significant improvement in the cure rate for this disease.

  12. Role of imaging in successful management of malignant ovarian vein thrombosis in RCC.

    PubMed

    Goyal, Ankur; Rangarajan, Krithika; Singh, Prabhjot; Das, Chandan Jyoti

    2014-02-07

    Renal cell carcinoma (RCC) is the most common renal malignancy in adults. Since complete surgical resection is the treatment of choice, accurate staging and extent delineation are imperative for optimal management. Owing to venous tropism, the tumour has a propensity to extend into renal vein and/or inferior vena cava. However, contiguous gonadal vein extension has rarely been reported. Here we present an unusual case of a 65-year-old woman who demonstrated a large left renal mass with extension of tumour thrombus into the left renal and ovarian veins with multiple retroperitoneal venous collaterals detected on multiphasic CT examination. This preoperative imaging information facilitated en bloc resection of the tumour and thrombosed vessels. To the best of our knowledge, this is the first case where comprehensive imaging evaluation enabled successful surgical management of RCC with malignant ovarian vein thrombosis and limited peroperative complications.

  13. Novel insights on the malignant transformation of endometriosis into ovarian carcinoma.

    PubMed

    Gadducci, Angiolo; Lanfredini, Nora; Tana, Roberta

    2014-09-01

    The malignant transformation of endometriosis is an uncommon event, which happens in 0.7-2.5% of the cases, and, when occurs, it usually involves the ovary. A 2 to 3-fold higher risk of ovarian endometrioid and clear cell carcinoma has been reported in women with endometriosis. Pathological studies have detected a morphological continuum of sequential steps from normal endometriotic cyst epithelium to atypical endometriosis and finally to invasive carcinoma. Ovarian endometrioid carcinoma harbors mutations of CTNNB1 in 16-53.3%, of PTEN in 14-20% and of ARID1A in 30-55% of the cases. Ovarian clear cell carcinoma harbors mutations of PIK3CA in 20-40% and of ARID1 in 15-75% of the cases. Whereas estrogen receptors and progesterone receptors are quite always absent, HNF-1b is often over-expressed in this histotype. Atypical endometriosis and endometriosis-related ovarian neoplasms share molecular alterations, such as PTEN mutations, ARID1A mutations and up-regulation of HNF-1b. Moreover, ARID1A mutations have been noted in clear cell tumors and contiguous atypical endometriosis, but not in distant endometriotic lesions. The loss of BAF250a protein expression is suggestive for the presence of ARID1A mutations, and represents an useful marker of malignant transformation of endometriosis.

  14. Role of primary surgery in advanced ovarian cancer

    PubMed Central

    Münstedt, Karsten; Franke, Folker E

    2004-01-01

    Background Major issues in surgery for advanced ovarian cancer remain unresolved. Existing treatment guidelines are supported by a few published reports and fewer prospective randomized clinical trials. Methods We reviewed published reports on primary surgical treatment, surgical expertise, inadequate primary surgery/quality assurance, neoadjuvant chemotherapy, interval debulking, and surgical prognostic factors in advanced ovarian cancer to help resolve outstanding issues. Results The aim of primary surgery is a well-planned and complete intervention with optimal staging and surgery. Surgical debulking is worthwhile as there are further effective treatments available to control unresectable residual disease. Patients of gynecologic oncology specialist surgeons have better survival rates. This may reflect a working 'culture' rather than better technical skills. One major problem though, is that despite pleas to restrict surgery to experienced surgeons, specialist centers are often left to cope with the results of inadequate primary surgical resections. Patients with primary chemotherapy or those who have had suboptimal debulking may benefit from interval debulking. A proposal for a better classification of residual tumor is given. Conclusions Optimal surgical interventions have definite role to play in advanced ovarian cancers. Improvements in surgical treatment in the general population will probably improve patients' survival when coupled with improvements in current chemotherapeutic approaches. PMID:15461788

  15. The clinical value of dynamic contrast-enhanced MRI in differential diagnosis of malignant and benign ovarian lesions.

    PubMed

    Li, Xian; Hu, Jun-Li; Zhu, Lai-Min; Sun, Xin-Hai; Sheng, Hua-Qiang; Zhai, Ning; Hu, Xi-Bin; Sun, Chu-Ran; Zhao, Bin

    2015-07-01

    Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is widely used in preoperative diagnosis of various tumors. We investigated the clinical value of DCE-MRI in differential diagnosis of malignant and benign ovarian lesions. The study involved 48 subjects with surgical pathology-confirmed ovarian tumors with solid components. Early dynamic phase enhancement performances of the ovarian lesions in patients were assessed, including the enhancement pattern, time-signal intensity curve (TIC), signal intensity rate at the initial 60 s (SI60), time to peak within 200 s (TTP200), and slope ratio. There were significant differences in enhancement patterns between benign and malignant ovarian tumors (P <  .05). A total of 30 malignant tumors (30/31) displayed type I TIC, 8 benign tumors (8/13) showed type III TIC, and significant differences were found in TIC type between malignant and benign ovarian lesions (P < 0.01). Benign ovarian tumors showed lower SI60 (%) and slope ratio, as well as significantly prolonged TTP20, compared to malignant ovarian tumors (all P < 0.01). The microvessel count (MVC) of malignant tumors was significantly higher than that of benign tumors (P < 0.05). Receiver operating characteristic (ROC) curve analyses revealed that DCE-MRI provided an optimal diagnostic performance with threshold values of SI60 at 83.40 %, TTP200 at 77.65 s, and slope ratio at 4.12. These findings revealed that DCE-MRI provides critical information required for differential diagnosis of malignant and benign ovarian lesions.

  16. Serum cystine aminopeptidase and leucine aminopeptidase activity in women with benign and malignant uterine and ovarian tumors.

    PubMed

    Blum, M; Sirota, P

    1977-09-01

    The serum enzymatic activities of cystine aminopeptidase and leucine aminopeptidase were measured in a group of 113 patients of whom 90 had benign uterine or ovarian tumors, and 23 had cancer of the endometrium or ovary. Thirty healthy nonpregnant women and 260 women at different stages of normal pregnancy served as control groups. The presence of pregnancy-specific enzymes in women with uterine or ovarian tumors showed once again that similar processes occur during pregnancy and malignancy. When ovarian or uterine malignancy is suspected on clinical examination, determination of the activities of these enzymes in serum may be of diagnostic value.

  17. Prevalence of Malignancies in Patients With Primary Aldosteronism.

    PubMed

    Lang, K; Weber, K; Quinkler, M; Dietz, A S; Wallaschofski, H; Hannemann, A; Friedrichs, N; Rump, L C; Heinze, B; Fuss, C T; Quack, I; Willenberg, H S; Reincke, M; Allolio, B; Hahner, S

    2016-04-01

    In the multicenter MEPHISTO study, the prevalence of benign and malignant tumors has been investigated in 335 patients with confirmed primary aldosteronism and compared to matched controls. Compared to hypertensive controls, the prevalence of malignancies was positively correlated with aldosterone levels, tended to be higher in PA patients, but did not differ significantly.

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

    ClinicalTrials.gov

    2016-10-26

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

  19. Role of diffusion-weighted magnetic resonance imaging in differentiating malignancies from benign ovarian tumors

    PubMed Central

    Fan, Xinhua; Zhang, Hongbin; Meng, Shuang; Zhang, Jing; Zhang, Chuge

    2015-01-01

    Objective: We conducted a case-control study to evaluate the diagnostic values of computed tomography (CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) in differentiating malignancies from benign ovarian tumors and a meta-analysis to further confirm our results on DW-MRI. Methods: Totally 64 patients pathologically confirmed as ovarian cancer were included in this study. CT scan and DWI-MRI were performed and analyzed to get compared with pathological results, thereby assessing their accuracy, sensitivity and specificity. Meta-analysis was conducted by database searching and strict eligibility criteria, using STATA 12.0 (Stata Corp, College Station, TX, USA) software. Results: The accuracy, sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of ovarian cancer in CT were 81.82%, 84.48%, 76.67%, 87.50% and 71.88%, respectively; those in DW-MRI were 89.77%, 93.10%, 83.33%, 91.53% and 86.21%, respectively. The Kappa coefficient of DW-MRI (K = 0.771) compared with pathological results was higher than CT (K = 0.602). The average apparent diffusion coefficient values of DW-MRI in diagnosis of benign and malignant ovarian tumors suggested statistically significant difference (1.325 ± 0.269×10-3 mm2/s vs. 0.878 ± 0.246×10-3 mm2/s, P < 0.001). Meta-analysis results showed that the combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio of DW-MRI in discriminating benign versus malignant ovarian tumors were 0.93, 0.88, 7.70, 0.08 and 101.24, respectively. The area under the summary receiver operating characteristic curve was 0.95. Conclusions: Both CT and DW-MRI were of great diagnostic value in differentiating malignancies from benign ovarian tumors, while DW-MRI was superior to CT with higher accuracy, sensitivity and specificity. PMID:26884905

  20. UNEXPECTED OVARIAN MALIGNANCY FOUND AFTER LAPAROSCOPIC SURGERY IN PATIENTS WITH ADNEXAL MASSES –A SINGLE INSTITUTIONAL EXPERIENCE–

    PubMed Central

    SAITO, SHIGEKO; KAJIYAMA, HIROAKI; MIWA, YOKO; MIZUNO, MIKA; KIKKAWA, FUMITAKA; TANAKA, SHIHO; OKAMOTO, TOMOMITSU

    2014-01-01

    ABSTRACT Laparoscopy has become the standard surgery for the treatment of benign ovarian tumors. The aim of this study was to evaluate the appropriateness of laparoscopy for ovarian tumors, including those with malignant potential. A total of 487 patients with adnexal masses underwent laparoscopic surgery in Social Insurance Chukyo Hospital from January 2000 to December 2012.We reviewed 471 cases that fulfilled the criteria set for this study, and examined 10 cases with unexpected ovarian malignancy to analyze their preoperative diagnosis, second surgery, postoperative chemotherapy, and prognosis. The ages of the 471 patients ranged from 13 to 50 years, with a median of 31. Nulliparous patients numbered 321(68.1%).Of all, 436 patients mostly consisted of those with endometrioma, benign ovarian neoplasm or functional cyst. In all, we histologically identified 10 women with malignancy: 6 with borderline ovarian tumors (BOT), 2 with ovarian cancer, and 2 with histologically rare tumors (immature teratoma and granulosa cell tumor). All patients with BOT were diagnosed with a mucinous histology. Two patients underwent both second radical surgery (hysterectomy and contra- or bilateral salpingo-oophorectomy) and chemotherapies that consisted of CBDCA and PTX or DTX. Thus, 2 patients underwent staging procedures, but the remaining 8 cases did not. None of them had evidence of recurrences. With accurate staging and careful postoperative follow-up, laparoscopic surgery could be a feasible initial operation for patients with adnexal masses including early-stage ovarian malignancy. PMID:25129994

  1. Unexpected ovarian malignancy found after laparoscopic surgery in patients with adnexal masses--a single institutional experience.

    PubMed

    Saito, Shigeko; Kajiyama, Hiroaki; Miwa, Yoko; Mizuno, Mika; Kikkawa, Fumitaka; Tanaka, Shiho; Okamoto, Tomomitsu

    2014-02-01

    Laparoscopy has become the standard surgery for the treatment of benign ovarian tumors. The aim of this study was to evaluate the appropriateness of laparoscopy for ovarian tumors, including those with malignant potential. A total of 487 patients with adnexal masses underwent laparoscopic surgery in Social Insurance Chukyo Hospital from January 2000 to December 2012. We reviewed 471 cases that fulfilled the criteria set for this study, and examined 10 cases with unexpected ovarian malignancy to analyze their preoperative diagnosis, second surgery, postoperative chemotherapy, and prognosis. The ages of the 471 patients ranged from 13 to 50 years, with a median of 31. Nulliparous patients numbered 321(68.1%). Of all, 436 patients mostly consisted of those with endometrioma, benign ovarian neoplasm or functional cyst. In all, we histologically identified 10 women with malignancy: 6 with borderline ovarian tumors (BOT), 2 with ovarian cancer, and 2 with histologically rare tumors (immature teratoma and granulosa cell tumor). All patients with BOT were diagnosed with a mucinous histology. Two patients underwent both second radical surgery (hysterectomy and contra- or bilateral salpingo-oophorectomy) and chemotherapies that consisted of CBDCA and PTX or DTX. Thus, 2 patients underwent staging procedures, but the remaining 8 cases did not. None of them had evidence of recurrences. With accurate staging and careful postoperative follow-up, laparoscopic surgery could be a feasible initial operation for patients with adnexal masses including early-stage ovarian malignancy. PMID:25129994

  2. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma. PMID:27660729

  3. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

    PubMed Central

    Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma.

  4. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor.

    PubMed

    Gleason, James Benjamin; Tashtoush, Basheer; Diacovo, Maria Julia

    2016-01-01

    Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT) scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma), with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid), supporting the diagnosis of biphasic malignant mesothelioma. PMID:27660729

  5. Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-11-04

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

  6. Pre-operative assessment of benign and malignant ovarian tumours using colour Doppler ultrasonography.

    PubMed

    Dasgupta, Shyamal; Malty, Saurav Prakash; Sharma, Partha Pratim; Mukhopadhyay, Amitava; Ghosh, Tarun Kumar

    2010-08-01

    Ultrasonography of 56 women with adenexal masses who were admitted for laparotomy were done mainly by transvaginal route. Though Gray scale morphologic evaluations of masses were done routinely, only colour Doppler imaging criteria were taken into consideration in this study. These are pulsatility index (PI), resistance index (RI), peak systolic velocity (PSV), timed average maximal velocity (TAMXV), vessels localisation and dicrotic notch. Histopathological examination was done and considered as gold standard. In 83.78% cases of benign tumour PI is equal or greater than 1, whereas it was less than 1 in 84.21% in malignant ovarian tumour. The sensitivity, specificity, PPV and NPV were respectively 84.21%, 83.78%, 72.72% and 91.11%. RI in benign tumours were equal to or more than 0.4 in 81.08% and less than 0.4 in 68.42% in case of malignant tumours. The sensitivity, specificity, PPV and NPV were respectively 68.42%, 81.08%, 65% and 83.33%. Considering the TAMXV>12 cm/second as a criterion for malignancy the sensitivity, specificity, PPV and NPV were respectively 89.45%, 89.19%, 80.95% and 94.28%, and also considering septal/central localisation of vessels as a criterion for malignancy, it was found the sensitivity, specificity, PPV and NPV were 89.47%, 62.16%, 54.84% and 92% respectively. Considering absence of dicrotic notch for malignant tumours we found sensitivity, specificity, PPV and NPV were 89.47%, 81.08%, 70.83% and 93.75% respectively. The above findings of the PI, TAMXV and dicrotic notch evaluation show most useful was colour Doppler parameters for pre-operative screening for ovarian malignancy in this study.

  7. Carboplatin and Gemcitabine Hydrochloride With or Without ATR Kinase Inhibitor VX-970 in Treating Patients With Recurrent and Metastatic Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-06-21

    High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

  8. Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis.

    PubMed

    Fuseya, Chiho; Horiuchi, Akiko; Hayashi, Akiko; Suzuki, Akihisa; Miyamoto, Tsutomu; Hayashi, Takuma; Shiozawa, Tanri

    2012-11-01

    Inflammation in the ovary, including ovulation and pelvic inflammatory disease, has been proposed to play a role in the pathogenesis of ovarian cancer. Endometriotic lesions trigger a local inflammatory reaction and have been reported to be associated with an increased risk of epithelial ovarian cancer. However, the precise molecular mechanisms of ovarian cancer arising from endometriosis are still to be elucidated. To clarify the involvement of mismatch repair (MMR) abnormalities in the inflammation-associated malignant transformation of endometriosis, the immunohistochemical expression of mismatch repair proteins (human mutL homolog 1 [hMLH1] and human mutS homolog 2 [hMSH2]) was examined in 27 cases of ovarian endometriosis, 25 cases of ovarian carcinoma accompanied by endometriosis, and 39 cases of solitary ovarian carcinoma. In addition, the relationship between mismatch repair abnormalities including the microsatellite instability, PTEN (phosphatase and tensin homolog) mutation, and clinicopathologic parameters was analyzed. The expression of mismatch repair proteins was stepwisely decreased in endometriosis, ovarian carcinoma accompanied by endometriosis, and ovarian carcinoma. Tumors harboring multiple microsatellite instability (high-frequency microsatellite instability [MSI-H]) were detected in 4 (14.8%) of 27 cases of endometriosis and 7 (30.4%) of 23 cases of ovarian carcinomas. The frequency of PTEN mutations was higher in MSI-H cases than in microsatellite instability-stable (MSI-S) cases. In 2 cases of ovarian carcinoma accompanied by endometriosis, the decreased expression of mismatch repair proteins and MSI-H was observed in both the endometriosis and carcinoma lesions. Clinicopathologically, the MSI-H cases were associated with elevated serum levels of C-reactive protein and higher white blood cell counts. These findings suggest that mismatch repair abnormalities might be involved in the malignant transformation of ovarian endometriosis and that

  9. Ovarian tumors of low malignant potential (borderline tumors): immune morphology and current status.

    PubMed

    Neunteufel, W; Gitsch, G; Schieder, K; Kölbl, H; Breitenecker, G

    1989-01-01

    CA 125, CA 19-9 and CEA were demonstrated in tissue samples of 30 ovarian borderline tumors by immunohistochemistry. Of the 21 serous and 9 mucinous borderline tumors, 23 were in stage I and 7 stage III. None of the patients died of disease. All mucinous borderline tumors were CA 125 negative, 89% CA 19-9 positive and 44% CEA positive. 62% of the serous borderline tumors were CA 125 positive, 52% CA 19-9 and 19% CEA positive. Tumors of low malignant potential responded to CA 19-9 like invasive carcinomas. The incidence of positive responses to CA 125 ands CEA fell between that of benign and malignant tumors. The marker pattern did not correlate with tumor stage and cytological grading. The biological behavior of ovarian borderline tumors ranges between that of benign tumors and invasive carcinomas and cannot be classified as definitely belonging to either group. It is plausible that they are primarily of the borderline type, and not benign tumors that undergo malignant degeneration.

  10. [Hormone dependence of malignant ovarian tumors--an in vitro model].

    PubMed

    Schieder, K; Bieglmayer, C; Kölbl, H

    1989-05-01

    The steroid hormone receptor content of 32 malignant ovarian tumors was compared with the in vitro effectiveness of 4 hydroxytamoxifen (OH-TAM) and medroxy-progesterone acetate (MPA) tested in the Human Tumor Colony Forming Assay (HTCFA). The sensitivity for the receptor determination was 5 fmol/mg cytosol protein. Estrogen receptors (ER) and progesterone receptors (PR) were found in 15 (47%) and 13 (41%) of the tumors respectively. As standard criteria for the HTCFA, a minimum of 30 colonies with a diameter of more than 60 microns and 100 microns was used in the control group. The in-vitro sensitivity of ovarian tumors to OH-TAM and MPA was independent on the ER or PR content, and amounted to 9% for OH-TAM and 6% for MPA. However, all 12 ER-PR-tumors proved resistant to OH-TAM and MPA. 18 ovarian tumors showed a sufficient colony growth, even in the size class exceeding 100 microns. With a minimum colony size of 60 microns and 100 microns, 17% and 33% respectively were sensitive to OH-TAM. A similar effect on the proliferative capacity of the Tumor Colony Forming Units (TCFUs), unrelated to PR, was observed with MPA. Dependent on colony size, we found an increasing sensitivity against MPA from 11% to 22%. The in-vitro effectiveness of both OH-TAM and MPA in the clonogenic assay of malignant ovarian tumors was certainly not as potent as suggested by the results obtained in biochemical steroid hormone receptor analysis. To prove the hormonal response in the HTCFA, it is necessary to determine number and size of the colonies as an expression of their proliferative potential.

  11. Palliative Care in Improving Quality of Life in Patients With High Risk Primary or Recurrent Gynecologic Malignancies

    ClinicalTrials.gov

    2015-10-15

    Cervical Carcinoma; Ovarian Carcinoma; Primary Peritoneal Carcinoma; Recurrent Cervical Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Uterine Corpus Carcinoma; Recurrent Vulvar Carcinoma; Uterine Corpus Cancer; Vulvar Carcinoma; Peritoneal Neoplasms

  12. Genetics and biology of human ovarian teratomas. III. Cytogenetics and origins of malignant ovarian germ cell tumors.

    PubMed

    Hoffner, L; Shen-Schwarz, S; Deka, R; Chakravarti, A; Surti, U

    1992-08-01

    This report presents cytogenetic data on three cases of malignant ovarian germ cell tumors. All were diagnosed as malignant teratoma; case 1 with yolk sac elements; case 2 with elements of endodermal sinus tumor, embryonal carcinoma, and choriocarcinoma; and case 3 with yolk sac elements and embryonal carcinoma. Metaphase cells from each tumor, and normal tissue from the host, were karyotyped and scored for centromeric heteromorphisms in an attempt to determine the mechanism of origin. The karyotypes were 79,XXX,+1,+3,-6,+8,+12,+14,-15,+17, +20,+21,+22;49,XX,+8,+12,+22; and 48,XX,+3,+14, respectively. The analysis of centromeric heteromorphisms and DNA fingerprints of host and teratoma using the M13 probe revealed that one case originated from a germ cell before the first meiotic division. Normal host tissue was not available in case 2, but several centromeric markers were heterozygous in the tumor, indicating either meiosis I error or complete failure of germ cell meiosis. In the third case the centromeric heteromorphisms that were heterozygous in the host appeared to be homozygous for certain chromosomes and heterozygous for others in the tumor. These results suggest that germ cell teratomas could arise by the fusion of two ova. PMID:1521236

  13. The association of benign and malignant ovarian adenofibromas with breast cancer and thyroid disorders.

    PubMed

    Silva, Elvio G; Tornos, Carmen; Malpica, Anais; Deavers, Michael T; Tortolero-Luna, Guillermo; Gershenson, David M

    2002-01-01

    An unexpected association with breast cancer and thyroid disorders was found during a review of 91 cases of benign and malignant ovarian adenofibromas. Sixty-three tumors were benign, 11 had areas of borderline neoplasms, and 17 had a component of carcinoma. Such tumors were divided into glandular/cystic (61 cases) and papillary (30 cases) according to their gross and microscopic appearance. Among the 61 patients with glandular/cystic adenofibromas, 13 (21%) had breast cancer and 19 (31%) also had thyroid disorders. Among the 30 patients with papillary adenofibromas there were no cases of breast cancer and only 2 patients had thyroid disorders. The average age of the patients with ovarian adenofibroma and breast cancer or thyroid disorders was higher (66 years) than that of patients without breast cancer or thyroid disorders (55 years). More patients with breast cancer and thyroid disorders had bilateral adenofibromas than patients without breast cancer or thyroid disorders. We also reviewed the medical records of 100 patients with ovarian cancer without adenofibroma component, 100 patients with breast cancer, and 100 patients with ovarian and breast cancer. Six percent of patients with ovarian cancer had breast cancer and 16% of each one of these groups had thyroid disorders. This unexpected association found between glandular/cystic adenofibromas, breast cancer, and thyroid disorders might be explained by defects common to these organs. Disorders of some of these organs have been linked by common genetic changes and it is known that these organs are under the influence of similar hormones. Mutations of PTEN have been found in breast and thyroid cancer. The thyroid and ovaries are controlled by glycoprotein hormones of the pituitary gland, which have common alpha subunits.

  14. Risk of ovarian failure and fertility preserving methods in girls and adolescents with a malignant disease.

    PubMed

    Schmidt, K T; Larsen, E C; Andersen, C Y; Andersen, A N

    2010-01-01

    Girls and young women suffering from a malignant disease that requires treatment with chemo- and/or radiotherapy are at risk of losing fertility. The most significant risk factors are age and type of treatment given. Preserving fertility is of high priority to both the young patient and her parents. This article reviews the effect of chemo- and radiotherapy on gonadal function, and thus fertility, and offers different fertility preserving methods based on the literature. Cryopreservation of ovarian tissue is a possible way of preserving fertility in this group of patients in the future. PMID:19874293

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

    ClinicalTrials.gov

    2013-03-18

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

  16. Olaparib or Cediranib Maleate and Olaparib Compared With Standard Platinum-Based Chemotherapy in Treating Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-10-17

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

  17. Differences in pteridine urinary levels in patients with malignant and benign ovarian tumors in comparison with healthy individuals.

    PubMed

    Zvarik, M; Martinicky, D; Hunakova, L; Sikurova, L

    2015-12-01

    Pteridines belong to a class of fluorescent metabolites that are excreted by humans in urine and their concentrations can reflect various pathophysiological states. We quantified the differences in urinary pteridine levels in patients with malignant and benign ovarian tumors and in healthy individuals. Urine samples were centrifuged and supernatants were oxidized by MnO2 before analysis. Levels of neopterin, biopterin, and pterin were assessed by fluorescence analysis of human urine after HPLC separation. We have revealed that the median neopterin levels were higher in urine samples from patients with malignant (0.226 μmol/mmol creatinine) and benign ovarian tumors (0.150 μmol/mmol creatinine) than in healthy subjects (0.056 μmol/mmol creatinine). The median neopterin levels of patients with malignant tumors were higher (1.5-times) than in patients with benign tumors. The median biopterin level in urine of patients with benign ovarian tumors (0.268 μmol/mmol creatinine) was found to be very close to the level in patients with malignant ovarian tumors (0.239 μmol/mmol creatinine), and both were higher than in healthy samples (0.096 μmol/mmol creatinine). The levels of urine pterin followed a pattern similar to neopterin levels for both ovarian tumors, but their concentrations were about three times lower than neopterin levels.

  18. Carboplatin, Paclitaxel, Bevacizumab, and Veliparib in Treating Patients With Newly Diagnosed Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-09-09

    Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Tumor; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  19. Targeting Nrf2 in healthy and malignant ovarian epithelial cells: Protection versus promotion.

    PubMed

    van der Wijst, Monique G P; Huisman, Christian; Mposhi, Archibold; Roelfes, Gerard; Rots, Marianne G

    2015-08-01

    Risk factors indicate the importance of oxidative stress during ovarian carcinogenesis. To tolerate oxidative stress, cells activate the transcription factor Nrf2 (Nfe2l2), the master regulator of antioxidant and cytoprotective genes. Indeed, for most cancers, hyperactivity of Nrf2 is observed, and siRNA studies assigned Nrf2 as therapeutic target. However, the cancer-protective role of Nrf2 in healthy cells highlights the requirement for an adequate therapeutic window. We engineered artificial transcription factors to assess the role of Nrf2 in healthy (OSE-C2) and malignant ovarian cells (A2780). Successful NRF2 up- and downregulation correlated with decreased, respectively increased, sensitivity toward oxidative stress. Inhibition of NRF2 reduced the colony forming potential to the same extent in wild-type and BRCA1 knockdown A2780 cells. Only in BRCA1 knockdown A2780 cells, the effect of Nrf2 inhibition could be enhanced when combined with PARP inhibitors. Therefore, we propose that this combination therapy of PARP inhibitors and Nrf2 inhibition can further improve treatment efficacy specifically in BRCA1 mutant cancer cells without acquiring the side-effects associated with previously studied Nrf2 inhibition combinations with either chemotherapy or radiation. Our findings stress the dual role of Nrf2 in carcinogenesis, while offering approaches to exploit Nrf2 as a potent therapeutic target in ovarian cancer.

  20. Malignant ascites in ovarian cancer and the role of targeted therapeutics.

    PubMed

    Smolle, Elisabeth; Taucher, Valentin; Haybaeck, Johannes

    2014-04-01

    Ovarian cancer (OC) is the eighth most lethal gynecological malignancy and the main cause of gynecological cancer death in industrialized countries. Malignant ascites is often found in OC, with about 10% of patients suffering from recurrent OC. Tumor cells in OC-associated malignant ascites promote disease recurrence and patient mortality is mainly associated with widespread metastasis to serosal surfaces and accompanying peritoneal effusions. Targeted therapies have recently been developed as novel therapeutic options for malignant ascites. The tri-functional anti-epithelial cell adhesion molecule and anti-cluster of differentiation 3 monoclonal antibody catumaxumab has been assessed in the therapy of malignant ascites, and proven to significantly reduce the ascitic flow rate when applied into the peritoneal cavity. The anti-angiogenic targeted agent bevacizumab has also shown good effects in the symptomatic treatment of malignant ascites, significantly prolonging the time until the next paracentesis. Vascular endothelial growth factor (VEGF) Trap, or aflibercept, is a fusion protein that inhibits VEGF-receptor binding. Aflibercept has proven to be effective in reduction of ascites, diminishing clinical symptoms of ascites and prolonging the time to next paracentesis. All three agents we review in the present article are effective in symptomatic control of ascites, leading to a rapid reduction of effusion and prolonging the time interval between paracenteses. However, no improvement in overall survival was observed in any of the clinical trials reported. We, thus, conclude that further investigations on larger patient series are needed to clarify whether the reduction of ascites by these targeted agents leads to a prolongation in tumor-related survival or not.

  1. Outcomes following percutaneous upper gastrointestinal decompressive tube placement for malignant bowel obstruction in ovarian cancer

    PubMed Central

    Rath, KS; Loseth, D; Muscarella, P; Phillips, GS; Fowler, JM; O’Malley, DM; Cohn, DE; Copeland, LJ; Eisenhauer, EL; Salani, R

    2014-01-01

    Objective The objective of this study was to evaluate peri-operative and survival outcomes of ovarian cancer patients undergoing percutaneous upper gastrointestinal decompression for malignant bowel obstruction (MBO). Methods Retrospective chart review was used to identify patients with ovarian, peritoneal, or fallopian tube cancer who underwent palliative decompressive treatment for MBO from 1/2002–12/2010. Kaplan-Meier methods were used to estimate the median survival (MS) and multivariate analysis used to determine if any variables were associated with the hazard of death. Results Fifty-three patients met inclusion criteria. Median length of diagnosis prior to intervention was 21 months. Fifteen (28.3%) patients experienced complications and 9 required revision. Forty-nine (92.5%) experienced relief of symptoms after placement, and 91% tolerated some form of oral intake. Following placement, 19 (36%) patients received additional chemotherapy and 21(41%) patients received total parental nutrition (TPN). Thirty-five patients were discharged home/outpatient facility, 16 to hospice care, and 2 died prior to discharge. MS for all patients was 46 days. Patients who received chemotherapy had a MS of 169 days compared to 33 days (p<0.001). We failed to find an association between survival and TPN or performance status. Conclusions Malignant bowel obstruction is a common complication of ovarian cancer. Management is palliative; risks and benefits of any therapy must be considered. Percutaneous decompressive therapy provides relief from associated symptoms, and allows patients to be discharged home. Median survival in this group is limited, and decisions regarding aggressive therapy should be individualized. PMID:23369942

  2. Pegylated Liposomal Doxorubicin Hydrochloride With Atezolizumab and/or Bevacizumab in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-09-12

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  3. Usefulness of diagnostic indices comprising clinical, sonographic, and biomarker data for discriminating benign from malignant ovarian masses.

    PubMed

    Stukan, Maciej; Dudziak, Miroslaw; Ratajczak, Karol; Grabowski, Jacek P

    2015-02-01

    The objective of this study was to review the accuracy of indices combining several diagnostic variables, in comparison to other models, sonography alone, and biomarker assays, for predicting benign or malignant ovarian lesions. Different single modalities were reviewed. The most useful complex models were International Ovarian Tumor Analysis (IOTA) sonographic logistic regression model 2 (area under the curve, 0.949), risk of malignancy index-cancer antigen 125-human epididymis protein 4 (0.950), risk of malignancy algorithm (0.953), pelvic mass score (0.960), non-IOTA logistic regression model (0.970), and histoscanning score logistic regression model (0.970). None of the indices was superior to an expert subjective sonographic assessment (0.968). For women with adnexal tumors, indices with high accuracy are available that are applicable in clinical practice and comparable to an expert subjective sonographic assessment for discriminating benign from malignant masses.

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

    ClinicalTrials.gov

    2016-08-12

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Tumor; Fallopian Tube Mucinous Neoplasm; Fallopian Tube Serous Neoplasm; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; 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

  5. Ovarian mucinous cystic tumor of borderline malignancy with a mural nodule of anaplastic spindle cell carcinoma: a case report.

    PubMed

    Yamazaki, Hitoshi; Matsuzawa, Akiyo; Shoda, Takashi; Iguchi, Hiroyoshi; Kyushima, Noriyuki

    2013-12-05

    Ovarian cystic tumors with a mural nodule are a rare entity. We report a case of a mural nodule of anaplastic spindle cell carcinoma in an ovarian mucinous cystic tumor of borderline malignancy. The patient was a 45-years-old Japanese woman who presented with an ovarian cyst. She suffered from mature cystic teratoma of both ovaries 9 years before the present history. Image analysis and laboratory data showing a high serum CA19-9 level suggested ovarian malignancy. She underwent bilateral salpingo-oophorectomy with hysterectomy and omentectomy. There was a mural nodule in the ovarian mucinous cystic lesion. Microscopically, the nodule was composed of spindle-shaped cells with severe nuclear atypia. Immunohistochemical analysis allowed the cells to be categorized as anaplastic spindle cell carcinoma. Fifteen months after the operation the patient is alive without any clinical findings of tumor recurrence. To the best of our knowledge in the English literature, this is the first report of a mural nodule of an anaplastic spindle cell carcinoma within an ovarian mucinous cystic borderline tumor harboring previously confirmed cystic teratoma.

  6. Distinguishing primary from secondary mucinous ovarian tumors: an algorithm using the novel marker DPEP1.

    PubMed

    Okamoto, Takako; Matsumura, Noriomi; Mandai, Masaki; Oura, Tomonori; Yamanishi, Yukio; Horiuchi, Akiko; Hamanishi, Junzo; Baba, Tsukasa; Koshiyama, Masafumi; Shiozawa, Tanri; Konishi, Ikuo

    2011-02-01

    Distinguishing primary mucinous ovarian cancers from ovarian metastases of digestive organ cancers is often challenging. Dipeptidase 1 was selected as the candidate novel marker of colorectal cancer based on an analysis of a gene expression microarray. Immunohistochemical analysis indicated that 13/16 ovarian metastases of colorectal cancers, but only 1/58 primary mucinous ovarian cancers, were dipeptidase 1-positive (threshold; ≧25% expression, P<0.0001). Next, five immunohistochemical markers (dipeptidase 1, estrogen receptor-α, cytokeratin 7, cytokeratin 20, and caudal type homeobox 2) were analyzed in combination. In a hierarchical clustering analysis, the mutually exclusive expression of cytokeratin 7 and dipeptidase 1 specifically identified the ovarian metastases of colorectal cancers (P<0.0001). In a decision tree analysis, cytokeratin 7, caudal type homeobox 2, and dipeptidase 1 classified primary mucinous ovarian cancers and ovarian metastases of digestive organ cancers with 90% accuracy. Finally, the five immunohistochemical markers were combined with six preoperative factors (patient's age, tumor size, laterality, serum CEA, CA19-9, and CA125) and combinations were analyzed. Of the 11 factors, 4 (dipeptidase 1, cytokeratin 7, caudal type homeobox 2, and tumor size) were used to generate a decision tree to classify primary mucinous ovarian cancers and metastases of digestive organ cancers with 93% accuracy. In conclusion, we identified a novel immunohistochemical marker, dipeptidase 1, to distinguish primary mucinous ovarian cancers from ovarian metastasis of colorectal cancers. The algorithm using immunohistochemical and clinical factors to distinguish metastases of digestive organ cancers from primary mucinous ovarian cancers will be useful to establish a protocol for the diagnosis of ovarian metastasis.

  7. Granisetron, Aprepitant, and Dexamethasone in Preventing Nausea and Vomiting in Patients Receiving Chemotherapy for Stage II, III, or IV Ovarian Cancer

    ClinicalTrials.gov

    2016-03-16

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

  8. 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

    ClinicalTrials.gov

    2014-06-18

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

  9. Ultrasonography of ovarian masses using a pattern recognition approach.

    PubMed

    Jung, Sung Il

    2015-07-01

    As a primary imaging modality, ultrasonography (US) can provide diagnostic information for evaluating ovarian masses. Using a pattern recognition approach through gray-scale transvaginal US, ovarian masses can be diagnosed with high specificity and sensitivity. Doppler US may allow ovarian masses to be diagnosed as benign or malignant with even greater confidence. In order to differentiate benign and malignant ovarian masses, it is necessary to categorize ovarian masses into unilocular cyst, unilocular solid cyst, multilocular cyst, multilocular solid cyst, and solid tumor, and then to detect typical US features that demonstrate malignancy based on pattern recognition approach.

  10. [Value of the tumor colony assay in therapy planning in malignant ovarian tumors].

    PubMed

    Schieder, K; Kölbl, H; Bieglmayer, C

    1987-01-01

    The aim of our study was to determine the clinical value of the human tumour colony assay for the treatment of patients suffering from advanced malignant ovarian tumours. Using this in vitro culture system the growth and chemosensitivity of clonogenic tumour cells could be studied. Cultures were obtained of only 52.6% of the 133 tumour samples; only 33 of 70 assays showed a sufficient growth of colonies. However, the significance of the stem cell assay for clinical use is represented by the prediction of drug resistance. In 17 trials the assay had a 67% true positive rate and a 100% true negative rate for predicting drug sensitivity and resistance, respectively. Apart from the methodical errors inherent in this method, the false positive prediction of drug sensitivity might be caused by the heterogeneity of the tumour.

  11. Rho GTPases in primary brain tumor malignancy and invasion.

    PubMed

    Khalil, Bassem D; El-Sibai, Mirvat

    2012-07-01

    Gliomas are the most common type of malignant primary brain tumor in humans, accounting for 80 % of malignant cases. Expression and activity of Rho GTPases, which coordinate several cellular processes including cell-cycle progression and cell migration, are commonly altered in many types of primary brain tumor. Here we review the suggested effects of deregulated Rho GTPase signaling on brain tumor malignancy, highlighting the controversy in the field. For instance, whereas expression of RhoA and RhoB has been found to be significantly reduced in astrocytic tumors, other studies have reported Rho-dependent LPA-induced migration in glioma cells. Moreover, whereas the Rac1 expression level has been found to be reduced in astrocytic tumor, it was overexpressed and induced invasion in medulloblastoma tumors. In addition to the Rho GTPases themselves, several of their downstream effectors (including ROCK, mDia, and N-WASP) and upstream regulators (including GEFs, GAPs, PI3K, and PTEN) have also been implicated in primary brain tumors.

  12. Radiofrequency Ablation of Unresectable Primary and Metastatic Hepatic Malignancies

    PubMed Central

    Curley, Steven A.; Izzo, Francesco; Delrio, Paolo; Ellis, Lee M.; Granchi, Jennifer; Vallone, Paolo; Fiore, Francesco; Pignata, Sandro; Daniele, Bruno; Cremona, Francesco

    1999-01-01

    Objective To describe the safety and efficacy of radiofrequency ablation (RFA) to treat unresectable malignant hepatic tumors in 123 patients. Background The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, or multifocality or inadequate functional hepatic reserve. Local application of heat is tumoricidal; therefore, the authors investigated a novel RFA system to treat patients with unresectable hepatic cancer. Patients and Methods Patients with hepatic malignancies were entered into a prospective, nonrandomized trial. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a novel LeVeen monopolar array needle electrode and an RF 2000 generator. All patients were followed to assess complications, treatment response, and recurrence of malignant disease. Results RFA was used to treat 169 tumors (median diameter 3.4 cm, range 0.5 to 12 cm) in 123 patients. Primary liver cancer was treated in 48 patients (39.1%), and metastatic liver tumors were treated in 75 patients (60.9%). Percutaneous and intraoperative RFA was performed in 31 patients (35.2%) and 92 patients (74.8%), respectively. There were no treatment-related deaths, and the complication rate after RFA was 2.4%. All treated tumors were completely necrotic on imaging studies after completion of RFA treatments. With a median follow-up of 15 months, tumor has recurred in 3 of 169 treated lesions (1.8%), but metastatic disease has developed at other sites in 34 patients (27.6%). Conclusions RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated. PMID:10400029

  13. Evaluation of HE4, CA-125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) in the Preoperative Assessment of Patients with Adnexal Mass

    PubMed Central

    Al Musalhi, Khawla; Al Kindi, Manal; Al Aisary, Faiza; Ramadhan, Fatma; Al Rawahi, Thuraya; Al Hatali, Khalsa; Mula-Abed, Waad-Allah

    2016-01-01

    Objectives To evaluate the validity and compare the performance of cancer antigen-125 (CA-125), human epididymis protein 4 (HE4), the risk of malignancy index (RMI), and the risk of ovarian malignancy algorithm (ROMA) in the diagnosis of ovarian cancer in patients with ovarian lesions discovered during their preoperative work-up investigations. Methods This prospective, cross-sectional study looked at patients who attended the gynecology department at the Royal Hospital, Muscat, from 1 March 2014 to 30 April 2015, for the evaluation of an ovarian lesion. The inclusion criteria included women who underwent surgical intervention and who had a preoperative pelvic ultrasound with laboratory investigation for CA-125 and HE4. The study validated the diagnostic performance of CA-125, RMI, HE4, and ROMA using histopathological diagnosis as the gold standard. Results The study population had a total of 213 cases of various types of benign (77%) and malignant (23%) ovarian tumors. CA-125 showed the highest sensitivity (79%) when looking at the total patient population. When divided by age, the sensitivity was 67% in premenopausal women. In postmenopausal women, CA-125 had lower sensitivity (89%) compared to RMI, HE4, and ROMA (93% each). A high specificity of 90% was found for HE4 in the total patient population, 93% in premenopausal women and 75% in postmenopausal women. CA-125 had the highest specificity (79%) in postmenopausal women. Both CA-125 and RMI were frequently elevated in benign gynecological conditions particularly in endometriosis when compared to HE4 and ROMA. We also studied modifications of the optimal cut-offs for the four parameters. Both CA-125 and RMI showed a significant increase in their specificity if the cut-off was increased to ≥ 60 U/mL for CA-125 and to ≥ 250 for RMI. For HE4, we noted an improvement in its specificity in postmenopausal women when its cut-off was increased to140 pmol/L. Conclusions HE4 and ROMA showed a very high specificity

  14. Evaluation of HE4, CA-125, Risk of Ovarian Malignancy Algorithm (ROMA) and Risk of Malignancy Index (RMI) in the Preoperative Assessment of Patients with Adnexal Mass

    PubMed Central

    Al Musalhi, Khawla; Al Kindi, Manal; Al Aisary, Faiza; Ramadhan, Fatma; Al Rawahi, Thuraya; Al Hatali, Khalsa; Mula-Abed, Waad-Allah

    2016-01-01

    Objectives To evaluate the validity and compare the performance of cancer antigen-125 (CA-125), human epididymis protein 4 (HE4), the risk of malignancy index (RMI), and the risk of ovarian malignancy algorithm (ROMA) in the diagnosis of ovarian cancer in patients with ovarian lesions discovered during their preoperative work-up investigations. Methods This prospective, cross-sectional study looked at patients who attended the gynecology department at the Royal Hospital, Muscat, from 1 March 2014 to 30 April 2015, for the evaluation of an ovarian lesion. The inclusion criteria included women who underwent surgical intervention and who had a preoperative pelvic ultrasound with laboratory investigation for CA-125 and HE4. The study validated the diagnostic performance of CA-125, RMI, HE4, and ROMA using histopathological diagnosis as the gold standard. Results The study population had a total of 213 cases of various types of benign (77%) and malignant (23%) ovarian tumors. CA-125 showed the highest sensitivity (79%) when looking at the total patient population. When divided by age, the sensitivity was 67% in premenopausal women. In postmenopausal women, CA-125 had lower sensitivity (89%) compared to RMI, HE4, and ROMA (93% each). A high specificity of 90% was found for HE4 in the total patient population, 93% in premenopausal women and 75% in postmenopausal women. CA-125 had the highest specificity (79%) in postmenopausal women. Both CA-125 and RMI were frequently elevated in benign gynecological conditions particularly in endometriosis when compared to HE4 and ROMA. We also studied modifications of the optimal cut-offs for the four parameters. Both CA-125 and RMI showed a significant increase in their specificity if the cut-off was increased to ≥ 60 U/mL for CA-125 and to ≥ 250 for RMI. For HE4, we noted an improvement in its specificity in postmenopausal women when its cut-off was increased to140 pmol/L. Conclusions HE4 and ROMA showed a very high specificity

  15. Ruxolitinib Phosphate, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-03-21

    Fallopian Tube Carcinosarcoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; 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

  16. Epacadostat Before Surgery in Treating Patients With Newly Diagnosed Stage III-IV Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-03-09

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

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

    ClinicalTrials.gov

    2015-05-22

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

  18. Primary anorectal malignant melanoma: an uncommon anorectal pathology.

    PubMed

    Juanmartiñena Fernández, José Francisco; Fernández-Urien, Ignacio; Córdoba, Alicia

    2016-09-01

    Anorectal malignant melanoma (AMM) is most common primary melanoma of gastrointestinal tract, accounting for 0.05% and 1% of all colorectal and anal cancers. We reported an 85 year-old woman with no significant past medical history who presented two-month period of rectal bleeding, abdominal pain, tenesmus and 2kg weight-loss. Laboratory markers were unremarkable, although rectal examination revealed two small haemorrhoids and a firm, non-obstructing mass in the lower rectum. Colonoscopy confirmed presence of an ulcerated pigmented neoplasm arising at dental line [A,B]. No distant metastases were found on computed tomography [C] although presented metastatic regional lymph nodes on pelvic MRI [D]. Therefore, abdominoperineal resection was performed, confirming loco-regional disease. Histopathology showed malignant melanoma with positive stains in immunohistochemistry for protein S100, HMB-45 and Melan-A [E,F,G,H] and stained negative for c-Kit.

  19. Hormone Treatment Restores Bone Density for Young Women with Menopause-Like Condition (Primary Ovarian Insufficiency)

    MedlinePlus

    ... determine the effects of hormone treatment on bone mineral density of women with primary ovarian insufficiency. Researchers ... insufficiency (POI) led to increases in their bone mineral density, restoring levels to normal. The study was ...

  20. Locomotor proteins in tissues of primary tumors and metastases of ovarian and breast cancer

    NASA Astrophysics Data System (ADS)

    Kondakova, I. V.; Yunusova, N. V.; Spirina, L. V.; Shashova, E. E.; Kolegova, E. S.; Kolomiets, L. A.; Slonimskaya, E. M.; Villert, A. B.

    2016-08-01

    The paper discusses the capability for active movement in an extracellular matrix, wherein remodeling of the cytoskeleton by actin binding proteins plays a significant role in metastases formation. We studied the expression of actin binding proteins and β-catenin in tissues of primary tumors and metastases of ovarian and breast cancer. Contents of p45 Ser β-catenin and the actin severing protein gelsolin were decreased in metastases of ovarian cancer relative to primary tumors. The level of the cofilin, functionally similar to gelsolin, was significantly higher in metastases compared to primary ovarian and breast tumor tissue. In breast cancer, significant increase in the number of an actin monomer binder protein thymosin-β4 was observed in metastases as compared to primary tumors. The data obtained suggest the involvement of locomotor proteins in metastases formation in ovarian and breast cancer.

  1. Benign and malignant ovarian steroid cell tumors, not otherwise specified: case studies, comparison, and review of the literature.

    PubMed

    Jiang, Wei; Tao, Xiang; Fang, Fang; Zhang, Shaofen; Xu, Congjian

    2013-01-01

    Ovarian steroid cell tumors, not otherwise specified (NOS) are rare sex cord-stromal tumors of the ovary with malignant potential. So far only a few cases were reported in English literature through the Pubmed search. Here we report two cases of such tumor, one was benign (first case underwent laparoscopic cystectomy) and the other was malignant (died 10 months later after initial diagnosis), both presented with amenorrhea and clinical signs or symptoms of virilization. In malignant case, we provided evidence (tumor embolus) in addition to the reported five characteristics associated with malignancy. On further evaluation, laboratory investigations revealed hyperandrogenism in the male range, while follicle stimulating hormone (FSH) and luteinising hormone (LH) levels were within normal limits. Various aspects of the presentation, diagnosis, and treatment of these tumors are discussed.

  2. A huge primary ovarian leiomyoma with degenerative changes-an unusual.

    PubMed

    Agrawal, Ranjan; Kumar, Mukta; Agrawal, Lata; Agrawal, Keshav Kumar

    2013-06-01

    Primary ovarian leiomyoma is a rare benign tumour of the ovary, which is seen in women who are aged between 20 years to 65 years. Ovarian leiomyomas can be confused with other spindle cell tumours which display gross anatomical and histological similarities. A case of a primary leiomyoma of the ovary in a pre-menopausal female is being presented here, due to its huge size and unusual presentation.

  3. Ovarian Carcinosarcoma and Its Association with Mature Cystic Teratoma and Primary Tubal Carcinoma

    PubMed Central

    Satabongkoch, Nopporn; Suprasert, Prapaporn; Khunamornpong, Surapan

    2016-01-01

    Introduction. Carcinosarcoma is an uncommon form of ovarian cancers, classified as being part of the group of mixed epithelial and mesenchymal tumors. The occurrence of carcinosarcoma in association with a mature cystic teratoma and synchronous tubal carcinoma is very rare. Case Report. A 69-year-old woman presented with a pelvic mass. An abdominal computerized tomographic scan detected a 15 cm right pelvic mass which was suggestive of malignant transformation of a dermoid cyst. Intraoperative, bilateral ovarian masses (left 10 cm and right 12 cm) with diffuse peritoneal metastatic nodules were identified. Histologically, the left ovarian mass was composed of 2 components including carcinosarcoma and mature cystic teratoma, whereas the right ovarian mass represented a mature cystic teratoma with serosal surface involvement of high-grade serous adenocarcinoma. The left fallopian tube was macroscopically unremarkable but contained a 5.0 mm focus of high-grade serous adenocarcinoma in the distal part, with adjacent serous tubal intraepithelial carcinoma. Conclusion. As the fallopian tube has recently been proposed to be an origin for a majority of pelvic or ovarian high-grade serous adenocarcinomas, tubal carcinoma may be the origin for ovarian carcinosarcomas through an epithelial-mesenchymal transition. The coexistence of ovarian carcinosarcoma and teratoma in the present case should represent a collision tumor. PMID:27807494

  4. Molecular subtypes of serous borderline ovarian tumor show distinct expression patterns of benign tumor and malignant tumor-associated signatures.

    PubMed

    Curry, Edward W J; Stronach, Euan A; Rama, Nona R; Wang, Yuepeng Y P; Gabra, Hani; El-Bahrawy, Mona A

    2014-03-01

    Borderline ovarian tumors show heterogeneity in clinical behavior. Most have excellent prognosis, although a small percentage show recurrence or progressive disease, usually to low-grade serous carcinoma. The aim of this study was to understand the molecular relationship between these entities and identify potential markers of tumor progression and therapeutic targets. We studied gene expression using Affymetrix HGU133plus2 GeneChip microarrays in 3 low-grade serous carcinomas, 13 serous borderline tumors and 8 serous cystadenomas. An independent data set of 18 serous borderline tumors and 3 low-grade serous carcinomas was used for validation. Unsupervised clustering revealed clear separation of benign and malignant tumors, whereas borderline tumors showed two distinct groups, one clustering with benign and the other with malignant tumors. The segregation into benign- and malignant-like borderline molecular subtypes was reproducible on applying the same analysis to an independent publicly available data set. We identified 50 genes that separate borderline tumors into their subgroups. Functional enrichment analysis of genes that separate borderline tumors to the two subgroups highlights a cell adhesion signature for the malignant-like subset, with Claudins particularly prominent. This is the first report of molecular subtypes of borderline tumors based on gene expression profiling. Our results provide the basis for identification of biomarkers for the malignant potential of borderline ovarian tumor and potential therapeutic targets for low-grade serous carcinoma.

  5. 25-Hydroxyvitamin D3 1alpha-hydroxylase splice variants in benign and malignant ovarian cell lines and tissue.

    PubMed

    Fischer, Dorothea; Thomé, Marlene; Becker, Steffi; Cordes, Tim; Diedrich, Klaus; Friedrich, Michael; Thill, Marc

    2009-09-01

    Calcitriol is judged to have a positive effect on control of the immune system, cell growth and differentiation and therefore, the prevention of cancer genesis. The aim of this study was to detect any possible differences in the 25-hydroxyvitamin D-1alpha-hydroxylase (1alphaOHase)-expression between benign and malignant ovarian tissue and cell lines. The analysis was conducted quantitatively, by means of nested "touchdown" PCR and Western blot, and qualitatively, with the use of real-time PCR and Western blot. The gene structure was sequenced. Compared to the benign cell line, the malignant cell lines showed a significantly higher expression of 1alphaOHase at the RNA level. A statistically lower expression of the 1alphaOHase protein was found in the malignant tissue. In the malignant cell lines and tissues, divergent bands were detected, which led to various splice variants on sequencing. Their increased expression in malignancy is possibly bound to the reduction of enzyme activity, which may lead to the genesis of ovarian cancer. In the future, preventive and therapeutic activities may result from these findings. PMID:19667158

  6. Four primary malignant neoplasms in a single patient

    SciTech Connect

    Craig, D.M.; Triedman, L.J.

    1986-05-01

    A 60-year-old Caucasian male, with a previous history of a 10-year occupational exposure to ionizing radiation, chemical carcinogens, and a long history of tobacco and alcohol abuse, developed synchronous squamous cell carcinoma of the floor of the mouth and adenocarcinoma of the lung. Four years later, squamous cell carcinoma of the larynx followed by squamous cell carcinoma of the tongue were diagnosed. In this case report, we suggest that increased exposure to multiple carcinogenic factors may result in an increased incidence of both synchronous and metachronous primary malignant neoplasms.

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

    MedlinePlus

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

  8. Primary and recurrent colorectal cancer masquerading as gynaecological malignancy.

    PubMed

    Brand, A; Scurry, J; Planner, R; Leung, S

    1996-05-01

    To make clinicians more aware of the phenomenon of primary and recurrent colorectal and anal carcinoma masquerading as primary gynaecological malignancy, we reviewed the records of 8 women referred to our gynaecological oncology unit with primary colorectal cancer (1), recurrent colorectal cancer (6) and primary anal cancer (1). Seven of these patients presented with abnormal vaginal bleeding or discharge. All patients had Papanicolaou smears performed; 7 were abnormal and 1 unsuitable for cytological assessment. None of the 6 patients with recurrent carcinoma had been previously treated with more than standard anterior or abdominoperineal resection; no radiotherapy had been given, and only 1 patient had received chemotherapy. These patients were treated in our gynaecological oncology unit for their recurrence by surgery and/or chemotherapy and/or irradiation. All 6 had further recurrences in the pelvis despite this aggressive therapy. Follow-up of colorectal cancer in women should involve gynaecological history, pelvirectal examination and Pap smear at each visit. Correct diagnosis of the colorectal origin of a genital tract tumour is made on careful history, examination and biopsy. An abnormal Pap smear may be the first indication of recurrent colorectal cancer in the cervix and vagina, although most patients ultimately present with abnormal vaginal bleeding. The presence of a tumour invading both cervix and posterior vaginal wall is suggestive of spread from a colorectal tumour compared to the more common lateral spread of a cervical primary.

  9. Sensitivity and resistance to treatment in the primary management of epithelial ovarian cancer.

    PubMed

    Colombo, Pierre-Emmanuel; Fabbro, Michel; Theillet, Charles; Bibeau, Frédéric; Rouanet, Philippe; Ray-Coquard, Isabelle

    2014-02-01

    Ovarian carcinoma is the most lethal gynaecologic malignancy. Despite wide initial sensibility to chemotherapy especially to platinum-based regimens, the vast majority of patients with advanced stages of the disease develop recurrences and subsequent resistance to treatments. Ovarian cancer is actually considered as a heterogeneous disease at the clinical, histological and molecular level. In this review, the mechanisms of intrinsic sensitivity or resistance to treatment, especially to platinum-based chemotherapy are considered with particular reference to the significance of tumour heterogeneity. The molecular features involved in acquired resistance are reviewed and the current hypotheses are discussed. In particular, potential disruptions of the DNA reparation pathways are highlighted.

  10. Paclitaxel, Polyglutamate Paclitaxel, or Observation in Treating Patients With Stage III or Stage IV Ovarian Epithelial, Peritoneal Cancer, or Fallopian Tube Cancer

    ClinicalTrials.gov

    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

  11. Mutations of the KIT gene and loss of heterozygosity of the PTEN region in a primary malignant melanoma arising from a mature cystic teratoma of the ovary.

    PubMed

    Tate, Genshu; Tajiri, Takuma; Suzuki, Takao; Mitsuya, Toshiyuki

    2009-04-01

    A tumor suppressor gene at 10q23.3, designated PTEN, encoding a dual-specificity phosphatase with lipid and protein phosphatase activity, has been shown to play a pivotal role in the pathogenesis of a variety of human cancers. A frequent loss of heterozygosity (LOH) at 10q is found in melanoma; however, little is known about the role of PTEN in the pathogenesis of a primary malignant melanoma derived from ovarian mature cystic teratoma, which is an extremely rare melanoma. This study examined the genetic alterations involved in the mitogen-activated protein kinase and phosphatidylinositol 3 kinase pathways in an ovarian malignant melanoma. A LOH analysis revealed hemizygous deletion around and in the PTEN gene not only in the ovarian melanoma but also in a mature cystic teratoma. Another case of ovarian mature cystic teratomas in the absence of melanoma also showed allelic loss of the PTEN region. To date, mutations of BRAF, NRAS, and KIT genes have been reported in malignant melanomas. In the present study, D816H and K558E mutations of the KIT gene were revealed in the melanoma arising from a mature cystic teratoma, but not in a mature cystic teratoma. No mutations of the BRAF and NRAS genes were found in the melanoma. These results indicate that LOH of the PTEN region is one of the molecular alterations of an ovarian mature cystic teratoma and a KIT mutation is an additional promotional event associated with the oncogenesis of a melanoma arising from an ovarian mature cystic teratoma.

  12. Limitations of the clonal agar assay for the assessment of primary human ovarian tumour biopsies.

    PubMed Central

    Bertoncello, I.; Bradley, T. R.; Campbell, J. J.; Day, A. J.; McDonald, I. A.; McLeish, G. R.; Quinn, M. A.; Rome, R.; Hodgson, G. S.

    1982-01-01

    114 biopsy specimens from 70 patients with ovarian carcinoma at all stages of disease were submitted for assessment of clonogenic capacity in agar. A highly significant correlation was found between agar clonogenicity and patient survival after biopsy. However, problems related to inherent tumour heterogeneity, quality of sample and tissue disaggregation indicate that this technique may have limited applicability in the routine assessment of patients. Only 41 biopsy specimens (36%) from 31 patients (44.3%) complied with the prerequisite criteria for agar clonogenic assessment, namely: (a) the confirmed presence of malignant cells in the biopsy, (b) the ability to prepare a single-cell suspension, and (c) adequate viable cell numbers for assay. Furthermore, although the dominant patterns of agar clonogenic growth could be identified and correlated with stage of disease, the heterogeneity in both initial clonogenic capacity and "self-renewal" capacity assessed by the ability of primary clones to propagate in liquid culture and reclone in agar was too inconsistent for the assay to be used as a prognostic index for the individual patient. Images Figure PMID:7093117

  13. Primary Malignant Melanoma of the Esophagus With Unusual Endoscopic Findings

    PubMed Central

    Liu, Hui; Yan, Yan; Jiang, Chun-Meng

    2016-01-01

    Abstract Primary malignant melanoma of the esophagus (PMME) is a rare disease with an extremely poor prognosis. We experienced a 79-year-old man with PMME who had unusual endoscopic findings. On endoscopy, an elongated lump was detected on 1 side of the vertical axis of the esophagus. The mass extended progressively for 15 cm along the esophageal longitudinal axis and invaded half of the esophageal circumference. These endoscopic findings were not characteristic of PMME, and the condition was confirmed with biopsy and immunohistochemical staining. Here, we present this rare case and review the recent relevant literature regarding PMME. Doctors should be aware that PMME might present with unusual endoscopic findings. PMID:27124046

  14. Primary malignant non-hodgkin lymphoma of the talus.

    PubMed

    Bansal, Saurabh; Dharra, Neetu

    2015-01-01

    Primary bone lymphoma (PBL) is a relatively uncommon entity. It represents approximately 5% of all non-Hodgkin lymphomas (NHLs) and 3% of all bone malignancies. The femur, tibia, and pelvis are the most common skeletal sites involved. It can occur at any age, with a peak incidence in the fourth and fifth decades.The most common grade identified is intermediate, followed by low-grade lesions. It can mimic other disease processes, especially infection. So, thorough and prompt investigatory workup is essential for adequate treatment. Localized disease responds well to combined modality treatment with chemotherapy and radiotherapy and is associated with good prognosis. We discuss the clinical findings, diagnosis, and treatment in a case of PBL involving the talus. This is an unique clinical presentation owing to its unusual site. PMID:26458619

  15. Primary malignant chest wall tumors: analysis of 40 patients

    PubMed Central

    2014-01-01

    Background Primary chest wall tumors originate from different constructions of thoracic wall. We report our multidisciplinary experience on primary thoracic tumor resection and thoracic reconstruction, the need to additional therapy and evaluating prognostic factors affecting survival. Methods We performed a retrospective review of our prospectively maintained database of 40 patients treated for malignant primary chest wall tumor from 1989 to 2009. Patients were evaluated in terms of age, sex, clinical presentation, type of imaging, tissue diagnosis methods, pathology, surgical technique, early complications, hospital mortality, prevalence of recurrence and distant metastases, additional treatment, 3 years survival and factors affecting survival. Results Male/Female (F/M) = 1, with median age of 43.72 years. Mass was the most common symptoms and the soft tissue sarcoma was the most common pathology. Resection without reconstruction was performed in 5 patients and Thirty-five patients (87.5%) had extensive resection and reconstruction with rotatory muscular flap, prosthetic mesh and/or cement. Overall, 12.5% (5/40) of patients received neoadjuvant therapy and 75% (30/40) of patients were treated with adjuvant therapy. The 3-year survival rate was 65%. Recurrences occurred in 24 patients (60%), 14 developed local recurrences, and 10 developed distant metastases. The primary treatment modality for both local and distant recurrences was surgical resection; among them, 10 underwent repeated resection, 9 adjuvant therapy and 5 were treated with lung metastasectomy. The most common site of distant metastasis was lung (n = 7). Factors that affected survival were type of pathology and evidence of distant metastasis. Conclusion Surgery with wide margin is the safe and good technique for treatment of primary chest wall tumors with acceptable morbidity and mortality. PMID:24947314

  16. Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis

    PubMed Central

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E.; Alagaratnam, Sharmini; Skotheim, Rolf I.; Abeler, Vera M.

    2013-01-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  17. Molecular characteristics of malignant ovarian germ cell tumors and comparison with testicular counterparts: implications for pathogenesis.

    PubMed

    Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E; Alagaratnam, Sharmini; Skotheim, Rolf I; Abeler, Vera M; Rajpert-De Meyts, Ewa; Lothe, Ragnhild A

    2013-06-01

    This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/β-catenin and TGF-β/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

  18. A novel somatic MAPK1 mutation in primary ovarian mixed germ cell tumors.

    PubMed

    Zou, Yang; Deng, Wei; Wang, Feng; Yu, Xiao-Hong; Liu, Fa-Ying; Yang, Bi-Cheng; Huang, Mei-Zhen; Guo, Jiu-Bai; Xie, Qiu-Hua; He, Ming; Huang, Ou-Ping

    2016-02-01

    A recent exome-sequencing study revealed prevalent mitogen-activated protein kinase 1 (MAPK1) p.E322K mutation in cervical carcinoma. It remains largely unknown whether ovarian carcinomas also harbor MAPK1 mutations. As paralogous gene mutations co‑occur frequently in human malignancies, we analyzed here a total of 263 ovarian carcinomas for the presence of MAPK1 and paralogous MAPK3 mutations by DNA sequencing. A previously unreported MAPK1 p.D321N somatic mutation was identified in 2 out of 18 (11.1%) ovarian mixed germ cell tumors, while no other MAPK1 or MAPK3 mutation was detected in our samples. Of note, OCC‑115, the MAPK1‑mutated sample with bilateral cancerous ovaries affected, harbored MAPK1 mutation in the right ovary while retained the left ovary intact, implicating that the genetic alterations underlying ovarian mixed germ cell tumor may be different, even in patients with similar genetic backgrounds and tumor microenvironments. The results of evolutionary conservation and protein structure modeling analysis implicated that MAPK1 p.D321N mutation may be pathogenic. Additionally, mutations in protein phosphatase 2 regulatory subunit α (PPP2R1A), ring finger protein 43 (RNF43), DNA directed polymerase ε (POLE1), ribonuclease type III (DICER1), CCCTC‑binding factor (CTCF), ribosomal protein L22 (RPL22), DNA methyltransferase 3α (DNMT3A), transformation/transcription domain‑associated protein (TRRAP), isocitrate dehydrogenase (IDH)1 and IDH2 were not detected in ovarian mixed germ cell tumors, implicating these genetic alterations may be not associated with MAPK1 mutation in the development of this malignancy. The present study identified a previously unreported MAPK1 mutation in ovarian mixed germ cell tumors for the first time, and this mutation may be actively involved in the tumorigenesis of this disease.

  19. Multiple Primary Malignancies in Patients With Hepatocellular Carcinoma

    PubMed Central

    Xu, Wei; Liao, Wenjun; Ge, Penglei; Ren, Jinjun; Xu, Haifeng; Yang, Huayu; Sang, Xinting; Lu, Xin; Mao, Yilei

    2016-01-01

    Abstract Multiple primary malignancies (MPMs) are defined as 2 or more malignancies without subordinate relationship detected in different organs of an individual patient. Reports addressing MPM patients with hepatocellular carcinoma (HCC) are rare. We perform a 26-year follow-up study to investigate characteristics and prognosis of MPM patients associated with HCC due to the scarcity of relative researches. We retrospectively analyzed records of 40 patients who were diagnosed with MPM including HCC at the Departments of Surgery at Peking Union Medical College Hospital during 1989 to 2010. Their clinical characteristics and postoperative survival were compared with those of 448 patients who had HCC only during the study period. Among the 40 MPM patients, 11 were diagnosed synchronously and 29 metachronously. The most common extra-hepatic malignancies were lung cancer (15%), colorectal (12.5%), and thyroid carcinoma (12.5%). MPM patients had a negative hepatitis B virus infection rate (P = 0.013) and lower median alfa-fetoprotein (AFP) level (P = 0.001). Post-operative 1-, 3-, and 5-year overall survival (OS) rates for MPM patients were 82.5%, 64.5%, and 38.6% respectively, and showed no significant difference with those of HCC-only patients (84.7%, 54.2%, and 38.3% P = 0.726). During follow-up, 24 MPM patients died, including 17 (70.8%) who died of HCC-related causes. In univariate analysis, synchronous diagnosis, higher gamma glutamyltransferase (GGT) and/or AFP levels, tumor >5 cm and vascular invasion were significantly associated with shorter OS, but only tumor size was an independent OS factor in Cox modeling analysis. HCC should be considered as a potential second primary for all cancer survivors. Most MPM patients died of HCC-related causes and showed no significant difference in OS compared with HCC-only patients. Tumor size of HCC, rather than MPMs itself, was the only independent OS predictor for the MPM patients. PMID:27124050

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

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for ovarian cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  1. Primary Ovarian Insufficiency Induced by Fanconi Anemia E Mutation in a Mouse Model.

    PubMed

    Fu, Chun; Begum, Khurshida; Overbeek, Paul A

    2016-01-01

    In most cases of primary ovarian insufficiency (POI), the cause of the depletion of ovarian follicles is unknown. Fanconi anemia (FA) proteins are known to play important roles in follicular development. Using random insertional mutagenesis with a lentiviral transgene, we identified a family with reduced fertility in the homozygous transgenic mice. We identified the integration site and found that the lentivirus had integrated into intron 8 of the Fanconi E gene (Fance). By RT-PCR and in situ hybridization, we found that Fance transcript levels were significantly reduced. The Fance homozygous mutant mice were assayed for changes in ovarian development, follicle numbers and estrous cycle. Ovarian dysplasias and a severe lack of follicles were seen in the mutant mice. In addition, the estrous cycle was disrupted in adult females. Our results suggest that POI has been induced by the Fance mutation in this new mouse model.

  2. Primary Ovarian Insufficiency Induced by Fanconi Anemia E Mutation in a Mouse Model

    PubMed Central

    Fu, Chun; Begum, Khurshida; Overbeek, Paul A.

    2016-01-01

    In most cases of primary ovarian insufficiency (POI), the cause of the depletion of ovarian follicles is unknown. Fanconi anemia (FA) proteins are known to play important roles in follicular development. Using random insertional mutagenesis with a lentiviral transgene, we identified a family with reduced fertility in the homozygous transgenic mice. We identified the integration site and found that the lentivirus had integrated into intron 8 of the Fanconi E gene (Fance). By RT-PCR and in situ hybridization, we found that Fance transcript levels were significantly reduced. The Fance homozygous mutant mice were assayed for changes in ovarian development, follicle numbers and estrous cycle. Ovarian dysplasias and a severe lack of follicles were seen in the mutant mice. In addition, the estrous cycle was disrupted in adult females. Our results suggest that POI has been induced by the Fance mutation in this new mouse model. PMID:26939056

  3. Primary Retroperitoneal Melanoma Presented in a Rare Extracutaneous Site for Malignant Melanoma

    PubMed Central

    Alsharedi, Mohamed; Zgheib, Nadim Bou; Khelfa, Yousef; Raufi, Ali; Elmsherghi, Nabiha; Lebowicz, Yehuda

    2016-01-01

    Malignant melanoma, as the name implies, is a malignant tumor of melanocytes, found in the skin, eyes, meningeal lining and the mucosal epithelium of the aero-digestive and genitourinary tracts. Malignant melanoma is typically skin malignancy, which rarely presents at extracutaneous site. Here we present a rare case of primary retroperitoneal melanoma and review the findings in comparison with other cases described in literature. PMID:27746882

  4. Metastatic Malignant Melanoma of Parotid Gland with a Regressed Primary Tumor

    PubMed Central

    Aynali, Giray; Ceyhan, Ali Murat; Çiriş, Metin

    2016-01-01

    Malignant melanoma of the parotid gland is often metastatic and mainly originates from malignant melanomas in the head and neck. Nevertheless, some malignant melanomas may metastasize and subsequently regress. Therefore, it may not be possible to observe a metastatic malignant melanoma and its primary melanoma simultaneously. The investigation of a patient's old photographs may help in the detection of preexisting and regressed pigmented lesions in the facial and neck regions. PMID:27478668

  5. A successful laparoscopic neovaginoplasty using peritoneum in Müllerian agenesis with inguinal ovaries accompanied by primary ovarian insufficiency

    PubMed Central

    Gweon, Seonghye; Lee, Jisun; Hwang, Suna; Hwang, Kyoung Joo

    2016-01-01

    The combination of Müllerian agenesis with inguinal ovaries accompanied by primary ovarian insufficiency is extremely rare. A 21-year-old Korean woman was referred to our center with primary amenorrhea. The patient was diagnosed with Müllerian agenesis with inguinal ovaries. Her hormonal profile showed hypergonadotrophic hypogonadism suggesting primary ovarian insufficiency. We performed laparoscopic neovaginoplasty using modified Davydov's procedure and reposition inguinal ovaries in the pelvic cavity. Oral estrogen replacement was applied for the treatment of primary ovarian insufficiency. This is a rare case report on Mayer-Rokitansky-Kuster-Hauser syndrome accompanied not only by inguinal ovaries but also with primary ovarian insufficiency. We present our first experience on the laparoscopic neovaginoplasty performed on the patient with müllerian agenesis accompanied by inguinal ovaries and primary ovarian insufficiency. PMID:27462606

  6. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report.

    PubMed

    Orsi, Nicolas M; Menon, Mini

    2016-08-01

    Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10-12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade), arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area. PMID:27508272

  7. Genetics of primary ovarian insufficiency: new developments and opportunities

    PubMed Central

    Qin, Yingying; Jiao, Xue; Simpson, Joe Leigh; Chen, Zi-Jiang

    2015-01-01

    BACKGROUND Primary ovarian insufficiency (POI) is characterized by marked heterogeneity, but with a significant genetic contribution. Identifying exact causative genes has been challenging, with many discoveries not replicated. It is timely to take stock of the field, outlining the progress made, framing the controversies and anticipating future directions in elucidating the genetics of POI. METHODS A search for original articles published up to May 2015 was performed using PubMed and Google Scholar, identifying studies on the genetic etiology of POI. Studies were included if chromosomal analysis, candidate gene screening and a genome-wide study were conducted. Articles identified were restricted to English language full-text papers. RESULTS Chromosomal abnormalities have long been recognized as a frequent cause of POI, with a currently estimated prevalence of 10–13%. Using the traditional karyotype methodology, monosomy X, mosaicism, X chromosome deletions and rearrangements, X-autosome translocations, and isochromosomes have been detected. Based on candidate gene studies, single gene perturbations unequivocally having a deleterious effect in at least one population include Bone morphogenetic protein 15 (BMP15), Progesterone receptor membrane component 1 (PGRMC1), and Fragile X mental retardation 1 (FMR1) premutation on the X chromosome; Growth differentiation factor 9 (GDF9), Folliculogenesis specific bHLH transcription factor (FIGLA), Newborn ovary homeobox gene (NOBOX), Nuclear receptor subfamily 5, group A, member 1 (NR5A1) and Nanos homolog 3 (NANOS3) seem likely as well, but mostly being found in no more than 1–2% of a single population studied. Whole genome approaches have utilized genome-wide association studies (GWAS) to reveal loci not predicted on the basis of a candidate gene, but it remains difficult to locate causative genes and susceptible loci were not always replicated. Cytogenomic methods (array CGH) have identified other regions of interest

  8. Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

    PubMed Central

    Garg, Abhishek D.; De Ruysscher, Dirk; Agostinis, Patrizia

    2016-01-01

    ABSTRACT The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale meta-analysis involving 3,983 patients (‘discovery’ dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in ‘validation’ datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICD-derived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) ‘attracted’ highly co-expressing sets of genes or convergent-metagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an ‘attractor’ for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a

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

    ClinicalTrials.gov

    2016-07-25

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

  10. [ULTRASOUND CRITERIA OR THE OPERABILITY AND EFFICACY OF THE TREATMENT OF THE MALIGNANT EPITHELIAL OVARIAN TUMOURS].

    PubMed

    Shkarbun, K D; Shkarbun, L I

    2015-01-01

    In order to isolate the main sonographic criteria of ovarian cancer operability the dynamical U.S. examination was performed on 65 women with epithelial tumors of II-III stages before and during 5 years after treatment beginning, which included (in different combinations) cytoreductive surgery and neoadjuvant chemotherapy. Only total 14 (21.5%) relapses were revealed. The U.S. prognostic criteria of the ovarian cancer treatment efficacy with and without neoadjuvant chemotherapy were defined. PMID:27491160

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

    ClinicalTrials.gov

    2016-05-02

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

  12. Fatty acid synthase is a metabolic marker of cell proliferation rather than malignancy in ovarian cancer and its precursor cells.

    PubMed

    Veigel, Daniel; Wagner, Renate; Stübiger, Gerald; Wuczkowski, Michael; Filipits, Martin; Horvat, Reinhard; Benhamú, Bellinda; López-Rodríguez, María Luz; Leisser, Asha; Valent, Peter; Grusch, Michael; Hegardt, Fausto G; García, Jordi; Serra, Dolors; Auersperg, Nelly; Colomer, Ramón; Grunt, Thomas W

    2015-05-01

    Ovarian cancer (OC) is caused by genetic aberrations in networks that control growth and survival. Importantly, aberrant cancer metabolism interacts with oncogenic signaling providing additional drug targets. Tumors overexpress the lipogenic enzyme fatty acid synthase (FASN) and are inhibited by FASN blockers, whereas normal cells are FASN-negative and FASN-inhibitor-resistant. Here, we demonstrate that this holds true when ovarian/oviductal cells reside in their autochthonous tissues, whereas in culture they express FASN and are FASN-inhibitor-sensitive. Upon subculture, nonmalignant cells cease growth, express senescence-associated β-galactosidase, lose FASN and become FASN-inhibitor-resistant. Immortalized ovarian/oviductal epithelial cell lines—although resisting senescence—reveal distinct growth activities, which correlate with FASN levels and FASN drug sensitivities. Accordingly, ectopic FASN stimulates growth in these cells. Moreover, FASN levels and lipogenic activities affect cellular lipid composition as demonstrated by thin-layer chromatography. Correlation between proliferation and FASN levels was finally evaluated in cancer cells such as HOC-7, which contain subclones with variable differentiation/senescence and corresponding FASN expression/FASN drug sensitivity. Interestingly, senescent phenotypes can be induced in parental HOC-7 by differentiating agents. In OC cells, FASN drugs induce cell cycle blockade in S and/or G2/M and stimulate apoptosis, whereas in normal cells they only cause cell cycle deceleration without apoptosis. Thus, normal cells, although growth-inhibited, may survive and recover from FASN blockade, whereas malignant cells get extinguished. FASN expression and FASN drug sensitivity are directly linked to cell growth and correlate with transformation/differentiation/senescence only indirectly. FASN is therefore a metabolic marker of cell proliferation rather than a marker of malignancy and is a useful target for future drug

  13. Assessing the Risk of Ovarian Malignancy in Asymptomatic Women With Abnormal CA 125 and Transvaginal Ultrasound in the Prostate, Lung, Colorectal, and Ovarian Screening Trial

    PubMed Central

    Partridge, Edward E.; Greenlee, Robert T.; Riley, Thomas L.; Commins, John; Ragard, Lawrence; Xu, Jian-Lun; Buys, Saundra S.; Prorok, Philip C.; Fouad, Mona N.

    2012-01-01

    Objective To estimate the risk of ovarian malignancy among asymptomatic women with abnormal transvaginal ultrasound or CA 125 and to provide guidance to physicians managing these women. Methods A cohort of women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial with abnormal ovarian results at the initial (T0) and subsequent (T1+) screens were analyzed to estimate which findings were associated with high risk of ovarian cancer. Risks of cancer of greater than 10% were designated as high and risks of 3% or less as low. Results For the T0 screen, two high-risk categories were identified: CA 125 of 70 or more with negative transvaginal ultrasound (positive predictive value [PPV] 15.9%, CI 14.7%–17.7%); and positive for both CA 125 and transvaginal ultrasound (PPV 25.0%, CI 23.3%–27.3%). For T1+ screens, three high-risk categories were identified: negative transvaginal ultrasound with change in CA 125 greater than 45 or more (PPV 29.0%, CI 28.3%–30.3%); increase in size of cyst 6 cm or greater with negative CA 125 (PPV 13.3%, CI 10.5%–18.0%); and positive for both tests (PPV 42.9%, CI 40.0%–46.0%). High-risk criteria for T0 provide a sensitivity of 60%, specificity 96.2%, PPV 19.7%, and a negative predictive value (NPV) of 99.3%. T1+ criteria yielded a sensitivity of 85.3%, specificity 95.6%, PPV 29.6% and NPV 99.7%. Conclusions High risk categories for predicting risk of cancer in women with abnormal CA 125, TVU or both at initial and subsequent screens have been identified. The large number of women in this study, the four year complete follow-up, and very small number of invasive cancers in the low risk categories provides guidance for clinical decisions regarding need for surgery in these women. PMID:23262924

  14. Primary ovarian serous adenocarcinoma with ipsilateral axillary lymph node metastasis: a case report.

    PubMed

    Saxena, Avanish Kumar; Goyal, Nitin; Singhal, Juhi; Kumar, Parveen

    2014-09-01

    Axillary lymph node metastasis from primary ovarian cancer is rare. Here, we reporting a unique case of 45 years old who presented with axillary lymph node metastasis which was thought from breast carcinoma but it turned out to be due to ovarian serous adenocarcinoma confirmed by histopathology & immunohistochemistry. Staging laparotomy (IIIc) with hysterectomy with bilateral salpingo-oophorectomy was done. Post-operatively, the patient was given adjuvant chemotherapy. No local or systemic recurrence was noted during 1 year follow up period. PMID:25419072

  15. Primary Anastomosis versus Ostomy after Colon Resection during Debulking of Ovarian Carcinomatosis: A NSQIP Analysis.

    PubMed

    Fleetwood, Vidya A; Kubasiak, John C; Janssen, Imke; Myers, Jonathan A; Millikan, Keith W; Deziel, Daniel J; Luu, Minh B

    2016-04-01

    Ovarian carcinomatosis poses a dilemma for the surgeon. When resecting colon for tumor invasion, one must decide between diversion and primary anastomosis (PA). We examined the National Surgical Quality Improvement Program to determine whether PA associated with more complications than ostomy. The National Surgical Quality Improvement Program dataset was queried for patients with ovarian carcinomatosis between 2007 and 2012. Current Procedural Terminology codes were used to further identify patients undergoing colectomy with PA or ostomy. Logistic regression was used to evaluate 30-day morbidity and mortality. The 1013 ovarian carcinomatosis patients who underwent elective colon surgery were divided into primary repair (n = 453, 43.5%) or ostomy (n = 586, 56.5%) groups. Preoperative demographics were similar; however, ostomy patients had more severe preoperative laboratory derangements. The 30-day mortality and postoperative transfusion requirements were higher in the ostomy group. On multivariate analysis controlling for confounders, the differences were no longer significant. In conclusion, 30-day mortality and postoperative complications were increased in the ostomy group. Given the laboratory derangements in this group, this may reflect tendency to allocate ostomies to more ill patients. Primary repair in a selected population does not worsen outcomes. Prospective evaluation would help determine the impact of PA in the ovarian carcinomatosis population.

  16. The time is now for a new approach to primary ovarian insufficiency

    PubMed Central

    Cooper, Amber R.; Baker, Valerie L.; Sterling, Evelina W.; Ryan, Mary E.; Woodruff, Teresa K.; Nelson, Lawrence M.

    2010-01-01

    Objective To articulate the need for a new approach to primary ovarian insufficiency. The condition, also known as premature menopause or premature ovarian failure, is defined by the presence of menopausal-level serum gonad otropins in association with irregular menses in adolescent girls or women younger than 40 years. It can be iatrogenic as related to cancer therapy or may arise spontaneously, either alone or as part of a host of ultrarare syndromes. In a large percentage of spontaneous cases no pathogenic mechanism can be identified. Design Literature review and consensus building at a multidisciplinary scientific workshop. Conclusion(s) There are major gaps in knowledge regarding the etiologic mechanisms, psychosocial effects, natural history, and medical and psychosocial management of primary ovarian insufficiency. An international research consortium and disease registry formed under the guidance of an umbrella organization would provide a pathway to comprehensively increase basic and clinical knowledge about the condition. Such a consortium and patient registry also would provide clinical samples and clinical data with a goal toward defining the specific pathogenic mechanisms. An international collaborative approach that combines the structure of a patient registry with the principles of integrative care and community-based participatory research is needed to advance the field of primary ovarian insufficiency. PMID:20188353

  17. Malignant and benign ovarian neoplasms among atomic bomb survivors, Hiroshima and Nagasaki, 1950-80.

    PubMed

    Tokuoka, S; Kawai, K; Shimizu, Y; Inai, K; Ohe, K; Fujikura, T; Kato, H

    1987-07-01

    For 1950-80, 194 ovarian cancer cases were ascertained among the 70,030 females of the Radiation Effects Research Foundation's Life-Span Study E-85 sample, and 106 autopsied cases with benign ovarian neoplasms were ascertained among all 3,046 autopsies performed in the same sample. On the basis of microscopic review, 66% of the cancer and 84% of the benign tumor cases were classified by histologic type. The age-adjusted ovarian cancer incidence rates showed a statistically significant increase with increased exposure dose, both in the entire exposed group (P less than .01) and in the microscopically reviewed subset (P less than .01). This dose response was only significant (P less than .01) in the latter half of the study period, 1965-80. The radiation effect was higher in the younger age group at the time of the bomb (ATB) for the specific attained age or was adjusted for attained age. In general, relative risk (greater than or equal to 100 rad vs. 0 rad) did not differ by attained age, except for the youngest age group, less than 20 years old ATB, where the relative risk tended to decrease with increased attained age, although cases were few in number and follow-up study was necessary. Estimated minimum latent period for radiation-induced ovarian cancer seemed to be 15-20 years. The proportion of autopsied cases with benign ovarian tumor increased with increasing exposure dose, both in the entire series of cases (P less than .05) and in the microscopically reviewed subset. Statistical significance, however, was not achieved in the latter group (P greater than .10). The distribution of histologic types of both cancer and benign tumor of the ovary did not vary significantly with radiation dose. The data are consistent with the hypothesis that radiation injury of the ovaries and secondary excess of gonadotropic hormones are important causative factors in the development of ovarian neoplasms.

  18. Primary Peritoneal Hydatid Cyst Presenting as Ovarian Cyst Torsion: A Rare Case Report.

    PubMed

    Gandhiraman, Kavitha; Balakrishnan, Renukadevi; Ramamoorthy, Rathna; Rajeshwari, Raja

    2015-08-01

    Hydatid cyst disease is a zoonotic disease caused by Echinococcus granulosus, E.multilocularis or E.Vogli. The most common primary site is liver (75%) followed by lungs (5-15%) and other organs constitute 10-20%. Peritoneal hydatid cysts are very rare especially primary peritoneal hydatid. Secondary peritoneal hydatid cysts are relatively common, which usually occurs due to rupture of primary hepatic hydatid cyst. We present a rare case of large primary peritoneal hydatid cyst misdiagnosed as torsion of ovarian cyst that underwent Laparotomy with cyst excision and postoperative Albendazole therapy. PMID:26436004

  19. Chromosome 3 anomalies investigated by genome wide SNP analysis of benign, low malignant potential and low grade ovarian serous tumours.

    PubMed

    Birch, Ashley H; Arcand, Suzanna L; Oros, Kathleen K; Rahimi, Kurosh; Watters, A Kevin; Provencher, Diane; Greenwood, Celia M; Mes-Masson, Anne-Marie; Tonin, Patricia N

    2011-01-01

    Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive

  20. Chromosome 3 Anomalies Investigated by Genome Wide SNP Analysis of Benign, Low Malignant Potential and Low Grade Ovarian Serous Tumours

    PubMed Central

    Birch, Ashley H.; Arcand, Suzanna L.; Oros, Kathleen K.; Rahimi, Kurosh; Watters, A. Kevin; Provencher, Diane; Greenwood, Celia M.; Mes-Masson, Anne-Marie; Tonin, Patricia N.

    2011-01-01

    Ovarian carcinomas exhibit extensive heterogeneity, and their etiology remains unknown. Histological and genetic evidence has led to the proposal that low grade ovarian serous carcinomas (LGOSC) have a different etiology than high grade carcinomas (HGOSC), arising from serous tumours of low malignant potential (LMP). Common regions of chromosome (chr) 3 loss have been observed in all types of serous ovarian tumours, including benign, suggesting that these regions contain genes important in the development of all ovarian serous carcinomas. A high-density genome-wide genotyping bead array technology, which assayed >600,000 markers, was applied to a panel of serous benign and LMP tumours and a small set of LGOSC, to characterize somatic events associated with the most indolent forms of ovarian disease. The genomic patterns inferred were related to TP53, KRAS and BRAF mutations. An increasing frequency of genomic anomalies was observed with pathology of disease: 3/22 (13.6%) benign cases, 40/53 (75.5%) LMP cases and 10/11 (90.9%) LGOSC cases. Low frequencies of chr3 anomalies occurred in all tumour types. Runs of homozygosity were most commonly observed on chr3, with the 3p12-p11 candidate tumour suppressor region the most frequently homozygous region in the genome. An LMP harboured a homozygous deletion on chr6 which created a GOPC-ROS1 fusion gene, previously reported as oncogenic in other cancer types. Somatic TP53, KRAS and BRAF mutations were not observed in benign tumours. KRAS-mutation positive LMP cases displayed significantly more chromosomal aberrations than BRAF-mutation positive or KRAS and BRAF mutation negative cases. Gain of 12p, which harbours the KRAS gene, was particularly evident. A pathology review reclassified all TP53-mutation positive LGOSC cases, some of which acquired a HGOSC status. Taken together, our results support the view that LGOSC could arise from serous benign and LMP tumours, but does not exclude the possibility that HGOSC may derive

  1. Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma: evidence of up-regulated Tn and Sialyl Tn antigen expression in effusions.

    PubMed

    Davidson, B; Berner, A; Nesland, J M; Risberg, B; Kristensen, G B; Tropé, C G; Bryne, M

    2000-09-01

    The object of this study was the investigation of carbohydrate antigen expression in malignant epithelial cells and benign mesothelial cells in serous effusions from patients diagnosed with epithelial ovarian carcinomas. In addition, to compare antigen expression in carcinoma cells in effusions with those of corresponding primary tumors and metastatic lesions. Sections from 63 malignant effusions from ovarian carcinoma patients and 15 reactive effusions were immunohistochemically stained, using 5 monoclonal antibodies for Lewis(y), Sialyl Lewis(x), Tn, and Sialyl Tn antigens. Tissue sections (n = 97) from corresponding primary ovarian carcinomas and metastatic lesions, as well as from 12 malignant mesotheliomas, were additionally stained using the above panel. Staining for the 4 antigens was seen in carcinoma cells in serous effusions in the majority of cases (range = 71% to 85%). In contrast, immunoreactivity was detected in mesothelial cells in only 6% to 23% of the specimens studied (P < .001 for all 5 markers). With the exception of B3 antibody against Lewis(y) antigen, malignant mesotheliomas stained negative, infrequently showing focal immunoreactivity. An up-regulation of Tn and Sialyl Tn expression was detected in carcinoma cells in effusions when compared with both primary tumors (P < .003 and P < .007, respectively) and metastatic lesions (P < .034 and .041, respectively). Cancer-associated carbohydrate antigens can thus be used as an adjunct in the differentiation between malignant epithelial and reactive mesothelial cells. Ovarian carcinoma cells in effusions show up-regulation of Tn and Sialyl Tn, possibly representing a transient phenotypic alteration facilitating metastasis. PMID:11014575

  2. Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-01-07

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

  3. Pattern of tissue expression of CA-125 and HE4 in primary epithelial ovarian tumours and correlation with serum CA-125 levels.

    PubMed

    Devan, Shobana Mukunda; Pailoor, Jayalakshmi; Sthaneshwar, Pavai; Narayanan, Vallikkanu

    2013-01-01

    The objective of this study is to assess tissue expression of CA-125 and HE4 protein in primary benign and malignant epithelial tumours of the ovary and correlate with serum CA-125 levels. A total of 100 formalin-fixed, paraffin embedded sections of ovarian tumours which included serous adenoma (11), mucinous adenoma (42), serous carcinoma (20), mucinous carcinoma (12) and endometrioid carcinoma (15), histologically diagnosed between 1st January 2004 to 31st December 2012 at the University Malaya Medical Centre, were stained for HE4 (rabbit polyclonal antibody, Abcam, UK) and CA-125 (mouse monoclonal antibody clone: OC125, Cell Marque Corporation, Rocklin, California, USA). Pre-operative serum CA-125 levels were obtained from the laboratory information system. Immunoscore (I score) for HE4 and CA-125 was given based on the intensity of staining and percentage of positive tumour cells and considered significant when it was >50 (intensity of staining multiplied by percentage of positive tumour cells). Serum CA-125 levels were compared with the I score of HE4 and CA-125 in tissues. We noted that the CA-125 levels in serum and tissues were significantly raised in malignant compared to benign ovarian tumours (p value<0.05). Tissue expression of HE4 protein was also significantly raised in malignant tumours compared to benign tumours (p value<0.05). We conclude that HE4 can be a useful tissue immunomarker in addition to CA-125.

  4. Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

    ClinicalTrials.gov

    2013-12-17

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

  5. Burden of malignancy after a primary skin cancer: recurrence, multiple skin cancers and second primary cancers.

    PubMed

    Krueger, Hans; Williams, Dan

    2010-01-01

    The current paper summarizes relevant recent research on the high risk of recurrence, multiple skin cancers and second primary cancers in the growing number of people with a history of skin cancer; the ultimate purpose is to better assess the burden of malignancy following skin cancer. A number of challenges exist in identifying and tracking both melanoma and non-melanoma skin cancer (NMSC) cases. Most jurisdictions do not routinely track NMSC cases and, even if they do, it is customary to only include the first diagnosis. There are variable rules for counting multiple melanoma cancers, and recurrences are not considered for either major type of skin cancer. Applying insights from recent studies of this issue to Canadian cancer statistics would increase reported diagnoses of NMSC by about 26% and melanoma by 10% in this country. This approach to a fuller assessment of the burden of skin cancers has been called a "diagnosis-based incidence approach" as compared with a "patient-based incidence approach". A further issue that is not usually taken into account when assessing the burden of skin cancers is the 20% to 30% elevated risk of noncutaneous second primary cancers following a primary skin tumour. In summary, individuals with skin cancer are subject to a high risk of recurrence, multiple skin cancers and second primary cancers. This burden should be a special concern in the large and growing pool of individuals with a history of skin cancer, as well as among prevention planners.

  6. What Is Ovarian Cancer?

    MedlinePlus

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

  7. Talazoparib and HSP90 Inhibitor AT13387 in Treating Patients With Metastatic Advanced Solid Tumor or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple Negative Breast Cancer

    ClinicalTrials.gov

    2016-07-22

    Adult Solid Neoplasm; Estrogen Receptor Negative; Fallopian Tube Serous Neoplasm; HER2/Neu Negative; Ovarian Serous Adenocarcinoma; Ovarian Serous Tumor; Primary Peritoneal Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  8. Primary malignant melanoma of the vermilion of the lip.

    PubMed

    Van Wingerden, Jan J; De Visscher, Jan G A M; Raubenheimer, Erich J

    2007-05-01

    Malignant melanoma of the vermilion of the lip is a rare entity, and because of the common occurrence of other benign pigmented lesions, it is easily overlooked. Early diagnosis is of the utmost importance, in the first instance to minimise the risk of haematogenous, lymphatic, perineural and trans- (salivary) ductal spread. The second reason for early diagnosis is that surgery is the only effective form of treatment. A number of important clinical lessons were learned from this cohort study of malignant melanoma of the vermilion of the lip. Two observations are of note--first, the absence of palpable regional lymph nodes does not exclude the presence of a malignant melanoma, yet all patients presenting with palpable nodes were suffering from a preterminal disease. Secondly, apart from 1 case (our case 2), melanoma of the lip seems to occur on the lower lip only. There are no clear guidelines regarding the necessary extent of extirpation for malignant melanoma of the vermilion of the lip, but we propose that clear margins of less than 10 mm are probably inadequate and margins of more than 20 mm are unnecessary. Concern about a resection resulting in a 20 mm clear margin all round is seldom justified as excellent methods of reconstruction achieving acceptable mobile, adequately sensate lips are available.

  9. AUTOIMMUNE DISORDERS IN WOMEN WITH TURNER SYNDROME AND WOMEN WITH KARYOTYPICALLY NORMAL PRIMARY OVARIAN INSUFFICIENCY

    PubMed Central

    Bakalov, Vladimir K.; Gutin, Liat; Cheng, Clara M; Zhou, Jian; Sheth, Puja; Shah, Kavita; Arepalli, Sruthi; Vanderhoof, Vien; Nelson, Lawrence M.; Bondy, Carolyn A.

    2012-01-01

    The higher prevalence of autoimmune diseases in women compared to men could be due to effects of ovarian hormones, pregnancy and/or the presence of a 2nd X chromosome. To elucidate the role of these factors, we investigated the prevalence and spectrum of autoimmune diagnoses in women with primary ovarian insufficiency associated with X chromosome monosomy (Turner syndrome, TS, n=244) and women with karyotypically normal (46,XX) primary ovarian insufficiency (POI, n=457) in a prospective study, conducted at the National Institutes of Health. We compared the study group prevalence to normative data for the U.S. population of women. Chronic lymphocytic (Hashimoto’s) thyroiditis (HT) occurred in 37% of women with TS vs. 15% with POI (P<0.0001); HT prevalence in both ovarian insufficiency groups significantly exceeded that in U.S. population of women (5.8%). Inflammatory bowel (IBD, 4%) and celiac disease (CD, 2.7%) were significantly increased in TS, but not in POI. No other autoimmune diagnosis, including Graves’ disease or Type 1 diabetes appears to be significantly increased in either group. Women with TS had higher pro-inflammatory IL6 and TGF β1 levels (p<0.0001 for both), and lower anti-inflammatory IL10 and TGF β2 levels (p<0.005 for both) compared to POI and to normal volunteers. Lifetime estrogen exposure and parity were significantly lower in TS compared to POI, which were in turn lower than the general population of women. The finding that lymphocytic thyroiditis is greatly increased in both women with TS and POI suggests that factors associated with ovarian insufficiency per se promote this form of autoimmunity. The absence of a normal second X-chromosome further contributes to increased autoimmunity in TS. PMID:22342295

  10. Cardiovascular autonomic dysfunction in primary ovarian insufficiency: clinical and experimental evidence

    PubMed Central

    Goldmeier, Silvia; De Angelis, Kátia; Rabello Casali, Karina; Vilodre, César; Consolim-Colombo, Fernanda; Belló Klein, Adriane; Plentz, Rodrigo; Spritzer, PoliMara; Irigoyen, Maria-Cláudia

    2014-01-01

    Objective: Women with primary ovarian insufficiency (POI) present an increased risk for cardiovascular disease. In this study we tested the hypothesis that POI in women under hormone therapy (HT) are associated with vascular vasodilatation attenuation and cardiovascular autonomic dysfunction and these impairments are related to changes in systemic antioxidant enzymes. Furthermore, the possibility that ovarian hormone deprivation can induce such changes and that HT cannot reverse all of those impairments was examined in an experimental model of POI. Methods: Fifteen control and 17 patients with primary ovarian insufficiency receiving HT were included in the study. To test the systemic and cardiac consequences of ovarian hormone deprivation, ovariectomy was induced in young female rats that were submitted or not to HT. Spectral analysis of RR interval and blood pressure signals were performed and oxidative stress parameters were determined. Results: POI women under HT have increased mean arterial pressure (94±10 vs. 86±5 mmHg) despite normal endothelial and autonomic modulation of vasculature. Additionally, they presented impaired baroreflex sensitivity (3.9±1.38 vs. 7.15±3.62 ms/mmHg) and reduced heart rate variability (2310±1173 vs. 3754±1921 ms2). Similar results obtained in ovariectomized female rats were accompanied by an increased lipoperoxidation (7433±1010 vs. 6180±289 cps/mg protein) and decreased antioxidant enzymes in cardiac tissue. As it was observed in women, the HT in animals did not restore hemodynamic and autonomic dysfunctions. Conclusion: These data provide clinical and experimental evidence that long term HT may not restore all cardiovascular risk factors associated with ovarian hormone deprivation. PMID:24349626

  11. Chemotherapy Toxicity On Quality of Life in Older Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian Epithelial, Primary Peritoneal Cavity, or Fallopian Tube Cancer

    ClinicalTrials.gov

    2016-02-09

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

  12. Primary Malignant Mixed Germ Cell Tumour with Squamous Cell Carcinoma of the Mandible; A Rare Entity

    PubMed Central

    Paul, Arun; Parmar, Harshad; Chacko, Rabin

    2015-01-01

    Germ cell Tumours (GCT) are neoplasm derived from germ cells. GCT usually occurs inside the gonads. Extragonadal GCT’s are rare. Most common GCT associated with head and neck region are the teratomas. Of the few teratomas found in the head and neck, malignant transformation of a teratomatous element is very uncommon, and primary bone involvement within the head and neck is even rare. We present a case of primary malignant mixed germ cell Tumour involving the mandible, the present case presented malignant transformation of the epithelial component showing foci of squamous cell carcinoma within the GCT. PMID:26266228

  13. Expression Profiling of Primary and Metastatic Ovarian Tumors Reveals Differences Indicative of Aggressive Disease

    PubMed Central

    Brodsky, Alexander S.; Fischer, Andrew; Miller, Daniel H.; Vang, Souriya; MacLaughlan, Shannon; Wu, Hsin-Ta; Yu, Jovian; Steinhoff, Margaret; Collins, Colin; Smith, Peter J. S.; Raphael, Benjamin J.; Brard, Laurent

    2014-01-01

    The behavior and genetics of serous epithelial ovarian cancer (EOC) metastasis, the form of the disease lethal to patients, is poorly understood. The unique properties of metastases are critical to understand to improve treatments of the disease that remains in patients after debulking surgery. We sought to identify the genetic and phenotypic landscape of metastatic progression of EOC to understand how metastases compare to primary tumors. DNA copy number and mRNA expression differences between matched primary human tumors and omental metastases, collected at the same time during debulking surgery before chemotherapy, were measured using microarrays. qPCR and immunohistochemistry validated findings. Pathway analysis of mRNA expression revealed metastatic cancer cells are more proliferative and less apoptotic than primary tumors, perhaps explaining the aggressive nature of these lesions. Most cases had copy number aberrations (CNAs) that differed between primary and metastatic tumors, but we did not detect CNAs that are recurrent across cases. A six gene expression signature distinguishes primary from metastatic tumors and predicts overall survival in independent datasets. The genetic differences between primary and metastatic tumors, yet common expression changes, suggest that the major clone in metastases is not the same as in primary tumors, but the cancer cells adapt to the omentum similarly. Together, these data highlight how ovarian tumors develop into a distinct, more aggressive metastatic state that should be considered for therapy development. PMID:24732363

  14. [The expression of MKP-1 and p-ERK(1/2) in primary ovarian epithelial tumor tissues].

    PubMed

    Zhou, Jian Wei; Gan, Ning Yue; Zhang, Wei Jiang

    2009-06-01

    To investigate the expression of mitogen activated protein kinase phosphatase-1 (MKP-1) and phosphorylation extracellular signal-regulated kinases (p-ERK(1/2)) in primary ovarian epithelial tumor tissues, and provide experiment's foundation on the new treatment in ovarian cancer. Expression of MKP-1 and p-ERK(1/2) in tissues from 64 patients with primary ovarian epithelial tumor, 35 patients with ovarian epithelial bordline tumor, 32 patients with ovarian epithelial benign tumor and 26 normal ovarian tissues was detected by immunohistochemistry. Western-blot was also used for detecting the expression of MKP-1 and p-ERK(1/2) protein in these tissues. Immunohistochemistry and Western-blot assay showed that the expression of MKP-1 was gradually decreased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were significant differences among them (P < 0.01). The MKP-1 expression level in the carcinoma tissues of stage III/IV patients was significantly lower than that of stage I/II patients. However, the expression of p-ERK(1/2) was gradually increased in normal ovarian tissues, benign tumor, bordline tumor and carcinoma respectively, and there were also significant differences among them (P < 0.01), the p-ERK(1/2) expression level in the carcinoma tissues of stage III/IV patients was significantly higher than that of stage I/II patients. Expression of MKP-1 and p-ERK(1/2) in same ovarian carcinoma tissues detected by immunohistochemistry and Western-blot assay showed significant negative correlation (r = -0.90, P < 0.01 and r = -0.78, P < 0.01 respectively). The expression changes of MKP-1 and ERKs may play a role in the development of ovarian carcinoma. The abnormal expression of MKP-1 and p-ERK(1/2) probably assists in promoting the development and progression of ovarian carcinoma.

  15. Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.

    PubMed

    Philip, R; Clary, B; Brunette, E; Kilinski, L; Murugesh, D; Sorich, M; Yau, J; Lebkowski, J; Lyerly, H K; Philip, M

    1996-01-01

    We have previously shown that cationic liposomes facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of breast and ovarian cancers, we have constructed an expression plasmid pMP6IL2 and investigated the use of liposome-mediated gene delivery into primary, uncultured human breast and ovarian tumor cells to produce interleukin 2 (IL-2)-secreting tumor cells. We have demonstrated significant levels of IL-2 expression in tumor cell lines and primary breast and ovarian tumor cells using this AAV-based expression plasmid complexed to cationic liposomes. Transfections with the non-AAV plasmid containing the identical expression cassette as the AAV plasmid induced IL-2 expression in the tumor cell line but failed to produce IL-2 in primary tumor cells. Significant levels of IL-2 were induced with the AAV plasmid regardless of liposome compositions used for transfection. The transfected breast cell line and primary tumor cells were able to express the transgene product for up to 28 days after lethal radiation. The transfection efficiency was comparable for both the tumor cell line and primary tumor cells and ranged from 20 to 50% for both cell types as assessed by intracellular IL-2 staining. Although the primary tumor cell preparations consist of mixed population of cells, at least 40% of the tumor cells expressed the transgene as assessed by immunostaining for IL-2. The ability to efficiently express transgenes in freshly isolated, nondividing tumor cells may potentiate active immunotherapy strategies for gene-based cancer treatment.

  16. Myxoid Malignant Fibrous Histiocytoma with Multiple Primary Sites

    PubMed Central

    Muler, Jeffrey H.; Paulino, Augusto F.; Roulston, Diane

    2002-01-01

    Malignant fibrous histiocytoma (MFH) is one of the most common types of soft tissue sarcomas in adults. The most common location of MFH are the extremities and the trunk, with the most common site for distant metastases being the lung. We describe a case with multiple synchronous sites of myxoid MFH but no lung metastases and presence of abnormalities of 19p13. PMID:18521346

  17. Non-genomic estrogen/estrogen receptor α promotes cellular malignancy of immature ovarian teratoma in vitro.

    PubMed

    Hung, Yao-Ching; Chang, Wei-Chun; Chen, Lu-Min; Chang, Ying-Yi; Wu, Ling-Yu; Chung, Wei-Min; Lin, Tze-Yi; Chen, Liang-Chi; Ma, Wen-Lung

    2014-06-01

    Malignant immature ovarian teratomas (IOTs) most often occur in women of reproductive age. It is unclear, however, what roles estrogenic signaling plays in the development of IOT. In this study, we examined whether estrogen receptors (ERα and β) promote the cellular malignancy of IOT. Estradiol (E2), PPT (propylpyrazole), and DPN (diarylpropionitrile) (ERα- and β-specific agonists, respectively), as well as ERα- or ERβ-specific short hairpin (sh)RNA were applied to PA-1 cells, a well-characterized IOT cell line. Cellular tumorigenic characteristics, for example, cell migration/invasion, expression of the cancer stem/progenitor cell marker CD133, and evidence for epithelial-mesenchymal transition (EMT) were examined. In PA-1 cells that expressed ERα and ERβ, we found that ERα promoted cell migration and invasion. We also found that E2/ERα signaling altered cell behavior through non-classical transactivation function. Our data show non-genomic E2/ERα activations of focal adhesion kinase-Ras homolog gene family member A (FAK-RhoA) and ERK governed cell mobility capacity. Moreover, E2/ERα signaling induces EMT and overexpression of CD133 through upregulation micro-RNA 21 (miR21; IOT stem/progenitor promoter), and ERK phosphorylations. Furthermore, E2/ERα signaling triggers a positive feedback regulatory loop within miR21 and ERK. At last, expression levels of ERα, CD133, and EMT markers in IOT tissue samples were examined by immunohistochemistry. We found that cytosolic ERα was co-expressed with CD133 and mesenchymal cell markers but not epithelial cell markers. In conclusion, estrogenic signals exert malignant transformation capacity of cancer cells, exclusively through non-genomic regulation in female germ cell tumors.

  18. Non-genomic estrogen/estrogen receptor α promotes cellular malignancy of immature ovarian teratoma in vitro.

    PubMed

    Hung, Yao-Ching; Chang, Wei-Chun; Chen, Lu-Min; Chang, Ying-Yi; Wu, Ling-Yu; Chung, Wei-Min; Lin, Tze-Yi; Chen, Liang-Chi; Ma, Wen-Lung

    2014-06-01

    Malignant immature ovarian teratomas (IOTs) most often occur in women of reproductive age. It is unclear, however, what roles estrogenic signaling plays in the development of IOT. In this study, we examined whether estrogen receptors (ERα and β) promote the cellular malignancy of IOT. Estradiol (E2), PPT (propylpyrazole), and DPN (diarylpropionitrile) (ERα- and β-specific agonists, respectively), as well as ERα- or ERβ-specific short hairpin (sh)RNA were applied to PA-1 cells, a well-characterized IOT cell line. Cellular tumorigenic characteristics, for example, cell migration/invasion, expression of the cancer stem/progenitor cell marker CD133, and evidence for epithelial-mesenchymal transition (EMT) were examined. In PA-1 cells that expressed ERα and ERβ, we found that ERα promoted cell migration and invasion. We also found that E2/ERα signaling altered cell behavior through non-classical transactivation function. Our data show non-genomic E2/ERα activations of focal adhesion kinase-Ras homolog gene family member A (FAK-RhoA) and ERK governed cell mobility capacity. Moreover, E2/ERα signaling induces EMT and overexpression of CD133 through upregulation micro-RNA 21 (miR21; IOT stem/progenitor promoter), and ERK phosphorylations. Furthermore, E2/ERα signaling triggers a positive feedback regulatory loop within miR21 and ERK. At last, expression levels of ERα, CD133, and EMT markers in IOT tissue samples were examined by immunohistochemistry. We found that cytosolic ERα was co-expressed with CD133 and mesenchymal cell markers but not epithelial cell markers. In conclusion, estrogenic signals exert malignant transformation capacity of cancer cells, exclusively through non-genomic regulation in female germ cell tumors. PMID:24142535

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

    ClinicalTrials.gov

    2016-07-05

    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

  20. Derivation and characterization of matched cell lines from primary and recurrent serous ovarian cancer

    PubMed Central

    2012-01-01

    Background Cell line models have proven to be effective tools to investigate a variety of ovarian cancer features. Due to the limited number of cell lines, particularly of the serous subtype, the heterogeneity of the disease, and the lack of cell lines that model disease progression, there is a need to further develop cell line resources available for research. This study describes nine cell lines derived from three ovarian cancer cases that were established at initial diagnosis and at subsequent relapse after chemotherapy. Methods The cell lines from three women diagnosed with high-grade serous ovarian cancer (1369, 2295 and 3133) were derived from solid tumor (TOV) and ascites (OV), at specific time points at diagnosis and relapse (R). Primary treatment was a combination of paclitaxel/carboplatin (1369, 3133), or cisplatin/topotecan (2295). Second line treatment included doxorubicin, gemcitabine and topotecan. In addition to molecular characterization (p53, HER2), the cell lines were characterized based on cell growth characteristics including spheroid growth, migration potential, and anchorage independence. The in vivo tumorigenicity potential of the cell lines was measured. Response to paclitaxel and carboplatin was assessed using a clonogenic assay. Results All cell lines had either a nonsense or missense TP53 mutations. The ability to form compact spheroids or aggregates was observed in six of nine cell lines. Limited ability for migration and anchorage independence was observed. The OV3133(R) cell line, formed tumors at subcutaneous sites in SCID mice. Based on IC50 values and dose response curves, there was clear evidence of acquired resistance to carboplatin for TOV2295(R) and OV2295(R2) cell lines. Conclusion The study identified nine new high-grade serous ovarian cancer cell lines, derived before and after chemotherapy that provides a unique resource for investigating the evolution of this common histopathological subtype of ovarian cancer. PMID:22931248

  1. Challenging diagnosis of a jejunal adenocarcinoma with ovarian metastasis: report of an unusual case

    PubMed Central

    Huang, Yang Yang; Pratt, Jeremy John; Dabner, Marcus; Tjhin, William

    2013-01-01

    We report the first documented case of ovarian metastasis from a jejunal primary adenocarcinoma in an Australian patient. The presentation was unusual, initially a suspicious abdominal nodule in the epigastric area, which turned out to be an adenocarcinoma of possible intestinal origin. Gastroscopy and colonoscopy were performed with no suspicious lesion identified. Abdominal and pelvic ultrasound imaging showed a complex pelvic mass suspicious of ovarian cancer. Laparoscopy was performed to exclude possibility of ovarian cancer and small bowel cancer. The ovarian mass showed similar features from the epigastric nodule, again suggestive of intestinal primary. Definitive diagnosis was obtained when the patient represented 2 months later with malignant bowel obstruction requiring palliative resection of the proximal jejunum. This case demonstrates the difficulty in diagnosing ovarian metastasis from a small bowel primary, which has the potential to mimic an ovarian primary tumour clinically, and a large bowel or ovarian primary pathologically. PMID:23580681

  2. Glycoproteomic Analysis of Malignant Ovarian Cancer Ascites Fluid Identifies Unusual Glycopeptides.

    PubMed

    Miyamoto, Suzanne; Ruhaak, L Renee; Stroble, Carol; Salemi, Michelle R; Phinney, Brett; Lebrilla, Carlito B; Leiserowitz, Gary S

    2016-09-01

    Ovarian cancer is a major cause of cancer mortality among women, largely due to late diagnosis of advanced metastatic disease. More extensive molecular analysis of metastatic ovarian cancer is needed to identify post-translational modifications of proteins, especially glycosylation that is particularly associated with metastatic disease to better understand the metastatic process and identify potential therapeutic targets. Glycoproteins in ascites fluid were enriched by affinity binding to lectins (ConA or WGA) and other affinity matrices. Separate glycomic, proteomic, and glycopeptide analyses were performed. Relative abundances of different N-glycan groups and proteins were identified from ascites fluids and a serum control. Levels of biomarkers CA125, MUC1, and fibronectin were also monitored in OC ascites samples by Western blot analysis. N-Glycan analysis of ascites fluids showed the presence of large, highly fucosylated and sialylated complex and hybrid glycans, some of which were not observed in normal serum. OC ascites glycoproteins, haptoglobin, fibronectin, lumican, fibulin, hemopexin, ceruloplasmin, alpha-1-antitrypsin, and alpha-1-antichymotrypsin were more abundant in OC ascites or not present in serum control samples. Further glycopeptide analysis of OC ascites identified N- and O-glycans in clusterin, hemopexin, and fibulin glycopeptides, some of which are unusual and may be important in OC metastasis. PMID:27500424

  3. Ovarian Malignant Mixed Germ Cell Tumor: A Case of Unusual Presentation as Molar Pregnancy

    PubMed Central

    Aminimoghaddam, Soheila; Mohseni, Iman; Afzalzadeh, Azadeh; Esmaeeli, Shooka

    2016-01-01

    Background: This research was conducted to introduce a patient with rare ovarian mixed germ cell tumor, presented as molar pregnancy. Case Presentation: The patient was a 16 year old woman admitted with diagnosis of molar pregnancy. Abdominal enlargement was the only complaint. She had a large pelvic mass in physical examination. The first diagnosis was molar pregnancy due to previous ultrasonic reports and positive βeta HCG. Urine pregnancy test was positive. As suction curettage was performed for her, surprisingly, the size of uterus was normal and no molar tissue was found in pathologic examination. At intraoperative ultrasound exam, an extra-uterine heterogeneous mass was found. Extra-uterine mass was confirmed by CT and MRI done after suction curettage. Mixed germ cell tumor was confirmed by histological examination after laparatomy and removing tumoral mass. Finally, she received Bleomycin, Etoposide and Cisplatin (BEP) regimen in four courses and Vincristine, Actinomycin D (Dactinomycin) and Cyclophosphamide (VAC) regimen in two courses and Diphereline for saving the other ovary. Conclusion: Some young patients misinterpret the early symptoms of an ovarian neoplasm as those of pregnancy which can lead to a delay in the diagnosis. PMID:27141469

  4. Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer

    PubMed Central

    Franz, Annika; Richter, Rolf; Dragun, Duska; Heidecke, Harald; Dechend, Ralf; Muller, Dominik N.; Sehouli, Jalid; Braicu, Elena I.

    2016-01-01

    Aim. The purpose of the present study was to analyze the predictive and prognostic role of soluble (pro)renin receptor (sPRR) as a biomarker for clinicopathological outcome in patients with primary epithelial ovarian cancer (EOC). As part of the renin-angiotensin system (RAS) whose activity is known to increase in ovarian cancer patients, the relation of sPRR and ovarian cancer should be further investigated. Patients and Methods. In this study 197 patients with primary EOC in our institution from 2000 to 2011 were included. sPRR was determined by enzyme-linked immunosorbent assay (ELISA) in preoperative taken blood sera. Associations with clinicopathological outcome were analyzed and serum levels of sPRR in patients have been compared to those in healthy specimen. Kaplan-Meier and logistic/Cox regression assessed the impact of the markers on progression-free survival (PFS) and overall survival (OS). Results. There have been no correlations proved of sPRR levels with neither clinicopathological factors nor prognostic data. Also the distribution of sPRR in patients and controls was normal. Conclusion. sPRR seems to have no predictive, prognostic, or diagnostic value in EOC. As several factors of the RAS which might indicate cancer events have been shown, sPRR seems not to be affected. PMID:27660742

  5. Predictive and Prognostic Value of sPRR in Patients with Primary Epithelial Ovarian Cancer

    PubMed Central

    Franz, Annika; Richter, Rolf; Dragun, Duska; Heidecke, Harald; Dechend, Ralf; Muller, Dominik N.; Sehouli, Jalid; Braicu, Elena I.

    2016-01-01

    Aim. The purpose of the present study was to analyze the predictive and prognostic role of soluble (pro)renin receptor (sPRR) as a biomarker for clinicopathological outcome in patients with primary epithelial ovarian cancer (EOC). As part of the renin-angiotensin system (RAS) whose activity is known to increase in ovarian cancer patients, the relation of sPRR and ovarian cancer should be further investigated. Patients and Methods. In this study 197 patients with primary EOC in our institution from 2000 to 2011 were included. sPRR was determined by enzyme-linked immunosorbent assay (ELISA) in preoperative taken blood sera. Associations with clinicopathological outcome were analyzed and serum levels of sPRR in patients have been compared to those in healthy specimen. Kaplan-Meier and logistic/Cox regression assessed the impact of the markers on progression-free survival (PFS) and overall survival (OS). Results. There have been no correlations proved of sPRR levels with neither clinicopathological factors nor prognostic data. Also the distribution of sPRR in patients and controls was normal. Conclusion. sPRR seems to have no predictive, prognostic, or diagnostic value in EOC. As several factors of the RAS which might indicate cancer events have been shown, sPRR seems not to be affected.

  6. Characterization of twenty-five ovarian tumour cell lines that phenocopy primary tumours

    PubMed Central

    Ince, Tan A.; Sousa, Aurea D.; Jones, Michelle A.; Harrell, J. Chuck; Agoston, Elin S.; Krohn, Marit; Selfors, Laura M.; Liu, Wenbin; Chen, Ken; Yong, Mao; Buchwald, Peter; Wang, Bin; Hale, Katherine S.; Cohick, Evan; Sergent, Petra; Witt, Abigail; Kozhekbaeva, Zhanna; Gao, Sizhen; Agoston, Agoston T.; Merritt, Melissa A.; Foster, Rosemary; Rueda, Bo R.; Crum, Christopher P.; Brugge, Joan S.; Mills, Gordon B.

    2015-01-01

    Currently available human tumour cell line panels consist of a small number of lines in each lineage that generally fail to retain the phenotype of the original patient tumour. Here we develop a cell culture medium that enables us to routinely establish cell lines from diverse subtypes of human ovarian cancers with >95% efficiency. Importantly, the 25 new ovarian tumour cell lines described here retain the genomic landscape, histopathology and molecular features of the original tumours. Furthermore, the molecular profile and drug response of these cell lines correlate with distinct groups of primary tumours with different outcomes. Thus, tumour cell lines derived using this methodology represent a significantly improved platform to study human tumour pathophysiology and response to therapy. PMID:26080861

  7. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.

    PubMed

    Greening, David W; Ji, Hong; Chen, Maoshan; Robinson, Bruce W S; Dick, Ian M; Creaney, Jenette; Simpson, Richard J

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.

  8. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    NASA Astrophysics Data System (ADS)

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-09-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.

  9. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    PubMed Central

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  10. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.

    PubMed

    Greening, David W; Ji, Hong; Chen, Maoshan; Robinson, Bruce W S; Dick, Ian M; Creaney, Jenette; Simpson, Richard J

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  11. The role of intratumoral lymphovascular density in distinguishing primary from secondary mucinous ovarian tumors

    PubMed Central

    de Lacerda Almeida, Bernardo Gomes; Bacchi, Carlos E; Carvalho, Jesus P; Ferreira, Cristiane R; Carvalho, Filomena M

    2014-01-01

    OBJECTIVE: Ovarian mucinous metastases commonly present as the first sign of the disease and are capable of simulating primary tumors. Our aim was to investigate the role of intratumoral lymphatic vascular density together with other surgical-pathological features in distinguishing primary from secondary mucinous ovarian tumors. METHODS: A total of 124 cases of mucinous tumors in the ovary (63 primary and 61 metastatic) were compared according to their clinicopathological features and immunohistochemical profiles. The intratumoral lymphatic vascular density was quantified by counting the number of vessels stained by the D2-40 antibody. RESULTS: Metastases occurred in older patients and were associated with a higher proportion of tumors smaller than 10.0 cm; bilaterality; extensive necrosis; extraovarian extension; increased expression of cytokeratin 20, CDX2, CA19.9 and MUC2; and decreased expression of cytokeratin 7, CA125 and MUC5AC. The lymphatic vascular density was increased among primary tumors. However, after multivariate analysis, the best predictors of a secondary tumor were a size of 10.0 cm or less, bilaterality and cytokeratin 7 negativity. Lack of MUC2 expression was an important factor excluding metastasis. CONCLUSIONS: The higher intratumoral lymphatic vascular density in primary tumors when compared with secondary lesions suggests differences in the microenvironment. However, considering the differential diagnosis, the best discriminator of a secondary tumor is the combination of tumor size, laterality and the pattern of expression of cytokeratin 7 and MUC2. PMID:25518016

  12. Surgical treatment of potentially primary malignant adrenal tumors: an unresolved issue.

    PubMed

    Zografos, George N; Perysinakis, Iraklis; Kyrodimou, Eustathia; Kassi, Eva; Kaltsas, Gregory

    2015-01-01

    Although the great majority of incidentalomas are adrenocortical adenomas, a number of them, depending on the size and radiological characteristics of the lesions, will turn out to be carcinomas. These tumors may present as suspicious on initial evaluation and potentially malignant or malignant on histology. Adrenocortical carcinoma is a rare and aggressive malignancy with evolving diagnostic and therapeutic approaches. Laparoscopic surgery has become the gold standard for surgery of benign adrenal tumors. Despite the extensive experience gained in laparoscopic adrenalectomy, controversy still remains in the management of adrenal tumors with high suspicion or evidence of malignancy. The aim of this review is to update the existing information regarding the diagnostic approach and surgical management of suspicious and potentially malignant primary adrenal tumors.The interpretation of radiologic characteristics is a cornerstone in pre-operative assessment of large adrenal masses, since open surgery remains the preferred procedure when malignancy is suspected in large tumors with possible local invasion. Despite the improvement of imaging techniques, they lack sufficient accuracy to exclude primary malignancy in tumors from 4 cm to 10 cm in size. An initial laparoscopic approach can be used in this group of patients, but early conversion to open technique is mandatory if curative resection cannot be performed. Adrenal tumors >10 cm of malignant potential should be treated by the open approach from the start. Solitary adrenal metastasis from another primary malignancy is usually amenable to laparoscopic surgery. Patients with suspected adrenal cancer should be referred to tertiary centers that perform laparoscopic and open adrenal surgery with minimal morbidity and mortality.

  13. Testosterone improves the transition of primary oocytes in artificial maturation eels (Anguilla japonica) by altering ovarian PTEN expression.

    PubMed

    Huang, Yung-Sen; Chen, Ya-Mei; Liao, Pei-Chi; Lee, Yan-Horn; Gwo, Jin-Chywan; Chen, Ming-Chyuan; Chang, Ching-Fong

    2012-06-01

    In mammals, androgens appear to enhance the development of primary ovarian follicles, but PI3K (phosphoinositide 3-kinases) pathway is well recognized as one of the critical pathways in early follicular development. Roles of the PI3K were revealed by deletion of PTEN (phosphatase and tensin homolog on chromosome 10). PTEN is demonstrated to play an important role in the early stage of follicle development. In the Japanese eel, two forms of PTEN have been cloned, but what their functions on the development of early ovarian follicles are still not clear. The natural blockage and inducible of ovarian development was a benefit to address this question in the eel. Testosterone (T) shows to ameliorate the early ovarian development in the eel. The aims of this study were to elucidate the two forms of PTEN by cellular and physiological criteria and to study the effects of T on the ovarian PTEN production in the exogenous pituitary extracts-stimulated eel. Our results suggested that two forms of PTEN are existing in the Japanese eel, and eel ovarian development corresponded to the decrease in ovarian PTEN expression, vice versa. In addition, the supplement of T on eel early ovarian development can be attributed to its PTEN inhibitor role.

  14. Bone Windows for Distinguishing Malignant from Benign Primary Bone Tumors on FDG PET/CT

    PubMed Central

    Costelloe, Colleen M.; Chuang, Hubert H.; Chasen, Beth A.; Pan, Tinsu; Fox, Patricia S.; Bassett, Roland L.; Madewell, John E.

    2013-01-01

    Objective. The default window setting on PET/CT workstations is soft tissue. This study investigates whether bone windowing and hybrid FDG PET/CT can help differentiate between malignant and benign primary bone tumors. Materials and methods. A database review included 98 patients with malignant (n=64) or benign primary bone (n=34) tumors. The reference standard was biopsy for malignancies and biopsy or >1 year imaging follow-up of benign tumors. Three radiologists and/or nuclear medicine physicians blinded to diagnosis and other imaging viewed the lesions on CT with bone windows (CT-BW) without and then with PET (PET/CT-BW), and separate PET-only images for malignancy or benignity. Three weeks later the tumors were viewed on CT with soft tissue windows (CT-STW) without and then with PET (PET/CT-STW). Results. Mean sensitivity and specificity for identifying malignancies included: CT-BW: 96%, 90%; CT-STW: 90%, 90%; PET/CT-BW: 95%, 85%, PET/CT-STW: 95%, 86% and PET-only: 96%, 75%, respectively. CT-BW demonstrated higher specificity than PET-only and PET/CT-BW (p=0.0005 and p=0.0103, respectively) and trended toward higher sensitivity than CT-STW (p=0.0759). Malignant primary bone tumors were more avid than benign lesions overall (p<0.0001) but the avidity of benign aggressive lesions (giant cell tumors and Langerhans Cell Histiocytosis) trended higher than the malignancies (p=0.08). Conclusion. Bone windows provided high specificity for distinguishing between malignant and benign primary bone tumors and are recommended when viewing FDG PET/CT. PMID:23983816

  15. Primary malignant peripheral nerve sheath tumor at unusual location

    PubMed Central

    Panigrahi, Souvagya; Mishra, Sudhansu Sekhar; Das, Srikant; Dhir, Manmath Kumar

    2013-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. Most arise in association with major nerve trunks. Their most common anatomical sites are the proximal portions of the upper and lower extremities and the trunk. MPNSTs have rarely been reported in literature to occur in other unusual body parts. We review all such cases reported till now in terms of site of origin, surgical treatment, adjuvant therapy and outcome and shortly describe our experience with two of these cases. Both of our case presented with lump at unusual sites resembling neurofibroma, one at orbitotemporal area and other in the paraspinal region with characteristic feature of neurofibroma with the exception that both had very short history of progression. They underwent gross total removal of the tumor with adjuvant radiotherapy postoperatively. At 6-month follow-up both are doing well with no evidence of recurrence. PMID:24174807

  16. Intrathymic primary intrathoracic goiter in a patient with breast malignancy.

    PubMed

    Barker, Thomas A; Daultrey, Charles R; Trotter, Simon E; Kalkat, Maninder

    2012-02-01

    We report a rare case of an intrathymic primary intrathoracic goiter. The patient with newly diagnosed breast carcinoma was also known to have a distinct large anterior mediastinal mass. This was removed via a median sternotomy, after a thorascopic biopsy had been performed in the past but a diagnosis had not been reached. A discussion relating to the extremely rare occurrence of intrathymic ectopic thyroid tissue and the surgical treatment of primary intrathoracic goiters is included. PMID:22269766

  17. Review of ovarian tumors in children and adolescents: radiologic-pathologic correlation.

    PubMed

    Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Seo In; Lim, Hyo Soon; Choi, Yoo Duk; Lee, Kyoung Hwa; Kang, Woo Dae; Jeong, Yong Yeon; Kang, Heoung Keun

    2014-01-01

    The incidence, histologic distribution, and clinical manifestations of ovarian tumors in the pediatric population are distinct from those in adults. Although ovarian neoplasms in childhood and adolescence are rare, the diagnosis should be considered in young girls with abdominal pain and a palpable mass. Differential diagnosis in children and adolescents with ovarian tumors should be conducted on the basis of unique clinical manifestations, elevated serum tumor marker levels, and distinctive imaging findings. Although the clinical manifestations are nonspecific and may overlap, they may assist in diagnosis of some types of ovarian tumors. Children who present with a palpable mass or symptoms of precocious puberty have a high likelihood of malignancy. Many ovarian tumors are associated with abnormal hormonal activity and/or abnormal sexual development. Elevated levels of serum tumor markers, including α-fetoprotein, the beta subunit of human chorionic gonadotropin, and CA-125, raise concern for ovarian malignancies. However, negative tumor markers do not exclude the possibility of malignancy. Identification of imaging features at ultrasonography, computed tomography, and magnetic resonance imaging can help differentiate benign from malignant ovarian tumors and, in turn, plays a crucial role in determining treatment options. At imaging, malignant ovarian tumors usually appear predominantly solid or heterogeneous and are larger than benign tumors. Because surgery is the primary treatment for ovarian tumors, ovarian salvage with fertility preservation and use of a minimally invasive surgical technique are important in children and adolescents.

  18. Review of ovarian tumors in children and adolescents: radiologic-pathologic correlation.

    PubMed

    Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Seo In; Lim, Hyo Soon; Choi, Yoo Duk; Lee, Kyoung Hwa; Kang, Woo Dae; Jeong, Yong Yeon; Kang, Heoung Keun

    2014-01-01

    The incidence, histologic distribution, and clinical manifestations of ovarian tumors in the pediatric population are distinct from those in adults. Although ovarian neoplasms in childhood and adolescence are rare, the diagnosis should be considered in young girls with abdominal pain and a palpable mass. Differential diagnosis in children and adolescents with ovarian tumors should be conducted on the basis of unique clinical manifestations, elevated serum tumor marker levels, and distinctive imaging findings. Although the clinical manifestations are nonspecific and may overlap, they may assist in diagnosis of some types of ovarian tumors. Children who present with a palpable mass or symptoms of precocious puberty have a high likelihood of malignancy. Many ovarian tumors are associated with abnormal hormonal activity and/or abnormal sexual development. Elevated levels of serum tumor markers, including α-fetoprotein, the beta subunit of human chorionic gonadotropin, and CA-125, raise concern for ovarian malignancies. However, negative tumor markers do not exclude the possibility of malignancy. Identification of imaging features at ultrasonography, computed tomography, and magnetic resonance imaging can help differentiate benign from malignant ovarian tumors and, in turn, plays a crucial role in determining treatment options. At imaging, malignant ovarian tumors usually appear predominantly solid or heterogeneous and are larger than benign tumors. Because surgery is the primary treatment for ovarian tumors, ovarian salvage with fertility preservation and use of a minimally invasive surgical technique are important in children and adolescents. PMID:25384300

  19. Phenotypic characterization of telomerase-immortalized primary non-malignant and malignant tumor-derived human prostate epithelial cell lines

    SciTech Connect

    Gu Yongpeng; Li Hongzhen; Miki, Jun; Kim, Kee-Hong; Furusato, Bungo; Sesterhenn, Isabell A.; Chu, Wei-Sing; McLeod, David G.; Srivastava, Shiv; Ewing, Charles M.; Isaacs, William B.; Rhim, Johng S. . E-mail: jrhim@cpdr.org

    2006-04-01

    In vitro human prostate cell culture models are critical for clarifying the mechanism of prostate cancer progression and for testing preventive and therapeutic agents. Cell lines ideal for the study of human primary prostate tumors would be those derived from spontaneously immortalized tumor cells; unfortunately, explanted primary prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we recently have generated five immortal human prostate epithelial cell cultures derived from both the benign and malignant tissues of prostate cancer patients with telomerase, a gene that prevents cellular senescence. Examination of these cell lines for their morphologies and proliferative capacities, their abilities to grow in low serum, to respond to androgen stimulation, to grow above the agar layer, to form tumors in SCID mice, suggests that they may serve as valid, useful tools for the elucidation of early events in prostate tumorigenesis. Furthermore, the chromosome alterations observed in these immortalized cell lines expressing aspects of the malignant phenotypes imply that these cell lines accurately recapitulate the genetic composition of primary tumors. These novel in vitro models may offer unique models for the study of prostate carcinogenesis and also provide the means for testing both chemopreventive and chemotherapeutic agents.

  20. Carcinoid heart disease from ovarian primary presenting with acute pericarditis and biventricular failure

    PubMed Central

    Vergani, D; Massironi, L; Lombardi, F; Fiorentini, C

    1998-01-01

    A case is described of a 54 year old woman who had acute pericarditis with large exudative effusion accompanied by severe right and left ventricular failure. The patient was finally diagnosed with carcinoid heart disease from an ovarian carcinoid teratoma. She was treated with octreotide—a somatostatin analogue—followed by radical surgical resection of the neoplasm. At one year follow up only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid heart disease from an ovarian primary have been described in literature. Moreover clinically manifest acute, non-metastatic pericarditis and left heart failure are not considered as possible presentations of carcinoid heart disease, whatever the origin. In a recent series a small pericardial effusion was considered an infrequent and unexpected echocardiographic finding in carcinoid heart patients. One case of "carcinoid pericarditis" has previously been described as a consequence of pericardial metastasis. Left sided heart involvement is usually caused by bronchial carcinoids or patency of foramen ovale; both were excluded in the case presented.

 Keywords: carcinoid heart disease;  ovarian tumour;  acute pericarditis;  heart failure PMID:10065036

  1. Fragile X premutation RNA is sufficient to cause primary ovarian insufficiency in mice

    PubMed Central

    Lu, Cuiling; Lin, Li; Tan, Huiping; Wu, Hao; Sherman, Stephanie L.; Gao, Fei; Jin, Peng; Chen, Dahua

    2012-01-01

    Spontaneous 46,XX primary ovarian insufficiency (POI), also known as ‘premature menopause’ or ‘premature ovarian failure’, refers to ovarian dysfunction that results in a range of abnormalities, from infertility to early menopause as the end stage. The most common known genetic cause of POI is the expansion of a CGG repeat to 55–199 copies (premutation) in the 5′ untranslated region in the X-linked fragile X mental retardation 1 (FMR1) gene. POI associated with the FMR1 premutation is referred to as fragile X-associated POI (FXPOI). Here, we characterize a mouse model carrying the human FMR1 premutation allele and show that FMR1 premutation RNA can cause a reduction in the number of growing follicles in ovaries and is sufficient to impair female fertility. Alterations in selective serum hormone levels, including FSH, LH and 17β-estradiol, are seen in this mouse model, which mimics findings in humans. In addition, we also find that LH-induced ovulation-related gene expression is specifically altered. Finally, we show that the FMR1 premutation allele can lead to reduced phosphorylation of Akt and mTOR proteins. These results together suggest that FMR1 premutation RNA could cause the POI associated with FMR1 premutation carriers, and the Akt/mTOR pathway may serve as a therapeutic target for FXPOI. PMID:22914733

  2. Primary glottic malignant melanoma of the larynx (PGMML): a very rare entity.

    PubMed

    Aggarwal, Sumeet; Kaushal, Vivek; Singla, Sujata; Sen, Rajeev

    2015-11-20

    Primary glottic malignant melanoma of the larynx (PGMML) is a very rare clinical entity with less than 20 cases reported in the literature so far. The most frequently reported subsite in primary malignant melanomas of the larynx is the supraglottic larynx. The vocal cord as a subsite for primary malignant melanoma is very rare. The present case is a primary glottic malignant melanoma involving both vocal cords. PGMML may present early due to associated hoarseness of voice, unlike other non-cutaneous melanomas in the head and neck. Non-cutaneous malignant melanomas in the head and neck are historically very aggressive in nature and known for poor outcomes and survival. Most non-cutaneous melanomas described in the literature have been superficial spreading or ulcerative in nature, unlike the present case, in which proliferative, polypoidal growth was seen. No associated risk factor was present in this case. Every reported case of this rare entity further adds to the better understanding of tumour biology and expression.

  3. OVSCORE - a validated score to identify ovarian cancer patients not suitable for primary surgery

    PubMed Central

    DORN, JULIA; BRONGER, HOLGER; KATES, RONALD; SLOTTA-HUSPENINA, JULIA; SCHMALFELDT, BARBARA; KIECHLE, MARION; DIAMANDIS, ELEFTHERIOS P.; SOOSAIPILLAI, ANTONINUS; SCHMITT, MANFRED; HARBECK, NADIA

    2015-01-01

    Following primary debulking surgery, the presence of a residual tumor mass is one of the most important prognostic factors in ovarian cancer. In a previous study, we established the OVSCORE, an algorithm to predict surgical outcome, based on the clinical factors of nuclear grading and ascitic fluid volume, plus the cancer biomarkers, kallikrein-related peptidases (KLKs), KLK6 and KLK13. In the present study, OVSCORE performance was tested in an independent ovarian cancer patient cohort consisting of 87 patients. The impact of KLKs, KLK5, 6, 7 and 13 and other clinical factors on patient prognosis and outcome was also evaluated. The OVSCORE proved to be a strong and statistically significant predictor of surgical success in terms of area under the receiver operating characteristic curve (ROC AUC, 0.777), as well as positive and negative predictive value in this independent study group. KLK6 and 13 individually did not show clinical relevance in this cohort, but two other KLKs, KLK5 and KLK7, were associated with advanced FIGO stage, higher nuclear grade and positive lymph node status. In the multivariate Cox regression analysis for overall survival (OS), KLK7 had a protective impact on OS. This study confirms the role of KLKs in ovarian cancer for surgical success and survival, and validates the novel OVSCORE algorithm in an independent collective. As a key clinical application, the OVSCORE could aid gynecological oncologists in identifying those ovarian cancer patients unlikely to benefit from radical surgery who could be candidates for alternative therapeutic approaches. PMID:25436002

  4. [An analysis of 117 cases of patients who died from tumor recurrence or from the progression of ovarian malignancies].

    PubMed

    Kano, T; Sakakibara, K; Kamiya, N; Mizuno, K; Miyazaki, T; Ohta, M; Tomoda, Y

    1987-10-01

    Out of 403 patients with ovarian with malignancies during 1978 to, 1985, 117 (29.0%) died from the progression of a non-curative cancer (56 cases, 47.9%) or from a cancer recurrence (61 cases, 52.1%). The mean survival rate 117 cases was 13.4 months, of which 103 (88.0%) cases concerned patients who died within 2 years and 114 (97.4%) who died within 3 years. A histological analysis revealed that patients with a serous or an endometrial cancer had a longer survival rate than others. Among 61 recurrent cases, 59 (96.7%) fell into recurrence within 2 years. Regarding the relationship between a recurrent of cancer and its prognosis, patients with a recurrence of an ascitic or a metastatic disease had a poorer prognosis than patients with a pelvic or an abdominal mass. An aggressive operation, such as a resection of a recurrent tumor, even if small in volume, led to a better prognostic result than no therapy. PMID:3694804

  5. Molecular Imaging of Ovarian Cancer

    PubMed Central

    Sharma, Sai Kiran; Nemieboka, Brandon; Sala, Evis; Lewis, Jason S.; Zeglis, Brian M.

    2016-01-01

    Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death in women. Over the past decade, medical imaging has played an increasingly valuable role in the diagnosis, staging, and treatment planning of the disease. In this “Focus on Molecular Imaging” review, we seek to provide a brief yet informative survey of the current state of the molecular imaging of ovarian cancer. The article is divided into sections according to modality, covering recent advances in the MR, PET, SPECT, ultrasound, and optical imaging of ovarian cancer. Although primary emphasis is given to clinical studies, preclinical investigations that are particularly innovative and promising are discussed as well. Ultimately, we are hopeful that the combination of technologic innovations, novel imaging probes, and further integration of imaging into clinical protocols will lead to significant improvements in the survival rate for ovarian cancer. PMID:27127223

  6. A Case Report of Dyschromatosis Universalis Hereditaria (DUH) with Primary Ovarian Failure (POF)

    PubMed Central

    Jayanthi, N.S; Anandan, V.; Jameela, W. Afthab; Kumar, V. Senthil

    2016-01-01

    Dyschromatosis Universalis Hereditaria (DUH) belongs to a group of congenital diffuse reticulate pigmentary disorders characterised by both hypo and hyper pigmented macules. It is both hereditary and sporadic. A number of associated cutaneous and systemic diseases have been reported. The recent discovery of the mutation in ATP binding cassette protein, ABCB6 in DUH attempts to explain the reason behind the pigmentary abnormalities and varied associations. We add a new association by reporting a case of DUH with primary ovarian failure (POF) and hypothyroidism. PMID:27134983

  7. A Case Report of Dyschromatosis Universalis Hereditaria (DUH) with Primary Ovarian Failure (POF).

    PubMed

    Jayanthi, N S; Anandan, V; Jameela, W Afthab; Kumar, V Senthil; Lavanya, P

    2016-03-01

    Dyschromatosis Universalis Hereditaria (DUH) belongs to a group of congenital diffuse reticulate pigmentary disorders characterised by both hypo and hyper pigmented macules. It is both hereditary and sporadic. A number of associated cutaneous and systemic diseases have been reported. The recent discovery of the mutation in ATP binding cassette protein, ABCB6 in DUH attempts to explain the reason behind the pigmentary abnormalities and varied associations. We add a new association by reporting a case of DUH with primary ovarian failure (POF) and hypothyroidism.

  8. An immunohistochemical perspective of PPAR beta and one of its putative targets PDK1 in normal ovaries, benign and malignant ovarian tumours.

    PubMed

    Ahmed, N; Riley, C; Quinn, M A

    2008-04-22

    Peroxisome proliferator-activated receptor beta (PPAR beta) is a member of the nuclear hormone receptor family and is a ligand-activated transcription factor with few known molecular targets including 3-phosphoinositide-dependent protein kinase 1(PDK1). In view of the association of PPAR beta and PDK1 with cancer, we have examined the expression of PPAR beta and PDK1 in normal ovaries and different histological grades of ovarian tumours. Normal ovaries, benign, borderline, grades 1, 2 and 3 ovarian tumours of serous, muciuous, endometrioid, clear cell and mixed subtypes were analysed by immunohistochemistry for PPAR beta and PDK1 expression. All normal ovarian tissues, benign, borderline and grade 1 tumours showed PPAR beta staining localised in the epithelium and stroma. Staining was predominantly nuclear, but some degree of cytoplasmic staining was also evident. Approximately 20% of grades 2 and 3 tumours lacked PPAR beta staining, whereas the rest displayed some degree of nuclear and cytoplasmic staining of the scattered epithelium and stroma. The extent of epithelial and stromal PPAR beta staining was significantly different among the normal and the histological grades of tumours (chi(2)=59.25, d.f.=25, P<0.001; chi(2)=64.48, d.f.=25, P<0.001). Significantly different staining of PPAR beta was observed in the epithelium and stroma of benign and borderline tumours compared with grades 1, 2 and 3 tumours (chi(2)=11.28, d.f.=4, P<0.05; chi(2)=16.15, d.f.=4, P<0.005). In contrast, PDK1 immunostaining was absent in 9 out of 10 normal ovaries. Weak staining for PDK1 was observed in one normal ovary and 40% of benign ovarian tumours. All borderline and malignant ovarian tumours showed positive cytoplasmic and membrane PDK1 staining. Staining of PDK1 was confined to the epithelium and the blood vessels, and no apparent staining of the stroma was evident. Significantly different PDK1 staining was observed between the benign/borderline and malignant ovarian tumours (chi

  9. Hemodynamic Consequences of Malignant Ascites in Epithelial Ovarian Cancer Surgery*: A Prospective Substudy of a Randomized Controlled Trial.

    PubMed

    Hunsicker, Oliver; Fotopoulou, Christina; Pietzner, Klaus; Koch, Mandy; Krannich, Alexander; Sehouli, Jalid; Spies, Claudia; Feldheiser, Aarne

    2015-12-01

    Malignant ascites (MA) is most commonly observed in patients scheduled for epithelial ovarian cancer (EOC) surgery and is supposed as a major risk factor promoting perioperative hemodynamic deterioration. We aimed to assess the hemodynamic consequences of MA on systemic circulation in patients undergoing cytoreductive EOC surgery.This study is a predefined post-hoc analysis of a randomized controlled pilot trial comparing intravenous solutions within a goal-directed algorithm to optimize hemodynamic therapy in patients undergoing cytoreductive EOC surgery. Ascites was used to stratify the EOC patients prior to randomization in the main study. We analyzed 2 groups according to the amount of ascites (NLAS: none or low ascites [<500 mL] vs HAS: high ascites group [>500 mL]). Differences in hemodynamic variables with respect to time were analyzed using nonparametric analysis for longitudinal data and multivariate generalized estimating equation adjusting the analysis for the randomized study groups of the main study.A total of 31 patients in the NLAS and 16 patients in the HAS group were analyzed. Although cardiac output was not different between groups suggesting a similar circulatory blood flow, the HAS group revealed higher heart rates and lower stroke volumes during surgery. There were no differences in pressure-based hemodynamic variables. In the HAS group, fluid demands, reflected by the time to reindication of a fluid challenge after preload optimization, increased steadily, whereas stroke volume could not be maintained at baseline resulting in hemodynamic instability after 1.5 h of surgery. In contrast, in the NLAS group fluid demands were stable and stroke volume could be maintained during surgery. Clinically relevant associations of the type of fluid replacement with hemodynamic consequences were particularly observed in the HAS group, in which transfusion of fresh frozen plasma (FFP) was associated to an improved circulatory flow and reduced

  10. Bone and Gallium scintigraphy in primary malignant and benign bone tumors of the extremities

    SciTech Connect

    Sepahdari, S.; Martin, W.B.; Ryan, J.; Simon, M.; Kirchner, P.

    1985-05-01

    A six yer prospective evaluation of 129 patients suspected of having a primary bone tumor included Tc-99m MDP bone scintigraphy followed by Ga-67 imaging at 48-72 hours. Blood pool images were part of bone scintigraphy in nearly half of the patients. Extent and intensity of tracer uptake in tumor and adjacent bone and joints were recorded for each tracer by two observers blind to the diagnosis. Tissue samples obtained in every patient by biopsy or tumor excision after scintigraphy, revealed 72 malignant and 57 benign bone tumors. The bone scan was positive in 95% (69/72) of malignancies. The scintigraphic intensity of benign and malignant lesions was comparable with both Tc-99m MDP and Ga-67. On the other hand, bone scintigraphy showed 72% (52/72) of bone malignancies to have abnormal proximal and distal bone/joint uptake whereas the Ga-67 images revealed this in only 6% (4/65) of malignancies. Benign lesions manifested this enhanced contiguous bone/joint uptake on only 8% (5/55) of bone and 0% of Ga-67 scans. This study concludes positive bone, blood pool, or Ga-67 images have less specificity for malignancy than the presence of increased Tc-99m MDP deposition in a contiguous bone/joint, but negative scintigraphic results strongly favor a benign lesion. Ga-67 was more accurate than Tc-99m MDP in portraying intraosseous extent of malignant tumors; however, this is now preferably done with C.T.

  11. Primary Malignant Melanoma of Maxilla: Report of a Case with Discussion

    PubMed Central

    Rani, G. Shirisha; Kumar, T. Vinay; Begum, Md Rezwana; Priya Srinivasan, Anu

    2014-01-01

    Primary oral malignant melanoma, very rare neoplasm of melanocytic origin, usually presents as a bluish black to tan-brown colored lesion Which is accounting for 0.2 to 8% of all melanomas, 1.6% of all head and neck malignancies, and 0.5% of all oral neoplasia. In general, the prognosis of oral melanoma is poor and worse than that of cutaneous melanoma. Here a case of oral malignant melanoma is presented, which was undetected during the first visit to a dental clinic. When a simple oral surgical treatment was carried out in that region, it resulted in the appearance of a massive pigmented lesion which was histopathologically diagnosed as malignant melanoma. This paper is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be viewed with suspicion and proper investigation (biopsy) should be carried out to rule out any untoward experiences later. PMID:25642350

  12. Primary Malignant B-cell Lymphoma of the Epididymis

    PubMed Central

    Suh, Jungyo; Jeong, Hyeon; Kim, Young A.

    2015-01-01

    Primary epididymal lymphomas are very rare condition, only 6 case report was published. In 4 of them, initial presentation was non-tender, continuous growth of testis. It can be misdiagnosed with epididymitis, 5 of them was treated by antibiotics before surgery. One patients treated by surgery another 5 makes neoadjuvant therapy, 2 of radiotherapy 3 of chemotherapy. Only one man died after treatment. This case is about 54-year male patients, diagnosed by diffuse large B-cell lymphoma, who treated by surgery and neoadjuvant chemotherapy combined with radiotherapy. PMID:26793572

  13. Variation in cell signaling protein expression may introduce sampling bias in primary epithelial ovarian cancer.

    PubMed

    Mittermeyer, Gabriele; Malinowsky, Katharina; Beese, Christian; Höfler, Heinz; Schmalfeldt, Barbara; Becker, Karl-Friedrich; Avril, Stefanie

    2013-01-01

    Although the expression of cell signaling proteins is used as prognostic and predictive biomarker, variability of protein levels within tumors is not well studied. We assessed intratumoral heterogeneity of protein expression within primary ovarian cancer. Full-length proteins were extracted from 88 formalin-fixed and paraffin-embedded tissue samples of 13 primary high-grade serous ovarian carcinomas with 5-9 samples each. In addition, 14 samples of normal fallopian tube epithelium served as reference. Quantitative reverse phase protein arrays were used to analyze the expression of 36 cell signaling proteins including HER2, EGFR, PI3K/Akt, and angiogenic pathways as well as 15 activated (phosphorylated) proteins. We found considerable intratumoral heterogeneity in the expression of proteins with a mean coefficient of variation of 25% (range 17-53%). The extent of intratumoral heterogeneity differed between proteins (p<0.005). Interestingly, there were no significant differences in the extent of heterogeneity between phosphorylated and non-phosphorylated proteins. In comparison, we assessed the variation of protein levels amongst tumors from different patients, which revealed a similar mean coefficient of variation of 21% (range 12-48%). Based on hierarchical clustering, samples from the same patient clustered more closely together compared to samples from different patients. However, a clear separation of tumor versus normal tissue by clustering was only achieved when mean expression values of all individual samples per tumor were analyzed. While differential expression of some proteins was detected independently of the sampling method used, the majority of proteins only demonstrated differential expression when mean expression values of multiple samples per tumor were analyzed. Our data indicate that assessment of established and novel cell signaling proteins as diagnostic or prognostic markers may require sampling of serous ovarian cancers at several distinct

  14. Variation in Cell Signaling Protein Expression May Introduce Sampling Bias in Primary Epithelial Ovarian Cancer

    PubMed Central

    Beese, Christian; Höfler, Heinz; Schmalfeldt, Barbara; Becker, Karl-Friedrich; Avril, Stefanie

    2013-01-01

    Although the expression of cell signaling proteins is used as prognostic and predictive biomarker, variability of protein levels within tumors is not well studied. We assessed intratumoral heterogeneity of protein expression within primary ovarian cancer. Full-length proteins were extracted from 88 formalin-fixed and paraffin-embedded tissue samples of 13 primary high-grade serous ovarian carcinomas with 5–9 samples each. In addition, 14 samples of normal fallopian tube epithelium served as reference. Quantitative reverse phase protein arrays were used to analyze the expression of 36 cell signaling proteins including HER2, EGFR, PI3K/Akt, and angiogenic pathways as well as 15 activated (phosphorylated) proteins. We found considerable intratumoral heterogeneity in the expression of proteins with a mean coefficient of variation of 25% (range 17–53%). The extent of intratumoral heterogeneity differed between proteins (p<0.005). Interestingly, there were no significant differences in the extent of heterogeneity between phosphorylated and non-phosphorylated proteins. In comparison, we assessed the variation of protein levels amongst tumors from different patients, which revealed a similar mean coefficient of variation of 21% (range 12–48%). Based on hierarchical clustering, samples from the same patient clustered more closely together compared to samples from different patients. However, a clear separation of tumor versus normal tissue by clustering was only achieved when mean expression values of all individual samples per tumor were analyzed. While differential expression of some proteins was detected independently of the sampling method used, the majority of proteins only demonstrated differential expression when mean expression values of multiple samples per tumor were analyzed. Our data indicate that assessment of established and novel cell signaling proteins as diagnostic or prognostic markers may require sampling of serous ovarian cancers at several

  15. Increased Incidence of Mitochondrial Cytochrome C Oxidase 1 Gene Mutations in Patients with Primary Ovarian Insufficiency

    PubMed Central

    Zhen, Xiumei; Wu, Bailin; Wang, Jian; Lu, Cuiling; Gao, Huafang; Qiao, Jie

    2015-01-01

    Primary ovarian insufficiency (POI), also known as premature ovarian failure (POF), is defined as more than six months of cessation of menses before the age of 40 years, with two serum follicle stimulating hormone (FSH) levels (at least 1 month apart) falling in the menopause range. The cause of POI remains undetermined in the majority of cases, although some studies have reported increased levels of reactive oxygen species (ROS) in idiopathic POF. The role of mitochondrial DNA in the pathogenesis of POI has not been studied extensively. This aim of this study was to uncover underlying mitochondrial genetic defects in patients with POI. The entire region of the mitochondrial genome was amplified in subjects with idiopathic POI (n=63) and age-matched healthy female controls (n=63) using nine pair sets of primers, followed by screening of the mitochondrial genome using an Illumina MiSeq. We identified a total of 96 non-synonymous mitochondrial variations in POI patients and 93 non-synonymous variations in control subjects. Of these, 21 (9 in POI and 12 in control) non-synonymous variations had not been reported previously. Eight mitochondrial cytochrome coxidase 1 (MT-CO1) missense variants were identified in POI patients, whereas only four missense mutations were observed in controls. A high incidence of MT-CO1 missense variants were identified in POI patients compared with controls, and the difference between the groups was statistically significant (13/63 vs. 5/63, p=0.042). Our results show that patients with primary ovarian insufficiency exhibit an increased incidence of mitochondrial cytochrome c oxidase 1 gene mutations, suggesting that MT-CO1 gene mutation may be causal in POI. PMID:26225554

  16. Metastatic malignant melanoma of the inguinal lymph node with unknown primary lesion.

    PubMed

    Eltawansy, Sherif Ali; Panasiti, Ryane; Hasanien, Samaa; Lourdusamy, Dennis; Sharon, David

    2015-01-01

    Background. Malignant melanoma could present with metastasis with unknown primary (MUP) and this happens in 2-3% according to the studies. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation. Case Report. We report a 58-year-old Caucasian male who presented with a right sided swelling in the inguinal region. Surgery was performed and biopsy showed metastatic malignant melanoma. No cutaneous lesions were identified by history or physical examination. Work up could not detect the primary lesion and patient was started on radiotherapy and immunotherapy. Conclusion. We present a case of malignant melanoma of unknown primary presenting in an unusual place which is the inguinal lymph node. Theories try to explain the pathway of development of such tumors and one of the theories mentions that it could be a spontaneous regression of the primary cutaneous lesion. Another theory is that it could be from transformation of aberrant melanocyte within the lymph node. Prognosis is postulated to be better in this case than in melanoma with a known primary. PMID:25705230

  17. Can primary optimal cytoreduction be predicted in advanced epithelial ovarian cancer preoperatively?

    PubMed Central

    2010-01-01

    Introduction Prediction of optimal cytoreduction in patients with advanced epithelial ovarian caner preoperatively. Methods Patients with advanced epithelial ovarian cancer who underwent surgery for the first time from Jan. to June 2008 at gynecologic oncology ward of TUMS (Tehran University of Medical Sciences) were eligible for this study. The possibility of predicting primary optimal cytoreduction considering multiple variables was evaluated. Variables were peritoneal carcinomatosis, serum CA125, ascites, pleural effusion, physical status and imaging findings. Univariate comparisons of patients underwent suboptimal cytoreduction carried out using Fisher's exact test for each of the potential predictors. The wilcoxon rank sum test was used to compare variables between patients with optimal versus suboptimal cytoreduction. Results 41 patients met study inclusion criteria. Statistically significant association was noted between peritoneal carcinomatosis and suboptimal cytoreduction. There were no statistically significant differences between physical status, pleural effusion, imaging findings, serum CA125 and ascites of individuals with optimal cytoreduction compared to those with suboptimal cytoreduction. Conclusions Because of small populations in our study the results are not reproducible in alternate populations. Only the patient who is most unlikely to undergo optimal cytoreduction should be offered neoadjuvant chemotherapy, unless her medical condition renders her unsuitable for primary surgery. PMID:20170515

  18. CD4+CD25+ T Cells in primary malignant hypertension related kidney injury

    PubMed Central

    Huang, Hongdong; Luo, Yang; Liang, Yumei; Long, Xidai; Peng, Youming; Liu, Zhihua; Wen, Xiaojun; Jia, Meng; Tian, Ru; Bai, Chengli; Li, Cui; He, Fuliang; Lin, Qiushi; Wang, Xueyan; Dong, Xiaoqun

    2016-01-01

    CD4+CD25+ T cells are critical for maintenance of immunologic self-tolerance. We measured the number of CD4+CD25+ cells in the patients with primary malignant hypertension related kidney injury, to explore the molecular pathogenesis of this disease. We selected 30 patients with primary malignant hypertension related kidney injury and 30 healthy volunteers. Information on clinical characteristics and laboratory tests was obtained from each subject. The number of CD4+CD25+ cells and glomerular injury were assessed by flow cytometry and histopathology, respectively. Both serum IL-2, IL-4, and IL-6 and endothelial cell markers were analyzed by ELISA. ADAMTS13 antibody was detected by Western blotting. CD4+CD25+ cells were significantly reduced in patients with primary malignant hypertension related kidney injury compared to controls (P < 0.05). The number of CD4+CD25+ cells was negatively related to blood urea nitrogen, serum uric acid, proteinuria, and supernatant IL-4; whereas positively associated with estimated glomerular filtration rate in patients. Gradually decreasing CD4+CD25+ cells were also found as increasing renal injury. Additionally, patients exhibited increasing supernatant IL-4, serum IL-2 and IL-6, endothelial cell markers, and anti-ADAMTS13 antibody compared with controls (all P < 0.05). CD4+CD25+ cells may play a key role in the pathogenesis of primary malignant hypertension related kidney injury. PMID:27278520

  19. Rare Skin Adnexal and Melanocytic Tumors Arising in Ovarian Mature Cystic Teratomas: A Report of 3 Cases and Review of the Literature.

    PubMed

    Moulla, Alexandra A; Magdy, Nesreen; Francis, Nicholas; Taube, Janis; Ronnett, Brigitte M; El-Bahrawy, Mona

    2016-09-01

    Mature teratoma of the ovary is the most common primary ovarian tumor accounting for 15% (10%-20%) of all ovarian neoplasms. Skin and skin adnexal structures are the most common elements identified in mature teratomas. Benign and malignant skin tumors can arise in ovarian teratomas, the most common being epithelial tumors. Melanocytic and adnexal tumors developing in a teratoma are rare and can be easily overlooked. We report 3 cases and review melanocytic and skin adnexal tumors encountered in ovarian teratomas.

  20. Delay in treatment of primary malignant and aggressive musculoskeletal tumours.

    PubMed

    Pan, K L; Zolqarnain, A; Chia, Y Y

    2006-02-01

    Patients with aggressive musculoskeletal tumours often arrive at specialised treatment centres late. Such a delay could mean disfavour for potentially curable or long-term disease-free outcome of limb preserving surgery. This study was undertaken to identify the underlying problem-related delay with a view to propose solution for solving it. We reviewed 30 patients to determine the periods of delay between onset of the first symptom and the definitive treatment. The delays were categorized as 'patient' delay, 'referral' delay and 'treatment' delay. There was 'patient' delay in 57% of patients (n=17), ranging from 1 to 18 months; 'referral' delay in 67% of patients (n=20) ranging from 1 to 19 months and 23% of patients (n=7) had treatment delay (average 23 days) at the treatment centre. The causes of late arrival are not solely patient-related but are multifactorial. Measures to minimize such delays include enhancing awareness only with high index of suspicion among primary care practitioners, creating a special lane specialized imaging studies and establishing a dedicated musculoskeletal tumour unit. PMID:17042231

  1. Statement by the Kommission Ovar of the AGO: The New FIGO and WHO Classifications of Ovarian, Fallopian Tube and Primary Peritoneal Cancer

    PubMed Central

    Meinhold-Heerlein, I.; Fotopoulou, C.; Harter, P.; Kurzeder, C.; Mustea, A.; Wimberger, P.; Hauptmann, S.; Sehouli, J.

    2015-01-01

    More than 25 years after the last revision, in 2012 the FIGO Oncology Committee began revising the FIGO classification for staging ovarian, Fallopian tube and primary peritoneal cancers. The new classification has become effective with its publication at the beginning of 2014. Following recent findings on the pathogenesis of ovarian, Fallopian tube and primary peritoneal cancer and reflecting standard clinical practice, the three entities have now been classified uniformly. The histological subtype is included (high-grade serous – HGSC; low-grade serous – LGSC; mucinous – MC; clear cell – CCC; endometrioid – EC). Stages III and IV have been fundamentally changed: stage IIIA now refers to a localized tumor limited to the pelvis with (only) retroperitoneal lymph node metastasis (formerly classified as IIIC). Stage IV has been divided into IVA and IVB, with IVA defined as malignant pleural effusion and IVB as parenchymatous or extra-abdominal metastasis including inguinal and mediastinal lymph node metastasis as well as umbilical metastasis. A new WHO classification was published almost concurrently. The classification of serous tumors addresses the issue of the tubal carcinogenesis of serous ovarian cancer, even if no tubal precursor lesions are found for up to 30 % of serous high-grade cancers. The number of subgroups was reduced and subgroups now include only high-grade serous, low-grade serous, mucinous, seromucinous, endometrioid, clear cell and Brenner tumors. The category “transitional cell carcinomas” has been dropped and the classification “seromucinous tumors” has been newly added. More attention has been focused on the role of borderline tumors as a stage in the progression from benign to invasive lesions. PMID:26556905

  2. Second primary malignancies among patients with myeloma-related-diseases in the KMF database.

    PubMed

    Kosugi, Satoru; Shibayama, Hirohiko; Nakatani, Eiji; Kida, Toru; Ohta, Kensuke; Kaneko, Hidemi; Yagi, Hideo; Tanaka, Hirokazu; Fuchida, Shin-Ichi; Nakaya, Aya; Kobayashi, Masayuki; Kuroda, Junya; Kamitsuji, Yuri; Uoshima, Nobuhiko; Adachi, Yoko; Tsudo, Mitsuru; Shimazaki, Chihiro; Nomura, Shosaku; Hino, Masayuki; Matsumura, Itaru; Taniwaki, Masashi; Kanakura, Yuzuru; Takaori-Kondo, Akifumi

    2016-07-01

    The incidence of second primary malignancies (SPMs) in Japanese patients with myeloma or myeloma-related diseases was studied by using the Kansai Myeloma Forum (KMF) database registered from November 2012 to March 2015. We studied 1,571 cases. Hematologic malignancies were documented in 10 patients, and solid tumors in 36 during this period. The cumulative 5-year incidence was estimated to be 1.0% for hematological malignancies and 3.7% for solid tumors. In the patients with smoldering myeloma or MGUS without treatment, solid tumors but not hematologic malignancies developed, though the cumulative incidence of each malignancy did not differ significantly from that in patients receiving treatment. Although statistical analysis showed that treatment with melphalan, bortezomib, lenalidomide, or thalidomide had no effect on the occurrence of hematological malignancies, lenalidomide administration was more frequent in the patients with solid tumors. To evaluate the SPMs in myeloma or myeloma-related diseases more accurately, accumulation of a larger number of patients and longer observation are needed. PMID:27498726

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

    PubMed Central

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

    2014-01-01

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

  4. Primary Malignant Melanoma of Renal Pelvis with Extensive Clear Cell Change

    PubMed Central

    Liapis, George; Sarlanis, Helen; Poulaki, Elpida; Stravodimos, Konstandinos; Lazaris, Andreas C

    2016-01-01

    Our presentation illustrates a rare case of primary renal pelvis malignant melanoma in a 35-year-old man. The diagnosis of malignant melanoma was based on immunophenotype and the detection of intracellular melanin pigment. The renal origin was proven by the presence of scattered melanocytes within the urothelium of the pelvis. The tumor exhibited extensive clear cell change that closely mimics clear cell renal cell carcinoma. The patient’s clinical history did not disclose any signs of previous melanocytic skin or mucosa lesions. Differential diagnosis includes tumors capable of synthesizing melanin or expressing melanocytic markers. PMID:27226943

  5. Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours.

    PubMed

    Swierzko, Anna St; Szala, Agnieszka; Sawicki, Sambor; Szemraj, Janusz; Sniadecki, Marcin; Sokolowska, Anna; Kaluzynski, Andrzej; Wydra, Dariusz; Cedzynski, Maciej

    2014-11-01

    Mannose-Binding Lectin (MBL) is a serum pattern recognition molecule, able to activate complement in association with MASP proteases. Serum levels of MBL and MASP-2, activities of MBL-MASP complexes, single nucleotide polymorphisms of the MBL2 and MASP2 genes and/or their specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary ovarian cancer (OC) and compared with 197 controls (C), encompassing both patients with benign ovarian tumours (n = 123) and others with no ovarian pathology (n = 74). MBL deficiency-associated genotypes were more common among OC patients than among controls. The O/O group of genotypes was associated with ovarian cancer (OR 3.5, p = 0.02). In A/A homozygotes, MBL concentrations and activities were elevated in the OC group and correlated with C-reactive protein. Moreover, high MBL serum levels were associated with more advanced disease stage. No differences in distribution of the MASP2 +359 A>G (D120G) SNP or MASP-2 serum levels were found between cancer patients and their controls. However, the highest frequency of the A/G (MASP2) and LXA/O or O/O (MBL2) genotypes was found among OC patients with tumours of G1-2 grade (well/moderately differentiated). Furthermore, MBL deficiency-associated genotypes predicted prolonged survival. None of the parameters investigated correlated with CA125 antigen or patients' age. The local expression of MBL2 and MASP2 genes was higher in women with ovarian cancer compared with controls. It is concluded that the expression of MBL and MASP-2 is altered in ovarian cancer, possibly indicating involvement of the lectin pathway of complement activation in the disease.

  6. FDG-PET on the trail of an unsuspected primary malignancy in the breast.

    PubMed

    Dockery, Keith F; Puri, Savita; Qazi, Raman; Davis, Delphine

    2008-03-01

    Proper identification of the primary malignancy can radically alter clinical management for the patient's benefit. This is a report of an unsuspected primary breast cancer in a patient being worked up for presumptive lymphoma. Prior investigation of lymphedema in the left lower extremity found widespread lymphadenopathy on computed tomography imaging, leading to initial biopsy revealing adenocarcinoma of unknown primary. F-18 fluorodeoxyglucose PET/computed tomography altered management by localizing an F-18 fluorodeoxyglucose avid breast nodule, directing breast biopsy with specific immunohistochemical analysis for breast cancer lineage in metastatic adenocarcinoma. The patient responded well to breast cancer-targeted chemotherapy.

  7. A non-sense MCM9 mutation in a familial case of primary ovarian insufficiency.

    PubMed

    Fauchereau, F; Shalev, S; Chervinsky, E; Beck-Fruchter, R; Legois, B; Fellous, M; Caburet, S; Veitia, R A

    2016-05-01

    Primary ovarian insufficiency (POI) results in an early loss of ovarian function, and remains idiopathic in about 80% of cases. Here, we have performed a complete genetic study of a consanguineous family with two POI cases. Linkage analysis and homozygosity mapping identified 12 homozygous regions with linkage, totalling 84 Mb. Whole-exome sequencing of the two patients and a non-affected sister allowed us to detect a homozygous causal variant in the MCM9 gene. The variant c.1483G>T [p.E495*], confirmed using Sanger sequencing, introduced a premature stop codon in coding exon 8 and is expected to lead to the loss of a functional protein. MCM9 belongs to a complex required for DNA repair by homologous recombination, and its impairment in mouse is known to induce meiotic recombination defects and oocyte degeneration. A previous study recently described two consanguineous families in which homozygous mutations of MCM9 were responsible for POI and short stature. Interestingly, the affected sisters in the family described here had a normal height. Altogether, our results provide the confirmation of the implication of MCM9 variants in POI and expand their phenotypic spectrum. PMID:26771056

  8. Differential in vitro effects of chemotherapeutic agents on primary cultures of human ovarian carcinoma.

    PubMed

    Kornblith, P; Ochs, R L; Wells, A; Gabrin, M J; Piwowar, J; Chattopadhyay, A; George, L D; Burholt, D

    2004-01-01

    The treatment of ovarian cancer principally relies on the use of platinum and taxane chemotherapeutic agents. Short-term clinical results have been encouraging, but long-term responses remain limited. In this report, an in vitro assay system that utilizes cells grown from human tumor explants has been used to quantitatively evaluate responses to relevant concentrations of alternative chemotherapeutic agents. The results suggest that there are significant differences in the responses of explant-derived cultured cells to the different agents tested. In an evaluation of 276 primary ovarian cancer specimens, five nonstandard drugs were tested in 51 cases. Of these 51 cases, cyclophosphamide had the highest rate of response at 67%, followed by doxorubicin at 61%, gemcitabine at 49%, etoposide at 48%, and topotecan at 14%. Venn diagrams, representing the in vitro responses to the platins and taxanes, as well as the responses to the nonstandard drugs, illustrate that there clearly are distinct differences among patients in a given population. These data underscore the potential importance of evaluating each patient's response to a number of different drugs to optimize the therapeutic decision-making process. PMID:15304154

  9. Macrophage Blockade Using CSF1R Inhibitors Reverses the Vascular Leakage Underlying Malignant Ascites in Late-Stage Epithelial Ovarian Cancer.

    PubMed

    Moughon, Diana L; He, Huanhuan; Schokrpur, Shiruyeh; Jiang, Ziyue Karen; Yaqoob, Madeeha; David, John; Lin, Crystal; Iruela-Arispe, M Luisa; Dorigo, Oliver; Wu, Lily

    2015-11-15

    Malignant ascites is a common complication in the late stages of epithelial ovarian cancer (EOC) that greatly diminishes the quality of life of patients. Malignant ascites is a known consequence of vascular dysfunction, but current approved treatments are not effective in preventing fluid accumulation. In this study, we investigated an alternative strategy of targeting macrophage functions to reverse the vascular pathology of malignant ascites using fluid from human patients and an immunocompetent murine model (ID8) of EOC that mirrors human disease by developing progressive vascular disorganization and leakiness culminating in massive ascites. We demonstrate that the macrophage content in ascites fluid from human patients and the ID8 model directly correlates with vascular permeability. To further substantiate macrophages' role in the pathogenesis of malignant ascites, we blocked macrophage function in ID8 mice using a colony-stimulating factor 1 receptor kinase inhibitor (GW2580). Administration of GW2580 in the late stages of disease resulted in reduced infiltration of protumorigenic (M2) macrophages and dramatically decreased ascites volume. Moreover, the disorganized peritoneal vasculature became normalized and sera from GW2580-treated ascites protected against endothelial permeability. Therefore, our findings suggest that macrophage-targeted treatment may be a promising strategy toward a safe and effective means to control malignant ascites of EOC.

  10. Primary Patency of Wallstents in Malignant Bile Duct Obstruction: Single vs. Two or More Noncoaxial Stents

    SciTech Connect

    Maybody, Majid Brown, Karen T.; Brody, Lynn A.; Covey, Anne M.; Sofocleous, Constantinos T.; Thornton, Raymond H.; Getrajdman, George I.

    2009-07-15

    The purpose of this study was to determine the primary patency of two or more noncoaxial self-expanding metallic Wallstents (Boston Scientific, Natick, MA) and to compare this with the primary patency of a single stent in malignant bile duct obstruction. From August 2002 to August 2004, 127 patients had stents placed for malignant bile duct obstruction. Forty-five patients were treated with more than one noncoaxial self-expanding metallic stents and 82 patients had a single stent placed. Two patients in the multiple-stent group were lost to follow-up. The primary patency period was calculated from the date of stenting until the first poststenting intervention for stent occlusion, death, or the time of last documented follow-up. The patency of a single stent was significantly different from that of multiple stents (P = 0.0004). In the subset of patients with high bile duct obstruction, the patency of a single stent remained significantly different from that of multiple stents (P = 0.02). In the single-stent group, there was no difference in patency between patients with high vs. those with low bile duct obstruction (P = 0.43). The overall median patency for the multistent group and the single-stent group was 201 and 261 days, respectively. In conclusion, the patency of a single stent placed for malignant low or high bile duct obstruction is similar, and significantly longer than, that of multiple stents placed for malignant high bile duct obstruction. Given the median patency of 201 days, when indicated, percutaneous stenting of multiple bile ducts is an effective palliative measure for patients with malignant high bile duct obstruction.

  11. Differentiating histologic malignancy of primary brain tumors: Pentavalent Technetium-99m-DMSA

    SciTech Connect

    Hirano, Tsuneo; Otake, Hidenori; Shibasaki, Takashi

    1997-01-01

    This study assessed pentavalent {sup 99m}Tc-DMSA uptake in primary brain tumors and evaluated the relationship between retention and histologic malignancy. SPECT images of the brain were obtained at 30 min and 3 hr after intravenous administration of approximately 555 MBq {sup 99m}Tc(V)-DMSA in patients with brain tumors. Sixty studies were performed in 57 patients and 63 lesions were demonstrated: 11 glioblastomas, 13 anaplastic astrocytomas (Grade 3), 11 astrocytomas (Grade 2), 18 meningiomas and 10 schwannomas. Uptake ratios, retention ratio and retention index were calculated and compared with tumor histology and malignancy grade. Approximately 95% of both benign and malignant primary brain tumors were demonstrated by {sup 99m}Tc(V)-DMSA SPECT images. False negative was noted in three cases. The early uptake ratios were closely related to the tumor vascularity but had no statistically significant difference in the tumor vascularity but had no statistically significant difference in the tumor histology or histologic malignancy. 16 refs., 6 figs., 2 tabs.

  12. One world, one woman: a transformational leader’s approach to primary ovarian insufficiency

    PubMed Central

    Nelson, Lawrence M.

    2011-01-01

    Lectureship endowment funds are created to honor major contributions that have clearly advanced a field. In some select cases they recognize the contributions of a transformational leader. Such was the case in the creation of the Wulf H. Utian Endowed Lectureship Fund. The express purpose of the fund is to provide travel to the annual meeting by a lecturer selected by the North American Menopause Society Scientific Program Committee. Wulf H. Utian changed the paradigm for menopause by creating an organization whose major purpose was to employ an integrated approach to the condition. Such an approach would benefit many areas of healthcare. This report summarizes my thoughts on how such an integrated approach might advance the field of primary ovarian insufficiency. PMID:21686065

  13. Primary ovarian insufficiency: different approaches in three cases and a review of literature

    PubMed Central

    Moreira, Ana Marina

    2016-01-01

    Summary Primary ovarian insufficiency (POI) is the condition of intermittent or permanent gonadal insufficiency that occurs in women before the age of 40. We describe three cases of POI referred to the outpatient endocrinology clinic of a university hospital. The three patients met diagnostic criteria for POI and were managed by specific approaches tailored to individualized goals. In the first case, the main concern was fertility and the reproductive prognosis. The second patient was a carrier of a common genetic cause of POI: premutation of the FMR1 gene. The third case was a patient diagnosed with a POI and established osteoporosis, a common complication of estrogen deprivation. This study reports the treatment and follow-up of these cases, with an emphasis on relevant aspects of individualized management, alongside a brief literature review. Learning points A diagnosis of POI should be considered in patients presenting with amenorrhea or irregular menses and high serum follicle-stimulating hormone (FSH) levels before age 40 years. Patients with POI without an established cause, especially in familial cases, should be tested for FMR1 mutations. Estrogen/progestin replacement therapy is indicated since diagnosis until at least the estimated age of menopause, and is the cornerstone for maintaining the good health of breast and urogenital tract and for primary or secondary osteoporosis prevention in POI. Fertility should be managed through an individualized approach based on patient possibilities, such as egg or embryo donation and ovarian cryopreservation; pregnancy can occur spontaneously in a minority of cases. Women with POI should be carefully monitored for cardiovascular risk factors. PMID:27252868

  14. Primary Malignant Vaginal Melanoma – Case Report and Review of the Literature

    PubMed Central

    Kühn, F.; Dieterich, M.; Klar, E.; Gerber, B.; Prinz, C.

    2012-01-01

    With fewer than 250 cases published worldwide, primary vaginal melanoma is an extremely rare malignant entity which is mostly diagnosed in advanced stages. The estimated incidence of vaginal melanoma is 0.026/100 000 women per year. The poor prognosis for advanced tumour stages and different therapies used in very limited numbers of patients require precise preoperative staging and a planned interdisciplinary therapeutic approach. PMID:25258467

  15. Somatic mutation profiles in primary colorectal cancers and matching ovarian metastases: Identification of driver and passenger mutations

    PubMed Central

    Crobach, Stijn; Ruano, Dina; van Eijk, Ronald; Schrumpf, Melanie; Fleuren, Gertjan; van Wezel, Tom

    2016-01-01

    Abstract The mutational profiles of primary colorectal cancers (CRCs) and corresponding ovarian metastases were compared. Using a custom‐made next generation sequencing panel, 115 cancer‐driving genes were analyzed in a cohort of 26 primary CRCs and 30 matching ovarian metastases (four with bilateral metastases). To obtain a complete overview of the mutational profile, low thresholds were used in bioinformatics analysis to prevent low frequency passenger mutations from being filtered out. A subset of variants was validated using Sanger and/or hydrolysis probe assays. The mutational landscape of CRC that metastasized to the ovary was not strikingly different from CRC in consecutive series. When comparing primary CRCs and their matching ovarian metastases, there was considerable overlap in the mutations of early affected genes. A subset of mutations demonstrated less overlap, presumably being passenger mutations. In particular, primary CRCs showed a substantially high number of passenger mutations. We also compared the primary CRCs and matching metastases for stratifying variants of six genes (KRAS, NRAS, BRAF, FBXW7, PTEN and PIK3CA) that select for established (EGFR directed) or future targeted therapies. In a total of 31 variants 12 were not found in either of the two locations. Tumours thus differed in the number of discordant variants between the primary tumours and matching metastases. Half of these discordant variants were definitive class 4/5 pathogenic variants. However, in terms of temporal heterogeneity, no clear relationship was observed between the number of discordant variants and the time interval between primary CRCs and the detection of ovarian metastases. This suggests that dormant metastases may be present from the early days of the primary tumours. PMID:27499925

  16. Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (Tumors of Low Malignant Potential) Based on Clinical Outcome.

    PubMed

    McKenney, Jesse K; Gilks, C Blake; Kalloger, Steve; Longacre, Teri A

    2016-09-01

    The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli. Follow-up of 156 (86%) patients ranged from 11 to 264 months (mean, 89 mo; median, 94 mo). Implants with low-power destructive invasion into underlying tissue were the best predictor of adverse patient outcome with 69% overall and 59% disease-free survival (P<0.01). In the evaluation of individual morphologic features, the low-power destructive tissue invasion criterion also had excellent reproducibility between observers (κ=0.84). Extraovarian implants with micropapillary architecture or solid nests with clefts were often associated with tissue invasion but did not add significant prognostic value beyond destructive tissue invasion alone. Implants without attached normal tissue were not associated with adverse outcome and appear to be noninvasive. Because the presence of invasion in an extraovarian implant is associated with an overall survival analogous to that of low-grade serous carcinoma, the designation low-grade serous carcinoma is recommended. Even though the low-power destructive tissue invasion criterion has excellent interobserver reproducibility, it is further

  17. Institutional experience using interstitial brachytherapy for the treatment of primary and recurrent pelvic malignancies

    PubMed Central

    Onderdonk, Benjamin; Cunningham, Mary; Daugherty, Emily; Du, Lingyun; Bunn, W. Douglas; Agarwal, Rinki; Hahn, Seung Shin

    2016-01-01

    Purpose The study assessed the outcomes of patients at a single institution with locally advanced primary and recurrent pelvic malignancies treated with interstitial high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy (BT), using a modified Syed-Neblett template. Material and methods Between 1996 and 2010, 60 patients with primary or recurrent pelvic malignancies were treated with interstitial BT. Thirty three patients had primary malignancies with 6.1% being stage I, 33.3% stage II, 45.5% stage III, and 15.2% stage IV; the remaining 27 patients were recurrent malignancies. Fifty four patients received external beam radiotherapy (EBRT) as part of their treatment course. The median EBRT, BT, and EBRT + BT doses were 45 Gy, 20 Gy, and 65 Gy, respectively. Thirty eight patients received concurrent chemotherapy with EBRT. Complete response (CR) was defined by absence of clinical and radiographic disease on first follow-up. Toxicity was graded as per Common Terminology Criteria for Adverse Events, version 4.0. Results The median follow-up was 37 months (4-234 months) and initial CR was achieved in 91%. For primary cancers at diagnosis, 5-year local control (LC), 5-year progression-free survival (PFS), 5-year overall survival (OS) were 65%, 64%, and 42% respectively. For recurrent cancers at diagnosis, 5-year LC, 5-year PFS, and 5-year OS were 80%, 51%, and 37%, respectively. There was a significant difference in both OS and PFS among different tumor sites (p < 0.05), with vaginal cancers having the best 5-year OS (55%) and PFS (84%). There was a total of 1 acute toxicity ≥ grade 3, 6 late grade 3 toxicities, and late grade 4 toxicity. Conclusions Our series suggests that interstitial BT using a modified Syed-Neblett template is a safe and effective treatment for primary or recurrent pelvic malignancies. This technique allowed effective LC and 97% of patients had preservation of both bladder and rectal function. PMID:27504125

  18. Primary hepatic solitary fibrous tumor with histologically benign and malignant areas.

    PubMed

    Silvanto, Anna; Karanjia, Nariman D; Bagwan, Izhar N

    2015-12-01

    Extrapleural solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm, presenting most commonly in the intrathoracic sites but which has been reported at numerous extrathoracic locations. The majority of intra-thoracic SFTs are benign, but 10%-15% behave aggressively. We report a case of primary hepatic SFT with histologically benign and malignant areas. A 65-year-old man underwent an abdominal CT scan following a cerebrovascular accident, which demonstrated a sharply demarcated large liver mass with a heterogenous enhancing area and occupying most of the left lobe of the liver. Histological examination following a hemihepatectomy showed an SFT with morphological patterns ranging from benign to malignant areas, including pleomorphism, increased cellularity, herringbone pattern, necrosis and a raised mitotic count. On review of the literature, only an occasional case report with malignant areas in a hepatic SFT was identified. This case highlights that SFT should be included in the differential diagnosis of a hepatic spindle cell lesion, and that on rare occasions, malignant areas can occur in this already uncommon neoplasm. PMID:26663016

  19. Primary hepatic solitary fibrous tumor with histologically benign and malignant areas.

    PubMed

    Silvanto, Anna; Karanjia, Nariman D; Bagwan, Izhar N

    2015-12-01

    Extrapleural solitary fibrous tumor (SFT) is an uncommon mesenchymal neoplasm, presenting most commonly in the intrathoracic sites but which has been reported at numerous extrathoracic locations. The majority of intra-thoracic SFTs are benign, but 10%-15% behave aggressively. We report a case of primary hepatic SFT with histologically benign and malignant areas. A 65-year-old man underwent an abdominal CT scan following a cerebrovascular accident, which demonstrated a sharply demarcated large liver mass with a heterogenous enhancing area and occupying most of the left lobe of the liver. Histological examination following a hemihepatectomy showed an SFT with morphological patterns ranging from benign to malignant areas, including pleomorphism, increased cellularity, herringbone pattern, necrosis and a raised mitotic count. On review of the literature, only an occasional case report with malignant areas in a hepatic SFT was identified. This case highlights that SFT should be included in the differential diagnosis of a hepatic spindle cell lesion, and that on rare occasions, malignant areas can occur in this already uncommon neoplasm.

  20. Cutaneous Metastases of the Synchronous Primary Endometrial and Bilateral Ovarian Cancer: An Infrequent Presentation and Literature Review.

    PubMed

    Kanyilmaz, Gul; Aktan, Meryem; Koc, Mehmet; Findik, Siddika

    2016-01-01

    There are limited data about the cutaneous metastases of gynecological malignancies in the literature. Based on this limited number of studies, cutaneous metastases from gynecological malignancies are uncommon occurrences. Cutaneous metastases from the synchronous endometrioid carcinoma of the uterine corpus and bilateral ovaries arising from endometriosis are extremely rare. Herein, we report a 51-year-old woman with FIGO Stage 1A Grade 1 endometrial endometrioid-type adenocarcinoma and synchronous bilateral Stage 1B ovarian endometrioid-type adenocarcinoma who presented 34 months following total abdominal hysterectomy and bilateral salpingo-oophorectomy with skin metastases. After the patient underwent an excisional biopsy, we applied a palliative radiotherapy. The patient received the combination therapy with cisplatin and doxorubicin after the completion of radiotherapy but the disease evolution was rapidly fatal and the patient died 4 months after her admission to our department due to widely disseminated disease. PMID:27597911

  1. Cutaneous Metastases of the Synchronous Primary Endometrial and Bilateral Ovarian Cancer: An Infrequent Presentation and Literature Review

    PubMed Central

    Koc, Mehmet; Findik, Siddika

    2016-01-01

    There are limited data about the cutaneous metastases of gynecological malignancies in the literature. Based on this limited number of studies, cutaneous metastases from gynecological malignancies are uncommon occurrences. Cutaneous metastases from the synchronous endometrioid carcinoma of the uterine corpus and bilateral ovaries arising from endometriosis are extremely rare. Herein, we report a 51-year-old woman with FIGO Stage 1A Grade 1 endometrial endometrioid-type adenocarcinoma and synchronous bilateral Stage 1B ovarian endometrioid-type adenocarcinoma who presented 34 months following total abdominal hysterectomy and bilateral salpingo-oophorectomy with skin metastases. After the patient underwent an excisional biopsy, we applied a palliative radiotherapy. The patient received the combination therapy with cisplatin and doxorubicin after the completion of radiotherapy but the disease evolution was rapidly fatal and the patient died 4 months after her admission to our department due to widely disseminated disease. PMID:27597911

  2. The clinical pathological features, diagnosis, treatment and prognosis of small intestine primary malignant tumors.

    PubMed

    Guo, Xiaochuan; Mao, Zhiyuan; Su, Dan; Jiang, Zhaocai; Bai, Li

    2014-04-01

    The aim of the study was to describe and analyze the clinicopathological features and diagnosis of Chinese patients with small intestine primary malignant tumors and to explore the best therapy to small bowel adenocarcinoma (SBA). More than 26,000 patients with digestive tract malignant tumors received treatment in PLA hospital from 2000 to 2011, and among them, there were 887 patients who had small intestine primary malignant tumors, and 666 of 887 patients had the completed basic clinical documents. We retrospectively analyzed the correlation between clinical and pathological features of the 666 patients and analyzed the survival and prognosis of 173 SBA patients with follow-up data. Both the number of patients with primary malignant tumors of the small intestine and the number of patients who received chemotherapy showed an increasing trend. The ratio of male to female was 1.58:1. The male patients significantly exceed the female patients with tumors of non-ampullary duodenum, jejunum and duodenal ampulla; and most of the patients are over 60 years of age. For patients burdened with either of the pathological types of tumors, the males exceeded the females, but there was no significant difference. Abdominal pain was the main clinical manifestation for patients with tumors of non-ampullary duodenum, jejunum and ileum, and the most common clinical manifestations were jaundice and abdominal pain for patients with ampullary duodenal tumors, adenocarcinoma, neuroendocrine tumors and sarcoma. In addition, patients with stromal tumors were prone to gastrointestinal bleeding. Gastrointestinal endoscopy was the most common examinational procedure. Patients under 60 years of age were prone to surgery and chemotherapy after surgery, and patients over 60 years of age were prone to supportive treatment and chemotherapy without surgery. The medium overall survival of patients who received surgery without chemotherapy, chemotherapy after surgery, chemotherapy without surgery

  3. STAG3 truncating variant as the cause of primary ovarian insufficiency

    PubMed Central

    Le Quesne Stabej, Polona; Williams, Hywel J; James, Chela; Tekman, Mehmet; Stanescu, Horia C; Kleta, Robert; Ocaka, Louise; Lescai, Francesco; Storr, Helen L; Bitner-Glindzicz, Maria; Bacchelli, Chiara; Conway, Gerard S

    2016-01-01

    Primary ovarian insufficiency (POI) is a distressing cause of infertility in young women. POI is heterogeneous with only a few causative genes having been discovered so far. Our objective was to determine the genetic cause of POI in a consanguineous Lebanese family with two affected sisters presenting with primary amenorrhoea and an absence of any pubertal development. Multipoint parametric linkage analysis was performed. Whole-exome sequencing was done on the proband. Linkage analysis identified a locus on chromosome 7 where exome sequencing successfully identified a homozygous two base pair duplication (c.1947_48dupCT), leading to a truncated protein p.(Y650Sfs*22) in the STAG3 gene, confirming it as the cause of POI in this family. Exome sequencing combined with linkage analyses offers a powerful tool to efficiently find novel genetic causes of rare, heterogeneous disorders, even in small single families. This is only the second report of a STAG3 variant; the first STAG3 variant was recently described in a phenotypically similar family with extreme POI. Identification of an additional family highlights the importance of STAG3 in POI pathogenesis and suggests it should be evaluated in families affected with POI. PMID:26059840

  4. Expression of WT1, CA 125, and GCDFP-15 as useful markers in the differential diagnosis of primary ovarian carcinomas versus metastatic breast cancer to the ovary.

    PubMed

    Tornos, Carmen; Soslow, Robert; Chen, Shirley; Akram, Muzaffar; Hummer, Amanda J; Abu-Rustum, Nadeen; Norton, Larry; Tan, Lee K

    2005-11-01

    Metastatic breast carcinoma to the ovary is sometimes difficult to differentiate from primary ovarian carcinoma. This problem is often encountered in breast carcinoma patients who develop adnexal masses. ER and PR can be positive in a high percentage of breast and ovarian carcinomas, and therefore cannot be used in the differential diagnosis of these entities. WT1 and CA125 have been identified as possible markers for ovarian cancer. However, no studies have been done that specifically compare the immunophenotype of breast carcinoma metastatic to ovary with that of primary ovarian cancer. Thirty-nine cases of metastatic breast carcinoma to the ovary, 36 primary breast carcinomas, and 42 primary ovarian carcinomas were examined immunohistochemically for the expression of WT1, CA125, carcinoembryonic antigen, MUC2, MUC1, and GCDFP. The percentage of cells stained and the intensity of staining were recorded. Thirty-two ovarian carcinomas (76%) were positive for WT1, including 31 of 33 (94%) serous carcinomas. Most of them had strong and diffuse staining. None of the breast cancers either primary or metastatic to the ovary expressed WT1. Thirty-eight (90%) ovarian carcinomas were positive for CA125, most of them with strong and diffuse staining. Most breast carcinomas were negative for CA125, with only 6 (16%) of the primary ones and 5 (12%) of the metastatic showing weak and focal positivity. All ovarian carcinomas were negative for GCDFP. Five primary breast cancers (14%) and 17 (43%) metastatic to the ovary were positive for GCDFP. Nine (21%) ovarian carcinomas, 8 (22%) primary breast carcinomas, and 13 (33%) metastatic to the ovary were positive for carcinoembryonic antigen. Almost all tumors examined were positive for MUC1 (100% ovarian carcinomas, 100% primary breast carcinomas, and 95% metastatic breast carcinomas to ovary). MUC2 was positive in 10 (24%) ovarian carcinomas, 3 (8%) primary breast cancers, and 12 (30%) metastases to the ovary. The presence of

  5. Primary mucosal malignant melanoma of the cervix: case report and review of the literature.

    PubMed

    Cetinkaya, Kadir; Benzer, Emine; Dervisoglu, Haluk

    2015-09-09

    The incidence of primary mucosal malignant melanoma (PMMM) is 1.3% among all malignant melanomas (MM). Cervical involvement is very rare; the number of cases of cervical PMMM reported so far is around 80. In our patient, a dark color, 2-cm diameter, nonulcerated tumor formation was observed upon examination of the cervix. Tumoral tissue consisted of atypical melanocytic cells containing numerous mitotic figures. In immunochemical studies, S-100, Melan-A, and HMB-45 positivity were observed. The tumor was 20 mm in invasion depth, Breslow IV, and FIGO stage IB1. Radical surgery was followed by adjuvant radiotherapy, and subsequently interferon treatment was applied. Examination and scans 20 months after surgery were free from tumor.

  6. Primary malignant melanoma of the esophagus treated by endoscopic submucosal dissection: A case report

    PubMed Central

    Wang, Mei; Chen, Jianping; Sun, Kewen; Zhuang, Yun; Xu, Fu; Xu, Bin; Zhang, Hongyu; Li, Qing; Zhang, Dachuan

    2016-01-01

    Primary malignant melanoma of the esophagus (PMME) is a rare malignant neoplasm of the esophagus. In the majority of cases, the disease originates in the mucosal layer of the esophagus, which is similar to other types of esophageal cancer. With the development of endoscopic submucosal dissection (ESD), endoscopic resection is possible for cases in which melanomas are limited to the mucosal and submucosal layer. However, few studies report the efficiency of ESD for PMME, and no studies perform long-term follow-up. The present study reported the case of a 71-year-old PMME patient who was successfully treated by ESD at The Third Affiliated Hospital of Soochow University (Changzhou, China) in Otober 2011, with a follow-up of >3 years conducted.

  7. Primary malignant melanoma of the esophagus treated by endoscopic submucosal dissection: A case report

    PubMed Central

    Wang, Mei; Chen, Jianping; Sun, Kewen; Zhuang, Yun; Xu, Fu; Xu, Bin; Zhang, Hongyu; Li, Qing; Zhang, Dachuan

    2016-01-01

    Primary malignant melanoma of the esophagus (PMME) is a rare malignant neoplasm of the esophagus. In the majority of cases, the disease originates in the mucosal layer of the esophagus, which is similar to other types of esophageal cancer. With the development of endoscopic submucosal dissection (ESD), endoscopic resection is possible for cases in which melanomas are limited to the mucosal and submucosal layer. However, few studies report the efficiency of ESD for PMME, and no studies perform long-term follow-up. The present study reported the case of a 71-year-old PMME patient who was successfully treated by ESD at The Third Affiliated Hospital of Soochow University (Changzhou, China) in Otober 2011, with a follow-up of >3 years conducted. PMID:27602062

  8. Primary penile adenocarcinoma with concurrent hypercalcaemia of malignancy in a dog.

    PubMed

    Furtado, A R R; Parrinello, L; Merlo, M; Di Bella, A

    2015-04-01

    A 13-year-old male neutered Siberian husky crossbreed dog was presented with a 3-week history of haematuria and penile swelling. Clinical examination and computed tomography demonstrated a soft-tissue mass located at the base of the penis without signs of other primary tumours or metastasis. Clinicopathological findings revealed paraneoplastic hypercalcaemia. Fine-needle aspiration cytology of the mass suggested an epithelial tumour with several criteria of malignancy present. Following surgical excision of the mass, the hypercalcaemia resolved. Histopathology and immunohistochemistry revealed features consistent with an adenocarcinoma. Despite thorough examination, no perineal or anal sac tumour was found. To the authors' knowledge, this is the first reported case of a penile adenocarcinoma with hypercalcaemia of malignancy.

  9. Primary malignant melanoma of oral cavity: A tertiary care center experience

    PubMed Central

    Kumar, Vijay; Vishnoi, Jeewan Ram; Kori, Channabasappa G.; Gupta, Sameer; Misra, Sanjeev; Akhtar, Naseem

    2015-01-01

    Background: Primary mucosal malignant melanoma is an extremely rare, aggressive neoplasm accounting for 0.5% of all oral malignancies. Any pigmented lesion in oral cavity should have an index of suspicion, which should be investigated to detect the disease at an early stage and managed appropriately. Melanomas tend to invade locally into the tissue or metastasize more commonly than other malignant tumors of the oral cavity. Materials and Methods: We report a retrospective case series of eight patients suffering from primary oral malignant melanoma treated in our department between 2012 and 2014. The details were recorded from the departmental computerized database and patients on follow-up. Results: There were six male and two female patients with a mean age of 46.8 years. Hard palate was the most common affected site in oral cavity. Pigmented lesion\\ulcer was the most common presenting symptom. Majority of patients (5 patients) were diagnosed with Stage III (distant metastasis), two patients in Stage II, and one patient in Stage I. Three patients were treated with definitive surgery and five patients with palliative chemotherapy in view of distant disease. Following surgery, two of them required adjuvant chemoradiotherapy in view of nodal spread. Patients had a mean follow-up of 10.5 months (range: 8–26 months). Patients treated with definitive surgery had a mean survival rate of 16 months (range: 10–26 months), with local recurrence in one patient. Metastatic melanoma patients treated with palliative chemotherapy had a mean disease control rate of 5 months (range 5–9 months). Conclusion: Oral melanoma carries dismal prognosis with a 5-year survival rate of 5–20%. Early detection of the lesion, proper evaluation, and appropriate treatment are very important to cure the disease. PMID:27390490

  10. Mammalian models of chemically induced primary malignancies exploitable for imaging-based preclinical theragnostic research

    PubMed Central

    Liu, Yewei; Yin, Ting; Feng, Yuanbo; Cona, Marlein Miranda; Huang, Gang; Liu, Jianjun; Song, Shaoli; Jiang, Yansheng; Xia, Qian; Swinnen, Johannes V.; Bormans, Guy; Himmelreich, Uwe; Oyen, Raymond

    2015-01-01

    Compared with transplanted tumor models or genetically engineered cancer models, chemically induced primary malignancies in experimental animals can mimic the clinical cancer progress from the early stage on. Cancer caused by chemical carcinogens generally develops through three phases namely initiation, promotion and progression. Based on different mechanisms, chemical carcinogens can be divided into genotoxic and non-genotoxic ones, or complete and incomplete ones, usually with an organ-specific property. Chemical carcinogens can be classified upon their origins such as environmental pollutants, cooked meat derived carcinogens, N-nitroso compounds, food additives, antineoplastic agents, naturally occurring substances and synthetic carcinogens, etc. Carcinogen-induced models of primary cancers can be used to evaluate the diagnostic/therapeutic effects of candidate drugs, investigate the biological influential factors, explore preventive measures for carcinogenicity, and better understand molecular mechanisms involved in tumor initiation, promotion and progression. Among commonly adopted cancer models, chemically induced primary malignancies in mammals have several advantages including the easy procedures, fruitful tumor generation and high analogy to clinical human primary cancers. However, in addition to the time-consuming process, the major drawback of chemical carcinogenesis for translational research is the difficulty in noninvasive tumor burden assessment in small animals. Like human cancers, tumors occur unpredictably also among animals in terms of timing, location and the number of lesions. Thanks to the availability of magnetic resonance imaging (MRI) with various advantages such as ionizing-free scanning, superb soft tissue contrast, multi-parametric information, and utility of diverse contrast agents, now a workable solution to this bottleneck problem is to apply MRI for noninvasive detection, diagnosis and therapeutic monitoring on those otherwise

  11. Targeting the Wnt/β-catenin pathway in primary ovarian cancer with the porcupine inhibitor WNT974.

    PubMed

    Boone, Jonathan D; Arend, Rebecca C; Johnston, Bobbi E; Cooper, Sara J; Gilchrist, Scott A; Oelschlager, Denise K; Grizzle, William E; McGwin, Gerald; Gangrade, Abhishek; Straughn, J Michael; Buchsbaum, Donald J

    2016-02-01

    Preclinical studies in ovarian cancer have demonstrated upregulation of the Wnt/β-catenin pathway promoting tumor proliferation and chemoresistance. Our objective was to evaluate the effect of the Wnt/β-catenin pathway inhibitor, WNT974, in primary ovarian cancer ascites cells. Ascites cells from patients with papillary serous ovarian cancer were isolated and treated with 1 μM WNT974±100 μM carboplatin. Viability was evaluated with the ATPlite assay. The IC50 was calculated using a dose-response analysis. Immunohistochemistry (IHC) was performed on ascites cells and tumor. Expression of R-spondin 2 (RSPO2), RSPO3, PORCN, WLS, AXIN2, and three previously characterized RSPO fusion transcripts were assessed using Taqman assays. Sixty ascites samples were analyzed for response to WNT974. The ascites samples that showed a decrease in ATP concentration after treatment demonstrated no difference from the untreated cells in percent viability with trypan blue staining. Flow cytometry demonstrated fewer cells in the G2 phase and more in the G1 and S phases after treatment with WNT974. Combination therapy with WNT974 and carboplatin resulted in a higher percentage of samples that showed ≥30% reduction in ATP concentration than either single drug treatment. IHC analysis of Wnt pathway proteins suggests cell cycle arrest rather than cytotoxicity after WNT974 treatment. QPCR indicated that RSPO fusions are not prevalent in ovarian cancer tissues or ascites. However, higher PORCN expression correlated to sensitivity to WNT974 (P=0.0073). In conclusion, WNT974 produces cytostatic effects in patient ascites cells with primary ovarian cancer through inhibition of the Wnt/β-catenin pathway. The combination of WNT974 and carboplatin induces cytotoxicity plus cell cycle arrest in a higher percentage of ascites samples than with single drug treatment. RSPO fusions do not contribute to WNT974 sensitivity; however, higher PORCN expression indicates increased WNT974 sensitivity.

  12. Veliparib and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer or Metastatic Breast Cancer

    ClinicalTrials.gov

    2016-10-04

    Estrogen Receptor Negative; HER2/Neu Negative; Male Breast Carcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Breast Cancer; Triple-Negative Breast Carcinoma

  13. Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

    ClinicalTrials.gov

    2016-10-28

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

  14. Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis.

    PubMed

    Yeung, Tsz-Lun; Leung, Cecilia S; Yip, Kay-Pong; Au Yeung, Chi Lam; Wong, Stephen T C; Mok, Samuel C

    2015-10-01

    Ovarian cancer is the most lethal gynecological malignancy. It is usually diagnosed at a late stage, with a 5-yr survival rate of <30%. The majority of ovarian cancer cases are diagnosed after tumors have widely spread within the peritoneal cavity, limiting the effectiveness of debulking surgery and chemotherapy. Owing to a substantially lower survival rate at late stages of disease than at earlier stages, the major cause of ovarian cancer deaths is believed to be therapy-resistant metastasis. Although metastasis plays a crucial role in promoting ovarian tumor progression and decreasing patient survival rates, the underlying mechanisms of ovarian cancer spread have yet to be thoroughly explored. For many years, researchers have believed that ovarian cancer metastasizes via a passive mechanism by which ovarian cancer cells are shed from the primary tumor and carried by the physiological movement of peritoneal fluid to the peritoneum and omentum. However, the recent discovery of hematogenous metastasis of ovarian cancer to the omentum via circulating tumor cells instigated rethinking of the mode of ovarian cancer metastasis and the importance of the "seed-and-soil" hypothesis for ovarian cancer metastasis. In this review we discuss the possible mechanisms by which ovarian cancer cells metastasize from the primary tumor to the omentum, the cross-talk signaling events between ovarian cancer cells and various stromal cells that play crucial roles in ovarian cancer metastasis, and the possible clinical implications of these findings in the management of this deadly, highly metastatic disease.

  15. A benign presentation of primary ductal adenocarcinoma of lacrimal gland: A rare malignancy.

    PubMed

    Lau, Lindfay Laura; Lung, Chong Ka; Ahmad, Syed Shoeb

    2015-11-01

    A 34-year-old patient with a swelling over the upper eyelid for nearly 1 year was seen in our clinic. The history, examination and investigations were suggestive of a benign lacrimal gland tumor. The tumor and lacrimal gland were resected. Subsequent histopathological examination revealed the tumor was a primary ductal adenocarcinoma of the lacrimal gland. This is a very rare tumor with less than half a dozen cases reported so far. This case report is being presented to highlight an unusual presentation of this rare malignancy.

  16. Primary malignant mediastinal germ cell tumours: improved prognosis with platinum-based chemotherapy and surgery.

    PubMed Central

    Childs, W. J.; Goldstraw, P.; Nicholls, J. E.; Dearnaley, D. P.; Horwich, A.

    1993-01-01

    A retrospective analysis was performed of 18 patients with primary malignant germ cell tumours of the mediastinum treated with platinum-based chemotherapy between 1977 and 1990. All seven patients with pure seminoma were treated initially with chemotherapy and four of these patients received additional mediastinal radiotherapy. Only one patient relapsed; his initial therapy had included radiotherapy and single-agent carboplatin and he was successfully salvaged with combination chemotherapy. With a follow-up of 11 to 117 months (median 41 months) all seven patients with seminoma remain alive and disease free giving an overall survival of 100%. Eleven patients had malignant non seminoma; following chemotherapy eight of these had elective surgical resection of residual mediastinal masses. Complete remission was achieved in nine (82%) patients, however, one of these patients died from bleomycin pneumonitis. With a follow-up of 12 to 113 months (median 55 months) eight of 11 (73%) patients with malignant mediastinal teratoma remain alive and disease free. PMID:8494705

  17. Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer

    PubMed Central

    Kummar, Shivaani; Oza, Amit M.; Fleming, Gini F.; Sullivan, Daniel M.; Gandara, David R.; Naughton, Michael J.; Villalona-Calero, Miguel A.; Morgan, Robert J.; Szabo, Peter M.; Youn, Ahrim; Chen, Alice P.; Ji, Jiuping; Allen, Deborah E.; Lih, Chih-Jian; Mehaffey, Michele G.; Walsh, William D.; McGregor, Paul M.; Steinberg, Seth M.; Williams, Paul M.; Kinders, Robert J.; Conley, Barbara A.; Simon, Richard M.; Doroshow, James H.

    2015-01-01

    Purpose Veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, demonstrated clinical activity in combination with oral cyclophosphamide in patients with BRCA-mutant solid tumors in a phase 1 trial. To define the relative contribution of PARP inhibition to the observed clinical activity, we conducted a randomized phase 2 trial to determine the response rate of veliparib in combination with cyclophosphamide compared to cyclophosphamide alone in patients with pretreated BRCA-mutant ovarian cancer or in patients with pretreated primary peritoneal, fallopian tube, or high-grade serous ovarian cancers (HGSOC). Methods Adult patients were randomized to receive cyclophosphamide alone (50 mg orally once daily) or with veliparib (60 mg orally once daily) in 21-day cycles. Crossover to the combination was allowed at disease progression. Results Seventy-five patients were enrolled and 72 were evaluable for response; 38 received cyclophosphamide alone and 37 the combination as their initial treatment regimen. Treatment was well tolerated. One complete response was observed in each arm, with three partial responses (PR) in the combination arm and six PRs in the cyclophosphamide alone arm. Genetic sequence and expression analyses were performed for 211 genes involved in DNA repair; none of the detected genetic alterations were significantly associated with treatment benefit. Conclusion This is the first trial that evaluated single agent, low dose cyclophosphamide in HGSOC, peritoneal, fallopian tube, and BRCA-mutant ovarian cancers. It was well tolerated and clinical activity was observed; the addition of veliparib at 60 mg daily did not improve either the response rate or the median progression free survival. PMID:25589624

  18. Risk Factors and Indications for 30-Day Readmission After Primary Surgery for Epithelial Ovarian Cancer

    PubMed Central

    AlHilli, Mariam; Langstraat, Carrie; Tran, Christine; Martin, Janice; Weaver, Amy; McGree, Michaela; Mariani, Andrea; Cliby, William; Bakkum-Gamez, Jamie

    2015-01-01

    Background To identify patients at risk for postoperative morbidities, we evaluated indications and factors associated with 30-day readmission after epithelial ovarian cancer surgery. Methods Patients undergoing primary surgery for epithelial ovarian cancer between January 2, 2003, and December 29, 2008, were evaluated. Univariable and multivariable logistic regression models were fit to identify factors associated with 30-day readmission. A parsimonious multivariable model was identified using backward and stepwise variable selection. Results In total, 324 (60.2%) patients were stage III and 91 (16.9%) were stage IV. Of all 538 eligible patients, 104 (19.3%) were readmitted within 30 days. Cytoreduction to no residual disease was achieved in 300 (55.8%) patients, and 167 (31.0%) had measurable disease (≤1 cm residual disease). The most common indications for readmission were surgical site infection (SSI; 21.2%), pleural effusion/ascites management (14.4%), and thromboembolic events (12.5%). Multivariate analysis identified American Society of Anesthesiologists score of 3 or higher (odds ratio, 1.85; 95% confidence interval, 1.18–2.89; P = 0.007), ascites [1.76 (1.11–2.81); P = 0.02], and postoperative complications during initial admission [grade 3–5 vs none, 2.47 (1.19–5.16); grade 1 vs none, 2.19 (0.98–4.85); grade 2 vs none, 1.28 (0.74–2.21); P = 0.048] to be independently associated with 30-day readmission (c-index = 0.625). Chronic obstructive pulmonary disease was the sole predictor of readmission for SSI (odds ratio, 3.92; 95% confidence interval, 1.07–4.33; P = 0.04). Conclusions Clinically significant risk factors for 30-day readmission include American Society of Anesthesiologists score of 3 or higher, ascites and postoperative complications at initial admission. The SSI and pleural effusions/ascites are common indications for readmission. Systems can be developed to predict patients needing outpatient management, improve care, and reduce

  19. TUMOR CONTAMINATION IN THE BIOPSY PATH OF PRIMARY MALIGNANT BONE TUMORS

    PubMed Central

    Oliveira, Marcelo Parente; Lima, Pablo Moura de Andrade; de Mello, Roberto José Vieira

    2015-01-01

    Objective: To study factors possibly associated with tumor contamination in the biopsy path of primary malignant bone tumors. Method: Thirty-five patients who underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and chondrosarcoma were studied retrospectively. The sample was analyzed to characterize the biopsy technique used, histological type of the tumor, neoadjuvant chemotherapy used, local recurrences and tumor contamination in the biopsy path. Results: Among the 35 patients studied, four cases of contamination occurred (11.43%): one from osteosarcoma, two from Ewing's tumor and one from chondrosarcoma. There was no association between the type of tumor and presence of tumor contamination in the biopsy path (p = 0.65). There was also no association between the presence of tumor contamination and the biopsy technique (p = 0.06). On the other hand, there were associations between the presence of tumor contamination and local recurrence (p = 0.01) and between tumor contamination and absence of neoadjuvant chemotherapy (p = 0.02). Conclusion: Tumor contamination in the biopsy path of primary malignant bone tumors was associated with local recurrence. On the other hand, the histological type of the tumor and the type of biopsy did not have an influence on tumor contamination. Neoadjuvant chemotherapy had a protective effect against this complication. Despite these findings, tumor contamination is a complication that should always be taken into consideration, and removal of the biopsy path is recommended in tumor resection surgery. PMID:27047877

  20. Secondary malignant neoplasms following radiotherapy for primary cancer in children and young adults.

    PubMed

    Harbron, Richard W; Feltbower, Richard G; Glaser, Adam; Lilley, John; Pearce, Mark S

    2014-04-01

    A study was conducted to investigate secondary malignant neoplasm (SMN) occurrence following radiotherapy (RT) for cancer in children and young adults, to examine the spatial distribution of SMNs in relation to the irradiated field, and to evaluate a possible role of bystander effects in SMN distribution. Forty-two SMNs were identified among 7257 subjects diagnosed with cancer while living in Yorkshire, UK. Thirty-two of these occurred in patients receiving RT. Distances between SMN locations and RT field edge were estimated along with dose at SMN site. Expected radiation-induced SMN frequency in remote tissues receiving less than 0.1 Gy was predicted using risk estimates based on atomic bombing data. After a median follow-up period of 7.58 years, patients treated with RT were at a nearly five-fold increased risk of developing a subsequent primary neoplasm than the general population in the 0-29 years age range. The most common type of secondary malignancy associated with RT was of the central nervous system (28%), followed by sarcoma (25%) and leukemia (19%). Considering only solid SMNs developing 5 years or more from treatment, the spatial distribution showed a strong pattern of proximity to the irradiated field, with 68% occurring in-field or within 8 cm of the field edge. The SMN frequency in distant tissues receiving doses of less than 0.1 Gy was low but compatible with local absorbed dose.

  1. Primary Malignancies of the Small Bowel: A Report of 96 Cases and Review of the Literature

    PubMed Central

    Wilson, James M.; Melvin, David B.; Gray, George F.; Thorbjarnarson, Bjorn

    1974-01-01

    The clinical records and histologic sections of 96 cases of primary small bowel malignancies (excluding lymphomas and periamullary lesions) were reviewed. The location, clinical presentation, pathologic findings, treatment and outcome are compared to the collected published experience, approximately 2400 cases. There were 48 adenocarcinomas, 37 carcinoids, and 11 leiomyosarcomas. Fifty-one men and 45 women ranged from 31 to 83 years old. Eighty-four caused symptoms leading to operative diagnosis; 12 carcinoids were incidental autopsy findings. The most common presentation was pain (33%) followed by weight loss (23%) obstruction (16%), hemorrhage (15%), jaundice (5%), intussusception (3%) and perforation (3%). Masses were felt in 30% of the cases, but were usually dilated bowel or intussusception rather than the tumor per se. Curative resection was attempted in 80 of 84 operatively diagnosed tumors. The 80% mortality among patients followed 5 years is attributed to the late appearance of symptoms and anatomic obstacles to a truly radical operation. PMID:4843046

  2. Primary Renal Hydatid Cyst: Mis-Interpretation as a Renal Malignancy

    PubMed Central

    Choi, Hoon; Park, Jae Young; Kim, Jae-Heon; Moon, Du Geon; Lee, Jeong-Gu

    2014-01-01

    Primary renal echinococcosis, a rare disease involving the kidney, accounts for 2-3% of human echinococcosis. A 64-year-old female patient from Uzbekistan presented with complaints of left flank pain. A CT scan revealed a cystic mass in the upper to midpole of the left kidney. We regarded this lesion as a renal malignancy and hand-assisted laparoscopic radical nephrectomy was performed to remove the renal mass. The mass consisted of a large unilocular cyst and multiple smaller cysts without any grossly visible renal tissue. The final pathologic diagnosis was a renal hydatid cyst. For patients from endemic areas, hydatid cyst should be included in the differential diagnosis. Here, we present a case of renal hydatid cyst in a female patient who relocated from Uzbekistan to Korea. PMID:25031471

  3. Primary malignant fibrous histiocytoma of the breast: report of one case

    PubMed Central

    Liu, Caigang; Zhao, Zuowei; Zhang, Qingfu; Wu, Yunfei; Jin, Feng

    2013-01-01

    Seven years ago, a 48-year-old female patient discovered a painless tumor in her right breast simply by chance. In the next year, the tumor increased significantly in size. At this point, the patient received a tumor resection, which was misdiagnosed as a benign mesenchymal tissue-originated tumor. Unfortunately, the tumor recurred just 10 days after resection. We subsequently resected the recurrent lesion and confirmed primary breast malignant fibrous histiocytoma. The tumor began to exhibit an unprecedented, massive, and uncontrolled growth, ulcerating soon after the operation. Treatment of the patient was limited by time. After the patient received a cycle of chemotherapy, she died of cachexia with the emergence of multiorgan metastasis 2 months after the operation. PMID:23589696

  4. [Primary malignant solitary fibrous tumor/hemangiopericytoma of the parotid gland].

    PubMed

    Messa-Botero, Oscar Alberto; Romero-Rojas, Alfredo Ernesto; Chinchilla Olaya, Sandra Isabel; Díaz-Pérez, Julio Alexander; Tapias-Vargas, Luis Felipe

    2011-01-01

    Solitary fibrous tumor (SFT) was first described in the pleura by Lietaud in 1767; later in 1870, Wagner described the localized nature of this type of tumor and Klemperer and Rabin classified pleural tumors into two types: diffuse mesotheliomas and localized mesotheliomas. Recent years have seen the redefinition of this neoplasm, due to better technology; it is now proven that this neoplasm may have multiple different extrapleural origins including the head and neck regions. This diversity of locations is related to the particular mesenchymal histogenesis of SFT which allows its development from very unusual sites such as the salivary glands (SGs). In this particular site, this neoplasm is very infrequent and most of reported cases refer to benign disease, with just one case informed so far of primary malignant SFT.

  5. Selective Internal Radiation Therapy (SIRT) as Conversion Therapy for Unresectable Primary Liver Malignancies

    PubMed Central

    Cucchetti, Alessandro; Cappelli, Alberta; Ercolani, Giorgio; Mosconi, Cristina; Cescon, Matteo; Golfieri, Rita; Pinna, Antonio Daniele

    2016-01-01

    Background Many patients with primary liver cancers are not candidates for surgery, and systemic therapies are seldom effective. Selective internal radiation therapy (SIRT) has been shown to obtain partial and even complete response in unresectable primary tumors. As a “side effect”, SIRT can induce contra-lateral liver hypertrophy. Tumor response to SIRT can be sufficient to allow disengagement from normal vital structures whose involvement is the cause of the initial unresectability. The contra-lateral hypertrophy can thereby increase the future liver remnant (FLR) volume to over the safe threshold so that extended hepatectomy can be performed. Summary A review of the available literature was performed to assess the tumor response and liver hypertrophy that can be expected after SIRT, in order to delineate whether SIRTcan play a role in conversion therapy for resectability of primary liver malignancies. Key Message Available data suggest that SIRT in unresectable hepatocellular and cholangiocellular carcinomas can provide a considerable down-sizing of the tumors to possibly allow resection. Hypertrophy of the contra-lateral lobe represents a favorable collateral effect that can help in achieving safer subsequent major hepatectomy. In patients whose FLR volume represents the only surgical concern, portal vein embolization remains the treatment of choice. PMID:27781202

  6. Expression of Yes-associated protein modulates Survivin expression in primary liver malignancies.

    PubMed

    Bai, Haibo; Gayyed, Mariana F; Lam-Himlin, Dora M; Klein, Alison P; Nayar, Suresh K; Xu, Yang; Khan, Mehtab; Argani, Pedram; Pan, Duojia; Anders, Robert A

    2012-09-01

    Hepatocellular carcinoma and intrahepatic cholangiocarcinoma account for 95% of primary liver cancer. For each of these malignancies, the outcome is dismal; incidence is rapidly increasing, and mechanistic understanding is limited. We observed abnormal proliferation of both biliary epithelium and hepatocytes in mice after genetic manipulation of Yes-associated protein, a transcription coactivator. Here, we comprehensively documented Yes-associated protein expression in the human liver and primary liver cancers. We showed that nuclear Yes-associated protein expression is significantly increased in human intrahepatic cholangiocarcinoma and hepatocellular carcinoma. We found that increased Yes-associated protein levels in hepatocellular carcinoma are due to multiple mechanisms including gene amplification and transcriptional and posttranscriptional regulation. Survivin, a member of the inhibitors-of-apoptosis protein family, has been reported as an independent prognostic factor for poor survival in both hepatocellular carcinoma and intrahepatic cholangiocarcinoma. We found that nuclear Yes-associated protein expression correlates significantly with nuclear Survivin expression for both intrahepatic cholangiocarcinoma and hepatocellular carcinoma. Furthermore, using mice engineered to conditionally overexpress Yes-associated protein in the liver, we found that Survivin messenger RNA expression depends upon Yes-associated protein levels. Our findings suggested that Yes-associated protein contributes to primary liver tumorigenesis and likely mediates its oncogenic effects through modulating Survivin expression.

  7. Accuracy of frozen-section analysis in the diagnosis of ovarian tumors: a systematic quantitative review.

    PubMed

    Medeiros, L R; Rosa, D D; Edelweiss, M I; Stein, A T; Bozzetti, M C; Zelmanowicz, A; Pohlmann, P R; Meurer, L; Carballo, M T

    2005-01-01

    A quantitative systematic review was performed to estimate the diagnostic accuracy of frozen sections in ovarian tumors. Studies that compared frozen sections and paraffin sections within subjects for diagnosis of ovarian tumors were included. Fourteen primary studies were analyzed, which included 3 659 women. For benign ovarian vs borderline/malignant tumor cases, the occurrence of a positive frozen-section result for benignity (pooled likelihood ratio [LR], 8.7; 95% confidence interval [CI], 7.3-10.4) and posttest probability for benign diagnosis was 95% (95% CI, 94-96%). A positive frozen-section result for malignant vs benign diagnosis (pooled LR, 303; 95% CI, 101-605) increased the probability of ovarian cancer to 98% (95% CI, 97-99%). In borderline vs benign ovarian tumor cases, a positive frozen-section result (pooled LR, 69; 95% CI, 45-106) increased the probability of borderline tumors to 79% (95% CI, 71-85%). In borderline vs malignant ovarian tumor cases, a positive frozen-section result (pooled LR, 18; 95% CI, 13-26) increased the probability of borderline tumors to 51% (95% CI, 42-60%). We conclude that diagnostic accuracy rates for frozen-section analysis is high for malignant and benign ovarian tumors, but the accuracy rates in borderline tumors remain relatively low.

  8. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases.

    PubMed Central

    Paridaens, A D; Minassian, D C; McCartney, A C; Hungerford, J L

    1994-01-01

    A series of 256 consecutive cases of invasive primary conjunctival malignant melanomas was examined to identify clinical and histopathological prognostic factors. The follow up period varied between 0.3 and 45.9 years (mean 9 years, median 6.3 years). The 5 year survival rate was estimated at 82.9%, the 10 year survival rate at 69.3%. Multiple regression analysis with the Cox proportional hazards model was used to assess sex, age, and a number of baseline features of conjunctival malignant melanoma as possible prognostic factors influencing melanoma related mortality. In assessing each potential prognostic factor, the effects of all other factors were taken into account in the modelling process. Tumours in unfavourable locations--that is, those involving the palpebral conjunctiva, fornices, plica, caruncle, and lid margins, were associated with 2.2 times higher mortality compared with (epi)bulbar melanomas. Patients with mixed cell type tumours had about three times higher mortality compared with those with pure spindle cell melanomas, and histological evidence of lymphatic invasion by tumour cells was also a prognostic feature, carrying a fourfold increase in the death rate. Multifocal tumours were associated with a fivefold increase in mortality among those with tumours in favourable (epi)bulbar locations, but were not prognostic in patients with melanomas in unfavourable sites. The death rate was significantly higher in those with initial tumour thickness of more than 4 mm, but only among patients with unfavourably located melanomas. Sex, age, and clinical origin of the tumour (primary acquired melanosis, pre-existing naevus, or de novo) were not useful prognostic indicators in this study. PMID:8199108

  9. A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies

    PubMed Central

    Parikh, Mukti R.; Belch, Andrew R.; Pilarski, Linda M; Kirshner, Julia

    2014-01-01

    Tissue culture has been an invaluable tool to study many aspects of cell function, from normal development to disease. Conventional cell culture methods rely on the ability of cells either to attach to a solid substratum of a tissue culture dish or to grow in suspension in liquid medium. Multiple immortal cell lines have been created and grown using such approaches, however, these methods frequently fail when primary cells need to be grown ex vivo. Such failure has been attributed to the absence of the appropriate extracellular matrix components of the tissue microenvironment from the standard systems where tissue culture plastic is used as a surface for cell growth. Extracellular matrix is an integral component of the tissue microenvironment and its presence is crucial for the maintenance of physiological functions such as cell polarization, survival, and proliferation. Here we present a 3-dimensional tissue culture method where primary bone marrow cells are grown in extracellular matrix formulated to recapitulate the microenvironment of the human bone (rBM system). Embedded in the extracellular matrix, cells are supplied with nutrients through the medium supplemented with human plasma, thus providing a comprehensive system where cell survival and proliferation can be sustained for up to 30 days while maintaining the cellular composition of the primary tissue. Using the rBM system we have successfully grown primary bone marrow cells from normal donors and patients with amyloidosis, and various hematological malignancies. The rBM system allows for direct, in-matrix real time visualization of the cell behavior and evaluation of preclinical efficacy of novel therapeutics. Moreover, cells can be isolated from the rBM and subsequently used for in vivo transplantation, cell sorting, flow cytometry, and nucleic acid and protein analysis. Taken together, the rBM method provides a reliable system for the growth of primary bone marrow cells under physiological conditions

  10. The Incidence Characteristics of Second Primary Malignancy after Diagnosis of Primary Colon and Rectal Cancer: A Population Based Study

    PubMed Central

    Guan, Xu; Jin, Yinghu; Chen, Yinggang; Jiang, Zheng; Liu, Zheng; Zhao, Zhixun; Yan, Peng; Wang, Guiyu; Wang, Xishan

    2015-01-01

    Background With the expanding population of colorectal cancer (CRC) survivors in the United States, one concerning issue is the risk of developing second primary malignancies (SPMs) for these CRC survivors. The present study attempts to identify the incidence characteristics of SPMs after diagnosis of first primary colon cancer (CC) and rectal cancer (RC). Methods 189,890 CC and 83,802 RC cases were identified from Surveillance, Epidemiology and End Results Program (SEER) database. We performed rate analysis on incidence trend of SPMs in both CC and RC. Expected incidence rates were stratified by age, race and stage, calendar year of first CRC diagnosis and latency period since first CRC diagnosis. The standardized incidence ratios (SIRs), measure for estimating risk of SPMs, were calculated for CC and RC respectively. Results The trends of incidence of SPMs in both CC and RC were decreasing from 1992 to 2012. Both CC and RC survivors had higher risk of developing SPMs (SIRCC = 1.13; SIRRC = 1.05). For CC patients, the highest risks of SPM were cancers of small intestine (SIR = 4.03), colon (SIR = 1.87) and rectum (SIR = 1.80). For RC patients, the highest risks of SPMs were cancers of rectum (SIR = 2.88), small intestine (SIR = 2.16) and thyroid (SIR = 1.46). According to stratified analyses, we also identified incidence characteristics which were contributed to higher risk of developing SPMs, including the age between 20 and 40, American Indian/Alaska Native, localized stage, diagnosed at calendar year from 2002 to 2012 and the latency between 12 and 59 months. Conclusions Both CC and RC survivors remain at higher risk of developing SPMs. The identification of incidence characteristics of SPMs is extremely essential for continuous cancer surveillance among CRC survivors. PMID:26571301

  11. Clinical Outcomes of Patients with Resected Oral Cavity Cancer and Simultaneous Second Primary Malignancies

    PubMed Central

    Kang, Chung-Jan; Lin, Chien-Yu; Chang, Joseph Tung-Chieh; Tsang, Ngan-Ming; Huang, Bing-Shen; Chao, Yin-Kai; Lee, Li-Yu; Hsueh, Chuen; Wang, Hung-Ming; Liau, Chi-Ting; Hsu, Cheng-Lung; Hsieh, Chia-Hsun; Ng, Shu-Hang; Lin, Chih-Hung; Tsao, Chung-Kan; Fang, Tuan-Jen; Huang, Shiang-Fu; Chang, Kai-Ping; Yen, Tzu-Chen

    2015-01-01

    Objectives Simultaneous second primary tumors (SSPT) are not uncommon in patients with oral cavity squamous cell carcinoma (OSCC) living in areas where the habit of betel quid chewing is widespread. We sought to identify the main prognostic factors in OSCC patients with SSPT and incorporate them into a risk stratification scheme. Methods A total of 1822 consecutive patients with primary OSCC treated between January 1996 and February 2014 were analyzed for the presence of SSPT. The 18-month and 5-year overall survival (OS) rates served as the main outcome measures. Results Of the 1822 patients, 77 (4%) were found to have SSPT (i.e, two malignancies identified within one month of each other). The 18-month and 5-year OS rates in patients without SSPT and with SSPT were 82% and 69%, and 72% and 53%, respectively (p = 0.0063). Patients with SSPT were further divided into patients with either esophageal cancer or hepatocellular carcinoma (eso-HCC subgroup, n = 8) and other tumors (NO eso-HCC subgroup, n = 69). After multivariate analysis, neck nodal extracapsular spread (ECS, n = 18) and the presence of eso-HCC were identified as independent adverse prognostic factors. The 18-month OS rates of SSPT patients with both eso-HCC and ECS (n = 5) vs. the remaining patients (n = 72) were 0% and 78%, respectively (p < 0.0001). Conclusion OSCC patients with neck nodal ECS and esophageal cancer or hepatocellular carcinoma as SSPT have a dismal short-term prognosis. PMID:26335067

  12. Characteristics and Surgical Outcomes for Primary Malignant Melanoma of the Esophagus.

    PubMed

    Gao, Shugeng; Li, Jiagen; Feng, Xiaoli; Shi, Susheng; He, Jie

    2016-01-01

    Primary malignant melanoma of the esophagus (PMME) is an extremely rare disease with poor prognosis. We summarized and analyzed the characteristics of 17 PMME patients (with average age of 57.5 ± 10.3 years) who had received surgical resection in our center. The majority (13/17, 76.5%) of the patients were male. The percentage of patients with smoking and alcohol consumption was 41.2% and 23.5%, respectively. The preoperative diagnosis rate was 35.3%. Lymph node metastasis mainly involved the mid-lower mediastinal and upper abdominal area. Primary tumors that invaded beyond the submucosa layer (T2-T4) had much higher tendency of lymph node metastasis than those restricted to the submucosa layer (T1) (6/8, 75.0% vs. 3/9, 33.3%, p = 0.086). The 1-year and 5-year survival rate of the patients was 51% and 10%, respectively, with median survival time being 18.1 months. Survival analysis showed that TNM stage was a predictor for PMME prognosis (median survival time of 47.3 months vs. 8.0 months for stage I/II vs. stage III, respectively, p = 0.018), and multivariable Cox regression analysis revealed the independence of its prognostic value [HR (95% CI): 5.678 (1.125-28.658), p = 0.035]. PMID:27033424

  13. Current knowledge and future research directions in treatment-related second primary malignancies

    PubMed Central

    Morton, Lindsay M.; Swerdlow, Anthony J.; Schaapveld, Michael; Ramadan, Safaa; Hodgson, David C.; Radford, John; van Leeuwen, Flora E.

    2014-01-01

    Currently, 17–19% of all new primary malignancies occur in survivors of cancer, causing substantial morbidity and mortality. Research has shown that cancer treatments are important contributors to second malignant neoplasm (SMN) risk. In this paper we summarise current knowledge with regard to treatment-related SMNs and provide recommendations for future research. We address the risks associated with radiotherapy and systemic treatments, modifying factors of treatment-related risks (genetic susceptibility, lifestyle) and the potential benefits of screening and interventions. Research priorities were identified during a workshop at the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer. Recently, both systemic cancer treatments and radiotherapy approaches have evolved rapidly, with the carcinogenic potential of new treatments being unknown. Also, little knowledge is available about modifying factors of treatment-associated risk, such as genetic variants and lifestyle. Therefore, large prospective studies with biobanking, high quality treatment data (radiation dose–volume, cumulative drug doses), and data on other cancer risk factors are needed. International collaboration will be essential to have adequate statistical power for such investigations. While screening for SMNs is included in several follow-up guidelines for cancer survivors, its effectiveness in this special population has not been demonstrated. Research into the pathogenesis, tumour characteristics and survival of SMNs is essential, as well as the development of interventions to reduce SMN-related morbidity and mortality. Prediction models for SMN risk are needed to inform initial treatment decisions, balancing chances of cure and SMNs and to identify high-risk subgroups of survivors eligible for screening. PMID:26217162

  14. Secondary Primary Malignancy Risk in Patients With Cervical Cancer in Taiwan

    PubMed Central

    Teng, Chung-Jen; Huon, Leh-Kiong; Hu, Yu-Wen; Yeh, Chiu-Mei; Chao, Yee; Yang, Muh-Hwa; Chen, Tzeng-Ji; Hung, Yi-Ping; Liu, Chia-Jen

    2015-01-01

    Abstract To evaluate the risk of secondary primary malignancy (SPM) in patients with cervical cancer using a nationwide population-based dataset. Patients newly diagnosed with cervical cancer between 1997 and 2011 were identified using Taiwan's National Health Insurance database. Patients with antecedent malignancies were excluded. Standardized incidence ratios (SIRs) for SPM were calculated by comparing with the cancer incidence in the general population. Risk factors for cancer development were analyzed using Cox proportional hazard models. During the 14-year study period (follow-up of 223,062 person-years), 2004 cancers developed in 35,175 patients with cervical cancer. The SIR for all cancers was 1.56 (95% confidence interval, 1.50–1.63, P < 0.001). SIRs for follow-up periods of >10, 5 to 10, 1 to 5, and <1 year were 1.37, 1.51, 1.34, and 2.59, respectively. After the exclusion of SPM occurring within 1 year of cervical cancer diagnosis, SIRs were significantly higher for cancers of the esophagus (2.05), stomach (1.38), colon, rectum, and anus (1.36); lung and mediastinum (2.28), bone and soft tissue (2.23), uterus (3.76), bladder (2.26), and kidneys (1.41). Multivariate analysis showed that age ≥60 was a significant SPM risk factor (hazard ratio [HR] 1.59). Different treatments for cervical cancer, including radiotherapy (HR 1.41) and chemotherapy (HR 1.27), had different impacts on SPM risk. Carboplatin and fluorouracil independently increased SPM risk in cervical cancer patients. Patients with cervical cancer are at increased risk of SPM development. Age ≥60 years, chemotherapy, and radiotherapy are independent risk factors. Carboplatin and fluorouracil also increased SPM risk independently. Close surveillance of patients at high risk should be considered for the early detection of SPMs. PMID:26512575

  15. Positive Selection in Bone Morphogenetic Protein 15 Targets a Natural Mutation Associated with Primary Ovarian Insufficiency in Human

    PubMed Central

    Meslin, Camille; Monestier, Olivier; Di Pasquale, Elisa; Pascal, Géraldine; Persani, Luca; Fabre, Stéphane

    2013-01-01

    Bone Morphogenetic Protein 15 (BMP15) is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. Alterations of the BMP15 gene have been found associated with different ovarian phenotypic effects depending on the species, from sterility to increased prolificacy in sheep, slight subfertility in mouse or associated with primary ovarian insufficiency (POI) in women. To investigate the evolving role of BMP15, a phylogenetic analysis of this particular TGFβ family member was performed. A maximum likelihood phylogenetic tree of several TGFβ/BMP family members expressed by the ovary showed that BMP15 has a very strong divergence and a rapid evolution compared to others. Moreover, among 24 mammalian species, we detected signals of positive selection in the hominidae clade corresponding to F146, L189 and Y235 residues in human BMP15. The biological importance of these residues was tested functionally after site directed-mutagenesis in a COV434 cells luciferase assay. By replacing the positively selected amino acid either by alanine or the most represented residue in other studied species, only L189A, Y235A and Y235C mutants showed a significant increase of BMP15 signaling when compared to wild type. Additionally, the Y235C mutant was more potent than wild type in inhibiting progesterone secretion of ovine granulosa cells in primary culture. Interestingly, the Y235C mutation was previously identified in association with POI in women. In conclusion, this study evidences that the BMP15 gene has evolved faster than other members of the TGFß family and was submitted to a positive selection pressure in the hominidae clade. Some residues under positive selection are of great importance for the normal function of the protein and thus for female fertility. Y235 represents a critical residue in the determination of BMP15 biological activity, thus indirectly confirming its role in the onset of POI in

  16. Positive selection in bone morphogenetic protein 15 targets a natural mutation associated with primary ovarian insufficiency in human.

    PubMed

    Auclair, Sylvain; Rossetti, Raffaella; Meslin, Camille; Monestier, Olivier; Di Pasquale, Elisa; Pascal, Géraldine; Persani, Luca; Fabre, Stéphane

    2013-01-01

    Bone Morphogenetic Protein 15 (BMP15) is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. Alterations of the BMP15 gene have been found associated with different ovarian phenotypic effects depending on the species, from sterility to increased prolificacy in sheep, slight subfertility in mouse or associated with primary ovarian insufficiency (POI) in women. To investigate the evolving role of BMP15, a phylogenetic analysis of this particular TGFβ family member was performed. A maximum likelihood phylogenetic tree of several TGFβ/BMP family members expressed by the ovary showed that BMP15 has a very strong divergence and a rapid evolution compared to others. Moreover, among 24 mammalian species, we detected signals of positive selection in the hominidae clade corresponding to F146, L189 and Y235 residues in human BMP15. The biological importance of these residues was tested functionally after site directed-mutagenesis in a COV434 cells luciferase assay. By replacing the positively selected amino acid either by alanine or the most represented residue in other studied species, only L189A, Y235A and Y235C mutants showed a significant increase of BMP15 signaling when compared to wild type. Additionally, the Y235C mutant was more potent than wild type in inhibiting progesterone secretion of ovine granulosa cells in primary culture. Interestingly, the Y235C mutation was previously identified in association with POI in women. In conclusion, this study evidences that the BMP15 gene has evolved faster than other members of the TGFß family and was submitted to a positive selection pressure in the hominidae clade. Some residues under positive selection are of great importance for the normal function of the protein and thus for female fertility. Y235 represents a critical residue in the determination of BMP15 biological activity, thus indirectly confirming its role in the onset of POI in

  17. Treatment of FIGO stage IV ovarian carcinoma: results of primary surgery or interval surgery after neoadjuvant chemotherapy: a retrospective study.

    PubMed

    Rafii, A; Deval, B; Geay, J-F; Chopin, N; Paoletti, X; Paraiso, D; Pujade-Lauraine, E

    2007-01-01

    The objective of the study is to determine whether surgery influences the outcome of stage IV ovarian cancer. The study design is as follows: From May 1995 to December 2000, 129 patients with FIGO stage IV ovarian cancer, recruited in 42 centers, were prospectively included in GINECO first-line randomized studies of platinum-based regimens with paclitaxel administered simultaneously or sequentially. In all, 109 were eligible for this study. Standard peritoneal cytoreductive surgery was defined as a procedure including at least total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal debulking. Surgery was considered optimal if residual lesions were smaller than 1 cm. The Kaplan-Meier method was used to compare survival. Initial abdominopelvic cytoreductive surgery was considered standard in 55 (54%) patients. Abdominopelvic surgery was optimal in 29 patients and nonoptimal in 26. Twenty-two (22%) patients had a simple biopsy, and 25 (24%) patients underwent substandard surgery. Twenty-two of these 47 patients without initial standard surgery underwent a second surgical procedure, and 17 of the 22 patients completed standard surgery. The median overall survival time in the entire population was 24.3 months (95% confidence interval [CI], 19.5-29.1 months). Patients treated without a cytoreductive surgical procedure had significantly worse median survival (15.1 months; 95% CI, 5.4-24.9 months) than patients who had optimal primary surgery (22.9 months; 95% CI, 15.6-30.1 months), nonoptimal primary surgery (27.1 months; 95% CI, 21.2-32.9 months), or neoadjuvant chemotherapy followed by surgery (45.5 months; 95% CI, 23.5-67.5 months) (P= .001). In conclusion, this study shows a significant benefit of debulking surgery in stage IV ovarian cancer patients who responded to neoadjuvant chemotherapy. Neoadjuvant chemotherapy can help to select patients for surgery.

  18. Vanishing ovarian mass: Sarcoidosis.

    PubMed

    Turkay, Rustu; Bakir, Baris; Golabi, Uygar Cenik; Topuz, Samet; Ilhan, Huseyin Ridvan

    2012-01-01

    A woman was referred to our hospital with the working diagnosis of ovarian malignancy. While she was undergoing both clinical and radiological evaluation and monitoring, a decrease in the size of the ovarian mass was noted. After further evaluation via laboratory findings and tissue biopsy, we arrived at a final diagnosis of sarcoidosis, which is very unusual in the ovaries. Our case places emphasis on the importance of considering rare entities, such as ovarian sarcoidosis, and the importance of radiologic changes in solid ovarian mass dimensions over time.

  19. 2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group

    PubMed Central

    Aronson, Daniel; Clapuyt, Philippe; Czauderna, Piotr; de Ville de Goyet, Jean; Gauthier, Frédéric; MacKinlay, Gordon; Maibach, Rudolf; McHugh, Kieran; Olsen, Øystein E.; Otte, Jean-Bernard; Pariente, Danièle; Plaschkes, Jack; Childs, Margaret; Perilongo, Giorgio

    2006-01-01

    Over the last 15 years, various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood. This paper, written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group (SIOPEL), presents various clarifications and revisions to the original PRETEXT system. PMID:17186233

  20. 2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group.

    PubMed

    Roebuck, Derek J; Aronson, Daniel; Clapuyt, Philippe; Czauderna, Piotr; de Ville de Goyet, Jean; Gauthier, Frédéric; Mackinlay, Gordon; Maibach, Rudolf; McHugh, Kieran; Olsen, Oystein E; Otte, Jean-Bernard; Pariente, Danièle; Plaschkes, Jack; Childs, Margaret; Perilongo, Giorgio

    2007-02-01

    Over the last 15 years, various oncology groups throughout the world have used the PRETEXT system for staging malignant primary liver tumours of childhood. This paper, written by members of the radiology and surgery committees of the International Childhood Liver Tumor Strategy Group (SIOPEL), presents various clarifications and revisions to the original PRETEXT system. PMID:17186233

  1. Endoscopic ultrasound fine-needle aspiration characteristics of primary adenocarcinoma versus other malignant neoplasms of the pancreas

    PubMed Central

    Gagovic, Veronika; Spier, Bret J; DeLee, Ryan J; Barancin, Courtney; Lindstrom, Mary; Einstein, Michael; Byrne, Siobhan; Harter, Josephine; Agni, Rashmi; Pfau, Patrick R; Frick, Terrence J; Soni, Anurag; Gopal, Deepak V

    2012-01-01

    BACKGROUND: Endoscopic ultrasound (EUS) with fine-needle aspiration (FNA) is often used to assist in the evaluation of pancreatic lesions and may help to diagnose benign versus malignant neoplasms. However, there is a paucity of literature regarding comparative EUS characteristics of various malignant pancreatic neoplasms (primary and metastatic). OBJECTIVE: To compare and characterize primary pancreatic adenocarcinoma versus other malignant neoplasms, hereafter referred to as nonprimary pancreatic adenocarcinoma (NPPA), diagnosed by EUS-guided FNA. METHODS: The present study was a retrospective analysis of a prospectively maintained database. The setting was a tertiary care, academic medical centre. Patients referred for suspected pancreatic neoplasms were evaluated. Based on EUS-FNA characteristics, primary pancreatic adenocarcinoma was differentiated from other malignant neoplasms. The subset of other neoplasms was defined as malignant lesions that were ‘NPPAs’ (ie, predominantly solid or solid/cystic based on EUS appearance and primary malignant lesions or metastatic lesions to the pancreas). Pancreatic masses that were benign cystic lesions (pseudocyst, simple cyst, serous cystadenoma) and focal inflammatory lesions (acute, chronic and autoimmune pancreatitis) were excluded. RESULTS: A total of 230 patients were evaluated using EUS-FNA for suspected pancreatic mass lesions. Thirty-eight patients were excluded because they were diagnosed with inflammatory lesions or had purely benign cysts. One hundred ninety-two patients had confirmed malignant pancreatic neoplasms (ie, pancreatic adenocarcinoma [n=144], NPPA [n=48]). When comparing adenocarcinoma with NPPA lesions, there was no significant difference in mean age (P=0.0675), sex (P=0.3595) or average lesion size (P=0.3801). On average, four FNA passes were necessary to establish a cytological diagnosis in both lesion subtypes (P=0.396). Adenocarcinomas were more likely to be located in the pancreatic head

  2. Kit ligand promotes the transition from primordial to primary follicles after in vitro culture of ovine ovarian tissue.

    PubMed

    Cavalcante, A Y P; Gouveia, B B; Barberino, R S; Lins, T L B G; Santos, L P; Gonçalves, R J S; Celestino, J J H; Matos, M H T

    2016-08-01

    This study evaluated the effects of kit ligand (KL) on the morphology and development of ovine preantral follicles (fresh control) and after 7 days of in vitro culture in α-Minimal Essential Medium (α-MEM; control medium) or the presence of KL (1, 10, 50, 100 or 200 ng/ml). There was an increase in the percentage of primary follicles at the concentration of 100 ng/ml KL, compared with the fresh control, control medium (α-MEM) and the other KL concentrations. Follicle diameter was significantly higher than the control medium only at concentrations of 50 and 100 ng/ml KL. In conclusion, 100 ng/ml KL promoted the transition from primordial to primary follicles (follicular activation) after in vitro culture of ovine ovarian tissue.

  3. [SF-1, a key player in adrenal and gonadal differentiation: implications in gonadal dysgenesis and primary ovarian insufficiency].

    PubMed

    Martinerie, L; Bouvattier, C; Lombes, M

    2009-09-01

    Steroidogenic factor 1 (SF-1) gene, identified by Keith Parker in 1992, encodes for an orphan nuclear receptor, NR5A1, whose expression is detected during fetal life in adrenal and gonadal steroidogenic tissues, but also in the developing hypothalamus and in pituitary gonadotropic cells. SF-1 knock-out mouse models exhibit complete adrenal and gonadal agenesis. Human mutations of this transcription factor, were initially associated with primary adrenal failure and male gonadal dysgenesis with various degrees of under androgenization. More recently, identification of novel SF-1 mutations responsible for isolated 46, XY gonadal dysgenesis or 46, XX primary ovarian insufficiency, underscores its central role in the control and maintenance of adrenal and reproductive functions. A better understanding in the regulatory mechanisms of SF-1 signaling pathway, will open new avenues for diagnostic and therapeutic managements of sex differentiation disorders and infertilities.

  4. Olaparib and Hsp90 Inhibitor AT13387 in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Recurrent Ovarian, Fallopian Tube, Primary Peritoneal, or Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2016-09-12

    Estrogen Receptor Negative; HER2/Neu Negative; High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Metastatic Solid Neoplasm; Primary Peritoneal High Grade Serous Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma; Unresectable Solid Neoplasm

  5. Differential effects of arsenic on calcium signaling in primary keratinocytes and malignant (HSC-1) cells.

    PubMed

    Hsu, W L; Tsai, M H; Lin, M W; Chiu, Y C; Lu, J H; Chang, C H; Yu, H S; Yoshioka, T

    2012-08-01

    Arsenic is highly toxic to living cells, especially skin, and skin cancer is induced by drinking water containing arsenic. The molecular mechanisms of arsenic-induced cancer, however, are not well understood. To examine the initial processes in the development of arsenic-induced cancer, we analyzed calcium signaling at an early stage of arsenic treatment of human primary cells and compared the effects with those observed with arsenic treatment in carcinoma-derived cells. We found that arsenic inhibited inositol trisphosphate receptor (IP3R) function in the endoplasmic reticulum by inducing phosphorylation, which led to decreased intracellular calcium levels. Blockade of IP3R phosphorylation by the serine/threonine protein kinase Akt inhibitor wortmannin rescued calcium signaling. In contrast, arsenic treatment of cells derived from a carcinoma (human squamous carcinoma; HSC-1) for 1h had no obvious effect. Taken together, these results suggest that arsenic-induced reduction in calcium signaling is one of the initial mechanisms underlying the malignant transformation in the development of skin cancer.

  6. Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

    PubMed Central

    Olsson, Richard F.; Logan, Brent R.; Chaudhury, Sonali; Zhu, Xiaochun; Akpek, Görgün; Bolwell, Brian J.; Bredeson, Christopher N.; Dvorak, Christopher C.; Gupta, Vikas; Ho, Vincent T.; Lazarus, Hillard M.; Marks, David I.; Ringdén, Olle T.H.; Pasquini, Marcelo C.; Schriber, Jeffrey R.; Cooke, Kenneth R.

    2015-01-01

    Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells. PMID:25772027

  7. An exploration of opioid medication management for non-malignant pain in primary care

    PubMed Central

    Foell, Jens

    2015-01-01

    The present study aimed to explore how prescription of opioid medication for chronic non-malignant pain (CNMP) is managed in primary care. We used audit as a research tool, and one general practitioner (GP) practice in West London acted as an exemplar. Of the practice population with CNMP, 1% had repeat prescription of at least 12 months duration for opioid analgesics at the time of data collection. These 1% are on highly controlled opioids. Our study showed the following: (1) long-term opioid prescription appears to follow a fluctuating course as opposed to staying the same; (2) we found that medication reviews were done in most cases (85.7%), but the quality of the process is difficult to assess and ascertain; and (3) we identified two incidences where opioid contract was implemented. In both cases, contracts were used as a last chance warning for patients who were already problematic, suggesting that opioid contracts served as a disciplinary tool rather than a preventative measure. Our findings highlight a need for a more structured and specific review of analgesic medication, and a need for a simple and effective way to identify patients at high risk of developing problematic use, to ensure better monitoring and early presentations. PMID:26516575

  8. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival.

    PubMed

    Kee, Kwong Ming; Wang, Jing-Houng; Wang, Chih-Chi; Cheng, Yu-Fan; Lu, Sheng-Nan

    2016-01-01

    Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60-4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers. PMID:27444261

  9. Exploring Spirituality in Family Caregivers of Patients With Primary Malignant Brain Tumors Across the Disease Trajectory

    PubMed Central

    Newberry, Alyssa G.; Jean Choi, Chien-Wen; Donovan, Heidi S.; Schulz, Richard; Bender, Catherine; Given, Barbara; Sherwood, Paula

    2013-01-01

    Purpose/Objectives To determine whether the perceived level of spirituality in family caregivers of patients with primary malignant brain tumors (PMBTs) changes across the disease trajectory. Design Ongoing descriptive, longitudinal study. Setting Southwestern Pennsylvania. Sample 50 family caregivers of patients with PMBT. Methods Caregivers and care recipients were recruited at time of diagnosis. Participants were interviewed at two subse-quent time points, four and eight months following diagnosis. Main Research Variables Care recipients’ symptoms, neuro-psychologic status, and physical function, as well as caregiver social support. Findings Results showed no significant difference in spirituality scores reported at baseline and eight months (p = 0.8), suggesting that spirituality may be a stable trait across the disease trajectory. Conclusions Spirituality remains relatively stable along the course of the disease trajectory. Reports of caregiver depressive symptoms and anxiety were lower when paired with higher reports of spirituality. Implications for Nursing Clinicians can better identify caregivers at risk for negative outcomes by identifying those who report lower levels of spirituality. Future interventions should focus on the development and implementation of interventions that provide protective buffers such as increased social support. Knowledge Translation Spirituality is a relatively stable trait. High levels of spirituality can serve as a protective buffer from negative mental health outcomes. Caregivers with low levels of spirituality may be at risk for greater levels of burden, anxiety, and stress. PMID:23615145

  10. Clinical Outcomes of Surgical Treatments for Primary Malignant Bone Tumors Arising in the Acetabulum

    PubMed Central

    Fujiwara, Tomohiro; Ogura, Koichi; Kobayashi, Eisuke; Tanzawa, Yoshikazu; Nakatani, Fumihiko; Chuman, Hirokazu; Kawai, Akira

    2015-01-01

    The functional and oncologic results of eighteen patients with primary malignant periacetabular tumors were reviewed to determine the impact of surgical treatment. The reconstruction procedures were endoprosthesis (11), hip transposition (4), iliofemoral arthrodesis (2), and frozen bone autograft (1). After a mean follow-up of 62 months, 13 patients were alive and 5 had died of their disease; the 5-year overall survival rate was 67.2%. The corresponding mean MSTS scores of patients with endoprosthesis (11) and other reconstructions (7) were 42% and 55% (49%, 68%, and 50%), respectively. Overall, postoperative complications including deep infection or dislocation markedly worsened the functional outcome. Iliofemoral arthrodesis provided better function than the other procedures, whereas endoprosthetic reconstruction demonstrated poor functional outcome except for patients who were reconstructed with the adequate soft tissue coverage. Avoiding postoperative complications is highly important for achieving better function, suggesting that surgical procedures with adequate soft tissue coverage or without the massive use of nonbiological materials are preferable. Appropriate selection of the reconstructive procedures for individual patients, considering the amount of remaining bone and soft tissues, would lead to better clinical outcomes. PMID:26451129

  11. Hepatocellular Carcinoma associated with Extra-hepatic Primary Malignancy: its Secular change, Clinical Manifestations and Survival

    PubMed Central

    Kee, Kwong Ming; Wang, Jing-Houng; Wang, Chih-Chi; Cheng, Yu-Fan; Lu, Sheng-Nan

    2016-01-01

    Clinical manifestations between hepatocellular carcinoma (HCC) and extra-hepatic primary malignancy (EHPM) are lack of large-scale study. We enrolled 14555 HCC patients between 1986 and 2013 retrospectively. The EHPM was classified as prior, synchronous and metachronous group based on before, within and after 6 months of HCC diagnosis, respectively. The incidence rate of EHPM is 3.91% (95% confidence interval [CI]: 3.60–4.23%). Urogenital cancers, kidney and bladder, were at unexpected higher ranks. Older in age, Child-Pugh A cirrhosis, negativity of HBsAg and anti-HCV, and earlier BCLC staging are independent factors associated with EHPM. The survival rates of EHPM improve over time and also better than HCC-alone. Cox proportional-hazards regression shows independent poor prognostic factors are age >60, male, AFP levels ≥400 ng/ml, positivity of HBsAg, Child-Pugh B vs. A, Non-metachronous group, respectively, treated with local ablation, transcatheter arterial embolization, radiotherapy and supportive care vs. surgery, respectively, TNM stage IIIA vs. I, and BCLC stages A, B, C and D vs. 0, respectively. Survival of EHPM improve could be explained by early diagnosis and improve treatment of cancers. PMID:27444261

  12. [Intraoperative extracorporeal irradiation and replantation in local treatment of primary malignant bone tumors].

    PubMed

    Sabo, D; Bernd, L; Buchner, M; Treiber, M; Wannenmacher, M; Ewerbeck, V; Parsch, D

    2003-11-01

    In 13 patients with primary malignant bone tumors (10 Ewing's sarcoma, 1 parosteal osteosarcoma, 1 adamantinoma recurrence, and 1 MFH) local therapy was performed as intraoperative extracorporeal irradiation and replantation (IEIR) of the involved bone segment (5 tibia, 2 femur, and 6 pelvis). Of the 13 patients (69%), 9 are alive at the time of the follow-up (5 CDF, 4 AWM(treated)) and 4 patients died of disease (DOD). Up to now during the follow-up of 32 months (6-57), no local recurrence was observed in the replanted bone segments. The complication rate was very high (18 complications in 11 of the 13 patients, including 6 cases with complication V degrees according to Ruggieri with loss of the reconstruction). The typical complication is severe local infection necessitating removal of the replant. In cases of mechanical failure, the replanted segment could mostly be preserved by surgical revision and autologous bone grafting. If serious complications can be managed or avoided, functional results can be achieved. IEIR must be seen as an extraordinary reconstruction procedure in cases where established procedures such as endoprosthesis, biological reconstructions, or rotationplasties cannot be used or are refused by the patient. PMID:14615850

  13. Critical reappraisal of primary osseous composite sarcoma (malignant mesenchymoma) - analysis of four cases and literature review.

    PubMed

    Chow, Louis T C

    2016-06-01

    In accordance with recent terminology, it is proposed that malignant mesenchymoma should be renamed 'composite sarcoma' and defined as 'a sarcoma composed of two or more cellular types each of which is sufficiently differentiated to permit clear recognition of its histogenetic type microscopically, immunohistochemically or ultrastructurally; excluding fibrosarcomatous and high-grade pleomorphic undifferentiated sarcomatous component, dedifferentiated sarcoma and the combination of osteosarcoma and chondrosarcoma which is regarded as a single histogenetic type'. Four cases of primary osseous composite sarcoma (POCS) were identified among 928 primary bone sarcomas. Their age ranged from 10 to 87 years, peak incidence in the second decade with equal sex distribution. Most presented with pain, commonest in the knee, affecting the metaphysis, appearing radiologically as expansile infiltrative osteolytic lesions with cortical erosion, periosteal reaction, variable extent of osteoblastic areas and soft tissue extension. All contained variable amounts of conventional high-grade osteosarcoma with or without chondrosarcoma component; the other constituents were liposarcoma, rhabdomyosarcoma and leiomyosarcoma. In all cases, Ki67 proliferative index was over 35%, there was no CDK4 and MDM2 amplification. The absence of low-grade component supported the de novo origin of POCS rather than derivation from divergent dedifferentiation. The two older patients with hitherto undescribed osteoleiomyosarcoma died 2 and 10 months after operation, whereas the two younger with osteorhabdomyosarcoma and osteoliposarcoma enjoyed disease-free survival at 16 and 6 years after chemotherapy despite the latter showing lung metastasis at presentation. Identification of the different lines of differentiation together with their approximate amounts and histological grades is therefore mandatory for POCS as multi-agent chemotherapy catered for each sarcoma component might offer hope for long

  14. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    ClinicalTrials.gov

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  15. Increased WD-repeat containing protein 1 in interstitial fluid from ovarian carcinomas shown by comparative proteomic analysis of malignant and healthy gynecological tissue.

    PubMed

    Haslene-Hox, Hanne; Oveland, Eystein; Woie, Kathrine; Salvesen, Helga B; Wiig, Helge; Tenstad, Olav

    2013-11-01

    We aimed to identify differentially expressed proteins in interstitial fluid from ovarian cancer employing multiple fractioning and high resolution mass spectrometry-based proteomic analysis, and asked whether specific proteins that may serve as biomarker candidates or therapeutic targets could be identified. High throughput proteomics was conducted on immunodepleted and fractioned interstitial fluid from pooled samples of ovarian carcinomas, using endometrial carcinomas and healthy ovarian tissue as controls. Differential analysis revealed the up-regulation of extracellular proteasomes in tumor interstitial fluid compared to the healthy control. Moreover, a number of differentially expressed proteins in interstitial fluid from ovarian carcinomas compared with control tissues were identified. Detection of proteasome 20S related proteins in TIF compared to IF from healthy tissue indicates that the 20S proteasome can have a role in the tumor microenvironment. Six selected proteins, CEACAM5, FREM2, MUC5AC, TFF3, PYCARD and WDR1, were independently validated in individual tumor lysates from ovarian carcinomas by multiple reaction monitoring initiated detection and sequence analysis, Western blot and/or selected reaction monitoring. Quantification of specific proteins revealed substantial heterogeneity between individual samples. Nevertheless, WD repeat-containing protein 1 was confirmed as being significantly overexpressed in interstitial fluid from ovarian carcinomas compared to healthy ovarian tissue by Orbitrap analysis of individual native interstitial fluid from ovarian and endometrial carcinomas and healthy ovarian tissue. We suggest that this protein should be explored as a therapeutic target in ovarian carcinomas. This article is part of a Special Issue entitled: An Updated Secretome.

  16. Promoting extracellular matrix remodeling via ascorbic acid enhances the survival of primary ovarian follicles encapsulated in alginate hydrogels.

    PubMed

    Tagler, David; Makanji, Yogeshwar; Tu, Tao; Bernabé, Beatriz Peñalver; Lee, Raymond; Zhu, Jie; Kniazeva, Ekaterina; Hornick, Jessica E; Woodruff, Teresa K; Shea, Lonnie D

    2014-07-01

    The in vitro growth of ovarian follicles is an emerging technology for fertility preservation. Various strategies support the culture of secondary and multilayer follicles from various species including mice, non-human primate, and human; however, the culture of early stage (primary and primordial) follicles, which are more abundant in the ovary and survive cryopreservation, has been limited. Hydrogel-encapsulating follicle culture systems that employed feeder cells, such as mouse embryonic fibroblasts (MEFs), stimulated the growth of primary follicles (70-80 µm); yet, survival was low and smaller follicles (<70 µm) rapidly lost structure and degenerated. These morphologic changes were associated with a breakdown of the follicular basement membrane; hence, this study investigated ascorbic acid based on its role in extracellular matrix (ECM) deposition/remodeling for other applications. The selection of ascorbic acid was further supported by a microarray analysis that suggested a decrease in mRNA levels of enzymes within the ascorbate pathway between primordial, primary, and secondary follicles. The supplementation of ascorbic acid (50 µg/mL) significantly enhanced the survival of primary follicles (<80 µm) cultured in alginate hydrogels, which coincided with improved structural integrity. Follicles developed antral cavities and increased to diameters exceeding 250 µm. Consistent with improved structural integrity, the gene/protein expression of ECM and cell adhesion molecules was significantly changed. This research supports the notion that modifying the culture environment (medium components) can substantially enhance the survival and growth of early stage follicles.

  17. Effect of second-line surgery on in vitro fertilization outcome in infertile women with ovarian endometrioma recurrence after primary conservative surgery for moderate to severe endometriosis

    PubMed Central

    Park, Hana; Kim, Eun-Young; Moon, Jei-Won; Kim, Sung-Hoon; Chae, Hee-Dong; Kang, Byung-Moon

    2015-01-01

    Objective To evaluate the effect of second-line conservative surgery on in vitro fertilization (IVF) outcome in comparison with IVF without second-line surgery in infertile women with ovarian endometrioma recurrence after primary conservative surgery. Methods In this retrospective cohort study, 121 consecutive IVF/intracytoplasmic sperm injection cycles that were performed after second-line surgery (n=53) or without second-line surgery (control group, n=68) between January 2006 and December 2011 in 121 infertile women with ovarian endometrioma(s) recurrence after primary conservative surgery for moderate to severe endometriosis were included. The two groups were compared in terms of controlled ovarian stimulation and IVF outcomes. Results There were no differences in patients' characteristics between the two groups. Total dose and days of gonadotropins administered were significantly higher in the second-line surgery group than in the control group (P<0.001, P=0.008). The numbers of oocytes retrieved, mature oocytes and grade 1 or 2 embryos were significantly lower in the second-line surgery group (P=0.007, P=0.001, P<0.001, respectively). Clinical pregnancy rate per cycle and embryo implantation rate were also significantly lower in the second-line surgery group of 24.5% and 11.8% compared with 48.5% and 25.3% in the control group (P=0.008, P=0.005, respectively). Conclusion Ovarian response to controlled ovarian stimulation and IVF outcome after second-line surgery is worse than those in IVF cycles without second-line surgery in infertile women with ovarian endometrioma recurrence after primary surgery for moderate or severe endometriosis. PMID:26623412

  18. CD40 is a prognostic marker in primary cutaneous malignant melanoma.

    PubMed Central

    van den Oord, J. J.; Maes, A.; Stas, M.; Nuyts, J.; Battocchio, S.; Kasran, A.; Garmyn, M.; De Wever, I.; De Wolf-Peeters, C.

    1996-01-01

    CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous

  19. NOBOX is a strong autosomal candidate gene in Tunisian patients with primary ovarian insufficiency.

    PubMed

    Bouali, N; Francou, B; Bouligand, J; Lakhal, B; Malek, I; Kammoun, M; Warszawski, J; Mougou, S; Saad, A; Guiochon-Mantel, A

    2016-05-01

    Premature ovarian insufficiency (POI) affects approximately 1% of women before the age of 40. Genetic contribution is a significant component of POI. In this context, heterozygous mutations in NOBOX, BMP15 and GDF9 have been reported. The objective of our study was to evaluate the prevalence of these genes mutations in 125 unrelated Tunisian patients diagnosed with POI. The screening of NOBOX gene revealed three missense mutations (p.Arg117Trp; p.Gly91Trp and p.Pro619Leu) in eight patients. These mutations were not found in a 200 ethnically matched women without fertility problem. The sequencing of BMP15 and GDF9 gene revealed only previously reported variants. In contrast to previous studies, the prevalence of BMP15 variations is not higher than in the control population. Conversely, 6.4% of the cases present a NOBOX mutations; this high prevalence strengthens the consideration of NOBOX gene as strong autosomal candidate for POI.

  20. Imatinib Mesylate in Treating Patients With Progressive, Refractory, or Recurrent Stage II or Stage III Testicular or Ovarian Cancer

    ClinicalTrials.gov

    2013-01-15

    Ovarian Dysgerminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage II Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Testicular Seminoma

  1. Effect of nickel (ni(2+)) on primary human ovarian granulosa cells in vitro.

    PubMed

    Révész, Csaba; Forgács, Zsolt; Lázár, Péter; Mátyás, Szabolcs; Rajczy, Klára; Krizsa, Ferenc; Bernard, Artúr; Gáti, István

    2004-01-01

    Human ovarian granulosa cells obtained from women undergoing in vitro fertilization were exposed to 15.6, 31.25, 62.5, 125, 250, 500, 1000 muM Ni(2+) for 48 h. To determine the site of action of Ni(2+), the granulosa cells were stimulated to produce progesterone (P) by using maximally stimulating amounts of human chorionic gonadotropin (0.1 IU/ml hCG) or dibutyryl cyclic adenosine monophosphate (1 mM db-cAMP). The luteinizing hormone (LH) analog hCG was chosen because resultant P production requires an intact membrane receptor and db-cAMP was used to test for post LH receptor defects caused by Ni(2+). Progesterone content of the culture medium was determined by radioimmunoassay (RIA), and viability of the cells was measured by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) reduction test. Concentration-dependent depression in both hGC and db-cAMP stimulated P production was seen at 15.625 muM or higher concentration of Ni(2+), which is not cytotoxic on human ovarian granulosa cells. The viability of cells was unaffected up to 31.25 muM and decreased significantly at 62.5 muM. Our results show a dose-related depression in stimulated P production of granulosa cells at a dose that does not induce significant cytotoxic action. These data indicate that the effect of Ni(2+) on P production is not due to cytotoxicity, and the cellular site(s) of inhibitory action appears to be subsequent to the membrane receptor and production of cAMP.

  2. Polyurethane-Covered Nitinol Strecker Stents as Primary Palliative Treatment of Malignant Biliary Obstruction

    SciTech Connect

    Kanasaki, Shuzo; Furukawa, Akira; Kane, Teruyuki; Murata, Kiyoshi

    2000-03-15

    Purpose: To evaluate the clinical efficacy of the polyurethane-covered Nitinol Strecker stent in the treatment of patients with malignant biliary obstruction.Methods: Twenty-three covered stents produced by us were placed in 18 patients with malignant biliary obstruction. Jaundice was caused by cholangiocarcinoma (n = 5), pancreatic cancer (n = 6), gallbladder cancer (n = 4), metastatic lymph nodes (n = 2), and tumor of the papilla (n 1).Results: The mean patency period of the stents was 37.5 weeks (5-106 weeks). Recurrent obstructive jaundice occurred in two patients (11%). Adequate biliary drainage over 50 weeks or until death was achieved in 17 of 18 patients (94.4%). Late cholangitis was observed in two patients whose stents bridged the ampulla of Vater. Other late severe complications were not encountered.Conclusion: Although more study is necessary, our results suggest the clinical efficacy of our covered Nitinol Strecker stent in the management of obstructive jaundice caused by malignant diseases.

  3. Cytological patterns of primary malignant uterine fibrous histiocytoma. A case report.

    PubMed

    Torrisi, A; Giorgino, F; Onnis, G L; Minucci, D

    1990-01-01

    The Authors have reported the cytological patterns of malignant primitive uterine fibrous histiocytoma of a 57 year old woman. The endometrial cytological sampling was performed by an aspiration technique using a feeding-tube; a necrotic-haemorrhagic background filled with hymphocytes and polymorphonuclear leukocytes, and a mixture of highly anaplastic histiocytic and fibroblastic type cells, associated with undifferentiated small round cells, has been described. The result of the histological examination performed on the surgical specimen was the following: polymorphic malignant neoplasia characterized by spindle-like and giant plurinucleated cells, phagocytosis features, endoluminal polypoid growth, wide infiltration of the miometrium two thirds deep, vascular space invasion of the uterine wall and the hilus of the ovaries. The histological features and immunohistochemical analysis were consistent with malignant fibrous histiocytoma in the pleomorphic variety. PMID:1965802

  4. Huge primary mucinous cystadenoma of the retroperitoneum mimicking a left ovarian tumor.

    PubMed

    Balat, O; Aydin, A; Sirikci, A; Kutlar, I; Aksoy, F

    2001-01-01

    Primary mucinous cystic tumors of the retroperitoneum are rarely encountered and have been reported in approximately 25 cases in the literature. The histogenesis of primary mucinous cystadenomas is not clear. Most authors suggest that it develops through mucinous metaplasia in a pre-existing mesothelium-lined cyst. Surgery is the only treatment. In this report we present an additional case of primary retroperitoneal mucinous cystadenoma in a 44-year-old female.

  5. Ovarian tissue characterization in ultrasound: a review.

    PubMed

    Acharya, U Rajendra; Molinari, Filippo; Sree, S Vinitha; Swapna, G; Saba, Luca; Guerriero, Stefano; Suri, Jasjit S

    2015-06-01

    Ovarian cancer is the most common cause of death among gynecological malignancies. We discuss different types of clinical and nonclinical features that are used to study and analyze the differences between benign and malignant ovarian tumors. Computer-aided diagnostic (CAD) systems of high accuracy are being developed as an initial test for ovarian tumor classification instead of biopsy, which is the current gold standard diagnostic test. We also discuss different aspects of developing a reliable CAD system for the automated classification of ovarian cancer into benign and malignant types. A brief description of the commonly used classifiers in ultrasound-based CAD systems is also given.

  6. Ovarian tissue characterization in ultrasound: a review.

    PubMed

    Acharya, U Rajendra; Molinari, Filippo; Sree, S Vinitha; Swapna, G; Saba, Luca; Guerriero, Stefano; Suri, Jasjit S

    2015-06-01

    Ovarian cancer is the most common cause of death among gynecological malignancies. We discuss different types of clinical and nonclinical features that are used to study and analyze the differences between benign and malignant ovarian tumors. Computer-aided diagnostic (CAD) systems of high accuracy are being developed as an initial test for ovarian tumor classification instead of biopsy, which is the current gold standard diagnostic test. We also discuss different aspects of developing a reliable CAD system for the automated classification of ovarian cancer into benign and malignant types. A brief description of the commonly used classifiers in ultrasound-based CAD systems is also given. PMID:25230716

  7. [A Case of Primary Renal Malignant Lymphoma Initially Managed as Severe Pyelonephritis in a Patient Undergoing Hemodialysis].

    PubMed

    Fujizuka, Yuji; Suzuki, Tomomi; Suzuki, Koichi; Kubota, Yutaka; Matsuo, Yasushige

    2016-03-01

    A 75-year-old male undergoing hemodialysis because of diabetic nephropathy was referred to our hospital complaining of high fever and swelling of the left kidney. Our initial clinical diagnosis was severe pyelonephritis. He was initially treated with intravenous antibiotics and his clinical symptoms subsequently improved but only temporarily. The high fever soon recurred, accompanied by progressive thrombocytopenia. His general condition deteriorated despite conservative treatment. He then underwent nephrectomy of the left kidney. However, the thrombocytopenia persisted and his general condition did not improve. The pathological diagnosis was malignant lymphoma (non-Hodgkin's lymphoma, diffuse large B-cell type). He received chemotherapy, but his status rapidly deteriorated and he died 1.5 months after the operation. Primary renal malignant lymphoma is very rare, because the kidney lacks lymphatic tissue. PMID:27133886

  8. Mathematical models of breast and ovarian cancers.

    PubMed

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

    2016-07-01

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

  9. Epidermal growth factor, oestrogen and progesterone receptor expression in primary ovarian cancer: correlation with clinical outcome and response to chemotherapy.

    PubMed Central

    Scambia, G.; Benedetti-Panici, P.; Ferrandina, G.; Distefano, M.; Salerno, G.; Romanini, M. E.; Fagotti, A.; Mancuso, S.

    1995-01-01

    The expression of epidermal growth factor receptor (EGFR), oestrogen receptor (ER) and progesterone receptor (PR) was assayed by a radioreceptor method in 117 primary ovarian cancers. EGFR was not significantly related to any of the clinicopathological parameters examined. In patients with stage II-IV disease who underwent second-look surgery after primary chemotherapy, a significant correlation between high EGFR levels and poor response to chemotherapy was demonstrated (P = 0.031). Moreover, post-operative residual tumour showed an independent role in predicting chemotherapy response (P = 0.0007) and EGFR status showed a borderline significance (P = 0.052) in the multivariate analysis. No correlation between steroid hormone receptors and clinicopathological parameters was observed. Whereas a significant relationship was shown between EGFR positivity and a shorter overall survival (OS) (P = 0.0022) and progression-free survival (PFS) (P = 0.0033), patient survival was not related to steroid hormone receptor status. Among the parameters tested only stage, ascites and EGFR status retained an independent prognostic value in the multivariate analysis. PMID:7640219

  10. Nonmalignant Diseases and Treatments Associated with Primary Ovarian Failure: An Expanded Role for Fertility Preservation

    PubMed Central

    Hirshfeld-Cytron, Jennifer; Gracia, Clarisa

    2011-01-01

    Abstract Cancer treatments can be detrimental to fertility; recent literature has focused on the efforts of fertility preservation for this patient population. It should be recognized, however, that several nonmalignant medical conditions and therapeutic interventions could be similarly hazardous to fertility. Some of these nonmalignant diseases and their treatments that can adversely impact the reproductive axis are gastrointestinal diseases, rheumatologic disorders, nonmalignant hematologic conditions, neurologic disorders, renal disorders, gynecologic conditions, and metabolic diseases. Their negative effects on reproductive function are only now being appreciated and include impaired ovarian function, endocrine function, or sexual function and inability to carry a pregnancy to term. Complications and comorbidities associated with certain diseases may limit the success of established fertility preservation options. Recent advances in fertility preservation techniques may provide these patients with new options for childbearing. Here, we review several fertility-threatening conditions and treatments, describe current established and experimental fertility preservation options, and present three initiatives that may help minimize the adverse reproductive effects of these medical conditions and treatments by raising awareness of the issues and options: (1) increase awareness among practitioners about the reproductive consequences of specific diseases and treatments, (2) facilitate referral of patients to fertility-sparing or restorative programs, and (3) provide patient education about the risk of infertility at the time of diagnosis before initiation of treatment. PMID:21827325

  11. PET Imaging of Ovarian Carcinoma With 18F-FSPG

    ClinicalTrials.gov

    2016-08-16

    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

  12. Knockdown of HVEM, a Lymphocyte Regulator Gene, in Ovarian Cancer Cells Increases Sensitivity to Activated T Cells.

    PubMed

    Zhang, Ting; Ye, Lei; Han, Lingfei; He, Qizhi; Zhu, Jianlong

    2016-01-01

    Ovarian cancer is highly malignant with a gradually increasing incidence and a high mortality rate. Immunosuppression is induced in ovarian cancer, although the mechanism detail is not clear. It has been indicated that HVEM (herpesvirus entry mediator) B- and T-lymphocyte attenuator (BTLA) negatively regulates the immune responses of T lymphocytes. Here, HVEM mRNA was found to be elevated in ovarian cancer tissue samples and primary ovarian cancer cells in comparison with benign tissue samples. We then knocked down HVEM expression in an ovarian cancer cell line, OVCAR3, by lentivirus-based small hairpin RNA (shRNA). Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis showed that HVEM-shRNA had no effect on the proliferation, early apoptosis, or cell cycle distribution of OVCAR3. We then isolated activated T cells and performed coculture experiments in Transwell. Remarkably, HVEM-silenced ovarian cancer cells (primary ovarian cancer cells and OVCAR3) increased the number of T cells and the secretion of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), while activated T cells promoted the apoptosis of HVEM-silenced ovarian cancer cells. The current study partially explains the immune escape mechanism of ovarian cancer cells and provides a possible target for immunotherapy. PMID:27458100

  13. Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients

    NASA Astrophysics Data System (ADS)

    Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.

    1996-12-01

    The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.

  14. Polyorethaoe-covered nitinol strecker stents as primary palliative treatment of malignant biliary obstruction

    SciTech Connect

    Kanasaki, Shuzo; Furukawa, Akira; Kane, Teruyuki; Murata, Kiyoshi

    2000-03-15

    Purpose: To evaluate the clinical efficacy of the polyure-thane-covered Nitinol Strecker stent in the treatment of patients with malignant biliary obstruction.Methods: Twenty-three covered stents produced by us were placed in 18 patients with malignant biliary obstruction. Jaundice was caused by cholangiocarcinoma (n=5), pancreatic Cancer (n=6), gallbladder Cancer (n=4), metastatic lymph nodes (n=2), and tumor of the papilla (n=1).Resulrs: The mean patency period of the Stents was 37.5 weeks (5-106 weeks). Recurrent obstructive jaundice occurred in two patients (11%). Adequate biliary drainage over 50 weeks or until death was achieved in 17 of 18 patients (94.4%). Late cholangitis was observed in two patients whose stents bridged the ampulla of Vater. Other late severe complications were not encountered.Conclusion: Although more study is necessary, our results suggest the clinical efficacy of our covered Nitinol Strecker stent in the management of obstructive jaundice caused by malignant diseases.

  15. Five mutations of mitochondrial DNA polymerase-gamma (POLG) are not a prevalent etiology for spontaneous 46,XX primary ovarian insufficiency.

    PubMed

    Tong, Zhi-Bin; Sullivan, Shannon D; Lawless, Lindsey M; Vanderhoof, Vien; Zachman, Keith; Nelson, Lawrence M

    2010-12-01

    The study objective was to determine if mutations in mitochondrial DNA polymerase gamma (POLG) are associated with spontaneous 46,XX primary ovarian insufficiency (sPOI) using restriction fragment length polymorphism analysis of genomic DNA. Of 201 women with 46,XX sPOI analyzed, we found only one case (0.5%, 95% confidence interval 0-3%) of heterozygosity for a POLG mutation, suggesting that this is not a common genetic etiology for this form of infertility. PMID:20701905

  16. Ovarian tumors in pregnancy: diagnosis and management.

    PubMed

    Husseinzadeh, Nader; Sibai, Baha; Siddiqi, Tariq A

    2012-05-01

    Ovarian tumors first diagnosed during pregnancy often present a challenge for both the obstetrician and gynecologists providing pregnancy care and for the consulting subspecialists. Although the vast majority of these tumors is benign, on rare occasions, patients present with tumors that turn out to be malignant requiring more comprehensive and extensive surgical procedures that are more likely to lead to pregnancy loss. Hence accurate knowledge of tumor characteristics, especially the ultrasound appearance and gestational age at diagnosis, are key prerequisite for establishing the most effective management plan not just for the index but also for future pregnancies. The primary objective of the current review is to provide practical guidelines for the evaluation and management of ovarian tumors first diagnosed during pregnancy.

  17. Direct Primary or Secondary Percutaneous Ureteral Stenting: What Is the Most Compliant Option in Patients with Malignant Ureteral Obstructions?

    SciTech Connect

    Carrafiello, Gianpaolo Lagana, Domenico; Lumia, Domenico; Giorgianni, Andrea; Mangini, Monica; Santoro, Domenico; Cuffari, Salvatore; Marconi, Alberto; Novario, Raffaele; Fugazzola, Carlo

    2007-09-15

    The objective of this study was to analyze three ureteral stenting techniques in patients with malignant ureteral obstructions, considering the indications, techniques, procedural costs, and complications. In the period between June 2003 and June 2006, 45 patients with bilateral malignant ureteral obstructions were evaluated (24 males, 21 females; average age, 68.3; range, 42-87). All of the patients were treated with ureteral stenting: 30 (mild strictures) with direct stenting (insertion of the stent without predilation), 30 (moderate/severe strictures) with primary stenting (insertion of the stent after predilation in a one-stage procedure), and 30 (mild/moderate/severe strictures with infection) with secondary stenting (insertion of the stent after predilation and 2-3 days after nephrostomy). The incidence of complications and procedural costs were compared by a statistical analysis. The primary technical success rate was 98.89%. We did not observe any major complications. The minor complication rate was 11.1%. The incidence of complications for the various techniques was not statistically significantly. The statistical analysis of costs demonstrated that the average cost of secondary stenting ( Euro 637; SD, Euro 115) was significantly higher than that of procedures which involved direct or primary stenting ( Euro 560; SD, Euro 108). We conclude that one-step stenting (direct or primary) is a valid option to secondary stenting in correctly selected patients, owing to the fact that when the procedure is performed by expert interventional radiologists there are high technical success rates, low complication rates, and a reduction in costs.

  18. Palmar fasciitis and arthritis with ovarian and non-ovarian carcinomas. New syndrome.

    PubMed

    Shiel, W C; Prete, P E; Jason, M; Andrews, B S

    1985-11-01

    Paraneoplastic syndromes affect a variety of organ systems and often suggest occult malignancy. Recently, a distinct syndrome of palmar fasciitis and arthritis has been associated with ovarian carcinomas. The two cases presented illustrate the fasciitis-arthritis association with other non-ovarian malignancies and suggest an immunologic cause for this disorder.

  19. Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis).

    PubMed

    Kim, Su-Min; Oh, Yeonsu; Oh, Suk-Hun; Han, Jeong-Hee

    2016-03-01

    A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk. PMID:26568187

  20. Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis).

    PubMed

    Kim, Su-Min; Oh, Yeonsu; Oh, Suk-Hun; Han, Jeong-Hee

    2016-03-01

    A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk.

  1. Primary diffuse malignant peritoneal mesothelioma in a striped skunk (Mephitis mephitis)

    PubMed Central

    KIM, Su-Min; OH, Yeonsu; OH, Suk-Hun; HAN, Jeong-Hee

    2015-01-01

    A 10-year-old female striped skunk (Mephitis mephitis) was admitted with severe abdominal distension and lethargy. Cytological examination of the peritoneal fluid revealed activated mesothelial cells. At necropsy, numerous growing together, projecting, 2 to 20 mm in diameter tawny to white masses were scattered throughout the peritoneum including the mesentery, omentum and intestinal serosa. Microscopically, the tumor was composed of prominent papillo-tubular structures, and immunohistochemically, the spindle to polygonal-shaped tumor cells with nuclear polymorphism were strongly reactive for calretinin. Based on those diagnostic features, the neoplasia was diagnosed as malignant mesothelioma. This is the first case report of mesothelioma in the skunk. PMID:26568187

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

    PubMed

    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.

  3. Hydrosalpinx as a Rare Presentation of Synchronous Ovarian and Endometrial Carcinoma – A Case Report

    PubMed Central

    Khan, Mahjabeen; Amin, Sapna Vinit; Shivananda, Roopa Padavagodu; Patil, Navin

    2016-01-01

    Hydrosalpinx in postmenopausal woman is rare. Most commonly it is due to primary ovarian malignancy with fallopian tube involvement or primary fallopian tube carcinoma. But hydrosalpinx with no malignancy in the fallopian tube, associated with synchronous malignancy of ovary and endometrium is rare. In a postmenopausal women, hydrosalpinx is commonly due to fallopian tube malignancy or rarely pelvic inflammatory disease. We present a rare and very interesting case of 65-year-old nulliparous postmenopausal women with bilateral hydrosalpinx and pyometra who was found to have papillary serous adenocarcinoma of the ovary and endometroid adenocarcinoma of endomertrium with normal fallopian tube. One should always suspect genital malignancy with this presentation, especially in this age group. PMID:27630913

  4. Hydrosalpinx as a Rare Presentation of Synchronous Ovarian and Endometrial Carcinoma – A Case Report

    PubMed Central

    Khan, Mahjabeen; Amin, Sapna Vinit; Shivananda, Roopa Padavagodu; Patil, Navin

    2016-01-01

    Hydrosalpinx in postmenopausal woman is rare. Most commonly it is due to primary ovarian malignancy with fallopian tube involvement or primary fallopian tube carcinoma. But hydrosalpinx with no malignancy in the fallopian tube, associated with synchronous malignancy of ovary and endometrium is rare. In a postmenopausal women, hydrosalpinx is commonly due to fallopian tube malignancy or rarely pelvic inflammatory disease. We present a rare and very interesting case of 65-year-old nulliparous postmenopausal women with bilateral hydrosalpinx and pyometra who was found to have papillary serous adenocarcinoma of the ovary and endometroid adenocarcinoma of endomertrium with normal fallopian tube. One should always suspect genital malignancy with this presentation, especially in this age group.

  5. Ovarian Cancer

    MedlinePlus

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

  6. Ovarian Cancer

    MedlinePlus

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

  7. Second malignancies in patients with differentiated thyroid carcinoma treated with low and medium activities of radioactive I-131

    PubMed Central

    PICIU, DOINA; PESTEAN, CLAUDIU; BARBUS, ELENA; LARG, MARIA IULIA; PICIU, ANDRA

    2016-01-01

    Background and aim This study aimed at determining whether there is a risk regarding the development of second primary malignancies after patient exposure to the low and medium radioiodine activity used during the treatment of differentiated thyroid cancers (DTC). Methods Second primary malignancies that occurred after DTC were detected in 1,990 patients treated between 1970 and 2003. The mean long-term follow-up period was 182 months. Results Radioiodine I-131was administrated at a mean dose of 63.2 mCi. There were 93 patients with at least one second primary malignancy. The relative risk of development of second malignancy in DTC patients was increased (p<0.0001) for breast, uterine and ovarian cancers compared with the general population. Conclusions The overall risk concerning the development of second primary malignancies was related to the presence of DTC, but not to exposure to the low and medium activities of radioiodine administered as adjuvant therapy. PMID:27547058

  8. Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer.

    PubMed

    Komiyama, Shinichi; Katabuchi, Hidetaka; Mikami, Mikio; Nagase, Satoru; Okamoto, Aikou; Ito, Kiyoshi; Morishige, Kenichiro; Suzuki, Nao; Kaneuchi, Masanori; Yaegashi, Nobuo; Udagawa, Yasuhiro; Yoshikawa, Hiroyuki

    2016-06-01

    The fourth edition of the Japan Society of Gynecologic Oncology guidelines for the treatment of ovarian cancer including primary peritoneal cancer and fallopian tube cancer was published in 2015. The guidelines contain seven chapters and six flow charts. The major changes in this new edition are as follows-(1) the format has been changed from reviews to clinical questions (CQ), and the guidelines for optimal clinical practice in Japan are now shown as 41 CQs and answers; (2) the 'flow charts' have been improved and placed near the beginning of the guidelines; (3) the 'basic points', including tumor staging, histological classification, surgical procedures, chemotherapy, and palliative care, are described before the chapter; (4) the FIGO surgical staging of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer was revised in 2014 and the guideline has been revised accordingly to take the updated version of this classification into account; (5) the procedures for examination and management of hereditary breast and ovarian cancer are described; (6) information on molecular targeting therapy has been added; (7) guidelines for the treatment of recurrent cancer based on tumor markers alone are described, as well as guidelines for providing hormone replacement therapy after treatment. PMID:27142770

  9. Diagnostic Accuracy of B-mode USG and Doppler Scan for Ovarian Lesions

    PubMed Central

    Agarwal, Vinish Kumar

    2016-01-01

    Introduction Ultrasonography (USG) is considered as the primary imaging modality for confirmation of ovarian mass and to differentiate them in to benign or malignant. Aim The present study was conducted with the aim to evaluate accuracy of B- mode USG and Doppler scan (Colour Doppler + Spectral Doppler) for ovarian lesions. Materials and Methods The patients included in the study were from those referred with either palpable adnexal mass or incidentally detected adnexal masses. Total 250 women were evaluated by USG, Doppler scan. Only fifty patients who had true ovarian mass intraoperatively and on histopathology were included in study, rest masses were excluded. Study parameters were morphological indexing on B- Mode USG, flow study, vessel arrangement, and vessel morphology and vessel location in Colour Doppler and resistive index and pulsatility index in spectral Doppler. Results Total 50 women were included in present study. Out of these 46% were pre-menopausal while 54% were menopaused women, 66.7% of post-menopausal women had malignant ovarian masses compared to 8.7% of premenopausal. Sensitivity, specificity, positive predictive value and negative predictive value of B-Mode USG for ovarian masses were 94.44%, 48.15%, 54.84% and 92.86% respectively, with p-value = 0.007, while sensitivity, specificity, positive predictive value and negative predictive value of Doppler scan were 85%, 90%, 85% and 90% respectively, with p-value = 0.0001. Conclusion USG and its different techniques are accepted as the primary imaging modality for early stage diagnosis of an ovarian malignancy. Statistical analysis suggests that Doppler Scan (Colour + Spectral) was more accurate (88%) than B-Mode USG (67%), but author is in view that both of these modalities should be used in conjunction to screen the ovarian lesions. PMID:27790544

  10. From Victim to Survivor to Thriver: Helping Women with Primary Ovarian Insufficiency Integrate Recovery, Self-Management, and Wellness

    PubMed Central

    Sterling, Evelina Weidman; Nelson, Lawrence M.

    2015-01-01

    Most women discover that they are infertile in a gradual manner after many failed attempts at conception. By contrast, most women with primary ovarian insufficiency (POI) uncover their infertility as part of an evaluation of other presenting complaints, frequently before attempts at conception have even been contemplated. The most common words women use to describe how they feel in the hours after getting the diagnosis of POI are “devastated,” “shocked,” and “confused.” Clearly, the news propels some patients onto a difficult journey. POI is a serious and incurable chronic disease. The diagnosis is more than infertility and affects a woman’s physical and emotional well-being. Management of the condition must address both. Patients face the acute shock of the diagnosis, associated stigma of infertility, grief from the death of dreams, anxiety from the disruption of life plans, confusion around the cause, symptoms of estrogen deficiency, worry over the associated potential medical sequelae such as reduced bone density and cardiovascular risk, and the uncertain future that all of these factors create. There is a need for an evidenced-based integrated program to assist women with POI in navigating the transition to acceptance of the diagnosis, ongoing management of the condition, and ongoing maintenance of wellness in the presence of the disorder. A health-centered approach can gradually replace the disease-centered approach and put patients in partnerships with professional health-care providers. Ideally, the journey transitions each patient from seeing herself as a victim, to a survivor, to a woman who is thriving. PMID:21969269

  11. Effects of Physiologic Testosterone Replacement on Quality of Life, Self-Esteem, and Mood in Women with Primary Ovarian Insufficiency

    PubMed Central

    Guerrieri, Gioia M.; Martinez, Pedro E.; Klug, Summer P.; Haq, Nazli A.; Vanderhoof, Vien H.; Koziol, Deloris E.; Popat, Vaishali B.; Kalantaridou, Sophia N.; Calis, Karim A.; Rubinow, David R.; Schmidt, Peter J.; Nelson, Lawrence M.

    2014-01-01

    Objective Low androgen levels occur in women with primary ovarian insufficiency(POI) and could contribute to mood and behavioral symptoms in this condition. We examined the effects of physiologic testosterone (T) replacement therapy added to standard estrogen/progestin replacement therapy (EPT) on quality of life, self-esteem, and mood in women with POI. Methods 128 women with 46XX spontaneous POI participated in a 12 month randomized, placebo-controlled, parallel-design investigation of the efficacy of T augmentation of EPT. Quality of life, self-esteem, and mood symptoms were evaluated with standardized rating scales and a structured clinical interview. Differences in outcome measures between the T and placebo treatments were analyzed by Wilcoxon rank-sum tests. Results No differences were found in baseline characteristics including serum hormone levels(P >0.05). Baseline mean(SD) CES-D scores were 10.7(8.6)(T) and 9.2(7.8)(placebo) (P = 0.35). After 12 months of treatment, measures of quality of life, self-esteem, and the presence of mood symptoms did not differ between treatment groups. Serum T levels achieved physiologic levels in the T group and were significantly higher compared to placebo (P < 0.001). Baseline T levels were not associated with either adverse or beneficial clinical effects. Conclusions The 150 microgram T patch achieves physiologic hormone levels in women with POI. Our findings suggest that augmentation of standard EPT with physiologic testosterone replacement in young women with POI neither aggravates nor improves baseline reports of quality of life, or self-esteem and had minimal effect on mood. Other mechanisms might play a role in the altered mood that accompanies this disorder. PMID:24473536

  12. [The rational preoperative diagnosis of ovarian tumors - imaging techniques and tumor biomarkers (review)].

    PubMed

    Fischerová, D; Zikán, M; Pinkavová, I; Sláma, S; Frühauf, F; Freitag, P; Dundr, P; Burgetová, A; Cibula, D

    2012-08-01

    The majority of patients who suffer from an early-stage or advanced-stage of ovarian cancer complain about symptoms, mainly gastrointestinal ones. The pelvic examination in ovarian cancer detection is limited by the adnexal position in the pelvis and frequent extraovarian spread of disease. Recently, any reliable tumor biomarker (CA 125 and/or HE4), which can be used in differential diagnosis between benign and malignant ovarian tumors, does not exist. According the results of the largest multicenter International Ovarian Trial Analysis (IOTA), ultrasound if performed by an experienced sonologist is an ideal diagnostic method in differential diagnosis between benign and malignant ovarian tumors. The experienced examiner is also able to detect extraovarian tumor spread and to assess tumor operability. Magnetic resonance imaging (MRI) is used only to complement ultrasound in cases when high tissue resolution is needed. Computed tomography (CT) is a useful method for detection of extraovarian spread, especially in cases when an ultrasound examiner experienced in abdominal scanning is not available. Similarly, fusion of positron emission tomography with CT (PET/CT) is a highly accurate method for the detection of abdominal and extraabdominal tumor spread, but its use is limited by cost and the low availability of this method. On the other hand, PET/CT is not recommended for primary ovarian cancer detection because of its lower sensitivity in comparison to ultrasound and its high false positive rates as well.

  13. Sleep Loss and Its Effects on Health of Family Caregivers of Individuals with Primary Malignant Brain Tumors

    PubMed Central

    Lee, Shih-Yu; Clark, Patricia C.; Sherwood, Paula R.

    2013-01-01

    Sleep loss places caregivers at risk for poor health. Understanding correlates of sleep loss and relationships to health may enable improvement of health of caregivers of individuals with primary malignant brain tumors (PMBT). In this cross-sectional, descriptive study of 133 caregivers, relationships were examined between sleep loss and physical, mental, emotional, and social health at time of patient diagnosis. Sleep loss was not related to physical health. Shorter total sleep time was associated with greater fatigue and social support. Sleep quality was positively associated with quality of life. Further study is needed of the role of sleep loss in the PMBT caregiving trajectory and its long-term relationship with health outcomes. PMID:23633116

  14. Sleep loss and its effects on health of family caregivers of individuals with primary malignant brain tumors.

    PubMed

    Pawl, Jean D; Lee, Shih-Yu; Clark, Patricia C; Sherwood, Paula R

    2013-08-01

    Sleep loss places caregivers at risk for poor health. Understanding correlates of sleep loss and relationships to health may enable improvement of health of caregivers of individuals with primary malignant brain tumors (PMBT). In this cross-sectional, descriptive study of 133 caregivers, relationships were examined between sleep loss and physical, mental, emotional, and social health at time of patient diagnosis. Sleep loss was not related to physical health. Shorter total sleep time was associated with greater fatigue and social support. Sleep quality was positively associated with quality of life. Further study is needed of the role of sleep loss in the PMBT caregiving trajectory and its long-term relationship with health outcomes.

  15. Intact PTEN Expression by Immunohistochemistry is Associated With Decreased Survival in Advanced Stage Ovarian/Primary Peritoneal High-grade Serous Carcinoma.

    PubMed

    Bakkar, Rania M; Xie, Su-Su; Urbauer, Diana L; Djordjevic, Bojana; Vu, Kim; Broaddus, Russell R

    2015-11-01

    Ovarian high-grade serous carcinoma is an aggressive malignancy with poor prognosis. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are 2 well-established prognostics for this tumor type. Molecular markers that identify more clinically aggressive tumors would potentially allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with nonendometrioid tumors. The prognostic and predictive value for PTEN has not been effectively explored in ovarian/peritoneal high-grade serous carcinoma. PTEN immunohistochemistry was assessed in 126 women with Stage III, high-grade serous carcinoma of the ovary/peritoneum treated with surgery and then a platinum-based regimen. Compared with PTEN-negative or PTEN-reduced tumors, positive PTEN immunohistochemistry, detected in 58% of tumors, was associated with decreased pS6 and increased PTEN mRNA levels. Positive PTEN expression was independent of surgical debulking status or platinum sensitivity. PTEN-positive tumors were associated with significantly decreased recurrence-free survival. Importantly, the devised PTEN immunohistochemistry scoring system was reproducible among pathologists.

  16. Five mutations of mitochondrial DNA polymerase-gamma (POLG) are not a prevalent etiology for spontaneous 46,XX primary ovarian insufficiency (sPOI)

    PubMed Central

    Tong, Zhi-Bin; Sullivan, Shannon D.; Lawless, Lindsey M.; Vanderhoof, Vien; Zachman, Keith; Nelson, Lawrence M.

    2010-01-01

    The etiology of most cases of spontaneous 46,XX primary ovarian insufficiency (sPOI) is unknown, however, associations have been made between mitochondrial diseases due to mutated mitochondrial DNA polymerase gamma (POLG) and sPOI. Here, we show that in 201 women with 46,XX sPOI, RFLP analysis of genomic DNA shows only one case (0.5%, 95% CI <3%) of heterozygosity for a mtDNA POLG mutation, suggesting that this is not a common genetic etiology for this form of infertility. PMID:20701905

  17. NPPB is a Novel Candidate Biomarker Expressed by Cancer-Associated Fibroblasts In Epithelial Ovarian Cancer

    PubMed Central

    Lawrenson, Kate; Grun, Barbara; Lee, Nathan; Mhawech-Fauceglia, Paulette; Kan, Jenny; Swenson, Steve; Lin, Yvonne G.; Pejovic, Tanja; Millstein, Joshua; Gayther, Simon A

    2014-01-01

    Most solid tumours contain cancer-associated fibroblasts (CAFs) that support tumourigenesis and malignant progression. However the cellular origins of CAFs in epithelial ovarian cancers (EOCs) remain poorly understood, and their utility as a source of clinical biomarkers for cancer diagnosis has not been explored in great depth. Here, we report establishing in vitro and in vivo models of CAFs in ovarian cancer development. Normal ovarian fibroblasts and mesenchymal stem cells cultured in the presence of EOC cells acquired a CAF-like phenotype, and promoted EOC cell migration in vitro. CAFs also promoted ovarian cancer growth in vivo in both subcutaneous and intraperitoneal murine xenograft assays. Molecular profiling of CAFs identified gene expression signatures that were highly enriched for extracellular and secreted proteins. We identified novel candidate CAF specific biomarkers for ovarian cancer including NPPB, which was expressed in the stroma of 60% primary ovarian cancer tissues (n=145) but not in the stroma of normal ovaries (n=4). NPPB is a secreted protein that was also elevated in the blood of 50% of women with ovarian cancer (n=8). Taken together these data suggest that the tumor stroma is a novel source of biomarkers, including NPPB, that may be of clinical utility for detection of EOC. PMID:25047817

  18. A distinct molecular profile associated with mucinous epithelial ovarian cancer

    PubMed Central

    Heinzelmann-Schwarz, V A; Gardiner-Garden, M; Henshall, S M; Scurry, J P; Scolyer, R A; Smith, A N; Bali, A; Bergh, P Vanden; Baron-Hay, S; Scott, C; Fink, D; Hacker, N F; Sutherland, R L; O'Brien, P M

    2006-01-01

    Mucinous epithelial ovarian cancers (MOC) are clinically and morphologically distinct from the other histological subtypes of ovarian cancer. To determine the genetic basis of MOC and to identify potential tumour markers, gene expression profiling of 49 primary ovarian cancers of different histological subtypes was performed using a customised oligonucleotide microarray containing >59 000 probesets. The results show that MOC express a genetic profile that both differs and overlaps with other subtypes of epithelial ovarian cancer. Concordant with its histological phenotype, MOC express genes characteristic of mucinous carcinomas of varying epithelial origin, including intestinal carcinomas. Differences in gene expression between MOC and other histological subtypes of ovarian cancer were confirmed by RT–PCR and/or immunohistochemistry. In particular, galectin 4 (LGALS4) was highly and specifically expressed in MOC, but expressed at lower levels in benign mucinous cysts and borderline (atypical proliferative) tumours, supporting a malignant progression model of MOC. Hence LGALS4 may have application as an early and differential diagnostic marker of MOC. PMID:16508639

  19. [A Case of Concurrent Primary Gastric Malignant T-Cell Lymphoma and Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma].

    PubMed

    Hashimoto, Tadayoshi; Tamura, Shigeyuki; Takeno, Atsushi; Taniguchi, Hirokazu; Ishida, Tomo; Sato, Yasufumi; Morimoto, Yoshihiro; Kusama, Hiroki; Matsushita, Katsunori; Kimura, Kei; Katsura, Yoshiteru; Nitta, Kanae; Ohmura, Yoshiaki; Kagawa, Yoshinori; Okishiro, Masatsugu; Sakisaka, Hideki; Egawa, Chiyomi; Takeda, Yutaka; Kato, Takeshi

    2015-11-01

    A 71-year-old man was admitted to our hospital for epigastric pain. Upper gastrointestinal endoscopy revealed a type 2- like ulcerative lesion in the posterior wall of the upper and middle part of the stomach. Endoscopic biopsies showed malignant T-cell lymphoma histologically. A chest CT scan revealed a nodule in the apex of right lung, suggestive of primary lung cancer. A total gastrectomy with D2 lymphadenectomy and distal pancreatectomy with splenectomy was performed. Seventy-three days after surgery, the patient developed a lung abscess in the middle lobe of the right lung. A wedge-shaped resection of the upper lobe and total resection of the middle lobe of the right lung was performed. Histological examination revealed a primary pulmonary mucosa-associated lymphoid tissue lymphoma in the upper lobe of right lung and an abscess caused by Pseudomonas aeruginosa in the middle lobe of the right lung. Twelve months after surgery the man died of suffocation because of aspiration due to esophageal stenosis caused by progression of metastasis of the paraesophageal lymph node. PMID:26805184

  20. [Primary Pituitary Malignant Lymphoma that was Difficult to Differentiate from Nonfunctioning Pituitary Adenoma:A Case Report].

    PubMed

    Murakami, Yuta; Sato, Taku; Jinguji, Shinya; Kishida, Yugo; Watanabe, Tadashi; Suzuki, Osamu; Ikeda, Kazuhiko; Homma, Miyuki; Midorikawa, Sanae; Saito, Kiyoshi

    2016-09-01

    We report a rare case of primary pituitary lymphoma in a 75-year-old immunocompetent woman. The patient was blind in the right eye and presented with visual disturbance in the left eye that started 2 months previously. She also exhibited right third and fifth cranial nerve palsy. Magnetic resonance imaging(MRI)revealed an intrasellar mass lesion with right cavernous sinus invasion and suprasellar extension with compression of the optic chiasm. The mass lesion was isointense on both T1WI and T2WI, and showed less enhancement than a normal pituitary gland on gadolinium-enhanced T1WI. We therefore suspected the tumor to be a nonfunctioning pituitary adenoma. The patient underwent endoscopic endonasal transsphenoidal surgery. The tumor was firm and grayish, and had an ill-defined border along the normal pituitary gland. Histological examination revealed a malignant CD5-positive diffuse large B-cell lymphoma. After surgery, the patient received both chemotherapy and radiotherapy. Although the visual acuity of the right eye did not improved, other symptoms improved. At the 34-month follow-up, no recurrence was detected on serial MRI. Patients with primary pituitary lymphoma often exhibit ophthalmoplegia and/or panhypopituitarism more frequently than expected from radiological findings. In cases of pituitary tumors with atypical symptoms, a biopsy and general physical examination should be performed immediately to determine the diagnosis and perform adjuvant therapy even when the tumor is assumed as nonfunctioning pituitary adenoma from the image findings. PMID:27605481

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

    ClinicalTrials.gov

    2014-01-15

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

  2. Primary Ovarian Insufficiency (POI)

    MedlinePlus

    ... of hormones, and the ovaries don’t make eggs every month. Hormone treatment is needed to protect ... normal amounts, and the ovaries don’t release eggs or release them just once in a while. ...

  3. Primary Ovarian Insufficiency (POI)

    MedlinePlus

    ... with questions about grants, contracts & research areas Training, Education & Career Development Support for Training at Universities & Other Institutions Extramural training, fellowships & career development opportunities Training at ...

  4. Primary Ovarian Insufficiency

    MedlinePlus

    ... y Cuidadores Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ... Women's Health Hormones and Health Journey Through the Endocrine System Endocrine Disrupting Chemicals (EDCs) Endocrine Glands and Types ...

  5. Primary tumors of the external and middle ear. Benign and malignant glandular neoplasms.

    PubMed

    Dehner, L P; Chen, K T

    1980-01-01

    Glandular neoplasms represented 14% of primary tumors of the external and middle ear at the University of Minnesota. Although the collective term "ceruminoma" has been used in the past, four distinctive histopathologic patterns were recognized among our 12 cases: adenoma (four cases), pleomorphic adenoma (one case), adenoid cystic carcinoma (two cases) and adenocarcinoma (five cases). The prognosis correlated with these subgroups. A thorough review of the English literature also tended to support the rationale for the subclassification of so-called ceruminomas. The prevailing histogenetic view is that these tumors are derived from the modified apocrine glands of the auditory canal, the ceruminous glands. In some instances, these tumors may originate from ectopic salivary gland tissue.

  6. Functional Proteomic Analysis of Advanced Serous Ovarian Cancer using Reverse Phase Protein Array: TGFβ Pathway Signaling Indicates Response to Primary Chemotherapy

    PubMed Central

    Carey, Mark S.; Agarwal, Roshan; Gilks, Blake; Swenerton, Kenneth; Kalloger, Steve; Santos, Jennifer; Ju, Zhenlin; Lu, Yiling; Zhang, Fan; Coombes, Kevin; Miller, Dianne; Huntsman, David; Mills, Gordon B.; Hennessy, Bryan T

    2010-01-01

    Purpose: Using Reverse Phase Protein Array (RPPA) we measured protein expression associated with response to primary chemotherapy in patients with advanced-stage high-grade serous ovarian cancer. Experimental Design: Tumor samples were obtained from forty-five patients with advanced high-grade serous cancers from the Gynecology Tumor Bank at the British Columbia Cancer Agency. Treatment consisted of platinum-based chemotherapy following debulking surgery. Protein lysates were prepared from fresh frozen tumor samples and 80 validated proteins from signaling pathways implicated in ovarian carcinogenesis were measured by RPPA. Normalization of Ca-125 by the 3rd cycle of chemotherapy was chosen as the primary outcome measure of chemotherapy response. Logistic regression was used for multivariate analysis to identify protein predictors of Ca-125 normalization, and Cox regression to test for the association between protein expression and PFS. A significance level of p ≤ 0.05 was used. Results: The mean age at diagnosis was 56.8 years. EGFR, YKL-40 and several TGFβ pathway proteins (c-Jun N-terminal kinase JNK, JNK phosphorylated at residues 183 and 185, PAI-1, Smad3, TAZ) showed significant associations with Ca-125 normalization on univariate testing. On multivariate analysis, EGFR (p < 0.02), JNK (p < 0.01), and Smad3 (p < 0.04) were significantly associated with normalization of Ca-125. Contingency table analysis of pathway-classified proteins revealed that the selection of TGFβ pathway proteins was unlikely due to false discovery (p < 0.007, Bonferroni-adjusted). Conclusion: TGFβ pathway signaling likely plays an important role as a marker or mediator of chemoresistance in advanced serous ovarian cancer. On this basis, future studies to develop and validate a useful predictor of treatment failure are warranted. PMID:20460476

  7. MicroRNA-106a regulates phosphatase and tensin homologue expression and promotes the proliferation and invasion of ovarian cancer cells.

    PubMed

    Chen, Liang; Zhang, Fang; Sheng, Xiu-Gui; Zhang, Shi-Qian; Chen, Yue-Ting; Liu, Bo-Wen

    2016-10-01

    Ovarian cancer is a leading cause of malignant gynecological tumor-related mortality among women. The treatment of ovarian cancer patients continues to be challenging. MicroRNA‑106a (miR‑106a) is widely expressed in diverse human tumors. In the present study, we investigated the biological and pathological roles of miR-106a in ovarian cancers. We found that miR-106a expression was significantly increased in primary ovarian cancer tissues and ovarian cancer cells compared with the level in normal tissues. Ectopic expression of an miR-106a inhibitor attenuated ovarian cancer cell proliferation and invasion. miR-106a promoted the growth and invasion of SKOV3 cells by targeting phosphatase and tensin homolog (PTEN). Furthermore, the present study revealed that IL-6 inhibited miR-106a expression by activating STAT3. Tocilizumab, a humanized anti-human IL-6R antibody, that competitively inhibits IL-6/IL-6R signaling, did not inhibit the proliferation and invasion of SKOV3 cells. In conclusion, our studies revealed that miR-106a was significantly increased in the ovarian cancer tissues and cell lines. Downregulation of the expression of miR-106a inhibited cell growth and metastasis of ovarian cancer cells. Together, the present study suggests that miR‑106a acts as an oncogene in ovarian cancers. PMID:27510094

  8. Synchronous double primary malignancies of the liver and kidney: A case report

    PubMed Central

    SUN, JUN-JUN; YANG, TIAN-BAO; YANG, YAN-HUI; LIU, WEI-FENG; SONG, JUN-XIN

    2016-01-01

    A 42-year-old male patient was admitted to the Department of General Surgery of The First Affiliated Hospital of Henan University of Science and Technology (Luoyang, China) presenting with abdominal discomfort. Enhanced computed tomography of the abdomen revealed a 15.1×7.0-cm, enhanced, double-spherical, exogenous, solid tumor originating from the left lateral hepatic lobe, in addition to a 4.3×4.2-cm mass in the mid portion of the left kidney. Pre-operative imaging analysis resulted in the diagnosis of double cancer, consisting of hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC). The patient subsequently underwent left hemihepatectomy and left nephrectomy. Histological examination confirmed that the tumor originating from the left lateral hepatic lobe was HCC, and the tumor arising from the mid portion of the left kidney was clear cell RCC (ccRCC). The post-operative follow-up was uneventful. To the best of our knowledge, the present case is the first of its kind to describe the resection of synchronous double cancer, consisting of primary HCC and ccRCC. PMID:26998121

  9. Culture of normal and malignant primary human mammary epithelial cells in a physiological manner simulates in vivo growth patterns and allows discrimination of cell type.

    PubMed

    Bergstraesser, L M; Weitzman, S A

    1993-06-01

    We cultured primary human mammary epithelial cells from five reduction mammoplasties and five breast carcinomas and attempted to improve culture conditions and define cell populations grown. Normal cells cultured on Matrigel basement membrane-like substance formed multicellular three-dimensional structures reminiscent of tissue ducts and alveoli, while malignant cells remained as single cells crawling through Matrigel much as malignant cells separate and invade basement membrane in vivo. This re-creation of normal and malignant breast cell morphology may facilitate studies of breast cancer cell biology and determination of malignant cell authenticity in culture. Growth of cells in a reduced oxygen concentration of 12% improved cell proliferation over room air (21%); however, cells could not proliferate in a completely physiological oxygen concentration of 6%, perhaps because of the medium used. We developed an improved medium for malignant cell growth, which lengthened their life span in culture, and a completely defined medium which supported cell proliferation for six passages. Methods to determine the epithelial nature of mammary epithelial cells are illustrated and discussed. The authenticity of malignant cells in culture was suggested by their proliferation without certain growth factors required for normal cell growth or with transforming growth factor-beta, which arrests normal cell proliferation, and by their contact independence.

  10. Prevalence of X-aneuploidies, X-structural abnormalities and 46,XY sex reversal in Turkish women with primary amenorrhea or premature ovarian insufficiency.

    PubMed

    Geckinli, B B; Toksoy, G; Sayar, C; Soylemez, M A; Yesil, G; Aydın, H; Karaman, A; Devranoglu, B

    2014-11-01

    Our objective was to identify the distribution of cytogenetic abnormalities of 175 Turkish women with primary amenorrhea (PA) or premature ovarian insufficiency (POI). A retrospective study was performed using medical records of 94 patients with PA and 81 patients with POI at the Genetics Department, Zeynep Kamil Women's and Children's Research and Training Hospital, Istanbul, Turkey. G-banded metaphase karyotype analysis were prepared and analyzed. Chromosomal abnormalities were present in 44 of 175 cases (25%). 15 were full blown or mosaic numerical X chromosome abnormalities (8.5%), 10 were full blown or mosaic X-chromosome structural anomalies (5.7%), one was X-autosome translocation (0.5%), 3 were autosomal anomalies (1.7%), 12 were XY karyotype (6.8%), one was 45,X/46,XY mosaic and 2 were full blown or mosaic structural anomalies of Y chromosome (1.7%). The prevalence of chromosomal abnormalities was 25% in this large series of Turkish women with primary amenorrhea or premature ovarian insufficiency, most cases involving X-aneuploidy or X-structural abnormalities or 46,XY karyotype. High prevalence of chromosomal abnormalities is associated with POI starting at an early age (average age: 26 years).

  11. Association between P16INK4a Promoter Methylation and Ovarian Cancer: A Meta-Analysis of 12 Published Studies

    PubMed Central

    Niu, Xun; Shi, Hao; Zhong, Yi

    2016-01-01

    Background Ovarian cancer is the primary cause of death in women diagnosed with gynecological malignancies worldwide. Absence of early symptoms prevents prompt diagnosis or successful therapeutic intervention. P16INK4a is a well-known tumor suppressor gene (TSG). Aberrant methylation of TSG promoter is an important epigenetic silencing mechanism leading to ovarian cancer progression. Studies have reported differences in methylation frequencies of the p16INK4a promoter between ovarian cancer and the corresponding control group. However, the association between p16INK4a promoter methylation and ovarian cancer remains unclear and controversial. Therefore, a meta-analysis was conducted to clarify the relationship between p16INK4a promoter methylation and ovarian cancer. Methods PubMed, Web of Science, EMBASE and CNKI were searched to identify eligible studies for the evaluation of the association between p16INK4a promoter methylation and ovarian cancer. Odds ratio (ORs) and 95% confidence intervals (95%CI) were calculated to determine the strength of association between p16INK4a promoter methylation and ovarian cancer. Results A total of 612 ovarian cancer patients and 289 controls from 12 eligible studies were included in the meta-analysis. Overall, a significant association was observed between p16INK4a methylation status and ovarian cancer risk using a fixed-effects model (OR = 2.02, 95% CI = 1.39–2.94). Conclusion The results of our meta-analysis show that aberrant methylation of p16INK4a promoter was significantly associated with ovarian cancer. It may represent a promising molecular marker to monitor the disease and provides new insights into the treatment of human ovarian cancer. PMID:27648827

  12. Bilateral ovarian metastases from ureteric urothelial cancer: Initial case report and distinguishing role of immunohistochemistry

    PubMed Central

    Venkatramani, Vivek; Banerji, John Samuel; Manojkumar, Ramani

    2015-01-01

    Urothelial cancers of the upper tract are aggressive malignancies with a propensity for distant metastases. Transitional cell carcinoma can also develop de novo in the ovaries and differentiation between these lesions requires immunohistochemistry. We report a case of right lower ureteric urothelial carcinoma with metastases to both ovaries. To our knowledge, this is the first reported case of bilateral ovarian metastases from an upper tract primary, diagnosed with immunohistochemistry. PMID:25624971

  13. Primary Non-Hodgkin's Lymphoma of the Ovary - A Case Report.

    PubMed

    Bhartiya, Richa; Kumari, Nawanita; Mallik, Mahasweta; Singh, Ran Vijoy Narayan

    2016-05-01

    The ovarian lymphoma is rare. Lymphoma presenting as an ovarian mass with initial manifestation is even rarer. We report a case of primary Non-Hodgkin's Lymphoma (NHL) of left ovary in a 52-year-old female presented with distension of abdomen and lower abdominal back pain. USG and CT-scan imaging suggested provisional diagnosis of ovarian tumour. The diagnosis of malignant lymphoma was made by histopathological examination of the excised tissue along with immunohistochemistry by using LCA, CD20, cytokeratin & CD3. The tumour was classified as diffuse large B cell lymphoma. Rarity of this lesion warrants its mention. PMID:27437236

  14. Autophagy mediated by arginine depletion activation of the nutrient sensor GCN2 contributes to interferon-γ-induced malignant transformation of primary bovine mammary epithelial cells.

    PubMed

    Xia, X-J; Gao, Y-Y; Zhang, J; Wang, L; Zhao, S; Che, Y-Y; Ao, C-J; Yang, H-J; Wang, J-Q; Lei, L-C

    2016-01-01

    Autophagy has been linked to the regulation of both the prevention and progression of cancer. IFN-γ has been shown to induce autophagy in multiple cell lines in vitro. However, whether IFN-γ can induce autophagy and whether autophagy promotes malignant transformation in healthy lactating bovine mammary epithelial cells (BMECs) remain unclear. Here, we provide the first evidence of the correlation between IFN-γ treatment, autophagy and malignant transformation and of the mechanism underlying IFN-γ-induced autophagy and subsequent malignant transformation in primary BMECs. IFN-γ levels were significantly increased in cattle that received normal long-term dietary corn straw (CS) roughage supplementation. In addition, an increase in autophagy was clearly observed in the BMECs from the mammary tissue of cows expressing high levels of IFN-γ. In vitro, autophagy was clearly induced in primary BMECs by IFN-γ within 24 h. This induced autophagy could subsequently promote dramatic primary BMEC transformation. Furthermore, we found that IFN-γ promoted arginine depletion, activated the general control nonderepressible-2 kinase (GCN2) signalling pathway and resulted in an increase in autophagic flux and the amount of autophagy in BMECs. Overall, our findings are the first to demonstrate that arginine depletion and kinase GCN2 expression mediate IFN-γ-induced autophagy that may promote malignant progression and that immunometabolism, autophagy and cancer are strongly correlated. These results suggest new directions and paths for preventing and treating breast cancer in relation to diet. PMID:27551491

  15. Autophagy mediated by arginine depletion activation of the nutrient sensor GCN2 contributes to interferon-γ-induced malignant transformation of primary bovine mammary epithelial cells

    PubMed Central

    Xia, X-j; Gao, Y-y; Zhang, J; Wang, L; Zhao, S; Che, Y-y; Ao, C-j; Yang, H-j; Wang, J-q; Lei, L-c

    2016-01-01

    Autophagy has been linked to the regulation of both the prevention and progression of cancer. IFN-γ has been shown to induce autophagy in multiple cell lines in vitro. However, whether IFN-γ can induce autophagy and whether autophagy promotes malignant transformation in healthy lactating bovine mammary epithelial cells (BMECs) remain unclear. Here, we provide the first evidence of the correlation between IFN-γ treatment, autophagy and malignant transformation and of the mechanism underlying IFN-γ-induced autophagy and subsequent malignant transformation in primary BMECs. IFN-γ levels were significantly increased in cattle that received normal long-term dietary corn straw (CS) roughage supplementation. In addition, an increase in autophagy was clearly observed in the BMECs from the mammary tissue of cows expressing high levels of IFN-γ. In vitro, autophagy was clearly induced in primary BMECs by IFN-γ within 24 h. This induced autophagy could subsequently promote dramatic primary BMEC transformation. Furthermore, we found that IFN-γ promoted arginine depletion, activated the general control nonderepressible-2 kinase (GCN2) signalling pathway and resulted in an increase in autophagic flux and the amount of autophagy in BMECs. Overall, our findings are the first to demonstrate that arginine depletion and kinase GCN2 expression mediate IFN-γ-induced autophagy that may promote malignant progression and that immunometabolism, autophagy and cancer are strongly correlated. These results suggest new directions and paths for preventing and treating breast cancer in relation to diet. PMID:27551491

  16. Somatostatin receptors in differentiated ovarian tumors.

    PubMed Central

    Reubi, J. C.; Horisberger, U.; Klijn, J. G.; Foekens, J. A.

    1991-01-01

    The presence of somatostatin receptors was investigated in 57 primary human ovarian tumors using in vitro receptor autoradiography with three different somatostatin radioligands, 125I-[Tyr11]-somatostatin-14, 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28, or 125I-[Tyr3]-SMS 201-995. Three cases, all belonging to epithelial tumors, were receptor positive; specifically 1 of 42 adenocarcinomas, 1 of 3 borderline malignancies, and 1 of 2 cystadenomas. Four other epithelial tumors (3 fibroadenomas, 1 Brenner tumor), 4 sex cord-stromal tumors (2 fibrothecomas, 2 granulosa cell tumors), and 2 germ cell tumors (1 dysgerminoma, 1 teratoma) were receptor negative. In the positive cases, the somatostatin receptors were localized on epithelial cells exclusively, were of high affinity (KD = 4.6 nmol/l [nanomolar]), and specific for somatostatin analogs. These receptors bound somatostatin-14 and somatostatin-28 radioligands with a higher affinity than the octapeptide [Tyr3]-SMS 201-995. Healthy ovarian tissue had no somatostatin receptors. A subpopulation of relatively well-differentiated ovarian tumors, therefore, was identified pathobiochemically on the basis of its somatostatin receptor content. This small group of somatostatin receptor-positive tumors may be a target for in vivo diagnostic imaging with somatostatin ligands. Images Figure 1 Figure 2 Figure 3 PMID:1850962

  17. Somatostatin receptors in differentiated ovarian tumors

    SciTech Connect

    Reubi, J.C.; Horisberger, U.; Klijn, J.G.; Foekens, J.A. )

    1991-05-01

    The presence of somatostatin receptors was investigated in 57 primary human ovarian tumors using in vitro receptor autoradiography with three different somatostatin radioligands, {sup 125}I-(Tyr11)-somatostatin-14, {sup 125}I-(Leu8, D-Trp22, Tyr25)-somatostatin-28, or {sup 125}I-(Tyr3)-SMS 201-995. Three cases, all belonging to epithelial tumors, were receptor positive; specifically 1 of 42 adenocarcinomas, 1 of 3 borderline malignancies, and 1 of 2 cystadenomas. Four other epithelial tumors (3 fibroadenomas, 1 Brenner tumor), 4 sex cord-stromal tumors (2 fibrothecomas, 2 granulosa cell tumors), and 2 germ cell tumors (1 dysgerminoma, 1 teratoma) were receptor negative. In the positive cases, the somatostatin receptors were localized on epithelial cells exclusively, were of high affinity (KD = 4.6 nmol/l (nanomolar)), and specific for somatostatin analogs. These receptors bound somatostatin-14 and somatostatin-28 radioligands with a higher affinity than the octapeptide (Tyr3)-SMS 201-995. Healthy ovarian tissue had no somatostatin receptors. A subpopulation of relatively well-differentiated ovarian tumors, therefore, was identified pathobiochemically on the basis of its somatostatin receptor content. This small group of somatostatin receptor-positive tumors may be a target for in vivo diagnostic imaging with somatostatin ligands.

  18. Ovarian cysts

    MedlinePlus

    ... Functional ovarian cysts are not the same as ovarian tumors, or cysts due to hormone-related conditions such ... Philadelphia, PA: Elsevier; 2016:chap 17. Katz VL. Benign gynecologic lesions. In: Lentz GM, Lobo RA, Gershenson ...

  19. Risk of second primary malignancies in a population-based study of adult patients with essential thrombocythemia

    PubMed Central

    Shrestha, Rajesh; Giri, Smith; Pathak, Ranjan; Bhatt, Vijaya Raj

    2016-01-01

    AIM To determine the risk of second primary malignancy (SPM) and survival of patients with essential thrombocythemia (ET). METHODS We identified all patients with ET diagnosed during 2001 to 2011 from the Surveillance, Epidemiology and End Results (SEER) 18 database. Actuarial and relative survival methods were used to calculate the survival statistics. We utilized the SEER 13 database to calculate SPM. We used multiple primary standardized incidence ratio (SIR) session of the SEER*Stat software (version 8.1.5) to calculate SIR and excess risk of SPM for ET patients. RESULTS Age standardized five-year cause-specific survival was greater for patients < 50 years vs those ≥ 50 years (99.4% vs 93.5%, P < 0.01). Five-year cause-specific survival was lower for men vs women (70.2% vs 79.7%). A total of 201 patients (2.46%) developed SPM at a median age of 75 years. SPMs occurred at an observed/expected (O/E) ratio of 1.26 (95%CI: 1.09-1.45, P = 0.002) with an absolute excess risk (AER) of 37.44 per 10000 population. A significantly higher risk was noted for leukemia (O/E 3.78; 95%CI: 2.20-6.05, P < 0.001; AER 11.28/10000). CONCLUSION ET patients have an excellent cause-specific five-year survival but are at an increased risk of SPM, particularly leukemia, which may contribute to excess deaths. PMID:27579252

  20. Ovarian Cyst

    MedlinePlus

    ... accurate way to tell if a woman has ovarian cancer. For example, some women who do have ovarian cancer have a normal CA-125 level. Also, this ... for women who show signs or symptoms of ovarian cancer or who have genetic mutations that increase the ...

  1. Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and Sensitizes Cells to Paclitaxel.

    PubMed

    Liu, Xianzhe; Gao, Yan; Shen, Jacson; Yang, Wen; Choy, Edwin; Mankin, Henry; Hornicek, Francis J; Duan, Zhenfeng

    2016-07-01

    Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary tumors. RNAi-mediated CDK11 silencing by synthetic siRNA or lentiviral shRNA decreased cell proliferation and induced apoptosis in ovarian cancer cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of paclitaxel to inhibit cell growth in ovarian cancer cells. Systemic in vivo administration of CDK11 siRNA reduced the tumor growth in an ovarian cancer xenograft model. Our findings suggest that CDK11 may be a promising therapeutic target for the treatment of ovarian cancer patients. Mol Cancer Ther; 15(7); 1691-701. ©2016 AACR. PMID:27207777

  2. Primary mixed malignant tumor of bone in an 18-year-old male: Report of a case with radiologic-pathologic correlation

    PubMed Central

    Courtier, Jesse; Robbins, Elizabeth; Soares, Bruno; Horvai, Andrew; Mackenzie, John D.

    2012-01-01

    We report a case of primary malignant mixed tumor (MMT) of bone in an 18-year-old boy with X-ray, CT, MR, scintigraphic, FDG PET, and pathologic correlation. Primary MMT of bone is a highly aggressive tumor and presents both a diagnostic and clinical treatment challenge. This tumor is extremely rare and to the best of our knowledge, this is the first report of the diagnostic imaging findings for primary MMT arising from bone in a patient of this age group. PMID:26909264

  3. Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Survey of Women's Health Study Group.

    PubMed

    Green, A; Purdie, D; Bain, C; Siskind, V; Russell, P; Quinn, M; Ward, B

    1997-06-11

    We have examined the effect of tubal sterilisation and hysterectomy on risk of ovarian cancer in a large case-control study in eastern Australia involving 824 women aged 18-79 years, diagnosed with epithelial ovarian cancer between 1990 and 1993, and 855 controls randomly selected from the electoral roll. Relative risks for ovarian cancer were estimated using multiple categorical regression to adjust for age, parity, oral contraceptive use and other risk factors. Tubal sterilisation was associated with a 39% reduction in risk of ovarian cancer (RR 0.61, 95% CI 0.46-0.85) and hysterectomy with a 36% reduction (RR 0.64, 95% CI 0.48-0.85). Risk remained low 25 years after surgery and was reduced irrespective of sterilisation technique, and estimates were similar among various types of epithelial ovarian cancer. The greatest reduction (74%) was observed among women with primary peritoneal tumours. Pelvic infection and use of vaginal sprays or contraceptive foams were not related to ovarian cancer, while use of talc in the perineal region slightly but significantly increased risk among women with patent fallopian tubes. Reportedly heavy or painful menses, perhaps associated with retrograde flow, were associated with ovarian cancer, and reduction in risk of disease after hysterectomy was greatest among women who had heavy periods. Our findings support the theory that contaminants from the vagina, such as talc, and from the uterus, such as endometrium, gain access to the peritoneal cavity through patent fallopian tubes and may enhance the malignant transformation of ovarian surface epithelium. Surgical tubal occlusion may reduce the risk of ovarian cancer by preventing the access of such agents.

  4. Primary retroperitoneal mucinous cystadenocarcinoma.

    PubMed

    Nelson, H; Benjamin, B; Alberty, R

    1988-05-15

    A case of primary retroperitoneal cystadenocarcinoma is presented as the fourth reported case in the world literature to date. The cyst was removed intact and demonstrated an infiltrating malignant process with nuclear pleomorphism and mitotic activity. No ovarian tissue was identified and a cancer antigen 125 (CA 125) test was normal. The patient underwent a staging procedure subsequently that included peritoneal washings, hysterectomy, bilateral salpingoophorectomy, and iliac node dissection. No metastases were found and the patient is without recurrence 22 months postoperative. The literature is reviewed to better define the origin and prognosis of these tumors.

  5. The epidemiology of ovarian cancer.

    PubMed

    Tortolero-Luna, G; Mitchell, M F

    1995-01-01

    Ovarian cancer is the second most common cancer of the female reproductive system and the leading cause of death from gynecologic malignancies. In 1995, 26,600 women will be diagnosed with ovarian cancer in the U.S., and 14,500 women will die from the disease. Between 1986-1900, the overall age-adjusted incidence was 14.3/100,000 women; mortality was 7.8/100,000 women. Ovarian cancer, rare before age 40, increases steeply thereafter and peaks at ages 65-75. Incidence and mortality rates are higher among white women than among African-American women. Over the last three decades, ovarian cancer incidence has remained stable in high-risk countries, while an increasing trend has been reported in low-risk countries. Despite recent advancements in treatment, the overall five-year survival rates continues to be low (39%). Over 70% of ovarian tumors are diagnosed when regional or distant involvement has already occurred, causing survival rates to remain stable. The etiology of ovarian cancer is poorly understood. Most studies have focused on the epidemiology of invasive epithelial ovarian tumors, while few have explored the epidemiology of epithelial tumors of low malignant potential and nonepithelial tumors. Factors associated with an increased risk for invasive epithelial ovarian cancer include age, race, nulliparity, family history of ovarian cancer, and history of endometrial or breast cancer. Factors associated with a reduced risk are history of one or more full-term pregnancies, use of oral contraceptives, history of breast feeding, tubal ligation, and hysterectomy. Other factors such as infertility drugs, hormone replacement therapy, age at menarche, age at menopause, dietary factors, lactose intolerance, talc use, coffee and alcohol consumption have been suggested, but their role is still inconclusive.

  6. Malignant characteristics of circulating tumor cells and corresponding primary tumor in a patient with esophageal squamous cell carcinoma before and after surgery.

    PubMed

    Ren, Chuanli; He, Ping; Zhang, Jinqiang; Zheng, Zhaoxu; Qiao, Yuanyuan; Zhao, Xiaohang

    2011-04-01

    We report the malignant characteristics of circulating tumor cells (CTCs) and the corresponding molecular features of the primary tumor in a patient with esophageal squamous cell carcinoma (ESCC). A 70-year-old male patient was diagnosed with TNM stage T3N0M0 ESCC. Before surgery, seven intact CTCs and 12 CTCs with a fragmented membrane were detected in 7.5 mL of peripheral blood by immunofluorescence staining. One week after radical resection of the primary tumor, four CTCs were identified in 7.5ml peripheral blood. All CTCs were confirmed as having a malignant phenotype by chromosomal analysis and routine cell staining. Ninety percent of the CTCs were found to have polysomic chromosomes 8 and 20 by fluorescence in situ hybridization (FISH). Immunofluorescence analysis showed that all of the primary tumor cells detected were cytokeratin8/18/19 (CK8/18/19)-positive, but only 1% were CD133-positive. The serum CA19-9 and CEA level were normal in the process of diseases. The patient died 6 months after surgery as a result of lung metastases and other complications. The results of this study suggest that the dynamics and malignant characteristics of both CTCs and the corresponding primary tumor during the disease process may predict tumor burden and the risk of relapse and metastasis.

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

    ClinicalTrials.gov

    2016-11-02

    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. Bone Mineral Density in Young Women With Primary Ovarian Insufficiency: Results of a Three-Year Randomized Controlled Trial of Physiological Transdermal Estradiol and Testosterone Replacement

    PubMed Central

    Calis, Karim A.; Kalantaridou, Sophia N.; Vanderhoof, Vien H.; Koziol, Deloris; Troendle, James F.; Reynolds, James C.; Nelson, Lawrence M.

    2014-01-01

    Context: Women with primary ovarian insufficiency have significantly lower serum estradiol and T levels compared with regularly menstruating women. They also have significantly reduced bone mineral density (BMD). Objective: The objective of the study was to evaluate the efficacy of hormone replacement in maintaining BMD in these young women. Design and Setting: This was a randomized, double-blind, single-center, placebo-controlled clinical trial at the National Institutes of Health clinical center (Bethesda, Maryland). Participants: Young women with primary ovarian insufficiency participated in the study. Interventions: We compared the effect of estradiol and progestin replacement (n = 72) vs estradiol, progestin, and T replacement (n = 73) on BMD. We also compared findings with a contemporaneous control group of normal women (n = 70). All patients received transdermal estradiol (100 μg/d) plus oral medroxyprogesterone acetate 10 mg/d (12 d/mo) for a 3-month run-in period before being randomized in a double-blinded fashion to the addition of transdermal T (150 μg/d) or placebo. Main Outcome Measure: Change in BMD at the femoral neck was measured by dual-energy x-ray absorptiometry. Results: At screening, patients had significantly lower femoral neck BMD compared with control women (0.77 vs 0.81 g/cm2, P = .001) and did not differ in body mass index, age at menarche, or education level. Normal control women lost femoral neck BMD over the study period, whereas patients on estradiol and progestin therapy gained BMD; and at the end of the study period, femoral neck BMD of patients on estradiol and progestin therapy did not differ from that of control women (0.80 g/cm2 in both groups, P = .9). The addition of T showed no further benefit (percentage change in BMD 3.9 vs 2.4, respectively, P = .9). Nonetheless, using a repeated-measures model, the T group achieved a mean BMD in the femoral neck 0.015 g/cm2 higher than the placebo group at 3 years (95% confidence

  9. Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer

    ClinicalTrials.gov

    2016-10-27

    Estrogen Receptor Negative; HER2/Neu Negative; Ovarian Endometrioid Adenocarcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Progesterone Receptor Negative; Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Triple-Negative Breast Carcinoma

  10. Local control and distant metastases in primary canine malignant melanomas treated with hyperthermia and/or radiotherapy.

    PubMed

    Dewhirst, M W; Sim, D A; Forsyth, K; Grochowski, K J; Wilson, S; Bicknell, E

    1985-01-01

    Forty-three dogs with primary malignant melanoma were randomized to receive radiotherapy alone (XRT) or hyperthermia plus radiotherapy (delta + XRT). Tumour responses were analysed in terms of complete response rates, rate of one year disease free survival and the incidence and time to develop distant metastasis. The frequency of complete responses (CR) was greater with adjuvant heat (76 per cent vs 21 per cent for XRT; P = 0.001). A trend towards an improvement in one year disease free survival was observed with delta + XRT (23.8 per cent) as compared with XRT (7.7 per cent), but the difference was not statistically significant. The frequency of distant metastases was not different between the two treatments. Descriptors of intratumoural temperatures achieved during therapy indicated that higher CR rates could be achieved with higher minima. When minima were less than and greater than 20 Equivalent minutes at 43 degrees C (Eq43) the CR rates were 64 and 90 per cent, respectively. One year disease free survival rates and frequencies of distant metastases seemed to be correlated with the intratumoural temperatures as well. This was reflected in analyses examining temperature minima and maxima. Examination of patterns of failure suggested that the most plausible explanation for the correlation between intratumoural temperature and metastases was the high local failure rate (70 per in the heated group). The results of this study emphasize the need for further investigation of the influence of local hyperthermia as a part of curative therapy on the frequency of distant metastases. PMID:3836269

  11. OVARIAN CANCER: INVOLVEMENT OF THE MATRIX METALLOPROTEINASES

    PubMed Central

    Al-Alem, Linah; Curry, Thomas E.

    2016-01-01

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

  12. A Case of Giant Uterine Lipoleiomyoma Simulating Malignancy

    PubMed Central

    Karaman, Erbil; Çim, Numan; Bulut, Gülay; Elçi, Gülhan; Andıç, Esra; Tekin, Mustafa; Kolusarı, Ali

    2015-01-01

    Introduction. Uterine leiomyoma is the most common benign pathology in women and lipoleiomyoma is an extremely rare and specific type of leiomyoma. Here, we report an unusual case of giant pedunculated subserous lipoleiomyoma misdiagnosed preoperatively as leiomyosarcoma. Case. A 45-year-old woman admitted to our gynecology outpatient clinic for complaints of abdominal distention, tiredness, and pelvic pain for the last 6 months. Sonography and abdominal magnetic resonance imaging (MRI) showed a giant semisolid mass that filled whole abdominal cavity from pelvis to subdiaphragmatic area. A primary diagnosis of uterine sarcoma or ovarian malignancy was made. On operation, total abdominal hysterectomy with a pedunculated mass of size 30 × 23 × 12 cm and weighing 5.4 kg and bilateral salpingo-oophorectomy were performed. The histopathology revealed a lipoleiomyoma with extensive cystic and fatty degeneration without any malignancy. Discussion. The diagnosis of leiomyoma is done usually with pelvic ultrasound but sometimes it is difficult to reach a correct diagnosis especially in cases of giant and pedunculated lipoleiomyoma that included fatty tissue which may mimick malignancy. Conclusion. Subserous pedunculated giant lipoleiomyoma should be kept in mind in the differential diagnosis of leiomyosarcoma or ovarian malignancy. PMID:26266066

  13. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas.

    PubMed

    Kurose, K; Zhou, X P; Araki, T; Cannistra, S A; Maher, E R; Eng, C

    2001-06-01

    PTEN (MMAC1/TEP1), a tumor suppressor gene on chromosome subband 10q23.3, is variably mutated and/or deleted in a variety of human cancers. Germline mutations in PTEN, which encode a dual-specificity phosphatase, have been implicated in at least two hamartoma tumor syndromes that exhibit some clinical overlap, Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. Among several series of ovarian cancers, the frequency of loss of heterozygosity (LOH) of markers flanking and within PTEN, is approximately 30 to 50%, and the somatic intragenic PTEN mutation frequency is <10%. In this study, we screened primary adenocarcinomas of the ovary for LOH of polymorphic markers within and flanking the PTEN gene and for intragenic mutations of the PTEN gene and compared them to PTEN expression using immunohistochemistry. Furthermore, we sought to detect the expression of the presumed downstream targets of PTEN, such as P-Akt, p27, and cyclin D1 by immunohistochemistry. LOH at 10q23 was observed in 29 of 64 (45%) cases. Of the 117 samples, 6 somatic intragenic PTEN mutations, 1 germline mutation, and 1 novel polymorphism were found in 7 (6%) patients. Immunostaining of 49 ovarian cancer samples revealed that 13 (27%) were PTEN immunostain-negative, 25 (51%) had reduced staining, and the rest (22%) were PTEN expression-positive. Among the 44 informative tumors assessed for 10q23 LOH and PTEN immunostaining, there was an association between 10q23 LOH and decreased or absent staining (P = 0.0317). Of note, there were five (11%) tumors with neither mutation nor deletion that exhibited no PTEN expression and 10 (25%) others without mutation or deletion but had decreased PTEN expression. Among the 49 tumors available for immunohistochemistry, 28 (57%) showed P-Akt-positive staining, 24 (49%) had decreased p27 staining, and cyclin D1 was overexpressed in 35 (79%) cases. In general, P-Akt expression was inversely correlated with PTEN expression (P = 0.0083). These data suggest that

  14. The value of intratumoral heterogeneity of 18F-FDG uptake to differentiate between primary benign and malignant musculoskeletal tumours on PET/CT

    PubMed Central

    Nakajo, Masayuki; Jinguji, Megumi; Fukukura, Yoshihiko; Nakabeppu, Yoshiaki; Tani, Atsushi; Yoshiura, Takashi

    2015-01-01

    Objective: The cumulative standardized uptake value (SUV)–volume histogram (CSH) was reported to be a novel way to characterize heterogeneity in intratumoral tracer uptake. This study investigated the value of fluorine-18 fludeoxyglucose (18F-FDG) intratumoral heterogeneity in comparison with SUV to discriminate between primary benign and malignant musculoskeletal (MS) tumours. Methods: The subjects comprised 85 pathologically proven MS tumours. The area under the curve of CSH (AUC-CSH) was used as a heterogeneity index, with lower values corresponding with increased heterogeneity. As 22 tumours were indiscernible on 18F-FDG positron emission tomography, maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean) and AUC-CSH were obtained in 63 positive tumours. The Mann–Whitney U test and receiver operating characteristic (ROC) analysis were used for analyses. Results: The difference between benign (n = 35) and malignant tumours (n = 28) was significant in AUC-CSH (p = 0.004), but not in SUVmax (p = 0.168) and SUVmean (p = 0.879). The sensitivity, specificity and accuracy for diagnosing malignancy were 61%, 66% and 64% for SUVmax (optical threshold value, >6.9), 54%, 60% and 57% for SUVmean (optical threshold value, >3) and 61%, 86% and 75% for AUC-CSH (optical threshold value, ≤0.42), respectively. The area under the ROC curve was significantly higher in AUC-CSH (0.71) than SUVmax (0.60) (p = 0.018) and SUVmean (0.51) (p = 0.005). Conclusion: The heterogeneity index, AUC-CSH, has a higher diagnostic accuracy than SUV analysis in differentiating between primary benign and malignant MS tumours, although it is not sufficiently high enough to obviate histological analysis. Advances in knowledge: AUC-CSH can assess the heterogeneity of 18F-FDG uptake in primary benign and malignant MS tumours, with significantly greater heterogeneity associated with malignant MS tumours. AUC-CSH is more diagnostically accurate

  15. Supplemented αMEM/F12-based medium enables the survival and growth of primary ovarian follicles encapsulated in alginate hydrogels

    PubMed Central

    Tagler, David; Makanji, Yogeshwar; Anderson, Nicholas R.; Woodruff, Teresa K.; Shea, Lonnie D.

    2013-01-01

    Hydrogel-encapsulating culture systems for ovarian follicles support the in vitro growth of secondary follicles from various species including mouse, non-primate human, and human; however, the growth of early stage follicles (primary and primordial) has been limited. While encapsulation maintains the structure of early stage follicles, feeder cell populations, such as mouse embryonic fibroblasts (MEFs), are required to stimulate growth and development. Hence, in this report, we investigated feeder-free culture environments for early stage follicle development. Mouse ovarian follicles were encapsulated within alginate hydrogels and cultured in various growth medium formulations. Initial studies employed embryonic stem cell medium formulations as a tool to identify factors that influence the survival, growth, and meiotic competence of early stage follicles. The medium formulation that maximized survival and growth was identified as αMEM/F12 supplemented with fetuin, insulin, transferrin, selenium, and follicle stimulating hormone (FSH). This medium stimulated the growth of late primary (average initial diameter of 80 µm) and early secondary (average initial diameter of 90 µm) follicles, which developed antral cavities and increased to terminal diameters exceeding 300 µm in 14 days. Survival ranged from 18% for 80 µm follicles to 36% for 90 µm follicles. Furthermore, 80% of the oocytes from surviving follicles with an initial diameter of 90–100 µm underwent germinal vesicle breakdown (GVBD), and the percentage of metaphase II (MII) eggs was 50%. Follicle/oocyte growth and GVBD/MII rates were not significantly different from MEF co-culture. Survival was reduced relative to MEF co-culture, yet substantially increased relative to the control medium that had been previously used for secondary follicles. Continued development of culture medium could enable mechanistic studies of early stage folliculogenesis and emerging strategies for fertility preservation. PMID

  16. Ezrin Is Associated with Disease Progression in Ovarian Carcinoma

    PubMed Central

    Horwitz, Vered; Davidson, Ben; Stern, Dganit; Tropé, Claes G.; Tavor Re’em, Tali; Reich, Reuven

    2016-01-01

    Objective Ezrin and p130Cas are structural proteins with an important role in signaling pathways and have been shown to promote cancer dissemination. We previously reported on overexpression of both ezrin and p130Cas in breast carcinoma effusions compared to primary carcinomas. Since ovarian and breast carcinomas share the ability to disseminate by forming malignant effusions, we sought to study the role of these molecules in ovarian carcinoma (OC). Methods OC cell lines were cultured in two different 3-dimensional conditions, on alginate scaffolds and as spheroids, which served as models for solid tumor and malignant effusions, respectively. shRNA was used to reduce protein expression in the cells. The malignant potential was evaluated by chemo-invasion assay, branching capacity on Matrigel and rate of proliferation. Subsequently, clinical specimens of high-grade serous carcinoma effusions, ovarian tumors and solid metastases were analyzed for ezrin and p130Cas expression. Results Higher ezrin expression was found in cells composing the spheroids compared to their counterparts cultured on alginate scaffold and in clinical samples of malignant effusions compared to solid tumors. In addition, reduced Ezrin expression impaired the invasion ability and the branching capacity of OC cells to a greater extent than reduced p130Cas expression. However, ezrin and p130Cas expression in effusions was unrelated to clinical outcome. Conclusions The 3-dimensional cell cultures were found to mimic the different tumor sites and be applicable as a model. The in vitro results concur with the clinical specimen analysis, suggesting that in OC, the role of ezrin in disease progression is more pronounced than that of p130Cas. PMID:27622508

  17. Small Cell Carcinoma of the Ovary (Hypercalcemic Type): Malignant Rhabdoid Tumor

    PubMed Central

    Kascak, Peter; Zamecnik, Michal; Bystricky, Branislav

    2016-01-01

    We present a rare case of malignant rhabdoid tumor (ovarian small cell carcinoma of hypercalcemic type) in a 24-year-old female with fulminant course. Clinically, hypercalcemia was not found at the time of primary diagnosis. However, it appeared later during the course of tumor progression. Histologically, the tumor showed classical features of small cell carcinoma of hypercalcemic type. Therapy included radical surgery with adjuvant chemotherapy. Despite this intensive therapy, the disease recurred and the patient died 10 months after the diagnosis. We discuss the diagnosis and therapy of this tumor, as well as its recent classification as malignant rhabdoid tumor. PMID:27462229

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

    ClinicalTrials.gov

    2016-03-16

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

  19. Benign epithelial ovarian tumours-cancer precursors or markers for ovarian cancer risk?

    PubMed

    Jordan, Susan; Green, Adèle; Webb, Penelope

    2006-06-01

    The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.

  20. Proliferative and antiproliferative effects of interferon-gamma and tumor necrosis factor-alpha on cell lines derived from cervical and ovarian malignancies

    SciTech Connect

    Mutch, D.G.; Massad, L.S.; Kao, M.S.; Collins, J.L. )

    1990-12-01

    Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed.

  1. The milk-derived hexapeptide PGPIPN inhibits the invasion and migration of human ovarian cancer cells by regulating the expression of MTA1 and NM23H1 genes.

    PubMed

    Zhao, Mengjing; Wei, Cai; Yang, Xue; Zhou, Juan; Wang, Jing; Gu, Fang; Lei, Ting; Qin, Yide

    2016-04-01

    Some bioactive peptides derived from natural resources or synthesized by rational design have been proved to have very good anticancer effect. We studied the inhibition of PGPIPN, a hexapeptide derived from bovine β-casein, on the invasion and metastasis of human ovarian cancer cells in vitro and its molecular mechanism. The human ovarian cancer cells studied include the cell line SKOV3 as well as the primary ovarian cancer cells from ovarian tumor tissues of 37 patients at initial debulking surgery, diagnosed as serous ovarian adenocarcinoma. We showed that PGPIPN inhibited the invasion of ovarian cancer cells with Transwell chamber assay, the migration of ovarian cancer cells with cell scratch assay and colony formation of ovarian cancer cells. The expression (mRNAs and proteins) of genes relevant to invasion and metastasis, MTA1, and NM23H1 were analyzed by real-time PCR and western blotting. PGPIPN repressed the expression of MTA1, and promoted NM23H1. The effects of PGPIPN were dose-dependent. Thus, our study suggests that PGPIPN is a potential therapeutic agent for adjuvant therapy of human malignant ovarian tumors.

  2. Early Detection Biomarkers for Ovarian Cancer

    PubMed Central

    Sarojini, Sreeja; Tamir, Ayala; Lim, Heejin; Li, Shihong; Zhang, Shifang; Goy, Andre; Pecora, Andrew; Suh, K. Stephen

    2012-01-01

    Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs. PMID:23319948

  3. Synchronous bilateral primary breast malignant phyllodes tumor and carcinoma of the breast with Paget’s disease: a case report and review of the literature

    PubMed Central

    Zhao, Hongyuan; Cheng, Xiaoming; Sun, Suhong; Yang, Weiming; Kong, Fanli; Zeng, Feng

    2015-01-01

    Synchronous bilateral primary breast malignant phyllodes tumor or/and carcinoma of the breast with Paget’s disease is rare. In the article, we present a case of bilateral carcinoma of the breast with Paget’s disease of the right breast and malignant phyllodes tumor of the left breast. A 44-years-old Chinese woman presented with a 1 month history of the right breast nipple with eczema and fester and growing and palpable mass of left breast. Molybdenum target X-ray revealed microcalcification in the right breast, which was highly suspected of malignant tumor, and round-like mass with smooth surface and homogeneous density in the left breast. Color ultrasound showed a lobulated lump which circumferential blood flows around in the left breast, and which did not show any mass in the right breast. The patient was undertaken the bilateral modified radical mastectomy. The histological diagnosis was Paget’s disease associated with infiltrating ductal carcinoma in the right breast and malignant phyllodes tumor the left breast. The patient also received 6 cycles of the postoperative adjuvant chemotherapy by using T.T. regimen comprised docetaxel (100 mg) and pirarubicin (60 mg). PMID:26770378

  4. A Population-Based Study of Subsequent Primary Malignancies After Endometrial Cancer: Genetic, Environmental, and Treatment-Related Associations

    SciTech Connect

    Brown, Aaron P.; Neeley, E. Shannon; Werner, Theresa

    2010-09-01

    Purpose: To examine the risk of subsequent primary malignancies (SPMs) in women diagnosed with endometrial cancer. Methods and Materials: The National Cancer Institute's Survival, Epidemiology, and End Results database was used to determine the risk of SPM after endometrial cancer in 69,739 women diagnosed between 1973 and 2005. Standardized incidence ratios were calculated (observed/expected [O/E]) for SPM sites. Results: Median follow-up was 11.2 years, representing 757,567 person-years of follow-up. The risk of SPM was significantly increased for small intestine (O/E = 1.48; 99% confidence interval [CI], 1.03-2.05), colon (O/E = 1.16; CI, 1.09-1.24), vagina (O/E = 2.71; CI, 1.86-3.8), and urinary bladder (O/E = 1.41; CI, 1.25-1.59) SPMs and decreased for oral cavity and pharynx (O/E = 0.75; CI, 0.6-0.93), lung and bronchus (O/E = 0.78; CI, 0.72-0.84), and esophagus (O/E = 0.58; CI, 0.37-0.86) SPMs. Patients receiving external-beam radiotherapy for endometrial cancer had an increased risk of colon (p < 0.001), bladder (p < 0.001), vagina (p = 0.04), and soft-tissue (p = 0.014) SPMs. Patients treated with brachytherapy had an increased risk of bladder SPM (p = 0.006). A positive bidirectional association with endometrial cancer was observed for colorectal cancer, with a negative bidirectional association for oropharyngeal and lung cancers. Conclusions: Genetic, environmental, and treatment-related factors influence SPM risk. Genetic factors may contribute to the increased risk of colorectal cancer. Smoking's negative effect on endometrial cancer risk factors might explain the decreased risk of lung and oropharyngeal cancer. Patients treated with radiotherapy likely have a small but significantly increased risk of bladder, vagina, colon, and soft-tissue SPM.

  5. Targeting Serous Epithelial Ovarian Cancer with Designer Zinc Finger Transcription Factors*

    PubMed Central

    Lara, Haydee; Wang, Yuhua; Beltran, Adriana S.; Juárez-Moreno, Karla; Yuan, Xinni; Kato, Sumie; Leisewitz, Andrea V.; Cuello Fredes, Mauricio; Licea, Alexei F.; Connolly, Denise C.; Huang, Leaf; Blancafort, Pilar

    2012-01-01

    Ovarian cancer is the leading cause of death among gynecological malignancies. It is detected at late stages when the disease is spread through the abdominal cavity in a condition known as peritoneal carcinomatosis. Thus, there is an urgent need to develop novel therapeutic interventions to target advanced stages of ovarian cancer. Mammary serine protease inhibitor (Maspin) represents an important metastasis suppressor initially identified in breast cancer. Herein we have generated a sequence-specific zinc finger artificial transcription factor (ATF) to up-regulate the Maspin promoter in aggressive ovarian cancer cell lines and to interrogate the therapeutic potential of Maspin in ovarian cancer. We found that although Maspin was expressed in some primary ovarian tumors, the promoter was epigenetically silenced in cell lines derived from ascites. Transduction of the ATF in MOVCAR 5009 cells derived from ascitic cultures of a TgMISIIR-TAg mouse model of ovarian cancer resulted in tumor cell growth inhibition, impaired cell invasion, and severe disruption of actin cytoskeleton. Systemic delivery of lipid-protamine-RNA nanoparticles encapsulating a chemically modified ATF mRNA resulted in inhibition of ovarian cancer cell growth in nude mice accompanied with Maspin re-expression in the treated tumors. Gene expression microarrays of ATF-transduced cells revealed an exceptional specificity for the Maspin promoter. These analyses identified novel targets co-regulated with Maspin in human short-term cultures derived from ascites, such as TSPAN12, that could mediate the anti-metastatic phenotype of the ATF. Our work outlined the first targeted, non-viral delivery of ATFs into tumors with potential clinical applications for metastatic ovarian cancers. PMID:22782891

  6. Case series of cerebral infarction with Trousseau's syndrome associated with malignant gynecological tumors

    PubMed Central

    ISHIKAWA, MASAKO; NAKAYAMA, KENTARO; ISHIBASHI, TOMOKA; SATO, EMI; NAKAMURA, KOHEI; KATAGIRI, HIROSHI; KYO, SATORU

    2016-01-01

    The association between neoplastic disease and thromboembolic disorders was first recognized by Trousseau in 1865. Blood coagulation abnormalities have been reported in the majority of patients with cancer, including those with ovarian carcinoma. However, Trousseau's syndrome (TS) has rarely been reported in women with ovarian carcinoma. We herein report a case series of TS, notably in the brain, in association with gynecological malignant disease, and emphasize the difficulties associated with the management of these thromboembolic effects. The aim of this study was to present our experience with 5 TS patients whose condition was effectively controlled through treatment of the primary malignant disease. Therefore, we suggest that patients with TS may be cured by tumor resection, even if they have severe thromboembolic disease, such as cerebral or pulmonary infarction. PMID:27330786

  7. Cost-effectiveness of primary debulking surgery when compared to neoadjuvant chemotherapy in the management of stage IIIC and IV epithelial ovarian cancer

    PubMed Central

    Forde, Gareth K; Chang, Jenny; Ziogas, Argyrios

    2016-01-01

    Objectives To examine the cost-effectiveness of primary debulking surgery (PDS) when compared to neoadjuvant chemotherapy (NACT) in the management of epithelial ovarian cancer (EOC) using Surveillance, Epidemiology, and End Results data linked to Medicare claims (SEER-Medicare). Methods Using a Markov model, the cost-effectiveness of PDS was compared to that of NACT. We modeled cost and survival inputs using data from women in the SEER-Medicare database with ovarian cancer treated by either PDS or NACT between 1992 and 2009. Direct and indirect costs were discounted by an annual rate of 3%. Utility weights were obtained from published data. The incremental cost-effectiveness ratio (ICER) of PDS compared to NACT was calculated. Results In our model, women with stage IIIC EOC had a higher mean adjusted treatment cost for PDS when compared to NACT ($31,945 vs $30,016) but yielded greater quality-adjusted life-years (QALYs) (1.79 vs 1.69). The ICER was $19,359/QALY gained. Women with stage IV EOC had a higher mean adjusted treatment cost following PDS when compared to NACT ($31,869 vs $27,338) but yielded greater QALYs (1.69 vs 1.66). The ICER was $130,083/QALY gained. A sensitivity analysis showed that for both PDS and NACT the ICER was sensitive to incremental changes in the utility weight. Conclusion PDS is significantly more cost-effective for women with stage IIIC when compared to NACT. In women with stage IV EOC, PDS is also more cost-effective though the QALYs gained are much more costly and exceed a $50,000 willingness to pay. PMID:27536150

  8. The use of non-linear analysis for differentiating the biomagnetic activity in ovarian lesions.

    PubMed

    Anninos, P A; Anastasiadis, P; Kotini, A

    1999-05-01

    In this study we investigated the biomagnetic activity measured with the superconducting quantum interference device (SQUID) in benign and malignant ovarian lesions using non-linear analysis. We used a single channel biomagnetometer SQUID in order to measure the magnetic field emitted from benign and malignant ovarian lesions. We can differentiate such biomagnetic activities using non-linear analysis. Using the application of non-linear analysis in the ovarian lesions together with the use of dimensional calculations we have observed a clear saturation value for the dimension of malignant ovarian lesions and non-saturation for benign ovarian lesions. The biomagnetic measurements with the SQUID and the application of non-linear analysis in benign and malignant ovarian lesions, is a promising procedure in assessing and differentiating ovarian tumours. PMID:15512296

  9. [Ovarian tumor markers of presumed benign ovarian tumors].

    PubMed

    Lahlou, N; Brun, J-L

    2013-12-01

    Cancer Antigen 125 (CA125) and Human Epididymis Protein 4 (HE4) are the most studied ovarian tumor markers. Their diagnostic performance for identification of ovarian cancer are superior to CA19-9, CA72-4, and carcinoembryonic antigen, which are no more recommended for the diagnosis of presumed benign ovarian tumor. HE4 (>140 pmol/L) is superior to CA125 (>30 U/mL) in terms of specificity and positive likelihood ratio. CA125 and HE4 can be combined into an algorithm ROMA, or associated to clinical information (composite index), biological data (OVA1) or imaging (Risk for Malignancy Index (RMI), LR2). ROMA algorithm is an exponential equation combining plasmatic concentrations of HE4 and CA125. ROMA is more sensitive and less specific than HE4 in predicting epithelial ovarian cancer. ROMA is more accurate in post-menopausal women. The performance of ROMA is lower than the ultrasound model LR2 in differentiating malignant from benign ovarian tumors, whatever the hormonal status. The composite index combining CA125 with a symptoms index (pain, abdominal distension, bloating, difficulty eating) has a good sensitivity in a screening program, but because of a 12% false positive rate, ultrasound is required before management. The RMI algorithm is based on serum CA125, ultrasound findings (septation, solid zones, metastases, ascite, bilaterality) and menopausal status. RMI is less sensitive, but more specific than ROMA or OVA1 for the classification of ovarian masses. The addition of HE4 to RMI seems to be the most accurate. The subjective evaluation of ovarian cysts by sonography and color Doppler is better than ROMA and RMI algorithms, and not affected by the hormonal status.

  10. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    PubMed

    Hong, Hao; Brown, Christine E; Ostberg, Julie R; Priceman, Saul J; Chang, Wen-Chung; Weng, Lihong; Lin, Paul; Wakabayashi, Mark T; Jensen, Michael C; Forman, Stephen J

    2016-01-01

    New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR)-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM) were then genetically modified to express an anti-L1-CAM CAR (CE7R), which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p.) administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer. PMID:26761817

  11. [Presumed benign ovarian tumors during pregnancy].

    PubMed

    Tariel, O; Huissoud, C; Rudigoz, R C; Dubernard, G

    2013-12-01

    The incidence of ovarian tumors diagnosed during pregnancy is between 0.3 and 5.4% (LE2). The most common ovarian tumors diagnosed during pregnancy are functional cysts diagnosed incidentally during the first trimester ultrasound (LE2) and spontaneous regression is often observed. Dermoid cysts and cystadenoma are the most frequent organic benign ovarian tumors diagnosed during pregnancy (LE2). The main complication of presumed benign ovarian tumor (PBOT) during pregnancy is adnexal torsion and is estimated at around 8% (LE2), especially at the end of the first trimester and during the second trimester (LE4). Tumor markers are not reliable during pregnancy to assess the risk of malignancy of ovarian tumor (LE2). Ultrasound remains the gold standard for characterizing an ovarian tumor during pregnancy (LE3), but with a lower specificity for the diagnosis of malignancy. Pelvic MRI is accurate in the diagnosis of ovarian tumors during pregnancy and brings additional information to ultrasound (LE4). Ultrasound-guided aspiration of ovarian tumors is not recommended during pregnancy (grade C). Expectation is recommended in cases of PBOT during pregnancy, which does not enlarge (grade C). Whatever the gestational age, surgery is recommended in patients with symptoms suggesting an adnexal torsion (grade C). Laparoscopy is possible during the first and second trimester of pregnancy for the management of symptomatic PBOT (LE3). The risk of miscarriage following surgery (laparoscopy and laparotomy) for ovarian tumor during pregnancy is estimated at 2.8% (LE3). The route of delivery should not be modified by the ovarian tumour, except in case of praevia cyst requiring a cesarean section, a complication or suspicion of malignancy (grade C). Surgical treatment of PBOT may be performed during a cesarean section indicated for another reason. The risk of torsion is increased during the postpartum period (LE4).

  12. Ovarian Cysts

    MedlinePlus

    ... or if the cyst does not go away. Birth control pills can help prevent new cysts. A health problem that may involve ovarian cysts is polycystic ovary syndrome (PCOS). Women with PCOS can have high levels of male hormones, irregular or no periods and small ovarian ...

  13. Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing

    PubMed Central

    Cole, Alexander J.; Dwight, Trisha; Gill, Anthony J.; Dickson, Kristie-Ann; Zhu, Ying; Clarkson, Adele; Gard, Gregory B.; Maidens, Jayne; Valmadre, Susan; Clifton-Bligh, Roderick; Marsh, Deborah J.

    2016-01-01

    The tumour suppressor p53 is mutated in cancer, including over 96% of high-grade serous ovarian cancer (HGSOC). Mutations cause loss of wild-type p53 function due to either gain of abnormal function of mutant p53 (mutp53), or absent to low mutp53. Massively parallel sequencing (MPS) enables increased accuracy of detection of somatic variants in heterogeneous tumours. We used MPS and immunohistochemistry (IHC) to characterise HGSOCs for TP53 mutation and p53 expression. TP53 mutation was identified in 94% (68/72) of HGSOCs, 62% of which were missense. Missense mutations demonstrated high p53 by IHC, as did 35% (9/26) of non-missense mutations. Low p53 was seen by IHC in 62% of HGSOC associated with non-missense mutations. Most wild-type TP53 tumours (75%, 6/8) displayed intermediate p53 levels. The overall sensitivity of detecting a TP53 mutation based on classification as ‘Low’, ‘Intermediate’ or ‘High’ for p53 IHC was 99%, with a specificity of 75%. We suggest p53 IHC can be used as a surrogate marker of TP53 mutation in HGSOC; however, this will result in misclassification of a proportion of TP53 wild-type and mutant tumours. Therapeutic targeting of mutp53 will require knowledge of both TP53 mutations and mutp53 expression. PMID:27189670

  14. Follow-up of patients who are clinically disease-free after primary treatment for fallopian tube, primary peritoneal, or epithelial ovarian cancer: a Program in Evidence-Based Care guideline adaptation

    PubMed Central

    Le, T.; Kennedy, E.B.; Dodge, J.; Elit, L.

    2016-01-01

    Background A need for follow-up recommendations for survivors of fallopian tube, primary peritoneal, or epithelial ovarian cancer after completion of primary treatment was identified by Cancer Care Ontario’s Program in Evidence-Based Care. Methods We searched for existing guidelines, conducted a systematic review (medline, embase, and cdsr, January 2010 to March 2015), created draft recommendations, and completed a comprehensive review process. Outcomes included overall survival, quality of life, and patient preferences. Results The Cancer Australia guidance document Follow Up of Women with Epithelial Ovarian Cancer was adapted for the Ontario context. A key randomized controlled trial found that the overall survival rate did not differ between asymptomatic women who received early treatment based on elevated serum cancer antigen 125 (ca125) alone and women who waited for the appearance of clinical symptoms before initiating treatment (hazard ratio: 0.98; 95% confidence interval: 0.80 to 1.20; p = 0.85); in addition, patients in the delayed treatment group reported good global health scores for longer. No randomized studies were found for other types of follow-up. We recommend that survivors be made aware of the potential harms and benefits of surveillance, including a discussion of the limitations of ca125 testing. Women could be offered the option of no formal follow-up or a follow-up schedule that is agreed upon by the woman and her health care provider. Education about the most common symptoms of recurrence should be provided. Alternative models of care such as nurse-led or telephone-based follow-up (or both) could be emerging options. Conclusions The recommendations provided in this guidance document have a limited evidence base. Recommendations should be updated as further information becomes available. PMID:27803599

  15. HE4 in the differential diagnosis of ovarian masses.

    PubMed

    Granato, Teresa; Porpora, Maria Grazia; Longo, Flavia; Angeloni, Antonio; Manganaro, Lucia; Anastasi, Emanuela

    2015-06-15

    Ovarian masses, a common finding among pre- and post-menopausal women, can be benign or malignant. Ovarian cancer is the leading cause of death from gynecologic malignancy among women living in industrialized countries. According to the current guidelines, measurement of CA125 tumor marker remains the gold standard in the management of ovarian cancer. Recently, HE4 has been proposed as emerging biomarker in the differential diagnosis of adnexal masses and in the early diagnosis of ovarian cancer. Discrimination of benign and malignant ovarian tumors is very important for correct patient referral to institutions specialized in care and management of ovarian cancer. Tumor markers CA125 and HE4 are currently incorporated into the "Risk of Ovarian Malignancy Algorithm" (ROMA) with menopausal status for discerning malignant from benign pelvic masses. The availability of a good biomarker such as HE4, closely associated with the differential and early diagnosis of ovarian cancer, could reduce medical costs related to more expensive diagnostic procedures. Finally, it is important to note that HE4 identifies platinum non-responders thus enabling a switch to second line chemotherapy and improved survival.

  16. Targeting the EGF Receptor for Ovarian Cancer Therapy

    PubMed Central

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

    2010-01-01

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

  17. Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer?

    PubMed Central

    Anastasi, Emanuela; Manganaro, Lucia; Granato, Teresa; Benedetti Panici, Pierluigi; Frati, Luigi; Porpora, Maria Grazia

    2013-01-01

    Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish if the serum marker CA72-4 could be helpful in the differential diagnosis between ovarian endometriosis and epithelial ovarian cancer. Methods. Serums CA125 and CA72-4 were measured in 72 patients with ovarian endometriomas and 55 patients with ovarian cancer. Results. High CA125 concentrations were observed in patients with ovarian endometriosis and in those with ovarian cancer. A marked difference in CA72-4 values was observed between women with ovarian cancer (71.0%) and patients with endometriosis (13.8%) (P < 0.0001). Conclusions. This study suggests that CA72-4 determination can be useful to confirm the benign nature of ovarian endometriomas in women with high CA125 levels. PMID:24191126

  18. General Information about Ovarian Epithelial Cancer

    MedlinePlus

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

  19. Massive Ovarian Oedema- A Case Report.

    PubMed

    Harke, Arun B; Sigamani, Karthik; Thukkaram, Chitra; Ramamurthy, Madhumittha; Sekar, Manjani

    2016-08-01

    Massive ovarian oedema is defined by WHO as formation of tumour like enlargement of one or both ovaries by oedema fluid. We report a case of a 18-year-old unmarried girl who presented with three months amenorrhoea and left sided lower abdominal pain with clinical and radiological diagnosis of cystic ovarian neoplasm. Patient underwent lapratomy with left salpingo-oophorectomy. A definitive diagnosis of Massive Ovarian Oedema (MOE) was offered on histopathological examination. The MOE should be differentiated from ovarian fibromatosis, ovarian fibroma, sclerosing stromal tumour and ovarian myxoma. The usual management of massive oedema of ovary is unilateral salpingo-oophorectomy, as the lesion is mistaken for primary ovarian neoplasm at laparotomy. Recognition of MOE is of great importance to prevent unnecessary oophorectomy in young patients and can be managed conservatively. We report this case of MOE for its rarity. PMID:27656451

  20. Increased expression of matrix metalloproteinases (MMP)-2, MMP-9, and the urokinase-type plasminogen activator is associated with progression from benign to advanced ovarian cancer.

    PubMed

    Schmalfeldt, B; Prechtel, D; Härting, K; Späthe, K; Rutke, S; Konik, E; Fridman, R; Berger, U; Schmitt, M; Kuhn, W; Lengyel, E

    2001-08-01

    Proteases are linked to the malignant phenotype of different solid tumors. Therefore, the expression of the matrix metalloproteinase (MMP)-2 and MMP-9 and of the serine protease urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) in the progression of ovarian cancer was investigated. Gelatinolytic activity and protein expression of MMP-2 and MMP-9 were analyzed in tissue extracts of 19 cystadenomas and 18 low malignant potential (LMP) tumors, as well as 41 primary tumors of advanced ovarian cancer stage International Federation of Gynecology and Obstetrics IIIc/IV and their corresponding omentum metastases by quantitative gelatin zymography and Western blot. In the same tissue extracts, antigen levels of uPA and its inhibitor PAI-1 were determined by ELISA. Protein expression of pro-MMP-2 (72 kDa) and pro-MMP-9 (92 kDa as well as antigen levels of uPA and PAI-1 were low in benign ovarian tumors but increased significantly from LMP tumors to advanced ovarian cancers. The highest values of all of the proteolytic factors were detected in omentum metastases. Active MMP-2 enzyme (62 kDa) was detected only in ovarian cancer (66%) and corresponding metastases (93%) but never in benign or LMP tumors. The activation rate of MMP-2 to its active isoform was higher in the metastases. Comparing both proteolytic systems, higher PAI-1 concentrations were consistently found in cancers with high pro-MMP-9 expression. These data indicate that members of the plasminogen activator system, as well as the metalloproteinases MMP-2/9, increase with growing malignant potential of ovarian tumors. These findings are of particular relevance to the development of protease inhibitors as new therapeutic approaches in ovarian cancer.

  1. Estimation of Optimal Brachytherapy Utilization Rate in the Treatment of Malignancies of the Uterine Corpus by a Review of Clinical Practice Guidelines and the Primary Evidence

    SciTech Connect

    Thompson, Stephen R. Delaney, Geoff; Gabriel, Gabriel S.; Jacob, Susannah; Das, Prabir; Barton, Michael

    2008-11-01

    Purpose: Brachytherapy (BT) is an important treatment technique for uterine corpus malignancies. We modeled the optimal proportion of these cases that should be treated with BT-the optimal rate of brachytherapy utilization (BTU). We compared this optimal BTU rate with the actual BTU rate. Methods and Materials: Evidence-based guidelines and the primary evidence were used to construct a decision tree for BTU for malignancies of the uterine corpus. Searches of the literature to ascertain the proportion of patients who fulfilled the criteria for BT were conducted. The robustness of the model was tested by sensitivity analyses and peer review. A retrospective Patterns of Care Study of BT in New South Wales for 2003 was conducted, and the actual BTU for uterine corpus malignancies was determined. The actual BTU in other geographic areas was calculated from published reports. The differences between the optimal and actual rates of BTU were assessed. Results: The optimal uterine corpus BTU rate was estimated to be 40% (range, 36-49%). In New South Wales in 2003, the actual BTU rate was only 14% of the 545 patients with uterine corpus cancer. The actual BTU rate in 2001 was 11% in the Surveillance, Epidemiology, and End Results areas and 30% in Sweden. Conclusion: The results of this study have shown that BT for uterine corpus malignancies is underused in New South Wales and in the Surveillance, Epidemiology, and End Results areas. Our model of optimal BTU can be used as a quality assurance tool, providing an evidence-based benchmark against which can be measured actual patterns of practice. It can also be used to assist in determining the adequacy of BT resource allocation.

  2. Ovarian Cancer FAQ

    MedlinePlus

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

  3. Estrogen Biosynthesis and Action in Ovarian Cancer

    PubMed Central

    Mungenast, Felicitas; Thalhammer, Theresia

    2014-01-01

    Ovarian cancer is still the deadliest of all gynecologic malignancies in women worldwide. This is attributed to two main features of these tumors, namely, (i) a diagnosis at an advanced tumor stage, and, (ii) the rapid onset of resistance to standard chemotherapy after an initial successful therapy with platin- and taxol-derivatives. Therefore, novel targets for an early diagnosis and better treatment options for these tumors are urgently needed. Epidemiological data show that induction and biology of ovarian cancer is related to life-time estrogen exposure. Also experimental data reveal that ovarian cancer cells share a number of estrogen regulated pathways with other hormone-dependent cancers, e.g., breast and endometrial cancer. However, ovarian cancer is a heterogeneous disease and the subtypes are quite different with respect to mutations, origins, behaviors, markers, and prognosis and respond differently to standard chemotherapy. Therefore, a characterization of ovarian cancer subtypes may lead to better treatment options for the various subtypes and in particular for the most frequently observed high-grade serous ovarian carcinoma. For this intention, further studies on estrogen-related pathways and estrogen formation in ovarian cancer cells are warranted. The review gives an overview on ovarian cancer subtypes and explains the role of estrogen in ovarian cancer. Furthermore, enzymes active to synthesize and metabolize estrogens are described and strategies to target these pathways are discussed. PMID:25429284

  4. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer--shifting the paradigm.

    PubMed

    Kurman, Robert J; Shih, Ie-Ming

    2011-07-01

    Recent morphologic, immunohistochemical, and molecular genetic studies have led to the development of a new paradigm for the pathogenesis and origin of epithelial ovarian cancer based on a dualistic model of carcinogenesis that divides epithelial ovarian cancer into 2 broad categories designated types I and II. Type I tumors comprise low-grade serous, low-grade endometrioid, clear cell and mucinous carcinomas, and Brenner tumors. They are generally indolent, present in stage I (tumor confined to the ovary), and are characterized by specific mutations, including KRAS, BRAF, ERBB2, CTNNB1, PTEN, PIK3CA, ARID1A, and PPP2R1A, which target specific cell signaling pathways. Type I tumors rarely harbor TP53 mutations and are relatively stable genetically. Type II tumors comprise high-grade serous, high-grade endometrioid, malignant mixed mesodermal tumors (carcinosarcomas), and undifferentiated carcinomas. They are aggressive, present in advanced stage, and have a very high frequency of TP53 mutations but rarely harbor the mutations detected in type I tumors. In addition, type II tumors have molecular alterations that perturb expression of BRCA either by mutation of the gene or by promoter methylation. A hallmark of these tumors is that they are genetically highly unstable. Recent studies strongly suggest that fallopian tube epithelium (benign or malignant) that implants on the ovary is the source of low-grade and high-grade serous carcinoma rather than the ovarian surface epithelium as previously believed. Similarly, it is widely accepted that endometriosis is the precursor of endometrioid and clear cell carcinomas and, as endometriosis, is thought to develop from retrograde menstruation; these tumors can also be regarded as involving the ovary secondarily. The origin of mucinous and transitional cell (Brenner) tumors is still not well established, although recent data suggest a possible origin from transitional epithelial nests located in paraovarian locations at the

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

    PubMed Central

    2012-01-01

    Background 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. Methods 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. Results 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. Conclusions This study found

  6. Ovarian serous carcinogenesis from tubal secretory cells.

    PubMed

    Zhang, Wenjing; Wei, Linxuan; Li, Lingmin; Yang, Binlie; Kong, Beihua; Yao, Guang; Zheng, Wenxin

    2015-11-01

    Due to a poor understanding of tumorigenesis, ovarian cancers remain the most lethal gynecologic malignancy and cause horrific deaths. In the last decade, a new dualistic model for ovarian cancer was proposed, wherein ovarian serous cancers are classified as either high-grade or low-grade, with each having different tumorigenic processes, and pathologic and clinical features. Surprisingly, both high- and low-grade ovarian serous cancers were recently found to originate not in the ovaries, but rather from the secretory cells of the fallopian tube, mostly from the tubal fimbriated ends. In this article, we review the evidentiary basis for the aforementioned paradigm shift in the cell origin of ovarian serous cancers, as well as its potential clinical implications. PMID:26174492

  7. Ovarian hypofunction

    MedlinePlus

    ... may be caused by genetic factors such as chromosome abnormalities. It may also occur with certain autoimmune disorders that disrupt the normal function of the ovaries. Chemotherapy and radiation therapy can also cause ovarian hypofunction.

  8. Ovarian Cysts

    MedlinePlus

    ... information Endometriosis fact sheet Ovarian cancer fact sheet Polycystic ovary syndrome fact sheet The javascript used in this widget ... ovaries make many small cysts. This is called polycystic ovary syndrome (PCOS). PCOS can cause problems with the ovaries ...

  9. Small-Molecule RA-9 Inhibits Proteasome-Associated DUBs and Ovarian Cancer in Vitro and in Vivo Via Exacerbating Unfolded Protein Responses

    PubMed Central

    Coughlin, Kathleen; Anchoori, Ravi; Iizuka, Yoshie; Meints, Joyce; MacNeill, Lauren; Vogel, Rachel Isaksson; Orlowski, Robert Z.; Lee, Michael K.; Roden, Richard BS; Bazzaro, Martina

    2014-01-01

    Purpose Ovarian cancer is the deadliest of the gynecological malignancies. Carcinogenic progression is accompanied by up-regulation of ubiquitin-dependent protein degradation machinery as a mechanism to compensate with elevated endogenous proteotoxic stress. Recent studies support the notion that deubiquitinating enzymes (DUBs) are essential factors in proteolytic degradation and that their aberrant activity is linked to cancer progression and chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian cancer. Experimental Design The potency and selectivity of RA-9 inhibitor for proteasome-associated DUBs was determined in ovarian cancer cell lines and primary cells. The anticancer activity of RA-9 and its mechanism of action was evaluated in multiple cancer cell lines in vitro and in vivo in immunodeficient mice bearing an intra-peritoneal ES-2 xenograft model of human ovarian cancer. Results Here we report the characterization of RA-9 as a small-molecule inhibitor of proteasome-associated DUBs. Treatment with RA-9 selectively induces onset of apoptosis, in ovarian cancer cell lines and primary cultures derived from donors. Loss of cell viability following RA-9 exposure is associated with an Unfolded Protein Response (UPR) as mechanism to compensate for unsustainable levels of proteotoxic stress. In vivo treatment with RA-9 retards tumor growth, increases overall survival and was well tolerated by the host. Conclusions Our preclinical studies support further evaluation of RA-9 as an ovarian cancer therapeutic. PMID:24727327

  10. Validating a mouse model of ovarian cancer for early detection through imaging | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Despite advances in treatment strategies, ovarian cancer remains the deadliest gynecological malignancy and the 5th largest cancer killer in women. Located deep in the body, with few early symptoms and no effective screening technique, ovarian cancer has remained stubbornly difficult to understand, much less effectively combat. Ovarian cancer is almost always discovered at an advanced stage. |

  11. Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC).

    PubMed

    Ricceri, Fulvio; Fasanelli, Francesca; Giraudo, Maria Teresa; Sieri, Sabina; Tumino, Rosario; Mattiello, Amalia; Vagliano, Liliana; Masala, Giovanna; Quirós, J Ramón; Travier, Noemie; Sánchez, María-José; Larranaga, Nerea; Chirlaque, María-Dolores; Ardanaz, Eva; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chang-Claude, Jenny; Kaaks, Rudolf; Boeing, Heiner; Clavel-Chapelon, Françoise; Kvaskoff, Marina; Dossus, Laure; Trichopoulou, Antonia; Benetou, Vassiliki; Adarakis, George; Bueno-de-Mesquita, H B As; Peeters, Petra H; Sund, Malin; Andersson, Anne; Borgquist, Signe; Butt, Salma; Weiderpass, Elisabete; Skeie, Guri; Khaw, Kay-Tee; Travis, Ruth C; Rinaldi, Sabina; Romieu, Isabelle; Gunter, Marc; Kadi, Mai; Riboli, Elio; Vineis, Paolo; Sacerdote, Carlotta

    2015-08-15

    Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer.

  12. Risk of second primary malignancies in women with breast cancer: Results from the European prospective investigation into cancer and nutrition (EPIC).

    PubMed

    Ricceri, Fulvio; Fasanelli, Francesca; Giraudo, Maria Teresa; Sieri, Sabina; Tumino, Rosario; Mattiello, Amalia; Vagliano, Liliana; Masala, Giovanna; Quirós, J Ramón; Travier, Noemie; Sánchez, María-José; Larranaga, Nerea; Chirlaque, María-Dolores; Ardanaz, Eva; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chang-Claude, Jenny; Kaaks, Rudolf; Boeing, Heiner; Clavel-Chapelon, Françoise; Kvaskoff, Marina; Dossus, Laure; Trichopoulou, Antonia; Benetou, Vassiliki; Adarakis, George; Bueno-de-Mesquita, H B As; Peeters, Petra H; Sund, Malin; Andersson, Anne; Borgquist, Signe; Butt, Salma; Weiderpass, Elisabete; Skeie, Guri; Khaw, Kay-Tee; Travis, Ruth C; Rinaldi, Sabina; Romieu, Isabelle; Gunter, Marc; Kadi, Mai; Riboli, Elio; Vineis, Paolo; Sacerdote, Carlotta

    2015-08-15

    Women with a diagnosis of breast cancer are at increased risk of second primary cancers, and the identification of risk factors for the latter may have clinical implications. We have followed-up for 11 years 10,045 women with invasive breast cancer from a European cohort, and identified 492 second primary cancers, including 140 contralateral breast cancers. Expected and observed cases and Standardized Incidence Ratios (SIR) were estimated using Aalen-Johansen Markovian methods. Information on various risk factors was obtained from detailed questionnaires and anthropometric measurements. Cox proportional hazards regression models were used to estimate the role of risk factors. Women with breast cancer had a 30% excess risk for second malignancies (95% confidence interval-CI 18-42) after excluding contralateral breast cancers. Risk was particularly elevated for colorectal cancer (SIR, 1.71, 95% CI 1.43-2.00), lymphoma (SIR 1.80, 95% CI 1.31-2.40), melanoma (2.12; 1.63-2.70), endometrium (2.18; 1.75-2.70) and kidney cancers (2.40; 1.57-3.52). Risk of second malignancies was positively associated with age at first cancer, body mass index and smoking status, while it was inversely associated with education, post-menopausal status and a history of full-term pregnancy. We describe in a large cohort of women with breast cancer a 30% excess of second primaries. Among risk factors for breast cancer, a history of full-term pregnancy was inversely associated with the risk of second primary cancer. PMID:25650288

  13. ETM study of electroporation influence on cell morphology in human malignant melanoma and human primary gingival fibroblast cells

    PubMed Central

    Skolucka, Nina; Daczewska, Malgorzata; Saczko, Jolanta; Chwilkowska, Agnieszka; Choromanska, Anna; Kotulska, Malgorzata; Kaminska, Iwona; Kulbacka, Julita

    2011-01-01

    Objective To estimate electroporation (EP) influence on malignant and normal cells. Methods Two cell lines including human malignant melanoma (Me-45) and normal human gingival fibroblast (HGFs) were used. EP parameters were the following: 250, 1 000, 1 750, 2 500 V/cm; 50 µs by 5 impulses for every case. The viability of cells after EP was estimated by MTT assay. The ultrastructural analysis was observed by transmission electron microscope (Zeiss EM 900). Results In the current study we observed the intracellular effect following EP on Me-45 and HGF cells. At the conditions applied, we did not observe any significant damage of mitochondrial activity in both cell lines treated by EP. Conversely, we showed that EP in some conditions can stimulate cells to proliferation. Some changes induced by EP were only visible in electron microscopy. In fibroblast cells we observed significant changes in lower parameters of EP (250 and 1 000 V/cm). After applying higher electric field intensities (2 500 V/cm) we detected many vacuoles, myelin-like bodies and swallowed endoplasmic reticulum. In melanoma cells such strong pathological modifications after EP were not observed, in comparison with control cells. The ultrastructure of both treated cell lines was changed according to the applied parameters of EP. Conclusions We can claim that EP conditions are cell line dependent. In terms of the intracellular morphology, human fibroblasts are more sensitive to electric field as compared with melanoma cells. Optimal conditions should be determined for each cell line. Summarizing our study, we can conclude that EP is not an invasive method for human normal and malignant cells. This technique can be safely applied in chemotherapy for delivering drugs into tumor cells. PMID:23569735

  14. Ovarian cancer: emerging molecular-targeted therapies

    PubMed Central

    Sourbier, Carole

    2012-01-01

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

  15. Surgery of ovarian tumors in children.

    PubMed

    Sarnacki, Sabine; Brisse, Hervé

    2011-01-01

    Surgery of ovarian tumors in children requires a good knowledge of these lesions. Complete resection is mandatory for malignant lesions, and in the case of benign tumors preservation of healthy ovarian tissue is crucial. Diagnosis is based on clinical features (age and hormonal status), imaging and tumor marker levels. Laparoscopy is of great help in making a diagnosis and staging when the lesion is malignant. Laparotomy by a supra-pubic approach is, however, the only way to ensure a safe treatment of the lesion by avoiding any risk of tumor spillage, which constitutes a chance loss. Surgical treatment consists of complete ovariectomy for a malignant tumor and partial ovariectomy when the lesion is surely benign. Preservation of fertility is based on conservative surgery for uni- or bilateral benign lesions, and may be discussed in some selected cases of bilateral malignant tumors. When the remaining ovarian tissue predicts precocious ovarian failure, ovarian tissue or oocyte cryopreservation may be proposed to patients and their families.

  16. Lenvatinib and Capecitabine in Patients With Advanced Malignancies

    ClinicalTrials.gov

    2016-09-23

    Advanced Cancer; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract

  17. Survival after resection of a primary malignant melanoma of the small intestine in a young patient: report of a case.

    PubMed

    Timmers, T K; Schadd, E M; Monkelbaan, J F; Meij, V

    2013-05-01

    The occurrence of primary melanoma of the small intestine is rare. We describe the case of a 25-year-old man found to have a primary melanoma of the ileum. The patient presented with gradual onset of abdominal pain, fever, diarrhea, weight loss and fatigue. A preoperative diagnosis of a small intestinal tumor was based on the findings of computed tomography scanning. This diagnosis was confirmed at laparoto-my and a partial small bowel resection was performed. Histopathological examination of the resected specimen clarified the exact nature of the lesion, confirming the diagnosis of melanoma. Thorough postoperative investigation did not reveal a primary lesion in the skin, gastrointestinal tract, oculus or brain. Thus, we diagnosed this tumor as a primary lesion. One year after his operation, the patient remains well without any evidence of recurrence. Thus, we diagnosed this small bowel tumor as a primary melanoma of the small intestine.

  18. Expression of the cancer/testis antigen NY-ESO-1 in primary and metastatic malignant melanoma (MM) - correlation with prognostic factors

    PubMed Central

    Velazquez, Elsa F.; Jungbluth, Achim A.; Yancovitz, Molly; Gnjatic, Sacha; Adams, Sylvia; O'Neill, David; Zavilevich, Kira; Albukh, Tatyana; Christos, Paul; Mazumdar, Madhu; Pavlick, Anna; Polsky, David; Shapiro, Richard; Berman, Russell; Spira, Joanna; Busam, Klaus; Osman, Iman

    2007-01-01

    Cancer/testis (CT) antigens are potential targets for cancer immunotherapy, with NY-ESO-1 being among the most immunogenic. In several clinical trials in malignant melanoma (MM) patients, NY-ESO-1 protein/peptides showed clear evidence of inducing specific immunity. However, little is known about NY-ESO-1 expression in primary and metastatic MM and its relationship to disease progression. We analyzed NY-ESO-1 expression immunohistochemically in a series of primary and metastatic MMs and its relation to prognostic parameters and survival. We studied 61 primary and 63 metastatic MM specimens (from 61 and 56 patients, respectively). The prevalence of NY-ESO-1 expression was significantly higher in metastatic versus primary tumors [18/56 (32%) versus 8/61 (13%), P = 0.015]. There was a significant association between initial stage at presentation and NY-ESO-1 expression [stage I (3.45%), stage II (9.52%) and stage III (45.45%), P = 0.0014]. Primary MMs expressing NY-ESO-1 were significantly thicker than NY-ESO-1 negative cases (median thickness 4.7 mm versus 1.53 mm respectively, P = 0.03). No significant difference was seen in overall survival. In conclusion, NY-ESO-1 is more frequently expressed in metastatic than in primary MM and its expression is associated with thicker primary lesions and a higher frequency of metastatic disease, indicative of a worse prognosis. Our study suggests that patients with metastatic MM who express NY-ESO-1 may benefit from NY-ESO-1-based immunotherapy. PMID:17625806

  19. [Sonographic diagnosis of presumed benign ovarian tumors].

    PubMed

    Marret, H; Cayrol, M

    2013-12-01

    To discriminate ovarian lesions is of particular importance in gynecological practice. Two main problems need answers: discrimination of benign and malignant adnexal masses and choice of the appropriate surgical treatment if necessary. Nearly 2% of the adnexal masses are ovarian carcinomas or borderline tumors. It is now, well established that ultrasonography is the gold standard for ovarian cyst diagnosis. The purpose of this data was to review the literature and to establish, with the evidence base medicine model, which parameters and existing diagnostic models using ultrasound and Doppler perform best in the evaluation of adnexal masses. Transvaginal sonography has demonstrated considerable advantage over conventional transabdominal sonography. However, transparietal sonography is still useful in large tumors. Definition of the nomenclature and classification was done and should be used. Unilocular ovarian cyst characterization seems easy using sonography and Doppler. In front of complication, discrimination of such functional cyst may be difficult but spontaneous regression confirms usually the expectative management. Dermoid cysts and endometriomas seem to be easier to discriminate from other adnexal masses. Ultrasound and morphologic parameters have a sensitivity of about 90% and a specificity of 80%; that makes this exam the gold standard for ovarian masses diagnosis. Only 50% of ovarian masses are characterized by sonography. Scoring systems help to differentiate benign from malignant masses (sensitivity of about 90%). Logistic regression and models are good methods especially for LR1 and 2 and RMI and may be useful for malignancy prediction but are difficult to use in current practice. Expert diagnosis is a subjective but most important performing parameter. Any suspicious ovarian mass or not easily diagnosed mass requires sonography by an expert, which can first use all the techniques and the different parameters to discriminate benign and malignant

  20. Electron microscopy, tissue culture,and immunology of ovarian carcinoma.

    PubMed

    Ioachim, H L; Dorsett, B H; Sabbath, M; Barber, H R

    1975-10-01

    The ultrastructure of the major histologic types of ovarian carcinoma was investigated as part of a multilateral study of this tumor. The nuclear and nucleolar changes in size, shape, and structure correlated well with the degree of malignancy and tumor grading. Cytoplasmic organelles and intercellular junctions were abundant and fairly well differentiated even in ovarian carcinomas of higher grade and stage. Active processes of synthesis and secretion taking place in most of these tumors were suggested by the presence of a richly granulated endoplasmic reticulum, dilated cisternae, and numerous secretory granules. Seventy-eight different ovarian carcinomas of all histologic types were cultured in vitro for periods of up to 300 days, and their morphology in light and electron microscopy was compared to that of the original tumors. The cultures displayed a consistent pattern of growth which led to the conclusion that ovarian cancer cells in vitro preserve their salient features and are representative of the tumors of origin. Heterologous antisera raised with pooled extracts of various types of ovarian carcinomas reacted specifically in immunodiffusion and immunofluorescence tests only with ovarian carcinomas and not with normal ovaries, benigh ovarian tumors, and nonovarian malignant neoplasms, indicating the presence of a cross-reacting specific antigen for ovarian carcinomas. In other studies, autologous antibodies were isolated from antigen-antibody complexes recovered from peritoneal effusions of patients with ovarian carcinomas. These antibodies displayed a high degree of specificity against ovarian carcinoma cells when tested in immunofluorescence assays.

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

    PubMed

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

    2015-01-01

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

  2. Ovarian cancer.

    PubMed

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

    2016-01-01

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

  3. Characterization of the specificity by immunohistology of a monoclonal antibody to a novel epithelial antigen of ovarian carcinomas.

    PubMed

    Mariani-Costantini, R; Agresti, R; Colnaghi, M I; Ménard, S; Andreola, S; Rilke, F

    1985-08-01

    An immunohistological study, using the avidin-biotin-peroxidase complex method, was carried out to define the reactivity profile of a murine monoclonal antibody, MOv2, which recognizes a novel glycoprotidic antigen associated with ovarian epithelial tumors. Among the primary ovarian tumors tested, MOv2 immunostained 93% of mucinous and 75% of serous cystadenomas, 100% of mucinous, 81% of serous and 73% of endometrioid carcinomas. Undifferentiated and clear cell tumors revealed more limited reactivity with the antibody, whereas ovarian sex cord-stromal and germinal tumors were immunonegative. Positive reactions were also documented in omental metastases from primary ovarian carcinomas. No immunoreactivity was detected in normal ovarian epithelium, whereas the cells lining Walthard's nests adjacent to the fallopian tubes and a variety of normal epithelia were consistently immunolabeled. These included the lining epithelia of the gastrointestinal tract, bronchi and endocervix, and the epithelium of salivary, biliary and pancreatic ducts and sweat glands. To a lesser extent, positive reactions were detected in other surface epithelia, such as squamous and transitional epithelia. Among tumors other than ovarian, MOv2 consistently reacted with adenocarcinomas and squamous cell carcinomas from different sites, most notably breast, lung and gastrointestinal tract, and with transitional cell carcinomas. In contrast, no staining was demonstrated in non-epithelial malignancies. The antigen defined by MOv2 may be operationally useful as a marker of epithelial lineage in tumor histopathology. Its pattern of immunohistochemical distribution indicates that an antigenic phenotype shared by normal surface epithelia and non-ovarian carcinomas is strongly associated with common epithelial neoplasms of the ovaries.

  4. More Complete Removal of Malignant Brain Tumors by Fluorescence-Guided Surgery

    ClinicalTrials.gov

    2016-05-13

    Benign Neoplasms, Brain; Brain Cancer; Brain Neoplasms, Benign; Brain Neoplasms, Malignant; Brain Tumor, Primary; Brain Tumor, Recurrent; Brain Tumors; Intracranial Neoplasms; Neoplasms, Brain; Neoplasms, Intracranial; Primary Brain Neoplasms; Primary Malignant Brain Neoplasms; Primary Malignant Brain Tumors; Gliomas; Glioblastoma

  5. Estrogen receptor beta, a possible tumor suppressor involved in ovarian carcinogenesis

    PubMed Central

    Lazennec, Gwendal

    2006-01-01

    Ovarian cancer is one of the leading cause of death from gynecological tumors in women. Several lines of evidence suggest that estrogens may play an important role in ovarian carcinogenesis, through their receptors, ERα and ERβ. Interestingly, malignant ovarian tumors originating from epithelial surface constitute about 90% of ovarian cancers and expressed low levels of ERβ, compared to normal tissues. In addition, restoration of ERβ in ovarian cancer cells, leads to strong inhibition of their proliferation and invasion, while apoptosis is enhanced. In this manuscript, recent data suggesting a possible tumor-suppressor role for ERβ in ovarian carcinogenesis are discussed. PMID:16399219

  6. Analysis of disseminated tumor cells before and after platinum based chemotherapy in primary ovarian cancer. Do stem cell like cells predict prognosis?

    PubMed Central

    Wimberger, Pauline; Neubauer, Hans; Fehm, Tanja; Kimmig, Rainer; Kasimir-Bauer, Sabine

    2016-01-01

    Background We recently reported that the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) of primary ovarian cancer patients (POC pts) correlated with reduced progression free survival (PFS) and overall survival (OS). Here we analyzed whether the negative prognostic influence was related to DTC persistence after platinum based chemotherapy and/or due to DTCs associated with stem cell character. Results DTCs were detected in 33/79 pts (42%) before and in 32/79 pts (41%) AT. Persistent DTCs were found in 13 pts, 20 pts were only positive BT, 19 pts AT and 27 pts had no DTCs. Whereas the presence of DTCs BT significantly correlated with reduced OS (p = 0.02), pts initially DTCneg BT but DTCpos AT had a significantly shorter PFS (p = 0.03). DTC persistence resulted in a shorter PFS and OS reaching borderline significance (p = 0.06; p = 0.07). LIN-28-and SOX-2 positive cells were detected in all eight pts AT. Patients and Methods 79 POC pts were studied for DTCs before therapy (BT) and after therapy (AT) using immunocytochemistry. Eight pts harboring at least five DTCs AT were further analyzed on two additional slides by four-fold immunofluorescence staining for DAPI, Cytokeratin (CK), SOX-2 or LIN-28, CD45 and CD34 (Cy5). A stem-like tumor cell was classified as Dapipos, CD45neg, CD34neg, SOX-2pos/LIN-28pos and CKpos or CKneg. Conclusions Stem cell associated proteins are expressed in DTCs that are present AT and their presence seem to be correlated with a worse outcome. Additional therapeutic regimens may be necessary to eliminate these cells. PMID:27049920

  7. Clinical significance of serum MMP-2 and MMP-7 in patients with ovarian cancer.

    PubMed

    Acar, Ayla; Onan, Anil; Coskun, Ugur; Uner, Aytug; Bagriacik, Umit; Atalay, Funda; Unsal, Diclehan Kilic; Guner, Haldun

    2008-01-01

    Matrix metalloproteinases (MMPs) are frequently expressed in malignant tumors and play an important role in tumor invasion and metastasis. The aim of this study was to evaluate role of serum MMP-2 and MMP-7 levels in patients with ovarian cancer. Serum levels of MMP-2 and MMP-7 were measured in 28 patients with ovarian carcinoma, 2 with borderline ovarian tumors, 10 with non-malignant gynecological disease and 30 healthy women by Enzyme-Linked Immunosorbent Assay (ELISA). Serum MMP-7 level was significantly (10.24+/-1.35 ng/ml) higher in the patients with ovarian malign tumors than healthy controls (3.29+/-1.64 ng/ml) (P<0.05). Postoperative levels of MMP-7 (7.68+/-1.17 ng/ml) were significantly lower in patients with malign ovarian tumors than those of preoperative level (10.24+/-1.35 ng/ml) (P<0.05). Serum MMP-2 levels were significantly lower in the patients with ovarian malign tumors (227.51+/-9.91 ng/ml) than those in the healthy controls (279.12+/-73 ng/ml) (P<0.05). There was no significant difference in serum levels of MMP-2 and MMP-7 in patients with benign ovarian disease when compared to healthy controls and patients with malignant disease (P>0.05). As a conclusion, MMP-7 can be a useful serum marker to show disease activity in malignant ovarian tumors.

  8. Metadherin, p50, and p65 expression in epithelial ovarian neoplasms: an immunohistochemical study.

    PubMed

    Giopanou, Ioanna; Bravou, Vasiliki; Papanastasopoulos, Panagiotis; Lilis, Ioannis; Aroukatos, Panagiotis; Papachristou, Dionysios; Kounelis, Sophia; Papadaki, Helen

    2014-01-01

    NF-κB signaling promotes cancer progression in a large number of malignancies. Metadherin, a coactivator of the NF-κB transcription complex, was recently identified to regulate different signaling pathways that are closely related to cancer. We assessed the immunohistochemical expression of p50, p65, and metadherin in 30 ovarian carcinomas, 15 borderline ovarian tumours, and 31 benign ovarian cystadenomas. Ovarian carcinomas exhibited significantly higher expression of all 3 markers compared to benign ovarian tumours. Borderline ovarian tumours demonstrated significantly higher expression for all 3 markers compared to benign cystadenomas. Ovarian carcinomas demonstrated significantly higher expression of p50 and metadherin compared to borderline ovarian tumours, whereas no significant difference was noted in p65 expression between ovarian carcinomas and borderline ovarian tumours. There was a strong correlation with the expression levels of p50, p65, and metadherin, whereas no correlation was observed with either grade or stage. Strong p50, p65, and metadherin expression was associated with a high probability to distinguish ovarian carcinomas over borderline and benign ovarian tumours, as well as borderline ovarian tumours over benign ovarian neoplasms. A gradual increase in the expression of these molecules is noted when moving across the spectrum of ovarian carcinogenesis, from borderline ovarian tumours to epithelial carcinomas.

  9. The Use of Radiation Therapy Appears to Improve Outcome in Patients With Malignant Primary Tracheal Tumors: A SEER-Based Analysis

    SciTech Connect

    Xie Liyi; Fan Min; Sheets, Nathan C.; Chen, Ronald C.; Jiang, Guo-Liang; Marks, Lawrence B.

    2012-10-01

    Purpose: To conduct a matched pair analysis assessing the impact of radiotherapy (RT) in patients with resectable and unresectable primary malignant tracheal tumors using Surveillance, Epidemiology and End Results (SEER) database. Patients and Methods: The SEER registry was used to identify every patient (or 'case') who received RT between 1988 and 2007 for primary malignant tracheal tumors, and to search for corresponding 'controls' (not treated with RT), with the same prognostic and treatment factors (surgery on the trachea, disease extension, histology, and gender). Overall survival (OS) was calculated with the Kaplan-Meier methods. Results of OS and cumulative incidence of death from tracheal cancer in the cases and controls, and in various subsets, were compared using log-rank and Gray's tests. Results: Two hundred fifty-eight patients who received RT were identified, and 78 of these had appropriate matched controls identified, forming the basis of this analysis. In the 78 (+RT) cases, the median follow-up was 60 months (range, 10-192) in the survivors vs. 55 months (range, 2-187) in the controls (no-RT group). Patients in RT group had significantly better OS, and a lower cumulative incidence of death from tracheal cancer than no-RT patients (p < 0.05). Treatment with radiation was associated with improved survival in patients with squamous cell histology [p < 0.0001], regional disease extension [p = 0.030], or those that did not undergo resection [p = 0.038]. There were four deaths in RT group and three in no-RT group attributed to cardiac and respiratory causes. Conclusion: Our data suggest a survival benefit for the use of RT broadly for all patients with tracheal cancer. Nevertheless, the retrospective nature of this observational study limits its interpretation.

  10. Stages of Ovarian Low Malignant Potential Tumors

    MedlinePlus

    ... ovaries are a pair of organs in the female reproductive system . They are in the pelvis , one on each ... eggs and female hormones . Enlarge Anatomy of the female reproductive system. The organs in the female reproductive system include ...

  11. Trabectedin therapy as an emerging treatment strategy for recurrent platinum-sensitive ovarian cancer

    PubMed Central

    López-Guerrero, José Antonio; Romero, Ignacio; Poveda, Andrés

    2015-01-01

    Epithelial ovarian cancer (OC) is a common gynecologic malignancy in women. The standard treatment for OC is maximal cytoreductive surgical debulking followed by platinum-based chemotherapy. Despite the high response rate to primary therapy, approximately 85% of patients will develop recurrent ovarian cancer (ROC). This review identifies the clinical use of trabectedin in the treatment algorithm for ROC, with specific emphasis on platinum-sensitive ROC, for which trabectedin in combination with pegylated liposomal doxorubicin has been approved as a treatment protocol. The main mechanisms of action of trabectedin at the cellular level and in the tumor microenvironment is also discussed as bases for identifying biomarkers for selecting patients who may largely benefit from trabectedin-based therapies. PMID:25556617

  12. Prediction of Postchemotherapy Ovarian Function Using Markers of Ovarian Reserve

    PubMed Central

    Xia, Rong; Schott, Anne F.; McConnell, Daniel; Banerjee, Mousumi; Hayes, Daniel F.

    2014-01-01

    Background. Reproductive-aged women frequently receive both chemotherapy and endocrine therapy as part of their treatment regimen for early stage hormone receptor-positive breast cancer. Chemotherapy results in transient or permanent ovarian failure in the majority of women. The difficulty in determining which patients will recover ovarian function has implications for adjuvant endocrine therapy decision making. We hypothesized that pretreatment serum anti-Müllerian hormone (AMH) and inhibin B concentrations would predict for ovarian function following chemotherapy. Methods. Pre- and perimenopausal women aged 25–50 years with newly diagnosed breast cancer were enrolled. Subjects underwent phlebotomy for assessment of serum AMH, inhibin B, follicle-stimulating hormone, and estradiol prior to chemotherapy and 1 month and 1 year following completion of treatment. Associations among hormone concentrations, clinical factors, and biochemically assessed ovarian function were assessed. Results. Twenty-seven subjects were evaluable for the primary endpoint. Median age was 41. Twenty subjects (74.1%) experienced recovery of ovarian function within 18 months. Of the 26 evaluable subjects assessed prior to chemotherapy, 19 (73.1%) had detectable serum concentrations of AMH. The positive predictive value of a detectable baseline serum AMH concentration for recovery of ovarian function was 94.7%, and the negative predictive value was 85.7%. On univariate analysis, younger age and detectable serum AMH concentration at chemotherapy initiation were predictive of increased likelihood of recovery of ovarian function. Conclusion. Prechemotherapy assessment of serum AMH may be useful for predicting postchemotherapy ovarian function. This finding has implications for decision making about adjuvant endocrine therapy in premenopausal women treated with chemotherapy. PMID:24319018

  13. Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions.

    PubMed

    Davidson, Ben; Stavnes, Helene Tuft; Holth, Arild; Chen, Xu; Yang, Yanqin; Shih, Ie-Ming; Wang, Tian-Li

    2011-03-01

    Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities.With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies,as well as to define tumour-specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef-8 BeadChip from Illumina.Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5-fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3,PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real-time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery.

  14. Genetic and molecular changes in ovarian cancer

    PubMed Central

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

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

  15. Improved selection of cortical ovarian strips for autotransplantation of ovarian tissue using full-field optical coherence tomography (FFOCT)

    NASA Astrophysics Data System (ADS)

    Stegehuis, Paulien L.; Peters, Inge T. A.; Eggermont, Jeroen; Kuppen, Peter J. K.; Trimbos, J. Baptist; Lelieveldt, Boudewijn P. F.; van de Velde, Cornelis J. H.; Bosse, Tjalling; Dijkstra, Jouke; Vahrmeijer, Alexander L.

    2016-02-01

    Premature ovarian failure is a major concern in women of reproductive age who undergo gonadotoxic cancer treatment. Autotransplantation of frozen-thawed cortical ovarian tissue allows the immediate start of cancer treatment, but risks reintroduction of cancer. Current tumor detection methods compromise the ovarian tissue's viability and can therefore only be used to exclude the presence of metastases in the cortical ovarian strips that are not transplanted. A non-invasive method is needed that can be used to exclude metastases in the actual ovarian autografts without affecting the tissue's viability. In this study we applied FFOCT - a non-fixative technique that uses white light interferometry to make highresolution images (1μm isotropic) of fresh tissue - to study healthy and malignant ovarian tissue. We created an image atlas of healthy ovarian tissues from premenopausal patients and ovarian tissues with breast cancer metastases. To get the best possible match between hematoxylin-and-eosin stained slides and FFOCT images formalinfixed paraffin-embedded tissue samples were deparaffinized and FFOCT images were acquired within a few minutes. FFOCT images were compared with histology images. All normal structures such as follicles in all phases, inclusion cysts, blood vessels, corpora lutea, and corpora albicantia were clearly recognizable. Ovarian metastases could be well distinguished from normal ovarian tissue. FFOCT is a promising technique in the field of fertility preservation: metastases can be detected and additionally cortical ovarian strips can be selected on the basis of high follicle density.

  16. [HE4, a novel marker for epithelial ovarian cancer: evaluation of analytical performances].

    PubMed

    Lamy, Pierre-Jean; Roques, Sylvie; Viglianti, Cathy; Fabbro, Michel; Montels, Frédéric

    2010-01-01

    Human epididymis protein 4 (HE4) is a novel marker for ovarian cancer. HE4 exhibits a high sensitivity to detect ovarian cancer and can be used with CA125 as a predictor of malignancy. Additional uses of HE4 are as an aid of monitoring response to therapy for patients with invasive ovarian cancer and as a marker to detect recurrences in the follow-up after treatment of the primary tumor. The HE4 EIA, an enzyme immunoassay for the quantitative determination of HE4 in human serum developed by Fujirebio Diagnostic Inc. (Tokyo, Japan), is now available with a CE-IVD label in Europe (Diasource, Nivelles, Belgium). The aim of the study was to evaluate according to the COFRAC LAB GTA 04 guide, the analytical performance of the test, using 4 standardized samples (target values: 49.8, 140.4, 167.6 and 415.2 pmol/L) and serum samples from patients with ovarian cancer treated in our institution. Intra- and inter-assay precisions showed coefficients of variation less than 10%. The low limit of detection (4 pmol/L) and the limit of quantitation (8 pmol/L) are suitable for clinical samples assessment. The assay mean dilution linearity is 100 +/- 10% (90 to 107% of recovery). Globally, the uncertainty varied from 13.1% (low values) to 28.1% (elevated values). We conclude that the HE4 EIA from Fujirebio Diagnostic Inc. displayed convenient analytical performances that allows its use it clinical practice.

  17. The use of HE4, CA125 and CA72-4 biomarkers for differential diagnosis between ovarian endometrioma and epithelial ovarian cancer

    PubMed Central

    2013-01-01

    Background Endometriosis is frequently associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ovarian malignancy. The aim of this study was to establish a panel of complementary biomarkers that could be helpful in the differential diagnosis between ovarian endometriosis or other ovarian benign masses and ovarian cancer. Methods Blood samples from 50 healthy women, 17 patients with benign ovarian tumors, 57 patients with ovarian endometrioma and 39 patients with ovarian cancer were analyzed and serum values were measured for the following biomarkers: CA125, HE4 and CA72-4. Results Serum CA125 concentration was elevated in both patients with ovarian endometriosis and ovarian cancer but not in patients with other benign ovarian masses. HE4 was never increased in patients with endometriosis or benign masses whereas it was significantly higher in all patients with ovarian cancer (p < 0.05). A marked difference in CA72-4 values was observed between women with ovarian cancer (67%) and those with endometriosis (p < 0.05). Conclusions The results of the study suggest that HE4 and CA72-4 determination is the best approach to confirm the benign nature of ovarian endometrioma in women with high CA125 levels. PMID:23816286

  18. Detection of Primary Malignancy and Metastases with FDG PET/CT in Patients with Cholangiocarcinomas: Lesion-based Comparison with Contrast Enhanced CT

    PubMed Central

    Elias, Youssef; Mariano, Aladin T.; Lu, Yang

    2016-01-01

    The current National Comprehensive Cancer Network (NCCN) Guidelines consider the role of 2-deoxy-2-18F-fluoro-d-glucose positron emission tomography/computer tomography (FDG PET/CT) in the evaluation of cholangiocarcinoma (CCA) as "uncertain," and have recommended contrast enhanced computed tomography (CECT) but not FDG PET/CT as a routine imaging test for CCA workup. We set out to compare the diagnostic performance of FDG PET/CT and CECT in patients with CCA. The retrospective study included patients with CCA who underwent FDG PET/CT and CECT within 2-month interval between 2011 and 2013 in our hospital. Lesion-based comparison was conducted. Final diagnoses were made based on the composite clinical and imaging data with minimal 6-month follow-up. A total of 18 patients with 28-paired tests were included. There is a total of 142 true malignant lesions as revealed by the 6-paired pre-treatment and 22-paired post-treatment tests. On a lesion-based analysis, the sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and accuracies of PET/CT and CECT for detection of CCA were 96.5%, 55.5%, 97.2%, 50.0%, 94.1% and 62.2%, 66.7%, 96.7%, 10.0%, 62.5%, respectively. FDG PET/CT detected more intrahepatic malignant and extrahepatic metastases; and had significant higher sensitivity, NPV, and accuracy than CECT, while similar in specificity and PPV. No true positive lesion detected on CECT that was missed on PET/CT, and none of the false negative lesions on PET/CT were detected on CECT. Six patients had paired pretreatment tests, and FDG PET/CT results changed planned management in three patients. Our data suggest that FDG PET/CT detect more primary and metastatic lesions and lead to considerable changes in treatment plan in comparison with CECT. PMID:27651736

  19. Detection of Primary Malignancy and Metastases with FDG PET/CT in Patients with Cholangiocarcinomas: Lesion-based Comparison with Contrast Enhanced CT

    PubMed Central

    Elias, Youssef; Mariano, Aladin T.; Lu, Yang

    2016-01-01

    The current National Comprehensive Cancer Network (NCCN) Guidelines consider the role of 2-deoxy-2-18F-fluoro-d-glucose positron emission tomography/computer tomography (FDG PET/CT) in the evaluation of cholangiocarcinoma (CCA) as "uncertain," and have recommended contrast enhanced computed tomography (CECT) but not FDG PET/CT as a routine imaging test for CCA workup. We set out to compare the diagnostic performance of FDG PET/CT and CECT in patients with CCA. The retrospective study included patients with CCA who underwent FDG PET/CT and CECT within 2-month interval between 2011 and 2013 in our hospital. Lesion-based comparison was conducted. Final diagnoses were made based on the composite clinical and imaging data with minimal 6-month follow-up. A total of 18 patients with 28-paired tests were included. There is a total of 142 true malignant lesions as revealed by the 6-paired pre-treatment and 22-paired post-treatment tests. On a lesion-based analysis, the sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and accuracies of PET/CT and CECT for detection of CCA were 96.5%, 55.5%, 97.2%, 50.0%, 94.1% and 62.2%, 66.7%, 96.7%, 10.0%, 62.5%, respectively. FDG PET/CT detected more intrahepatic malignant and extrahepatic metastases; and had significant higher sensitivity, NPV, and accuracy than CECT, while similar in specificity and PPV. No true positive lesion detected on CECT that was missed on PET/CT, and none of the false negative lesions on PET/CT were detected on CECT. Six patients had paired pretreatment tests, and FDG PET/CT results changed planned management in three patients. Our data suggest that FDG PET/CT detect more primary and metastatic lesions and lead to considerable changes in treatment plan in comparison with CECT.

  20. Detection of Primary Malignancy and Metastases with FDG PET/CT in Patients with Cholangiocarcinomas: Lesion-based Comparison with Contrast Enhanced CT.

    PubMed

    Elias, Youssef; Mariano, Aladin T; Lu, Yang

    2016-09-01

    The current National Comprehensive Cancer Network (NCCN) Guidelines consider the role of 2-deoxy-2-(18)F-fluoro-d-glucose positron emission tomography/computer tomography (FDG PET/CT) in the evaluation of cholangiocarcinoma (CCA) as "uncertain," and have recommended contrast enhanced computed tomography (CECT) but not FDG PET/CT as a routine imaging test for CCA workup. We set out to compare the diagnostic performance of FDG PET/CT and CECT in patients with CCA. The retrospective study included patients with CCA who underwent FDG PET/CT and CECT within 2-month interval between 2011 and 2013 in our hospital. Lesion-based comparison was conducted. Final diagnoses were made based on the composite clinical and imaging data with minimal 6-month follow-up. A total of 18 patients with 28-paired tests were included. There is a total of 142 true malignant lesions as revealed by the 6-paired pre-treatment and 22-paired post-treatment tests. On a lesion-based analysis, the sensitivities, specificities, positive predictive values (PPVs), negative predictive values (NPVs), and accuracies of PET/CT and CECT for detection of CCA were 96.5%, 55.5%, 97.2%, 50.0%, 94.1% and 62.2%, 66.7%, 96.7%, 10.0%, 62.5%, respectively. FDG PET/CT detected more intrahepatic malignant and extrahepatic metastases; and had significant higher sensitivity, NPV, and accuracy than CECT, while similar in specificity and PPV. No true positive lesion detected on CECT that was missed on PET/CT, and none of the false negative lesions on PET/CT were detected on CECT. Six patients had paired pretreatment tests, and FDG PET/CT results changed planned management in three patients. Our data suggest that FDG PET/CT detect more primary and metastatic lesions and lead to considerable changes in treatment plan in comparison with CECT. PMID:27651736

  1. Ovarian Kaleidoscope database: ten years and beyond.

    PubMed

    Hsueh, Aaron J; Rauch, Rami

    2012-06-01

    Ovarian Kaleidoscope database (OKdb) is an online, searchable, public database containing text-based and DNA microarray data to facilitate research by ovarian researchers. Using key words and predetermined categories, users can search ovarian gene information based on gene function, cell type of expression, cellular localization, hormonal regulation, mutant phenotypes, chromosomal location, ligand-receptor relationship, and other criteria, either alone or in combination. For individual genes, users can access more than 10 extensive DNA microarray datasets to interrogate gene expression patterns in a development-specific and cell type-specific manner. All ligand and receptor genes expressed in the ovary are matched to facilitate investigation of paracrine/autocrine signaling. More than 3500 ovarian genes in the database are matched to 185 gene pathways in the Kyoto Encyclopedia of Genes and Genomes to allow for elucidation of gene interactions and relationships. In addition to >400 genes with infertility or subfertility phenotypes when mutated in mice or humans, the OKdb also lists ~50 and ~40 genes associated with polycystic ovarian syndrome and primary ovarian insufficiency, respectively. The expanding OKdb is updated weekly and allows submission of new genes by ovarian researchers to allow instant access to DNA microarray datasets for newly submitted genes. The present database is a virtual community for ovarian researchers and allows users to instantaneously provide their comments for individual gene pages based on an automated Web-discussion system. In the coming years, we will continue to add new features to serve the ovarian research community. PMID:22441797

  2. YY1 modulates taxane response in epithelial ovarian cancer

    SciTech Connect

    Matsumura, Noriomi; Huang, Zhiqing; Baba, Tsukasa; Lee, Paula S.; Barnett, Jason C.; Mori, Seiichi; Chang, Jeffrey T.; Kuo, Wen-Lin; Gusberg, Alison H.; Whitaker, Regina S.; Gray, JoeW.; Fujii, Shingo; Berchuck, Andrew; Murphy, Susan K.

    2008-10-10

    The results of this study show that a high YY1 gene signature (characterized by coordinate elevated expression of transcription factor YY1 and putative YY1 target genes) within serous epithelial ovarian cancers is associated with enhanced response to taxane-based chemotherapy and improved survival. If confirmed in a prospective study, these results have important implications for the potential future use of individualized therapy in treating patients with ovarian cancer. Identification of the YY1 gene signature profile within a tumor prior to initiation of chemotherapy may provide valuable information about the anticipated response of these tumors to taxane-based drugs, leading to better informed decisions regarding chemotherapeutic choice. Survival of ovarian cancer patients is largely dictated by their response to chemotherapy, which depends on underlying molecular features of the malignancy. We previously identified YIN YANG 1 (YY1) as a gene whose expression is positively correlated with ovarian cancer survival. Herein we investigated the mechanistic basis of this association. Epigenetic and genetic characteristics of YY1 in serous epithelial ovarian cancer (SEOC) were analyzed along with YY1 mRNA and protein. Patterns of gene expression in primary SEOC and in the NCI60 database were investigated using computational methods. YY1 function and modulation of chemotherapeutic response in vitro was studied using siRNA knockdown. Microarray analysis showed strong positive correlation between expression of YY1 and genes with YY1 and transcription factor E2F binding motifs in SEOC and in the NCI60 cancer cell lines. Clustering of microarray data for these genes revealed that high YY1/E2F3 activity positively correlates with survival of patients treated with the microtubule stabilizing drug paclitaxel. Increased sensitivity to taxanes, but not to DNA crosslinking platinum agents, was also characteristic of NCI60 cancer cell lines with a high YY1/E2F signature. YY1

  3. Neferine induces autophagy of human ovarian cancer cells via p38 MAPK/ JNK activation.

    PubMed

    Xu, Limei; Zhang, Xiyu; Li, Yinuo; Lu, Shuhua; Lu, Shan; Li, Jieyin; Wang, Yuqiong; Tian, Xiaoxue; Wei, Jian-Jun; Shao, Changshun; Liu, Zhaojian

    2016-07-01

    Ovarian cancer is the most lethal gynecological malignancy. Patients usually have poor prognosis because of late diagnosis, relapse, and chemoresistance. It is pressing to seek novel agent for the treatment of ovarian cancer. Neferine is a bisbenzylisoquinoline alkaloid isolated from the embryos of lotus (Nelumbo nucifera). In this study, we investigated the antitumor effect of neferine on ovarian cancer cells. We found that neferine exhibited growth-inhibitory effect on human ovarian cancer cells, whereas showing less cytotoxic to non-malignant fallopian tube epithelial cells. Furthermore, we demonstrated that neferine induced autophagy and inactivated the mTOR pathway. Finally, we found that both p38 MAPK and JNK signaling pathways were activated by neferine treatment and contributed to the induction of autophagy in ovarian cancer cells. In conclusion, our findings showed that neferine induced autophagy of human ovarian cancer cells via p38 MAPK/JNK activation. Neferine may be explored as a promising antitumoral agent in ovarian cancer. PMID:26738868

  4. Inhibition of RUNX2 Transcriptional Activity Blocks the Proliferation, Migration and Invasion of Epithelial Ovarian Carcinoma Cells

    PubMed Central

    Bachvarova, Magdalena; Gobeil, Stephane; Morin, Chantale; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Trinh, Xuan Bich; Bachvarov, Dimcho

    2013-01-01

    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. PMID:24124450

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

    PubMed

    Wang, Zhi-Qiang; Keita, Mamadou; Bachvarova, Magdalena; Gobeil, Stephane; Morin, Chantale; Plante, Marie; Gregoire, Jean; Renaud, Marie-Claude; Sebastianelli, Alexandra; Trinh, Xuan Bich; Bachvarov, Dimcho

    2013-01-01

    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.

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

    PubMed

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

    2011-03-01

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

  7. Malignant hematopoietic cell lines: in vitro models for the study of primary mediastinal B-cell lymphomas.

    PubMed

    Drexler, Hans G; Ehrentraut, Stefan; Nagel, Stefan; Eberth, Sonja; MacLeod, Roderick A F

    2015-01-01

    Primary mediastinal B-cell lymphoma (PMBL) is a highly aggressive disease with a unique set of biological, clinical, morphological, immunological and in particular genetic features that in the molecular era of defining lymphomas clearly distinguishes it as a separate entity from other diffuse large B-cell lymphomas (DLBCL). A precise molecular diagnosis of PMBL can be achieved by gene expression profiling. The signature gene expression profile of PMBL is more closely related to classic Hodgkin lymphoma (cHL) than to other DLBCL subgroups. A number of common genetic aberrations in PMBL and cHL further underscore their close relationship. To investigate the pathobiology of lymphomas in depth, many groups have turned to cell lines that are suitable models facilitating molecular studies and providing unique insights. For the purposes of the current perspective, we focus on four bona fide PMBL-derived cell lines (FARAGE, KARPAS-1106, MEDB-1, U-2940) that we identified and validated as such through hierarchical cluster analysis among a large collection of leukemia-lymphoma cell lines. These gene expression profiles showed that the four PMBL cell lines represent a distinct entity and are most similar to cHL cell lines, confirming derivation from a related cell type. A validated cell line resource for PMBL should assist those seeking druggable targets in this entity. This review aims to provide a comprehensive overview of the currently available cellular models for the study of PMBL. PMID:25480038

  8. Cytokines and Prognostic Factors in Epithelial Ovarian Cancer

    PubMed Central

    Jammal, Millena Prata; Martins-Filho, Agrimaldo; Silveira, Thales Parenti; Murta, Eddie Fernando Candido; Nomelini, Rosekeila Simões

    2016-01-01

    INTRODUCTION Ovarian cancer has a high mortality and delayed diagnosis. Inflammation is a risk factor for ovarian cancer, and the inflammatory response is involved in almost all stages of tumor development. Immunohistochemical staining in stroma and epithelium of a panel of cytokines in benign and malignant ovarian neoplasm was evaluated. In addition, immunostaining was related to prognostic factors in malignant tumors. METHOD The study group comprised 28 ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5, IL-6, and IL-10; and TNFR1). Chi-square test with Yates’ correction was used, which was considered significant if less than 0.05. RESULTS TNFR1, IL-5, and IL-10 had more frequent immunostaining 2/3 in benign neoplasms compared with malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2 in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of the ovarian cancer stroma showed that histological grade 3 was significantly correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more frequently. CONCLUSION IL-2 and TNFR1 stromal immunostaining are related prognostic factors in ovarian cancer and can be the target of new therapeutic strategies. PMID:27512342

  9. Immunoglobulin G4+ B‐cell receptor clones distinguish immunoglobulin G 4‐related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies

    PubMed Central

    Doorenspleet, Marieke E.; Hubers, Lowiek M.; Culver, Emma L.; Maillette de Buy Wenniger, Lucas J.; Klarenbeek, Paul L.; Chapman, Roger W.; Baas, Frank; van de Graaf, Stan F.; Verheij, Joanne; van Gulik, Thomas M.; Barnes, Eleanor; de Vries, Niek

    2016-01-01

    Immunoglobulin G4 (IgG4)‐related disease (IgG4‐RD) of the biliary tree and pancreas is difficult to distinguish from sclerosing cholangitis and biliary/pancreatic malignancies (CA). An accurate noninvasive test for diagnosis and monitoring of disease activity is lacking. We demonstrate that dominant IgG4+ B‐cell receptor (BCR) clones determined by next‐generation sequencing accurately distinguish patients with IgG4‐associated cholangitis/autoimmune pancreatitis (n = 34) from those with primary sclerosing cholangitis (n = 17) and CA (n = 17). A novel, more affordable, and widely applicable quantitative polymerase chain reaction (qPCR) protocol analyzing the IgG4/IgG RNA ratio in blood also achieves excellent diagnostic accuracy (n = 125). Moreover, this qPCR test performed better than serum IgG4 levels in sensitivity (94% vs. 86%) and specificity (99% vs. 73%) and correlates with treatment response (n = 20). Conclusions: IgG4+ BCR clones and IgG4/IgG RNA ratio markedly improve delineation, early diagnosis, and monitoring of IgG4‐RD of the biliary tree and pancreas. (Hepatology 2016;64:501‐507) PMID:27015613

  10. Panuveal malignant mesenchymoma.

    PubMed

    Pe'er, J; Neudorfer, M; Ron, N; Anteby, I; Lazar, M; Rosenmann, E

    1995-09-01

    Intraocular malignant mesenchymal tumors are very rare, and only a few case reports of such primary and metastatic tumors have been reported. We report a case of a malignant mesenchymoma involving the entire uveal tract. A 21-year-old woman presented with a tumor on the whole iris of the right eye, which caused intractable glaucoma. Upon enucleation of the eye, a very anaplastic tumor was found to occupy the whole uveal tract; its features were compatible with a tumor of mesenchymal origin, including rhabdomyosarcomatous and liposarcomatous characteristics. Choroidal osteoma was a coincidental finding. The histologic findings of the tumor were of two types of malignant mesenchymal tumors, and therefore the diagnosis of malignant mesenchymoma was made. This is to our knowledge the first tumor of its kind to be reported intraocularly. PMID:7668945

  11. Ovarian cancer stem cells enrichment.

    PubMed

    Yang, Lijuan; Lai, Dongmei

    2013-01-01

    The concept of cancer stem cells (CSCs) provides a new paradigm for understanding cancer biology. Cancer stem cells are defined as a minority of cancer cells with stem cell properties responsible for maintenance and growth of tumors. The targeting of CSCs is a potential therapeutic strategy to combat ovarian cancer. Ovarian epithelial cancer cells cultured in serum-free medium can form sphere cells. These sphere cells may be enriched for cancer stem cells (CSCs). The isolation of sphere cells from solid tumors is an important technique in studying cancer cell biology. Here we describe the isolation of sphere cells from primary ovarian cancer tissue, ascites fluid, and the cancer cell line SKOV3 with stem cell selection medium. PMID:23913228

  12. Delayed puberty in spontaneously hypertensive rats involves a primary ovarian failure independent of the hypothalamic KiSS-1/GPR54/GnRH system.

    PubMed

    Pinilla, L; Castellano, J M; Romero, M; Tena-Sempere, M; Gaytán, F; Aguilar, E

    2009-06-01

    Spontaneously hypertensive (SH) rats, extensively used as experimental models of essential human hypertension, display important alterations in the neuroendocrine reproductive axis, which manifest as markedly delayed puberty onset in females but whose basis remains largely unknown. We analyze herein in female SH rats: 1) possible alterations in the expression and function of KiSS-1/GPR54 and GnRH/GnRH-receptor systems, 2) the integrity of feedback mechanisms governing the hypothalamic-pituitary-ovarian axis, and 3) the control of ovarian function by gonadotropins. Our data demonstrate that, despite overtly delayed puberty, no significant decrease in hypothalamic KiSS-1, GPR54, or GnRH mRNA levels was detected in this strain. Likewise, in vivo gonadotropin responses to ovariectomy and systemic kisspeptin-10 or GnRH administration, as well as in vitro gonadotropin responses to GnRH, were fully preserved in SH rats. Moreover, circulating LH levels were grossly conserved during prepubertal maturation, whereas FSH levels were even enhanced from d 20 postpartum onwards. In striking contrast, ovarian weight and hormone (progesterone and testosterone) responses to human chorionic gonadotropin (CG) in vitro were profoundly decreased in SH rats, with impaired follicular development and delayed ovulation at puberty. Such reduced hormonal responses to human CG could not be attributed to changes in LH/CG or FSH-receptor mRNA expression but might be linked to blunted P450scc, 3beta-hydroxy steroid dehydrogenase, and aromatase mRNA levels in ovaries from SH rats. In conclusion, our results indicate that the expression and function of KiSS-1/GPR54 and GnRH/GnRH-receptor systems is normal in SH rats, whereas ovarian development, steroidogenesis, and responsiveness to gonadotropins are strongly compromised.

  13. Comparative diagnostic values of grey-scale USS versus CT scan in the primary management of gynaecological pelvic mass with emphasis on ovarian cancer detection and staging.

    PubMed

    Onyeka, B A; Atalla, A; Deemer, H

    2001-09-01

    Thirty-one consecutive patients with clinical pelvic masses suspected to be gynaecological in origin were initially investigated by transabdominal grey-scale ultrasound (TAUS) and then by computed tomography (CT) prior to surgery and or chemotherapy. Retrospective comparative review of the reports of the two imaging methods was carried out on each patient and then correlated with surgical findings and histopathology report. The diagnostic potentials of the two imaging methods with respect to ovarian cancer detection and staging were particularly emphasised. The results were analysed and compared with published results of similar studies in the literature. Compared with TAUS we found CT scan more sensitive in making an overall presumptive diagnosis of pelvic mass (15/31, 48% vs. 9/31, 29%). The sensitivity of CT scan for all ovarian cancer detection was greater than that of TAUS (5/6, 83% vs. 4/6, 67%) but TAUS was more specific. The false negative and false positive values for cancer detection were comparable. Both methods were equally efficacious in detecting and staging advanced ovarian cancer cases (4/4, 100%). Visualisation of the ovaries occurred more readily with TAUS, which in addition offered a more precise assessment of ovarian tumour size. There were no significant differences in the two methods regarding tumour localisation (organ of origin), characterisation and the details of descriptive report when no presumptive diagnosis is offered. Overall CT did not offer significant additional features and did not result in changes in management plan in any of the patients reviewed. The marginal benefit of CT scan over TAUS will not warrant its routine usage in the diagnosis of gynaecological pelvic mass. Our findings largely reflected the conclusions of published reports in the literature. PMID:12521811

  14. Primary peritoneal carcinoma metastasizing to breast: a single case report and literature review from clinic to biology

    PubMed Central

    Sun, Ji-Yuan; Gebre, Wondwossen; Dong, Yi-Min; Shaun, Xiao; Robbins, Rachel; Podrumar, Alida

    2016-01-01

    Primary peritoneal carcinoma (PPC) is a type of rare malignant epithelial tumor. Metastasis from PPC to breast has been rarely reported. PPC originates de novo from the peritoneal tissues rather than invasion or metastasis from adjacent or remote organs. PPCs have been implicated in many cases of carcinomas of unknown primary origin. It is similar to ovarian cancer (OvCa), because it shares the same common embryonic origin, the coelomic epithelium (mesodermal origin). The mechanism of oncogenesis remains elusive. In this article, we report a rare case of PPC in a patient 10 years after total abdominal hysterectomy and bilateral salpingooophorectomy for uterine leiomyoma, which was widely spread in the abdomen and metastasized to the colon, liver and distant organs including breast. The treatment is similar to that of primary ovarian cancer. We also reviewed the primary peritoneal cancer metastatic to breast and discuss the possible mechanisms and biology of primary peritoneal cancer, using experimental and animal model. PMID:27807506

  15. Ovarian tissue characterization using bulk optical properties

    NASA Astrophysics Data System (ADS)

    Tavakoli, B.; Xu, Y.; Zhu, Q.

    2013-03-01

    Ovarian cancer, the deadliest of all gynecologic cancers, is not often found in its early stages due to few symptoms and no reliable screening test. Optical imaging has a great potential to improve the ovarian cancer detection and diagnosis. In this study we have characterized the bulk optical properties of 26 ex-vivo human ovaries using a Diffuse Optical Tomography system. The quantitative values indicated that, in the postmenopausal group, malignant ovaries showed significantly lower scattering coefficient than normal ones. The scattering parameter is largely related to the collagen content that has shown a strong correlation with the cancer development.

  16. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial

    PubMed Central

    Jacobs, Ian J; Menon, Usha; Ryan, Andy; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Kalsi, Jatinderpal K; Amso, Nazar N; Apostolidou, Sophia; Benjamin, Elizabeth; Cruickshank, Derek; Crump, Danielle N; Davies, Susan K; Dawnay, Anne; Dobbs, Stephen; Fletcher, Gwendolen; Ford, Jeremy; Godfrey, Keith; Gunu, Richard; Habib, Mariam; Hallett, Rachel; Herod, Jonathan; Jenkins, Howard; Karpinskyj, Chloe; Leeson, Simon; Lewis, Sara J; Liston, William R; Lopes, Alberto; Mould, Tim; Murdoch, John; Oram, David; Rabideau, Dustin J; Reynolds, Karina; Scott, Ian; Seif, Mourad W; Sharma, Aarti; Singh, Naveena; Taylor, Julie; Warburton, Fiona; Widschwendter, Martin; Williamson, Karin; Woolas, Robert; Fallowfield, Lesley; McGuire, Alistair J; Campbell, Stuart; Parmar, Mahesh; Skates, Steven J

    2016-01-01

    Summary Background Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. Methods In this randomised controlled trial, we recruited postmenopausal women aged 50–74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. Findings Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202 638 women: 50 640 (25·0%) to MMS, 50 639 (25·0%) to USS, and 101 359 (50·0%) to no screening. 202 546 (>99·9%) women were eligible for analysis: 50 624 (>99·9%) women in the MMS group, 50 623 (>99·9%) in the USS group, and 101 299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345 570 MMS and 327 775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0–12·0), we diagnosed ovarian cancer in

  17. EGFR/HER-targeted therapeutics in ovarian cancer.

    PubMed

    Wilken, Jason A; Badri, Tayf; Cross, Sarah; Raji, Rhoda; Santin, Alessandro D; Schwartz, Peter; Branscum, Adam J; Baron, Andre T; Sakhitab, Adam I; Maihle, Nita J

    2012-03-01

    Despite decades of research and evolving treatment modalities, survival among patients with epithelial ovarian cancer has improved only incrementally. During this same period, the development of biologically targeted therapeutics has improved survival for patients with diverse malignancies. Many of these new drugs target the human epidermal growth factor receptor (EGFR/HER/ErbB) family of tyrosine kinases, which play a major role in the etiology and progression of many carcinomas, including epithelial ovarian cancer. While several HER-targeted therapeutics are US FDA approved for the treatment of various malignancies, none have gained approval for the treatment of ovarian cancer. Here, we review the published literature on HER-targeted therapeutics for the treatment of ovarian cancer, including novel HER-targeted therapeutics in various stages of clinical development, as well as the challenges that have limited the use of these inhibitors in clinical settings.

  18. EGFR/HER-targeted therapeutics in ovarian cancer

    PubMed Central

    Wilken, Jason A; Badri, Tayf; Cross, Sarah; Raji, Rhoda; Santin, Alessandro D; Schwartz, Peter; Branscum, Adam J; Baron, Andre T; Sakhitab, Adam I; Maihle, Nita J

    2013-01-01

    Despite decades of research and evolving treatment modalities, survival among patients with epithelial ovarian cancer has improved only incrementally. During this same period, the development of biologically targeted therapeutics has improved survival for patients with diverse malignancies. Many of these new drugs target the human epidermal growth factor receptor (EGFR/HER/ErbB) family of tyrosine kinases, which play a major role in the etiology and progression of many carcinomas, including epithelial ovarian cancer. While several HER-targeted therapeutics are US FDA approved for the treatment of various malignancies, none have gained approval for the treatment of ovarian cancer. Here, we review the published literature on HER-targeted therapeutics for the treatment of ovarian cancer, including novel HER-targeted therapeutics in various stages of clinical development, as well as the challenges that have limited the use of these inhibitors in clinical settings. PMID:22416774

  19. Environmentally induced epigenetic transgenerational inheritance of ovarian disease.

    PubMed

    Nilsson, Eric; Larsen, Ginger; Manikkam, Mohan; Guerrero-Bosagna, Carlos; Savenkova, Marina I; Skinner, Michael K

    2012-01-01

    The actions of environmental toxicants and relevant mixtures in promoting the epigenetic transgenerational inheritance of ovarian disease was investigated with the use of a fungicide, a pesticide mixture, a plastic mixture, dioxin and a hydrocarbon mixture. After transient exposure of an F0 gestating female rat during embryonic gonadal sex determination, the F1 and F3 generation progeny adult onset ovarian disease was assessed. Transgenerational disease phenotypes observed included an increase in cysts resembling human polycystic ovarian disease (PCO) and a decrease in the ovarian primordial follicle pool size resembling primary ovarian insufficiency (POI). The F3 generation granulosa cells were isolated and found to have a transgenerational effect on the transcriptome and epigenome (differential DNA methylation). Epigenetic biomarkers for environmental exposure and associated gene networks were identified. Epigenetic transgenerational inheritance of ovarian disease states was induced by all the different classes of environmental compounds, suggesting a role of environmental epigenetics in ovarian disease etiology.

  20. "Malignant Cutaneous Ulcer".

    PubMed

    Sundriyal, Deepak; Kotwal, Sumedha

    2016-09-01

    Renal cell carcinoma (RCC) is an aggressive malignancy and the rich vascular supply enables it to metastasize early via haematogenous route. Skin lesions are a late manifestation of the disease. Clinicians should be aware of cutaneous presentation of RCC while evaluating a case of unknown primary with skin lesions. PMID:27651705

  1. Potential tumor biomarkers identified in ovarian cyst fluid by quantitative proteomic analysis, iTRAQ

    PubMed Central

    2013-01-01

    Background Epithelial-derived ovarian adenocarcinoma (EOC) is the most deadly gynecologic tumor, and the principle cause of the poor survival rate is diagnosis at a late stage. Screening and diagnostic biomarkers with acceptable specificity and sensitivity are lacking. Ovarian cyst fluid should harbor early ovarian cancer biomarkers because of its closeness to the tumor. We investigated ovarian cyst fluid as a source for discovering biomarkers for use in the diagnosis of EOC. Results Using quantitative mass spectrometry, iTRAQ MS, we identified 837 proteins in cyst fluid from benign, EOC stage I, and EOC stage III. Only patients of serous histology were included in the study. Comparing the benign (n = 5) with the malignant (n = 10) group, 87 of the proteins were significantly (p < 0.05) differentially expressed. Two proteins, serum amyloid A-4 (SAA4) and astacin-like metalloendopeptidase (ASTL), were selected for verification of the iTRAQ method and external validation with immunoblot in a larger cohort with mixed histology, in plasma (n = 68), and cyst fluid (n = 68). The protein selections were based on either high significance and high fold change or abundant appearance and several peptide recognitions in the sample sets (p = 0.04, FC = 1.95) and (p < 0.001, FC = 8.48) for SAA4 and ASTL respectively. Both were found to be significantly expressed (p < 0.05), but the methods did not correlate concerning ASTL. Conclusions Fluid from ovarian cysts connected directly to the primary tumor harbor many possible new tumor-specific biomarkers. We have identified 87 differentially expressed proteins and validated two candidates to verify the iTRAQ method. However several of the proteins are of interest for validation in a larger setting. PMID:23557354

  2. Localisation and expression of aquaporin subtypes in epithelial ovarian tumours.

    PubMed

    Yang, Jian-Hua; Yu, Yu-Qun; Yan, Chun-xiao

    2011-09-01

    To characterise AQP subtype localisation and expression in epithelial ovarian tumours, immunohistochemistry was used to assess the localisation and expression of AQP1-9 in 30 benign tumour cases, 30 borderline tumour cases, 50 malignant tumour cases and 20 normal ovarian tissue cases. Multiple AQP subtypes were expressed in epithelial ovarian tumours, with each AQP subtype displaying a different pattern of localisation and expression. AQP1 was mainly expressed in the microvascular endothelium, and AQP 2-9 were mainly expressed in tumour cells. Most AQP subtypes co-localised in the basolateral membranes of the epithelia of benign tumours and plasma membranes of malignant tumour cells. The positive rates for AQP1, 5, 6, 7, 8, and 9 were over 50%, but those for AQP2, 3 and 4 were only 10-40%. The expression of AQP1, 5 and 9 in malignant and borderline tumours was significantly higher than that in benign tumours (P<0.05) and normal ovarian tissue (P<0.05). However, AQP6 expression in ovarian malignant and borderline tumours was significantly lower than that in benign tumours (P<0.01) or normal ovarian tissue (P<0.01). AQP1 expression was increased in cases with ascites volumes greater than 1000 mL (P<0.05), AQP5 expression was greater in cases with lymph node metastasis (P<0.05), and more AQP9 expression was observed in G3 cases versus G1 and G2 cases (P<0.01). These results suggest that changes in the distribution and expression of AQP subtypes may be involved in ovarian carcinogenesis. This study presents a novel avenue of research that could illuminate the mechanism of ovarian carcinogenesis and treatment.

  3. Pathogenesis of ovarian cancer: clues from selected overexpressed genes

    PubMed Central

    Shih, Ie-Ming; Davidson, Ben

    2010-01-01

    Ovarian cancer is the most malignant gynecologic neoplasm. Although new chemotherapeutic agents have improved patients' 5-year survival rate, the overall mortality of ovarian cancer has remained largely unchanged in the past several decades. The main reason for the lack of success in effectively treating ovarian cancer is our limited understanding of its etiology and the very few molecular diagnostic markers and therapeutic targets known so far. Identification and characterization of ovarian cancer-associated genes are fundamental for unveiling the pathogenesis of its initiation and progression, especially the development of recurrent diseases. As there are a vast number of genes for which molecular genetic changes and aberrant gene expression have been reported in ovarian cancer, this review will only focus on summarizing those exemplified genes that have been demonstrated to have biological functions in promoting ovarian cancer development and potential clinical significance. The genes to be discussed include nuclear proteins (Notch3, HBXAP [Rsf-1], NAC1 and NFκB), cytoplasmic proteins (fatty acid synthase and apolipoprotein E) and cell surface/secretory proteins (mucin-4, mesothelin, claudin, HLA-G, kallikrein and folate receptor and osteopontin). Since the study of ovarian cancer-associated genes is complicated by several factors unique to ovarian cancer, we will also present our views on the limitations and challenges of current ovarian cancer research. PMID:20001801

  4. [Dualistic classification of epithelial ovarian cancer: Is it clinically relevant?].

    PubMed

    Devouassoux-Shisheboran, Mojgan; Genestie, Catherine; Ray-Coquard, Isabelle

    2016-03-01

    Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and the most lethal gynecological malignancies. Based on their heterogeneous morphology, a dualistic model of carcinogenesis was proposed in 2004. Type I carcinomas, composed of low grade serous, endometrioid, mucinous, clear cell carcinomas and malignant Brenner tumors, were distinct from type II carcinomas (high grade serous, undifferentiated carcinomas and carcinosarcomas). However, clinical studies failed to demonstrate the prognostic value of such a classification. The main reproach to this dualistic model was that it lumped together in type I tumors, heterogeneous lesions such as clear cell and mucinous carcinomas. Recent advances on molecular genetic alterations and precursor lesions favor the classification of ovarian carcinomas as five distinct diseases. The dualistic model of carcinogenesis in type I and II can finally be applied only to serous ovarian carcinomas (low grade and high grade).

  5. Genomic and Molecular Characterization of Malignant Peripheral Nerve Sheath Tumor Identifies the IGF1R Pathway as a Primary Target for Treatment

    PubMed Central

    Yang, Jilong; Ylipää, Antti; Sun, Yan; Zheng, Hong; Chen, Kexin; Nykter, Matti; Trent, Jonathan; Ratner, Nancy; Lev, Dina C.; Zhang, Wei

    2011-01-01

    Purpose Malignant peripheral nerve sheath tumor (MPNST) is a rare sarcoma that lacks effective therapeutic strategies. We gain insight into the most recurrent genetically altered pathways with the purpose of scanning possible therapeutic targets. Experimental design We performed a microarray based-comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center and 26 patients from Tianjin Cancer Hospital. IHC and cell biology detection and validation were performed on human MPNST tissues and cell lines. Results Genomic characterization of 51 MPNST tissue samples identified several frequently amplified regions harboring 2,599 genes and regions of deletion including 4,901 genes. At the pathway level, we identified a significant enrichment of copy number–altering events in the insulin-like growth factor 1 receptor (IGF1R) pathway, including frequent amplifications of the IGF1R gene itself. To validate the IGF1R pathway as a potential target in MPNSTs, we first confirmed that high IGF1R protein correlated with worse tumor-free survival in an independent set of samples using immunohistochemistry. Two MPNST cell lines (ST88-14 and STS26T) were used to determine the effect of attenuating IGF1R. Inhibition of IGF1R in ST88-14 cells using small interfering RNAs or an IGF1R inhibitor, MK-0646, led to significant decreases in cell proliferation, invasion, and migration accompanied by attenuation of the PI3K/AKT and MAPK pathways. Conclusion These integrated genomic and molecular studies provide evidence that the IGF1R pathway is a potential therapeutic target for patients with MPNST. PMID:22042973

  6. Oncolytic reovirus against ovarian and colon cancer.

    PubMed

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

    2002-03-15

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

  7. [Bone marrow involvement in ovarian cancer determined by immunohistochemical methods].

    PubMed

    Gabriel, M; Obrebowska, A; Spaczyński, M

    2000-01-01

    Atypical epithelial cells in the bone marrow of patients with ovarian cancer were evaluated using immunohistochemical techniques. We investigated cytospin preparations of bone marrow taken from 9 women with benign ovarian tumors and 59 women with malignant ovarian tumors. Two monoclonal antibodies (NCL-C11 and NCL-CA 125) were used. With both antibodies we were able to detect keratin and CA 125 antigen expression in the bone marrow of 9 (18.4%) of the patients with ovarian cancer. With regard to the wide histological differentiation of ovarian carcinomas, the presence of atypical epithelial cells in the bone marrow was required as a prognostic factor for survival and relapses. This should be investigated in a larger study group. PMID:11326158

  8. An Introduction to The Royan Human Ovarian Tissue Bank.

    PubMed

    Abtahi, Naeimeh Sadat; Ebrahimi, Bita; Fathi, Rouhollah; Khodaverdi, Sepideh; Mehdizadeh Kashi, Abolfazl; Valojerdi, Mojtaba Rezazadeh

    2016-01-01

    From December 2000 until 2010, the researchers at Royan Institute conducted a wide range of investigations on ovarian tissue cryopreservation with the intent to provide fertility pres- ervation to cancer patients that were considered to be candidates for these services. In 2010, Royan Institute established the Royan Human Ovarian Tissue Bank as a subgroup of the Embryology Department. Since its inception, approximately 180 patients between the ages of 747 years have undergone consultations. Ovarian samples were cryopreserved from 47 patients (age: 7-35 years) diagnosed with cervical adenocarcinoma (n=9); breast carcinoma (n=7), Ewing's sarcoma (n=7), opposite side ovarian tumor (n=7), endometrial adenocarci- noma (n=4), malignant colon tumors (n=3), as well as Hodgkin's lymphoma, major thalas- semia and acute lymphoblastic leukemia (n=1-2 patients for each disease). Additionally, two patients requested ovarian tissue transplantation after completion of their treatments. PMID:27441061

  9. An Introduction to The Royan Human Ovarian Tissue Bank

    PubMed Central

    Abtahi, Naeimeh Sadat; Ebrahimi, Bita; Fathi, Rouhollah; Khodaverdi, Sepideh; Mehdizadeh Kashi, Abolfazl; Valojerdi, Mojtaba Rezazadeh

    2016-01-01

    From December 2000 until 2010, the researchers at Royan Institute conducted a wide range of investigations on ovarian tissue cryopreservation with the intent to provide fertility pres- ervation to cancer patients that were considered to be candidates for these services. In 2010, Royan Institute established the Royan Human Ovarian Tissue Bank as a subgroup of the Embryology Department. Since its inception, approximately 180 patients between the ages of 747 years have undergone consultations. Ovarian samples were cryopreserved from 47 patients (age: 7-35 years) diagnosed with cervical adenocarcinoma (n=9); breast carcinoma (n=7), Ewing’s sarcoma (n=7), opposite side ovarian tumor (n=7), endometrial adenocarci- noma (n=4), malignant colon tumors (n=3), as well as Hodgkin’s lymphoma, major thalas- semia and acute lymphoblastic leukemia (n=1-2 patients for each disease). Additionally, two patients requested ovarian tissue transplantation after completion of their treatments. PMID:27441061

  10. Malignant adenolymphoma.

    PubMed

    Moosavi, H; Ryan, C; Schwartz, S; Donnelly, J A

    1980-01-01

    Adenolymphoma (Warthin's tumor) is a well studied benign tumor of the salivary gland. Malignant transformation of such a tumor is rare and not well documented in the literature. The light microscopic and ultrastructural features of an undifferentiated carcinoma arising in an adenolymphoma in the parotid gland of a middle aged male are described, and the relevant literature is reviewed. Similarities between the benign adenolymphoma and the undifferentiated malignant tumor, such as the presence of interstitial lymphoplasmacytic cell infiltrates, dark and light epithelial cells, similar cytoplasmic organelles, and nuclear morphology, suggest a malignant transformation of a previously existing benign adenolymphoma.

  11. [Active radiation telethermometry in the complex diagnosis of ovarian tumors].

    PubMed

    Hozhenko, A I; Peresun'ko, O P; Orenchuk, V S; Vysochyna, K V

    1999-07-01

    An active remote radiation thermometry was used in the diagnosis and differential diagnosis of ovarian tumours by determining the heat flow from the area of projection of the ovaries and control background. Overall fourty three patients with ovarian tumours were examined by this method. Significance of the results secured was verified during the histological technique-aided operation. The authors have come to the conclusion that remote thermometry involving loading tests is a simple supplementary method of investigation that is helpful in diagnosing of both benign and malignant ovarian tumours.

  12. Precursors and pathogenesis of ovarian carcinoma.

    PubMed

    Lim, D; Oliva, E

    2013-04-01

    The ultimate goal of defining cancer specific precursors is to facilitate early detection and intervention before the development of invasive malignancy. Unlike other malignancies involving the female genital tract such as cervical or endometrial carcinomas, precursor lesions of ovarian carcinomas have not been well characterised, resulting in a failure to develop effective screening programs. Recent clinicopathological and molecular studies have provided new insight into the origin and pathogenesis of ovarian carcinomas. It has been shown that ovarian cancer is comprised of different tumour types differing not only in morphology, but also in pathogenesis, molecular alterations and clinical progression. A dualistic model of ovarian carcinogenesis has been proposed. Type I tumours which include low grade serous, low grade endometrioid, clear cell, mucinous carcinomas and Brenner tumours, are generally indolent and tend to be g