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

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

ClinicalTrials.gov

2018-04-17

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

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

ClinicalTrials.gov

2018-01-31

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

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

ClinicalTrials.gov

2018-05-03

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

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

ClinicalTrials.gov

2017-05-02

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

Mammaglobin expression in gynecologic adenocarcinomas.

PubMed

Hagemann, Ian S; Pfeifer, John D; Cao, Dengfeng

2013-04-01

Mammaglobin (MGB) has been proposed as a sensitive and specific immunohistochemical marker for adenocarcinoma of the breast. The differential diagnosis of breast adenocarcinoma versus a gynecologic primary frequently arises. We performed a semiquantitative survey of MGB immunoreactivity in 26 benign gynecologic tissues (6 ectocervices, 9 endocervices, 11 endometria), 86 ovarian adenocarcinomas, 70 endometrial adenocarcinomas, and 10 endocervical adenocarcinomas. Among ovarian tumors, MGB was present in 40% of endometrioid carcinomas; 36%, serous carcinomas; 21%, clear cell carcinomas; and 6%, mucinous carcinomas. Among endometrial cancers, MGB reactivity was present in 57% of endometrioid carcinomas, but only 30% of serous carcinomas and 6% of clear cell carcinomas. MGB was absent in endocervical adenocarcinomas. Across all tumor types with positive staining, MGB was focal or patchy (ie, less than diffuse) in 50 of 57 cases. Using a scale of 0 to 3+, the only 3 tumors with 3+ MGB reactivity were all serous carcinomas (1 ovarian and 2 endometrial). There were no cases with diffuse 3+ MGB expression. On the other hand, diffuse 2+ MGB was seen in 4 cases: 1 endometrioid carcinoma of ovary, 1 serous carcinoma of ovary, and 2 clear cell carcinomas of ovary. In conclusion, a diagnostically significant proportion of gynecologic carcinomas are immunoreactive for MGB. Gynecologic primaries should be considered in the differential diagnosis of MGB-positive malignancies of unknown origin. Copyright © 2013 Elsevier Inc. All rights reserved.

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

ClinicalTrials.gov

2018-06-20

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

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

ClinicalTrials.gov

2017-05-03

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 Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; 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

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

2018-06-06

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

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

2018-05-25

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

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

2018-06-15

Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid 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

Trametinib in Treating Patients With Recurrent or Progressive Low-Grade Ovarian Cancer or Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-06-11

Low Grade Ovarian Serous Adenocarcinoma; Micropapillary Serous Carcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

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

ClinicalTrials.gov

2018-06-18

Deleterious BRCA1 Gene Mutation; Deleterious 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

Guanylyl Cyclase C Is a Specific Marker for Differentiating Primary and Metastatic Ovarian Mucinous Neoplasms

PubMed Central

Ciocca, Vincenzo; Bombonati, Alessandro; Palazzo, Juan P.; Schulz, Stephanie; Waldman, Scott A.

2011-01-01

Distinguishing primary ovarian mucinous neoplasms from metastatic mucinous adenocarcinomas with ovarian involvement can be difficult, especially when characteristic gross and microscopic features are not present. CK7/CK20 expression appears to be more useful for distinguishing metastatic gastrointestinal adenocarcinomas from the lower tract. The addition of CDX2 for distinguishing metastatic upper gastrointestinal tract adenocarcinomas from primary ovarian mucinous neoplasms offers little advantage over CK7/CK20 coordinate expression. Guanylyl cyclase C (GCC) is a brush border membrane receptor for the endogenous peptides guanylin and uroguanylin, and the homologous diarrheagenic bacterial heat-stable enterotoxins that is selectively expressed by epithelial cells from the duodenum to the rectum, but not by normal epithelia of the stomach or esophagus, or normal extramucosal cells in humans. We studied 50 ovarian tumors: 27 primary ovarian mucinous neoplasms (7 cystadenomas, 10 borderline tumors, and 10 cystadenocarcinomas) and 23 metastatic mucinous adenocarcinomas with ovarian involvement (13 colorectal adenocarcinomas, 4 gastric adenocarcinomas, 6 appendiceal mucinous tumors (4 adenocarcinomas, 1 with neuroendocrine features, and 2 appendiceal mucinous cystadenomas). For primary ovarian mucinous neoplasms, 25 of 27 were negative for GCC. Twelve of thirteen cases of colorectal adenocarcinoma (except for 1 neuroendocrine adenocarcinoma) were positive for GCC. Three of four appendiceal mucinous adenocarcinomas were positive for GCC in both the primary and metastatic tumors (except for 1 neuroendocrine adenocarcinoma). Two of two appendiceal mucinous cystadenomas were positive for GCC. Of four cases of gastric adenocarcinoma with ovarian involvement, only one (primary tumor) exhibited focal GCC staining. These findings suggest GCC may be a useful marker for differentiating primary and secondary ovarian mucinous neoplasms. PMID:19694825

Ovarian transitional cell carcinoma represents a poorly differentiated form of high-grade serous or endometrioid adenocarcinoma.

PubMed

Takeuchi, Tadahisa; Ohishi, Yoshihiro; Imamura, Hiroko; Aman, Murasaki; Shida, Kaai; Kobayashi, Hiroaki; Kato, Kiyoko; Oda, Yoshinao

2013-07-01

Ovarian transitional cell tumors include Brenner tumors (BTs) and transitional cell carcinoma (TCC; non-BTs) according to the most recent World Health Organization classification. However, it remains a matter of debate whether TCC represents a distinct entity or a morphologic variant of high-grade serous adenocarcinoma (HG-SC). The purpose of this study was to resolve the above question by clarifying the morphologic, immunohistochemical, and molecular features of TCC. We reviewed 488 cases of epithelial ovarian carcinomas and reclassified them on the basis of the most recent World Health Organization classification with the modifications proposed by Köbel and colleagues, and 35 cases of TCC were identified; 25 and 6 TCCs were admixed with HG-SC and endometrioid adenocarcinoma (EC), respectively, and the remaining 4 cases were pure TCC. TCC components were not observed in any clear cell carcinomas or mucinous adenocarcinomas. Only 2 cases of malignant BT were identified. In addition to TCCs, malignant BTs, and related adenocarcinomas, benign and borderline BTs were included in the following immunohistochemical and molecular analyses. Immunohistochemically, pure TCCs, TCCs admixed with HG-SC, and pure HG-SCs were characterized by frequent aberrant p53 expression (diffuse or null pattern) and WT1+/ER+/PR+/IMP2+ immunophenotype, whereas BTs, including benign, borderline, and malignant BTs, were characterized by lack of aberrant p53 expression and WT1-/ER-/PR-/IMP2- immunophenotype. In contrast to the BTs, pure ECs and TCCs admixed with EC showed an ER+/PR+ immunophenotype. Nearly all the tumors with a TP53 gene mutation by molecular analysis showed aberrant p53 staining patterns. In conclusion, TCC is not a distinct entity but a poorly differentiated form of serous or EC, as (1) most TCCs coexist with HG-SC (mostly) or EC (occasionally), and (2) the immunophenotype and molecular features are similar to those of HG-SC or EC but different from those of BTs.

Selumetinib Sulfate in Treating Woman With Recurrent Low-Grade Ovarian Cancer or Peritoneum Cancer

ClinicalTrials.gov

2018-03-30

Borderline Ovarian Epithelial Tumor; Low Grade Ovarian Serous Adenocarcinoma; Primary Peritoneal Carcinoma; Primary Peritoneal Low Grade Serous Adenocarcinoma; Recurrent Borderline Ovarian Surface Epithelial-Stromal Tumor

Intratumor Heterogeneity of ALK-Rearrangements and Homogeneity of EGFR-Mutations in Mixed Lung Adenocarcinoma

PubMed Central

Marino, Federica Zito; Liguori, Giuseppina; Aquino, Gabriella; La Mantia, Elvira; Bosari, Silvano; Ferrero, Stefano; Rosso, Lorenzo; Gaudioso, Gabriella; De Rosa, Nicla; Scrima, Marianna; Martucci, Nicola; La Rocca, Antonello; Normanno, Nicola; Morabito, Alessandro; Rocco, Gaetano; Botti, Gerardo; Franco, Renato

2015-01-01

Background Non Small Cell Lung Cancer is a highly heterogeneous tumor. Histologic intratumor heterogeneity could be ‘major’, characterized by a single tumor showing two different histologic types, and ‘minor’, due to at least 2 different growth patterns in the same tumor. Therefore, a morphological heterogeneity could reflect an intratumor molecular heterogeneity. To date, few data are reported in literature about molecular features of the mixed adenocarcinoma. The aim of our study was to assess EGFR-mutations and ALK-rearrangements in different intratumor subtypes and/or growth patterns in a series of mixed adenocarcinomas and adenosquamous carcinomas. Methods 590 Non Small Cell Lung Carcinomas tumor samples were revised in order to select mixed adenocarcinomas with available tumor components. Finally, only 105 mixed adenocarcinomas and 17 adenosquamous carcinomas were included in the study for further analyses. Two TMAs were built selecting the different intratumor histotypes. ALK-rearrangements were detected through FISH and IHC, and EGFR-mutations were detected through IHC and confirmed by RT-PCR. Results 10/122 cases were ALK-rearranged and 7 from those 10 showing an intratumor heterogeneity of the rearrangements. 12/122 cases were EGFR-mutated, uniformly expressing the EGFR-mutated protein in all histologic components. Conclusion Our data suggests that EGFR-mutations is generally homogeneously expressed. On the contrary, ALK-rearrangement showed an intratumor heterogeneity in both mixed adenocarcinomas and adenosquamous carcinomas. The intratumor heterogeneity of ALK-rearrangements could lead to a possible impact on the therapeutic responses and the disease outcomes. PMID:26422230

Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-03-05

Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

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

ClinicalTrials.gov

2018-03-22

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 AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Genome profiling of ovarian adenocarcinomas using pangenomic BACs microarray comparative genomic hybridization

PubMed Central

Caserta, Donatella; Benkhalifa, Moncef; Baldi, Marina; Fiorentino, Francesco; Qumsiyeh, Mazin; Moscarini, Massimo

2008-01-01

Background Routine cytogenetic investigations for ovarian cancers are limited by culture failure and poor growth of cancer cells compared to normal cells. Fluorescence in situ Hybridization (FISH) application or classical comparative genome hybridization techniques are also have their own limitations in detecting genome imbalance especially for small changes that are not known ahead of time and for which FISH probes could not be thus designed. Methods We applied microarray comparative genomic hybridization (A-CGH) using one mega base BAC arrays to investigate chromosomal disorders in ovarian adenocarcinoma in patients with familial history. Results Our data on 10 cases of ovarian cancer revealed losses of 6q (4 cases mainly mosaic loss), 9p (4 cases), 10q (3 cases), 21q (3 cases), 22q (4 cases) with association to a monosomy X and gains of 8q and 9q (occurring together in 8 cases) and gain of 12p. There were other abnormalities such as loss of 17p that were noted in two profiles of the studied cases. Total or mosaic segmental gain of 2p, 3q, 4q, 7q and 13q were also observed. Seven of 10 patients were investigated by FISH to control array CGH results. The FISH data showed a concordance between the 2 methods. Conclusion The data suggest that A-CGH detects unique and common abnormalities with certain exceptions such as tetraploidy and balanced translocation, which may lead to understanding progression of genetic changes as well as aid in early diagnosis and have an impact on therapy and prognosis. PMID:18492273

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

ClinicalTrials.gov

2018-02-05

Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma

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

ClinicalTrials.gov

2018-02-14

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Serous Neoplasm; High Grade Ovarian Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage III Fallopian Tube Cancer AJCC v7; Stage III Ovarian Cancer AJCC v6 and v7; Stage III Primary Peritoneal Cancer AJCC v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

[Analysis of familial aggregation of ovarian and breast cancer in patients with ovarian cancer].

PubMed

Ichikawa, Y; Nishida, M; Sugita, M; Arisawa, Y; Satoh, T; Oki, A; Kohno, K; Shigemitsu, S; Tsunoda, H; Kubo, T

1995-09-01

In 118 patients with common epithelial ovarian tumors (carcinomas and tumors of borderline malignancy) treated at Tsukuba University Hospital and Tsukuba-Gakuen Hospital, family histories of ovarian and breast cancer were obtained from medical records or in interviews, and familial aggregation of these cancers was examined. 1. A positive family history was found in 10 patients (8.5%). The high incidences of familial ovarian cancer and ovarian cancer in patients who were previously affected with breast cancer were statistically significant. 2. Patients with serous adenocarcinoma showed a significantly greater rate of positive family history than those with mucinous adenocarcinoma. 3. No significant correlation was seen between the clinical stage and a positive family history. 4. Every patient except one with a positive family history had onset of ovarian cancer after menopause. The age at onset for familial ovarian cancer cases was younger than that for the patients' relatives who were affected previously. 5. There were 14 healthy women considered to be at high risk for ovarian cancer among 5 familial ovarian and 2 familial ovarian and breast cancer aggregations. These preliminary findings suggest that screening for early ovarian cancer should be conducted in high risk relatives of familial cancer patients and women affected with breast cancer previously. More detailed studies are needed to define the occurrence of familial or hereditary ovarian and breast cancers in Japan.

Mangiferin induces apoptosis in human ovarian adenocarcinoma OVCAR3 cells via the regulation of Notch3

PubMed Central

Zou, Bingyu; Wang, Hailian; Liu, Yilong; Qi, Ping; Lei, Tiantian; Sun, Minghan; Wang, Yi

2017-01-01

Ovarian cancer is the most lethal gynecological malignancy in the world. Our previous studies showed that mangiferin, purified from plant source, possessed anti-neoplasm effect on human lung adenocarcinoma A549 cells. This study aimed to determine the apoptosis-inducing effect of mangiferin on human ovarian carcinoma OVCAR3 cells. By in vitro studies, we found mangiferin significantly inhibited viability of OVCAR3 cells, and remarkably increased the sensitivity of OVCAR3 cells to cisplatin. In addition, the activation of caspase-dependent apoptosis was observed in mangiferin treated ovarian cancer cells. Importantly, we observed an obviously downregulated Notch expression after mangiferin treatment, indicating the crucial role of Notch in mangiferin mediated apoptosis. In contrast, overexpression of Notch3 abrogated the apoptosis-inducing efficacy of mangiferin, further demonstrating that mangiferin induced apoptosis via Notch pathway. Furthermore, OVCAR3 cell xenograft models revealed that mangiferin treatment inhibited tumor growth and expanded survival of tumor xenograft mice. Based on these results, we concluded that mangiferin could significantly inhibit the proliferation and induce apoptosis in OVCAR3 cells. Our study also suggested the anti-neoplasm effect of mangiferin might be via the regulation of Notch3. Taken together, by targeting cell apoptosis pathways and enhancing the response to cisplatin treatment, mangiferin may represent a potential new drug for the treatment of human ovarian cancer. PMID:28714011

Mangiferin induces apoptosis in human ovarian adenocarcinoma OVCAR3 cells via the regulation of Notch3.

PubMed

Zou, Bingyu; Wang, Hailian; Liu, Yilong; Qi, Ping; Lei, Tiantian; Sun, Minghan; Wang, Yi

2017-09-01

Ovarian cancer is the most lethal gynecological malignancy in the world. Our previous studies showed that mangiferin, purified from plant source, possessed anti-neoplasm effect on human lung adenocarcinoma A549 cells. This study aimed to determine the apoptosis-inducing effect of mangiferin on human ovarian carcinoma OVCAR3 cells. By in vitro studies, we found mangiferin significantly inhibited viability of OVCAR3 cells, and remarkably increased the sensitivity of OVCAR3 cells to cisplatin. In addition, the activation of caspase-dependent apoptosis was observed in mangiferin treated ovarian cancer cells. Importantly, we observed an obviously downregulated Notch expression after mangiferin treatment, indicating the crucial role of Notch in mangiferin mediated apoptosis. In contrast, overexpression of Notch3 abrogated the apoptosis-inducing efficacy of mangiferin, further demonstrating that mangiferin induced apoptosis via Notch pathway. Furthermore, OVCAR3 cell xenograft models revealed that mangiferin treatment inhibited tumor growth and expanded survival of tumor xenograft mice. Based on these results, we concluded that mangiferin could significantly inhibit the proliferation and induce apoptosis in OVCAR3 cells. Our study also suggested the anti-neoplasm effect of mangiferin might be via the regulation of Notch3. Taken together, by targeting cell apoptosis pathways and enhancing the response to cisplatin treatment, mangiferin may represent a potential new drug for the treatment of human ovarian cancer.

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

ClinicalTrials.gov

2018-06-04

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

Birinapant and Carboplatin in Treating Patients With Recurrent High Grade Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-04-26

High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Primary Peritoneal High Grade Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma

The Safety of Ovarian Preservation in Stage I Endometrial Endometrioid Adenocarcinoma Based on Propensity Score Matching.

PubMed

Hou, Ting; Sun, Yidi; Li, Junyi; Liu, Chenglin; Wang, Zhen; Li, Yixue; Lu, Yuan

2017-01-01

Most patients with early stage endometrial endometrioid adenocarcinoma (EEAC) are treated with hysterectomy and bilateral oophorectomy. But this surgical menopause leads to long-term sequelae for premenopausal women, especially for young women of childbearing age. This population-based study was to evaluate the safety of ovarian preservation in young women with stage I EEAC. Patients of age 50 or younger with stage I EEAC were explored from the Surveillance, Epidemiology and End Results program database during 2004 to 2013. Propensity score matching was used to randomize the data set and reduce the selection biases of doctors. Univariate analysis and multivariate cox proportional hazards model were utilized to estimate the safety of ovarian preservation. A total of 7183 patients were identified, and ovarian preservation was performed in 863 (12 %) patients. Compared with women treated with oophorectomy, patients with ovarian preservation significantly tend to be younger at diagnosis (P-value < 0.001) and more likely diagnosed as stage IA EEAC, to have better differentiated tumor tissues and smaller tumors, as well as less likely to undergo radiation and lymphadenectomy. 863 patients treated with oophorectomy were selected by propensity score matching. After propensity score matching, the differences of all characteristics between ovarian preservation and oophorectomy were not significant and potential confounders in the two groups decreased. In univariate analysis of matched population, ovarian preservation had no effect on overall (P-value=0.928) and cancer-specific (P-value=0.390) mortality. In propensityadjusted multivariate analysis, ovarian preservation was not significantly associated with overall (HR=0.69, 95%CI=0.41-1.68, P-value=0.611) and cancer-specific (HR=1.65, 95%CI=0.54-5.06, Pvalue= 0.379) survival. Ovarian preservation is safe for young women with stage I EEAC, which is not significantly associated with overall and cancer-specific mortality

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

ClinicalTrials.gov

2017-10-12

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

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

2018-02-14

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; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Tazemetostat in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Endometrial Cancer

ClinicalTrials.gov

2018-03-02

Grade 1 Endometrial Endometrioid Adenocarcinoma; Grade 2 Endometrial Endometrioid Adenocarcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

Recent advances in immunohistochemistry in the diagnosis of ovarian neoplasms

PubMed Central

McCluggage, W

2000-01-01

This leader reviews recent advances in immunohistochemistry that are useful in the diagnosis of ovarian neoplasms. These include the value of different anticytokeratin antibodies in the distinction between a primary ovarian adenocarcinoma and a metastatic adenocarcinoma, especially of colorectal origin. These antibodies have also helped to clarify the origin of the peritoneal disease in most cases of pseudomyxoma peritonei. The value of antibodies against so called tumour specific antigens, such as CA125 and HAM56, in determining the ovarian origin of an adenocarcinoma is also reviewed. In recent years, several studies have investigated the value of a variety of monoclonal antibodies in the diagnosis of ovarian sex cord stromal tumours and in the distinction between these neoplasms and their histological mimics. These antibodies include those directed against inhibin, CD99, Mullerian inhibiting substance, relaxin like factor, melan A, and calretinin. Of these, anti-α inhibin appears to be of most diagnostic value. It is stressed that these antibodies should always be used as part of a larger panel and not in isolation.J Clin Pathol(J Clin Pathol 2000;53:327–334) Key Words: ovarian neoplasms • diagnosis • immunohistochemistry PMID:10889812

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

2018-06-11

BRCA Rearrangement; Deleterious BRCA1 Gene Mutation; Deleterious BRCA2 Gene Mutation; 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

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

ClinicalTrials.gov

2018-04-27

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

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

ClinicalTrials.gov

2017-07-10

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

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

ClinicalTrials.gov

2017-07-24

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

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

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

ClinicalTrials.gov

2017-05-04

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

Risk of metachronous ovarian cancer after ovarian conservation in young women with stage I cervical cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Horowitz, Max P; Shahzad, Mian M K; Guntupalli, Saketh R; Roman, Lynda D; Wright, Jason D

2017-11-01

While there is an increasing trend of ovarian conservation at the time of surgical treatment for young women with stage I cervical cancer, the risk for subsequent ovarian cancer after ovarian conservation has not been well studied. We sought to examine the incidence of and risk factors for metachronous ovarian cancer among young women with stage I cervical cancer who had ovarian conservation at the time of hysterectomy. The Surveillance, Epidemiology, and End Results Program was used to identify women aged <50 years who underwent hysterectomy with ovarian conservation for stage I cervical cancer from 1983 through 2013 (n = 4365). Time-dependent analysis was performed for ovarian cancer risk after cervical cancer diagnosis. Mean age at cervical cancer diagnosis was 37 years, and the majority of patients had stage IA disease (68.2%) and squamous histology (72.9%). Median follow-up time was 10.8 years, and there were 13 women who developed metachronous ovarian cancer. The 10- and 20-year cumulative incidences of metachronous ovarian cancer were 0.2% (95% confidence interval, 0.1-0.4) and 0.5% (95% confidence interval, 0.2-0.8), respectively. Mean age at the time of diagnosis of metachronous ovarian cancer was 47.5 years, and stage III-IV disease was seen in 55.6%. Age (≥45 vs <45 years, hazard ratio, 4.22; 95% confidence interval, 1.16-15.4; P = .018), ethnicity (non-white vs white, hazard ratio, 4.29; 95% confidence interval, 1.31-14.0; P = .009), cervical cancer histology (adenocarcinoma or adenosquamous vs squamous, hazard ratio, 3.50; 95% confidence interval, 1.17-10.5; P = .028), and adjuvant radiotherapy use (yes vs no, hazard ratio, 3.69; 95% confidence interval, 1.01-13.4; P = .034) were significantly associated with metachronous ovarian cancer risk. The presence of multiple risk factors was associated with a significantly increased risk of metachronous ovarian cancer compared to the no risk factor group: 1 risk factor (hazard ratio range, 2.96-8.43), 2

OVARIAN HILUS CELLS AND ENDOMETRIAL CARCINOMA WITH REFERENCE TO RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ames, S.; Janovski, N.A.

1963-07-01

A survey of the relation of hilus cell genesis and frequency of detection in ovaries to adenocarcinoma of the endometrium is presented. Results were based on the examination of 281 ovaries obtained from patients with endometrial carcinoma. The results showed that there was no statistical difference between the occurrence of hilus cells in the endometrial carcinoma group and a control group (33 and 25% respectively). However, if mode of treatment was taken into consideration, and patients undergoing irradiation for endometrial adenocarcinoma prior to operation separated into an individual group, there was a significant difference in the distribution of hilus cellsmore » in those patients as compared with the nonirradiated carcinoma group, at the level of 5%. The radiotherapy in these cases consisisted mainly of 50100 mg intracavitary Ra for approximates 72 hr. A surprisingly high incidence (60%) of ovarian hilus cells was found in patients who underwent radioinduced menopause for benign gynecologic conditions prior to developing adenocarcinoma of the endometrium. The incidence in all postmenopausal patients was only 37%. Ovarian hilus cells were more prevalent in postmenopausal women irrespective of endometrial carcinoma. Premenopausal women with endometrial carcinoma who received no irradiation prior to definitive operation are, therefore, the ideal subjects for further investigation of the relation between endometrial adenocarcinoma and ovarian hilus cells. (BBB)« less

VSV-hIFNbeta-NIS in Treating Patients With Stage IV or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-05-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Recurrent Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Adenocarcinoma of the urinary bladder

PubMed Central

Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

2015-01-01

Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

Olaparib and Onalespib 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

2018-05-18

Estrogen Receptor Negative; HER2/Neu Negative; High Grade Fallopian Tube Serous Adenocarcinoma; High Grade Ovarian Serous Adenocarcinoma; Metastatic Malignant 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

[Clinicopathological characteristics of hereditary ovarian cancer syndrome].

PubMed

Zhong, Yan; Sheng, Xiu-gui; Ma, Zhi-fang; Ma, Yue-bing; Liu, Nai-fu; Chen, Yue-ting; Gao, Rong; Wang, Ying-ying; Sun, Li

2009-09-01

To explore the clinicopathological characteristics of hereditary ovarian cancer syndrome (HOCS). From Jan. 2000 to Jan. 2007, among 580 cases of primary ovarian cancer, 42 cases (hereditary group), who had a positive family history of ovarian cancer and met the diagnostic criteria of HOCS, were analyzed retrospectively. One hundred cases without a family history of ovarian cancer were enrolled randomizely as control group (sporadic group). The incidence of HOCS was 7.2% (42/580). Forty-two cases associated tumors affected at least 2 successive generations in 31 families and affected 1 generation in 8 families. Eighty-seven percent (27/31) was from maternal lineage, while 13% (4/31) from paternal lineage. Earlier age of onset was significantly difference between two groups [(49 +/- 10) years vs. (55 +/- 10) years, P < 0.05]. There were 90% belong to serous adenocarcinoma in the hereditary group, while 84% in the sporadic group. There was statistical difference in the proportion of mucinous adenocarcinoma (0 vs. 11%, P < 0.05). The most common clinical manifestations were abdominal distention and anorexia (64% vs. 70%, P > 0.05), International Federational of Gynecology Obstetrics (FIGO) stage III (62% vs. 63%, P > 0.05) between two groups. Fourteen cases (33%,14/42) were previously untreated in the hereditary group, while 40 cases (40%, 40/100) in the sporadic group. There were 15 cases (36%, 15/42) underwent secondary surgery and 15 cases (36%, 15/42) underwent third surgery or more in hereditary group, while 50 cases (50%,50/100) and 27 cases (27%, 27/100) in the sporadic group. The mean number of chemotherapy cycles received in two groups was 13.3 and 11.8 (P > 0.05). The 3-year and 5-year survival rate in hereditary group were 73.6% and 54.9% respectively, compared with 47.4% and 21.2% (P < 0.05) in sporadic group. Hereditary ovarian cancer mostly from maternal lineage are featuring in early age of onset, serous adenocarcinoma, advanced stage (stage III), and

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

2018-04-11

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

A rare case of recurrent ovarian cancer presenting as a round ligament metastasis.

PubMed

Togami, Shinichi; Kato, Tomoyasu; Oi, Takateru; Ishikawa, Mitsuya; Onda, Takashi; Ikeda, Shun-ichi; Kasamatsu, Takahiro

2011-11-07

We report a rare case of recurrent ovarian cancer presenting as a round ligament metastasis. A 44-year-old woman presented with a lower abdominal mass. Computed tomography showed a pelvic mass. Primary surgery was performed. A histopathological examination showed an ovarian serous adenocarcinoma of Stage IIIb. The patient received 6 cycles of paclitaxel and carboplatin. Almost 2 years after the initial operation, the patient noticed a left inguinal mass. Computed tomography showed a left inguinal mass, 18 mm in size. An excisional biopsy was performed and the tumor was found to originate in the left round ligament. A histopathological examination showed serous adenocarcinoma and there was no evidence of lymph node tissue. Recurrence of ovarian cancer in the round ligament is extremely rare. This unique case suggests, however, that the round ligament in rare cases may be a recurrence site for ovarian cancer, and that accurate differentiation including confirmation by diagnostic imaging and excisional biopsy, is necessary for a definitive pathological diagnosis.

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

PubMed

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

2015-05-01

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

Three-photon imaging of ovarian cancer

NASA Astrophysics Data System (ADS)

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

2016-02-01

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

Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry.

PubMed

Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

2013-01-01

Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma.

Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry

PubMed Central

Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

2013-01-01

Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma. PMID:24228101

Ovarian mixed germ cell tumor with yolk sac and teratomatous components in a dog.

PubMed

Robinson, Nicholas A; Manivel, J Carlos; Olson, Erik J

2013-05-01

Mixed germ cell tumors of the ovary have rarely been reported in veterinary species. A 3-year-old intact female Labrador Retriever dog was presented for lethargy, abdominal distention, and a midabdominal mass. An exploratory laparotomy revealed a large (23 cm in diameter) left ovarian tumor and multiple small (2-3 cm in diameter) pale tan masses on the peritoneum and abdominal surface of the diaphragm. Histological examination of the left ovary revealed a mixed germ cell tumor with a yolk sac component with rare Schiller-Duval bodies and a teratomatous component comprised primarily of neural differentiation. The abdominal metastases were solely comprised of the yolk sac component. The yolk sac component was diffusely immunopositive for cytokeratin with scattered cells reactive for α-fetoprotein and placental alkaline phosphatase. Within the teratomatous component, the neuropil was diffusely immunopositive for S100, neuron-specific enolase, and neurofilaments with a few glial fibrillary acidic protein immunopositive cells. Ovarian germ cell tumors may be pure and consist of only 1 germ cell element or may be mixed and include more than 1 germ cell element, such as teratoma and yolk sac tumor.

Computed tomography findings of gaseous necrosis in epithelial ovarian cancer: a report of three cases.

PubMed

Cronin, Paul; Crosse, Barbara; Lane, Geoff; Spencer, John A

2002-01-01

Necrosis in pathologic specimens of ovarian cancer is well documented; however, computed tomography (CT) evidence of gaseous necrosis in the absence of fistulation with bowel has not yet been described. We report three cases of ovarian adenocarcinoma that on CT showed evidence of gross gaseous necrosis, mimicking a pelvic abscess.

Endometrioid Adenocarcinoma of Caecum Causing Intussusception

PubMed Central

Verma, Rashmi; Osborn, Sally; Horgan, Kieran

2013-01-01

Malignant transformation of endometriosis is rare and is usually seen in ovarian endometriosis. The colon and rectum are the most common sites for extragonadal endometriosis, and although serosal involvement is commonly seen, mucosal involvement is rare. Malignant transformation of endometriosis is a rare but a well-known complication of endometriosis. We report an unusual presentation of endometrioid adenocarcinoma with lymph node metastasis, arising from endometriosis in the caecal wall and causing ileocaecal intussusception. The patient presented with sudden onset of abdominal pain with features suggestive of acute appendicitis. Diagnostic laparoscopy revealed an ileocaecal intussusception. Conversion to open surgery confirmed a caecal mass causing ileocaecal intussusception, and a radical right hemicolectomy was performed. Histology revealed endometrioid adenocarcinoma arising in a focus of endometriosis in the muscularis propria and involving the mucosa, with one regional metastatic lymph node. PMID:23710407

Brain metastasis from ovarian cancer: case report and review of the literature.

PubMed

Hu, Xi-Quan; Imitola, Jaime; Kim, Ryan Y; Mahta, Ali; Kesari, Santosh

2012-06-01

We present an 80-year-old lady with a history of ovarian cancer, who manifested with seizure and left upper extremity weakness. The imaging revealed a multilobulated mass within right parietal lobe. She underwent surgical resection and the pathology was compatible with metastasis from ovarian adenocarcinoma. She received a whole brain radiation therapy and she has been in remission for more than 2 years.

Recurrent mucinous adenocarcinoma of the ovary presenting as an inguino-labial hernia.

PubMed

Ben-Hur, H; Schachter, M; Mashiah, A; Lifschitz-Mercer, B; Pfeffermann, R

1996-01-01

We report a case of a 65-year-old woman who nine years previously had undergone total abdominal hysterectomy and bilateral salpingoophorectomy for a large ovarian cyst. During surgery the cyst had ruptured and some mucinous material had been spilled intraabdominally. Histopathological studies demonstrated the cyst to be a mucinous adenocarcinoma of low malignant potential. Appendectomy had also been performed due to an enlarged appendix, which proved to be a mucocoele. The patient had been lost to subsequent follow-up. Her current presenting symptom was a giant inguino-labial hernia of 25 cm diameter with two small skin perforations leaking a gelatinous discharge. Subsequent laparotomy and inguinal exploration have disclosed herniated small intestine with an attached metastatic multicystic mucinous adenocarcinoma. This case represents a case of borderline mucinous adeno-carcinoma-pseudomyxoma peritonei recurring in a unique pattern as a huge inguino-labial hernia, and serves to emphasize the possible consequences of spillage of ovarian cyst contents during surgery.

Malignant tumors associated with ovarian mature teratoma: A single institution experience.

PubMed

Trabzonlu, Levent; Durmaz, Guray; Vural, Cigdem; Muezzinoglu, Bahar; Corakci, Aydin

2017-05-01

The aims of this study are to present demographical features of cases diagnosed with malignant tumor associated with ovarian mature teratoma and to analyze histopathological features and clinical follow up of these tumors. Single-institution retrospective charts were reviewed to identify all cases of ovarian mature teratoma diagnosed from 1998 to 2015. Clinicopathological parameters that were analyzed include age, tumor size, tumor stage, histological type, laterality, IOC diagnosis and whether or not patient has received adjuvant chemotherapy. A total of 218 ovarian mature teratoma cases were identified during the study period. Of the 218 ovarian mature teratoma specimens, eight (3.7%) exhibited malignant tumors. The average age for cases of malignancy associated with ovarian mature teratoma was 44.6 years. The average size of tumors was 10.36cm. On final pathology, histological types of tumors were as follows: two cases each of squamous cell carcinoma and papillary thyroid carcinoma; one case each of mucinous adenocarcinoma, metastatic adenocarcinoma, sebaceous carcinoma and oligodendroglioma. Only one patient with Stage IIB tumor died of disease. One patient was alive with metastatic disease two months after initial diagnosis. Mean and median follow-up times were 64.1 and 49 months, respectively. An ovarian mass that has characteristics of a teratoma in a postmenopausal patient should alert for malignancy -regardless of tumor size. IOC is a valuable tool for the detection of malignancy and should be requested to determine the modality of surgical approach. Copyright © 2017 Elsevier GmbH. All rights reserved.

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.

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

ClinicalTrials.gov

2018-06-27

Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma

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

2018-03-16

High Grade Ovarian Serous Adenocarcinoma; Ovarian Endometrioid Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

Low meprin α expression differentiates primary ovarian mucinous carcinoma from gastrointestinal cancers that commonly metastasise to the ovaries

PubMed Central

Heinzelmann‐Schwarz, Viola A; Scolyer, Richard A; Scurry, James P; Smith, Alison N; Gardiner‐Garden, Margaret; Biankin, Andrew V; Baron‐Hay, Sally; Scott, Carolyn; Ward, Robyn L; Fink, Daniel; Hacker, Neville F; Sutherland, Robert L; O'Brien, Philippa M

2007-01-01

Background Currently, no specific immunohistochemical markers are available to differentiate primary mucinous epithelial ovarian cancer (MOC) from adenocarcinomas originating at other sites that have metastasised to the ovary, which may have an impact on patient management and prognosis. Aim To investigate the expression of two intestinal markers, galectin 4 and meprin α, in mucinous carcinomas of the ovary and gastrointestinal tract. Methods Using immunohistochemical analysis, the expression of galectin 4 and meprin α was investigated in 10 MOCs and in 38 mucinous adenocarcinomas of colon, pancreas, stomach and appendix, the most common sites of origin of ovarian metastases. Results Total cytoplasmic galectin 4 expression was relatively consistent between the different carcinomas. Membranous meprin α expression was significantly lower in MOCs compared with gastrointestinal carcinomas. Moreover, meprin α expression showed greater discrimination between the ovarian and gastrointestinal carcinomas than the cytokeratins CK7 and CK20, the current standard immunohistochemical markers used to determine the tissue origin of mucinous carcinomas involving the ovaries. Conclusions Meprin α is a useful additional marker in differentiating primary from secondary mucinous adenocarcinomas of the ovary. PMID:16822880

Integrative analysis of copy number alteration and gene expression profiling in ovarian clear cell adenocarcinoma.

PubMed

Sung, Chang Ohk; Choi, Chel Hun; Ko, Young-Hyeh; Ju, Hyunjeong; Choi, Yoon-La; Kim, Nyunsu; Kang, So Young; Ha, Sang Yun; Choi, Kyusam; Bae, Duk-Soo; Lee, Jeong-Won; Kim, Tae-Joong; Song, Sang Yong; Kim, Byoung-Gie

2013-05-01

Ovarian clear cell adenocarcinoma (Ov-CCA) is a distinctive subtype of ovarian epithelial carcinoma. In this study, we performed array comparative genomic hybridization (aCGH) and paired gene expression microarray of 19 fresh-frozen samples and conducted integrative analysis. For the copy number alterations, significantly amplified regions (false discovery rate [FDR] q <0.05) were 1q21.3 and 8q24.3, and significantly deleted regions were 3p21.31, 4q12, 5q13.2, 5q23.2, 5q31.1, 7p22.1, 7q11.23, 8p12, 9p22.1, 11p15.1, 12p13.31, 15q11.2, 15q21.2, 18p11.31, and 22q11.21 using the Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. Integrative analysis revealed 94 genes demonstrating frequent copy number alterations (>25% of samples) that correlated with gene expression (FDR <0.05). These genes were mainly located on 8p11.21, 8p21.2-p21.3, 8q22.1, 8q24.3, 17q23.2-q23.3, 19p13.3, and 19p13.11. Among the regions, 8q24.3 was found to contain the most genes (30 of 94 genes) including PTK2. The 8q24.3 region was indicated as the most significant region, as supported by copy number, GISTIC, and integrative analysis. Pathway analysis using differentially expressed genes on 8q24.3 revealed several major nodes, including PTK2. In conclusion, we identified a set of 94 candidate genes with frequent copy number alterations that correlated with gene expression. Specific chromosomal alterations, such as the 8q24.3 gain containing PTK2, could be a therapeutic target in a subset of Ov-CCAs. Copyright © 2013. Published by Elsevier Inc.

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

ClinicalTrials.gov

2018-04-24

Nausea and Vomiting; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; 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

Laparoscopic Treatment of Mixed Malignant Ovarian Germ Cell Tumor in a 16-Year-Old Female Adolescent.

PubMed

Friedman, Caroline; Fenster, Tamatha

2016-12-01

Malignant ovarian germ cell tumors are rare entities, although they account for a large proportion of ovarian masses in young women. These tumors have traditionally been removed via laparotomy, because of their large size and solid nature. The use of laparoscopy for treatment of adnexal masses in adolescents has been heavily debated and poorly studied to date. A 16-year-old female patient presented with abdominal pain and an 11-cm adnexal mass on ultrasound. An emergent laparoscopic salpingo-oophorectomy was performed without complication. Pathology revealed a mixed malignant ovarian germ cell tumor. Laparoscopic fertility-sparing surgery offers many benefits over laparotomy, and should be considered in cases of young women with large adnexal masses, even if potential for malignancy exists. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.

PubMed

Suprasert, Prapaporn; Manopunya, Manatsawee; Cheewakriangkrai, Chalong

2014-01-01

Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

The sebaceous gland antigen defined by the OM-1 monoclonal antibody is expressed at high density on the surface of ovarian carcinoma cells.

PubMed

de Kretser, T A; Thorne, H J; Jacobs, D J; Jose, D G

1985-09-01

A monoclonal antibody, designated OM-1, was raised against ovarian serous papillary cystadenocarcinoma (stage IV) cells. This antibody was found to react strongly with primary and metastatic ovarian serous cystadenocarcinomas and endometrioid carcinomas but the antigen detected was either absent or at very low levels in ovarian mucinous adenocarcinomas, clear cell carcinomas, benign serous and mucinous cystadenomas and Brenner tumours. The OM-1 antibody gave no detectable reaction with 93 other human tumours, including examples of breast and colon adenocarcinomas. In normal tissues the OM-1 antibody reacted with normal sebaceous gland cells, lung type II pneumocytes and placental syncytial trophoblasts. In the normal ovary OM-1 reactivity was confined to extremely weak staining of the surface epithelium. No reaction with any other ovarian cell type could be detected. No evidence of reaction with other normal cell populations present in 24 adult and seven foetal tissues was found. The antigen detected is compared with other ovarian tumour-associated antigens. The OM-1 antibody is likely to prove of value in the detection and diagnosis of ovarian carcinoma.

Identification of candidate biomarkers with cancer-specific glycosylation in the tissue and serum of endometrioid ovarian cancer patients by glycoproteomic analysis

PubMed Central

Abbott, Karen L.; Lim, Jae-Min; Wells, Lance; Benigno, Benedict B.; McDonald, John F.; Pierce, Michael

2016-01-01

Epithelial ovarian cancer is diagnosed less than 25% of the time when the cancer is confined to the ovary, leading to 5-year survival rates of less than 30%. Therefore, there is an urgent need for early diagnostics for ovarian cancer. Our study using glycotranscriptome comparative analysis of endometrioid ovarian cancer tissue and normal ovarian tissue led to the identification of distinct differences in the transcripts of a restricted set of glycosyltransferases involved in N-linked glycosylation. Utilizing lectins that bind to glycan structures predicted to show changes, we observed differences in lectin-bound glycoproteins consistent with some of the transcript differences. In this study, we have extended our observations by the use of selected lectins to perform a targeted glycoproteomic analysis of ovarian cancer and normal ovarian tissues. Our results have identified several glycoproteins that display tumor-specific glycosylation changes. We have verified these glycosylation changes on glycoproteins from tissue using immunoprecipitation followed by lectin blot detection. The glycoproteins that were verified were then analyzed further using existing microarray data obtained from benign ovarian adenomas, borderline ovarian adenocarcinomas, and malignant ovarian adenocarcinomas. The verified glycoproteins found to be expressed above control levels in the microarray data sets were then screened for tumor-specific glycan modifications in serum from ovarian cancer patients. Results obtained from two of these glycoprotein markers, periostin and thrombospondin, have confirmed that tumor-specific glycan changes can be used to distinguish ovarian cancer patient serum from normal serum. PMID:19953551

Laparoscopic optical coherence tomography imaging of human ovarian cancer

PubMed Central

Hariri, Lida P.; Bonnema, Garret T.; Schmidt, Kathy; Winkler, Amy M.; Korde, Vrushali; Hatch, Kenneth D.; Davis, John R.; Brewer, Molly A.; Barton, Jennifer K.

2011-01-01

Objectives Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10–20 μm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo. Methods A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue. Results Thirty ovaries in 17 primarily peri or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma. Conclusions We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and imaging modality for further evaluation of ovarian cancer pathogenesis. PMID:19481241

Replication protein A in nonearly ovarian adenocarcinomas: correlation with MCM-2, MCM-5, Ki-67 index and prognostic significance.

PubMed

Levidou, Georgia; Ventouri, Kiriaki; Nonni, Afroditi; Gakiopoulou, Hariklia; Bamias, Aristotle; Sotiropoulou, Maria; Papaspirou, Irene; Dimopoulos, Meletios A; Patsouris, Efstratios; Korkolopoulou, Penelope

2012-07-01

Replication protein A (RPA) is an ssDNA-binding protein required for the initiation of DNA replication and the stabilization of ssDNA. Collaboration with several molecules, that is, the MCM2-7 complex, has been suggested to be imperative for its multifaceted role. In this study, we investigated the immunohistochemical expression of the RPA2 subunit in correlation with the MCM-2 and MCM-5 and Ki67 index, and assessed its prognostic significance in 76 patients with nonearly ovarian adenocarcinomas, the majority of whom had a serous histotype. RPA2 protein expression was observed in all cases, whereas the staining intensity varied from weak to strong. RPA2 expression was correlated with the tumor stage in the entire cohort and in serous tumors (P=0.0053 in both relationships). Moreover, RPA2 immunoexpression was positively correlated with MCM-2 (P=0.0001) and MCM-5 (P<0.0001) expression, but was unrelated to the Ki67 index (P>0.10). In multivariate survival analysis, RPA2 expression emerged as an independent predictor of adverse outcome (P<0.0001) along with tumor histologic grade. RPA2 remained an independent predictor of survival (P=0.002) even after adjustment for MCM-2 and MCM-5 expression and when analysis was restricted to serous carcinomas (P=0.004). Our results further support the interrelation of RPA2 protein with MCM-2 and MCM-5 in OCs. Moreover, RPA2 protein may play an important role in ovarian tumorigenesis, and may serve as a useful independent molecular marker for stratifying patients with OC in terms of prognosis.

High Grade Serous Cystadenocarcinoma of Testis-Case Report of a Rare Ovarian Epithelial Type Tumour

PubMed Central

Nayanar, Sangeetha K; Varadharajaperumal, R; Satheeshbabu, TV; Balasubramanian, Satheesan

2017-01-01

Ovarian epithelial type tumour of testis are extremely rare tumours that resemble ovarian surface epithelial tumours. They usually present as testicular or paratesticular tumours and can be serous, mucinous, endometrioid or Brenner tumour. Serous and mucinous types account for the majority of tumours. The tumours are benign, borderline or malignant, commonly borderline. Here, we report a case of high grade serous cyst adenocarcinoma of testis which manifested as extensive metastasis in supraclavicular, mediastinal and abdominopelvic groups of lymph nodes, lung and adrenal gland without clinical evidence of an overt primary tumour. We report this case so as to make clinicians and pathologists aware of this rare entity and to stress on the fact that this rare entity should be kept in mind when evaluating cases of metastatic adenocarcinoma in male patients. PMID:28764180

Irinotecan, Cisplatin, and Bevacizumab in Treating Patients With Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

ClinicalTrials.gov

2013-06-03

Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Recurrent Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Gastric Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer

Expression and function of activin receptors in human endometrial adenocarcinoma cells.

PubMed

Tanaka, Tetsuji; Toujima, Saori; Otani, Tsutomu; Minami, Sawako; Yamoto, Mareo; Umesaki, Naohiko

2003-09-01

Menstrual cycle-dependent expressions of activin A in normal human endometrial tissues have been reported. Expression of activin receptor mRNAs and increased activin A production were also observed in human endometrial adenocarcinoma tissues, suggesting that activin A might enhance cell proliferation and inhibit apoptotic signaling in endometrial cancer cells. In this study, we have examined the effects of activin A on cell proliferation, anticancer drug-induced apoptosis and Fas-mediated apoptosis in 3 differentiated human endometrial adenocarcinoma cell lines, namely HEC-1, HHUA and Ishikawa. Flow cytometric analyses revealed moderate expressions of all 4 types of activin receptor subunits on the cell surfaces of the 3 cell lines. The proliferations of the 3 endometrial cancer cells were completely unaffected by activin A, whereas it suppressed the cell proliferation of a human ovarian endometrioid adenocarcinoma cell line, OVK-18, in a dose-dependent manner. Moreover, activin A did not affect the apoptotic changes in the 3 endometrial adenocarcinoma cells treated with 4 different anticancer drugs, namely CDDP, paclitaxel, etoposide and SN38. The apoptotic changes in HHUA cells treated with anti-Fas IgM were also unaffected by activin A. These results indicate that the increased activin A production in human endometrial adenocarcinoma tissues in vivo may not stimulate carcinoma cell proliferation or inhibit apoptotic signaling in carcinoma cells. Insensitivity to the usual growth suppression signals induced by activin A might be one of the mechanisms of immortality of human endometrial adenocarcinoma cells.

Plasminogen activator inhibitor-1 is an independent prognostic factor of ovarian cancer and IMD-4482, a novel plasminogen activator inhibitor-1 inhibitor, inhibits ovarian cancer peritoneal dissemination.

PubMed

Nakatsuka, Erika; Sawada, Kenjiro; Nakamura, Koji; Yoshimura, Akihito; Kinose, Yasuto; Kodama, Michiko; Hashimoto, Kae; Mabuchi, Seiji; Makino, Hiroshi; Morii, Eiichi; Yamaguchi, Yoichi; Yanase, Takeshi; Itai, Akiko; Morishige, Ken-Ichirou; Kimura, Tadashi

2017-10-27

In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer.

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report.

PubMed

Suwannarurk, Komsun; Thaweekul, Yudthadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Tangtiang, Kaan; Piyawang, Wichet; Bhamarapravatana, Kornkarn

2015-04-01

Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growthfactor (VEGF), has been approvedfor concurrent treatment with first line chemotherapy in advanced epithelial ovarian cancer. A case of an advanced stage epithelial ovarian cancer (EOC) receiving a combination of bevacizumab, carboplatin andpaclitaxel chemotherapy was reported. A 44-year-old woman was presented with abdominal discomfort and distention for 4 months. Bilateral 12 cm diameter ovarian tumors were diagnosed as FIGO stage IIIc after surgical staging operation. Histopathology report showed the mixed type of serous and endometriod adenocarcinoma. The patient was then started on carboplatin/paclitaxel combination chemotherapy for 6 cycles after surgery every 3 weeks. Bevacizumab (7.5 mg/ m2) was concurrently administered with chemotherapy every 3 weeks startingfrom the 2nd cycle. A complete remission was achieved after the end of the chemotherapy treatment. Bevacizumab was continued for one year after the completion of the standard chemotherapy. Bone marrow suppression, hypertension and proteinuria were not found during Bevacizumab treatment. At bevacizumab treatment completion, a platinum-sensitive recurrent ovarian cancer was diagnosed at the two weeks postprogram routine check-up. The patient was counseled to start second line chemotherapy treatment and has yet to come back with her decision. Combination of bevacizumab, carboplatin and paclitaxelfor first line chemotherapy in advanced EOC in this case had no serious side effects and need further study.

Plasminogen activator inhibitor-1 is an independent prognostic factor of ovarian cancer and IMD-4482, a novel plasminogen activator inhibitor-1 inhibitor, inhibits ovarian cancer peritoneal dissemination

PubMed Central

Nakatsuka, Erika; Sawada, Kenjiro; Nakamura, Koji; Yoshimura, Akihito; Kinose, Yasuto; Kodama, Michiko; Hashimoto, Kae; Mabuchi, Seiji; Makino, Hiroshi; Morii, Eiichi; Yamaguchi, Yoichi; Yanase, Takeshi; Itai, Akiko; Morishige, Ken-ichirou; Kimura, Tadashi

2017-01-01

In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer. PMID:29163796

Tracking the origin of simultaneous endometrial and ovarian cancer by next-generation sequencing - a case report.

PubMed

Valtcheva, Nadejda; Lang, Franziska M; Noske, Aurelia; Samartzis, Eleftherios P; Schmidt, Anna-Maria; Bellini, Elisa; Fink, Daniel; Moch, Holger; Rechsteiner, Markus; Dedes, Konstantin J; Wild, Peter J

2017-01-19

Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations. In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary. The patient developed a metachronous lung metastasis of an endometrioid adenocarcinoma four years after hyster- and adnexectomy, vaginal brachytherapy and treatment with the synthetic steroid tibolone. Removal of the metastasis and megestrol treatment for seven years led to a complete remission. A total of 409 genes from the Ampliseq Comprehensive Cancer Panel (Ion Torrent, Thermo Fisher) were analysed by next generation sequencing and mutations in 10 genes, including ARID1A, CTNNB1, PIK3CA and PTEN were identified and confirmed by Sanger sequencing. Primary endometrial as well as ovarian cancer showed an identical mutational profile, suggesting the presence of an ovarian metastasis of the endometrial cancer, rather than a simultaneous endometrial and ovarian cancer. The metachronous lung metastasis showed a different mutational profile compared to the primary cancer. Immunohistochemical staining of the corresponding proteins suggested that the tumour development was driven by alterations in the protein function rather than by changes of the protein abundance in the cell. Our results have demonstrated next generation sequencing as a valuable tool in the differentiation of synchronous primary tumours and metastases, which has an important impact on the clinical decision making process. Similar to breast cancer, targeted therapies based on mutational tumour profiling will become increasingly important in endometrial and ovarian cancer. In summary

Optical Biomarkers of Serous and Mucinous Human Ovarian Tumor Assessed with Nonlinear Optics Microscopies

PubMed Central

Adur, Javier; Pelegati, Vitor B.; de Thomaz, Andre A.; Baratti, Mariana O.; Almeida, Diogo B.; Andrade, L. A. L. A.; Bottcher-Luiz, Fátima; Carvalho, Hernandes F.; Cesar, Carlos L.

2012-01-01

Background Nonlinear optical (NLO) microscopy techniques have potential to improve the early detection of epithelial ovarian cancer. In this study we showed that multimodal NLO microscopies, including two-photon excitation fluorescence (TPEF), second-harmonic generation (SHG), third-harmonic generation (THG) and fluorescence lifetime imaging microscopy (FLIM) can detect morphological and metabolic changes associated with ovarian cancer progression. Methodology/Principal Findings We obtained strong TPEF + SHG + THG signals from fixed samples stained with Hematoxylin & Eosin (H&E) and robust FLIM signal from fixed unstained samples. Particularly, we imaged 34 ovarian biopsies from different patients (median age, 49 years) including 5 normal ovarian tissue, 18 serous tumors and 11 mucinous tumors with the multimodal NLO platform developed in our laboratory. We have been able to distinguish adenomas, borderline, and adenocarcinomas specimens. Using a complete set of scoring methods we found significant differences in the content, distribution and organization of collagen fibrils in the stroma as well as in the morphology and fluorescence lifetime from epithelial ovarian cells. Conclusions/Significance NLO microscopes provide complementary information about tissue microstructure, showing distinctive patterns for serous and mucinous ovarian tumors. The results provide a basis to interpret future NLO images of ovarian tissue and lay the foundation for future in vivo optical evaluation of premature ovarian lesions. PMID:23056557

Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens

PubMed Central

Sahin, Kazim; Yenice, Engin; Tuzcu, Mehmet; Orhan, Cemal; Mizrak, Cengizhan; Ozercan, Ibrahim H.; Sahin, Nurhan; Yilmaz, Bahiddin; Bilir, Birdal; Ozpolat, Bulent

2018-01-01

Background Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene’s molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. Methods In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. Results We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence (P < 0.01) as well as the number and the size of the tumors (P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes (P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds (P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Conclusions Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms. PMID:29629346

Lycopene Protects Against Spontaneous Ovarian Cancer Formation in Laying Hens.

PubMed

Sahin, Kazim; Yenice, Engin; Tuzcu, Mehmet; Orhan, Cemal; Mizrak, Cengizhan; Ozercan, Ibrahim H; Sahin, Nurhan; Yilmaz, Bahiddin; Bilir, Birdal; Ozpolat, Bulent; Kucuk, Omer

2018-03-01

Dietary intake of lycopene has been associated with a reduced risk of ovarian cancer, suggesting its chemopreventive potential against ovarian carcinogenesis. Lycopene's molecular mechanisms of action in ovarian cancer have not been fully understood. Therefore, in the present study, we investigated the effects of lycopene on the ovarian cancer formation using the laying hen model, a biologically relevant animal model of spontaneous ovarian carcinogenesis due to high incidence rates similar to humans. In this study, a total of 150 laying hens at age of 102 weeks were randomized into groups of 50: a control group (0 mg of lycopene per kg of diet) and two treatment groups (200 mg or 400 mg of lycopene per kg of diet, or ~26 and 52 mg/d/hen, respectively). At the end of 12 months, blood, ovarian tissues and tumors were collected. We observed that lycopene supplementation significantly reduced the overall ovarian tumor incidence ( P < 0.01) as well as the number and the size of the tumors ( P < 0.004 and P < 0.005, respectively). Lycopene also significantly decreased the rate of adenocarcinoma, including serous and mucinous subtypes ( P < 0.006). Moreover, we also found that the serum level of oxidative stress marker malondialdehyde was significantly lower in lycopene-fed hens compared to control birds ( P < 0.001). Molecular analysis of the ovarian tumors revealed that lycopene reduced the expression of NF-κB while increasing the expression of nuclear factor erythroid 2 and its major target protein, heme oxygenase 1. In addition, lycopene supplementation decreased the expression of STAT3 by inducing the protein inhibitor of activated STAT3 expression in the ovarian tissues. Taken together, our findings strongly support the potential of lycopene in the chemoprevention of ovarian cancer through antioxidant and anti-inflammatory mechanisms.

Somatostatin receptors in differentiated ovarian tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reubi, J.C.; Horisberger, U.; Klijn, J.G.

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 epithelialmore » 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.« less

Germline Mutations of Inhibins in Early-Onset Ovarian Epithelial Tumors

PubMed Central

Tournier, Isabelle; Marlin, Régine; Walton, Kelly; Charbonnier, Françoise; Coutant, Sophie; Théry, Jean-Christophe; Charbonnier, Camille; Spurrell, Cailyn; Vezain, Myriam; Ippolito, Lorena; Bougeard, Gaëlle; Roman, Horace; Tinat, Julie; Sabourin, Jean-Christophe; Stoppa-Lyonnet, Dominique; Caron, Olivier; Bressac-de Paillerets, Brigitte; Vaur, Dominique; King, Mary-Claire; Harrison, Craig; Frebourg, Thierry

2014-01-01

To identify novel genetic bases of early-onset epithelial ovarian tumors, we used the trio exome sequencing strategy in a patient without familial history of cancer who presented metastatic serous ovarian adenocarcinomas at 21 years of age. We identified a single de novo mutation (c.1157A>G/p.Asn386Ser) within the INHBA gene encoding the βA-subunit of inhibins/activins, which play a key role in ovarian development. In vitro, this mutation alters the ratio of secreted activins and inhibins. In a second patient with early-onset serous borderline papillary cystadenoma, we identified an unreported germline mutation (c.179G>T/p.Arg60Leu) of the INHA gene encoding the α-subunit, the partner of the βA-subunit. This mutation also alters the secreted activin/inhibin ratio, by disrupting both inhibin A and inhibin B biosynthesis. In a cohort of 62 cases, we detected an additional unreported germline mutation of the INHBA gene (c.839G>A/p.Gly280Glu). Our results strongly suggest that inhibin mutations contribute to the genetic determinism of epithelial ovarian tumors. PMID:24302632

Histological grading of ovarian clear cell adenocarcinoma: proposal for a simple and reproducible grouping system based on tumor growth architecture.

PubMed

Yamamoto, Sohei; Tsuda, Hitoshi; Shimazaki, Hideyuki; Takano, Masashi; Yoshikawa, Tomoyuki; Kuzuya, Kazuo; Tsuda, Hiroshi; Kurachi, Hirohisa; Kigawa, Junzo; Kikuchi, Yoshihiro; Sugiyama, Toru; Matsubara, Osamu

2012-03-01

In this study, we aimed to develop a histological grading system for ovarian clear cell adenocarcinoma (CCA), based on the tumor growth architectures. Cases were defined as Group A if ≥90% of a tumor examined was composed of well-differentiated tubulocystic and/or papillary architectures; Group C if at least 10% of the tumor was composed of very poorly differentiated histology (i.e. solid masses or individual infiltrating tumor cells with no or little glandular/papillary differentiation); and tumors not corresponding to the first 2 descriptions were defined as Group B. The interobserver reproducibility and prognostic value of the assigned groups were analyzed for 159 CCAs from 5 institutions. The level of agreement in assigning the groups between 2 pathologists was 88.7% (=0.82). After consensus was reached, 46 (29%), 79 (50%), and 34 (21%) tumors were classified in Groups A, B, and C, respectively. In early-stage cases [International Federation of Gynecology and Obstetrics (FIGO) stage I-II], Group A tumors had significantly better outcomes (100% 5-yr survival) than Group B tumors (82% 5-yr survival, P=0.024 by log-rank test) or Group C tumors (56% 5-yr survival, P=0.00054 by log-rank test). Moreover, early-stage Group B tumors had significantly better outcomes than Group C tumors (P<0.001 by a generalized Wilcoxon test). In advanced cases (FIGO stage III-IV), Group A tumors had significantly better outcomes than Group C tumors (52% vs. 16% 5-yr survival, respectively, P=0.043). Group A and C tumors defined with our system were identified to have favorable and unfavorable prognostic factors, respectively, independent of the clinical stage of the disease and presence of residual tumors after the initial surgery. The proposed grouping system could divide patients with CCA into 3 subgroups with distinct prognostic indications, providing a 3-tier histological grading system for ovarian CCA.

Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAs

DTIC Science & Technology

2015-02-01

OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE 2. REPORT TYPE Annual 3 . DATES COVERED (From - To) 1/30...specimens from women diagnosed with stage III, grade 3 , papillary serous adenocarcinoma all treated with platinum-based chemotherapy. Furthermore, we...and reveal that targeting this miRNA as a novel therapeutic option in ovarian cancer (Task 3 ). 15. SUBJECT TERMS microRNA, ovarian cancer, platinum

Successful treatment of ovarian cancer with apatinib combined with chemotherapy

PubMed Central

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-01-01

Abstract Rationale: The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. Patients concerns: A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Diagnosis: Ovarian cancer. Interventions: The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand–foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. Outcomes: The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Lessons: Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially

Recurrence of Ovarian Cancer with Placental Metastasis: A Case Report

PubMed Central

Honda, Michiko; Yamada, Manabu; Kumasaka, Toshio; Samejima, Taiki; Satoh, Hirohisa; Sugimoto, Mitsuhiro

2017-01-01

A 39-year-old primiparous Japanese female was admitted to the obstetrical emergency department of our hospital because of respiratory distress resulting from a large amount of pleural effusion, soon after a caesarean delivery (CD) at another hospital. While she was undergoing the CD, a giant ovarian tumour was identified. However, the tumour could not be removed at that facility and she was transferred to our hospital. Three days after the CD, a left salpingo-oophorectomy was performed with the purpose of controlling pleural and peritoneal effusions. Based on her past treatment history and the information gathered from this surgery, recurrence of ovarian cancer was considered the final diagnosis. Earlier, at the age of 37 years, she had been diagnosed with stage IC ovarian adenocarcinoma arising from a mature cystic teratoma detected after a right salpingo-oophorectomy. These kinds of situations of accidental detection of recurrent advanced ovarian cancer in a newly pregnant patient in the emergency department are rare. Amongst them, we have identified an extremely rare case showing placental metastasis. The important lesson learnt from this case report is that detailed medical interviews and physical examinations are crucial when a pregnant woman visits a hospital without a letter of referral, especially in the third trimester of pregnancy. PMID:29070997

HRCT features of surgically resected invasive mucinous adenocarcinoma associated with interstitial pneumonia.

PubMed

Miyamoto, Atsushi; Kurosaki, Atsuko; Fujii, Takeshi; Kishi, Kazuma; Homma, Sakae

2017-05-01

Lung cancer is prevalent among patients with interstitial pneumonia (IP). HRCT findings mucinous adenocarcinoma in patients with IP have not been described. In 112 consecutive patients with 120 surgically resected IP-associated lung cancers, 42 patients had pathologically proven invasive adenocarcinoma (IA). A total of 14 out of 42 patients (10 men, 4 women, mean age, 68.4 years) had invasive mucinous adenocarcinoma. We reviewed the patients' medical records and HRCT scans. Invasive mucinous adenocarcinoma were most commonly associated with idiopathic IP (n = 13) affecting the lower lobe adjacent to a fibrocystic changes. In 11 patients with invasive mucinous adenocarcinoma or other types of IA, the tumour was adjacent to a fibrocystic lesion. In invasive mucinous adenocarcinoma, malignant signs included lobulation (n = 11), spiculation (n = 9), vascular convergence (n = 10) and pleural indentation (n = 2). Characteristic findings of mucinous adenocarcinoma (i.e. vague margins (n = 10), lobular-bounded margins (n = 11), air bronchogram (n = 11) and bubble-like low attenuation (n = 8)) were more common in invasive mucinous adenocarcinoma than in other IA types. All invasive mucinous adenocarcinoma tumours (n = 11) were closely associated with fibrosis. Mixed ground-glass opacity and consolidation adjacent to a fibrocystic lesion with malignant signs and characteristic features of mucinous adenocarcinoma indicate malignancy. © 2016 Asian Pacific Society of Respirology.

Identification and Characterization of Genomic Amplifications in Ovarian Serous Carcinoma

DTIC Science & Technology

2006-01-01

Wang (2005) Exploring cancer genome using innovative technologies. Curr Opin Oncol, 17:33-38. • G Singer, R Stohr, L Cope, R Dehari, A Hartmann, D -F...tions/plate × 6 plates/ d ). This high-throughput platform permits a systemic scan of cancer genome at the nucleo- tide level in a short time [35]. This...Carter D , Foellmer HG, et al.: Neu proto-oncogene amplification and expression in ovarian adenocarcinoma cell lines. Am J Pathol 1992, 140:23–31. 12

TMPRSS2-ERG gene fusions are infrequent in prostatic ductal adenocarcinomas.

PubMed

Lotan, Tamara L; Toubaji, Antoun; Albadine, Roula; Latour, Mathieu; Herawi, Mehsati; Meeker, Alan K; DeMarzo, Angelo M; Platz, Elizabeth A; Epstein, Jonathan I; Netto, George J

2009-03-01

Ductal adenocarcinoma of the prostate is an unusual subtype that may be associated with a more aggressive clinical course, and is less responsive to conventional therapies than the more common prostatic acinar adenocarcinoma. However, given its frequent association with an acinar component at prostatectomy, some have challenged the concept of prostatic ductal adenocarcinoma as a distinct clinicopathologic entity. We studied the occurrence of the TMPRSS2-ERG gene fusion, in 40 surgically resected ductal adenocarcinoma cases, and in their associated acinar component using fluorescence in situ hybridization. A group of 38 'pure' acinar adenocarcinoma cases matched with the ductal adenocarcinoma group for pathological grade and stage was studied as a control. Compared with the matched acinar adenocarcinoma cases, the TMPRSS2-ERG gene fusion was significantly less frequently observed in ductal adenocarcinoma (45 vs 11% of cases, P=0.002, Fisher's exact test). Here, of the ductal adenocarcinoma cases with the gene fusion, 75% were fused through deletion, and the remaining case was fused through translocation. The TMPRSS2-ERG gene fusion was also rare in the acinar component of mixed ductal-acinar tumors when compared with the pure acinar adenocarcinoma controls (5 vs 45%, P=0.001, Fisher's exact test). In 95% of the ductal adenocarcinoma cases in which a concurrent acinar component was analyzed, there was concordance for presence/absence of the TMPRSS2-ERG gene fusion between the different histologic subtypes. In the control group of pure acinar adenocarcinoma cases, 59% were fused through deletion and 41% were fused through translocation. The presence of the TMPRSS2-ERG gene fusion in some cases of prostatic ductal adenocarcinoma supports the concept that ductal adenocarcinoma and acinar adenocarcinoma may be related genetically. However, the significantly lower rate of the gene fusion in pure ductal adenocarcinoma cases underscores the fact that genetic and biologic

Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

PubMed

Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

2000-11-01

Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

Mixed micelles for encapsulation of doxorubicin with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines versus Doxil®.

PubMed

Cagel, Maximiliano; Bernabeu, Ezequiel; Gonzalez, Lorena; Lagomarsino, Eduardo; Zubillaga, Marcela; Moretton, Marcela A; Chiappetta, Diego A

2017-11-01

Doxorubicin (DOX) is used as a "first-line" antineoplastic drug in ovarian and metastatic breast cancer. However, serious side effects, such as cardiotoxicity have been reported after DOX intravenous administration. Hence, we investigated different micelle-former biomaterials, as Soluplus ® , Pluronic F127, Tetronic T1107 and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) to develop a potential mixed micellar nanocarrier for DOX delivery. Since DOX hydrochloride is a poor candidate to be encapsulated inside the hydrophobic core of the mixed micelles, we assayed a hydrophobic complex between DOX and sodium deoxycholate (NaDC) as an excellent candidate to be encapsulated within polymeric micelles. The combination of T1107:TPGS (1:3, weight ratio) demonstrated the best physicochemical properties together with a high DL capacity (6.43% w/v). Particularly, DOX in vitro release was higher at acidic tumour microenvironment pH value (5.5) than at physiological counterpart (7.4). The hydrodynamic diameter of the DOX/NaDC-loaded mixed micellar system was 10.7nm (PDI=0.239). The in vitro cytotoxicity of the mixed micellar formulation resulted significantly (p<0.05) higher than Doxil ® against ovarian (SKOV-3) and triple-negative breast cancer cells (MDA-MB- 231). Further, the in vitro cellular uptake assays demonstrated a significant increment (p<0.05) of the DOX intracellular content for the mixed micelles versus Doxil ® for both, SKOV-3 (at 2, 4 and 6h of incubation) and MDA-MB-231 (at 4h of incubation) cells. These findings suggest that T1107:TPGS (1:3) mixed micelles could be employed as a potential nanotechnological platform for drug delivery of DOX. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium

PubMed Central

Lawrenson, Kate; Pakzamir, Elham; Liu, Biao; Lee, Janet M.; Delgado, Melissa K.; Duncan, Kara; Gayther, Simon A.; Liu, Song; Roman, Lynda; Mhawech-Fauceglia, Paulette

2015-01-01

Background The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses. Methodology/Principal Findings We studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035). Conclusion Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future. PMID:26132201

Paradoxical expression of AHCYL1 affecting ovarian carcinogenesis between chickens and women.

PubMed

Jeong, Wooyoung; Kim, Hee Seung; Kim, Yong Beom; Kim, Min A; Lim, Whasun; Kim, Jinyoung; Jang, Hyun-Jun; Suh, Dong Hoon; Kim, Kidong; Chung, Hyun Hoon; Bazer, Fuller W; Song, Yong Sang; Han, Jae Yong; Song, Gwonhwa

2012-07-01

We investigated S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) gene expression in human epithelial ovarian cancer (EOC) using the chicken, which is the most relevant animal model. Ovarian cancer was detected in 10 of 136 laying hens (7.4%). Results of the present study indicated that AHCYL1 mRNA and protein are most abundant in the glandular epithelium of adenocarcinoma of cancerous, but not normal, ovaries of hens. In addition, bisulfite sequencing to examine methylation patterns in the promoter region of the AHCYL1 gene revealed that 30-38% of the three CpG sites were demethylated in ovarian cancer cells as compared with normal ovarian cells. Furthermore, in human ovarian cancer cells such as OVCAR-3, AHCYL1 protein was predominantly in the nucleus and had a similar expression pattern to that in chicken ovarian cancer cells. Thereafter, we examined the prognostic value of AHCYL1 expression in patients with EOC using multivariate linear logistic regression and Cox's proportional hazard analyses. In 109 human patients with EOC, 14 (12.8%), 41 (37.6%) and 54 (49.6%) patients showed weak, moderate and strong expression of AHCYL1 protein, respectively. However, intermediate or high expression of AHCYL1 protein was a favorable factor for overall responses (adjusted odds ratio, 7.23; 95% confidence interval [CI], 1.36-38.39), and for progression-free survival (adjusted hazard ratio, 0.20; 95% CI, 0.07-0.55). From these results, we conclude that AHCYL1 expression is associated with ovarian carcinogenesis as an oncogene in chickens, whereas it plays the role of tumor suppressor in human EOC, suggesting a paradoxical function of AHCYL1 in ovarian carcinogenesis.

Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

PubMed Central

Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

2010-01-01

Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

Complexity of expression of the intermediate filaments of six new human ovarian carcinoma cell lines: new expression of cytokeratin 20.

PubMed

Yanagibashi, T; Gorai, I; Nakazawa, T; Miyagi, E; Hirahara, F; Kitamura, H; Minaguchi, H

1997-01-01

Six permanent human ovarian carcinoma cell lines (OVISE, OVTOKO, OVMANA and OVSAYO from clear cell adenocarcinoma, and OVSAHO and OVKATE from serous papillary adenocarcinoma) were established from solid tumours. The cell lines have been in culture for 5-8 years, the passage number varying from 62 to 246. Immunohistochemical analysis has shown that five of the six cell lines express at least six cytokeratin (CK) polypeptides. OVISE and OVSAYO expressed CKs 6, 7, 8, 18, 19 and 15 and/or 16. OVTOKO was positive for CKs 7, 8, 18, 19 and 15 and/or 16. OVSAHO expressed CKs 6, 7, 8, 14, 18, 19 and 15 and/or 16. OVMANA expressed CKs 6, 7, 8, 18, 19, 20 and 15 and/or 16. OVKATE expressed CKs 6, 7, 8, 13, 17, 18, 19, 20 and 15 and/or 16. The expression of CK7, additional expression of vimentin, and clinical and histopathological findings enabled us to confirm that six cell lines had been established from primary ovarian cancers. Two of the six cell lines were positive for CK20, although CK20 was not expressed in the original tumours. The heterotransplanted tumours produced by CK20-positive cells also expressed CK20. This is the first report of ovarian carcinoma cell lines that express CK20 irrespective of their histological type. CK20 has been found in all colon carcinoma cell lines, but only in the mucinous type of ovarian tumours. These new ovarian carcinoma cell lines will therefore provide a relevant experimental system for elucidating the regulatory control mechanisms of intermediate filament expression.

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

PubMed

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

2014-01-01

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

MALAT1 affects ovarian cancer cell behavior and patient survival

PubMed Central

Lin, Qunbo; Guan, Wencai; Ren, Weimin; Zhang, Lingyun; Zhang, Jinguo; Xu, Guoxiong

2018-01-01

Epithelial ovarian cancer (EOC) is one of the most lethal malignancies of the female reproductive organs. Increasing evidence has revealed that long non-coding RNAs (lncRNAs) participate in tumorigenesis. Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is an lncRNA and plays a role in various types of tumors. However, the function of MALAT1 on cellular behavior in EOC remains unclear. The current study explored the expression of MALAT1 in ovarian cancer tissues and in EOC cell lines. Quantitative RT-PCR analysis revealed that the expression of MALAT1 was higher in human ovarian malignant tumor tissues and EOC cells than in normal ovarian tissues and non-tumorous human ovarian surface epithelial cells, respectively. By analyzing the online database Kaplan-Meier Plotter, MALAT1 was identified to be correlated with the overall survival (OS) and progression-free survival (PFS) of patients with ovarian cancer. Furthermore, knockdown of MALAT1 by small interfering RNA (siRNA) significantly decreased EOC cell viability, migration, and invasion. Finally, dual-luciferase reporter assays demonstrated that MALAT1 interacted with miR-143-3p, a miRNA that plays a role in EOC as demonstrated in our previous study. Inhibition of MALAT1 resulted in an increase of miR-143-3p expression, leading to a decrease of CMPK protein expression. In conclusion, our results indicated that MALAT1 was overexpressed in EOC. Silencing of MALAT1 decreased EOC cell viability and inhibited EOC cell migration and invasion. These data revealed that MALAT1 may serve as a new therapeutic target of human EOC. PMID:29693187

Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

ClinicalTrials.gov

2018-02-14

Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

Successful treatment of ovarian cancer with apatinib combined with chemotherapy: A case report.

PubMed

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-11-01

The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Ovarian cancer. The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand-foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially adenocarcinomas.

Ovarian stimulation and embryo banking for fertility preservation in a woman with severe mixed connective tissue disease: Is it safe?

PubMed

Sioulas, Vasileios D; Gracia, Clarisa R

2012-03-01

To report the first case of using assisted reproductive technologies (ART) for fertility preservation in a patient with mixed connective tissue disease (MCTD), secondary pulmonary hypertension (PH) and antiphospholipid syndrome (APS). Case-report and review of the literature. Academic infertility practice and tertiary care center. A 25-year-old woman with MCTD, complicated with PH and APS, who was scheduled for gonadotoxic therapy Controlled ovarian hyperstimulation, egg retrieval, embryo banking. Successful ART cycle leading to embryo banking without worsening her underlying disease. Following successful embryo cryopreservation, the patient experienced respiratory failure and other severe complications, resulting in a prolonged hospital stay. Controlled ovarian hyperstimulation for embryo banking in women with MCTD, PH and APS may pose a risk for potentially catastrophic complications. A multidisciplinary approach to these patients is necessary to optimize the outcomes of such procedures. More data are needed regarding the safety of fertility preservation technologies in patients with complex medical diseases.

Presence of gonadotropin-releasing hormone and its messenger ribonucleic acid in human ovarian epithelial carcinoma.

PubMed

Ohno, T; Imai, A; Furui, T; Takahashi, K; Tamaya, T

1993-09-01

The purpose of this study was to investigate the expression of gonadotropin-releasing hormone messenger ribonucleic acid and the presence of gonadotropin-releasing hormone in human ovarian carcinoma known to have gonadotropin-releasing hormone binding sites and to be affected by gonadotropin-releasing hormone analog. Human ovarian carcinomas surgically removed and human ovarian carcinoma cell lines were examined. Gonadotropin-releasing hormone was determined by a radioimmunoassay and a bioassay. Gonadotropin-releasing hormone messenger ribonucleic acid was determined by reverse transcription polymerase chain reaction using oligonucleotide primers synthesized according to the published human gonadotropin-releasing hormone sequence. Gonadotropin-releasing hormone was shown to be present in extracts of ovarian mucinous cystadenocarcinoma sample (0.8 +/- 0.12 pg/mg of protein) and ovarian adenocarcinoma cell line SK-OV3 (0.92 +/- 0.17 pg/mg of protein) but not in the normal ovary and placenta. Two of two extract samples from individual cases evoked dose-dependent phosphoinositide breakdown in rat granulosa cells similar to that caused by authentic gonadotropin-releasing hormone. Gonadotropin-releasing hormone messenger ribonucleic acid was detected in two of two mucinous cystadenocarcinoma specimens, one of one serous cystadenocarcinoma, and SK-OV3 cells but not in the dysgerminoma, mucinous cystadenoma, and normal ovary and placenta. The demonstration of gonadotropin-releasing hormone and its messenger ribonucleic acid raises the possibility that gonadotropin-releasing hormone may play an autocrine regulatory role in the growth of ovarian carcinoma.

[Bilateral ovarian Burkitt's lymphoma. A case presentation].

PubMed

Briseño-Hernández, Andrés Alejandro; Quezada-López, Deissy Roxana; Castañeda-Chávez, Agar; Dassaejv Macías-Amezcua, Michel; Pintor-Belmontes, Julio Cesar

2014-01-01

Burkitt lymphoma, is described as an aggressive form of non-Hodgkin lymphoma of B cells which occurs most often in children and young adults, ovarian lymphoma can appear as a primary lesion or more commonly referred to as a metastasis. Primary ovarian lesions are rare manifestations corresponding to 0.5% of non-Hodgkin lymphoma and 1.5% of ovarian tumors. Clinic case: 31 years old female with general weakness, march incapacity, dyspnea, hyporexia, fever, diaphoresis, weight loss of 20 kg, flat abs with abdominal pain; Ca125 610 U/ml. Abdominal computed tomography shows a solid aspect tumor which affects the right pelvic cavity. Bilateral ovarian tumors were removed. Microscopically, both lesions show a "starry sky" pattern composed by a monotonous infiltration of lymphocytes mixed with large and clear macrophages, several atypical mitoses, and necrosis and hemorrhage areas. Immunohistochemistry was positive for CD10, CD20, and negative for CD3 and high Ki67 proliferation index. Bilateral ovarian Burkitt's lymphoma was diagnosed. Bilateral ovarian Burkitt's lymphoma is a rare entity, with a variability of presentations, the abdominal pain and abdominal tumors are the most frequent. The patient's prognosis at short term is poor, therefore it's necessary to know this entity and make an early diagnosis.

[Expressions of Ras and Sos1 in epithelial ovarian cancer tissues and their clinical significance].

PubMed

Xiao, Zheng-Hua; Linghu, Hua; Liu, Qian-Fen

2016-11-20

To detect the expressions of Ras and Sos1 proteins in human epithelial ovarian cancer (EOC) tissues and explore their correlation with the clinicopathological features of the patients. The expressions of Ras and Sos1 proteins were detected immunohistochemically in 62 EOC tissues, 5 borderline ovarian cancer tissues, 15 benign epithelial ovarian neoplasm tissues, and 18 normal ovarian tissues. The EOC tissues showed significantly higher expression levels of both Ras and Sos1 than the other tissues tested (P<0.05). In EOC tissues, Ras and Sos1 proteins were expressed mostly on the cell membrane and in the cytoplasm. The expression level of Ras was correlated with pathological types of the tumor (P<0.05) and was the highest in serous cystadenomcarcinoma; Sos1 expression did not show significant correlation with the clinicopathological indexes of the patients. High expressions of both Ras and Sos1 proteins were associated with shorter progression-free survival of the patients, but this association was not statistically significant. Ras and Sos1 protein may participate in in the occurrence and development of EOC. The tissue-specific variation of Ras expression can lend support to a specific diagnosis of ovarian serous adenocarcinoma. The association of Ras and Sos1 protein expression with the tumor-free survival time of the patients awaits further investigation with a larger sample size.

Increased risk of gastric adenocarcinoma after treatment of primary gastric diffuse large B-cell lymphoma.

PubMed

Inaba, Koji; Kushima, Ryoji; Murakami, Naoya; Kuroda, Yuuki; Harada, Ken; Kitaguchi, Mayuka; Yoshio, Kotaro; Sekii, Shuhei; Takahashi, Kana; Morota, Madoka; Mayahara, Hiroshi; Ito, Yoshinori; Sumi, Minako; Uno, Takashi; Itami, Jun

2013-10-26

There have been sporadic reports about synchronous as well as metachronous gastric adenocarcinoma and primary gastric lymphoma. Many reports have dealt with metachronous gastric adenocarcinoma in mucosa-associated lymphoid tissue lymphoma of stomach. But to our knowledge, there have been no reports that document the increased incidence of metachronous gastric adenocarcinoma in patients with gastric diffuse large B-cell lymphoma. This retrospective study was conducted to estimate the incidence of metachronous gastric adenocarcinoma after primary gastric lymphoma treatment, especially in diffuse large B-cell lymphoma. The retrospective cohort study of 139 primary gastric lymphoma patients treated with radiotherapy at our hospital. Mean observation period was 61.5 months (range: 3.7-124.6 months). Patients profile, characteristics of primary gastric lymphoma and metachronous gastric adenocarcinoma were retrieved from medical records. The risk of metachronous gastric adenocarcinoma was compared with the risk of gastric adenocarcinoma in Japanese population. There were 10 (7.2%) metachronous gastric adenocarcinoma patients after treatment of primary gastric lymphomas. It was quite high risk compared with the risk of gastric carcinoma in Japanese population of 54.7/100,000. Seven patients of 10 were diffuse large B-cell lymphoma and other 3 patients were mixed type of diffuse large B-cell lymphoma and mucosa associated lymphoid tissue lymphoma. Four patients of 10 metachronous gastric adenocarcinomas were signet-ring cell carcinoma and two patients died of gastric adenocarcinoma. Metachronous gastric adenocarcinoma may have a more malignant potential than sporadic gastric adenocarcinoma. Old age, Helicobacter pylori infection and gastric mucosal change of chronic gastritis and intestinal metaplasia were possible risk factors for metachronous gastric adenocarcinoma. There was an increased risk of gastric adenocarcinoma after treatment of primary gastric lymphoma

Adenocarcinoma arising from intracranial recurrent mature teratoma and featuring mutated KRAS and wild-type BRAF genes.

PubMed

Kim, Eun Soo; Kwon, Mi Jung; Song, Joon Ho; Kim, Dong Hoon; Park, Hye-Rim

2015-02-01

Malignant transformation or recurrence of intracranial mature teratoma is an extremely rare occurrence, compared to the usual ovarian counterpart. Previously, yolk sac tumor elements have been considered to be selective progenitors of enteric-type adenocarcinoma arising from intracranial germ cell tumors. However, the present case demonstrates the occurrence of enteric-type adenocarcinoma in recurrent intracranial mature cystic teratoma 12 years after gross total removal, a case of which has not previously been documented in the literature. The 11.5-cm long, dura mater-based tumor on the right fronto-temporal lobe displaced the brain; however, the patient had no neurologic symptoms or discomfort other than pus-like discharge on the scalp. Microscopic examinations revealed a small focus of adenocarcinoma and dysplastic colonic mucosa in the mature cystic teratoma. No immature elements were seen. The cystic wall was almost denuded and showed an exuberant xanthogranulomatous reaction with foreign-body type giant cells engulfing keratin materials and cholesterol clefts, suggesting that chronic inflammation due to repeated cyst wall rupture and the previous resection may contribute to malignant transformation. The adenocarcinoma showed strong immunohistochemical expression of CK20 and p53, but CK7 in patches. The molecular profile of the adenocarcinoma showed a mutation in KRAS and wild-type BRAF, which might be associated with malignant transformation of intracranial mature teratomas. In conclusion, the intracranial mature teratomas should require long-term follow-up, and clinicians, radiologists and pathologists should be aware of the potential for malignant progression of recurrent intracranial mature cystic teratoma despite gross total resection and no neurologic symptoms. © 2014 Japanese Society of Neuropathology.

184AA3: a xenograft model of ER+ breast adenocarcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hines, William C.; Kuhn, Irene; Thi, Kate

Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER +) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER + adenocarcinomas that had a high proliferative rate and other features consistentmore » with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44 High  subpopulation was discovered, yet their tumor forming ability was far less than CD44 Low  cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER +  cancers. In conclusion, this model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.« less

184AA3: a xenograft model of ER+ breast adenocarcinoma

DOE PAGES

Hines, William C.; Kuhn, Irene; Thi, Kate; ...

2015-12-12

Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER +) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Xenografts of one cell line, 184AA3, consistently formed ER + adenocarcinomas that had a high proliferative rate and other features consistentmore » with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44 High  subpopulation was discovered, yet their tumor forming ability was far less than CD44 Low  cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER +  cancers. In conclusion, this model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing, and drug development.« less

Canine ovarian neoplasms: a clinicopathologic study of 71 cases, including histology of 12 granulosa cell tumors.

PubMed

Patnaik, A K; Greenlee, P G

1987-11-01

In a retrospective study of 71 primary ovarian tumors in the dog, epithelial tumors (46%) were more common than sex cord stromal (34%) and germ cell tumors (20%). There were more adenocarcinomas (64%) than adenomas. Sex cord stromal tumors were equally divided into Sertoli-Leydig (12/24) and granulosa cell tumors (12/24). There were equal numbers (7/14) of dysgerminomas and teratomas among the germ cell tumors. Most teratomas (6/7) were malignant. Most granulosa cell tumors were solid; two were mostly cystic. Patterns included sheets of round and ovoid to spindle-shaped cells separated by thin, fibrovascular stroma; neoplastic cells formed rosettes or Call-Exner bodies. In some areas, neoplastic cells were in cords or columns and formed cyst-like structures. Four granulosa cell tumors were macrofollicular, having cysts lined with granulosa cells. Median ages of dogs with different ovarian neoplasms were similar; all were more than 10 years old, except the dogs with teratoma (mean age, 4 years). Most neoplasms were unilateral (84%), except the Sertoli-Leydig cell tumors, many of which were bilateral (36%). Size of ovarian neoplasms varied (2 cm3 to 15,000 cm3). Twenty-nine percent of neoplasms metastasized; adenocarcinomas (48%) and malignant teratomas (50%) had the highest rates, and distant metastasis was more common in malignant teratoma. Endometrial hyperplasia was in 67% of the dogs; it was most common in dogs with sex cord stromal tumors (95%). Uterine malignancy was not seen in dogs with granulosa cell tumors, although hyperplasia endometrium was in all dogs with this tumor. Cysts in the contralateral ovaries were most common in dogs with sex cord stromal tumors.

Differential diagnosis and cancer staging of a unique case with multiple nodules in the lung - lung adenocarcinoma, metastasis of colon adenocarcinoma, and colon adenocarcinoma metastasizing to lung adenocarcinoma.

PubMed

Bai, Yun; Qiu, Jianxing; Shang, Xueqian; Liu, Ping; Zhang, Ying; Wang, Ying; Xiong, Yan; Li, Ting

2015-05-01

Lung cancer is the most common cancer in the world. Despite this, there have been few cases of simultaneous primary and metastatic cancers in the lung reported, let alone coexisting with tumor-to-tumor metastasis. Herein, we describe an extremely unusual case. A 61-year-old man with a history of colon adenocarcinoma was revealed as having three nodules in the lung 11 months after colectomy. The nodule in the left upper lobe was primary lung adenocarcinoma, the larger one in the right upper lobe was a metastasis of colon adenocarcinoma, and the smaller one in the right upper lobe was colon adenocarcinoma metastasizing to lung adenocarcinoma. Our paper focused on the differential diagnosis and cancer staging of this unique case, and discussed the uncommon phenomenon of the lung acting as a recipient in tumor-to-tumor metastasis.

Ovarian Autoantibodies Predict Ovarian Cancer

DTIC Science & Technology

2010-11-01

2000. 48(10): 541- 549. 10 7. Barua, A., et al., Anti-ovarian and anti-tumor antibodies in women with ovarian cancer. Am J Reprod Immunol, 2007 . 57...Med 2007 . 26: 909-919. 9. Barua, A., et al., Prevalence of anti-tumor antibodies in the laying hen model of human ovarian cancer. International... 2007 ; 25:4159– 4161. 6. Bosse K, Rhiem K, Wappenschmidt B, et al. Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in

Induction of a menopausal state alters the growth and histology of ovarian tumors in a mouse model of ovarian cancer.

PubMed

Laviolette, Laura A; Ethier, Jean-François; Senterman, Mary K; Devine, Patrick J; Vanderhyden, Barbara C

2011-05-01

Ovarian cancer is often diagnosed in women after menopause when the levels of the serum gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are increased because of the depletion of growing follicles within the ovary. The ability of FSH and LH to modulate the disease has not been well studied owing to a lack of physiologically relevant models of ovarian cancer. In this study, 4-vinylcyclohexene diepoxide (VCD) was used to deplete ovarian follicles and increase the levels of circulating FSH and LH in the tgCAG-LS-TAg mouse model of ovarian cancer. VCD-induced follicle depletion was performed either before or after induction of the oncogene SV40 large and small T-antigens in the ovarian surface epithelial cells of tgCAG-LS-TAg mice, which was mediated by the intrabursal delivery of an adenovirus expressing Cre recombinase (AdCre). tgCAG-LS-TAg mice injected with AdCre developed undifferentiated ovarian tumors with mixed epithelial and stromal components and some features of sex cord stromal tumors. Treatment with VCD before or after AdCre injection yielded tumors of similar histology, but with the unique appearance of Sertoli cell nests. In mice treated with VCD before the induction of tumorigenesis, the ovarian tumors tended to grow more slowly. The human ovarian cancer cell lines SKOV3 and OVCAR3 responded similarly to increased levels of gonadotropins in a second model of menopause, growing more slowly in ovariectomized mice compared with cycling controls. These results suggest that follicle depletion and increased gonadotropin levels can alter the histology and the rate of growth of ovarian tumors.

The zinc-finger transcription factor SALL4 is frequently expressed in human cancers: association with clinical outcome in squamous cell carcinoma but not in adenocarcinoma of the esophagus.

PubMed

Kilic, Ergin; Tennstedt, Pierre; Högner, Anica; Lebok, Patrick; Sauter, Guido; Bokemeyer, Carsten; Izbicki, Jakob R; Wilczak, Waldemar

2016-04-01

SALL4 is a transcription factor originally identified as a homeotic gene essential for organ development. Early studies suggested that SALL4 is a useful marker to identify testicular and ovarian germ cell tumors. The aim of the study was to evaluate the diagnostic potential of SALL4 immunohistochemistry. Immunohistochemical staining was performed on a tissue microarray (TMA) with 3966 samples from 94 different tumor types and on a further TMA with 492 esophagus carcinomas. SALL4 immunostaining was by far most prevalent and most intensive in testicular tumors with a positivity rate of 93.1% in seminomas, 80% in mixed germ cell tumors (embryonic carcinomas/yolk sac tumors), and 18.5% in teratomas, respectively. However, SALL4 expression is not specific to germ cell tumors. We observed SALL4 positivity in non-germ cell tumors as carcinomas of the kidney (28.9% of chromophobe, 34.4% of clear cell carcinoma), in intestinal type adenocarcinoma of the stomach (10.9%), in adenocarcinoma (10.5%) and squamous cell carcinoma (7.2%) of the esophagus, and in malignant melanoma (8.1%) and invasive urothelial bladder carcinoma (20%). SALL4 expression was not found in lymphomas, in soft tissue tumors or breast tumors. At analysis of esophagus carcinoma TMA, no significant association was seen between SALL4 expression and overall survival in adenocarcinoma. However, SALL4 expression was strongly associated with worse overall survival in squamous cell carcinoma. SALL4 expression can be found at relevant frequencies in various tumors of different primary sites. SALL4 expression in squamous cell carcinoma of the esophagus may constitute a sign of dedifferentiation leading to poor patient prognosis.

Risk of Epithelial Ovarian Cancer in Relation to Benign Ovarian Conditions and Ovarian Surgery

PubMed Central

Rossing, Mary Anne; Cushing-Haugen, Kara L.; Wicklund, Kristine G.; Doherty, Jennifer A.; Weiss, Noel S.

2009-01-01

Objective Some forms of ovarian neoplasms may be preventable through the removal of precursor lesions. We assessed risk associated with a prior diagnosis of, and ovarian surgery following, ovarian cysts and endometriosis, with a focus on characterizing risk among tumor subgroups. Methods Information was collected during in-person interviews with 812 women with ovarian cancer diagnosed in western Washington State from 2002–2005 and 1,313 population-based controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results The risk of a borderline mucinous ovarian tumor associated with a history of an ovarian cyst was increased (OR=1.7, 95% CI 1.0–2.8) but did not vary notably according to receipt of subsequent ovarian surgery. While risk of invasive epithelial ovarian cancer was slightly increased among women with a cyst who had no subsequent ovarian surgery, it was reduced when a cyst diagnosis was followed by surgery (OR= 0.6, 95% CI 0.4–0.9). This reduction in risk was most evident for serous invasive tumors. Women with a history of endometriosis had a three-fold increased risk of endometrioid and clear cell invasive tumors, with a lesser risk increase among women who underwent subsequent ovarian surgery. Conclusions Our results suggest differences in the relation of ovarian cysts and endometriosis with risk of specific subtypes of ovarian cancer, as well as the possibility that ovarian surgery in women with these conditions may lower the risk of invasive disease. PMID:18704718

Ovarian size and response to laparoscopic ovarian electro-cauterization in polycystic ovarian disease.

PubMed

Alborzi, S; Khodaee, R; Parsanejad, M E

2001-09-01

To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size. Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared. Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences. Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.

TORC1/2 Inhibitor MLN0128 and Bevacizumab in Treating Patients With Recurrent Glioblastoma or Advanced Solid Tumors

ClinicalTrials.gov

2018-05-14

Adult Glioblastoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma; Solid Neoplasm; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7

Ovarian Stem Cell Nests in Reproduction and Ovarian Aging.

PubMed

Ye, Haifeng; Zheng, Tuochen; Li, Wei; Li, Xiaoyan; Fu, Xinxin; Huang, Yaoqi; Hu, Chuan; Li, Jia; Huang, Jian; Liu, Zhengyv; Zheng, Liping; Zheng, Yuehui

2017-01-01

The fixed primordial follicles pool theory, which monopolized reproductive medicine for more than one hundred years, has been broken by the discovery, successful isolation and establishment of ovarian stem cells. It has brought more hope than ever of increasing the size of primordial follicle pool, improving ovarian function and delaying ovarian consenescence. Traditional view holds that stem cell aging contributes to the senility of body and organs. However, in the process of ovarian aging, the main factor leading to the decline of the reproductive function is the aging and degradation of ovarian stem cell nests, rather than the senescence of ovarian germ cells themselves. Recent studies have found that the immune system and circulatory system are involved in the formation of ovarian germline stem cell niches, as well as regulating the proliferation and differentiation of ovarian germline stem cells through cellular and hormonal signals. Therefore, we can improve ovarian function and delay ovarian aging by improving the immune system and circulatory system, which will provide an updated program for the treatment of premature ovarian failure (POF) and infertility. © 2017 The Author(s). Published by S. Karger AG, Basel.

Ovarian cancer in Lynch syndrome; a systematic review.

PubMed

Helder-Woolderink, J M; Blok, E A; Vasen, H F A; Hollema, H; Mourits, M J; De Bock, G H

2016-03-01

The aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS. All studies between 1979 and 2015 of women with ovarian cancer and LS or at 50% risk of LS were evaluated. Two reviewers independently evaluated eligible studies and extracted data on age at diagnosis, histological type, FIGO stage, and way of detection according to pre-specified criteria. The studies were assessed for quality using the Newcastle-Ottawa quality assessment scales. The quality score of the 49 identified studies was at least 6 out of 8 and provide clinical information on 747 LS women with ovarian cancer. The mean age at diagnosis was 45.3 (range 19-82) years. Most frequent mutations were MSH2 (47%) and MLH1 (38%). Histopathological data were available for 445 women. The most frequently reported histological type was mixed type (mucinous/endometrioid/clear cell carcinomas) (n = 136; 31%). Most tumours (281, 65%) were diagnosed at an early stage (FIGO I/II). Six studies evaluating the effect of surveillance of ovarian cancer, reported that seven of 22 (32%) ovarian cancers were found during surveillance, 6/7 (86%) were detected at an early stage. This systematic review describes that ovarian cancer in women with LS has a wide age-range of onset, is often diagnosed at an early stage with frequently endometrioid/clear cell histology. Data about the role of surveillance in detection of ovarian cancer in women with LS are scarce however detection at an early stage seems possible. Copyright © 2015 Elsevier Ltd. All rights reserved.

Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

ClinicalTrials.gov

2013-01-24

Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

BRCA1 and BRCA2 mutations in Japanese patients with ovarian, fallopian tube, and primary peritoneal cancer.

PubMed

Sakamoto, Ikuko; Hirotsu, Yosuke; Nakagomi, Hiroshi; Ouchi, Hidetaka; Ikegami, Atsushi; Teramoto, Katsuhiro; Amemiya, Kenji; Mochizuki, Hitoshi; Omata, Masao

2016-01-01

The contribution of BRCA1 and BRCA2 to ovarian cancer in Japanese patients is still unclear. This study investigated the frequency of germline mutations in BRCA1/2 in Japanese patients with ovarian, peritoneal, or fallopian tube cancer, regardless of their family histories, which were suggestive of hereditary breast and ovarian cancer. Ninety-five unselected women with ovarian cancer who were seen from 2013 to 2015 at Yamanashi Prefectural Central Hospital were enrolled. Analyses of BRCA1/2 gene mutations were performed with next-generation sequencing. Twelve of the 95 patients (12.6%), including 5 in the BRCA1 (5.3%) and 7 in the BRCA2 (7.4%), had deleterious mutations. Among the 36 cases with a family history, 6 (16.7%) were found to carry mutations in BRCA1 and BRCA2. Notably, 6 of the 59 cases (10.2%) without a family history also had BRCA1/2 germline mutations. There was no statistical difference between the 2 groups (P = .36). The presence of mutations and their clinical relevance were studied. Mutation carriers were diagnosed at advanced stages (100% of positive cases among stage III or IV cases) and had poor prognostic histological subtypes (100% of positive cases had high-grade serous adenocarcinomas). In this unselected Japanese population, approximately 13% of the cases with ovarian cancer appeared to be associated with an inherited risk, regardless of a family history. This finding indicates that BRCA1/2 genetic testing should be performed for all patients with ovarian cancers. © 2015 American Cancer Society.

BAG3 upregulates Mcl-1 through downregulation of miR-29b to induce anticancer drug resistance in ovarian cancer.

PubMed

Sugio, Asuka; Iwasaki, Masahiro; Habata, Shutaro; Mariya, Tasuku; Suzuki, Miwa; Osogami, Hiroyuki; Tamate, Masato; Tanaka, Ryoichi; Saito, Tsuyoshi

2014-09-01

Ovarian cancer is the leading cause of death from gynecologic cancer, reflecting its often late diagnosis and its chemoresistance. We identified a set of microRNAs whose expression is altered upon BAG3 knockdown. Our primary objective was to examine the relationships between BAG3, miR-29b and Mcl-1, an antiapoptotic Bcl-2 family protein, in ovarian cancer cells. Ovarian cancer cells were cultured and their responsiveness to paclitaxel was tested. Microarray analysis was performed to identify microRNAs differentially expressed in ES2 BAG3 knockdown ovarian cancer cells and their control cells. Primary ovarian cancer tissues were obtained from 56 patients operated on for ovarian cancer. The patients' clinical and pathological data were obtained from their medical records. BAG3 knockdown increased the chemosensitivity to paclitaxel of ES2 ovarian clear cell carcinoma cells to a greater degree than AMOC2 serous adenocarcinoma cells. qRT-PCR analysis showed that miR-29b expression was significantly upregulated in primary cancer tissue expressing low levels of BAG3, as compared to tissue expressing high levels. Moreover, levels of miR-29b correlated significantly with progression-free survival. Upregulation of miR-29b also reduced levels of Mcl-1 and sensitized ES2 cells to low-dose paclitaxel. BAG3 knockdown appears to downregulate expression of Mcl-1 through upregulation of miR-29b, thereby increasing the chemosensitivity of ovarian clear cell carcinoma cells. This suggests that BAG3 is a key determinant of the responsiveness of ovarian cancer cells, especially clear cell carcinoma, to paclitaxel and that BAG3 may be a useful therapeutic target for the treatment of ovarian cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Experimental characterization of recurrent ovarian immature teratoma cells after optimal surgery.

PubMed

Tanaka, Tetsuji; Toujima, Saori; Utsunomiya, Tomoko; Yukawa, Kazunori; Umesaki, Naohiko

2008-07-01

Minimal optimal surgery without chemotherapy is often performed for patients with ovarian immature teratoma, which frequently occurs in young women who hope for future pregnancies. If tumors recur after the operation, anticancer drug chemotherapy is often administered, although few studies have highlighted differences between the recurrent and the primary tumor cells. Therefore, we have established experimental animal models of recurrent ovarian immature teratoma cells after optimal surgery and characterized the anticancer drug sensitivity and antigenicity of the recurrent tumors. Surgically-excised tumor cells of a grade II ovarian immature teratoma were cultured in vitro and transplanted into nude mice to establish stable cell lines. Differential drug sensitivity and antigenicity of the tumor cells were compared between the primary and the nude mouse tumors. Nude mouse tumor cells showed a normal 46XX karyotype. Cultured primary cells showed a remarkably high sensitivity to paclitaxel, docetaxel, adriamycin and pirarubicin, compared to peritoneal cancer cells obtained from a patient with ovarian adenocarcinomatous peritonitis. The drug sensitivity of teratoma cells to 5-fluorouracil, bleomycin or peplomycin was also significantly higher. However, there was no significant difference in sensitivity to platinum drugs between the primary teratoma and the peritoneal adenocarcinoma cells. As for nude mouse tumor cells, sensitivity to 12 anticancer drugs was significantly lower than that of the primary tumor cells, while there was little difference in sensitivity to carboplatin or peplomycin between the primary and nude mouse tumor cells. Flow cytometry showed that the expression of smooth muscle actin (SMA) significantly decreased in nude mouse tumor cells when compared to cultured primary cells. In conclusion, ovarian immature teratomas with normal karyotypes have a malignant potential to recur after minimal surgery. During nude mouse transplantation, SMA

Metabolomic Markers of Altered Nucleotide Metabolism in Early Stage Adenocarcinoma

PubMed Central

Wikoff, William R.; Grapov, Dmitry; Fahrmann, Johannes F.; DeFelice, Brian; Rom, William; Pass, Harvey; Kim, Kyoungmi; Nguyen, UyenThao; Taylor, Sandra L.; Kelly, Karen; Fiehn, Oliver; Miyamoto, Suzanne

2015-01-01

Adenocarcinoma, a type of non-small-cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and non-malignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and non-malignant lung tissue pairs from current or former smokers with early stage (Stage IA–IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared to non-malignant tissue. Cancer-associated biochemical alterations were characterized by: 1) decreased glucose levels, consistent with the Warburg effect, 2) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, 3) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, 4) increased 5'-deoxy-5'-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis and 5) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring. PMID:25657018

Relationship between methylation status of RASSF2A gene promoter and endometriosis-associated ovarian cancer.

PubMed

Xia, Y; Xiong, N; Huang, Y

2018-01-01

Relationship between the methylation status of the RASSF2A gene promoter and endometriosis-associated ovarian cancer (EAOC) was explored. Between January 2013 and January 2016, tissue samples were collected from 30 patients diagnosed with ovarian endometriosis cyst (EC group), 30 patients diagnosed with ovarian endometrial adenocarcinoma (OEA group) and 30 patients diagnosed with ovarian clear cell carcinoma (OCC group). Additionally, 30 cases of normal endometrium tissues were collected for the control group. The methylation status of the RASSF2A promoter was evaluated by combined bisulfite restriction enzyme analysis (COBRA). RT-PCR was used to detect the expression level of RASSF2A mRNA in tissues. Relationship between methylation status and RASSF2A mRNA expression level and the patient age, tumor clinical stage, tumor grading and pathological type were analyzed. Results showed that in the OEA and OCC groups, the methylation degrees of the RASSF2A promoter were obviously higher than that of the other two groups. The expression level of RASSF2A mRNA in the OEA and OCC groups was lower than that of the other two groups. The methylation degree of the RASSF2A promoter was related to clinical staging and grading. No relationship between the methylation degree of the RASSF2A promoter and patient’s age and the pathological type of the tissue was detected. We concluded that the methylation status of the RASSF2A gene promoter could be considered an excellent indicator for early detection of ovarian cancers.

Adenocarcinoma of the lung with scattered consolidation: radiological-pathological correlation and prognosis.

PubMed

Jiang, Binghu; Takashima, Shodayu; Hakucho, Tomoaki; Hodaka, Numasaki; Yasuhiko, Tomita; Masahiko, Higashiyama

2013-10-01

To investigate the clinicopathological features and prognosis in patients with adenocarcinoma of the lung with scattered consolidation (ALSC). Between January 2006 and March 2010, 139 consecutive patients with lung adenocarcinoma of ≤3 cm, who underwent pulmonary resection for lung cancer, were investigated retrospectively. Radiologic classification was based on the findings of thin-section CT such as the presence of consolidation or ground-glass opacity (GGO). Type I (n=15) and Type II (n=14), showed a pure GGO and a mixed GGO with consolidation <50%, respectively. Type IV (n=38) and Type V (n=52) showed a mixed GGO with consolidation ≥50% and a pure consolidation, respectively. Type III (n=20) was the adenocarcinoma of the lung with scattered consolidation (ALSC). The clinicopathological features and prognosis of ALSC was investigated with comparative analysis and survival analysis. Because of the similar recurrence rate for Type I and Type II (P=1.000), Type IV and Type V (P=0.343), we merged Type I and Type II as Type I+II, Type IV and Type V as Type IV+V, respectively. In the 20 (14.4%) patients with ALSC, lymph node metastasis was not observed, and it was rare in lymphatic invasion and vascular invasion. On the basis of IASLC/ATS/ERS 2011 classification, 80% of the ALSC were preinvasive lesions. In Noguchi classification, there was no significant difference between Type I+II and ALSC (P=0.260). The prognosis of ALSC was similar to Type I+II (P=0.408), but better than Type IV+V (P=0.040). Adenocarcinoma of the lung with scattered consolidation (ALSC) on thin-section CT was a relatively favorable prognostic factor. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Intestinal adenocarcinoma in a herd of farmed Sika deer (Cervus nippon): a novel syndrome.

PubMed

Kelly, P A; Toolan, D; Jahns, H

2015-01-01

Intestinal adenocarcinomas were identified in 76 adult deer from a closed herd of 193 breeding animals grazing pasture heavily infested with bracken fern (Pteridium aquilinum). Tumors were observed postmortem in 32 animals with rapid weight loss, and similar neoplasms were detected in a further 44 clinically normal deer at "cull." Tumors were located in distal ileum, cecum, and proximal colon and presented as single (26%) or multiple (74%), variably sized, pale-gray, firm, poorly circumscribed neoplasms with associated intestinal strictures. Histopathologically tumors were well-differentiated, locally infiltrative, low-grade adenocarcinomas of tubular (51%), mucinous (33.5%), or mixed (15.5%) types. Extraintestinal metastases were not observed. The high incidence of intestinal adenocarcinoma within this herd suggests a specific and novel syndrome, and genetic and/or environmental factors may be involved in the pathogenesis. © The Author(s) 2014.

Inovium Ovarian Rejuvenation Trials

ClinicalTrials.gov

2018-05-18

Perimenopausal Disorder; Menopause; Menopause, Premature; Menopause Related Conditions; Menopause Premature Symptomatic; Menopause Premature Asymptomatic; Premature Ovarian Failure; Premature Ovarian Failure, Familial; Premature Ovarian Failure 2A; Premature Ovarian Failure 3; Premature Ovarian Failure 4; Premature Ovarian Failure 1; Premature Ovarian Failure 5; Premature Ovarian Failure 6; Premature Ovarian Failure 7; Premature Ovarian Failure 9; Premature Ovarian Failure 8; Infertility; Infertility, Female; Infertility Unexplained

A prospective study of dietary acrylamide intake and the risk of breast, endometrial, and ovarian cancers

PubMed Central

Wilson, Kathryn M.; Mucci, Lorelei A.; Rosner, Bernard A.; Willett, Walter C.

2010-01-01

Background Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiological studies of acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk of breast, endometrial, and ovarian cancers in a prospective cohort study. Methods We assessed acrylamide intake among 88,672 women in the Nurses’ Health Study using food frequency questionnaires administered every four years. Between 1980 and 2006 we identified 6301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk. Results We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk of endometrial cancer among high acrylamide consumers (adjusted relative risk [RR] for highest versus lowest quintile=1.41, 95% CI: 1.01–1.97, p-value for trend=0.03). We observed a non-significant suggestion of increased risk for ovarian cancer overall (RR 1.25, CI: 0.88–1.77, p-trend=0.12), with a significantly increased risk for serous tumors (RR 1.58, CI: 0.99–2.52, p-trend=0.04). Associations did not differ by smoking status. Conclusions We observed no association between acrylamide and breast cancer. Risk of endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers. Impact This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy. PMID:20693310

Sonographic features of incidentally detected, small, nonpalpable ovarian dermoids.

PubMed

Serafini, G; Quadri, P G; Gandolfo, N G; Gandolfo, N; Martinoli, C; Derchi, L E

1999-09-01

We describe the transvaginal sonographic features of incidentally detected, small, nonpalpable ovarian dermoid cysts. A total of 38 small (less than 3 cm in diameter), nonpalpable, incidentally discovered ovarian dermoids in 35 women were retrospectively reviewed; 3 patients had small bilateral lesions, and 7 had a small ovarian dermoid detected during preoperative evaluation of a symptomatic, large, contralateral lesion. Transvaginal sonography permitted identification of all 38 dermoids, whereas abdominal sonography detected only 22 of the lesions. Three main structural patterns were observed with transvaginal sonography: (1) 20 of 38 lesions had a solid, hyperechoic appearance, either homogeneous (11) or heterogeneous (9); (2) a fluid-filled area with a hyperechoic focus in its wall was seen in 10 cases; and (3) a mixed pattern, with solid and liquid areas, was seen in 8 cases. Calcifications were appreciated in 7 lesions. Acoustic shadowing was noted in 30 cases, either as a shadow posterior to the hyperechoic portion of the mass or as an edge shadow lateral to the lesion. Doppler studies were obtained for 20 lesions but proved inconclusive: 4 mixed-pattern dermoids had a few internal signals with a low resistance pattern; in the remaining cases, there were signals at the periphery of the cysts, but it could not be determined whether these were from vessels within the lesions or from vessels in the surrounding ovarian parenchyma. Surgery confirmed benign cystic dermoids in all 38 cases. Sonographically, small ovarian dermoids have a variety of textural patterns quite similar to those encountered in large, symptomatic lesions. The increased resolution capabilities provided by transvaginal sonography allow incidental detection of previously unsuspected dermoids and permit identification of their nature. Copyright 1999 John Wiley & Sons, Inc.

Epidermal growth factor receptor mutations in Japanese men with lung adenocarcinomas.

PubMed

Tomita, Masaki; Ayabe, Takanori; Chosa, Eiichi; Kawagoe, Katsuya; Nakamura, Kunihide

2014-01-01

Epidermal growth factor receptor (EGFR) mutations play a vital role in the prognosis of patients with lung adenocarcinoma. Such somatic mutations are more common in women who are non-smokers with adenocarcinoma and are of Asian origin. However, to our knowledge, there are few studies that have focused on men. One hundred and eighty-four consecutive patients (90 men and 94 women) of resected lung adenocarcinoma were studied retrospectively. EGFR mutations were positive in 48.9% and negative (wild type) in 51.1%. Overall mutation was significant in women (66.0% vs. 32.2%) compared with men (p<0.001). For overall patients, EGFR mutation status was associated with gender, pStage, pT status, lepidic dominant histologic subtype, pure or mixed ground-glass nodule type on computed tomography and smoking status. However, in men, EGFR mutation status was only associated with lepidic dominant histologic subtype and not the other variables. Interestingly, the Brinkman index of men with mutant EGFR also did not differ from that for the wild type (680.0±619.3 vs. 813.1±552.1 p=0.1077). The clinical characteristics of men with lung adenocarcinoma related to EGFR mutation are not always similar to that of overall patients. Especially we failed to find the relationship between EGFR mutations and smoking status in men.

Comparing long term impact on ovarian reserve between laparoscopic ovarian cystectomy and open laprotomy for ovarian endometrioma

PubMed Central

2013-01-01

Objective To compare the long term impact on ovarian reserve between laparoscopic ovarian cystectomy with bipolar electrocoagulation and laparotomic cystectomy with suturing for ovarian endometrotic cyst. Patient and method(s) 121 patients with benign ovarian endometroitic cysts were randomised to either laparoscopic ovarian cystectomy using bipolar electrocoagulation (61 patients) or laparotomic ovarian cystectomy using sutures (60 patients). Serum follicle-stimulating hormone, Antimullerian hormon, Basal antral follicle Count, mean ovarian diameter, and ovarian stromal blood flow velocity were measured at 6, 12 and 18 months after surgery and compared in both groups. Result(s) A statistically significant increase of serum FSH was found in the laproscopic bipolar group at 6-, 12 and 18-month postoperativly compared to open laparotomy suture group. Also, a statistically significant decrease of the mean AMH value occurred in laproscopic bipolar group at 6-, 12 and 18-month follow- up compared to open laparotomy suture group. Basal antral follicle number, mean ovarian diameter and peak systolic velocity were significantly decreased during the 6-, 12,18 -month follow-up in laproscopic bipolar group compared to open laparotomy suture group. Conclusion(s) After laproscopic ovarian cystecomy for endometrioma all pareameter of ovarian reseve are significantly decreased on long term follow up as compared to open laprotomy. PMID:24180348

Metastasis of ovarian cancer to the breast: A report of two cases and a review of the literature

PubMed Central

TEMPFER, CLEMENS B.; EL FIZAZI, NARIMAN; ERGONENC, HASSAN; SOLASS, WIEBKE

2016-01-01

Metastasis of ovarian cancer to the breast (MOCB) is a rare event. Clinical presentations of MOCB vary and surgery is the mainstay of treatment. The current study presents two cases of MOCB in women with recurrent ovarian cancer first diagnosed in April 2011 and October 2013, respectively. The patients presented to the clinic with a localized, palpable, painful mass in the upper outer quadrant of the right breast and a centrally localized, palpable, painful mass of the left breast, respectively. Breast sonography and mammography showed a singular, round, homogenous tumor with irregular borders in each case. An ipsilateral enlarged axillary node was palpable in one case. Tumor biopsy revealed an undifferentiated adenocarcinoma of unknown origin in one case and a moderately-differentiated adenocarcinoma suspected to be breast cancer in the other case. Tumor cells were positive for estrogen receptor and paired box 8, and negative for GATA binding protein 3 in the two cases. Palliative mastectomy was performed in one case and lumpectomy with ipsilateral axillary sentinel node biopsy in the other case, and the final histology revealed MOCB in each. The post-operative course of the disease was uneventful and the patients continued with their ovarian cancer-specific chemotherapy. One patient succumbed to disease progression 2 months after breast surgery. The other patient remains alive and is currently undergoing systemic chemotherapy. The current study also presents a review of 110 cases of MOCB identified in a literature search of Pubmed. Data from these studies, including the clinical and histological characteristics of MOCB, and the clinical management and prognosis are discussed. Overall, MOCB is rare, with distinct clinical and histological features. The disease is usually treated with local surgical excision or mastectomy and has a poor prognosis. PMID:27313731

Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies.

PubMed

Sipak-Szmigiel, Olimpia; Włodarski, Piotr; Ronin-Walknowska, Elżbieta; Niedzielski, Andrzej; Karakiewicz, Beata; Słuczanowska-Głąbowska, Sylwia; Laszczyńska, Maria; Malinowski, Witold

2017-04-04

Although immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases. The study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively. Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers. Elevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid

Ovarian preservation in locally advanced cervical cancer undergoing neoadjuvant chemotherapy and radical surgery: our experience and analysis of the literature.

PubMed

Signorelli, Mauro; Bogani, Giorgio; Chiappa, Valentina; Ditto, Antonino; Scaffa, Cono; Martinelli, Fabio; Lorusso, Domenica; Raspagliesi, Francesco

2018-03-30

The aim of this study was to estimate the rate of ovarian metastases and recurrences among patients affected by locally advanced stage cancer patients (LACC), undergoing neoadjuvant chemotherapy (NACT) and radical surgery with conservation of ovaries. Retrospective evaluation of consecutive patients affected by LACC (stage IB2- IIB), treated by NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990-2015. Overall, 331 patients were included. Stage at presentation included stage IB2, IIA and IIB in 120 (36.3%), 63 (19%) and 148 (44.7%) patients, respectively. Main histotype was squamous cell carcinoma (n=265, 80.1%) followed by adenocarcinoma/adenosquamous (n=51, 15.4%), and more than half of patients had a grade 3 carcinoma . Overall, 102 (30.8%) women had at least one ovary preserved during surgery, while 229 (69.2%) had bilateral salpingo-oophorectomy. Comparing patients who had ovarian preservation with patients who had not, we observed that the two groups were comparable in terms of baseline characteristics. Survival outcomes were not influenced by ovarian preservation (disease-free (p=0.93) and overall (p=0.65) survivals). One (1%) woman had a localized ovarian recurrence. Our data suggest that ovarian preservation at the time of surgery is a safe option among women with LACC after NACT with no detrimental impact on oncologic outcome. Further prospective studies are warranted.

Ovulation and extra-ovarian origin of ovarian cancer

PubMed Central

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

2014-01-01

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

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 ...

Next-Generation Sequencing of Matched Primary and Metastatic Rectal Adenocarcinomas Demonstrates Minimal Mutation Gain and Concordance to Colonic Adenocarcinomas.

PubMed

Crumley, Suzanne M; Pepper, Kristi L; Phan, Alexandria T; Olsen, Randall J; Schwartz, Mary R; Portier, Bryce P

2016-06-01

-Colorectal carcinoma is the third most common cause of cancer death in males and females in the United States. Rectal adenocarcinoma can have distinct therapeutic and surgical management from colonic adenocarcinoma owing to its location and anatomic considerations. -To determine the oncologic driver mutations and better understand the molecular pathogenesis of rectal adenocarcinoma in relation to colon adenocarcinoma. -Next-generation sequencing was performed on 20 cases of primary rectal adenocarcinoma with a paired lymph node or solid organ metastasis by using an amplicon-based assay of more than 2800 Catalogue of Somatic Mutations in Cancer (COSMIC)-identified somatic mutations. -Next-generation sequencing data were obtained on both the primary tumor and metastasis from 16 patients. Most rectal adenocarcinoma cases demonstrated identical mutations in the primary tumor and metastasis (13 of 16, 81%). The mutations identified, listed in order of frequency, included TP53, KRAS, APC, FBXW7, GNAS, FGFR3, BRAF, NRAS, PIK3CA, and SMAD4. -The somatic mutations identified in our rectal adenocarcinoma cohort showed a strong correlation to those previously characterized in colonic adenocarcinoma. In addition, most rectal adenocarcinomas harbored identical somatic mutations in both the primary tumor and metastasis. These findings demonstrate evidence that rectal adenocarcinoma follows a similar molecular pathogenesis as colonic adenocarcinoma and that sampling either the primary or metastatic lesion is valid for initial evaluation of somatic mutations and selection of possible targeted therapy.

Lynch syndrome-related small intestinal adenocarcinomas.

PubMed

Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

2017-03-28

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

Lynch syndrome-related small intestinal adenocarcinomas

PubMed Central

Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

2017-01-01

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas. PMID:28206961

PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

ClinicalTrials.gov

2018-06-24

Small Cell Lung Cancer; Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Castration Resistant Prostate Adenocarcinoma; Soft Tissue Sarcoma; Ovarian Adenocarcinoma; Advanced Well-differentiated Neuroendocrine Tumors; Diffuse Large B Cell Lymphoma

Primary peritoneal adenocarcinoma as content of an incarcerated umbilical hernia: A case-report and review of the literature.

PubMed

Varga-Szabó, D; Papadakis, M; Pröpper, S; Zirngibl, H

2016-01-01

Umbilical hernia is a common finding in many cases, posing potentially life-threatening complications, such as incarceration or strangulation. The presence of malignancy in hernia sacs is, however, rather rare. Here we report on a case of primary peritoneal adenocarcinoma found through histological examination of omental tissue, resected due to an incarcerated umbilical hernia of an 84-years-old woman. There was no macroscopic sign of malignancy during operation; only after routine examination of histological sections the diagnosis was found. To our knowledge this is the first report of primary peritoneal cancer as content of an umbilical hernia. This is a rare neoplasm and histologically identical to epithelial ovarian carcinoma. For this reason, the diagnosis is usually based on the histological finding and exclusion of a primary ovarian tumor. Primary peritoneal cancer has a poor outcome in general. Early diagnosis is, therefore, essential for effective treatment. Histological analysis of resected hernia sac or content should be performed routinely to discover malignant diseases in the background of a hernia. Copyright © 2015. Published by Elsevier Ltd.

CT imaging of ovarian yolk sac tumor with emphasis on differential diagnosis

PubMed Central

Li, Yang-Kang; Zheng, Yu; Lin, Jian-Bang; Xu, Gui-Xiao; Cai, Ai-Qun; Zhou, Xiu-Guo; Zhang, Guo-Jun

2015-01-01

Ovarian yolk sac tumors (YSTs) are rare neoplasms. No radiological study has been done to compare the imaging findings between this type of tumor and other ovarian tumors. Here we analyzed the CT findings of 11 pathologically proven ovarian YSTs and compared their imaging findings with 18 other types of ovarian tumors in the same age range. Patient age, tumor size, tumor shape, ascites and metastasis of two groups did not differ significantly (P > 0.05). A mixed solid-cystic nature, intratumoral hemorrhage, marked enhancement and dilated intratumoral vessel of two groups differed significantly (P < 0.05). The area under the ROC curve of four significant CT features was 0.679, 0.707, 0.705, and 1.000, respectively. Multivariate logistic regression analysis identified two independent signs of YST: intratumoral hemorrhage and marked enhancement. Our results show that certain suggestive CT signs that may be valuable for improving the accuracy of imaging diagnosis of YST and may be helpful in distinguishing YST from other ovarian tumors. PMID:26074455

Lead, selenium and nickel concentrations in epithelial ovarian cancer, borderline ovarian tumor and healthy ovarian tissues.

PubMed

Canaz, Emel; Kilinc, Metin; Sayar, Hamide; Kiran, Gurkan; Ozyurek, Eser

2017-09-01

Wide variation exists in ovarian cancer incidence rates suggesting the importance of environmental factors. Due to increasing environmental pollution, trace elements and heavy metals have drawn attention in studies defining the etiology of cancer, but scant data is available for ovarian cancer. Our aim was to compare the tissue concentrations of lead, selenium and nickel in epithelial ovarian cancer, borderline tumor and healthy ovarian tissues. The levels of lead, selenium and nickel were estimated using atomic absorption spectrophotometry in formalin-fixed paraffin-embedded tissue samples. Tests were carried out in 20 malignant epithelial ovarian cancer, 15 epithelial borderline tumor and 20 non-neoplastic healthy ovaries. Two samples were collected for borderline tumors, one from papillary projection and one from the smooth surface of cyst wall. Pb and Ni concentrations were found to be higher both in malignant and borderline tissues than those in healthy ovaries. Concentrations of Pb and Ni in malignant tissues, borderline papillary projections and capsular tissue samples were not different. Comparison of Se concentrations of malignant, borderline and healthy ovarian tissues did not reveal statistical difference. Studied metal levels were not found to be different in either papillary projection or in cyst wall of the borderline tumors. This study revealed the accumulation of lead and nickel in ovarian tissue is associated with borderline and malignant proliferation of the surface epithelium. Accumulation of these metals in epithelial ovarian cancer and borderline ovarian tumor has not been demonstrated before. Copyright © 2017 Elsevier GmbH. All rights reserved.

Gastric choriocarcinoma admixed with an α-fetoprotein-producing adenocarcinoma and separated adenocarcinoma

PubMed Central

Eom, Bang Wool; Jung, So-Youn; Yoon, Hongman; Kook, Myeong-Cherl; Ryu, Keun Won; Lee, Jun Ho; Kim, Young-Woo

2009-01-01

We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adenocarcinoma. A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum. The patient underwent radical subtotal gastrectomy with D2 lymph node dissection and Billroth II gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively. PMID:19860007

Pemetrexed-carboplatin with intercalated icotinib in the treatment of patient with advanced EGFR wild-type lung adenocarcinoma

PubMed Central

Xu, Tongpeng; Wu, Hao; Jin, Shidai; Min, Huang; Zhang, Zhihong; Shu, Yongqian; Wen, Wei; Guo, Renhua

2017-01-01

Abstract Rationale: Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. Patient concerns: Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. Diagnoses: We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib. Interventions: In this case, we reported the successful long-term maintenance treatment of a patient with EGFR wt NSCLC with pemetrexed and Icotinib. The patient (40-year-old female) was found with ovarian masses and lung masses. Pathological, immunohistochemical, and amplification refractory mutation system (ARMS) assay examinations of ovarian specimen suggested the expression of metastatic lung adenocarcinoma with wt EGFR. After failure treatment with paclitaxel-carboplatin, the patient received 4 cycles of pemetrexed plus platinum with intercalated icotinib and then remained on pemetrexed and icotinib. Outcomes: A partial response was achieved after the treatment. The patient's condition had remained stable on pemetrexed and icotinib for more than 20 months, with no evidence of progression. Lessons: To our knowledge, this is the first report using the long-term maintenance treatment with pemetrexed and intercalated icotinib in EGFR wt patient. The therapeutic strategies warrant further exploration in selected populations of NSCLC. PMID:28816950

The immunohistochemical expression of endocrine gland-derived-VEGF (EG-VEGF) as a prognostic marker in ovarian cancer.

PubMed

Bălu, Sevilla; Pirtea, L; Gaje, Puşa; Cîmpean, Anca Maria; Raica, M

2012-01-01

Ovarian cancer-related angiogenesis is a complex process orchestrated by many positive and negative regulators. Many growth factors are involved in the development of the tumor-associated vasculature, and from these, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) seems to play a crucial role. EG-VEGF is the first organ-specific angiogenic factor and its effects are restricted to the endothelial cells of the endocrine glands. Although EG-VEGF was detected in both normal and neoplastic ovaries, its clinical significance remains controversial. In the present study, we analyzed 30 patients with epithelial ovarian cancer, and the immunohistochemical expression of EG-VEGF was compared with the conventional clinico-pathological parameters of prognosis. Neoplastic cells of the ovarian carcinoma expressed EG-VEGF in 73.33% of the cases, as a cytoplasmic granular product of reaction. We found a strong correlation between the expression of EG-VEGF at protein level and tumor stage, grade, and microscopic type. The expression of EG-VEGF was found in patients with stage III and IV, but not in stage II. The majority of serous adenocarcinoma, half of the cases with clear cell carcinoma and two cases with endometrioid carcinoma showed definite expression in tumor cells. No positive reaction was found in the cases with mucinous carcinoma. Our results showed that EG-VEGF expression is an indicator not only of the advanced stage, but also of ovarian cancer progression. Based on these data, we concluded that EG-VEGF expression in tumor cells of the epithelial ovarian cancer is a good marker of unfavorable prognosis and could be an attractive therapeutic target in patients with advanced-stage tumors, refractory conventional chemotherapy.

Mucinous (colloid) adenocarcinomas secrete distinct O-acylated forms of sialomucins: a histochemical study of gastric, colorectal and breast adenocarcinomas.

PubMed

Sáez, C; Japón, M A; Poveda, M A; Segura, D I

2001-12-01

Mucinous (colloid) adenocarcinomas represent a distinct group of tumours defined by the presence of large amounts of extracellular mucins. By using histochemical methods, we analysed mucins secreted by mucinous versus non-mucinous adenocarcinomas and looked for differential secretion profiles. Sixty-four adenocarcinomas were studied (23 colorectal, 17 gastric, and 24 breast tumours). Thirty-two tumours were of the colloid type. The following methods were applied to paraffin tissue sections: (i) Alcian blue (pH 2.5) and periodic acid-Schiff (PAS); (ii) high iron diamine and Alcian blue (pH 2.5); (iii) periodic acid borohydride, potassium hydroxide, and PAS; (iv) periodic acid-thionine Schiff, potassium hydroxide, and PAS; and (v) periodic acid-borohydride and PAS. Most adenocarcinomas secreted acidic mucins, with sialomucins predominating over sulfomucins, except for non-mucinous adenocarcinomas of the breast which showed predominant neutral mucins. All mucinous adenocarcinomas contained C9-O-acyl sialic acid as mono, di(C8,C9)-, or tri(C7,C8,C9)-O-acyl forms. Acidic mucins secreted by the majority of non-colloid adenocarcinomas consisted of non-O-acylated sialomucins. C9-O-acylation of sialic acid is a characteristic feature of mucinous adenocarcinomas and can be readily detected by histochemical methods.

[LAPAROSCOPIC SURGERY FOR EARLY OVARIAN CANCER: EXPERIENCE AT THE P. A. HERZEN ONCOLOGY RESEARCH INSTITUTE].

PubMed

Shevchuk, A S; Novikova, E G; Utkina, A B

2015-01-01

For the period from 2003 to 2014 at the Oncogynecology Department laparoscopic surgery for ovarian cancer was performed in 49 patients aged 19 to 76 years. During the surgical interventions special attention was paid to the principles of oncological radicalism and ablastics, the volume of surgery depended on the extent of tumor process, morphological characteristics of tumor, a patient's age and the desire to preserve reproductive function. In 42 (85.7%) cases laparoscopic procedures were conducted to restaging (after non-radical operations in gynecological hospitals). In all 49 patients a histological form of ovarian tumor corresponded to adenocarcinoma. Mean operative time was 140 ± 10,5 minutes, the average blood loss--80,2 ± 14,3 ml. Postoperative complications (bleeding from the omentum) were recorded in 1 (2%) patient, the need for conversion was occurred in 4 (8.2%) cases due to the adhesive process or signs of dissemination. As a result of laparoscopic surgery an increase in staging of disease was fixed in 14 cases (28.6%). Follow-up median was 45 months, relapses occurred in 5 (10.2%) patients. Of 49 patients 2 (4.1%) died from disease progression. Disease-free and overall survival rates were 89.8% and 95.9%, respectively. Thus, data of world literature and our own experience indicate the potential equivalent of laparoscopic and laparotomy approaches in treatment for early ovarian cancer.

Monoclonal antibody DS6 detects a tumor-associated sialoglycotope expressed on human serous ovarian carcinomas.

PubMed

Kearse, K P; Smith, N L; Semer, D A; Eagles, L; Finley, J L; Kazmierczak, S; Kovacs, C J; Rodriguez, A A; Kellogg-Wennerberg, A E

2000-12-15

A newly developed murine monoclonal antibody, DS6, immunohistochemically reacts with an antigen, CA6, that is expressed by human serous ovarian carcinomas but not by normal ovarian surface epithelium or mesothelium. CA6 has a limited distribution in normal adult tissues and is most characteristically detected in fallopian tube epithelium, inner urothelium and type 2 pneumocytes. Pre-treatment of tissue sections with either periodic acid or neuraminidase from Vibrio cholerae abolishes immunoreactivity with DS6, indicating that CA6 is a neuraminidase-sensitive and periodic acid-sensitive sialic acid glycoconjugate ("sialoglycotope"). SDS-PAGE of OVCAR5 cell lysates has revealed that the CA6 epitope is expressed on an 80 kDa non-disulfide-linked glycoprotein containing N-linked oligosaccharides. Two-dimensional non-equilibrium pH gradient gel electrophoresis indicates an isoelectric point of approximately 6.2 to 6.5. Comparison of the immunohistochemical distribution of CA6 in human serous ovarian adenocarcinomas has revealed similarities to that of CA125; however, distinct differences and some complementarity of antigen expression were revealed by double-label, 2-color immunohistochemical studies. The DS6-detected CA6 antigen appears to be distinct from other well-characterized tumor-associated antigens, including MUC1, CA125 and the histo-blood group-related antigens sLea, sLex and sTn. Copyright 2000 Wiley-Liss, Inc.

Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

PubMed

Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

2016-01-01

There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

[Peripubertal ovarian cyst torsion as an early complication of undiagnosed polycystic ovarian syndrome].

PubMed

Ságodi, László; Schmidt, Ildikó; Vámosi, Ildikó; Barkai, László

2013-01-20

The aim of the authors is to present two cases which raise the possibility of an association between polycystic ovarian syndrome/hyperandrogenism and ovarian cyst torsion in peripubertal girls. Androgen excess may cause more frequently ovarian cyst formation in premenarcheal or young adolescents with undiagnosed polycystic ovarian syndrome than in adults. The authors recommend that polycystic ovarian syndrome as well as late onset congenital adrenal hyperplasia should be considered in peripubertal adolescents with ovarian cyst torsion. In case polycystic ovarian syndrome is confirmed, adequate management according to age and pubertal development of the patients should be commenced.

Pemetrexed-carboplatin with intercalated icotinib in the treatment of patient with advanced EGFR wild-type lung adenocarcinoma: A case report.

PubMed

Xu, Tongpeng; Wu, Hao; Jin, Shidai; Min, Huang; Zhang, Zhihong; Shu, Yongqian; Wen, Wei; Guo, Renhua

2017-08-01

Tyrosine kinase inhibitors (TKIs) are known to have greater efficacy in epidermal growth factor receptor (EGFR) mutation nonsmall cell lung cancer (NSCLC). However, about 10% of EGFR wild-type (wt) patients respond to TKIs. Several strategies to increase the efficacy of TKIs in wt NSCLC are the subjects of ongoing investigations. One of them is combining EGFR TKI with intercalated chemotherapy. We describe a patient with EGFR wt NSCLC, who was found with ovarian and lung metastasis, was treated with pemetrexed and intercalated icotinib. In this case, we reported the successful long-term maintenance treatment of a patient with EGFR wt NSCLC with pemetrexed and Icotinib. The patient (40-year-old female) was found with ovarian masses and lung masses. Pathological, immunohistochemical, and amplification refractory mutation system (ARMS) assay examinations of ovarian specimen suggested the expression of metastatic lung adenocarcinoma with wt EGFR. After failure treatment with paclitaxel-carboplatin, the patient received 4 cycles of pemetrexed plus platinum with intercalated icotinib and then remained on pemetrexed and icotinib. A partial response was achieved after the treatment. The patient's condition had remained stable on pemetrexed and icotinib for more than 20 months, with no evidence of progression. To our knowledge, this is the first report using the long-term maintenance treatment with pemetrexed and intercalated icotinib in EGFR wt patient. The therapeutic strategies warrant further exploration in selected populations of NSCLC.

Changes in ovarian reserve and ovarian blood flow in patients with polycystic ovary syndrome following laparoscopic ovarian drilling.

PubMed

Kamal, Nasser; Sanad, Zakaria; Elkelani, Osama; Rezk, Mohamed; Shawky, Mohamed; Sharaf, Abd-Elbar

2018-04-10

This prospective cohort study was conducted on 80 patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome undergoing laparoscopic ovarian drilling (LOD). Pre- and post-LOD ovarian reserve parameters (anti-Mullerian hormone: AMH, ovarian volume: OV, and antral follicle count: AFC) and ovarian stromal blood flow indices (Vascularization index: VI, flow index: FI, and vascularization flow index: VFI) were measured to explore the effect of LOD and to find out the correlation between serum AMH and different clinical, hormonal, and ultrasonic variables. There was a highly significant reduction of the serum AMH (p < .001) after LOD with significant reduction in OV, AFC and vascular indices (VI, FI and VFI) of the right and left ovaries (p < .05). LOD significantly reduced ovarian reserve parameters (AMH, OV and AFC) and ovarian stromal blood flow indices (VI, FI and VFI) with no observed correlation between AMH levels and Doppler indices.

Cells of origin of ovarian cancer: ovarian surface epithelium or fallopian tube?

PubMed

Klotz, Daniel Martin; Wimberger, Pauline

2017-12-01

Ovarian cancer is the fifth most common cancer in women and one of the leading causes of death from gynecological malignancies. Despite of its clinical importance, ovarian tumorigenesis is poorly understood and prognosis remains poor. This is particularly true for the most common type of ovarian cancer, high-grade serous ovarian cancer. Two models are considered, whether it arises from the ovarian surface epithelium or from the fallopian tube. The first model is based on (1) the pro-inflammatory environment caused by ovulation events, (2) the expression pattern of ovarian inclusion cysts, and (3) biomarkers that are shared by the ovarian surface epithelium and malignant growth. The model suggesting a non-ovarian origin is based on (1) tubal precursor lesions, (2) genetic evidence of BRCA1/2 mutation carriers, and (3) recent animal studies. Neither model has clearly demonstrated superiority over the other. Therefore, one can speculate that high-grade serous ovarian cancer may arise from two different sites that undergo similar changes. Both tissues are derived from the same embryologic origin, which may explain how progenitor cells from different sites can respond similar to stimuli within the ovaries. However, distinct molecular drivers, such as BRCA deficiency, may still preferentially arise from one site of origin as precancerous mutations are frequently seen in the fallopian tube. Confirming the origin of ovarian cancer has important clinical implications when deciding on cancer risk-reducing prophylactic surgery. It will be important to identify key biomarker to uncover the sequence of ovarian tumorigenesis.

Effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women.

PubMed

El-Mazny, Akmal; Kamel, Ahmed; Ramadan, Wafaa; Gad-Allah, Sherine; Abdelaziz, Suzy; Hussein, Ahmed M

2016-01-01

Angiogenesis has been found to be among the most important factors in the pathogenesis of endometriosis. The formation of new blood vessels is critical for the survival of newly implanted endometriotic foci. The use of 3-D power Doppler allows for the demonstration of the dynamic vascular changes that occur during the process of in vitro fertilization (IVF). We aimed to evaluate the effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women. In a case-control study at a university teaching hospital, 138 women with unilateral ovarian endometrioma scheduled for IVF were compared to 138 women with male-factor or unexplained infertility. In the mid-luteal (peri-implantation) phase of the cycle, endometrial thickness, uterine and ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, 3-D power Doppler vascularization index (VI), flow index (FI), and vascularization FI (VFI) values were measured in both groups. There were no significant differences ( P >0.05) in endometrial thickness, uterine ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, or VI, FI, and VFI between the two groups. Furthermore, the endometrial and ovarian Doppler indices were not influenced by endometrioma size. No significant differences were observed in the ovarian Doppler indices between endometrioma-containing ovaries and contralateral ovaries. Ovarian endometrioma is not associated with impaired endometrial and ovarian blood flows in infertile women scheduled for IVF, and it is not likely to affect endometrial receptivity or ovarian function through a vascular mechanism.

Ovarian preservation in a young patient with Gorlin syndrome and multiple bilateral ovarian masses.

PubMed

Morse, Christopher B; McLaren, Janet F; Roy, Darshan; Siegelman, Evan S; Livolsi, Virginia A; Gracia, Clarisa R

2011-07-01

To report a case of bilateral ovarian fibromas and ovarian leiomyomas in a young patient with Gorlin syndrome and to highlight issues of fertility preservation, ovarian conservation, and preimplantation genetic diagnosis in this population. Case report. University hospital. A 15-year-old female patient with Gorlin syndrome and bilateral ovarian masses. Ultrasound, magnetic resonance imaging, hormone analysis, and laparotomy with resection of ovarian fibromas. Preservation of ovarian function, pathologic diagnosis. Our patient represented an adolescent case of bilateral ovarian fibromas and leiomyomas in Gorlin syndrome presenting with menstrual irregularities. She was managed surgically with resection of the lesions and conservation of normal ovarian tissue. In Gorlin syndrome, ovarian fibromas are a common clinical manifestation. Patients with ovarian involvement may present with complex gynecologic needs and may have decreased fertility potential. Careful surgical management, follow-up, and counseling on options for future fertility should be offered to all patients. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers.

PubMed

Grisendi, Valentina; La Marca, Antonio

2017-06-01

In assisted reproduction technologies (ART) the controlled ovarian stimulation (COS) therapy is the starting point from which a good oocytes retrieval depends. Treatment individualization is based on ovarian response prediction, which largely depends on a woman's ovarian reserve. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are considered the most accurate and reliable markers of ovarian reserve. A literature search was carried out for studies that addressed the ability of AMH and AFC to predict poor and/or excessive ovarian response in IVF cycles. According to the predicted response to ovarian stimulation (poor- normal- or high-response) is today possible not only to personalize pre-treatment counseling with the couple, but also to individualize the ovarian stimulation protocol, choosing among GnRH-agonists or antagonists for endogenous follicle-stimulating hormone (FSH) suppression and formulating the FSH starting dose most adequate for the single patients. In this review we discuss how to choose the best COS therapy for the single patient, on the basis of the markers-guided ovarian response prediction.

Risk of borderline ovarian tumors among women with benign ovarian tumors: A cohort study.

PubMed

Guleria, Sonia; Jensen, Allan; Kjær, Susanne K

2018-01-01

A growing number of studies suggest that some ovarian cancers can arise from benign and borderline ovarian tumors. However, studies on the association between benign and borderline ovarian tumors are lacking. We studied the overall- and histotype-specific risk of borderline ovarian tumors among women with a benign ovarian tumor. This nationwide cohort study included all Danish women diagnosed with a benign ovarian tumor (n=139,466) during 1978-2012. The cohort was linked to the Danish Pathology Data Bank and standardized incidence ratios (SIR) with 95% confidence intervals (CI) were calculated. Women with benign ovarian tumors had increased risks for subsequent borderline ovarian tumors (SIR 1.62, 95% CI 1.43-1.82), and this applied to both serous (SIR 1.69, 95% CI 1.39-2.03) and mucinous (SIR 1.75, 95% CI 1.45-2.10) histotypes of borderline ovarian tumors. The risk for borderline ovarian tumors was primarily increased for women diagnosed with a benign ovarian tumor before 40years of age. The risk remained increased up to 9years after a benign ovarian tumor diagnosis. Finally, the associations did not change markedly when analyzed for the different histotypes of benign (solid and cystic tumors) and borderline (serous and mucinous tumors) ovarian tumors. Women with benign ovarian tumors have a long-term increased risk for borderline ovarian tumors. However, as all associations in this study were only adjusted for age and calendar period of diagnosis, more studies that are able to adjust for additional potential confounding variables are required to further understand these associations. Copyright © 2017 Elsevier Inc. All rights reserved.

Cutaneous metastases of prostatic adenocarcinoma

PubMed Central

Patne, Shashikant C.U.; Naik, Bitan; Patnaik, Pranab; Trivedi, Sameer

2015-01-01

Prostatic adenocarcinoma (PA) is a common visceral malignancy of elderly men. Cutaneous metastasis of PA is rare. The incidence is <1%. A 55-year-old man presented with urinary symptoms and multiple cutaneous nodules around suprapubic region, inner aspect of both thighs and scrotum. Fine-needle aspiration cytology (FNAC) of cutaneous nodules was suggestive of metastatic adenocarcinoma. Skin and prostatic biopsies confirmed the cytological diagnosis. Serum level of prostate specific antigen was raised. Total prostatectomy revealed adenocarcinoma of Gleason's score 7 (3 + 4). Though rare, cutaneous metastases of PA must be known to cytopathologists. Meticulously performed FNAC in such cases may help in early diagnosis. PMID:26229250

Prognostic value of estrogen receptor and progesterone receptor tumor expression in Danish ovarian cancer patients: from the 'MALOVA' ovarian cancer study.

PubMed

Høgdall, Estrid V S; Christensen, Lise; Høgdall, Claus K; Blaakaer, Jan; Gayther, Simon; Jacobs, Ian J; Christensen, Ib Jarle; Kjaer, Susanne K

2007-11-01

Estrogen and progesterone are important hormones secreted by the ovary acting through specific receptors. Tumor tissue expression profiles of these have demonstrated prognostic value in malignancies such as breast, uterine and prostate cancer. In this study, including tissue samples from 773 Danish patients with an ovarian tumor, we evaluated whether estrogen receptor (ER) and progesterone receptor (PR) expression correlated with clinico-pathological parameters, and a possible prognostic impact on ovarian cancer (OC) patients was investigated. Using tissue array and immunohistochemistry, we analyzed the ER and PR expression levels in tissues from 582 women with OC and 191 women with low malignancy potential (LMP) ovarian tumors. Our results demonstrated that ER was expressed in 30 of the 191 LMP tumors (16%) and in 207 of the 582 OC (36%). PR was expressed in 38 LMP tumors (20%) and in 115 OC (20%). For both tumor types an excess of positive tumors was found in the serous compared to the mucinous subtype (p< or =0.00001). The frequency of ER expression-positive OC increased with increasing FIGO stage (p=0.0003), and the frequency of PR-positive tumors increased with increasing histological grade (p=0.0006). In a Cox survival analysis, a tissue ER and PR expression 10% or higher was found to imply an independent significant advantageous course of patient disease-specific survival (ER: hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.63-0.99; PR: HR, 0.69; 95% CI, 0.51-0.94) together with FIGO stage, residual tumor after primary surgery, age at diagnosis and other histological types vs. serous adenocarcinoma. The histological grade of tumor was found to have no independent prognostic value. The prognostic value of ER and PR was found additive with a HR for patients with high ER and PR expression of 0.48 (95% CI, 0.31-0.74) compared to patients with <10% expression for both receptors. In conclusion, our results predict that an elevated expression of ER and PR

Evaluation of the new IASLC/ATS/ERS proposed classification of adenocarcinoma based on lepidic pattern in patients with pathological stage IA pulmonary adenocarcinoma.

PubMed

Nakagiri, Tomoyuki; Sawabata, Noriyoshi; Morii, Eiichi; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Okumura, Meinoshin

2014-11-01

The International association for the study of cancer (IASLC)/American thoracic society (ATS)/European respiratory society (ERS) has established a new subclassification of lung adenocarcinoma, especially for the lepidic pattern component, formerly called bronchioloalveolar adenocarcinoma (BAC). According to the new classification, BAC has been classified into the following 4 main subtypes: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IA), and variants of invasive adenocarcinoma (VIA). An observational study was conducted to validate this classification in patients with pathological stage IA pulmonary adenocarcinoma. 147 patients treated for pathological stage IA lung adenocarcinoma by complete resection at Osaka University Medical Hospital from January 1993 to December 2002 were assessed. The tumor specimens of the cohort were classified into the 4 subgroups. In addition, these groups were compared for various prognostic factors. Adenocarcinoma in situ was observed in 30 patients, MIA in 8, IA in 104, and VIA in 5 patients, with 5-year survival rates of 100, 100, 85.5, and 60.0 %, respectively. The relationship between the histological classification and K-ras mutation was significant (p < 0.001), especially when comparing the VIA group with the others (p ≪ 0.001). Ki67-labeling indices were significantly different between the AIS and IA groups (p = 0.040). This study validated the proposed IASLC/ATS/ERS classification for pulmonary adenocarcinoma in patients with pathological stage IA pulmonary adenocarcinoma. The difference between AIS and IA may depend on the proliferation of the carcinoma. In addition, the difference between VIA and the other adenocarcinoma types may depend on genetic factors, especially K-ras mutations.

Endometrioid adenocarcinoma of the uterus with a minimal deviation invasive pattern.

PubMed

Landry, D; Mai, K T; Senterman, M K; Perkins, D G; Yazdi, H M; Veinot, J P; Thomas, J

2003-01-01

Minimal deviation adenocarcinoma of endometrioid type is a rare pathological entity. We describe a variant of typical endometrioid adenocarcinoma associated with minimal deviation adenocarcinoma of endometrioid type. One 'pilot' case of minimal deviation adenocarcinoma of endometrioid type associated with typical endometrioid adenocarcinoma was encountered at our institution in 2001. A second case of same type was received in consultation. We reviewed 168 consecutive hysterectomy specimens diagnosed with 'endometrioid adenocarcinoma' specifically to identify areas of minimal deviation adenocarcinoma of endometrioid type. Immunohistochemistry was done with the following antibodies: MIB1, p53, oestrogen receptor (ER), progesterone receptor (PR), cytokeratin 7 (CK7), cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), and vimentin (VIM). Four additional cases of minimal deviation adenocarcinoma of endometrioid type were identified. All six cases of minimal deviation adenocarcinoma of endometrioid type were associated with superficial endometrioid adenocarcinoma. In two cases with a large amount of minimal deviation adenocarcinoma of endometrioid type, the cervix was involved. The immunoprofile of two representative cases was ER+, PR+, CK7+, CK20-, CEA-, VIM+. MIB1 immunostaining of four cases revealed little proliferative activity of the minimal deviation adenocarcinoma of endometrioid type glandular cells (0-1%) compared with the associated 'typical' endometrioid adenocarcinoma (20-30%). The same four cases showed no p53 immunostaining in minimal deviation adenocarcinoma of endometrioid type compared with a range of positive staining in the associated endometrioid adenocarcinoma. Minimal deviation adenocarcinoma of endometrioid type more often develops as a result of differentiation from typical endometrioid adenocarcinoma than de novo. Due to its deceptively benign microscopic appearance, minimal deviation adenocarcinoma of endometrioid type may be overlooked and

Pulmonary adenocarcinoma: A renewed entity in 2011

PubMed Central

Kadara, Humam; Kabbout, Mohamed; Wistuba, Ignacio I.

2014-01-01

Lung cancer, of which non-small-cell lung cancer comprises the majority, is the leading cause of cancer-related deaths in the United States and worldwide. Lung adenocarcinomas are a major subtype of non-small-cell lung cancers, are increasing in incidence globally in both males and females and in smokers and non-smokers, and are the cause for almost 50% of deaths attributable to lung cancer. Lung adenocarcinoma is a tumour with complex biology that we have recently started to understand with the advent of various histological, transcriptomic, genomic and proteomic technologies. However, the histological and molecular pathogenesis of this malignancy is still largely unknown. This review will describe advances in the molecular pathology of lung adenocarcinoma with emphasis on genomics and DNA alterations of this disease. Moreover, the review will discuss recognized lung adenocarcinoma preneoplastic lesions and current concepts of the early pathogenesis and progression of the disease. We will also portray the field cancerization phenomenon and lineage-specific oncogene expression pattern in lung cancer and how both remerging concepts can be exploited to increase our understanding of lung adenocarcinoma pathogenesis for subsequent development of biomarkers for early detection of adenocarcinomas and possibly personalized prevention. PMID:22040022

Immunohistochemistry of ductal adenocarcinoma of the prostate and adenocarcinomas of non-prostatic origin: a comparative study.

PubMed

Seipel, Amanda H; Samaratunga, Hemamali; Delahunt, Brett; Wiklund, Peter; Clements, Mark; Egevad, Lars

2016-04-01

Ductal adenocarcinoma of the prostate (DAC) has morphological similarities to adenocarcinomas of other organs. DAC behaves in an aggressive manner and may present with metastases. These metastases may occur at unusual sites, which itself may cause diagnostic difficulties. It is important for therapeutic decisions that a prostatic origin of these metastases be established. Our aim was to compare the protein expression of DAC and adenocarcinomas of colon, endometrium, lung, pancreas, stomach and urinary bladder. A tissue microarray was constructed using 60 DAC, 6 colonic, 7 endometrial, 7 lung, 5 pancreatic, 5 gastric, and 9 urinary bladder adenocarcinomas. Slides were stained for estrogen, progesterone and androgen receptor, prolactin, PSA, prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK, p63, p504s, c-Myc, EGFR, Ki-67, p16, p21, p27, p53, PTEN, ERG, and PAX-8. Androgen receptor, prostein, PSA, and PSAP were almost invariably expressed in DAC. Ki-67-labeling index was lower in DAC than in other adenocarcinomas. The expression patterns of intestinal markers and cytokeratins in DAC were less specific and may lead to diagnostic errors if not combined with prostate-specific markers. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Ethmoidal sinus adenocarcinoma with orbital invasion.

PubMed

Koukoulomatis, P; Charakidas, A; Papakrivopoulos, A; Giotakis, I

2001-01-01

To report a rare case of massive ethmoidal adenocarcinoma with orbital invasion but minimal ophthalmic symptoms on presentation. Case report of a 69-year-old, otherwise healthy, retired carpenter who was referred for treatment of bilateral senile cataract. A relative afferent pupillary defect and sectorial disc atrophy on ophthalmic examination led to further investigation and identification of an extensive ethmoidal neoplasm with orbital invasion. An incisional biopsy was performed and histopathologic examination revealed an adenocarcinoma of low-grade malignancy. Ethmoidal adenocarcinomas with orbital involvement may occasionally be relatively asymptomatic and masked by coexisting ocular disease.

ELF5 in epithelial ovarian carcinoma tissues and biological behavior in ovarian carcinoma cells.

PubMed

Yan, Hongchao; Qiu, Linglin; Xie, Xiaolei; Yang, He; Liu, Yongli; Lin, Xiaoman; Huang, Hongxiang

2017-03-01

The expression of E74-like factor 5 (ELF5) in epithelial ovarian carcinoma tissues and its effects on biological behavior in ovarian carcinoma cells were assessed in search for a new approach for gene treatment of epithelial ovarian carcinoma. RT-PCR technology was applied to detect the expression of ELF5 mRNA in epithelial ovarian carcinoma (n=49), borderline ovarian epithelial tumor (n=19), benign ovarian epithelial tumor (n=31) and normal ovarian tissues (n=40). Then, we transfected recombinant plasmid pcDNA3.1‑ELF5+EGFP into human ovarian carcinoma SKOV3 cells (recombinant plasmid group) in vitro and screened out stably transfected cells to conduct multiplication culture. Western blot analysis was performed to detect the expression of ELF5 protein in the different groups. Flow cytometry was employed to detect cell apoptosis and cycles. ELF5 mRNA in epithelial ovarian carcinoma and borderline ovarian epithelial tumor tissues were significantly lower (P<0.05) than those in benign ovarian epithelial tumor and normal ovarian tissues. ELF5 protein expression in the cells of recombinant plasmid group was significantly higher compared with empty plasmid and blank control groups. The capacity of cell reproductive recombinant plasmid group at each time point decreased (P<0.05). Flow cytometry detection showed that 67.03% of cells in recombinant plasmid group was blocked in G0/G1 phase (P<0.05), compared with empty plasmid group (37.17%) and blank control group (38.24%). Apoptotic rate of recombinant plasmid group was significantly lower (31.4±1.9%; P<0.05), compared with that of empty plasmid group (9.1±2.2%) and blank control group (8.7±1.5%), and the differences were statistically significant. In conclusion, ELF5 interfered with cell cycle of human ovarian carcinoma SKOV3 cells and promoted apoptosis of human ovarian carcinoma SKOV3 cells inhibiting their growth and invasive capacity; and thus providing a new approach to gene treatment of ovarian carcinoma.

Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-01-09

Mixed Mesodermal (Mullerian) Tumor; Ovarian Carcinosarcoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Sarcoma AJCC v7; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Sarcoma AJCC v7; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Uterine Sarcoma AJCC v7; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Uterine Sarcoma AJCC v7; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Uterine Sarcoma AJCC v7; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIA Uterine Sarcoma AJCC v7; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIB Uterine Sarcoma AJCC v7; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IIIC Uterine Sarcoma AJCC v7; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer; Stage IVA Uterine Sarcoma AJCC v7; Stage IVB Uterine Sarcoma AJCC v7; Uterine Carcinosarcoma

Ovarian Disorders

MedlinePlus

... a pregnancy can occur. Ovaries also make the female hormones estrogen and progesterone. When a woman goes through menopause, her ovaries stop making those hormones and releasing eggs. Problems with the ovaries include Ovarian cancer Ovarian ...

Complete remission of platinium refractory ovarian cancer with second line tegafur with uracil monotherapy: a case report.

PubMed

Camci, Celalettin; Sevinc, Alper; Aslan, Yilmaz; Kalender, Mehmet Emin; Buyukberber, Suleyman

2009-03-01

Ovarian cancer remains one of the most lethal of all gynecologic malignancies, accounting for more deaths than cervical and uterine cancer combined. Advanced ovarian cancer is a chemosensitive tumor and most patients initially respond to platinum-based combination chemotherapy with response rates of about 70%, including a high proportion of complete responses. However, despite aggressive surgery and chemotherapy, more than 80% of patients will relapse and will then be treated with second line chemotherapy with objective responses in about 20% of patients and even lower percentages of complete responses. We observed a 42-months of complete response with administration of 1-[2-tetrahydrofuryl]-5-fluorouracil mixed with uracil (UFT) in patient with platinium refractory ovarian cancer. We report a complete remission of platinium refractory epithelial ovarian cancer with UFT monotherapy that was not reported previously.

Prognostic relevance of TTF-1 expression in stage I adenocarcinoma.

PubMed

Zhou, Chao; Zhao, Jikai; Shao, Jinchen; Li, Wentao

2017-12-08

Tyroid transcription factor-1 (TTF-1) motivates the differentiation and development of bronchioloalveolar cells. The association of TTF-1 expression with prognosis in stage I adenocarcinoma is unclear. This study enrolled patients with resected stage I pulmonary adenocarcinoma who had TTF-1 immunostaining. All the corresponding clinicopathologic data including sex, age, smoking history, pathologic T stage, pathologic disease stage, surgical procedure, subtypes, follow-up records and adjuvant chemotherapy were investigated. Totally, 126 adenocarcinomas with TTF-1- and 2687 adenocarcinomas with TTF-1+ were subjected to the study. Among adenocarcinomas with TTF-1-, the major subtype was acinar-predominant adenocarcinomas, followed by invasive mucinous and papillary subtypes while acinar, papillary and minimally invasive adenocarcinoma were in the majority among adenocarcinomas with TTF-1+. The status of TTF-1 expression was not a significant factor for relapse-free survival (RFS) and overall survival (OS). Furthermore, there was no survival difference between the two groups (RFS: p = 0.2474; OS: p = 0.1480). When confined to stage IB adenocarcinomas with TTF-1-, whether received adjuvant chemotherapy made no difference to RFS and OS (RFS: p = 0.2707; OS: p = 1.000), as was the case in stage IB adenocarcinomas with TTF-1+ (RFS: p = 0.9161; OS: p = 0.1100). Within follow-up period, there was significant difference in post-recurrence survival (PRS) for TTF-1- patients compared with those TTF-1+ patients (Log-rank p = 0.0113). However, regarding to the recurrence site, there was no difference between TTF-1- patients and TTF-1+ patients in patients with stage I adenocarcinoma ( p = 0.771) In conclusion, there is no significant difference in RFS and OS between TTF-1- group and TTF-1+ group, but TTF-1 negative adenocarcinoma has significantly worse PFS in patients with stage I adenocarcinoma. Moreover, chemotherapeutic efficacy between TTF-1+ and TTF-1- stage IB

Anal sac adenocarcinoma in a Siamese cat.

PubMed

Mellanby, R J; Foale, R; Friend, E; Woodger, N; Herrtage, M E; Dobson, J D

2002-12-01

A 12-year-old male neutered Siamese cat presented with a history of inappetance and lethargy and an enlarged left anal sac. The anal sac was surgically excised and histopathology confirmed the diagnosis of anal sac adenocarcinoma. Perianal tumours are rare in the cat and anal sac adenocarcinoma has not been previously reported. This is in contrast to the dog where anal sac adenocarcinoma is a well recognised albeit uncommon tumour.

Treatment and survival in a population-based sample of patients diagnosed with gastroesophageal adenocarcinoma

PubMed Central

Cronin-Fenton, Deirdre P; Mooney, Margaret M; Clegg, Limin X; Harlan, Linda C

2008-01-01

AIM: To examine the extent of use of specific therapies in clinical practice, and their relationship to therapies validated in clinical trials. METHODS: The US National Cancer Institutes’ Patterns of Care study was used to examine therapies and survival of patients diagnosed in 2001 with histologically-confirmed gastroesophageal adenocarcinoma (n = 1356). The study re-abstracted data and verified therapy with treating physicians for a population-based stratified random sample. RESULTS: Approximately 62% of patients had stomach adenocarcinoma (SAC), while 22% had gastric-cardia adenocarcinoma (GCA), and 16% lower esophageal adenocarcinoma (EAC). Stage IV/unstaged esophageal cancer patients were most likely and stage I-III stomach cancer patients least likely to receive chemotherapy as all or part of their therapy; gastric-cardia patients received chemotherapy at a rate between these two. In multivariable analysis by anatomic site, patients 70 years and older were significantly less likely than younger patients to receive chemotherapy alone or chemoradiation for all three anatomic sites. Among esophageal and stomach cancer patients, receipt of chemotherapy was associated with lower mortality; but no association was found among gastric-cardia patients. CONCLUSION: This study highlights the relatively low use of clinical trials-validated anti-cancer therapies in community practice. Use of chemotherapy-based treatment was associated with lower mortality, dependent on anatomic site. Findings suggest that physicians treat lower esophageal and SAC as two distinct entities, while gastric-cardia patients receive a mix of the treatment strategies employed for the two other sites. PMID:18506920

Adenocarcinoma of urinary bladder: A report of two patients.

PubMed

Kumari, Nitu; Vasudeva, Pawan; Kumar, Anup; Agrawal, Usha

2015-01-01

Adenocarcinoma of the bladder is a rare tumor. Primary and metastatic adenocarcinomas of urinary bladder are morphologically similar, but histogenetically different. We present two cases, a signet ring cell adenocarcinoma with follow-up and another of glandular adenocarcinoma of urinary bladder. Pathological evaluation and immunohistochemical panel of eight markers (E-cadherin, CK20, CK7, CDX2, estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP15), 34bE12, and prostate specific antigen (PSA) provides a diagnostic confirmation of primary adenocarcinoma with the positive expression of E-cadherin and CK20 in case 1 and metastatic adenocarcinoma of prostate with profile of E-cadherin+, CK20-, GCDFP15+, 34bE12+, and PSA+ in case 2.

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

PubMed Central

Travis, William D.; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G.; Geisinger, Kim R.; Yatabe, Yasushi; Beer, David G.; Powell, Charles A.; Riely, Gregory J.; Van Schil, Paul E.; Garg, Kavita; Austin, John H. M.; Asamura, Hisao; Rusch, Valerie W.; Hirsch, Fred R.; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M.; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean-Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan-Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A.; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David

2015-01-01

Introduction Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. Methods An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. Results The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤5 mm invasion (MIA) to define patients who, if they undergo complete resection

International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma.

PubMed

Travis, William D; Brambilla, Elisabeth; Noguchi, Masayuki; Nicholson, Andrew G; Geisinger, Kim R; Yatabe, Yasushi; Beer, David G; Powell, Charles A; Riely, Gregory J; Van Schil, Paul E; Garg, Kavita; Austin, John H M; Asamura, Hisao; Rusch, Valerie W; Hirsch, Fred R; Scagliotti, Giorgio; Mitsudomi, Tetsuya; Huber, Rudolf M; Ishikawa, Yuichi; Jett, James; Sanchez-Cespedes, Montserrat; Sculier, Jean-Paul; Takahashi, Takashi; Tsuboi, Masahiro; Vansteenkiste, Johan; Wistuba, Ignacio; Yang, Pan-Chyr; Aberle, Denise; Brambilla, Christian; Flieder, Douglas; Franklin, Wilbur; Gazdar, Adi; Gould, Michael; Hasleton, Philip; Henderson, Douglas; Johnson, Bruce; Johnson, David; Kerr, Keith; Kuriyama, Keiko; Lee, Jin Soo; Miller, Vincent A; Petersen, Iver; Roggli, Victor; Rosell, Rafael; Saijo, Nagahiro; Thunnissen, Erik; Tsao, Ming; Yankelewitz, David

2011-02-01

Adenocarcinoma is the most common histologic type of lung cancer. To address advances in oncology, molecular biology, pathology, radiology, and surgery of lung adenocarcinoma, an international multidisciplinary classification was sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. This new adenocarcinoma classification is needed to provide uniform terminology and diagnostic criteria, especially for bronchioloalveolar carcinoma (BAC), the overall approach to small nonresection cancer specimens, and for multidisciplinary strategic management of tissue for molecular and immunohistochemical studies. An international core panel of experts representing all three societies was formed with oncologists/pulmonologists, pathologists, radiologists, molecular biologists, and thoracic surgeons. A systematic review was performed under the guidance of the American Thoracic Society Documents Development and Implementation Committee. The search strategy identified 11,368 citations of which 312 articles met specified eligibility criteria and were retrieved for full text review. A series of meetings were held to discuss the development of the new classification, to develop the recommendations, and to write the current document. Recommendations for key questions were graded by strength and quality of the evidence according to the Grades of Recommendation, Assessment, Development, and Evaluation approach. The classification addresses both resection specimens, and small biopsies and cytology. The terms BAC and mixed subtype adenocarcinoma are no longer used. For resection specimens, new concepts are introduced such as adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) for small solitary adenocarcinomas with either pure lepidic growth (AIS) or predominant lepidic growth with ≤ 5 mm invasion (MIA) to define patients who, if they undergo complete resection, will have 100% or near 100

Analysis of papillary renal adenocarcinoma.

PubMed

Mydlo, J H; Bard, R H

1987-12-01

A retrospective review was conducted comparing the angiographic findings, tumor volumes, staging, and survival of patients with papillary renal adenocarcinoma as compared with the more common clear and granular cell renal adenocarcinoma. The data suggest that the papillary histopathologic organization confers an improved prognosis, which concurs with previous findings. We speculate on why this tumor behaves differently from clear cell carcinoma.

Charged-Iron-Particles Found in Galactic Cosmic Rays are Potent Inducers of Epithelial Ovarian Tumors.

PubMed

Mishra, Birendra; Lawson, Gregory W; Ripperdan, Ryan; Ortiz, Laura; Luderer, Ulrike

2018-05-21

Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer. Therefore, we hypothesized that charged-iron-particle irradiation induces ovarian tumorigenesis in mice. In this study, three-month-old female mice were exposed to 0 cGy (sham) or 50 cGy iron ions and aged to 18 months. The 50 cGy irradiated mice had increased weight gain with age and lack of estrous cycling, consistent with ovarian failure. A total of 47% and 7% of mice irradiated with 50 cGy had unilateral and bilateral ovarian tumors, respectively, whereas 14% of mice in the 0 cGy group had unilateral tumors. The tumors contained multiple tubular structures, which were lined with cells positive for the epithelial marker cytokeratin, and had few proliferating cells. In some tumors, packets of cells between the tubular structures were immunopositive for the granulosa cell marker FOXL2. Based on these findings, tumors were diagnosed as tubular adenomas or mixed tubular adenoma/granulosa cell tumors. In conclusion, charged-iron-particle-radiation induces ovarian tumors in mice, raising concerns about ovarian tumors as late sequelae of deep space travel in female astronauts.

[Fertility preservation, contraception and menopause hormone therapy in women treated for rare ovarian tumors: Guidelines from the French national network dedicated to rare gynaecological cancer].

PubMed

Rousset-Jablonski, Christine; Selle, Fréderic; Adda-Herzog, Elodie; Planchamp, François; Selleret, Lise; Pomel, Christophe; Chabbert-Buffet, Nathalie; Daraï, Emile; Pautier, Patricia; Trémollières, Florence; Guyon, Frederic; Rouzier, Roman; Laurence, Valérie; Chopin, Nicolas; Faure-Conter, Cécile; Bentivegna, Enrica; Vacher-Lavenu, Marie-Cécile; Lhomme, Catherine; Floquet, Anne; Treilleux, Isabelle; Lecuru, Fabrice; Gouy, Sébastien; Kalbacher, Elsa; Genestie, Catherine; de la Motte Rouge, Thibault; Ferron, Gwenael; Devouassoux-Shisheboran, Mojgan; Kurtz, Jean-Emmanuel; Namer, Moise; Joly, Florence; Pujade-Lauraine, Eric; Grynberg, Michael; Querleu, Denis; Morice, Philippe; Gompel, Anne; Ray-Coquard, Isabelle

2018-03-01

Rare ovarian tumors include complex borderline ovarian tumors, sex-cord tumors, germ cell tumors, and rare epithelial tumors. Indications and modalities of fertility preservation, infertility management and contraindications for hormonal contraception or menopause hormone therapy are frequent issues in clinical practice. A panel of experts from the French national network dedicated to rare gynaecological cancers, and of experts in reproductive medicine and gynaecology have worked on guidelines about fertility preservation, contraception and menopause hormone therapy in women treated for ovarian rare tumors. A panel of 39 experts from different specialties contributed to the preparation of the guidelines, following the DELPHI method (formal consensus method). Statements were drafted after a systematic literature review, and then rated through two successive rounds. Thirty-five recommendations were selected, and concerned indications for fertility preservation, contraindications for ovarian stimulation (in the context of fertility preservation or for infertility management), contraceptive options (especially hormonal ones), and menopause hormone therapy for each tumor type. Overall, prudence has been recommended in the case of potentially hormone-sensitive tumors such as sex cord tumors, serous and endometrioid low-grade adenocarcinomas, as well as for high-risk serous borderline ovarian tumors. In the context of a scarce literature, a formal consensus method allowed the elaboration of guidelines, which will help clinicians in the management of these patients. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Synchronous Endometrial and Ovarian Cancer in Young Women: Case Report and Review of the Literature.

PubMed

Dogan, Askin; Schultheis, Beate; Rezniczek, Günther A; Hilal, Ziad; Cetin, Cem; Häusler, Günther; Tempfer, Clemens B

2017-03-01

Young women with endometrial cancer (EC) have an increased risk of synchronous ovarian cancer. The prognosis of women with synchronous endometrial and ovarian cancer (SEOC) is good. A high proportion of affected women have hereditary non-polyposis colon cancer syndrome (HNPCC). We present the case of a 45-year-old woman with histologically proven endometrioid adenocarcinoma of the endometrium (pT1B, G2, R0 without lymphovascular space invasion). She underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. Final histology revealed a synchronous bilateral endometrioid ovarian cancer (pT1A, G2, R0). HNPCC analysis by immunohistochemistry showed no microsatellite instability in MSH2, MSH6, MLH1, and PMS2. No adjuvant therapy was administered, clinical follow-up with regular gynecological examinations was recommended. In a systematic literature review, 2,904 cases of women with SEOC were identified with 1,035 (36%) of them being premenopausal or <50 years of age. The proportion of women with SEOC among all reported EC cases was 842/23,498 (3%) and the proportion of young women with SEOC among all reported EC cases was 261/23,498 (1%). In summary, microsatellite instability and subsequent mutations in mismatch repair genes compatible with HNPCC were identified in 6/15 (40%) women analyzed. The mean recurrence-free and overall survival times of young women with SEOC were 1.9 (min 0.2, max 3) and 4.0 (min 0.2, max 22.1) years, respectively. Young women with EC have a high risk of synchronous ovarian cancer. Thus, in young women with EC, bilateral salpingo-oophorectomy or careful histological assessment of both ovaries are recommended in order to confirm or rule out SEOC. HNPCC testing should be offered to all women. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[Ultrasound semiotics in recurrent ovarian cancer after optimal cytoreductive surgery].

PubMed

Baklanova, N S; Kolomiets, L A; Frolova, I G; Viatkina, N V; Krasil'nikov, S É

2014-01-01

Features of ultrasound picture of morphologically verified recurrence of ovarian cancer in 21 patients are presented, who received combined treatment including cytoreductive surgery in the form of hysterectomy with oophorectomy, resection of the greater omentum and 6 courses of chemotherapy CAP for ovarian cancer stage III (FIGO). In all patients cytoreductive surgery was optimal--without residual tumor. Recurrence of the disease was detected in 12-48 months in 80.9% of the cases. Three variants of recurrence was revealed by ultrasonography: isolated peritoneal dissemination, in 14.2% of the cases, which was mainly detected during the first 12 months; single entities in the projection of the small pelvis (61.9%) and mixed form (local lesions of small pelvis and peritoneal dissemination) in 23.8% of the cases.

Enhanced expression of peroxisome proliferator-activated receptor gamma in epithelial ovarian carcinoma.

PubMed

Zhang, G Y; Ahmed, N; Riley, C; Oliva, K; Barker, G; Quinn, M A; Rice, G E

2005-01-17

The peroxisome proliferator-activated receptors (PPARs) belong to a subclass of nuclear hormone receptor that executes important cellular transcriptional functions. Previous studies have demonstrated the expression of PPARgamma in several tumours including colon, breast, bladder, prostate, lung and stomach. This study demonstrates the relative expression of PPARgamma in normal ovaries and different pathological grades of ovarian tumours of serous, mucinous, endometrioid, clear cell and mixed subtypes. A total of 56 ovarian specimens including 10 normal, eight benign, 10 borderline, seven grade 1, nine grade 2 and 12 grade 3 were analysed using immunohistochemistry. Immunoreactive PPARgamma was not expressed in normal ovaries. Out of eight benign and 10 borderline tumours, only one tumour in each group showed weak cytoplasmic PPARgamma expression. In contrast, 26 out of 28 carcinomas studied were positive for PPARgamma expression with staining confined to cytoplasmic and nuclear regions. An altered staining pattern of PPARgamma was observed in high-grade ovarian tumours with PPARgamma being mostly localized in the nuclei with little cytoplasmic immunoreactivity. On the other hand, predominant cytoplasmic staining was observed in lower-grade tumours. Significantly increased PPARgamma immunoreactivity was observed in malignant ovarian tumours (grade 1, 2 and 3) compared to benign and borderline tumours (chi2 = 48.80, P < 0.001). Western blot analyses showed significant elevation in the expression of immunoreactive PPARgamma in grade 3 ovarian tumours compared with that of normal ovaries and benign ovarian tumours (P < 0.01). These findings suggest an involvement of PPARgamma in the onset and development of ovarian carcinoma and provide an insight into the regulation of this molecule in the progression of the disease.

Experimental induction of ovarian Sertoli cell tumors in rats by N-nitrosoureas.

PubMed Central

Maekawa, A; Onodera, H; Tanigawa, H; Furuta, K; Kanno, J; Ogiu, T; Hayashi, Y

1987-01-01

Spontaneous ovarian tumors are very rare in ACI, Wistar, F344 and Donryu rats; the few neoplasms found are of the granulosa/theca cell type. Ovarian tumors were also rare in these strains of rats when given high doses of N-alkyl-N-nitrosoureas continuously in the drinking water for their life-span; however, relatively high incidences of Sertoli cell tumors or Sertoli cell tumors mixed with granulosa cell tumors were induced in Donryu rats after administration of either a 400 ppm N-ethyl-N-nitrosourea solution in the drinking water for 4 weeks or as a single dose of 200 mg N-propyl-N-nitrosourea per kg body weight by stomach tube. Typical Sertoli cell tumors consisted of solid areas showing tubular formation. The tubules were lined by tall, columnar cells, with abundant, faintly eosinophilic, often vacuolated cytoplasm, and basally oriented, round nuclei, resembling seminiferous tubules in the testes. In some cases, Sertoli cell tumor elements were found mixed with areas of granulosa cells. The induction of ovarian Sertoli cell tumors in Donryu rats by low doses of nitrosoureas may provide a useful model for these tumors in man. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PMID:3665856

Nuclear microanalysis of platinum and trace elements in cisplatin-resistant human ovarian adenocarcinoma cells

NASA Astrophysics Data System (ADS)

Moretto, P.; Ortega, R.; Llabador, Y.; Simonoff, M.; Bénard, J.; Moretto, Ph.

1995-09-01

Macro-and Micro-PIXE analysis were applied to study the mechanisms of cellular resistance to cisplatin, a chemotherapeutic agent, widely used nowadays for the treatment of ovarian cancer. Two cultured cell lines, a cisplatin-sensitive and a resistant one, were compared for their trace elements content and platinum accumulation following in vitro exposure to the drug. Bulk analysis revealed significant differences in copper and iron content between the two lines. Subsequent individual cell microanalysis permitted us to characterize the response of the different morphological cell types of the resistant line. This study showed that the metabolism of some trace metals in cisplatin-resistant cells could be affected but the exact relationship with the resistant phenotype remains to be determined. From a technical point of view, this experiment demonstrated that an accurate measurement of trace elements could be derived from nuclear microprobe analysis of individual cell.

R-ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis

PubMed Central

Guo, Yuna; Kenney, Shelby Ray; Muller, Carolyn Y.; Adams, Sarah; Rutledge, Teresa; Romero, Elsa; Murray-Krezan, Cristina; Prekeris, Rytis; Sklar, Larry A.; Hudson, Laurie G.; Wandinger-Ness, Angela

2015-01-01

Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high throughput screening and computational shape homology approaches we identified R-ketorolac as a Cdc42 and Rac1 inhibitor; distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip), and primary, patient-derived ovarian cancer cells show R-ketorolac is a robust inhibitor of growth factor or serum dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration and invasion. In sum, we provide evidence for R-ketorolac as direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiological responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA approved drug-racemic ketorolac that can be used in humans. PMID:26206334

R-Ketorolac Targets Cdc42 and Rac1 and Alters Ovarian Cancer Cell Behaviors Critical for Invasion and Metastasis.

PubMed

Guo, Yuna; Kenney, S Ray; Muller, Carolyn Y; Adams, Sarah; Rutledge, Teresa; Romero, Elsa; Murray-Krezan, Cristina; Prekeris, Rytis; Sklar, Larry A; Hudson, Laurie G; Wandinger-Ness, Angela

2015-10-01

Cdc42 (cell division control protein 42) and Rac1 (Ras-related C3 botulinum toxin substrate 1) are attractive therapeutic targets in ovarian cancer based on established importance in tumor cell migration, adhesion, and invasion. Despite a predicted benefit, targeting GTPases has not yet been translated to clinical practice. We previously established that Cdc42 and constitutively active Rac1b are overexpressed in primary ovarian tumor tissues. Through high-throughput screening and computational shape homology approaches, we identified R-ketorolac as a Cdc42 and Rac1 inhibitor, distinct from the anti-inflammatory, cyclooxygenase inhibitory activity of S-ketorolac. In the present study, we establish R-ketorolac as an allosteric inhibitor of Cdc42 and Rac1. Cell-based assays validate R-ketorolac activity against Cdc42 and Rac1. Studies on immortalized human ovarian adenocarcinoma cells (SKOV3ip) and primary patient-derived ovarian cancer cells show that R-ketorolac is a robust inhibitor of growth factor or serum-dependent Cdc42 and Rac1 activation with a potency and cellular efficacy similar to small-molecule inhibitors of Cdc42 (CID2950007/ML141) and Rac1 (NSC23766). Furthermore, GTPase inhibition by R-ketorolac reduces downstream p21-activated kinases (PAK1/PAK2) effector activation by >80%. Multiple assays of cell behavior using SKOV3ip and primary patient-derived ovarian cancer cells show that R-ketorolac significantly inhibits cell adhesion, migration, and invasion. In summary, we provide evidence for R-ketorolac as a direct inhibitor of Cdc42 and Rac1 that is capable of modulating downstream GTPase-dependent, physiologic responses, which are critical to tumor metastasis. Our findings demonstrate the selective inhibition of Cdc42 and Rac1 GTPases by an FDA-approved drug, racemic ketorolac, that can be used in humans. ©2015 American Association for Cancer Research.

Prognostic relevance of TTF-1 expression in stage I adenocarcinoma

PubMed Central

Zhou, Chao; Zhao, Jikai; Shao, Jinchen; Li, Wentao

2017-01-01

Tyroid transcription factor-1 (TTF-1) motivates the differentiation and development of bronchioloalveolar cells. The association of TTF-1 expression with prognosis in stage I adenocarcinoma is unclear. This study enrolled patients with resected stage I pulmonary adenocarcinoma who had TTF-1 immunostaining. All the corresponding clinicopathologic data including sex, age, smoking history, pathologic T stage, pathologic disease stage, surgical procedure, subtypes, follow-up records and adjuvant chemotherapy were investigated. Totally, 126 adenocarcinomas with TTF-1− and 2687 adenocarcinomas with TTF-1+ were subjected to the study. Among adenocarcinomas with TTF-1−, the major subtype was acinar-predominant adenocarcinomas, followed by invasive mucinous and papillary subtypes while acinar, papillary and minimally invasive adenocarcinoma were in the majority among adenocarcinomas with TTF-1+. The status of TTF-1 expression was not a significant factor for relapse-free survival (RFS) and overall survival (OS). Furthermore, there was no survival difference between the two groups (RFS: p = 0.2474; OS: p = 0.1480). When confined to stage IB adenocarcinomas with TTF-1−, whether received adjuvant chemotherapy made no difference to RFS and OS (RFS: p = 0.2707; OS: p = 1.000), as was the case in stage IB adenocarcinomas with TTF-1+ (RFS: p = 0.9161; OS: p = 0.1100). Within follow-up period, there was significant difference in post-recurrence survival (PRS) for TTF-1− patients compared with those TTF-1+ patients (Log-rank p = 0.0113). However, regarding to the recurrence site, there was no difference between TTF-1− patients and TTF-1+ patients in patients with stage I adenocarcinoma (p = 0.771) In conclusion, there is no significant difference in RFS and OS between TTF-1− group and TTF-1+ group, but TTF-1 negative adenocarcinoma has significantly worse PFS in patients with stage I adenocarcinoma. Moreover, chemotherapeutic efficacy between TTF-1+ and TTF-1− stage IB

18β-glycyrrhetinic acid potentiates Hsp90 inhibition-induced apoptosis in human epithelial ovarian carcinoma cells via activation of death receptor and mitochondrial pathway.

PubMed

Yang, Jae Chon; Myung, Soon Chul; Kim, Wonyong; Lee, Chung Soo

2012-11-01

The Hsp90 inhibition has been shown to induce apoptosis in various cancer cells. The licorice compounds may enhance the anti-cancer drug effect. However, effect of the licorice compounds on the Hsp90 inhibition-induced apoptosis in ovarian cancer cells has not been studied. To assess the ability of 18β-glycyrrhetinic acid to promote apoptosis, we examined whether 18β-glycyrrhetinic acid potentiated the Hsp90 inhibitor-induced apoptosis in the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. Radicicol and geldanamycin induced a decrease in Bid, Bcl-2, Bcl-xL and survivin protein levels, an increase in Bax levels, the mitochondrial transmembrane potential loss, cytochrome c release, activation of caspases (-8, -9, and -3), cleavage of PARP-1, and an increase in the tumor suppressor p53 levels. 18β-Glycyrrhetinic acid enhanced Hsp90 inhibitor-induced apoptosis-related protein activation, nuclear damage, and cell death. The results suggest that 18β-glycyrrhetinic acid may potentiate the Hsp90 inhibition-induced apoptosis in ovarian carcinoma cell lines via the activation of the caspase-8- and Bid-dependent pathways and the mitochondria-mediated cell death pathway, leading to activation of caspases. Combination of Hsp90 inhibitors and 18β-glycyrrhetinic acid may confer a benefit in the treatment of epithelial ovarian adenocarcinoma.

A phase II study of intraperitoneal radioimmunotherapy with iodine-131-labeled monoclonal antibody OC-125 in patients with residual ovarian carcinoma.

PubMed

Mahé, M A; Fumoleau, P; Fabbro, M; Guastalla, J P; Faurous, P; Chauvot, P; Chetanoud, L; Classe, J M; Rouanet, P; Chatal, J F

1999-10-01

Standard treatment of advanced ovarian cancer is a combination of surgery and chemotherapy. Additional therapies using the i.p. route are considered as a potential means of improving the locoregional control rate. This Phase II study evaluated the efficacy of i.p. radioimmunotherapy (RIT) in patients with minimal residual ovarian adenocarcinoma after primary treatment with surgery and chemotherapy. Between February 1995 and March 1996, six patients with residual macroscopic (<5 mm) or microscopic disease as demonstrated by laparotomy and multiple biopsies received i.p. RIT. All had initial stage III epithelial carcinoma and were treated with debulking surgery and one line (four patients) or two lines (two patients) of chemotherapy. RIT was performed with 60 mg of OC 125 F(ab')2 monoclonal antibody labeled with 4.44 GBq (120 mCi) of 131I injected 5-10 days after the surgical procedure. Systematic laparoscopy or laparotomy with multiple biopsies performed 3 months after RIT in five patients (clinical progression was seen in one patient) showed no change in three patients and progression in two patients. Toxicity was mainly hematological, with grade III neutropenia and thrombocytopenia in two patients. Human antimouse antibody production was demonstrated in all six patients. This study showed little therapeutic benefit from i.p. RIT in patients with residual ovarian carcinoma.

Detection of tumor angiogenesis factor in adenocarcinoma of kidney.

PubMed

Bard, R H; Mydlo, J H; Freed, S Z

1986-05-01

Implantation of human renal adenocarcinoma in the rabbit cornea has resulted in new vascular growth from the limbus toward the tumor implant. This suggests that renal adenocarcinoma elaborates tumor angiogenesis factor (TAF) which stimulates endothelial cell growth. Such a substance could conceivably be responsible for the luxuriant vascularity of most renal adenocarcinomas. Conversely, absence or diminished secretion of TAF may be responsible for the hypovascular papillary renal adenocarcinomas and their recognized relatively benign clinical behavior.

Epidemiology of ovarian cancer.

PubMed

Permuth-Wey, Jennifer; Sellers, Thomas A

2009-01-01

Ovarian cancer represents the sixth most commonly diagnosed cancer among women in the world, and causes more deaths per year than any other cancer of the female reproductive system. Despite the high incidence and mortality rates, the etiology of this disease is poorly understood. Established risk factors for ovarian cancer include age and having a family history of the disease, while protective factors include increasing parity, oral contraceptive use, and oophorectomy. Lactation, incomplete pregnancies, and surgeries such as hysterectomy and tubal ligation may confer a weak protective effect against ovarian cancer. Infertility may contribute to ovarian cancer risk among nulliparous women. Other possible risk factors for ovarian cancer include postmenopausal hormone-replacement therapy and lifestyle factors such as cigarette smoking and alcohol consumption. Many of the causes of ovarian cancer are yet to be identified. Additional research is needed to better understand the etiology of this deadly disease.

A novel serum microRNA panel to discriminate benign from malignant ovarian disease.

PubMed

Langhe, Ream; Norris, Lucy; Saadeh, Feras Abu; Blackshields, Gordon; Varley, Rachel; Harrison, Ashling; Gleeson, Noreen; Spillane, Cathy; Martin, Cara; O'Donnell, Dearbhaile M; D'Arcy, Tom; O'Leary, John; O'Toole, Sharon

2015-01-28

Ovarian cancer is the seventh most common cancer in women and the most frequent cause of gynaecological malignancy-related mortality in women. Currently, no standardized reliable screening test exists. MicroRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis and response to treatment of human tumours. The aim of this study was to determine if a microRNA signature could distinguish between malignant and benign ovarian disease. A training set of 5 serous ovarian carcinomas and 5 benign serous cystadenomas were selected for the initial experiments. The validation set included 20 serous ovarian carcinomas and 20 benign serous cystadenomas. The serum/plasma focus microRNA Exiqon panel was used for the training set. For the validation set a pick and mix Exiqon panel, which focuses on microRNAs of interest was used. A panel of 4 microRNAs (let-7i-5p, miR-122, miR-152-5p and miR-25-3p) was significantly down regulated in cancer patients. These microRNAs target WNT signalling, AKT/mTOR and TLR-4/MyD88, which have previously been found to play a role in ovarian carcinogenesis and chemoresistance. let-7i-5p, miR-122, miR-152-5p and miR-25-3p could act as diagnostic biomarkers in ovarian cancer. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis

PubMed Central

Schwede, Matthew; Spentzos, Dimitrios; Bentink, Stefan; Hofmann, Oliver; Haibe-Kains, Benjamin; Harrington, David; Quackenbush, John; Culhane, Aedín C.

2013-01-01

Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable

Cell cycle arrest or survival signaling through αv integrins, activation of PKC and ERK1/2 lead to anoikis resistance of ovarian cancer spheroids.

PubMed

Carduner, Ludovic; Picot, Cédric R; Leroy-Dudal, Johanne; Blay, Lyvia; Kellouche, Sabrina; Carreiras, Franck

2014-01-15

Ovarian cancer is the most lethal gynecologic cancer mainly due to spheroids organization of cancer cells that disseminate within the peritoneal cavity. We have investigated the molecular mechanisms by which ovarian cancer spheroids resist anoikis, choosing as models the 2 well-characterized human ovarian cancer cell lines IGROV1 and SKOV3. These cell lines have the propensity to float as clusters, and were isolated from tumor tissue and ascites, respectively. To form spheroids, IGROV1 and SKOV3 ovarian adenocarcinoma cells were maintained under anchorage-independent culture conditions, in which both lines survive at least a week. A short apoptotic period prior to a survival signaling commitment was observed for IGROV1 cells whereas SKOV3 cells entered G0/G1 phase of the cell cycle. This difference in behavior was due to different signals. With regard to SKOV3 cells, activation of p38 and an increase in p130/Rb occurred once anchorage-independent culture was established. Analyses of the survival signaling pathway switched on by IGROV1 cells showed that activation of ERK1/2 was required to evade apoptosis, an effect partly dependent on PKC activation and αv integrins. αv-integrin expression is essential for survival through activation of ERK1/2 phosphorylation. The above data indicate that ovarian cancer cells can resist anoikis in the spheroid state by arrest in the cell cycle or through activation of αv-integrin-ERK-mediated survival signals. Such signaling might result in the selection of resistant cells within disseminating spheroids, favoring further relapse in ovarian cancers. © 2013 Elsevier Inc. All rights reserved.

Towards prevention of ovarian cancer.

PubMed

Ali, Aus Tariq

2018-01-01

Ovarian cancer is the leading cause of death of all gynaecological cancers. To date, there is no reliable, specific screening procedure for detecting ovarian cancer. The risk factors of ovarian cancer include modifiable and non-modifiable factors. The main goal of the ovarian cancer prevention program is to significantly reduce the risk of development of ovarian cancer and other cancers such as breast and/or peritoneal cancer. The application of non-surgical preventive approaches such as oral contraceptives, parity and breastfeeding has been shown to be highly protective against ovarian cancer development. Targeting inflammation has been also reported to be associated with a protective trend against ovarian cancer and can be achieved through either non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or lifestyle modifications or both. Lifestyle modification that includes regular exercise, healthy diet supplemented with anti-oxidants and anti-inflammatory elements reduces the risk of the disease even further. Surgical protective approaches include; tubal ligation, hysterectomy and prophylactic bilateral salpingo-oophorectomy and the former is the most effective approach to protect against ovarian cancer. A better understanding of the risk factors of ovarian cancer and the current approaches to prevent it may increase the awareness and help to decrease the incidence of ovarian cancer, increase the five-year survival rate and decrease the mortality rate significantly in the general population especially among those at high risk for ovarian cancer. This review is an attempt to outline a potential program of ovarian cancer prevention and the potential challenges. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ovarian Cancer

MedlinePlus

... Knowledge is an initiative that supports the Gynecologic Cancer Education and Awareness Act of 2005, or Johanna’s Law, which was unanimously passed by the U.S. House and Senate in December of 2006, and ... and symptoms of ovarian cancer? Ovarian cancer may cause one or more of ...

Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study.

PubMed

Etter, John Lewis; Eng, Kevin; Cannioto, Rikki; Kaur, Jasmine; Almohanna, Hani; Alqassim, Emad; Szender, J Brian; Joseph, Janine M; Lele, Shashikant; Odunsi, Kunle; Moysich, Kirsten B

2018-04-01

Although family history of testicular cancer is well-established as a risk factor for testicular cancer, it is unknown whether family history of ovarian cancer is associated with risk of testicular cancer. Using data from the Familial Ovarian Cancer Registry on 2636 families with multiple cases of ovarian cancer, we systematically compared relative frequencies of ovarian cancer among relatives of men with testicular and non-testicular cancers. Thirty-one families with cases of both ovarian and testicular cancer were identified. We observed that, among men with cancer, those with testicular cancer were more likely to have a mother with ovarian cancer than those with non-testicular cancers (OR = 3.32, p = 0.004). Zero paternal grandmothers of men with testicular cancer had ovarian cancer. These observations provide compelling preliminary evidence for a familial association between ovarian and testicular cancers Future studies should be designed to further investigate this association and evaluate X-linkage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

PubMed

La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

2014-01-01

Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

Adenocarcinoma with BAC Features Presented as the Nonsolid Nodule Is Prone to Be False-Negative on 18F-FDG PET/CT

PubMed Central

Wu, Hu-bing; Wang, Lijuan; Wang, Quan-shi; Han, Yan-jian; Li, Hong-sheng; Zhou, Wen-lan; Tian, Ying

2015-01-01

Purpose. The present study investigated which type of adenocarcinoma with BAC features was prone to be false-negative on 18F-FDG PET/CT. Materials and Methods. A retrospective study was performed on 51 consecutive patients with localized adenocarcinoma with BAC features. CT and PET were assessed for lesion size, GGO percentage, and SUVmax. Lesions with FDG uptake the same as or more than mediastinal blood-pool activity were considered as PET-positive. Results. Of the 51 cases, 19.6% presented as pure GGO nodules, 31.4% as mixed nodules, and 49.0% as solid nodules. None of the pure GGO nodules was 18F-FDG avid, compared with 37.5% of mixed nodules and 96.0% of solid nodules (χ 2 = 31.55, P = 0.000). In the mixed nodule group, SUVmax was negatively correlated with GGO percentage (r = −0.588; P = 0.021). The positive detection rate of 18F-FDG PET/CT was 50.0%, 55.6%, and 100% in tumors 1.1–2.0 cm, 2.1–3.0 cm, and >3.0 cm in diameter, respectively (χ 2 = 5.815, P = 0.055). General linear model factor analysis showed that the GGO was an important factor contributing to false-negative PET/CT results (F = 23.992, P = 0.000), but lesion size was not (F = 0.602, P = 0.866). Conclusions. The present study indicated that the adenocarcinoma with BAC features presented as nonsolid nodule is prone to be false negative on 18F-FDG PET/CT. PMID:25879020

CD8+ T cells induce complete regression of advanced ovarian cancers by an interleukin (IL)-2/IL-15 dependent mechanism.

PubMed

Yang, Taimei; Wall, Erika M; Milne, Katy; Theiss, Patty; Watson, Peter; Nelson, Brad H

2007-12-01

In vitro studies suggest that ovarian cancer evades immune rejection by fostering an immunosuppressive environment within the peritoneum; however, the functional responses of ovarian cancer-specific T cells have not been directly investigated in vivo. Therefore, we developed a new murine model to enable tracking of tumor-specific CD8(+) T-cell responses to advanced ovarian tumors. The ovarian tumor cell line ID8 was transfected to stably express an epitope-tagged version of HER-2/neu (designated Neu(OT-I/OT-II)). After i.p. injection into C57BL/6 mice, ID8 cells expressing Neu(OT-I/OT-II) gave rise to disseminated serous adenocarcinomas with extensive ascites. CD8(+) T cells expressing a transgenic T-cell receptor specific for the OT-I epitope of Neu(OT-I/OT-II) were adoptively transferred into tumor-bearing mice, and functional responses were monitored. Cytokine signaling requirements were evaluated by comparing the responses of wild-type donor T cells with those with genetic deletion of the interleukin (IL)-2/IL-15 receptor beta subunit (CD122) or the IL-2 receptor alpha subunit (CD25). On adoptive transfer into tumor-bearing hosts, wild-type OT-I T cells underwent a striking proliferative response, reaching peak densities of approximately 40% and approximately 90% of CD8(+) T cells in peripheral blood and ascites, respectively. OT-I cells infiltrated and destroyed tumor tissue, and ascites completely resolved within 10 days. By contrast, CD122(-/-) OT-I cells and CD25(-/-) OT-I cells proliferated in blood but failed to accumulate in ascites or tumor tissue or induce tumor regression. Contrary to expectation, advanced ovarian cancers can support extraordinary CD8(+) T-cell proliferation and antitumor activity through an IL-2/IL-15-dependent mechanism.

The relationship between ovarian function and ovarian limited dose in radiotherapy postoperation of ovarian transposition in young patients with cervical cancer.

PubMed

Du, Zhenhua; Qu, Hui

2017-03-01

In this study, the relationship between ovarian function and ovarian limited dose in radiotherapy was evaluated in young patients with cervical cancer who underwent ovarian transposition (Fig1B). Moreover, the novel ovarian dose limit for a better preservation of ovarian function in intensity-modulated radiation therapy (IMRT) was determined. We retrospectively analyzed data from 86 patients with cervical cancer who received radical hysterectomy and ovarian transposition from January 2013 to June 2015. In agreement with the National Comprehensive Cancer Network Guidelines (NCCN) for Cervical Cancer Version 2.2015, 65 patients with pathological high-risk factors were administered adjuvant radiotherapy-20 of them received three-dimensional conformal radiotherapy (Observation Group A), 24 patients received IMRT with no limitation on radiation dose to ovaries (Observation Group B), and 21 patients underwent IMRT with limited radiation dose(V 10 <20%) to ovaries (Observation Group C). Twenty-one patients without any predetermined high-risk factors did not received radiation therapy (Control Group D). Patients from all four groups were followed up, and sex hormone levels (E 2 , P, follicle-stimulating hormone [FSH], LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy were measured by electrochemiluminescence immunoassay. Subsequently, changes in sex hormone levels in all four groups of patients at various time points were analyzed. The levels of sexual hormones (E 2 , P, FSH, LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy in patients from all three observation groups were significantly lower than those in patients of the control group (P < 0.05). There was no statistically significant difference in the levels of sex hormones in patients of the control group at different time points (P > 0.05). Within each observation group, there was a statistically significant difference in the sex hormone

Tuba-ovarian auto-amputation caused by ovarian teratoma in an adolescent girl.

PubMed

Atıcı, Ahmet; Yılmaz, Engin; Karaman, Ayşe; Apaydın, Sema; Afşarlar, Çağatay Evrim

2017-01-01

Atıcı A, Yılmaz E, Karaman A, Apaydın S, Afşarlar ÇE. Tuba-ovarian auto-amputation caused by ovarian teratoma in an adolescent girl. Turk J Pediatr 2017; 59: 90-92. Ovarian auto-amputation is an extremely rare condition commonly encountered in the perinatal period. Spontaneous or secondary torsion of the ovary caused by an ovarian lesion may result in infarction and subsequent auto-amputation of the ovary. This paper demonstrates a case that underwent laparoscopic appendectomy with an incidental calcified auto-amputated right ovary. A 16-year-old adolescent girl was admitted to our department with a history of one-day abdominal pain. Physical examination of the patient revealed abdominal tenderness and rigidity on right lower quadrant. Her white blood cell count was 11x103/mL, and C-reactive protein was 69 mg/L. The patient underwent a laparoscopic appendectomy with a provisional diagnosis of acute appendicitis, and further exploration revealed a 2x2 cm white ovoid mass floating freely in the pelvis. The left ovary was clearly identified in its usual localization, but the right tuba was blindly ending without any fimbria or ovary. Postoperative course of the patient was uneventful, and she was discharged on postoperative day 2. The histopathological examination revealed a necrotic calcified ovarian teratoma. Auto-amputated ovary is a rare occasion mostly encountered during perinatal period, and it may be unilateral or bilateral. An auto-amputated ovarian mass may rarely be a teratoma although the most common cause of auto-amputation during perinatal and adolescent period is ovarian torsion due to an ovarian cyst.

GATA6 expression in Barrett's oesophagus and oesophageal adenocarcinoma.

PubMed

Pavlov, Kirill; Honing, Judith; Meijer, Coby; Boersma-van Ek, Wytske; Peters, Frans T M; van den Berg, Anke; Karrenbeld, Arend; Plukker, John T M; Kruyt, Frank A E; Kleibeuker, Jan H

2015-01-01

Barrett's oesophagus can progress towards oesophageal adenocarcinoma through a metaplasia-dysplasia-carcinoma sequence, but the underlying mechanisms are poorly understood. The transcription factor GATA6 is known to be involved in columnar differentiation and proliferation, and GATA6 gene amplification was recently linked with poor survival in oesophageal adenocarcinoma. To study the expression of GATA6 during Barrett's oesophagus development and malignant transformation. To determine the prognostic value of GATA6 in oesophageal adenocarcinoma. Two retrospective cohorts were derived from the pathological archive of the University Medical Center Groningen. The first cohort contained 130 tissue samples of normal squamous epithelium, metaplasia, dysplasia and oesophageal adenocarcinoma. The second cohort consisted of a tissue microarray containing tissue from 92 oesophageal adenocarcinoma patients. Immunohistochemistry was used to examine GATA6 protein expression and to correlate GATA6 expression in oesophageal adenocarcinoma with overall and disease-free survival. The percentage of GATA6-positive cells was low in squamous epithelium (10%) but increased progressively in Barrett's oesophagus (30%, P < 0.001) and high-grade dysplasia (82%, P = 0.005). GATA6 expression was not associated with overall or disease-free survival in oesophageal adenocarcinoma patients (P = 0.599 and P = 0.700 respectively). GATA6 expression is progressively increased during Barrett's oesophagus development and its malignant transformation. However, no prognostic value of GATA6 expression could be found in oesophageal adenocarcinoma. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Different histological status of gastritis in superficial adenocarcinoma of the esophagogastric junction.

PubMed

Yamada, Masayoshi; Kushima, Ryoji; Oda, Ichiro; Mojtahed, Kaveh; Nonaka, Satoru; Suzuki, Haruhisa; Yoshinaga, Shigetaka; Matsubara, Akiko; Taniguchi, Hirokazu; Sekine, Shigeki; Saito, Yutaka; Shimoda, Tadakazu

2014-01-01

Although many gastric cancers arise in chronic gastritis, the association between adenocarcinoma of the esophagogastric junction and the status of background gastritis remains unclear. We aim to investigate the histological status of gastritis in the background fundic gland mucosa of adenocarcinoma of the esophagogastric junction. The present study included 121 consecutive patients with superficial adenocarcinoma of the esophagogastric junction obtained by surgical and/or endoscopic resection. We re-evaluated the histogenesis of adenocarcinoma of the esophagogastric junction, including the background fundic gland mucosa using the Updated Sydney System. The prevalence of histologic atrophic gastric mucosa with gastritis (positive gastritis), non-atrophic gastric mucosa without gastritis (negative gastritis) and Barrett's adenocarcinoma was examined. Histologic-positive gastritis was found in 67 (55%) of all patients, in 24 (38%) of 63 Barrett's adenocarcinoma patients and in 43 (74%) of 58 non-Barrett's adenocarcinoma patients (P < 0.01). A higher female ratio in non-Barrett's adenocarcinoma with gastritis patients `and younger age in non-Barrett's adenocarcinoma without gastritis patients were shown. There were no differences in clinicopathological features related to the gastritis status in Barrett's adenocarcinoma patients. Reflux esophagitis was observed in most (81%) of all patients, and 32 (74%) of the non-Barrett's adenocarcinoma with gastritis patients. In the 67 positive gastritis patients, the mean Updated Sydney System scores of glandular atrophy and intestinal metaplasia were 1.45 and 1.10, respectively, and these scores were higher in the non-Barrett's adenocarcinoma patients than in the Barrett's adenocarcinoma patients. This study suggests that about half of the patients with adenocarcinoma of the esophagogastric junction harbor histological gastritis. Adenocarcinoma of the esophagogastric junction is considered to be a heterogeneous entity, including

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

PubMed

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

The bimanual ovarian palpation examination in the Prostate, Lung, Colorectal and Ovarian cancer screening trial: Performance and complications.

PubMed

Doroudi, Maryam; Kramer, Barnett S; Pinsky, Paul F

2017-12-01

Objective To provide evidence about the performance characteristics and consequences of bimanual ovarian palpation. Setting and methods The Prostate, Lung, Colorectal and Ovarian cancer screening trial randomized 154,900 individuals to either an intervention or control arm. Enrolled eligible participants were aged 55-74, had no history of trial cancers, and no current treatment for cancer. Intervention arm women received CA-125 tests and transvaginal ultrasound. Bimanual ovarian palpation was offered annually during the first four years of the trial. Bimanual ovarian palpation-specific sensitivity and specificity were calculated, as were rates of diagnostic procedures and resulting complications following positive bimanual ovarian palpation screens. Results A total of 20,872 women received at least one bimanual ovarian palpation, with 50,498 total bimanual ovarian palpation examinations performed. The sensitivity and specificity of bimanual ovarian palpation were 5.1% (2/39) and 99.0% (49,957/50,459), respectively; no cases were detected by bimanual ovarian palpation alone. Rates for most follow-up procedures for abnormal results in women without ovarian cancer were higher among the group with another screening test positive, except for pelvic exam, where rates were similar. No complications were reported in the bimanual ovarian palpation-only positive group. Conclusion Low sensitivity of bimanual ovarian palpation alone and in combination with other tests argue against using bimanual ovarian palpation as a screening test for ovarian cancer in asymptomatic women.

[Association between obesity and ovarian cancer].

PubMed

Valladares, Macarena; Corsini, Gino; Romero, Carmen

2014-05-01

Obesity is a risk factor for cancer. Epidemiological evidences associate ovarian cancer with obesity. Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer and accounts for a high rate of mortality. The association between ovarian cancer and obesity could be explained by molecular factors secreted by adipose tissue such as leptin. In EOC, leptin increases cell proliferation and inhibits apoptosis. Additionally, adipose tissue synthesizes endogenous estrogens, which increase cell proliferation of epithelial ovarian cells. Also, obesity associated hyperinsulinism could increase ovarian estrogen secretion.

Single Nucleotide Polymorphisms in the TP53 Region and Susceptibility to Invasive Epithelial Ovarian Cancer

PubMed Central

Schildkraut, Joellen M.; Goode, Ellen L; Clyde, Merlise A.; Iversen, Edwin S.; Moorman, Patricia G.; Berchuck, Andrew; Marks, Jeffrey R.; Lissowska, Jolanta; Brinton, Louise; Peplonska, Beata; Cunningham, Julie M.; Vierkant, Robert A.; Rider, David N.; Chenevix-Trench, Georgia; Webb, Penelope M.; Beesley, Jonathan; Chen, Xiaoqing; Phelan, Catherine; Sutphen, Rebecca; Sellers, Thomas A.; Pearce, Leigh; Wu, Anna H.; Van Den Berg, David; Conti, David; Elund, Christopher K.; Anderson, Rebecca; Goodman, Marc T.; Lurie, Galina; Carney, Michael E.; Thompson, Pamela J.; Gayther, Simon A.; Ramus, Susan J.; Jacobs, Ian; Kjaer, Susanne Krüger; Hogdall, Estrid; Blaakaer, Jan; Hogdall, Claus; Easton, Douglas F.; Song, Honglin; Pharoah, Paul D.P.; Whittemore, Alice S.; McGuire, Valerie; Quaye, Lydia; Anton-Culver, Hoda; Ziogas, Argyrios; Terry, Kathryn L.; Cramer, Daniel W.; Hankinson, Susan E.; Tworoger, Shelley S.; Calingaert, Brian; Chanock, Stephen; Sherman, Mark; Garcia-Closason, Montserrat

2009-01-01

The p53 protein is critical for multiple cellular functions including cell growth and DNA repair. We assessed whether polymorphisms in the region encoding TP53 were associated with risk of invasive ovarian cancer. The study population includes a total of 5,206 invasive ovarian cancer cases (2,829 of which were serous) and 8,790 controls from 13 case-control or nested case-control studies participating in the Ovarian Cancer Association Consortium (OCAC). Three of the studies performed independent discovery investigations involving genotyping of up to 23 single nucleotide polymorphisms (SNPs) in the TP53 region. Significant findings from this discovery phase were followed up for replication in the other OCAC studies. Mixed effects logistic regression was used to generate posterior median per allele odds ratios (ORs), 95% probability intervals (PIs) and Bayes factors (BFs) for genotype associations. Five SNPs showed significant associations with risk in one or more of the discovery investigations and were followed up by OCAC. Mixed effects analysis confirmed associations with serous invasive cancers for two correlated (r2 = 0.62) SNPs: rs2287498 (median per allele OR = 1.30; 95% PI = 1.07-1.57) and rs12951053 (median per allele OR = 1.19; 95% PI = 1.01 - 1.38). Analyses of other histological subtypes suggested similar associations with endometrioid but not with mucinous or clear cell cancers. This large study provides statistical evidence for a small increase in risk of ovarian cancer associated with common variants in the TP53 region. PMID:19276375

Ovarian Cancer FAQ

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

PubMed Central

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

2016-01-01

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

Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice

PubMed Central

David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

2017-01-01

Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte®. Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30–40 ng/mL 30 days after implantation. Absence of allo-MHC—specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth. PMID:28028710

Restoring Ovarian Endocrine Function with Encapsulated Ovarian Allograft in Immune Competent Mice.

PubMed

David, Anu; Day, James Ronald; Cichon, Alexa Leigh; Lefferts, Adam; Cascalho, Marilia; Shikanov, Ariella

2017-07-01

Premature ovarian insufficiency (POI) is a major complication of cytotoxic treatments due to extreme ovarian sensitivity to chemotherapy and radiation. In pediatric cancer patients modern therapy has improved the long-term survival to over 80% in the United States. However, these cancer survivors face long-term health problems related to treatment toxicity. In female cancer survivors POI leads to sterility, along with the consequences of estrogen deficiency such as premature osteopenia, muscle wasting, accelerated cardiovascular diseases and a vast array of other health and developmental problems. These long-lasting effects are particularly significant for young girls reaching puberty. As such, restoring ovarian endocrine function is paramount in this population. In the present study, we evaluated the feasibility of restoring ovarian endocrine function in ovariectomized mice by transplanting syngeneic and allogeneic ovarian tissue encapsulated in alginate capsules or TheraCyte ® . Histological analysis of the implants retrieved after 7 and 30 days' post implantation showed follicular development up to the secondary and antral stages in both syngeneic and allogeneic implants. Implantation of syngeneic and allogeneic ovarian grafts encapsulated in TheraCyte devices restored ovarian endocrine function, which was confirmed by decreased serum FSH levels from 60 to 70 ng/mL in ovariectomized mice to 30-40 ng/mL 30 days after implantation. Absence of allo-MHC-specific IgG and IgM antibodies in the sera of implanted mice with allogeneic ovarian tissue encapsulated in TheraCyte indicate that the implants did not evoke an allo-immune response, while the allogeneic controls were rejected 21 days after implantation. Our results show that TheraCyte effectively isolates the graft from immune recognition but also supports follicular growth.

Frequent homozygosity in both mature and immature ovarian teratomas: a shared genetic basis of tumorigenesis.

PubMed

Snir, Olivia L; DeJoseph, Maura; Wong, Serena; Buza, Natalia; Hui, Pei

2017-10-01

Although homozygosity is well documented in mature teratomas, the genetic zygosity of ovarian immature teratomas and mixed germ cell tumors is less well studied. Ten cases of mature cystic teratomas, eleven cases of grade 2 or 3 immature teratomas, and seven cases of mixed germ cell tumors with an immature teratoma component were investigated by short tandem repeat genotyping to interrogate their genetic zygosity. DNA genotyping was informative in eight mature teratomas, seven immature teratomas and six cases of mixed germ cell tumors. Out of the eight mature teratomas, five cases showed partial or complete homozygosity (63%) with two cases demonstrating complete homozygosity (25%). Of the immature teratomas, six cases showed partial or complete homozygosity (86%) with two cases demonstrating complete homozygosity (29%). For the mixed germ cell tumors, two cases showed partial homozygosity (33%) and none displayed complete homozygosity. Long-term clinical follow-up was available for five immature teratomas (mean follow-up 110 months) and five mixed germ cell tumors (mean follow-up 66 months). None of the five patients with pure immature teratoma had a recurrence; in contrast, four out of five mixed ovarian germ cell tumors recurred between 4 months to 8 years (P=0.048). In conclusion, both immature and mature teratomas harbor frequent genetic homozygosity suggesting a common cellular origin involving germ cells at the same developmental stage. The difference in the rate of homozygosity and tumor recurrence between pure immature teratomas and mixed germ cell tumors suggests that the two entities may involve different pathogenetic pathways and likely pursue different biological behaviors.

TMPRSS2-ERG gene fusion status in minute (minimal) prostatic adenocarcinoma.

PubMed

Albadine, Roula; Latour, Mathieu; Toubaji, Antoun; Haffner, Michael; Isaacs, William B; A Platz, Elizabeth; Meeker, Alan K; Demarzo, Angelo M; Epstein, Jonathan I; Netto, George J

2009-11-01

Minute prostatic adenocarcinomas are considered to be of insufficient virulence. Given recent suggestions of TMPRSS2-ERG gene fusion association with aggressive prostatic adenocarcinoma, we evaluated the incidence of TMPRSS2-ERG fusion in minute prostatic adenocarcinomas. A total of 45 consecutive prostatectomies with minute adenocarcinoma were used for tissue microarray construction. A total of 63 consecutive non-minimal, Gleason Score 6 tumors, from a separate PSA Era prostatectomy tissue microarray, were used for comparison. FISH was carried out using ERG break-apart probes. Tumors were assessed for fusion by deletion (Edel) or split (Esplit), duplicated fusions and low-level copy number gain in normal ERG gene locus. Minute adenocarcinomas: Fusion was evaluable in 32/45 tumors (71%). Fifteen out of 32 (47%) tumors were positive for fusion. Six (19%) were of the Edel class and 7 (22%) were classified as combined Edel+Esplit. Non-minute adenocarcinomas (pT2): Fusion was identified in 20/30 tumors (67%). Four (13%) were of Edel class and 5 (17%) were combined Edel+Esplit. Duplicated fusions were encountered in 5 (16%) tumors. Non-minute adenocarcinomas (pT3): Fusion was identified in 19/33 (58%). Fusion was due to a deletion in 6 (18%) tumors. Seven tumors (21%) were classified as combined Edel+Esplit. One tumor showed Esplit alone. Duplicated fusions were encountered in 3 (9%) cases. The incidence of duplicated fusions was higher in non-minute adenocarcinomas (13 vs 0%; P=0.03). A trend for higher incidence of low-level copy number gain in normal ERG gene locus without fusion was noted in non-minute adenocarcinomas (10 vs 0%; P=0.07). We found a TMPRSS2-ERG fusion rate of 47% in minute adenocarcinomas. The latter is not significantly different from that of grade matched non-minute adenocarcinomas. The incidence of duplicated fusion was higher in non-minute adenocarcinomas. Our finding of comparable rate of TMPRSS2-ERG fusion in minute adenocarcinomas may argue

Robotic-assisted fertility-sparing surgery for early ovarian cancer.

PubMed

Finger, Tamara Natasha; Nezhat, Farr Reza

2014-01-01

To show the feasibility and safety of robotic-assisted laparoscopic fertility-sparing surgery for earlystage ovarian cancer in women of reproductive age. The first patient was a 29-year-old para 0 woman with well-differentiated endometrioid adenocarcinoma of the ovary and complex endometrial hyperplasia with marked atypia. The second patient was a 31-year-old para 0 woman with an immature grade 1 teratoma. Both patients underwent robotic-assisted laparoscopic surgical staging. In the first patient, there were no intra- or postoperative complications. Operative time was 5 hours 43 minutes and estimated blood loss was 100 mL. She was discharged home on postoperative day 1. She received 3 cycles of carboplatin and paclitaxel, as well as medroxyprogesterone acetate for the duration of chemotherapy. She conceived twice spontaneously since surgery and had two successful deliveries. She currently has no evidence of disease. In the second patient, there were no intra- or postoperative complications. Operative time was 2 hours 52 minutes and estimated blood loss was 200 mL. She was discharged home on postoperative day 1. She declined adjuvant chemotherapy with bleomycin, etoposide, and cisplatin. She conceived spontaneously 4 months later and had a normal vaginal delivery. She currently has no evidence of disease. Because fertility-sparing surgery is now accepted as a viable option in young women with earlystage ovarian cancer, less invasive techniques are being used. With the advent of robotic-assisted surgery and its advantages over conventional laparoscopy, we show that it is a safe and feasible approach in select patients. This is the first reported series on robotic fertility-sparing surgery, but more research is needed.

Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma.

PubMed

Moy, Andrea P; Arora, Kshitij; Deshpande, Vikram

2016-09-01

Bile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well-differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma. We studied 26 bile duct adenomas, three bile duct hamartomas, and 158 pancreatic ductal adenocarcinomas. Branched-chain in-situ hybridization (bISH) for albumin was performed; bISH is based on the branched DNA technology, wherein signal amplification is achieved via a series of sequential steps. Additionally, BRAFV600E immunohistochemistry (IHC) was performed on a subset of cases. Twenty-three of 25 (92%) bile duct adenomas were positive for albumin; 18 (72%) showed diffuse staining, and five showed focal staining (20%), including two challenging examples. Two bile duct hamartomas also stained positively. All pancreatic adenocarcinomas were negative for albumin. Seven of 16 (44%) bile duct adenomas and five of 106 (5%) pancreatic ductal adenocarcinomas were positive for BRAFV600E by IHC. The sensitivity and specificity of expression of albumin, as detected by bISH, for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 92% and 100%, respectively; the sensitivity and specificity of BRAFV600E IHC for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 43.8% and 95.3%, respectively. Diagnostically challenging examples of bile duct adenoma may be distinguished from metastatic pancreatic adenocarcinoma by the use of albumin bISH. © 2016 John Wiley & Sons Ltd.

Ureteric stricture secondary to unusual extension of prostatic adenocarcinoma.

PubMed

Chalasani, Venu; Macek, Petr; O'Neill, Gordon F; Barret, Wade

2010-02-01

This article describes an unusual finding in a patient who presented with an adenocarcinoma of the prostate and right hydronephrosis. A 68-year-old male presented with right hydronephrosis and a PSA of 96. DRE was consistent with cT3 carcinoma. Cystoscopy showed an exophytic superficial transitional cell carcinoma (TCC) of the bladder and a transrectal biopsy of the prostate confirmed adenocarcinoma Gleason score 4+3. Staging investigations (CT pelvis and bone scan) were negative; androgen deprivation therapy was therefore initiated for the prostatic adenocarcinoma. Upper tract imaging showed multiple filling defects in the proximal ureter. Ureteroscopy showed a stricture at the level of the iliac vessels. With a working diagnosis of upper tract TCC, right open nephroureterectomy was performed. Final histology showed prostatic adenocarcinoma infiltrating the adventitia of the entire ureter up to the level of the renal pelvis. A rare cause of ureteric stricture, contiguous spread of prostatic adenocarcinoma, should be considered in the differential diagnosis of patients presenting with upper tract obstruction and a known history of prostatic adenocarcinoma. Androgen deprivation therapy for several months did not seem to cause resolution of the tumor in the periureteric, ureteric and perihilar tissues.

Quantitative proteomics of bronchoalveolar lavage fluid in lung adenocarcinoma.

PubMed

Almatroodi, Saleh A; McDonald, Christine F; Collins, Allison L; Darby, Ian A; Pouniotis, Dodie S

2015-01-01

The most commonly reported primary lung cancer subtype is adenocarcinoma, which is associated with a poor prognosis and short survival. Proteomic studies on human body fluids such as bronchoalveolar lavage fluid (BALF) have become essential methods for biomarker discovery, examination of tumor pathways and investigation of potential treatments. This study used quantitative proteomics to investigate the up-regulation of novel proteins in BALF from patients with primary lung adenocarcinoma in order to identify potential biomarkers. BALF samples from individuals with and without primary lung adenocarcinoma were analyzed using liquid chromatography-mass spectrometry. One thousand and one hundred proteins were identified, 33 of which were found to be consistently overexpressed in all lung adenocarcinoma samples compared to non-cancer controls. A number of overexpressed proteins have been previously shown to be related to lung cancer progression including S100-A8, annexin A1, annexin A2, thymidine phosphorylase and transglutaminase 2. The overexpression of a number of specific proteins in BALF from patients with primary lung adenocarcinoma may be used as a potential biomarker for lung adenocarcinoma. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis

PubMed Central

Reid, Brian J.; Li, Xiaohong; Galipeau, Patricia C.; Vaughan, Thomas

2010-01-01

The public health importance of Barrett’s oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world and there are indications that the incidence of this disease is on the rise in Asian populations where it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma and data indicate that patients with Barrett’s oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinoma arise in individuals without a prior diagnosis of Barrett’s oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma? PMID:20094044

Ovarian parameters and ovarian blood flow of women living in the area of environmental crisis.

PubMed

Balmagambetova, Aru; Abdelazim, Ibrahim A; Bekmukhambetov, Erbol; Zhurabekova, Gulmira; Yehia, Amr H; AbuFaza, Mohannad

2016-05-01

Exposure to environmental hazards will destroy a number of ovarian primordial follicles, reduce ovarian reserve and subsequent reproductive ability. This study designed to evaluate ovarian parameters and ovarian blood flow of women living in the area of environmental crisis Shalkar city (Kazakhstan) compared to women living in Aktobe city (Kazakhstan). 220 women in their reproductive age studied and classified into two groups; study (Shalkar) group and control (Aktobe) group. Blood sample taken from studied women during follicular phase (day 3) for hormonal level evaluation including; follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH). Studied women evaluated using trans-vaginal ultrasound (TVS) to detect antral follicle count (AFC) during follicular scan and ovarian volume (OV), ovarian blood flow (OBF) using pulsatility index (PI) during follicular scan and luteal scan. Both ovaries AFC was significantly less in study (Shalkar) group compared to and control (Aktobe) group (p=0.0001). Mean ovarian volume was significantly less in Shalkar group in both follicular phase and luteal phase (5.86±0.23 and 6.19±0.22Cm(3); respectively) compared to Aktobe group (6.85±0.19 and 6.92±0.18Cm(3); respectively). In addition, mean ovarian pulsatility index was significantly high with subsequent decrease in ovarian blood flow in Shalkar group in both follicular phase and luteal phase (3.36±0.20 and 3.45±0.19Cm/s; respectively) compared to Aktobe group (2.96±0.16 and 2.92±0.15Cm/s; respectively). This study suggests definite environmental effect on ovarian parameters as indicated by decreased AFC, decreased both follicular and luteal OV and OBF in women living in environmental crisis Shalkar group compared to Aktobe group. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.

PubMed

Peluso, John J

2011-08-01

Various ovarian cell types including granulosa cells and ovarian surface epithelial cells express the progesterone (P4) binding protein, progesterone receptor membrane component-1 (PGRMC1). PGRMC1 is also expressed in ovarian tumors. PGRMC1 plays an essential role in promoting the survival of both normal and cancerous ovarian cell in vitro. Given the clinical significance of factors that regulate the viability of ovarian cancer, this review will focus on the role of PGRMC1 in ovarian cancer, while drawing insights into the mechanism of PGRMC1's action from cell lines derived from healthy ovaries as well as ovarian tumors. Studies using PGRMC1siRNA demonstrated that P4's ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1. To confirm the importance of PGRMC1, the ability of PGRMC1-deplete ovarian cancer cell lines to form tumors in intact nude mice was assessed. Compared to PGRMC1-expressing ovarian cancer cells, PGRMC1-deplete ovarian cancer cells formed tumors in fewer mice (80% compared to 100% for controls). Moreover, the number of tumors derived from PGRMC1-deplete ovarian cancer cells was 50% of that observed in controls. Finally, the tumors that formed from PGRMC1-deplete ovarian cancer cells were about a fourth the size of tumors derived from ovarian cancer cells with normal levels of PGRMC1. One reason for PGRMC1-deplete tumors being smaller is that they had a poorly developed microvasculature system. How PGRMC1 regulates cell viability and in turn tumor growth is not known but part of the mechanism likely involves the regulation of genes that promote cell survival and inhibit apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Plasma and ovarian tissue sphingolipids profiling in patients with advanced ovarian cancer.

PubMed

Knapp, Paweł; Bodnar, Lubomir; Błachnio-Zabielska, Agnieszka; Świderska, Magdalena; Chabowski, Adrian

2017-10-01

The role of lipids in carcinogenesis through induction of abnormal cell lines in the human body is currently undisputable. Based on the literature, bioactive sphingolipids play an essential role in the development and progression of cancer and are involved in the metastatic process. The aim of this study was to determine the concentration of selected sphingolipids in patients with advanced ovarian cancer (AOC, FIGO III/IV, high grade ovarian cancer). Seventy-four patients with ovarian cancer were enrolled. Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were assessed by LC/MS/MS. The content of tissue sphingolipids was measured using a UHPLC/MS/MS. Plasma concentration of 3 ceramides: C16-Cer, C18:1-Cer and C18-Cer was significantly elevated in women with advanced ovarian cancer compared to control group (P=0.031; 0.022; 0.020; respectively). There were increases in concentration of 5 ceramides: C16-Cer, C18:1-Cer, C18-Cer, C24:1-Cer, C24-Cer (P=0.025; 0.049; 0.032; 0.005; 0.013, respectively) and S1P (P=0.004) in ovarian tissue of women with advanced ovarian cancer compared to healthy individuals. Importantly, significantly higher risk of ovarian cancer when the plasma concentration of C16-Cer>311.88ng/100μl (AUC: 0.76, P=0.0261); C18:1-Cer>4.75ng/100μl (AUC: 0.77, P=0.0160) and C18-Cer>100.76ng/100μl (AUC:0.77, P=0.0136) was noticed. Bioactive sphingolipids play an essential role in the development and progression of cancer and they also take part in the process of metastasizing. This study suggests that some sphingolipids can be used as potential biomarkers of advanced ovarian cancer and that they can play an important role in the pathogenesis of this disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Coexistence of gastrointestinal stromal tumors and gastric adenocarcinomas.

PubMed

Yan, Yan; Li, Ziyu; Liu, Yiqiang; Zhang, Lianhai; Li, Jiyou; Ji, Jiafu

2013-04-01

The purpose of this study is to detect the clinicopathology of gastrointestinal stromal tumors (GISTs) occurring synchronously with gastric adenocarcinomas and to unveil the potential underlying relationship between the synchronous GIST and gastric adenocarcinoma. This study included 15 patients with incidental GISTs found during operations for gastric adenocarcinoma and 30 patients who underwent gastrectomy for gastric cancer without discovering GIST between January 2005 and December 2010 at the Beijing Cancer Institute. We collected the clinicopathological data and analyzed the KIT/PDGFRA mutational status of GISTs, corresponding gastric adenocarcinoma specimens, and the normal tissue around the cancer lesions. Additionally, as a control group, the mutational status of the patients with gastric adenocarcinoma and no other tumors was assayed. Overall, 18 GISTs were found in 15 gastric adenocarcinoma patients. Multiple GIST lesions were found in three cases (20 %). The patients' age ranged from 46 to 85 years, with an average of 67.6 years. The average size of the GISTs was 0.85 cm. All mesenchymal lesions showed low proliferative activity, were of low or very low risk, and were identified as CD117-positive by immunostaining. In GIST lesions, mutations in KIT were detected in 7 out of 13 cases, and of these mutations, 6 were found in exon 11 (46.2 %), and 1 was found in exon 9 (7.7 %). A total of five deletions and one point mutation were in exon 11, and one insertion was in exon 9. Mutations were not detected in exon 17 or 13 of KIT. There was no remarkable mutation analyzed in the gastric adenocarcinoma lesions or normal tissues from either the test or control groups. Clinicopathological profiles and molecular analysis of KIT/PDGFRA showed no obvious relationship between gastric cancer and GISTs in tumor genesis, such as similar oncogene mutations.

Malignant ovarian germ cell tumor - role of surgical staging and gonadal dysgenesis.

PubMed

Lin, Ken Y; Bryant, Stefanie; Miller, David S; Kehoe, Siobhan M; Richardson, Debra L; Lea, Jayanthi S

2014-07-01

To evaluate the effect of comprehensive surgical staging and gonadal dysgenesis on the outcomes of patients with malignant ovarian germ cell tumor. We performed a retrospective review of patients with ovarian germ cell tumors who were treated at our institution between 1976 and 2012. Malignant ovarian germ cell tumors (MOGCTs) were identified in 50 females. The median age was 24 years (range 13 to 49). Of all MOGCT patients, 42% had dysgerminoma, 20% immature teratoma, 16% endodermal sinus tumor, and 22% mixed germ cell tumor. Univariate analyses revealed that the lack of surgical staging (p=0.048) and endodermal sinus tumor (p=0.0085) were associated with disease recurrence, while age at diagnosis, ethnicity, and stage of the disease were not. Multivariate analyses revealed that the lack of surgical staging (p=0.029) and endodermal sinus tumor (p=0.016) were independently associated with disease recurrence. In addition, 7 patients (14%) had 46 XY karyotype, including 6 with pure dysgerminoma and 1 with mixed germ cell tumor. Five had Swyer syndrome and 2 had complete androgen insensitivity syndrome. Concurrent gonadoblastoma was found in 5 of the patients. No difference was found in the mean age at presentation, stage distribution, or recurrence rate for MOGCT patients with or without XY phenotype. Comprehensive surgical staging was associated with a lower rate of recurrence. Fourteen percent of phenotypic females with MOGCT and 29% of those with dysgerminoma had XY karyotype. The clinical outcome of these patients is similar to that of MOGCT patients with XX karyotype. Published by Elsevier Inc.

Lung adenocarcinoma mimicking pulmonary fibrosis-a case report.

PubMed

Mehić, Bakir; Duranović Rayan, Lina; Bilalović, Nurija; Dohranović Tafro, Danina; Pilav, Ilijaz

2016-09-13

Lung cancer is usually presented with cough, dyspnea, pain and weight loss, which is overlapping with symptoms of other lung diseases such as pulmonary fibrosis. Pulmonary fibrosis shows characteristic reticular and nodular pattern, while lung cancers are mostly presented with infiltrative mass, thick-walled cavitations or a solitary nodule with spiculated borders. If the diagnosis is established based on clinical symptoms and CT findings, it would be a misapprehension. We report a case of lung adenocarcinoma whose symptoms as well as clinical images overlapped strongly with pulmonary fibrosis. The patient's non-productive cough, progressive dyspnea, restrictive pattern of pulmonary function test and CT scans (showing reticular interstitial opacities) were all indicative of pulmonary fibrosis. The patient underwent a treatment consisting of corticosteroids and antibiotics, to no avail. Histopathology of the lung showed that the patient suffered from mucinous adenocarcinoma. Albeit the immunohistochemical staining was not consistent with lung adenocarcinoma, tumor's morphological characteristics were consistent, and were used to make the definitive diagnosis. Given the fact that radiography cannot always make a clear-cut difference between pulmonary fibrosis and lung adenocarcinomas, and that clinical symptoms often overlap, histological examination should be considered as gold standard for diagnosis of lung adenocarcinoma.

[Surgical treatment of perinatal ovarian cysts].

PubMed

Armas Alvarez, A L; Taboada Santomil, P; Pradillos Serna, J M; Rivera Chavez, L L; Méndez Gallart, R; Estévez Martínez, E; Rodríguez Barca, P; Bautista Casasnovas, A; Varela Cives, R

2010-10-01

Actually, the perinatal ovarian cysts are increasingly being diagnosed by prenatal and neonatal ultrasound. We reported our experience in the surgical management of perinatal ovarian cysts. Patients and methods. We have reviewed the clinical charts of 10 female newborns diagnosed of ovarian cysts who underwent surgical management in our hospital from 1989 to 2009. The ovarian cysts were diagnosed antenatally in 8 cases and period neonatal in 2 cases. The clinical presentation was asymptomatic abdominal mass in 7 cases. Ultrasound confirmed the ovarian mass in 8 patients. CT scan and MRI were necessary for confirm suspected diagnosis in two patients. Ultrasonography showed 7 complex cysts and 3 simple cysts. Surgery of the complicated cysts revealed ovarian torsion in 5 cases and 1 hemorragic cyst. At surgery, 5 patients underwent salpingooophorectomy, 2 patients needed oophorectomy and in 3 cases only cystectomy were necessary. The ovarian torsion is the most common complication and the cause of loss of the ovary. The neonatal ovarian cysts greater than 5 centimetres, symptomatic cysts, complex cysts and cysts persisting for more than 6 months need surgical intervention.

Is cervical screening preventing adenocarcinoma and adenosquamous carcinoma of the cervix?

PubMed Central

Landy, Rebecca; Sasieni, Peter D.

2016-01-01

While the incidence of squamous carcinoma of the cervix has declined in countries with organised screening, adenocarcinoma has become more common. Cervical screening by cytology often fails to prevent adenocarcinoma. Using prospectively recorded cervical screening data in England and Wales, we conducted a population‐based case–control study to examine whether cervical screening leads to early diagnosis and down‐staging of adenocarcinoma. Conditional logistic regression modelling was carried out to provide odds ratios (ORs) and 95% confidence intervals (CIs) on 12,418 women with cervical cancer diagnosed between ages 30 and 69 and 24,453 age‐matched controls. Of women with adenocarcinoma of the cervix, 44.3% were up to date with screening and 14.6% were non‐attenders. The overall OR comparing women up to date with screening with non‐attenders was 0.46 (95% CI: 0.39–0.55) for adenocarcinoma. The odds were significantly decreased (OR: 0.22, 95% CI: 0.15–0.33) in up to date women with Stage 2 or worse adenocarcinoma, but not for women with Stage1A adenocarcinoma 0.71 (95% CI: 0.46–1.09). The odds of Stage 1A adenocarcinoma was double among lapsed attenders (OR: 2.35, 95% CI: 1.52–3.62) compared to non‐attenders. Relative to women with no negative cytology within 7 years of diagnosis, women with Stage1A adenocarcinoma were very unlikely to be detected within 3 years of a negative cytology test (OR: 0.08, 95% CI: 0.05–0.13); however, the odds doubled 3–5 years after a negative test (OR: 2.30, 95% CI: 1.67–3.18). ORs associated with up to date screening were smaller for squamous and adenosquamous cervical carcinoma. Although cytology screening is inefficient at preventing adenocarcinomas, invasive adenocarcinomas are detected earlier than they would be in the absence of screening, substantially preventing Stage 2 and worse adenocarcinomas. PMID:27096255

Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports

PubMed Central

HINO, MAYO; YAMAGUCHI, KEN; ABIKO, KAORU; YOSHIOKA, YUMIKO; HAMANISHI, JUNZO; KONDOH, EIJI; KOSHIYAMA, MASAFUMI; BABA, TSUKASA; MATSUMURA, NORIOMI; MINAMIGUCHI, SACHIKO; KIDO, AKI; KONISHI, IKUO

2016-01-01

Our group previously documented the first, very rare case of primary gastric-type mucinous adenocarcinoma of the uterine corpus. Although this type of endometrial cancer appears to be similar to the gastric-type adenocarcinoma of the uterine cervix, its main symptoms, appearance on magnetic resonance imaging (MRI) and prognosis have not been fully elucidated due to its rarity. We herein describe an additional case of gastric-type mucinous adenocarcinoma of the endometrium and review the relevant literature. The two cases at our institution (Kyoto University Hospital, Kyoto, Japan) involved postmenopausal women with a primary complaint of abnormal genital bleeding. Microscopic examination of the hysterectomy specimens indicated a highly differentiated mucinous adenocarcinoma with a desmoplastic stromal reaction. Immunohistochemistry for HIK1083 and/or MUC6 was positive in both cases, suggesting a gastric phenotype. Both patients were diagnosed at an advanced stage, they relapsed or recurred immediately after adjuvant chemotherapy, and eventually succumbed to the disease. The main symptom of gastric-type mucinous adenocarcinoma of the uterine cervix is watery discharge, whereas abnormal genital bleeding in addition to watery discharge is mainly observed in the mucinous type of endometrial adenocarcinoma. Cystic cavities in the tumor are present on MRI in cases of endometrial origin, and prognosis is very poor due to resistance to chemotherapy. Thus, gastric-type mucinous adenocarcinoma of the uterine endometrium exhibits a clinical behavior that is similar to tumors originating from the uterine cervix, but is associated with distinguishing clinical symptoms. The incidence of gastric-type endometrial adenocarcinoma may be higher than expected. PMID:27123265

Magnetic resonance imaging findings and prognosis of gastric-type mucinous adenocarcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: Two case reports.

PubMed

Hino, Mayo; Yamaguchi, Ken; Abiko, Kaoru; Yoshioka, Yumiko; Hamanishi, Junzo; Kondoh, Eiji; Koshiyama, Masafumi; Baba, Tsukasa; Matsumura, Noriomi; Minamiguchi, Sachiko; Kido, Aki; Konishi, Ikuo

2016-05-01

Our group previously documented the first, very rare case of primary gastric-type mucinous adenocarcinoma of the uterine corpus. Although this type of endometrial cancer appears to be similar to the gastric-type adenocarcinoma of the uterine cervix, its main symptoms, appearance on magnetic resonance imaging (MRI) and prognosis have not been fully elucidated due to its rarity. We herein describe an additional case of gastric-type mucinous adenocarcinoma of the endometrium and review the relevant literature. The two cases at our institution (Kyoto University Hospital, Kyoto, Japan) involved postmenopausal women with a primary complaint of abnormal genital bleeding. Microscopic examination of the hysterectomy specimens indicated a highly differentiated mucinous adenocarcinoma with a desmoplastic stromal reaction. Immunohistochemistry for HIK1083 and/or MUC6 was positive in both cases, suggesting a gastric phenotype. Both patients were diagnosed at an advanced stage, they relapsed or recurred immediately after adjuvant chemotherapy, and eventually succumbed to the disease. The main symptom of gastric-type mucinous adenocarcinoma of the uterine cervix is watery discharge, whereas abnormal genital bleeding in addition to watery discharge is mainly observed in the mucinous type of endometrial adenocarcinoma. Cystic cavities in the tumor are present on MRI in cases of endometrial origin, and prognosis is very poor due to resistance to chemotherapy. Thus, gastric-type mucinous adenocarcinoma of the uterine endometrium exhibits a clinical behavior that is similar to tumors originating from the uterine cervix, but is associated with distinguishing clinical symptoms. The incidence of gastric-type endometrial adenocarcinoma may be higher than expected.

Impact of transvaginal hydrolaparoscopy ovarian drilling on ovarian stromal blood flow and ovarian volume in clomiphene citrate-resistant PCOS patients: a case-control study.

PubMed

Giampaolino, Pierluigi; Morra, Ilaria; De Rosa, Nicoletta; Cagnacci, Angelo; Pellicano, Massimiliano; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

2017-09-01

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in gynecology. In PCOS patients vascularization parameters are altered. Transvaginal hydrolaparoscopy (THL) is a mini-invasive approach for ovarian drilling in PCOS patients. In this study, we assessed the effect of ovarian drilling using THL on ovarian volume (OV) and vascularization index (VI) using 3D power Doppler ultrasonography in CC-resistant PCOS patients. A case-control study on 123 CC-resistant PCOS women who underwent THL ovarian drilling was performed. Patients underwent 3D ultrasound and power Doppler to measure VI, flow index (FI), vascularization flow index (VFI) and to evaluate OV before and after the procedure, at six months, and on the early follicular phase of the menstrual cycle. After THL ovarian drilling, OV and power Doppler flow indices were significantly reduced compared to pre-operative values (OV: 7.85 versus 11.72 cm 3 , p < 0.01; VI: 2.50 versus 4.81, p < 0.01; VFI: 1.10 versus 2.16, p < 0.01; FI: 32.05 versus 35.37, p < 0.01). In conclusion, THL ovarian drilling seems to reduce OV and 3D power Doppler indices, and could therefore be a viable alternative to LOD in PCOS patients resistant to medical therapy.

Computed tomography findings of ovarian metastases from colon cancer: comparison with primary malignant ovarian tumors.

PubMed

Choi, Hyuck Jae; Lee, Joo-Hyuk; Seo, Sang-Soo; Lee, Sun; Kim, Seok Ki; Kim, Joo-Young; Lee, Jong Seok; Park, Sang-Yoon; Kim, Young Hoon

2005-01-01

The computed tomography (CT) findings of ovarian metastases from colon cancer were evaluated and were compared with those of primary malignant ovarian tumors. Sixteen patients with 21 masses from colon cancer and 20 patients with 31 primary malignant ovarian tumors were included in this study. The CT findings (laterality, size, margin, shape, mass characteristic, strong enhancement of cyst wall, enhancement of solid portion, amount of ascites, peritoneal seeding, lymph node enlargement, and metastasis) and ages of the patients in both groups were compared. Univariate analysis, the Pearson chi test, and the independent-samples t test were used to distinguish them. A smooth margin of the tumor (odds ratio=24.3, 95% confidence interval: 2.9-204.2) and cystic nature of the mass (Pearson chi=12.96, P=0.005) were strong predictors of ovarian metastasis from colon cancer. Ovarian metastases from colon cancer show a smooth margin and more cystic nature on CT compared with primary malignant ovarian tumors.

Nedd4L expression is decreased in ovarian epithelial cancer tissues compared to ovarian non-cancer tissue.

PubMed

Yang, Qiuyun; Zhao, Jinghe; Cui, Manhua; Gi, Shuting; Wang, Wei; Han, Xiaole

2015-12-01

Recent studies have demonstrated that the neural precursor cell expressed, developmentally downregulated 4-like (Nedd4L) gene plays a role in the progression of various cancers. However, reports describing Nedd4L expression in ovarian cancer tissues are limited. A cohort (n = 117) of archival formalin-fixed, paraffin embedded resected normal ovarian epithelial tissues (n = 10), benign ovarian epithelial tumor tissues (n = 10), serous borderline ovarian epithelial tumor tissues (n = 14), mucous borderline ovarian epithelial tumor tissues (n = 11), and invasive ovarian epithelial cancer tissues (n = 72) were assessed for Nedd4L protein expression using immunohistochemistry. Nedd4L protein expression was significantly decreased in invasive ovarian epithelial cancer tissues compared to non-cancer tissues (P < 0.05). Decreased Nedd4L protein expression correlated with clinical stage, pathological grade, lymph node metastasis and survival (P < 0.05). Nedd4L protein expression may be an independent prognostic marker of ovarian cancer development. © 2015 Japan Society of Obstetrics and Gynecology.

Targeting Src in Mucinous Ovarian Carcinoma

PubMed Central

Matsuo, Koji; Nishimura, Masato; Bottsford-Miller, Justin N.; Huang1, Jie; Komurov, Kakajan; Armaiz-Pena, Guillermo N.; Shahzad, Mian M. K.; Stone, Rebecca L.; Roh, Ju Won; Sanguino, Angela M.; Lu, Chunhua; Im, Dwight D.; Rosenshien, Neil B.; Sakakibara, Atsuko; Nagano, Tadayoshi; Yamasaki, Masato; Enomoto, Takayuki; Kimura, Tadashi; Ram, Prahlad T.; Schmeler, Kathleen M.; Gallick, Gary E.; Wong, Kwong K.; Frumovitz, Michael; Sood, Anil K.

2014-01-01

PURPOSE Mucinous ovarian carcinomas have a distinct clinical pattern compared to other subtypes of ovarian carcinoma. Here, we evaluated (i) stage-specific clinical significance of mucinous ovarian carcinomas in a large cohort and (ii) the functional role of src kinase in pre-clinical models of mucinous ovarian carcinoma. EXPERIMENTAL DESIGN 1302 ovarian cancer patients including 122 (9.4%) cases of mucinous carcinoma were evaluated for survival analyses. Biological effects of src kinase inhibition were tested in a novel orthotopic mucinous ovarian cancer model (RMUG-S-ip2) using dasatinib-based therapy. RESULTS Patients with advanced-stage mucinous ovarian cancer had significantly worse survival compared to those with serous histology: median overall survival, 1.67 versus 3.41 years, p=0.002; and median survival time after recurrence of 0.53 versus 1.66 years, p<0.0001. Among multiple ovarian cancer cell lines, RMUG-S-ip2 mucinous ovarian cancer cells showed the highest src kinase activity. Moreover, oxaliplatin treatment induced phosphorylation of src kinase. This induced activity by oxaliplatin therapy was inhibited by concurrent administration of dasatinib. Targeting src with dasatinib in vivo showed significant anti-tumor effects in the RMUG-S-ip2 model, but not in the serous ovarian carcinoma (SKOV3-TR) model. Combination therapy of oxaliplatin with dasatinib further demonstrated significant effects on reducing cell viability, increasing apoptosis, and in vivo anti-tumor effects in the RMUG-S-ip2 model. CONCLUSIONS Our results suggest that poor survival of women with mucinous ovarian carcinoma is associated with resistance to cytotoxic therapy. Targeting src kinase with combination of dasatinib and oxaliplatin may be an attractive approach in this disease. PMID:21737505

Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas

PubMed Central

Sayar, İlyas; Gökçe, Aysun; Demirtas, Levent; Eken, Hüseyin; Çimen, Ferda Keskin; Çimen, Orhan

2017-01-01

Background There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. Material/Methods Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. Results In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. Conclusions Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas. PMID:28561015

Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

PubMed

Sayar, İlyas; Gökçe, Aysun; Demirtas, Levent; Eken, Hüseyin; Çimen, Ferda Keskin; Çimen, Orhan

2017-05-31

BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

Silver nanoparticles of different sizes induce a mixed type of programmed cell death in human pancreatic ductal adenocarcinoma

PubMed Central

Zielinska, Ewelina; Zauszkiewicz-Pawlak, Agata; Wojcik, Michal; Inkielewicz-Stepniak, Iwona

2018-01-01

Pancreatic ductal adenocarcinoma, with the high resistance to chemotherapeutic agents, remains the fourth leading cause of cancer-death in the world. Due to the wide range of biological activity and unique properties, silver nanoparticles (AgNPs) are indicated as agents with potential to overcome barriers involved in chemotherapy failure. Therefore, in our study we decided to assess the ability of AgNPs to kill pancreatic cancer cells, and then to identify the molecular mechanism underlying this effect. Moreover, we evaluated the cytotoxicity of AgNPs against non-tumor cell of the same tissue (hTERT-HPNE cells) for comparison. Our results indicated that AgNPs with size of 2.6 and 18 nm decreased viability, proliferation and caused death of pancreatic cancer cells in a size- and concentration-dependent manner. Ultrastructural analysis identified that cellular uptake of AgNPs resulted in apoptosis, autophagy, necroptosis and mitotic catastrophe. These alterations were associated with increased pro-apoptotic protein Bax and decreased level of anti-apoptotic protein Bcl-2. Moreover, AgNPs significantly elevated the level of tumor suppressor p53 protein as well as necroptosis- and autophagy-related proteins: RIP-1, RIP-3, MLKL and LC3-II, respectively. In addition, we found that PANC-1 cells were more vulnerable to AgNPs-induced cytotoxicity compared to pancreatic non-tumor cells. In conclusion, AgNPs by inducing mixed type of programmed cell death in PANC-1 cells, could provide a new therapeutic strategy to overcome chemoresistance in one of the deadliest human cancer. PMID:29435134

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.

A variant c-KIT mutation, D816H, fundamental to the sequential development of an ovarian mixed germ cell tumor and systemic mastocytosis with chronic myelomonocytic leukemia.

PubMed

Mitchell, Sarah G; Bunting, Silvia T; Saxe, Debra; Olson, Thomas; Keller, Frank G

2017-04-01

An activating point mutation of the c-KIT tyrosine kinase receptor gene, D816H, has been described in germ cell tumors (GCTs). We report an adolescent diagnosed with an ovarian mixed GCT and systemic mastocytosis with chronic myelomonocytic leukemia (SM-CMML). The teratoma and dysgerminoma differed by copy number aberrations via single nucleotide polymorphism (SNP) microarray, but were inclusive of the same c-KIT D816H point mutation (c.2446G>C) also identified in blood and bone marrow mast cells. These findings indicate not only a clonal origin of the GCT and hematologic malignancy, but also suggest a rare KIT mutation may be playing a fundamental role in malignancy development. © 2016 Wiley Periodicals, Inc.

Antidepressants and Breast and Ovarian Cancer Risk: A Review of the Literature and Researchers' Financial Associations with Industry

PubMed Central

Cosgrove, Lisa; Shi, Ling; Creasey, David E.; Anaya-McKivergan, Maria; Myers, Jessica A.; Huybrechts, Krista F.

2011-01-01

Background Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results [1]–[6]. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions [7]. Methods and Findings We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers' financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 (95% CI, 1.03–1.20). Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher's Exact test P = 0.0012). Conclusions Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009

Antidepressants and breast and ovarian cancer risk: a review of the literature and researchers' financial associations with industry.

PubMed

Cosgrove, Lisa; Shi, Ling; Creasey, David E; Anaya-McKivergan, Maria; Myers, Jessica A; Huybrechts, Krista F

2011-04-06

Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions. We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers' financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 (95% CI, 1.03-1.20). Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher's Exact test P = 0.0012). Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009 USPSTF guidelines for breast cancer screening and for the

Ovarian transposition in young women and fertility sparing.

PubMed

Mossa, B; Schimberni, M; Di Benedetto, L; Mossa, S

2015-09-01

Ovarian transposition is a highly effective surgical procedure used to preserve ovarian function in premenopausal patients with cancers requiring postoperative or primary pelvic radiotherapy. Pelvic irradiation determines severe damage of ovarian DNA and iatrogenic ovarian failure with premature menopause, necessity of long-term hormone replacement therapy and infertility. We conducted an extensive research of the literature in Medline between January 2000 and April 2015 using the key-words "ovarian transposition radiotherapy", "radiotherapy gonadal function", radiotherapy fertility sparing". The population included young women with normal ovarian function affected by cancers that required pelvic radiotherapy. We have examined 32 articles reporting on 1189 women undergoing ovarian transposition. Median age was 32.5 years, follow up was median 48 months. The procedure has been performed in patients less than 40 years of age. Surgery has been achieved by laparotomy or laparoscoy. We have analyzed effects of radiotherapy on ovarian function. The proportion of women treated by ovarian transposition preserved ovarian function was 70%. About 86% of patients did not develop ovarian cysts and in 98-99% of cases did not occur any metastatic disease. Ovarian transposition is associated with significant preservation of ovarian function and a low frequency of complications as cysts and metastasis. In 31% of cases the procedure can fail. Further studies are needed to evaluate the efficacy of ovarian transposition and the follow up. Ovarian transposition should be discussed at the time of cancer diagnosis in every premenopausal woman requiring pelvic radiotherapy.

Lymphocytic gastritis, gastric adenocarcinoma, and primary gastric lymphoma.

PubMed Central

Griffiths, A P; Wyatt, J; Jack, A S; Dixon, M F

1994-01-01

A series of primary gastric lymphomas and adenocarcinomas was reviewed to assess the prevalence of lymphocytic gastritis in these conditions. Lymphocytic gastritis was more prevalent in patients with gastric adenocarcinoma (16 of 130 cases; 12.3%) and primary gastric lymphoma (six of 45 cases; 13.7%) than in unselected patients undergoing endoscopy (0.83-2.5%). This suggests that these two disparate gastric tumours may share an immunological dysfunction or a common pathogenesis, and this is of interest given that Helicobacter pylori is thought to have a role in the evolution of gastric adenocarcinoma and lymphoma. PMID:7876391

Adenocarcinoma arising in urinary bladder endocervicosis.

PubMed

Nakaguro, Masato; Tsuzuki, Toyonori; Shimada, Satoko; Taki, Tetsuro; Tsuchiyama, Mari; Kitamura, Atsuko; Suzuki, Yasuhiko; Nakano, Yojiro; Ono, Kenzo

2016-02-01

Endocervicosis is a rare benign condition characterized by the presence of endocervical-type mucinous glands. Urinary bladder endocervicosis forms an elevated lesion in the posterior wall of the urinary bladder and is sometimes misdiagnosed as a malignant tumor clinically and pathologically. Herein we describe the first case of adenocarcinoma arising in urinary bladder endocervicosis. The patient, a 58-year-old woman, presented with asymptomatic hematuria. Cystoscopy revealed a nodular mass measuring 4 cm in diameter in the posterior wall, and total cystectomy was performed. Histology revealed that the elevated lesion of the bladder wall was composed of haphazard proliferation of cystic glands lined by benign endocervical-type epithelium. An adenocarcinoma arose at the center of this endocervicosis. Mucin histochemistry revealed the presence of sulfomucin in both the endocervicosis and adenocarcinoma components. Immunohistochemically, the endocervicosis was positive for cytokeratin (CK) 7, AE1/AE3, CAM5.2, HBME1, CA19-9, and estrogen receptor (ER), and negative for CK20, CDX2, progesterone receptor (PR), MUC5AC, and β-catenin. The adenocarcinoma showed similar immunohistochemical results, except for loss of ER expression and a slight increase in the ratio of Ki-67-positive cells. This case indicates that endocervicosis, known as a benign lesion, harbors the possibility of malignant transformation. © 2016 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

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

ClinicalTrials.gov

2016-10-20

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

Post-operative ovarian adhesion formation after ovarian drilling: a randomized study comparing conventional laparoscopy and transvaginal hydrolaparoscopy.

PubMed

Giampaolino, Pierluigi; Morra, Ilaria; Tommaselli, Giovanni Antonio; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

2016-10-01

To compare conventional laparoscopic ovarian drilling (LOD) with transvaginal hydrolaparoscopy (THL) ovarian drilling in terms of ovarian adhesion formation, evaluated using office THL during follow-up in CC-resistant anovulatory patients affected by PCOS. Prospective randomized study on 246 CC-resistant women with PCOS. The patients enrolled were divided into two groups, 123 were scheduled to undergo LOD and 123 to undergo THL ovarian drilling. Six months after the procedure all patients were offered office transvaginal hydrolaparoscopy (THL) follow-up, under local anesthesia to evaluate adhesion formation. Duration of the procedure was significantly shorter in the THL group in comparison with LOD group (p < 0.0001). No intra- or post-operative complication was observed in any of the patients in both groups. Post-operative THL follow-up after 6 months showed that 15 (15.5 %) patients in the THL group and 73 (70.2 %) in the LOD group showed the presence of ovarian adhesion. This difference was highly significant with a p value <0.0001 and a relative risk of 0.22 [95 % IC 0.133-0.350]. This study seems to indicate that THL ovarian drilling may reduce the risk of ovarian adhesion formation and could be used as a safe and effective option to reduce ovarian adhesion formation in patients undergoing ovarian drilling.

Molecular profiling identifies prognostic markers of stage IA lung adenocarcinoma.

PubMed

Zhang, Jie; Shao, Jinchen; Zhu, Lei; Zhao, Ruiying; Xing, Jie; Wang, Jun; Guo, Xiaohui; Tu, Shichun; Han, Baohui; Yu, Keke

2017-09-26

We previously showed that different pathologic subtypes were associated with different prognostic values in patients with stage IA lung adenocarcinoma (AC). We hypothesize that differential gene expression profiles of different subtypes may be valuable factors for prognosis in stage IA lung adenocarcinoma. We performed microarray gene expression profiling on tumor tissues micro-dissected from patients with acinar and solid predominant subtypes of stage IA lung adenocarcinoma. These patients had undergone a lobectomy and mediastinal lymph node dissection at the Shanghai Chest Hospital, Shanghai, China in 2012. No patient had preoperative treatment. We performed the Gene Set Enrichment Analysis (GSEA) analysis to look for gene expression signatures associated with tumor subtypes. The histologic subtypes of all patients were classified according to the 2015 WHO lung Adenocarcinoma classification. We found that patients with the solid predominant subtype are enriched for genes involved in RNA polymerase activity as well as inactivation of the p53 pathway. Further, we identified a list of genes that may serve as prognostic markers for stage IA lung adenocarcinoma. Validation in the TCGA database shows that these genes are correlated with survival, suggesting that they are novel prognostic factors for stage IA lung adenocarcinoma. In conclusion, we have uncovered novel prognostic factors for stage IA lung adenocarcinoma using gene expression profiling in combination with histopathology subtyping.

The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.

PubMed

Kojima, Yoko; Okudela, Koji; Matsumura, Mai; Omori, Takahiro; Baba, Tomohisa; Sekine, Akimasa; Woo, Tetsukan; Umeda, Shigeaki; Takemura, Tamiko; Mitsui, Hideaki; Suzuki, Takehisa; Tateishi, Yoko; Iwasawa, Tae; Arai, Hiromasa; Tajiri, Michihiko; Ogura, Takashi; Kameda, Yoichi; Masuda, Munetaka; Ohashi, Kenich

2017-03-01

To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features. © 2016 John Wiley & Sons Ltd.

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

PubMed Central

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

2011-01-01

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

Features of ovarian cancer in Lynch syndrome (Review).

PubMed

Nakamura, Kanako; Banno, Kouji; Yanokura, Megumi; Iida, Miho; Adachi, Masataka; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Nomura, Hiroyuki; Hirasawa, Akira; Tominaga, Eiichiro; Aoki, Daisuke

2014-11-01

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

Ovarian tumor antigens.

PubMed

Bhattacharya, M; Barlow, J J

1978-09-01

Evidence has been reported for at least two common tumor-associated antigens, or antigenic determinants, in human cystadenocarcinomas of the ovary that are apparently absent in tissues of normal reproductive organs. These antigenic determinants are immunologically distinct from carcinoembryonic antigen, alpha-fetoprotein, ferritins and histocompatibility antigens. One of these two ovarian cystadenocarcinoma-associated antigens (OCAA) is not detectable in any ovarian carcinomas except serous or mucinous types, other gynecologic or nongynecologic malignancies thus far tested, while the second antigen is present in about 90% of all gynecologic tumors and occasionally in breast and colon tumors. OCAA has been purified and partially characterized. It is a high molecular weight glycoprotein which carries the unique ovarian tumor-specific antigenic determinant along with some normal cross-reacting determinants. High levels of this glycoprotein antigen have been detected in the sera of ovarian cancer patients with advanced disease by the radioimmunoassay inhibition technique. The serial determination of circulating OCAA appeared to correlate with tumor volume as well as the clinical status of the patients.

Cytoplasmic mislocalization of overexpressed FOXF1 is associated with the malignancy and metastasis of colorectal adenocarcinomas

PubMed Central

Lo, Pang-Kuo; Lee, Ji Shin; Chen, Hexin; Reisman, David.; Berger, Franklin G.; Sukumar, Saraswati

2012-01-01

Our previous studies have revealed that the human FOXF1 gene, encoding a transcription factor member of the forkhead box (FOX) family, functions as a tumor suppressor and its expression is frequently silenced in breast cancer via DNA hypermethylation. Moreover, we recently reported that FOXF1 expression is preferentially silenced in colorectal cancer cell lines with inactive p53 and knockdown of FOXF1 caused genomic instability in FOXF1-expressing colorectal cancer cells with a defect in the p53-p21WAF1 checkpoint, suggesting that FOXF1 plays a key role in colorectal tumorigenesis. Given that the in vivo role of FOXF1 in colorectal cancer remains unknown, the study here was aimed at delineating the clinical relevance of FOXF1 in colorectal adenocarcinomas. To characterize FOXF1 protein expression in colorectal cancer, designed tissue microarrays, comprising 50 cases of primary colorectal adenocarcinoma paired with matched adjacent normal tissue, were utilized in the immunohistochemistry (IHC) study. The IHC results showed that for adjacent normal colorectal tissue, the FOXF1 protein was only detected in stroma, not in epithelium, with either cytoplasmic staining (70% of total cases) or a mix of cytoplasmic and nuclear staining (6%). In contrast, for colorectal adenocarcinomas, FOXF1 staining was predominately identified in the cytoplasm of tumor epithelial cells (40% of total cases) and tumor-associated stromal cells of some cases (10%) also exhibited FOXF1 positivity in their cytoplasm. Cytoplasmic FOXF1 protein expression in tumor epithelial cells positively correlated with the histologic grade, depth of invasion, stage and lymphatic metastasis of colorectal adenocarcinomas (p < 0.05). Moreover, in silico meta-analysis of Oncomine’s cancer microarray database indicates that FOXF1 mRNA is overexpressed in a significant subset of colorectal adenocarcinoma tumors compared with normal colorectal tissue and other types of cancers. Our findings for the first time

Symptoms of Ovarian Cancer

MedlinePlus

... Informed Cancer Home What Are the Symptoms of Ovarian Cancer? Language: English (US) Español (Spanish) Recommend on Facebook Tweet Share Compartir Be Brave (:60) Ovarian cancer may cause the following signs and symptoms— Vaginal ...

Fertility drugs and ovarian cancer.

PubMed

Ali, Aus Tariq

2017-06-20

The aetiology of ovarian cancer is multifactorial with both endogenous and exogenous risk factors playing an important role. The exact pathogenesis of ovarian cancer is still not well understood, despite the number of hypotheses published. Due to an increase in the number of women using fertility drugs, much attention has been focused on the long-term health effects of such drugs. Although fertility drugs facilitate the ovulation process, it is however associated with a significant increase in hormone concentrations, placing exposed women at increased risk of gynaecological cancer. Many clinical and epidemiological studies have examined the association between fertility drugs and ovarian cancer risk. Results from these studies have been contradictory, as some studies have reported an increased risk of ovarian cancer while others reported no increased risk. Nevertheless, recent studies have shown that women who used fertility drugs and did not conceive had a higher risk of developing ovarian cancer, compared to women who used fertility drugs and conceived and delivered successfully. This review discusses the effect of fertility drugs on the risk of developing ovarian cancer, providing details on four possible scenarios associated with fertility treatment. In addition, the limitations of previous studies and their impact on our understanding of the association between fertility drugs and ovarian cancer also have been highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Primary adenocarcinoma of bladder.

PubMed

Wilson, T G; Pritchett, T R; Lieskovsky, G; Warner, N E; Skinner, D G

1991-09-01

Between April 1983 and December 1987, we have treated and followed 16 patients at the University of Southern California for adenocarcinoma of the bladder. In 10 patients, the cancer originated from a nonurachal source; all underwent radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion. The other 6 patients had an apparent urachal origin of their cancer. Half of these patients were treated with radical cystectomy and urinary diversion and half were treated initially with segmental cystectomy. Presenting characteristics (age, sex ratio, and symptoms) were similar for both groups. Three-year adjusted acturial tumor-free survival rates for the two groups were 48 percent and 31 percent, respectively. We advocate an aggressive approach of radical cystectomy, bilateral pelvic lymph node dissection, and urinary diversion for all invasive adenocarcinoma of the bladder, regardless of location.

Immunotherapy in ovarian cancer.

PubMed

Odunsi, K

2017-11-01

Immunological destruction of tumors is a multistep, coordinated process that can be modulated or targeted at several critical points to elicit tumor rejection. These steps in the cancer immunity cycle include: (i) generation of sufficient numbers of effector T cells with high avidity recognition of tumor antigens in vivo; (ii) trafficking and infiltration into the tumor; (iii) overcoming inhibitory networks in the tumor microenvironment; (iv) direct recognition of tumor antigens and generation of an effector anti-tumor response; and (v) persistence of the anti-tumor T cells. In an effort to understand whether the immune system plays a role in controlling ovarian cancer, our group and others demonstrated that the presence of tumor infiltrating lymphocytes (TILs) is associated with improved clinical outcome in ovarian cancer patients. Recently, we hypothesized that the quality of infiltrating T cells could also be a critical determinant of outcome in ovarian cancer patients. In the past decade, several immune-based interventions have gained regulatory approval in many solid tumors and hematologic malignancies. These interventions include immune checkpoint blockade, cancer vaccines, and adoptive cell therapy. There are currently no approved immune therapies for ovarian cancer. Immunotherapy in ovarian cancer will have to consider the immune suppressive networks within the ovarian tumor microenvironment; therefore, a major direction is to develop biomarkers that would predict responsiveness to different types of immunotherapies, and allow for treatment selection based on the results. Moreover, such biomarkers would allow rational combination of immunotherapies, while minimizing toxicities. In this review, the current understanding of the host immune response in ovarian cancer patients will be briefly reviewed, progress in immune therapies, and future directions for exploiting immune based strategies for long lasting durable cure. © The Author 2017. Published by Oxford

A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.

PubMed

Youssef, M A; van Wely, M; Al-Inany, H; Madani, T; Jahangiri, N; Khodabakhshi, S; Alhalabi, M; Akhondi, M; Ansaripour, S; Tokhmechy, R; Zarandi, L; Rizk, A; El-Mohamedy, M; Shaeer, E; Khattab, M; Mochtar, M H; van der Veen, F

2017-01-01

In subfertile women with poor ovarian reserve undergoing IVF does a mild ovarian stimulation strategy lead to comparable ongoing pregnancy rates in comparison to a conventional ovarian stimulation strategy? A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF leads to similar ongoing pregnancy rates as a conventional ovarian stimulation strategy. Women diagnosed with poor ovarian reserve are treated with a conventional ovarian stimulation strategy consisting of high-dose gonadotropins and pituitary downregulation with a long mid-luteal start GnRH-agonist protocol. Previous studies comparing a conventional strategy with a mild ovarian stimulation strategy consisting of low-dose gonadotropins and pituitary downregulation with a GnRH-antagonist have been under powered and their effectiveness is inconclusive. This open label multicenter randomized trial was designed to compare one cycle of a mild ovarian stimulation strategy consisting of low-dose gonadotropins (150 IU FSH) and pituitary downregulation with a GnRH-antagonist to one cycle of a conventional ovarian stimulation strategy consisting of high-dose gonadotropins (450 IU HMG) and pituitary downregulation with a long mid-luteal GnRH-agonist in women of advanced maternal age and/or women with poor ovarian reserve undergoing IVF between May 2011 and April 2014. Couples seeking infertility treatment were eligible if they fulfilled the following inclusion criteria: female age ≥35 years, a raised basal FSH level >10 IU/ml irrespective of age, a low antral follicular count of ≤5 follicles or poor ovarian response or cycle cancellation during a previous IVF cycle irrespective of age. The primary outcome was ongoing pregnancy rate per woman randomized. Analyses were on an intention-to-treat basis. We randomly assigned 195 women to the mild ovarian stimulation strategy and 199 women to the conventional ovarian stimulation strategy. Ongoing pregnancy rate was 12.8% (25/195) for mild

The effect of bipolar electrocoagulation during ovarian cystectomy on ovarian reserve: a systematic review.

PubMed

Pergialiotis, Vasilios; Prodromidou, Anastasia; Frountzas, Maximos; Bitos, Konstantinos; Perrea, Despina; Doumouchtsis, Stergios K

2015-11-01

The aim of the present systematic review was to study the effect of bipolar electrocoagulation during ovarian cystectomy on ovarian reserve. We searched Medline (1966-2015), Scopus (2004-2015), ClinicalTrials.gov (2008-2015), and Cochrane Central Register (CENTRAL) databases along with reference lists of electronically retrieved studies. The levels of antimullerian hormone (AMH) and antral follicle count (AFC) at 1, 3, 6, and 12 months following the excision of the benign ovarian cyst were defined as primary outcomes. Eight studies were finally included in our systematic review, which recruited 545 women. A metaanalysis was precluded because of significant heterogeneity in the methodological characteristics of the included studies. Data from the included studies suggest that the use of bipolar coagulation compared with ovarian sutures seems to result in significantly lower AMH and AFC during the first 3 months following the excision of the ovarian cyst. Two studies reported that this effect seems to persist at 6 and 12 months postoperatively. Bipolar electrodiathermy seems to be accompanied by increased damage to ovarian reserve, which is indicated by the lower levels of AMH and AFC. However, definitive results are precluded because of the significant heterogeneity of included studies and the potential bias. Copyright © 2015 Elsevier Inc. All rights reserved.

Screening and identification of gastric adenocarcinoma metastasis-related genes using cDNA microarray coupled to FDD-PCR.

PubMed

Wang, Jianhua; Chen, Shishu

2002-10-01

To identify certain gastric adenocarcinoma metastasis-related genes, an RF-1 cell line (primary tumor from a gastric adenocarcinoma patient) and an RF-48 cell line (its metastatic counterpart) were used as a model for studying the molecular mechanism of tumor metastasis. Two fluorescent cDNA probes, labeled with Cy3 and Cy5 dyes, were prepared from RF-1 and RF-48 mRNA samples by the reverse transcription method. The two color probes were then mixed and hybridized to a cDNA chip constructed with double-dots from 4,096 human genes, and scanned at two wavelengths. The experiment was repeated twice. Differentially expressedn genes from the above two cells were analyzed by use of computer. Of the total genes, 138 (3.4%) revealed differential expression in RF-48 cells compared with RF-1 cells: 81 (2.1%) genes revealed apparent up-regulation, and 56 (1.3%) genes revealed down-regulation. Forty-five genes involved in gastric adenocarcinoma metastasis were cloned using fluorescent differential display-PCR (FDD-PCR), including three novel genes. There were seven differentially expressed genes that presented the same behaviour under both detection methods. The possible roles of some differentially expressed genes, which may be involved in the mechanism of tumor metastasis, were discussed. cDNA chip was used to analyze gene expression in a high-throughput and large-scale manner in combination with FDD-PCR for cloning unknown novel genes. Some genes related to metastasis were preliminarily scanned, which would contribute to disclose the molecular mechanism of gastric adenocarcinoma metastasis and provide new targets for therapeutic intervention.

ETV5 transcription factor is overexpressed in ovarian cancer and regulates cell adhesion in ovarian cancer cells.

PubMed

Llauradó, Marta; Abal, Miguel; Castellví, Josep; Cabrera, Sílvia; Gil-Moreno, Antonio; Pérez-Benavente, Asumpció; Colás, Eva; Doll, Andreas; Dolcet, Xavier; Matias-Guiu, Xavier; Vazquez-Levin, Mónica; Reventós, Jaume; Ruiz, Anna

2012-04-01

Epithelial ovarian cancer is the most lethal gynecological malignancy and the fifth leading cause of cancer deaths in women in the Western world. ETS transcription factors are known to act as positive or negative regulators of the expression of genes that are involved in various biological processes, including those that control cellular proliferation, differentiation, apoptosis, tissue remodeling, angiogenesis and transformation. ETV5 belongs to the PEA3 subfamily. PEA3 subfamily members are able to activate the transcription of proteases, matrix metalloproteinases and tissue inhibitor of metalloproteases, which is central to both tumor invasion and angiogenesis. Here, we examined the role of the ETV5 transcription factor in epithelial ovarian cancer and we found ETV5 was upregulated in ovarian tumor samples compared to ovarian tissue controls. The in vitro inhibition of ETV5 decreased cell proliferation in serum-deprived conditions, induced EMT and cell migration and decreased cell adhesion to extracellular matrix components. ETV5 inhibition also decreased cell-cell adhesion and induced apoptosis in anchorage-independent conditions. Accordingly, upregulation of ETV5 induced the expression of cell adhesion molecules and enhanced cell survival in a spheroid model. Our findings suggest that the overexpression of ETV5 detected in ovarian cancer cells may contribute to ovarian tumor progression through the ability of ETV5 to enhance proliferation of ovarian cancer cells. In addition, upregulation of ETV5 would play a role in ovarian cancer cell dissemination and metastasis into the peritoneal cavity by protecting ovarian cancer cells from apoptosis and by increasing the adhesion of ovarian cancer cells to the peritoneal wall through the regulation of cell adhesion molecules. Copyright © 2011 UICC.

Vanishing large ovarian cyst with thyroxine therapy.

PubMed

Dharmshaktu, Pramila; Kutiyal, Aditya; Dhanwal, Dinesh

2013-01-01

A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the condition of the patient significantly. This case report highlights the rare and often missed association between hypothyroidism and ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian cysts in an adult should always be kept in the differential diagnosis to avoid unnecessary ovarian surgery. Hypothyroidism should be considered in the differential diagnosis of adult females presenting with multicystic ovarian tumours.Adequate thyroid hormone replacement therapy can prevent these patients from undergoing unnecessary and catastrophic ovarian resection.Surgical excision should be considered only when adequate thyroid replacement therapy fails to resolve ovarian enlargement.In younger women with ovarian cysts, it is also desirable to avoid unnecessary surgery so as to not compromise fertility in the future.

Vanishing large ovarian cyst with thyroxine therapy

PubMed Central

Dharmshaktu, Pramila; Kutiyal, Aditya; Dhanwal, Dinesh

2013-01-01

Summary A 21-year-old female patient recently diagnosed with severe hypothyroidism was found to have a large ovarian cyst. In view of the large ovarian cyst, she was advised to undergo elective laparotomy in the gynaecology department. She was further evaluated in our medical out-patient department (OPD), and elective surgery was withheld. She was started on thyroxine replacement therapy, and within a period of 4 months, the size of the cyst regressed significantly, thereby improving the condition of the patient significantly. This case report highlights the rare and often missed association between hypothyroidism and ovarian cysts. Although very rare, profound hypothyroidism that can cause ovarian cysts in an adult should always be kept in the differential diagnosis to avoid unnecessary ovarian surgery. Learning points Hypothyroidism should be considered in the differential diagnosis of adult females presenting with multicystic ovarian tumours.Adequate thyroid hormone replacement therapy can prevent these patients from undergoing unnecessary and catastrophic ovarian resection.Surgical excision should be considered only when adequate thyroid replacement therapy fails to resolve ovarian enlargement.In younger women with ovarian cysts, it is also desirable to avoid unnecessary surgery so as to not compromise fertility in the future. PMID:24683475

Primary appendicular adenocarcinoma presenting as haematuria

PubMed Central

Amr, Bassem; Santana-Vaz, Natasha; Munir, Komal

2014-01-01

Adenocarcinoma of the vermiform appendix is a rare malignant neoplasm of the gastrointestinal tract encountered rarely within general surgical practice. We present the case of a 49-year-old man who, while undergoing investigations for haematuria, was diagnosed with an appendicular adenocarcinoma following bladder biopsy. Consequently he underwent right hemicolectomy and partial cystectomy followed by adjuvant chemotherapy. By discussing this case we hope to raise awareness within the medical profession of this rare presentation so that it may be considered within clinicians’ differential diagnoses. PMID:25358831

Soluplus/TPGS mixed micelles for dioscin delivery in cancer therapy.

PubMed

Zhao, Jing; Xu, Youwei; Wang, Changyuan; Ding, Yanfang; Chen, Manyu; Wang, Yifei; Peng, Jinyong; Li, Lei; Lv, Li

2017-07-01

Dioscin has shown cytotoxicity against cancer cells, but its poor solubility and stability have limited its clinical application. In this study, we designed mixed micelles composed of TPGS and Soluplus ® copolymers entrapping the poorly soluble anticancer drug dioscin. In order to improve the aqueous solubility and bioactivity of dioscin, TPGS/Soluplus ® mixed micelles with an optimal ratio were prepared using a thin-film hydration method, and their physicochemical properties were characterized. Cellular cytotoxicity and uptake of the dioscin-loaded TPGS/Soluplus ® mixed micelles were studied in MCF-7 breast cancer cells and A2780s ovarian cancer cells. The pharmacokinetics of free dioscin and dioscin-loaded TPGS/Soluplus ® mixed micelles was studied in vivo in male Sprague-Dawley rats via a single intravenous injection in the tail vein. The average size of the optimized mixed micelle was 67.15 nm, with 92.59% drug encapsulation efficiency and 4.63% drug loading efficiency. The in vitro release profile showed that the mixed micelles presented sustained release behavior compared to the anhydrous ethanol solution of dioscin. In vitro cytotoxicity assays were conducted on human cancer cell lines including A2780s ovarian cancer cells and MCF-7 breast cancer cells. The mixed micelles exhibited better antitumor activity compared to free dioscin against all cell lines, which may benefit from the significant increase in the cellular uptake of dioscin from mixed micelles compared to free dioscin. The pharmacokinetic study showed that the mixed micelle formulation achieved a 1.3 times longer mean residual time (MRT) in circulation and a 2.16 times larger area under the plasma concentration-time curve (AUC) than the free dioscin solution. Our results suggest that the dioscin-loaded mixed micelles developed in this study might be a potential nano drug-delivery system for cancer chemotherapy.

Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy

PubMed Central

2014-01-01

Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma. PMID:24636424

A case of alpha-fetoprotein-producing esophageal adenocarcinoma.

PubMed

Chen, Yi-Yu; Hsu, Wen-Hung; Hu, Huang-Ming; Wu, Deng-Chyang; Lin, Wen-Yi

2013-02-01

Alpha-fetoprotein is a well-known tumor marker in the screening and follow-up of hepatocellular carcinoma. In Taiwanese society, a high prevalence of hepatitis and hepatoma and elevation of alpha-fetoprotein associated with liver function impairment usually suggested clinics undertake further examination for liver or genital tumor. We report the case of 45-year-old man who was found to have an alpha-fetoprotein-producing esophageal adenocarcinoma with an initial presentation of liver function impairment and rapid elevation of alpha-fetoprotein. Esophageal cancer was diagnosed via endoscope and a biopsy proved the presence of adenocarcinoma. A small endoscopic biopsy specimen failed to identify the alpha-fetoprotein positive tumor cell. Esophagectomy was performed and histopathological study of surgical specimen revealed grade II adenocarcinoma with regional metastatic lymphadenopathy. Immunohistochemical study was focal positive for alpha-fetoprotein. Serum alpha-fetoprotein declined transiently after esophagectomy and fluctuation of alpha-fetoprotein level was noted during the treatment with adjuvant chemotherapy. Finally, 19 months after the operation, the patient died due to multiple organ metastases with multiple organ failure. Thus, a small specimen for upper endoscopy may not be sufficient in the presence of alpha-fetoprotein-producing adenocarcinoma. Monitoring of serum alpha-fetoprotein may be useful in the evaluation and follow-up of esophageal alpha-fetoprotein-producing adenocarcinoma. Copyright © 2012. Published by Elsevier B.V.

Dendritic cells in Barrett's esophagus and esophageal adenocarcinoma.

PubMed

Bobryshev, Yuri V; Tran, Dinh; Killingsworth, Murray C; Buckland, Michael; Lord, Reginald V N

2009-01-01

Like other premalignant conditions that develop in the presence of chronic inflammation, the development and progression of Barrett's esophagus is associated with the development of an immune response, but how this immune response is regulated is poorly understood. A comprehensive literature search failed to find any report of the presence of dendritic cells in Barrett's intestinal metaplasia and esophageal adenocarcinoma and this prompted our study. We used immunohistochemical staining and electron microscopy to examine whether dendritic cells are present in Barrett's esophagus and esophageal adenocarcinoma. Immunohistochemical staining with CD83, a specific marker for dendritic cells, was performed on paraffin-embedded sections of Barrett's intestinal metaplasia (IM, n = 12), dysplasia (n = 11) and adenocarcinoma (n = 14). CD83+ cells were identified in the lamina propria surrounding intestinal type glands in Barrett's IM, dysplasia, and cancer tissues. Computerized quantitative analysis showed that the numbers of dendritic cells were significantly higher in cancer tissues. Double immunostaining with CD83, CD20, and CD3, and electron microscopy demonstrated that dendritic cells are present in Barrett's esophagus and form clusters with T cells and B cells directly within the lamina propria. These findings demonstrate that dendritic cells are present in Barrett's tissues, with a significant increase in density in adenocarcinoma compared to benign Barrett's esophagus. Dendritic cells may have a role in the pathogenesis and immunotherapy treatment of Barrett's esophagus and adenocarcinoma.

Cryopreservation of human ovarian tissue.

PubMed

Fabbri, Raffaella; Pasquinelli, Gianandrea; Bracone, Graziella; Orrico, Catia; Di Tommaso, Barbara; Venturoli, Stefano

2006-01-01

New and often aggressive treatment schemes allow the successful healing of many young patients with cancer, but the price the young women have to pay is high: many of them lose ovarian function and fertility. Due to the improved long-term survival of adolescents and young women with malignancies undergoing gonadotoxic chemotherapy, preservation of future fertility has been the focus of recent ubiquitarian interest. A feasible solution is the cryopreservation of ovarian tissue. Ovarian tissue, after thawing, can be used in three different ways: 1. grafted into its normal site (orthotopic); 2. grafted into a site other than its normal position (heterotopic), necessitating recourse to in vitro fertilization (IVF); 3. grown and in vitro matured in order to obtain metaphase II oocytes for an IVF program. It is believed that protein supplementation, in cryopreservation solution, is essential for improving ovarian tissue cryopreservation. The aim of this study was to evaluate the ultrastructural appearance of human ovarian tissue cryopreserved in 1.5 M 1,2 propanediol (PROH), 0.2 M sucrose using different protein sources: fetal calf serum (FCS), plasmanate or syntetic serum substitute (SSS). Fresh and frozen/thawed ovarian tissues were compared by transmission electron microscope (TEM), to evaluate the appearance of stromal and follicle cells as affected by different protein sources. Our data indicate that FCS is a better protein support for ovarian tissue cryopreservation when compared to SSS or Plasmanate. In addition the follicles are more resistant to the cryopreservation with respect to stroma.

How to personalize ovarian stimulation in clinical practice.

PubMed

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

Epidemiology of epithelial ovarian cancer.

PubMed

Webb, Penelope M; Jordan, Susan J

2017-05-01

Globally, ovarian cancer is the seventh most common cancer in women and the eighth most common cause of cancer death, with five-year survival rates below 45%. Although age-standardised rates are stable or falling in most high-income countries, they are rising in many low and middle income countries. Furthermore, with increasing life-expectancy, the number of cases diagnosed each year is increasing. To control ovarian cancer we need to understand the causes. This will allow better prediction of those at greatest risk for whom screening might be appropriate, while identification of potentially modifable causes provides an opportunity for intervention to reduce rates. In this paper we will summarise the current state of knowledge regarding the known and possible causes of epithelial ovarian cancer and discuss some of the main theories of ovarian carcinogenesis. We will also briefly review the relationship between lifestyle and survival after a diagnosis of ovarian cancer. Copyright © 2016. Published by Elsevier Ltd.

Oncolytic virotherapy for ovarian cancer

PubMed Central

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

2012-01-01

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

Intermittent Ovarian Torsion in Pregnancy

PubMed Central

Young, Randall; Cork, Kelly

2017-01-01

Ovarian torsion during pregnancy is a fairly uncommon complication with a high patient morbidity and fetal mortality if not immediately treated. Ovarian torsion should be considered a clinical diagnosis, and a high level of clinical suspicion is needed by the practitioner to ensure that this diagnosis is not missed. We present an unusual case of intermittent ovarian torsion discussing both the presentation and the operative and post-operative management. PMID:29849404

Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

PubMed Central

Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

2016-01-01

Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

[Sinonasal adenocarcinomas: our experience].

PubMed

Llorente, José Luis; Núñez, Faustino; Rodrigo, Juan Pablo; Fernández León, Ramón; Alvarez, César; Hermsen, Mario; Suárez, Carlos

2008-05-01

Sinonasal adenocarcinoma is a rare epithelial cancer of the nasal cavities and paranasal sinuses and exposure to sawdust particles is a strong aetiological factor. Seventy-nine patients (78 men and 1 woman) operated on between 1986 and 2002 were studied. In 62 patients (78.5 %) there was a history of exposure to wood dust. The clinical factors presenting statistical significance in the multivariate analysis with prognosis were: the exclusive invasion of the middle concha (as good prognosis), recurrence and invasion of the dura mater (as bad prognosis). The actuarial survival rate was 36 % at 5 years falling to 28 % at 10 years. Exposure to wood dust, even over a short period of time, must be considered as a high risk factor for the development of a sinonasal adenocarcinoma. This tumour must be ruled out in all patients suffering any type of sinonasal pathology.

Pattern of SMARCB1 (INI1) and SMARCA4 (BRG1) in poorly differentiated endometrioid adenocarcinoma of the uterus: analysis of a series with emphasis on a novel SMARCA4-deficient dedifferentiated rhabdoid variant.

PubMed

Strehl, Johanna D; Wachter, David L; Fiedler, Jutta; Heimerl, Engelbert; Beckmann, Matthias W; Hartmann, Arndt; Agaimy, Abbas

2015-08-01

The role of the switch/sucrose nonfermenting chromatin remodeling complex in the initiation and progression of cancer is emerging. In the female genital tract, only ovarian small cell carcinoma, hypercalcemic type harbors recurrent inactivating SMARCA4 mutations. Otherwise, only rare case reports documented SMARCB1 involvement in endometrial cancer. We analyzed 24 grade 3 uterine endometrioid adenocarcinomas and 2 undifferentiated carcinomas for immunohistochemical expression of SMARCB1 and SMARCA4. All tumors showed high-grade nuclear features with a predominance of solid growth pattern. All cases showed intact nuclear SMARCB1 expression in all tumor cells. However, 1 case of a 78-year-old woman showed complete loss of SMARCA4 in 90% of the tumor with retained expression in 10% of the tumor. The SMARCA4-intact component was a moderate-to-poorly differentiated endometrioid adenocarcinoma. The SMARCA4-deficient dominating component showed solid growth of highly anaplastic undifferentiated large cells with prominent rhabdoid features. None of the 25 SMARCA4-intact cases showed rhabdoid cell morphology. To our knowledge, this is the first systematic study of SMARCB1 and SMARCA4 expression in endometrioid adenocarcinoma of uterus and the first description of a novel SMARCA4-deficient variant of dedifferentiated/undifferentiated endometrial carcinoma. The presence of a differentiated SMARCA4-intact endometrioid component points to a novel pathway of dedifferentiation in endometrioid adenocarcinoma as a consequence of a "second hit." This case further underlines the close link between the "rhabdoid phenotype" and the SWI/SNF pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.

PubMed

Flesken-Nikitin, Andrea; Hwang, Chang-Il; Cheng, Chieh-Yang; Michurina, Tatyana V; Enikolopov, Grigori; Nikitin, Alexander Yu

2013-03-14

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer deaths among women in the United States, but its pathogenesis is poorly understood. Some epithelial cancers are known to occur in transitional zones between two types of epithelium, whereas others have been shown to originate in epithelial tissue stem cells. The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been defined unequivocally. Here we identify the hilum region of the mouse ovary, the transitional (or junction) area between the OSE, mesothelium and tubal (oviductal) epithelium, as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are cycling slowly and express stem and/or progenitor cell markers ALDH1, LGR5, LEF1, CD133 and CK6B. These cells display long-term stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and long-term lineage-tracing assays. Importantly, the hilum cells show increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are altered frequently in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma. Our study supports experimentally the idea that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis.

Alpha-fetoprotein-producing ovarian clear cell adenocarcinoma with fetal gut differentiation: a rare case report and literature review.

PubMed

Chao, Wei-Ting; Liu, Chia-Hao; Lai, Chiung-Ru; Chen, Yi-Jen; Chuang, Chi-Mu; Wang, Peng-Hui

2018-06-22

Alpha-fetoprotein (AFP) is a useful tumor marker for ovarian germ cell tumors, particularly yolk sac tumor (YST). It is valuable for both diagnosis and further follow-up. Epithelial ovarian carcinoma (EOC) rarely secretes AFP, especially for clear cell type and in the postmenopausal women. Based on the limited knowledge about AFP-producing clear cell type EOC, a case and literature review on this topic is extensively reviewed. We report a 55-year-old postmenopausal woman experienced vaginal spotting for one month, and serum level of AFP was 60,721 ng/ml initially. Histological examination was clear cell type EOC. Tumor cells revealed strong immunoreactivity for glypican-3 (GPC3) and AFP and weak for hepatocyte nuclear factor-1 beta (HNF-1 beta), but negative for CD30, making the diagnosis of AFP-producing clear cell type EOC with fetal gut differentiation in focal areas, FIGO (International Federation of Gynecology and Obstetrics) IIIc. Although the patient underwent an intensive treatment, including optimal debulking surgery and multi-agent chemotherapy, the patient died of disease. To provide a better understanding of clinical and molecular characteristics of the AFP-producing clear cell type EOC, we conducted a systematic literature review. A total of three papers described the AFP-producing clear cell type EOC are available. The overall survival rate of these cases, including the current case is 50%. Although immunohistochemical examination is not always needed in routine for the diagnosis of clear cell type EOC, to distinguish from other tumors, especially germ cell tumors, or to provide the better way to monitor therapeutic response or to evaluate the disease status, immunostaining, including GPC3, HNF-1 beta, CD30, cytokeratin 7 or 20, and AFP is taken into account. Due to rarity, the appropriate chemotherapy regimen and the biological behavior of AFP-producing clear cell type EOC are still unclear.

The prevention of ovarian hyperstimulation syndrome.

PubMed

Corbett, Shannon; Shmorgun, Doron; Claman, Paul

2014-11-01

To review the clinical aspects of ovarian hyperstimulation syndrome and provide recommendations on its prevention. Preventative measures, early recognition, and prompt systematic supportive care will help avoid poor outcomes. Establish guidelines to assist in the prevention of ovarian hyperstimulation syndrome, early recognition of the condition when it occurs, and provision of appropriate supportive measures in the correct setting. Published literature was retrieved through searches of Medline, Embase, and the Cochrane Library from 2011 to 2013 using appropriate controlled vocabulary ([OHSS] ovarian hyperstimulation syndrome and: agonist IVF, antagonist IVF, metformin, HCG, gonadotropin, coasting, freeze all, agonist trigger, progesterone) and key words (ovarian hyperstimulation syndrome, ovarian stimulation, gonadotropin, human chorionic gonadotropin, prevention). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to February 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Summary Statements 1. The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I) 2. Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III) 3. Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2) 4. The use of either luteinizing hormone or human

Biomarkers in the Detection of Prostate Cancer in African Americans

DTIC Science & Technology

2014-09-01

tissues by Taqman low density array: application to Hedgehog and Wnt pathway analysis in ovarian endome- trioid adenocarcinoma . J. Mol. Diagn. 8 : 76...2007) Hedgehog pathway expression in heterogeneous pancreatic adenocarcinoma: implications for the molecular analysis of clinically available

A Study Evaluating MM-310 in Patients With Solid Tumors

ClinicalTrials.gov

2018-02-26

Solid Tumors; Urothelial Carcinoma; Gastric Carcinoma; Squamous Cell Carcinoma of the Head and Neck; Ovarian Cancer; Pancreatic Ductal Adenocarcinoma; Prostate Adenocarcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Triple Negative Breast Cancer; Endometrial Carcinoma; Soft Tissue Sarcoma

Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?

PubMed

Boots, Christina E; Gustofson, Robert L; Feinberg, Eve C

2013-12-01

To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Different time trend and management of esophagogastric junction adenocarcinoma in three Asian countries.

PubMed

Hatta, Waku; Tong, Daniel; Lee, Yeong Yeh; Ichihara, Shin; Uedo, Noriya; Gotoda, Takuji

2017-04-01

Esophagogastric junction (EGJ) adenocarcinoma has been on the increase in Western countries. However, in Asian countries, data on the incidence of EGJ adenocarcinoma are evidently lacking. In the present review, we focus on the current clinical situation of EGJ adenocarcinoma in three Asian countries: Japan, Hong Kong, and Malaysia. The incidence of EGJ adenocarcinoma has been reported to be gradually increasing in Malaysia and Japan, whereas it has stabilized in Hong Kong. However, the number of cases in these countries is comparatively low compared with Western countries. A reason for the reported difference in the incidence and time trend of EGJ adenocarcinoma among the three countries may be explained by two distinct etiologies: one arising from chronic gastritis similar to distal gastric cancer, and the other related to gastroesophageal reflux disease similar to esophageal adenocarcinoma including Barrett's adenocarcinoma. This review also shows that there are several concerns in clinical practice for EGJ adenocarcinoma. In Hong Kong and Malaysia, many EGJ adenocarcinomas have been detected at a stage not amenable to endoscopic resection. In Japan, histological curability criteria for endoscopic resection cases have not been established. We suggest that an international collaborative study using the same definition of EGJ adenocarcinoma may be helpful not only for clarifying the characteristics of these cancers but also for improving the clinical outcome of these patients. © 2017 The Authors. Digestive Endoscopy © 2017 Japan Gastroenterological Endoscopy Society.

Screening and identification of gastric adenocarcinoma metastasis-related genes by using cDNA microarray coupled to FDD-PCR.

PubMed

Wang, Jian-Hua; Chen, Shi-Shu

2002-07-01

To clone gastric adenocarcinoma metastasis related genes, RF-1 cell line (primary tumor of a gastric adenocarcinoma patient ) and RF-48 cell line (its metastatic counterpart) were used as a model for studying the molecular mechanism of tumor metastasis. Two fluorescent cDNA probes, labeled with Cy3 and Cy5 dyes, were prepared from RF-1 and RF-48 mRNA samples by reverse transcription method. The two color probes were then mixed and hybridized to the cDNA chip constructed by double-dots of 4 096 human genes, and scanned at two wavelengths. The experiment was repeated for 2 times. Differential expression genes from the above two cells were analyzed using the computer. 138 in all genes (3.4%) revealed differential expression in RF-48 cells compared with RF-1 cells: 81(2.1%) genes revealed apparent up-regulation, and 56(1.3%) genes revealed down-regulation. 45 genes involved in gastric adenocarcinoma metastasis were cloned using fluorescent differential display-PCR (FDD-PCR), including 3 novel genes. There were 7 differential expression genes that agreed with each other in two detection methods. The possible roles of some differential expressed genes, which maybe involved in the mechanism of tumor metastasis, were discussed. cDNA chip was used to analyze gene expression in a high-throughput and large scale manner, in combination with FDD-PCR for cloning unknown novel genes. In conclusion, some genes related to metastasis were preliminarily scanned, which would contribute to disclose the molecular mechanism of gastric adenocarcinoma metastasis.

Ovarian Cancer Incidence Corrected for Oophorectomy

PubMed Central

Baldwin, Lauren A.; Chen, Quan; Tucker, Thomas C.; White, Connie G.; Ore, Robert N.; Huang, Bin

2017-01-01

Current reported incidence rates for ovarian cancer may significantly underestimate the true rate because of the inclusion of women in the calculations who are not at risk for ovarian cancer due to prior benign salpingo-oophorectomy (SO). We have considered prior SO to more realistically estimate risk for ovarian cancer. Kentucky Health Claims Data, International Classification of Disease 9 (ICD-9) codes, Current Procedure Terminology (CPT) codes, and Kentucky Behavioral Risk Factor Surveillance System (BRFSS) Data were used to identify women who have undergone SO in Kentucky, and these women were removed from the at-risk pool in order to re-assess incidence rates to more accurately represent ovarian cancer risk. The protective effect of SO on the population was determined on an annual basis for ages 5–80+ using data from the years 2009–2013. The corrected age-adjusted rates of ovarian cancer that considered SO ranged from 33% to 67% higher than age-adjusted rates from the standard population. Correction of incidence rates for ovarian cancer by accounting for women with prior SO gives a better understanding of risk for this disease faced by women. The rates of ovarian cancer were substantially higher when SO was taken into consideration than estimates from the standard population. PMID:28368298

Prostatic adenocarcinoma with glomeruloid features.

PubMed

Pacelli, A; Lopez-Beltran, A; Egan, A J; Bostwick, D G

1998-05-01

A wide variety of architectural patterns of adenocarcinoma may be seen in the prostate. We have recently encountered a hitherto-undescribed pattern of growth characterized by intraluminal ball-like clusters of cancer cells reminiscent of renal glomeruli, which we refer to as prostatic adenocarcinoma with glomeruloid features. To define the architectural features, frequency, and distribution of prostatic adenocarcinoma with glomeruloid features, we reviewed 202 totally embedded radical prostatectomy specimens obtained between October 1992 and April 1994 from the files of the Mayo Clinic. This series was supplemented by 100 consecutive needle biopsies with prostatic cancer from January to February 1996. Prostatic adenocarcinoma with glomeruloid features was characterized by round to oval epithelial tufts growing within malignant acini, often supported by a fibrovascular core. The epithelial cells were sometimes arranged in semicircular concentric rows separated by clefted spaces. In the radical prostatectomy specimens, nine cases (4.5%) had glomeruloid features. The glomeruloid pattern constituted 5% to 20% of each cancer (mean, 8.33%) and was usually located at the apex or in the peripheral zone of the prostate. Seven cases were associated with a high Gleason score (7 or 8), one with a score of 6, and one with a score of 5. All cases were associated with high-grade prostatic intraepithelial neoplasia and extensive perineural invasion. Pathological stages included T2c (three cases), T3b (four cases), and T3c (two cases); one of the T3b cases had lymph node metastases (N1). Three (3%) of 100 consecutive routine needle biopsy specimens with cancer showed glomeruloid features, and this pattern constituted 5% to 10% of each cancer (mean, 6.7%). The Gleason score was 6 for two cases and 8 for one case. Two cases were associated with high-grade prostatic intraepithelial neoplasia, and one case had perineural invasion. Glomeruloid features were not observed in any benign or

Mutational landscape of goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix is distinct from typical carcinoids and colorectal adenocarcinomas.

PubMed

Johncilla, Melanie; Stachler, Matthew; Misdraji, Joseph; Lisovsky, Mikhail; Yozu, Masato; Lindeman, Neal; Lauwers, Gregory Y; Odze, Robert D; Srivastava, Amitabh

2018-02-08

There is limited data on the spectrum of molecular alterations in goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix. We used next generation sequencing to determine mutations of potential pathogenetic and therapeutic significance in this rare group of tumors. Adequate DNA was successfully extracted in 34/46 cases and the final group included 18 goblet cell carcinoids and 16 adenocarcinoma ex goblet cell carcinoids. Illumina TruSeq™ was used for sequencing exons of a custom 282 gene panel using an Illumina HiSeq 2000. All cases had a minimum coverage depth of at least 50 reads. After filtering through the Exome Sequencing Project, the number of mutations per case ranged from 0-9 (mean:3). The mutational burden in adenocarcinoma ex goblet cell carcinoids was significantly higher than goblet cell carcinoids (mean 5 vs. 3; p < 0.05) but the spectrum of alterations overlapped between the two groups. The most frequent mutations included ARID1A (4/34), ARID2 (4/34), CDH1 (4/34), RHPN2 (4/34), and MLL2 (3/34). Some mutations typically seen in conventional colorectal adenocarcinomas were also identified but with much lower frequency (APC :4/34; KRAS :2/34). MLL2 and KRAS mutations were only seen in adenocarcinoma ex goblet cell carcinoids and TP53 mutations were limited to poorly differentiated adenocarcinoma ex goblet cell carcinoids (2/34). Copy number changes could be evaluated in 15/34 cases and showed low copy number gains in CDKN1B (6/15) and NFKBIA (6/15), among others. The overlapping molecular alterations suggest that goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids are best considered two grades of differentiation of the same tumor rather than two distinct histological types. Mutations in TP53, CDH1 and MLL2 mutations were predominantly present in the adenocarcinoma ex goblet cell carcinoid group consistent with transformation to a higher grade lesion. The unique mutational profile also offers an

Epithelial ovarian cancer: the molecular genetics of epithelial ovarian cancer.

PubMed

Krzystyniak, J; Ceppi, L; Dizon, D S; Birrer, M J

2016-04-01

Epithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide, despite gains in diagnostics and treatments made over the last three decades. Existing markers of ovarian cancer possess very limited clinical relevance highlighting the emerging need for identification of novel prognostic biomarkers as well as better predictive factors that might allow the stratification of patients who could benefit from a more targeted approach. A summary of molecular genetics of EOC. Large-scale high-throughput genomic technologies appear to be powerful tools for investigations into the genetic abnormalities in ovarian tumors, including studies on dysregulated genes and aberrantly activated signaling pathways. Such technologies can complement well-established clinical histopathology analysis and tumor grading and will hope to result in better, more tailored treatments in the future. Genomic signatures obtained by gene expression profiling of EOC may be able to predict survival outcomes and other important clinical outcomes, such as the success of surgical treatment. Finally, genomic analyses may allow for the identification of novel predictive biomarkers for purposes of treatment planning. These data combined suggest a pathway to progress in the treatment of advanced ovarian cancer and the promise of fulfilling the objective of providing personalized medicine to women with ovarian cancer. The understanding of basic molecular events in the tumorigenesis and chemoresistance of EOC together with discovery of potential biomarkers may be greatly enhanced through large-scale genomic studies. In order to maximize the impact of these technologies, however, extensive validation studies are required. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Menstrual pain and risk of epithelial ovarian cancer: Results from the Ovarian Cancer Association Consortium.

PubMed

Babic, Ana; Harris, Holly R; Vitonis, Allison F; Titus, Linda J; Jordan, Susan J; Webb, Penelope M; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Kjaer, Susanne K; Schildkraut, Joellen; Berchuck, Andrew; Pearce, Celeste L; Wu, Anna H; Cramer, Daniel W; Terry, Kathryn L

2018-02-01

Menstrual pain, a common gynecological condition, has been associated with increased risk of ovarian cancer in some, but not all studies. Furthermore, potential variations in the association between menstrual pain and ovarian cancer by histologic subtype have not been adequately evaluated due to lack of power. We assessed menstrual pain using either direct questions about having experienced menstrual pain, or indirect questions about menstrual pain as indication for use of hormones or medications. We used multivariate logistic regression to calculate the odds ratio (OR) for the association between severe menstrual pain and ovarian cancer, adjusting for potential confounders and multinomial logistic regression to calculate ORs for specific histologic subtypes. We observed no association between ovarian cancer and menstrual pain assessed by indirect questions. Among studies using direct question, severe pain was associated with a small but significant increase in overall risk of ovarian cancer (OR = 1.07, 95% CI: 1.01-1.13), after adjusting for endometriosis and other potential confounders. The association appeared to be more relevant for clear cell (OR = 1.48, 95% CI: 1.10-1.99) and serous borderline (OR = 1.31, 95% CI: 1.05-1.63) subtypes. In this large international pooled analysis of case-control studies, we observed a small increase in risk of ovarian cancer for women reporting severe menstrual pain. While we observed an increased ovarian cancer risk with severe menstrual pain, the possibility of recall bias and undiagnosed endometriosis cannot be excluded. Future validation in prospective studies with detailed information on endometriosis is needed. © 2017 UICC.

PHASE II TRIAL OF THE CYCLIN-DEPEDENT KINASE INHIBITOR PD 0332991 IN PATIENTS WITH CANCER

ClinicalTrials.gov

2016-08-24

Adult Solid Tumor; Adenocarcinoma of the Colon; Adenocarcinoma of the Rectum; Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Benign Teratoma; Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Familial Testicular Germ Cell Tumor; HER2-negative Breast Cancer; HER2-positive Breast Cancer; Male Breast Cancer; Ovarian Immature Teratoma; Ovarian Mature Teratoma; Ovarian Monodermal and Highly Specialized Teratoma; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Extragonadal Germ Cell Tumor; Recurrent Extragonadal Non-seminomatous Germ Cell Tumor; Recurrent Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Melanoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Rectal Cancer; Stage III Extragonadal Non-seminomatous Germ Cell Tumor; Stage III Extragonadal Seminoma; Stage III Malignant Testicular Germ Cell Tumor; Stage III Ovarian Germ Cell Tumor; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Extragonadal Non-seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Melanoma; Stage IV Ovarian Germ Cell Tumor; Stage IV Rectal Cancer; Testicular Immature Teratoma; Testicular Mature Teratoma

Right-sided lateralisation of ovarian cancer and right bias asymmetry for involved pelvic lymph nodes by ovarian cancer cells.

PubMed

Dane, Senol; Borekci, Bunyamin; Kadanali, Sedat

2008-09-01

The aim of the present study was to investigate if there is a possible lateralisation for ovarian cancers, to re-examine left-right asymmetry in pelvic lymph nodes distribution in patients with ovarian cancer, and to investigate if pelvic lymph node involvement by metastatic invasion of ovarian cancer cells is ipsilateral or contralateral. There was right-sided lateralisation for ovarian cancer. The numbers of external iliac and hypogastric+obturator lymph nodes were higher on the right side in patients with ovarian cancer on the right side; but they were about equal for right and left sides in patients with ovarian cancer in their left side. The numbers of external iliac and hypogastric+obturator lymph nodes involved by metastatic cancer cells were higher on the right side in patients with ovarian cancer on the both right and left sides. This case may result from the stronger cell-mediated immune activity in the left sides of humans.

Concomitant endometriosis in malignant and borderline ovarian tumours.

PubMed

Oral, Engin; Aydin, Ovgu; Kumbak, Banu Aygun; İlvan, Sennur; Yilmaz, Handan; Tustas, Esra; Bese, Tugan; Demirkiran, Fuat; Arvas, Macit

2018-06-08

The aim of the study was to reveal the prevalence of concomitant endometriosis in malignant and borderline ovarian tumours. A retrospective analysis was performed of 530 patients with malignant ovarian tumours and 131 with borderline ovarian tumours, who underwent surgery in our hospital between 1995 and 2011. Forty-eight (7.3%) of 661 patients with malignant and borderline ovarian tumours were associated with endometriosis. Of the 48 endometriosis cases, 73% of those were atypical. Infertility was noted in 38% of patients with endometriosis-associated ovarian tumours. The most frequently endometriosis-associated subtypes were endometrioid (33%) and clear cell (18%) histologies. Of endometriosis-associated endometrioid and clear cell ovarian tumours, 70% were early stage and 60% were premenopausal. The prevalence of concomitant endometriosis in borderline tumours (12%) was found to be significantly higher than that found in the malignant ones (6%; p = .02). Of 32 endometriosis-associated malignant ovarian tumours, 69% were FIGO stages I and II. In conclusion, ovarian endometriosis is seen with both malignant and borderline ovarian tumours, the association being significant with borderline tumours. Fortunately, the endometriosis-associated malignant ovarian tumours are mostly early stage. Impact statement What is already known on this subject? Epidemiologic data suggest that endometriosis has malignant potential. However, a subgroup of women with endometriosis at a high risk for ovarian cancer is yet to be clarified. Currently, endometriosis and ovarian cancer association does not seem to have a clinical implication. What do the results of this study add? The findings of this study revealed that nearly 75% of endometriosis-associated ovarian tumours were of atypical endometriosis. Half of endometriosis-associated ovarian tumour cases were of endometrioid/clear cell histology and 70% were early-stage. Endometriosis was significantly associated with borderline

Orbital adenocarcinoma of lacrimal gland origin in a dog.

PubMed

Wang, F I; Ting, C T; Liu, Y S

2001-03-01

A 13-year-old intact female mixed-breed dog was presented for a progressive enlargement of the right eye, which had been treated previously for conjunctivitis. A round, firm mass, approximately 4 cm in diameter, was protruding from the superotemporal aspect of the right orbit, displacing the eyeball anteriorly and ventromedially. The mass was encapsulated, distinct from the eyeball, and not associated with the eyelids. On cut surface, there was a pale multilobulated periphery, with a dark red, soft, and depressed core. Histologically, tumor cells formed cords and tubules, which were stained with mouse anti-human cytokeratin antibody AE1/AE3. Residual glands were serous, and the majority of tumor cells were negative for mucin. The supraorbital location, encapsulation, and residual serous glands suggest that this mass was a low-grade adenocarcinoma of the lacrimal gland.

Glutamate Cysteine Ligase Modifier Subunit (Gclm) Null Mice Have Increased Ovarian Oxidative Stress and Accelerated Age-Related Ovarian Failure

PubMed Central

Lim, Jinhwan; Nakamura, Brooke N.; Mohar, Isaac; Kavanagh, Terrance J.

2015-01-01

Glutathione (GSH) is the one of the most abundant intracellular antioxidants. Mice lacking the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have decreased GSH. Our prior work showed that GSH plays antiapoptotic roles in ovarian follicles. We hypothesized that Gclm−/− mice have accelerated ovarian aging due to ovarian oxidative stress. We found significantly decreased ovarian GSH concentrations and oxidized GSH/oxidized glutathione redox potential in Gclm−/− vs Gclm+/+ ovaries. Prepubertal Gclm−/− and Gclm+/+ mice had similar numbers of ovarian follicles, and as expected, the total number of ovarian follicles declined with age in both genotypes. However, the rate of decline in follicles was significantly more rapid in Gclm−/− mice, and this was driven by accelerated declines in primordial follicles, which constitute the ovarian reserve. We found significantly increased 4-hydroxynonenal immunostaining (oxidative lipid damage marker) and significantly increased nitrotyrosine immunostaining (oxidative protein damage marker) in prepubertal and adult Gclm−/− ovaries compared with controls. The percentage of small ovarian follicles with increased granulosa cell proliferation was significantly higher in prepubertal and 2-month-old Gclm−/− vs Gclm+/+ ovaries, indicating accelerated recruitment of primordial follicles into the growing pool. The percentages of growing follicles with apoptotic granulosa cells were increased in young adult ovaries. Our results demonstrate increased ovarian oxidative stress and oxidative damage in young Gclm−/− mice, associated with an accelerated decline in ovarian follicles that appears to be mediated by increased recruitment of follicles into the growing pool, followed by apoptosis at later stages of follicular development. PMID:26083875

An economic evaluation of laparoscopic ovarian diathermy versus gonadotrophin therapy for women with clomiphene citrate-resistant polycystic ovarian syndrome.

PubMed

Farquhar, Cynthia M

2005-08-01

Women with polycystic ovarian syndrome are typically anovulatory and require ovulation induction. Ovarian wedge resection was the first treatment for anovulation but was eventually abandoned because of the increased risk of postsurgical adhesions and as medical ovulation induction with clomiphene and gonadotrophins was introduced. However, with the advent of laparoscopy, there has been a return to surgical approaches. The potential advantages of laparoscopic surgery include avoidance of hyperstimulation and the lowered costs make ovarian surgery an attractive alternative to gonadotrophins. Clinical trials in New Zealand and the Netherlands have compared costs of laparoscopic ovarian drilling with gonadotrophins. The total cost of treatment in the Netherlands study for the ovarian drilling group was euro 4664 and for the gonadotrophins group was euro 5418. Without the cost of monitoring and the diagnostic laparoscopy then the difference was euro 2110 in favour of ovarian drilling. It was estimated that the cost per term pregnancy would be euro 14,489 for gonadotrophin and euro 11,301 for ovarian drilling (22% lower). The higher rates of multiple pregnancy in the gonadotrophin group were considered to be responsible for the increased costs. In the New Zealand trial the costs of a live birth were one-third lower in the group that underwent laparoscopic ovarian diathermy compared with those women who received gonadotrophins (NZ$19,640 and 29,836, respectively). Treating women with clomiphene-resistant polycystic ovarian syndrome with laparoscopic ovarian diathermy results in reduced direct and indirect costs. The reduction in multiple pregnancies makes the alternative of surgery particularly attractive.

Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma

PubMed Central

2015-01-01

Objective Irreversible electroporation (IRE) of locally advanced pancreatic adenocarcinoma of the neck has been used to palliate appropriate stage 3 pancreatic cancers without evidence of metastasis and who have undergone appropriate induction therapy. Currently there has not been a standardized reported technique for pancreatic mid-body tumors for patient selection and intra-operative technique. Patients Subjects are patients with locally advanced pancreatic adenocarcinoma of the body/neck who have undergone appropriate induction chemotherapy for a reasonable duration. Main outcome measures Technique of open IRE of locally advanced pancreatic adenocarcinoma of the neck/body is described, with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open IRE of the pancreatic neck/body with bracketing of the celiac axis and superior mesenteric artery with continuous intraoperative ultrasound imaging and consideration of intraoperative navigational system is described. Conclusions IRE of locally advanced pancreatic adenocarcinoma of the body/neck is feasible for appropriate patients with locally advanced unresectable pancreatic cancer. PMID:26029461

Polycystic Ovary Syndrome, Oligomenorrhea, and Risk of Ovarian Cancer Histotypes: Evidence from the Ovarian Cancer Association Consortium.

PubMed

Harris, Holly R; Babic, Ana; Webb, Penelope M; Nagle, Christina M; Jordan, Susan J; Risch, Harvey A; Rossing, Mary Anne; Doherty, Jennifer A; Goodman, Marc T; Modugno, Francesmary; Ness, Roberta B; Moysich, Kirsten B; Kjær, Susanne K; Høgdall, Estrid; Jensen, Allan; Schildkraut, Joellen M; Berchuck, Andrew; Cramer, Daniel W; Bandera, Elisa V; Wentzensen, Nicolas; Kotsopoulos, Joanne; Narod, Steven A; Phelan, Catherine M; McLaughlin, John R; Anton-Culver, Hoda; Ziogas, Argyrios; Pearce, Celeste L; Wu, Anna H; Terry, Kathryn L

2018-02-01

Background: Polycystic ovary syndrome (PCOS), and one of its distinguishing characteristics, oligomenorrhea, have both been associated with ovarian cancer risk in some but not all studies. However, these associations have been rarely examined by ovarian cancer histotypes, which may explain the lack of clear associations reported in previous studies. Methods: We analyzed data from 14 case-control studies including 16,594 women with invasive ovarian cancer ( n = 13,719) or borderline ovarian disease ( n = 2,875) and 17,718 controls. Adjusted study-specific ORs were calculated using logistic regression and combined using random-effects meta-analysis. Pooled histotype-specific ORs were calculated using polytomous logistic regression. Results: Women reporting menstrual cycle length >35 days had decreased risk of invasive ovarian cancer compared with women reporting cycle length ≤35 days [OR = 0.70; 95% confidence interval (CI) = 0.58-0.84]. Decreased risk of invasive ovarian cancer was also observed among women who reported irregular menstrual cycles compared with women with regular cycles (OR = 0.83; 95% CI = 0.76-0.89). No significant association was observed between self-reported PCOS and invasive ovarian cancer risk (OR = 0.87; 95% CI = 0.65-1.15). There was a decreased risk of all individual invasive histotypes for women with menstrual cycle length >35 days, but no association with serous borderline tumors ( P heterogeneity = 0.006). Similarly, we observed decreased risks of most invasive histotypes among women with irregular cycles, but an increased risk of borderline serous and mucinous tumors ( P heterogeneity < 0.0001). Conclusions: Our results suggest that menstrual cycle characteristics influence ovarian cancer risk differentially based on histotype. Impact: These results highlight the importance of examining ovarian cancer risk factors associations by histologic subtype. Cancer Epidemiol Biomarkers Prev; 27(2); 174-82. ©2017 AACR . ©2017 American

Activated RET and ROS: two new driver mutations in lung adenocarcinoma

PubMed Central

Bos, Marc; Gardizi, Masyar; Schildhaus, Hans-Ulrich; Buettner, Reinhard

2013-01-01

Rearrangements of ROS1 and RET have been recently described as new driver mutations in lung adenocarcinoma with a frequency of about 1% each. RET and ROS1 rearrangements both represent unique molecular subsets of lung adenocarcinoma with virtually no overlap with other known driver mutations described so far in lung adenocarcinoma. Specific clinicopathologic characteristics have been described and several multitargeted receptor kinase inhibitors have shown in vitro activity against NSCLC cells harbouring these genetic alterations. In addition, the MET/ALK/ROS inhibitor crizotinib has already shown impressive clinical activity in patients with advanced ROS1-positive lung cancer. Currently, several early proof of concept clinical trials are testing various kinase inhibitors in both molecular subsets of lung adenocarcinoma patients. Most probably, personalized treatment of these genetically defined new subsets of lung adenocarcinoma will be implemented in routine clinical care of lung cancer patients in the near future. PMID:25806222

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Esophageal/Gastric Cardia Adenocarcinoma Among Men.

PubMed

Petrick, Jessica L; Hyland, Paula L; Caron, Patrick; Falk, Roni T; Pfeiffer, Ruth M; Dawsey, Sanford M; Abnet, Christian C; Taylor, Philip R; Weinstein, Stephanie J; Albanes, Demetrius; Freedman, Neal D; Gapstur, Susan M; Bradwin, Gary; Guillemette, Chantal; Campbell, Peter T; Cook, Michael B

2018-05-17

Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA in a nested case-control study drawn from participants in three prospective cohort studies. Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA risk. All statistical tests were two-sided. Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA = 0.62, 95% CI = 0.47 to 0.82, Ptrend = .001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, Ptrend = .05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men.

Ovarian surface epithelium at the junction area contains cancer-prone stem cell niche

PubMed Central

Flesken-Nikitin, Andrea; Hwang, Chang-Il; Cheng, Chieh-Yang; Michurina, Tatyana V.; Enikolopov, Grigori; Nikitin, Alexander Yu.

2014-01-01

Epithelial ovarian cancer (EOC) is the fifth-leading cause of cancer death among women in the United States, but its pathogenesis is poorly understood 1-3. Some epithelial cancers are known to occur in transitional zones between two types of epithelium, while others have been shown to originate in epithelial tissue stem cells 4-6. The stem cell niche of the ovarian surface epithelium (OSE), which is ruptured and regenerates during ovulation, has not yet been unequivocally defined. Here we identify the hilum region of the mouse ovary, the transitional/junction area between OSE, mesothelium and tubal (oviductal) epithelium as a previously unrecognized stem cell niche of the OSE. We find that cells of the hilum OSE are slowly-cycling and express stem/progenitor cell markers ALDH1, Lgr5, Lef1, CD133, and CK6b. These cells display long-term stem cell properties ex vivo and in vivo, as shown by our serial sphere generation and by long-term lineage tracing assays. Importantly, the hilum cells exhibit increased transformation potential after inactivation of tumour suppressor genes Trp53 and Rb1, whose pathways are frequently altered in the most aggressive and common type of human EOC, high-grade serous adenocarcinoma 7,8. Our study experimentally supports the notion that susceptibility of transitional zones to malignant transformation may be explained by the presence of stem cell niches in those areas. Identification of a stem cell niche for the OSE may have important implications for understanding EOC pathogenesis. PMID:23467088

Two patients with rare mixed adenoneuroendocrine carcinomas of the rectum.

PubMed

Gül-Klein, Safak; Sinn, Marianne; Jurmeister, Philipp Sebastian; Biebl, Matthias; Weiß, Sascha; Rau, Beate; Bläker, Hendrik; Pratschke, Johann; Aigner, Felix

2018-01-01

Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract are until today poorly understood and thus very challenging for interdisciplinary therapy. We herewith report the first case series of patients with a primary mixed adenoneuroendocrine carcinoma of the rectum. Both cases were initially diagnosed as adenocarcinoma and only secondarily with mixed adenoneuroendocrine carcinoma and had a poor outcome due to a rapid tumor progression and resistance to chemotherapy. A 65-year-old female presented with local tumor recurrence and hepatopulmonary metastasis 1 year after primary surgery for adenocarcinoma of the rectum and consecutive radiochemotherapy regimen. Fluorouracil (5-FU) was followed by bevacizumab- and capecitabine-based chemotherapy but had to be discontinued due to side effects and progressive disease. Progressive local pain syndrome accompanied by recurrent bleeding episodes led to a local tumor-debulking operation. Afterward, mixed adenoneuroendocrine carcinoma as the underlying diagnosis in the final histopathological examination was detected. The patient died 3 months after the operation in the context of a fulminant tumor progress. A 63-year-old male patient underwent neoadjuvant radiochemotherapy and laparoscopic rectum resection. After 5 months, postoperative oxaliplatin/capecitabine-based adjuvant chemotherapy was switched to carboplatin/etopsid due to a progressive polyneuropathy and biopsy-proven pulmonary metastasis. The patient then had to be switched to local radiation of cerebral metastases and Topotecan due to cerebral bleeding episodes but died 18 months after the initial diagnosis. In conclusion of our case series, mixed adenoneuroendocrine carcinomas of the rectum should be considered as a rare but aggressive tumor entity. An early and detailed histopathological diagnosis is required in order to establish an individual interdisciplinary treatment concept.

Optimizing patient derived mesenchymal stem cells as virus carriers for a Phase I clinical trial in ovarian cancer

PubMed Central

2013-01-01

Background Mesenchymal stem cells (MSC) can serve as carriers to deliver oncolytic measles virus (MV) to ovarian tumors. In preparation for a clinical trial to use MSC as MV carriers, we obtained cells from ovarian cancer patients and evaluated feasibility and safety of this approach. Methods MSC from adipose tissues of healthy donors (hMSC) and nine ovarian cancer patients (ovMSC) were characterized for susceptibility to virus infection and tumor homing abilities. Results Adipose tissue (range 0.16-3.96 grams) from newly diagnosed and recurrent ovarian cancer patients yielded about 7.41×106 cells at passage 1 (range 4–9 days). Phenotype and doubling times of MSC were similar between ovarian patients and healthy controls. The time to harvest of 3.0×108 cells (clinical dose) could be achieved by day 14 (range, 9–17 days). Two of nine samples tested had an abnormal karyotype represented by trisomy 20. Despite receiving up to 1.6×109 MSC/kg, no tumors were seen in SCID beige mice and MSC did not promote the growth of SKOV3 human ovarian cancer cells in mice. The ovMSC migrated towards primary ovarian cancer samples in chemotaxis assays and to ovarian tumors in athymic mice. Using non-invasive SPECT-CT imaging, we saw rapid co-localization, within 5–8 minutes of intraperitoneal administration of MV infected MSC to the ovarian tumors. Importantly, MSC can be pre-infected with MV, stored in liquid nitrogen and thawed on the day of infusion into mice without loss of activity. MV infected MSC, but not virus alone, significantly prolonged the survival of measles immune ovarian cancer bearing animals. Conclusions These studies confirmed the feasibility of using patient derived MSC as carriers for oncolytic MV therapy. We propose an approach where MSC from ovarian cancer patients will be expanded, frozen and validated to ensure compliance with the release criteria. On the treatment day, the cells will be thawed, washed, mixed with virus, briefly centrifuged and

Persistent ovarian masses and pregnancy outcomes.

PubMed

Goh, William A; Rincon, Monica; Bohrer, Justin; Tolosa, Jorge E; Sohaey, Roya; Riaño, Rene; Davis, James; Zalud, Ivica

2013-07-01

To determine if persistent ovarian masses in pregnancy are associated with increased adverse outcomes. This is a retrospective cohort of 126 pregnant women with a persistent ovarian mass measuring 5 cm or greater who delivered at two university hospitals between 2001 and 2009. Maternal outcomes included gestational age (GA) at diagnosis, delivery and surgery as well as miscarriage, preterm birth (PTB), ovarian torsion and hospital admission for pain. Neonatal outcomes included birth weight, respiratory distress syndrome (RDS), intra-ventricular hemorrhage (IVH), death and sepsis. A total of 1225 ovarian masses were identified (4.9%) in 24,868 patients. A persistent ovarian mass was found in 0.7%. Average GA at diagnosis was 17.8 weeks. Miscarriage rate was 3.3%. Average GA at delivery was 37.9 weeks. Of the patients, 8.5% had ovarian torsion, 10.3% had admission for pain and 9.3% had PTBs. The mean cesarean delivery rate was 46.3%. The average neonatal weight was 3273 g. There was one neonatal death in this cohort. The rate of RDS was 2.8%, IVH 0.9% and neonatal sepsis 1.9%. The most common surgical pathologic diagnosis was dermoids (37.6%). No overt malignancies were seen. A persistent ovarian mass in pregnancy does not confer an increased risk of adverse pregnancy outcomes.

Ovarian Germ Cell Tumors Treatment

MedlinePlus

... Tube, & Primary Peritoneal Cancer Screening Research Ovarian Germ Cell Tumors Treatment (PDQ®)–Patient Version Treatment Option Overview ... types of treatment for patients with ovarian germ cell tumors. Different types of treatment are available for ...

Antitumor Activity and Induction of TP53-Dependent Apoptosis toward Ovarian Clear Cell Adenocarcinoma by the Dual PI3K/mTOR Inhibitor DS-7423

PubMed Central

Kashiyama, Tomoko; Oda, Katsutoshi; Ikeda, Yuji; Shiose, Yoshinobu; Hirota, Yasuhide; Inaba, Kanako; Makii, Chinami; Kurikawa, Reiko; Miyasaka, Aki; Koso, Takahiro; Fukuda, Tomohiko; Tanikawa, Michihiro; Shoji, Keiko; Sone, Kenbun; Arimoto, Takahide; Wada-Hiraike, Osamu; Kawana, Kei; Nakagawa, Shunsuke; Matsuda, Koichi; McCormick, Frank; Aburatani, Hiroyuki; Yano, Tetsu; Osuga, Yutaka; Fujii, Tomoyuki

2014-01-01

DS-7423, a novel, small-molecule dual inhibitor of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), is currently in phase I clinical trials for solid tumors. Although DS-7423 potently inhibits PI3Kα (IC50 = 15.6 nM) and mTOR (IC50 = 34.9 nM), it also inhibits other isoforms of class I PI3K (IC50 values: PI3Kβ = 1,143 nM; PI3Kγ = 249 nM; PI3Kδ = 262 nM). The PI3K/mTOR pathway is frequently activated in ovarian clear cell adenocarcinomas (OCCA) through various mutations that activate PI3K-AKT signaling. Here, we describe the anti-tumor effect of DS-7423 on a panel of nine OCCA cell lines. IC50 values for DS-7423 were <75 nM in all the lines, regardless of the mutational status of PIK3CA. In mouse xenograft models, DS-7423 suppressed the tumor growth of OCCA in a dose-dependent manner. Flow cytometry analysis revealed a decrease in S-phase cell populations in all the cell lines and an increase in sub-G1 cell populations following treatment with DS-7423 in six of the nine OCCA cell lines tested. DS-7423-mediated apoptosis was induced more effectively in the six cell lines without TP53 mutations than in the three cell lines with TP53 mutations. Concomitantly with the decreased phosphorylation level of MDM2 (mouse double minute 2 homolog), the level of phosphorylation of TP53 at Ser46 was increased by DS-7423 in the six cell lines with wild-type TP53, with induction of genes that mediate TP53-dependent apoptosis, including p53AIP1 and PUMA at 39 nM or higher doses. Our data suggest that the dual PI3K/mTOR inhibitor DS-7423 may constitute a promising molecular targeted therapy for OCCA, and that its antitumor effect might be partly obtained by induction of TP53-dependent apoptosis in TP53 wild-type OCCAs. PMID:24504419

Follicular fluid placental growth factor is increased in polycystic ovarian syndrome: correlation with ovarian stimulation.

PubMed

Tal, Reshef; Seifer, David B; Grazi, Richard V; Malter, Henry E

2014-08-20

Polycystic ovarian syndrome (PCOS) is characterized by increased ovarian angiogenesis and vascularity. Accumulating evidence indicates that vascular endothelial growth factor (VEGF) is increased in PCOS and may play an important role in these vascular changes and the pathogenesis of this disease. Placental growth factor (PlGF), a VEGF family member, has not been previously characterized in PCOS women. We investigated levels and temporal expression patterns of PlGF and its soluble receptor sFlt-1 (soluble Fms-like tyrosine kinase) in serum and follicular fluid (FF) of women with PCOS during controlled ovarian stimulation. This was a prospective cohort study of 14 PCOS women (Rotterdam criteria) and 14 matched controls undergoing controlled ovarian stimulation. Serum was collected on day 3, day of hCG and day of oocyte retrieval. FF was collected on retrieval day. PlGF, sFlt-1 and anti-mullerian hormone (AMH) protein concentrations were measured using ELISA. Since sFlt-1 binds free PlGF, preventing its signal transduction, we calculated PlGF bioavailability as PlGF/sFlt-1 ratio. Serum PlGF and sFlt-1 levels were constant throughout controlled ovarian stimulation, and no significant differences were observed in either factor in PCOS women compared with non-PCOS controls at all three measured time points. However, FF PlGF levels were increased 1.5-fold in PCOS women compared with controls (p < 0.01). Moreover, FF PlGF correlated positively with number of oocytes retrieved and the ovarian reserve marker anti-mullerian hormone (AMH) and negatively with age. In addition, FF sFlt-1 levels were decreased 1.4-fold in PCOS women compared to controls (p = 0.04). PlGF bioavailability in FF was significantly greater (2-fold) in PCOS women compared with non-PCOS controls (p < 0.01). These data provide evidence that FF PlGF correlates with ovarian stimulation and that its bioavailability is increased in women with PCOS undergoing controlled ovarian stimulation. This

Testing for NRAS Mutations in Serous Borderline Ovarian Tumors and Low-Grade Serous Ovarian Carcinomas

PubMed Central

Grzanka, Dariusz; Grabiec, Marek

2018-01-01

The Idylla NRAS Mutation Test, performed on the Biocartis Idylla system, is an in vitro diagnostic tool for the qualitative assessment of 18 NRAS mutations in codons 12, 13, 59, 61, 117, and 146. Low-grade serous ovarian cancer (LGSC) represents less than 10% of all serous ovarian carcinomas. LGSCs are believed to arise from preexisting cystadenomas or serous borderline tumors (SBOTs) that eventually progress to an invasive carcinoma. The molecular analysis of cancer-causing mutations and the development of targeted biological therapies constitute a milestone in the diagnosis and therapy of ovarian malignancies. According to some authors, NRAS may be an important oncogene for the progression of SBOT to a frankly invasive disease. The primary aim of this study was to verify if a fully integrated, real-time PCR-based Idylla system can be used for the rapid determination of the NRAS mutation status in patients with serous borderline ovarian tumors and low-grade serous ovarian carcinomas. The study included tissue specimens from 12 patients with histopathologically verified ovarian masses, operated on at the Department of Obstetrics and Gynecology, Nicolaus Copernicus University, Collegium Medicum in Bydgoszcz (Poland), between January 2009 and June 2012. The mean age of the study patients was 52.5 years (range 27–80 years). NRAS mutation in codon 13 (G13D, p.Gly13Asp; nucleotide: c.38G>A) was found in one patient, a woman with low-grade serous ovarian carcinoma. To the best of our knowledge, our experiment was the first published study using the novel Idylla NRAS Mutation Test for the evaluation of ovarian tumors in a clinical setting. The Idylla platform is an interesting ancillary first-line rapid and fully automated instrument to detect NRAS mutations in SBOTs and LGSCs. However, the clinical usefulness of this method still needs to be verified in larger groups of cancer patients. PMID:29682098

Environmental and developmental origins of ovarian reserve.

PubMed

Richardson, M C; Guo, M; Fauser, B C J M; Macklon, N S

2014-01-01

BACKGROUND Oocyte number is established early in life before a gradual loss of this ovarian reserve during reproductive life until oocyte availability becomes limiting at the menopause. Although there is a large genetic component to the ovarian reserve achieved before birth, other influences including the maternal endocrine and nutritional milieu, and environmental factors may represent important developmental determinants. Environmental and nutritional factors may also modify the downward trajectory of ovarian reserve in adult life. The combination of these early and later life influences has the potential to lead to diminished ovarian reserve, compromising fertility in later reproductive years and altering age at natural menopause. METHODS Literature searches of the ISI Web of Knowledge database were carried out using the main terms 'ovarian reserve' and 'menopause AND age' in conjunction with a range of other terms encompassing a variety of factors with potential effects on ovarian reserve. The various searches were inspected manually and the relevant papers selected for critical analysis and interpretation. RESULTS Evidence was identified supporting the view that elevated prenatal androgens have an adverse effect on the early establishment of ovarian reserve, although the implications for ovarian reserve in the polycystic ovary syndrome (which may also be programmed through prenatal androgen exposure) remain uncertain. Recent evidence is cited suggesting that effects of maternal nutrient restriction on ovarian reserve may also involve changes in prenatal androgen exposure. A general rationale is developed through examination of evidence which emphasizes the roles of the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) systems in ovarian reserve modulation. Because of their similarity to the natural ligands, many environmental compounds have the ability to bind to these receptors (albeit at lower affinities) and thereby have the potential to

Duodenal adenocarcinoma presenting as a mass with aneurismal dilatation.

PubMed

Mama, Nadia; Ben Slama, Aïda; Arifa, Nadia; Kadri, Khaled; Sriha, Badreddine; Ksiaa, Mehdi; Jemni, Hela; Tlili-Graiess, Kalthoum

2014-01-01

Duodenal adenocarcinoma is frequent. Aneurysmal dilatation of the small bowel is reported to be a lymphoma characteristic imaging finding. A 57-year-old male was found to have a duodenal adenocarcinoma with aneurismal dilatation on imaging which is an exceptional feature. On laparotomy, the wall thickening of the dilated duodenum extended to the first jejunal loop, with multiple mesenteric lymph nodes and ascites. Segmental palliative resection with gastro-entero-anastomosis was done. Histopathology revealed a moderately differentiated adenocarcinoma with neuro-endocrine differentiation foci. Wide areas of necrosis and vascular emboli were responsible for the radiological feature of the dilated duodenum with wall thickening. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypocalcemia following surgical treatment of metastatic anal sac adenocarcinoma in a dog.

PubMed

Saba, Corey; Ellis, Angela; Cornell, Karen

2011-01-01

A 9 yr old neutered male mixed-breed dog was presented for an anal sac apocrine gland adenocarcinoma with regional nodal metastases. At presentation, ionized calcium was 1.91 mmol/L (NOVA Stat reference range, 1.1-1.3 mmol/L). Surgical excision of the primary tumor and metastatic lymph nodes was performed. Following surgery, symptomatic hypocalcemia was noted. Repeated ionized calcium measurements confirmed hypocalcemia, and hypercalcemia of malignancy panels suggested parathyroid gland suppression as the cause. The calcium normalized with parenteral calcium administration, but calcium later became elevated with tumor recurrence and an increase in the parathormone-related peptide. Disrupted calcium homeostasis is a potential complication following the treatment of long-standing humoral hypercalcemia of malignancy.

Adjuvant ovarian suppression in premenopausal breast cancer.

PubMed

Francis, Prudence A; Regan, Meredith M; Fleming, Gini F; Láng, István; Ciruelos, Eva; Bellet, Meritxell; Bonnefoi, Hervé R; Climent, Miguel A; Da Prada, Gian Antonio; Burstein, Harold J; Martino, Silvana; Davidson, Nancy E; Geyer, Charles E; Walley, Barbara A; Coleman, Robert; Kerbrat, Pierre; Buchholz, Stefan; Ingle, James N; Winer, Eric P; Rabaglio-Poretti, Manuela; Maibach, Rudolf; Ruepp, Barbara; Giobbie-Hurder, Anita; Price, Karen N; Colleoni, Marco; Viale, Giuseppe; Coates, Alan S; Goldhirsch, Aron; Gelber, Richard D

2015-01-29

Suppression of ovarian estrogen production reduces the recurrence of hormone-receptor-positive early breast cancer in premenopausal women, but its value when added to tamoxifen is uncertain. We randomly assigned 3066 premenopausal women, stratified according to prior receipt or nonreceipt of chemotherapy, to receive 5 years of tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The primary analysis tested the hypothesis that tamoxifen plus ovarian suppression would improve disease-free survival, as compared with tamoxifen alone. In the primary analysis, 46.7% of the patients had not received chemotherapy previously, and 53.3% had received chemotherapy and remained premenopausal. After a median follow-up of 67 months, the estimated disease-free survival rate at 5 years was 86.6% in the tamoxifen-ovarian suppression group and 84.7% in the tamoxifen group (hazard ratio for disease recurrence, second invasive cancer, or death, 0.83; 95% confidence interval [CI], 0.66 to 1.04; P=0.10). Multivariable allowance for prognostic factors suggested a greater treatment effect with tamoxifen plus ovarian suppression than with tamoxifen alone (hazard ratio, 0.78; 95% CI, 0.62 to 0.98). Most recurrences occurred in patients who had received prior chemotherapy, among whom the rate of freedom from breast cancer at 5 years was 82.5% in the tamoxifen-ovarian suppression group and 78.0% in the tamoxifen group (hazard ratio for recurrence, 0.78; 95% CI, 0.60 to 1.02). At 5 years, the rate of freedom from breast cancer was 85.7% in the exemestane-ovarian suppression group (hazard ratio for recurrence vs. tamoxifen, 0.65; 95% CI, 0.49 to 0.87). Adding ovarian suppression to tamoxifen did not provide a significant benefit in the overall study population. However, for women who were at sufficient risk for recurrence to warrant adjuvant chemotherapy and who remained premenopausal, the addition of ovarian suppression improved disease outcomes. Further

Fibulin-1 functions as a prognostic factor in lung adenocarcinoma.

PubMed

Cui, Yuan; Liu, Jian; Yin, Hai-Bing; Liu, Yi-Fei; Liu, Jun-Hua

2015-09-01

Fibulin-1 is a member of the fibulin gene family, characterized by tandem arrays of epidermal growth factor-like domains and a C-terminal fibulin-type module. Fibulin-1 plays important roles in a range of cellular functions including morphology, growth, adhesion and mobility. It acts as a tumor suppressor gene in cutaneous melanoma, prostate cancer and gastric cancer. However, whether fibulin-1 also acts as a tumor suppressor gene in lung adenocarcinoma remains unknown. We also determined the association of fibulin-1 expression with various clinical and pathological parameters, which would show its potential role in clinical prognosis. We investigated and followed up 140 lung adenocarcinoma patients who underwent lung resection without pre- and post-operative systemic chemotherapy at the Affiliated Hospital of Nantong University from 2009 to 2013. Western blot assay and immunohistochemistry were used to evaluate the expression of fibulin-1 in lung adenocarcinoma tissues. We then analyzed the correlations between fibulin-1 expression and clinicopathological variables as well as the patients' overall survival rate. Both western blot assay and immunohistochemistry demonstrated that the level of fibulin-1 was downregulated in human lung adenocarcinoma tissues compared with that of normal lung tissues. Fibulin-1 expression significantly correlated with histological differentiation (P = 0.046), clinical stage (P< 0.01), lymph node status (P = 0.038) and expression of Ki-67 (P = 0.013). More importantly, multivariate analysis revealed that fibulin-1 was an independent prognostic marker for lung adenocarcinoma, and high expression of fibulin-1 was significantly associated with better prognosis of lung adenocarcinoma patients. The results supported our hypothesis that fibulin-1 can act as a prognostic factor in lung adenocarcinoma progression. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Endometrioid Adenocarcinoma Arising from Endometriosis of the Uterine Cervix: A Case Report

PubMed Central

Park, Han Moie; Lee, Sang Soo; Eom, Dae Woon; Kang, Gil Hyun; Yi, Sang Wook

2009-01-01

Endometrioid adenocarcinoma arising from endometriosis of the uterine cervix is rare in premenopausal woman. We describe here a patient with this condition and review the clinical and pathological features of these tumors. A 48-yr-old woman complaining of severe dysmenorrhea was referred for investigation of a pelvic mass. Total abdominal hysterectomy and bilateral salpingo-oophorectomy were performed. Histological examination revealed an endometrioid adenocarcinoma directly adjacent to the endometriosis at the uterine cervix, with a transition observed between endometriosis and endometrioid adenocarcinoma. The patient was diagnosed as having endometrioid adenocarcinoma arising from endometriosis of the uterine cervix and underwent postoperative chemotherapy. Gynecologists and pathologists should be aware of the difficulties associated with a delay in diagnosis of endometrioid adenocarcinoma arising from endometriosis when the tumor presents as a benign looking endometrioma. PMID:19654969

Ovarian cancer statistics, 2018.

PubMed

Torre, Lindsey A; Trabert, Britton; DeSantis, Carol E; Miller, Kimberly D; Samimi, Goli; Runowicz, Carolyn D; Gaudet, Mia M; Jemal, Ahmedin; Siegel, Rebecca L

2018-05-29

In 2018, there will be approximately 22,240 new cases of ovarian cancer diagnosed and 14,070 ovarian cancer deaths in the United States. Herein, the American Cancer Society provides an overview of ovarian cancer occurrence based on incidence data from nationwide population-based cancer registries and mortality data from the National Center for Health Statistics. The status of early detection strategies is also reviewed. In the United States, the overall ovarian cancer incidence rate declined from 1985 (16.6 per 100,000) to 2014 (11.8 per 100,000) by 29% and the mortality rate declined between 1976 (10.0 per 100,000) and 2015 (6.7 per 100,000) by 33%. Ovarian cancer encompasses a heterogenous group of malignancies that vary in etiology, molecular biology, and numerous other characteristics. Ninety percent of ovarian cancers are epithelial, the most common being serous carcinoma, for which incidence is highest in non-Hispanic whites (NHWs) (5.2 per 100,000) and lowest in non-Hispanic blacks (NHBs) and Asians/Pacific Islanders (APIs) (3.4 per 100,000). Notably, however, APIs have the highest incidence of endometrioid and clear cell carcinomas, which occur at younger ages and help explain comparable epithelial cancer incidence for APIs and NHWs younger than 55 years. Most serous carcinomas are diagnosed at stage III (51%) or IV (29%), for which the 5-year cause-specific survival for patients diagnosed during 2007 through 2013 was 42% and 26%, respectively. For all stages of epithelial cancer combined, 5-year survival is highest in APIs (57%) and lowest in NHBs (35%), who have the lowest survival for almost every stage of diagnosis across cancer subtypes. Moreover, survival has plateaued in NHBs for decades despite increasing in NHWs, from 40% for cases diagnosed during 1992 through 1994 to 47% during 2007 through 2013. Progress in reducing ovarian cancer incidence and mortality can be accelerated by reducing racial disparities and furthering knowledge of etiology and

Rare coexistence of sarcoidosis and lung adenocarcinoma.

PubMed

Kachalia, Amit Girish; Ochieng, Pius; Kachalia, Kinjal; Rahman, Habibur

2014-01-01

An eighty year old African-American female was evaluated for cough, chest pain, asymptomatic anemia and 21 pound weight loss over a six month period. Computerized tomography (CT) revealed a spiculated 2.8 cm right upper lobe lung nodule, other smaller nodules and lymphadenopathy. Gallium scan revealed abnormal uptake of radiotracer in lacrimal, hilar and mediastinal glands. Broncho-alveolar lavage showed CD4/CD8 ratio of 2:1 with 15% lymphocytes. Biopsy of right upper lobe lesion and mediastinoscopic lymph node biopsy showed numerous matured uniform non-caseating granulomatous inflammation, however stains and culture for Acid fast bacilli (AFB)/fungal organisms were negative. Patient improved on oral steroids. Six months later she returned with worsening dyspnea and chest X-ray showed bilateral pleural effusions. Thoracocentesis revealed Thyroid transcription factor 1 (TTF1) positive adenocarcinoma cells and Video assisted thoracic surgery (VATS) procedure revealed numerous pleural, pericardial, diaphragmatic metastasis. Biopsy also was positive for TTF1 adenocarcinoma and positive for Epidermal Growth Factor receptor (EGFR) mutation, however negative for Anaplastic Lymphoma Kinase (ALK). Talc pleurodesis was performed. She was treated with erlotinib while steroid was kept on hold. Initial tumor burden decreased but follow-up PET scan six months later showed progression of tumor with lymphadenopathy. After discussion with patient and family, patient opted for hospice care. Oncocentric theory postulates sarcoidosis as an immunological reaction to dispersal of tumor antigen. Sarcocentric theory postulates that cell-mediated immune abnormalities induced by sarcoidosis in CD4 and CD8 cells is involved in the onset of lung cancer. Thus considerable controversy exists regarding sarcoidosis and malignancy. In our case, TTF1 adenocarcinoma cells from thoracocentesis suggest peripheral nodules in right upper lobe and lingula were likely metastatic, presenting as malignant

Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model

PubMed Central

Lee, Jae-Hwan; Lee, Myeongho; Ahn, Changhwan; Kang, Hee Young; Tran, Dinh Nam; Jeung, Eui-Bae

2017-01-01

Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh). All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles. PMID:28208728

Dysregulated Estrogen Receptor Signaling in the Hypothalamic-Pituitary-Ovarian Axis Leads to Ovarian Epithelial Tumorigenesis in Mice

PubMed Central

Laws, Mary J.; Kannan, Athilakshmi; Pawar, Sandeep; Haschek, Wanda M.; Bagchi, Milan K.; Bagchi, Indrani C.

2014-01-01

The etiology of ovarian epithelial cancer is poorly understood, mainly due to the lack of an appropriate experimental model for studying the onset and progression of this disease. We have created a mutant mouse model in which aberrant estrogen receptor alpha (ERα) signaling in the hypothalamic-pituitary-ovarian axis leads to ovarian epithelial tumorigenesis. In these mice, termed ERαd/d, the ERα gene was conditionally deleted in the anterior pituitary, but remained intact in the hypothalamus and the ovary. The loss of negative-feedback regulation by estrogen (E) at the level of the pituitary led to increased production of luteinizing hormone (LH) by this tissue. Hyperstimulation of the ovarian cells by LH resulted in elevated steroidogenesis, producing high circulating levels of steroid hormones, including E. The ERαd/d mice exhibited formation of palpable ovarian epithelial tumors starting at 5 months of age with 100% penetrance. By 15 months of age, 80% of ERαd/d mice die. Besides proliferating epithelial cells, these tumors also contained an expanded population of luteinized stromal cells, which acquire the ability to express P450 aromatase and synthesize E locally. In response to the elevated levels of E, the ERα signaling was accentuated in the ovarian epithelial cells of ERαd/d mice, triggering increased ERα-dependent gene expression, abnormal cell proliferation, and tumorigenesis. Consistent with these findings, treatment of ERαd/d mice with letrozole, an aromatase inhibitor, markedly reduced circulating E and ovarian tumor volume. We have, therefore, developed a unique animal model, which serves as a useful tool for exploring the involvement of E-dependent signaling pathways in ovarian epithelial tumorigenesis. PMID:24603706

Chemosensitivity of BRCA1-Mutated Ovarian Cancer Cells and Established Cytotoxic Agents.

PubMed

van Haaften, Caroline; van Eendenburg, Jaap; Boot, Arnoud; Corver, Willem E; Haans, Lucien; van Wezel, Tom; Trimbos, J Baptist

2017-10-01

Serous adenocarcinomas that arise in patients with inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 are initially well treatable with platinum/paclitaxel. For recurrent disease in patients with BRCA1 or BRCA2 mutations, olaparib treatment is available. To study additional therapeutic regimens, a better understanding of the cellular and molecular mechanisms of the tumors in in vitro models is important. From a high-grade serous ovarian tumor of a BRCA1 mutation carrier, we established 3 distinct cell line subclones, OVCA-TR3.1, -2, and -3. Immunohistochemical characterization, flow cytometric analyses, chemosensitivity, and somatic mutation profiling were performed. The cell lines expressed AE1/AE3, Pax8, WT-1, OC125, estrogen receptor (ER), and p53, comparable to the primary tumor. Synergism could be shown in the combination treatment eremophila-1-(10)-11(13)-dien-12,8β-olide (EPD), with cisplatin, whereas combination with olaparib did not show synergism. Eremophila-1-(10)-11(13)-dien-12,8β-olide, a sesquiterpene lactone, is a novel chemotherapeutic agent. The inherited BRCA1 c.2989_2990dupAA mutation was confirmed in the cell lines. Loss of heterozygosity of BRCA1 was detected in each cell line, as well as a homozygous TP53 c.722C>A mutation. Flow cytometry showed that all cell lines had a distinct DNA index. Three new isogenic ovarian cancer cell lines were developed from a patient with a germ line BRCA1 mutation. Chemosensitivity profiling of the cell lines showed high tolerance for olaparib. Treatment with EPD proved synergistic with cisplatin. The effects of EPD will be further investigated for future clinical efficacy.

Individualization of controlled ovarian stimulation in IVF using ovarian reserve markers: from theory to practice.

PubMed

La Marca, Antonio; Sunkara, Sesh Kamal

2014-01-01

The main objective of individualization of treatment in IVF is to offer every single woman the best treatment tailored to her own unique characteristics, thus maximizing the chances of pregnancy and eliminating the iatrogenic and avoidable risks resulting from ovarian stimulation. Personalization of treatment in IVF should be based on the prediction of ovarian response for every individual. The starting point is to identify if a woman is likely to have a normal, poor or a hyper response and choose the ideal treatment protocol tailored to this prediction. The objective of this review is to summarize the predictive ability of ovarian reserve markers, such as antral follicle count (AFC) and anti-Mullerian hormone (AMH), and the therapeutic strategies that have been proposed in IVF after this prediction. A systematic review of the existing literature was performed by searching Medline, EMBASE, Cochrane library and Web of Science for publications in the English language related to AFC, AMH and their incorporation into controlled ovarian stimulation (COS) protocols in IVF. Literature available to May 2013 was included. The search generated 305 citations of which 41 and 25 studies, respectively, reporting the ability of AMH and AFC to predict response to COS were included in this review. The literature review demonstrated that AFC and AMH, the most sensitive markers of ovarian reserve identified to date, are ideal in planning personalized COS protocols. These sensitive markers permit prediction of the whole spectrum of ovarian response with reliable accuracy and clinicians may use either of the two markers as they can be considered interchangeable. Following the categorization of expected ovarian response to stimulation clinicians can adopt tailored therapeutic strategies for each patient. Current scientific trend suggests the elective use of the GnRH antagonist based regimen for hyper-responders, and probably also poor responders, as likely to be beneficial. The

Dietary Factors and the Risks of Esophageal Adenocarcinoma and Barrett’s Esophagus

PubMed Central

Kubo, Ai; Corley, Douglas A.; Jensen, Christopher D.; Kaur, Rubinder

2010-01-01

Incidence rates for esophageal adenocarcinoma have increased by over 500% during the past few decades without clear reasons. Gastroesophageal reflux disease (GERD), obesity, and smoking have been identified as risk factors, although the demographic distribution of these risk factors is not consistent with the demographic distribution of esophageal adenocarcinoma, which is substantially more common among whites and males than any other demographic groups. Numerous epidemiological studies have suggested associations between dietary factors and the risks of esophageal adenocarcinoma and its precursor, Barrett’s esophagus, though a comprehensive review is lacking. The main aim of the present review is to consider the evidence linking dietary factors with the risks of esophageal adenocarcinoma, Barrett’s esophagus, and the progression from Barrett’s esophagus to esophageal adenocarcinoma. The existing epidemiological evidence is strongest for an inverse relationship between intake of vitamin C, β-carotene, fruits and vegetables, particularly raw fruits and vegetables and dark-green, leafy and cruciferous vegetables, carbohydrates, fiber and iron and the risk of esophageal adenocarcinoma and Barrett’s esophagus. Patients at higher risk for Barrett’s esophagus and esophageal adenocarcinoma may benefit from increasing their consumption of fruits and vegetables and reducing their intake of red meat and other processed food items. Further research is needed to evaluate the relationship between diet and the progression of Barrett’s esophagus to esophageal adenocarcinoma. Evidence from cohort studies will help determine whether randomized chemoprevention trials are warranted for the primary prevention of Barrett’s esophagus or its progression to cancer. PMID:20624335

Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors: Results from a Danish case-control study.

PubMed

Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan; Høgdall, Estrid; Høgdall, Claus; Jensen, Allan

2015-01-01

Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. From 1995 through 1999, we included 267 women with ovarian cancer, 115 women with borderline ovarian tumors and 911 randomly selected control women. All women completed a beverage frequency questionnaire with detailed information on coffee and tea consumption. Analyses were performed using multiple logistic regression models. Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer. No relation between tea consumption and ovarian cancer risk was observed. The risk estimates for borderline ovarian tumors resembled those observed for ovarian cancer, but did not reach statistical significance. Our results indicate that coffee consumption and total caffeine consumption from coffee and tea combined is associated with a modest decreased risk of ovarian cancer. However, more biological studies are needed to identify bioactive chemical compounds in coffee that potentially could affect ovarian cancer development.

Apolipoprotein concentrations are elevated in malignant ovarian cyst fluids suggesting that lipoprotein metabolism is dysregulated in epithelial ovarian cancer.

PubMed

Podzielinski, Iwona; Saunders, Brook A; Kimbler, Kimberly D; Branscum, Adam J; Fung, Eric T; DePriest, Paul D; van Nagell, John R; Ueland, Frederick R; Baron, Andre T

2013-05-01

SELDI-TOF MS analysis of ovarian cyst fluids revealed that peaks m/z 8696 and 8825 discriminate malignant, borderline, and benign tumors. These peaks correspond to isoforms of apoA2. ELISA demonstrates that apoA1, A2, B, C2, C3, and E cyst fluid concentrations are uncorrelated and higher in malignant ovarian tumors, but only apoA2, apoE, and age are independent classifiers of malignant ovarian tumors, yielding 55.1% sensitivity, 95% specificity, and 88.1% accuracy to discern malignant from benign and borderline tumors. These data suggest that lipoprotein metabolism is dysregulated in ovarian cancer and that apoA2 and apoE warrant further investigation as ovarian tumor biomarkers.

Immune cells in the normal ovary and spontaneous ovarian tumors in the laying hen (Gallus domesticus) model of human ovarian cancer.

PubMed

Bradaric, Michael J; Penumatsa, Krishna; Barua, Animesh; Edassery, Seby L; Yu, Yi; Abramowicz, Jacques S; Bahr, Janice M; Luborsky, Judith L

2013-01-01

Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. Hens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis. T and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors. The results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials.

Immune Cells in the Normal Ovary and Spontaneous Ovarian Tumors in the Laying Hen (Gallus domesticus) Model of Human Ovarian Cancer

PubMed Central

Bradaric, Michael J.; Penumatsa, Krishna; Barua, Animesh; Edassery, Seby L.; Yu, Yi; Abramowicz, Jacques S.; Bahr, Janice M.; Luborsky, Judith L.

2013-01-01

Background Spontaneous ovarian cancer in chickens resembles human tumors both histologically and biochemically. The goal was to determine if there are differences in lymphocyte content between normal ovaries and ovarian tumors in chickens as a basis for further studies to understand the role of immunity in human ovarian cancer progression. Methods Hens were selected using grey scale and color Doppler ultrasound to determine if they had normal or tumor morphology. Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a) cells. Ovarian sections from another set of hens (n = 26) were assessed to verify tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by morphometric analysis. Results T and B cells were more numerous in ovarian tumors than in normal ovaries by flow cytometry and immunohistochemistry. There were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found in the stroma of normal ovaries and ovarian tumors but were not associated with follicles. The number of immune cells was highest in late stage serous tumors compared to endometrioid and mucinous tumors. Conclusions The results suggest that similar to human ovarian cancer there are comparatively more immune cells in chicken ovarian tumors than in normal ovaries, and the highest immune cell content occurs in serous tumors. Thus, this study establishes a foundation for further study of tumor immune responses in a spontaneous model of ovarian cancer which will facilitate studies of the role of immunity in early ovarian cancer progression and use of the hen in pre-clinical vaccine trials. PMID:24040191

Mature Teratoma Associated with Bilateral Ovarian Carcinosarcoma - Accidental Association or Etiopathogenetic Determinism? - Case Report.

PubMed

Birla, Rodica; Catanescu, Elena-Roxana; Caragui, Andrei; Constantinoiu, Silviu

2016-01-01

Carcinosarcoma is a rare form of ovarian cancer with mixed origin, and its association with mature teratoma is extremely rare. We present the case of patient T. M. aged 67, admitted into our clinic on the 15/05/2016, F.O. 4877 for the increase of the abdominal volume. On admission, the patient was afebrile, conscious, cooperative, cardio-respiratory balanced, having the abdomen distended in volume, sharp dullness in the flanks, positive wave sign bioumoral within normal limits except: uric acid = 6.64 mg / dL, serum glucose = 113.7 mg / dl, serum total proteins = 8.65 g / dl, the albumin / globulin subunit, CRP 33.63 mg / l, sideremia 51 ug / dl, CA 125 = 588.4 IU. Abdominal ultrasound: high volume fluid and multiple perihepatic formations and multiple formations with cystic transformation in the abdomen and pelvis. CT exam describes multiple tissular masses localized intraperitoneal in the abdominal-pelvic region, sheath fluid effusion, infiltrative, with mass effect on the digestive lumens, without visible CT obstruction. Surgical treatment consisted in evacuation of the ascites fluid, excision of the tumoral lumps situated in the great omentum, omentectomy, excision of the lumps of the gastrocolic ligament, bilateral ovariectomy and hysterectomy. Postoperative simple evolution. Histopathology confirmed the diagnosis of bilateral ovarian carcinosarcoma associated with tridermic mature teratoma (presence of brain tissue areas associated with cartilage, transitional type epithelium, tubal type epithelium, endometrial stroma type and fatty tissue). IHC confirms the compatibility with the diagnosis of ovarian carcinosarcoma (mixed malignant Mullerian tumor). The patient followed adjuvant polichemotherapy. The association of teratoma with carcinosarcomatoase elements confers a poor prognosis case. Celsius.

Ovarian cancer mortality and industrial pollution.

PubMed

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

2015-10-01

We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997-2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tumor infiltrating lymphocytes in ovarian cancer

PubMed Central

Santoiemma, Phillip P; Powell, Daniel J

2015-01-01

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

Massive ovarian edema, due to adjacent appendicitis.

PubMed

Callen, Andrew L; Illangasekare, Tushani; Poder, Liina

2017-04-01

Massive ovarian edema is a benign clinical entity, the imaging findings of which can mimic an adnexal mass or ovarian torsion. In the setting of acute abdominal pain, identifying massive ovarian edema is a key in avoiding potential fertility-threatening surgery in young women. In addition, it is important to consider other contributing pathology when ovarian edema is secondary to another process. We present a case of a young woman presenting with subacute abdominal pain, whose initial workup revealed marked enlarged right ovary. Further imaging, diagnostic tests, and eventually diagnostic laparoscopy revealed that the ovarian enlargement was secondary to subacute appendicitis, rather than a primary adnexal process. We review the classic ultrasound and MRI imaging findings and pitfalls that relate to this diagnosis.

Infected colonic mass revealing a lung adenocarcinoma.

PubMed

Doussot, Alexandre; Chalumeau, Claire; Combier, Christophe; Cheynel, Nicolas; Facy, Olivier

2013-12-01

We report the case of lung adenocarcinoma revealed by infected colonic tumor in a 62-year-old man. An en bloc surgical resection was performed with uneventful recovery. The pathologic report concluded in a right mesocolic lymph node metastases from a mildly differentiated adenocarcinoma from pulmonary origin. GI metastases of lung cancer are described in the literature and are frequently asymptomatic in patient with a known primary cancer. In this patient, the complication of the metastases revealed the primary and immunochemistry permitted to adapt the systemic chemotherapy. Copyright © 2012. Published by Elsevier Masson SAS.

Impact of laparoscopic ovarian drilling on serum anti-mullerian hormone levels in patients with anovulatory Polycystic Ovarian syndrome.

PubMed

Paramu, Sobhana

2016-12-01

Anti-mullerian hormone (AMH) is a marker of the activity of recruitable ovarian follicles. It is useful in the prediction of ovarian reserve. Women with polycystic ovarian syndrome (PCOS) have elevated circulating and intrafollicular AMH levels. Laparoscopic ovarian drilling (LOD) in patients with PCOS destroys ovarian androgen-producing tissue and reduces their peripheral conversion to estrogens. Identifying factors that determine the response of patients with PCOS to LOD will help in selecting the patients who would likely benefit from this treatment. AMH is one such marker that can predict the response to LOD. To evaluate the effect of LOD on serum AMH levels among PCOS responders and non-responders and the usefulness of AMH as a tool in predicting the response to LOD, and to whether there was loss of ovarian function after LOD. This is a prospective cohort study including 30 clomiphene-resistant women with anovulatory PCOS undergoing LOD. Statistical analysis was performed to evaluate the effect of LOD on serum levels of AMH on these women. A significant fall in the levels of AMH was observed after LOD in both responders and non-responders (p<0.001). Women with AMH >8.3 ng/mL showed a significantly lower ovulation rate (33.3%). LOD was not associated with a risk of diminished ovarian reserve. LOD is an effective first-line treatment for women with PCOS who are clomiphene resistant. LOD has no negative effect on ovarian reserve. AMH is a useful marker in predicting the outcome of LOD.

Primary mucinous adenocarcinoma of the vulva, intestinal type

PubMed Central

Lee, In Ho; Kim, Mi Kyung; Lee, Yoo Kyung; Hong, Sung Ran

2017-01-01

Primary vulva malignancy is a rare gynecologic malignancy. Most of them are squamous cell carcinomas and adenocarcinomas are much less common. Intestinal type is a rare variant of primary adenocarcinoma of the vulva. It histologically resembles mucinous colonic carcinomas. Origin from cloacal remnants has been suggested but remains speculative. A 64-year-old woman was referred to our clinic with a 1-month history of an itching vulva mass. An incisional biopsy was performed at other hospital and disclosed adenocarcinoma of intestinal type. Extensive workups were performed to detect other underlying carcinomas but revealed nothing abnormal. She underwent wide local excision without lymph node dissection for a primary vulva carcinoma. She received no adjuvant therapy and has been free from recurrent disease for 12 months after surgery. The authors report a rare case and review the relevant literature. PMID:28791269

Environmentally Induced Epigenetic Transgenerational Inheritance of Ovarian Disease

PubMed Central

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. PMID:22570695

Photoacoustic characterization of ovarian tissue

NASA Astrophysics Data System (ADS)

Aguirre, Andres; Gamelin, John; Guo, Puyun; Yan, Shikui; Sanders, Mary; Brewer, Molly; Zhu, Quing

2009-02-01

Ovarian cancer has the highest mortality of all gynecologic cancers with a five-year survival rate of only 30%. Because current imaging techniques (ultrasound, CT, MRI, PET) are not capable of detecting ovarian cancer early, most diagnoses occur in later stages (III/IV). Thus many women are not correctly diagnosed until the cancer becomes widely metastatic. On the other hand, while the majority of women with a detectable ultrasound abnormality do not harbor a cancer, they all undergo unnecessary oophorectomy. Hence, new imaging techniques that can provide functional and molecular contrasts are needed for improving the specificity of ovarian cancer detection and characterization. One such technique is photoacoustic imaging, which has great potential to reveal early tumor angiogenesis through intrinsic optical absorption contrast from hemoglobin or extrinsic contrast from conjugated agents binding to appropriate molecular receptors. To better understand the cancer disease process of ovarian tissue using photoacoustic imaging, it is necessary to first characterize the properties of normal ovarian tissue. We have imaged ex-vivo ovarian tissue using a 3D co-registered ultrasound and photoacoustic imaging system. The system is capable of volumetric imaging by means of electronic focusing. Detecting and visualizing small features from multiple viewing angles is possible without the need for any mechanical movement. The results show strong optical absorption from vasculature, especially highly vascularized corpora lutea, and low absorption from follicles. We will present correlation of photoacoustic images from animals with histology. Potential application of this technology would be the noninvasive imaging of the ovaries for screening or diagnostic purposes.

Biological Basis for Chemoprevention of Ovarian Cancer

DTIC Science & Technology

2000-10-01

potent apoptotic effect on ovarian epithelial cells, the use of levonorgestrel in chemoprevention of ovarian cancer is being explored in chickens and women...A chemoprevention trial is ongoing in chickens and we will begin a trial to determine whether levonorgestrel induces apoptosis in the ovarian epithelium of women undergoing oophorectomy.

Ovarian cancer susceptibility alleles and risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

PubMed

Ramus, Susan J; Antoniou, Antonis C; Kuchenbaecker, Karoline B; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M; Nathanson, Katherine L; Rebbeck, Timothy R; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E; Aalfs, Cora M; Meijers-Heijboer, Hanne E J; van Asperen, Christi J; van Roozendaal, K E P; Hoogerbrugge, Nicoline; Collée, J Margriet; Kriege, Mieke; van der Luijt, Rob B; Peock, Susan; Frost, Debra; Ellis, Steve D; Platte, Radka; Fineberg, Elena; Evans, D Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J; Walker, Lisa; Porteous, Mary E; Kennedy, M John; Pathak, Harsh; Godwin, Andrew K; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v O; Ejlertsen, Bent; Johannsson, Oskar Th; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Ewart Toland, Amanda; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Issacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Iganacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B; Karlan, Beth Y; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A; Beattie, Mary S; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B; Neuhausen, Susan L; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H; Mai, Phuong L; Andrulis, Irene L; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D P; Gayther, Simon A; Simard, Jacques; Easton, Douglas F; Couch, Fergus J; Chenevix-Trench, Georgia

2012-04-01

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67-0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21-1.83) P-trend = 1.8 × 10(-4), rs717852 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.6 × 10(-4), rs9303542 HR = 1.16 (95% CI: 1.02-1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81-0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10-1.42) P-trend = 6.1 × 10(-4). The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. © 2012 Wiley Periodicals, Inc.

Ovarian Cancer Susceptibility Alleles and Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers

PubMed Central

Ramus, Susan J.; Antoniou, Antonis C; Kuchenbaecker, Karoline B.; Soucy, Penny; Beesley, Jonathan; Chen, Xiaoqing; McGuffog, Lesley; Sinilnikova, Olga M.; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Thomassen, Mads; Gerdes, Anne-Marie; Kruse, Torben A.; Jensen, Uffe Birk; Skytte, Anne-Bine; Caligo, Maria A.; Liljegren, Annelie; Lindblom, Annika; Olsson, Håkan; Kristoffersson, Ulf; Stenmark-Askmalm, Marie; Melin, Beatrice; Domchek, Susan M.; Nathanson, Katherine L.; Rebbeck, Timothy R.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna; Złowocka, Elżbieta; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Cybulski, Cezary; Toloczko-Grabarek, Aleksandra; Osorio, Ana; Benitez, Javier; Duran, Mercedes; Tejada, Maria-Isabel; Hamann, Ute; Rookus, Matti; van Leeuwen, Flora E.; Aalfs, Cora M.; Meijers-Heijboer, Hanne E.J.; van Asperen, Christi J.; van Roozendaal, K.E.P.; Hoogerbrugge, Nicoline; Collée, J. Margriet; Kriege, Mieke; van der Luijt, Rob B.; Peock, Susan; Frost, Debra; Ellis, Steve D.; Platte, Radka; Fineberg, Elena; Evans, D. Gareth; Lalloo, Fiona; Jacobs, Chris; Eeles, Ros; Adlard, Julian; Davidson, Rosemarie; Eccles, Diana; Cole, Trevor; Cook, Jackie; Paterson, Joan; Douglas, Fiona; Brewer, Carole; Hodgson, Shirley; Morrison, Patrick J.; Walker, Lisa; Porteous, Mary E.; Kennedy, M. John; Pathak, Harsh; Godwin, Andrew K.; Stoppa-Lyonnet, Dominique; Caux-Moncoutier, Virginie; de Pauw, Antoine; Gauthier-Villars, Marion; Mazoyer, Sylvie; Léoné, Mélanie; Calender, Alain; Lasset, Christine; Bonadona, Valérie; Hardouin, Agnès; Berthet, Pascaline; Bignon, Yves-Jean; Uhrhammer, Nancy; Faivre, Laurence; Loustalot, Catherine; Buys, Saundra; Daly, Mary; Miron, Alex; Terry, Mary Beth; Chung, Wendy K.; John, Esther M; Southey, Melissa; Goldgar, David; Singer, Christian F; Tea, Muy-Kheng; Pfeiler, Georg; Fink-Retter, Anneliese; Hansen, Thomas v. O.; Ejlertsen, Bent; Johannsson, Oskar Th.; Offit, Kenneth; Kirchhoff, Tomas; Gaudet, Mia M.; Vijai, Joseph; Robson, Mark; Piedmonte, Marion; Phillips, Kelly-Anne; Van Le, Linda; Hoffman, James S; Toland, Amanda Ewart; Montagna, Marco; Tognazzo, Silvia; Imyanitov, Evgeny; Isaacs, Claudine; Janavicius, Ramunas; Lazaro, Conxi; Blanco, Ignacio; Tornero, Eva; Navarro, Matilde; Moysich, Kirsten B.; Karlan, Beth Y.; Gross, Jenny; Olah, Edith; Vaszko, Tibor; Teo, Soo-Hwang; Ganz, Patricia A.; Beattie, Mary S.; Dorfling, Cecelia M; van Rensburg, Elizabeth J; Diez, Orland; Kwong, Ava; Schmutzler, Rita K.; Wappenschmidt, Barbara; Engel, Christoph; Meindl, Alfons; Ditsch, Nina; Arnold, Norbert; Heidemann, Simone; Niederacher, Dieter; Preisler-Adams, Sabine; Gadzicki, Dorotehea; Varon-Mateeva, Raymonda; Deissler, Helmut; Gehrig, Andrea; Sutter, Christian; Kast, Karin; Fiebig, Britta; Schäfer, Dieter; Caldes, Trinidad; de la Hoya, Miguel; Nevanlinna, Heli; Aittomäki, Kristiina; Plante, Marie; Spurdle, Amanda B.; Neuhausen, Susan L.; Ding, Yuan Chun; Wang, Xianshu; Lindor, Noralane; Fredericksen, Zachary; Pankratz, V. Shane; Peterlongo, Paolo; Manoukian, Siranoush; Peissel, Bernard; Zaffaroni, Daniela; Bonanni, Bernardo; Bernard, Loris; Dolcetti, Riccardo; Papi, Laura; Ottini, Laura; Radice, Paolo; Greene, Mark H.; Mai, Phuong L.; Andrulis, Irene L.; Glendon, Gord; Ozcelik, Hilmi; Pharoah, Paul D.P.; Gayther, Simon A.; Simard, Jacques; Easton, Douglas F.; Couch, Fergus J.; Chenevix-Trench, Georgia

2012-01-01

Germline mutations in BRCA1 and BRCA2 are associated with increased risks of breast and ovarian cancer. A genome-wide association study (GWAS) identified six alleles associated with risk of ovarian cancer for women in the general population. We evaluated four of these loci as potential modifiers of ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Four single-nucleotide polymorphisms (SNPs), rs10088218 (at 8q24), rs2665390 (at 3q25), rs717852 (at 2q31), and rs9303542 (at 17q21), were genotyped in 12,599 BRCA1 and 7,132 BRCA2 carriers, including 2,678 ovarian cancer cases. Associations were evaluated within a retrospective cohort approach. All four loci were associated with ovarian cancer risk in BRCA2 carriers; rs10088218 per-allele hazard ratio (HR) = 0.81 (95% CI: 0.67–0.98) P-trend = 0.033, rs2665390 HR = 1.48 (95% CI: 1.21–1.83) P-trend = 1.8 × 10−4, rs717852 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.6 × 10−4, rs9303542 HR = 1.16 (95% CI: 1.02–1.33) P-trend = 0.026. Two loci were associated with ovarian cancer risk in BRCA1 carriers; rs10088218 per-allele HR = 0.89 (95% CI: 0.81–0.99) P-trend = 0.029, rs2665390 HR = 1.25 (95% CI: 1.10–1.42) P-trend = 6.1 × 10−4. The HR estimates for the remaining loci were consistent with odds ratio estimates for the general population. The identification of multiple loci modifying ovarian cancer risk may be useful for counseling women with BRCA1 and BRCA2 mutations regarding their risk of ovarian cancer. PMID:22253144

Effect of the aqueous extract of Justicia insularis T. Anders (Acanthaceae) on ovarian folliculogenesis and fertility of female rats.

PubMed

Telefo, Phelix Bruno; Tagne, Simon Richard; Koona, Olga Elodie Sandrine; Yemele, Didiane M; Tchouanguep, Félicité M

2012-01-01

Justicia insularis T. Anders (Acanthaceae) is a medicinal plant whose leaves and those of three other plants are mixed for the preparation of a concoction used to improve fertility and to reduce labour pains in women of the Western Region of Cameroon. Previous studies have demonstrated the inducing potential on ovarian folliculogenesis and steroidogenesis of the aqueous extract of the leaf mixture (ADHJ) of four medicinal plants (Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis) among which the later represented the highest proportion. This study was aimed at evaluating the ovarian inducing potential of J. insularis in immature female rats. Various doses of the aqueous extract of J. insularis were daily and orally given, for 20 days, to immature female rats distributed into four experimental groups of twenty animals each. At the end of the experimental period some biochemical and physiological parameters of ovarian function were assayed. The administration of the aqueous extract of Justicia insularis significantly induced an early vaginal opening in all treated groups (P < 0.001) as well as an increase (at doses of 50 or 100 mg/kg) in the number of hemorrhagic points, Corpus luteum, implantation sites, ovarian weight, uterine and ovarian proteins. Ovarian cholesterol level (P < 0.05) significantly decreased in animals treated with the lowest dose (12.5 mg/kg). The evaluation of the toxicological effects of the extract on pregnancy showed that it significantly increased pre- and post-implantation losses, resorption index and decreased the rate of nidation as well as litter's weight. These results suggest that the aqueous extract of Justicia insularis induces ovarian folliculogenesis thus justifying its high proportion in the leaf mixture of ADHJ.

Ovarian torsion in a three-year-old girl.

PubMed

Ochsner, Todd Justin; Roos, Joel A; Johnson, Andrew S; Henderson, Janet L

2010-05-01

Ovarian torsion is the fifth most encountered gynecological emergency requiring surgery. Representing only 2.7% of surgical emergencies, it is an entity that is worth being familiar with in the emergency department (ED). Untreated ovarian torsion may result in loss of ovarian function, tissue necrosis, and death from thromboembolism or sepsis. Presenting with vague symptoms and abdominal pain, diagnosing ovarian torsion can be difficult, especially in children. The objective of this article is to present a case of pediatric ovarian torsion and to review its epidemiology, diagnosis, and treatment. A 3-year-old girl presented to the ED with vomiting, fever, anorexia, and abdominal pain. Initially diagnosed with appendicitis by physical examination and computed tomography scan, this patient was taken to the operating room for surgical exploration. The patient was subsequently found to have ovarian torsion, which was treated appropriately. Although a rare phenomenon, this case serves to increase awareness of the clinical presentation of ovarian torsion in the pediatric patient. Abdominal pain in the female child represents a challenging differential diagnosis, for which a physician must consider ovarian torsion. Copyright (c) 2010. Published by Elsevier Inc.

Ovarian minimal residual disease in chronic myeloid leukaemia.

PubMed

Abir, Ronit; Aviram, Adina; Feinmesser, Meora; Stein, Jerry; Yaniv, Isaac; Parnes, Doris; Ben-Haroush, Avi; Meirow, Dror; Rabizadeh, Esther; Fisch, Benjamin

2014-02-01

The options for fertility preservation include cryopreservation of ovarian tissue. Although transplantation of cryopreserved-thawed ovarian tissue in cancer survivors has resulted in live births, there is evidence of malignancy involvement in ovarian tissue, especially in leukaemia. The objectives of this study were to investigate the involvement of chronic myeloid leukaemia (CML) in ovaries by both pathological/immunohistochemical methods and PCR for the identification of the Philadelphia chromosome (BCR-ABL transcripts). The patient was a survivor of paediatric CML whose ovaries were cryopreserved. The patient became infertile and requested ovarian reimplantation in adulthood. Pathological examinations of ovarian tissue with immunohistochemical stainings, quantitative PCR and two-step nested PCR were applied to identify BCR-ABL transcripts. Despite the lack of positive pathological/immunohistochemical evidence, PCR and two-step nested PCR revealed that the ovary was contaminated by malignant minimal residual CML. Survivors of childhood CML may harbour minimal residual disease in the ovaries. This finding stresses the danger of reseeding cancer by ovarian grafting, especially in patients with leukaemia. If ovarian grafting is considered, reimplantation should be preceded by examination of ovarian samples both pathologically and by molecular techniques. On the basis of molecular findings, ovarian autografting was not recommended in this case report. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Association of Ovarian Tumor β2-Adrenergic Receptor Status with Ovarian Cancer Risk Factors and Survival.

PubMed

Huang, Tianyi; Tworoger, Shelley S; Hecht, Jonathan L; Rice, Megan S; Sood, Anil K; Kubzansky, Laura D; Poole, Elizabeth M

2016-12-01

The β 2 -adrenergic signaling pathway mediates the effects of chronic stress on ovarian cancer progression in mouse models. The relevance of this pathway to human ovarian cancer remains unknown. We assessed tumor expression of β 2 -adrenergic receptor (ADRB2) using tissue microarrays in 237 ovarian cancer cases from the Nurses' Health Studies (NHS/NHSII). Competing risks Cox regression was used to evaluate whether associations of reproductive, hormonal, and psychosocial factors with ovarian cancer risk differed by ADRB2. We also examined the association between tumor ADRB2 expression and ovarian cancer survival. Forty-five (19%) cases were positive for ADRB2 staining. High levels of anxiety symptoms were positively associated with ADRB2-positive tumors (HR, 2.59; 95% confidence interval [CI], 1.15-5.84) but not with ADRB2-negative tumors (HR, 1.16; 95% CI, 0.81-1.66; P heterogeneity = 0.07). We observed similar results for depression. No associations were observed for job strain, caregiving stress, or widowhood for either positive or negative ADRB2 status. Lifetime ovulatory years were more strongly associated with ADRB2-positive tumors (HR per 5 years, 1.60; 95% CI, 1.15-2.21) compared with ADRB2-negative tumors (HR, 1.11; 95% CI, 0.96-1.27; P heterogeneity = 0.04). Significant heterogeneity by ADRB2 was also observed for parity (P heterogeneity = 0.01), oral contraceptive use (P heterogeneity = 0.03), and age at menopause (P heterogeneity = 0.04). Tumor expression of ADRB2 was not associated with ovarian cancer mortality (HR, 1.05; 95% CI, 0.69-1.59). Several stress- and ovulation-related factors were differentially associated with ovarian tumors responsive to β 2 -adrenergic signaling. Replication in larger studies is warranted to confirm the role of β 2 -adrenergic signaling in ovarian cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1587-94. ©2016 AACR. ©2016 American Association for Cancer Research.

Ovarian aging: latest thoughts on assessment and management.

PubMed

Younis, Johnny S

2011-12-01

In the past few decades, women have been intentionally delaying pregnancy and ovarian aging has become one of the most detrimental factors of pregnancy achievement. This review will discuss contemporary methods of ovarian aging assessment and present an overview of current management strategies. Antimullerian hormone (AMH) and antral follicle count (AFC) seem to be the most reliable predictors of ovarian aging appraisal. Nevertheless, they have not been shown to predict pregnancy achievement in assisted reproduction. Heritability has a high impact on ovarian aging. Employing several genetic approaches, it is now being widely investigated, but the task is far from being accomplished. Although multivariate models have not been proven to be superior to AFC, new data support the notion that chronological age and genetic markers inclusion may increase their reliability. Several strategies have been suggested to treat ovarian aging in assisted reproductive technology (ART) settings. None of the stimulation protocol manipulations have been found to be advantageous and individualization of treatment is still recommended. Ovarian priming by different androgen preparations has been shown to be promising but more randomized controlled trials are needed to support these findings. Except for oocyte donation other ART strategies have not shown a convincing benefit for ovarian aging. The new development of oocyte vitrification may well introduce opportunities for fertility preservation to women at risk of ovarian aging. Proper assessment and detection of ovarian aging, employing current or developing predictors of ovarian reserve, especially genetic tests, may enable health providers to recommend, at appropriate biological time, early pregnancy achievement or fertility preservation in women at risk.

Anthropometric characteristics and ovarian cancer risk and survival.

PubMed

Minlikeeva, Albina N; Moysich, Kirsten B; Mayor, Paul C; Etter, John L; Cannioto, Rikki A; Ness, Roberta B; Starbuck, Kristen; Edwards, Robert P; Segal, Brahm H; Lele, Sashikant; Odunsi, Kunle; Diergaarde, Brenda; Modugno, Francesmary

2018-02-01

Multiple studies have examined the role of anthropometric characteristics in ovarian cancer risk and survival; however, their results have been conflicting. We investigated the associations between weight change, height and height change and risk and outcome of ovarian cancer using data from a large population-based case-control study. Data from 699 ovarian cancer cases and 1,802 controls who participated in the HOPE study were included. We used unconditional logistic regression adjusted for age, race, number of pregnancies, use of oral contraceptives, and family history of breast or ovarian cancer to examine the associations between self-reported height and weight and height change with ovarian cancer risk. Cox proportional hazards regression models adjusted for age and stage were used to examine the association between the exposure variables and overall and progression-free survival among ovarian cancer cases. We observed an increased risk of ovarian cancer mortality and progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI 1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining it back multiple times was inversely associated with both ovarian cancer risk, OR 0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times, and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller during adolescence and adulthood was associated with increased risk of mortality. Taller stature and weight gain over lifetime were not related to ovarian cancer risk. Our results suggest that height and weight and their change over time may influence ovarian cancer risk and survival. These findings suggest that biological mechanisms underlying these associations may be hormone driven and may play an important role in relation to ovarian carcinogenesis and tumor progression.

Global ovarian cancer health disparities

PubMed Central

Chornokur, Ganna; Amankwah, Ernest K.; Schildkraut, Joellen M.; Phelan, Catherine M.

2013-01-01

Objective The objective of this article is to broadly review the scientific literature and summarize the most up-to-date findings on ovarian cancer health disparities worldwide and in the United States (U.S.). Methods The present literature on disparities in ovarian cancer was reviewed. Original research and relevant review articles were included. Results Ovarian cancer health disparities exist worldwide and in the U.S. Ovarian cancer disproportionately affect African American women at all stages of the disease, from presentation through treatment, and ultimately increased mortality and decreased survival, compared to non-Hispanic White women. Increased mortality is likely to be explained by unequal access to care and non-standard treatment regimens frequently administered to African American women, but may also be attributed to genetic susceptibility, acquired co-morbid conditions and increased frequency of modifiable risk factors, albeit to substantially lesser extent. Unequal access to care is, in turn, largely a consequence of lower socioeconomic status and lack of private health insurance coverage among the African American population. Conclusions Our findings suggest the need for policy changes aimed at facilitating equal access to quality medical care. At the same time, further research is necessary to fully resolve racial disparities in ovarian cancer. PMID:23266352

Problems Experienced by Ovarian Cancer Survivors During Treatment.

PubMed

Keim-Malpass, Jessica; Mihalko, Shannon L; Russell, Greg; Case, Doug; Miller, Brigitte; Avis, Nancy E

To identify problems at different treatment points (early treatment, mid-treatment, early posttreatment, and late posttreatment) among women with ovarian cancer. Longitudinal and cross-sectional study design. An academic and community clinical cancer center in the Southeastern United States. Sixty-eight women with Stage I to IV ovarian cancer. Variables assessed included reported problems (physical, psychosocial, pain, marital, medical interaction), social support, optimism, and responses to open-ended questions. Analysis involved mixed models for longitudinal repeated measures and unpaired t tests and content analysis to describe responses to open-ended questions. Physical and psychosocial problems were greatest during early treatment and decreased throughout the treatment trajectory. Women with greater levels of social support and optimism at baseline had fewer problems over time. Women who did not have trouble paying for basics had fewer problems related to pain and psychological problems. Problems across all domains must be addressed throughout the treatment trajectory, even after chemotherapy has ended. Nurses are well positioned to refer women appropriately to social workers and clinical navigators across all domains of care and should consider systematic assessment of patient-reported problems as a routine form of practice. Copyright © 2017 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.

Health care professionals' attitudes towards population-based genetic testing and risk-stratification for ovarian cancer: a cross-sectional survey.

PubMed

Hann, Katie E J; Fraser, Lindsay; Side, Lucy; Gessler, Sue; Waller, Jo; Sanderson, Saskia C; Freeman, Madeleine; Jacobs, Ian; Lanceley, Anne

2017-12-16

Ovarian cancer is usually diagnosed at a late stage when outcomes are poor. Personalised ovarian cancer risk prediction, based on genetic and epidemiological information and risk stratified management in adult women could improve outcomes. Examining health care professionals' (HCP) attitudes to ovarian cancer risk stratified management, willingness to support women, self-efficacy (belief in one's own ability to successfully complete a task), and knowledge about ovarian cancer will help identify training needs in anticipation of personalised ovarian cancer risk prediction being introduced. An anonymous survey was distributed online to HCPs via relevant professional organisations in the UK. Kruskal-Wallis tests and pairwise comparisons were used to compare knowledge and self-efficacy scores between different types of HCPs, and attitudes toward population-based genetic testing and risk stratified management were described. Content analysis was undertaken of free text responses concerning HCPs willingness to discuss risk management options with women. One hundred forty-six eligible HCPs completed the survey: oncologists (31%); genetics clinicians (30%); general practitioners (22%); gynaecologists (10%); nurses (4%); and 'others'. Scores for knowledge of ovarian cancer and genetics, and self-efficacy in conducting a cancer risk consultation were generally high but significantly lower for general practitioners compared to genetics clinicians, oncologists, and gynaecologists. Support for population-based genetic testing was not high (<50%). Attitudes towards ovarian cancer risk stratification were mixed, although the majority of participants indicated a willingness to discuss management options with patients. Larger samples are required to investigate attitudes to population-based genetic testing for ovarian cancer risk and to establish why some HCPs are hesitant to offer testing to all adult female patients. If ovarian cancer risk assessment using genetic testing and non

[In situ adenocarcinoma of the uterus cervix: difficulties of its cytohistological diagnosis].

PubMed

Tranbaloc, P

2002-04-01

In situ adenocarcinoma is regarded as the precursor of invasive adenocarcinoma. It is asymptomatic and early diagnosis relies solely on cytopathologist. It is usually discovered on a cone for squamous CIN. When diagnosis is made by biopsy, conisation is required to exclude invasive adenocarcinoma. Lesion is histologically characterised by epitheliomatous transformation of endocervical glands without invasion of the chorion. By the appearance of glandular cells, different histological varieties are described. They have no influence on the prognosis. Several benign lesions may mimic adenocarcinoma: tubal metaplasia, glandular atypia due to inflammation or irradiation, mesonephric remnants and microglandular hyperplasia. Precursor lesions (atypical hyperplasia, glandular dysplasia, CIGNI and II) are badly morphologically defined. Preferential location of in situ adenocarcinoma is the transformation zone. Because of this topography, if the surgical margins are disease free, conisation alone may be adequate therapy. HPV infection (mainly HPV 18) are incriminated in its pathogenesis.

Cytomorphological features of ALK-positive lung adenocarcinomas: psammoma bodies and signet ring cells.

PubMed

Pareja, Fresia; Crapanzano, John P; Mansukhani, Mahesh M; Bulman, William A; Saqi, Anjali

2015-03-01

Correlation between histology and genotype has been described in lung adenocarcinomas. For example, studies have demonstrated that adenocarcinomas with an anaplastic lymphoma kinase (ALK) gene rearrangement may have mucinous features. The objective of the current study was to determine whether a similar association can be identified in cytological specimens. A retrospective search for ALK-rearranged cytopathology (CP) and surgical pathology (SP) lung carcinomas was conducted. Additional ALK-negative (-) lung adenocarcinomas served as controls. For CP and SP cases, the clinical data (i.e., age, sex, and smoking history), architecture, nuclear features, presence of mucin-containing cells (including signet ring cells), and any additional salient characteristics were evaluated. The search yielded 20 ALK-positive (+) adenocarcinomas. Compared with patients with ALK(-) lung adenocarcinomas (33 patients; 12 with epidermal growth factor receptor [EGFR]-mutation, 11 with Kristen rat sarcoma [KRAS]-mutation, and 10 wild-type adenocarcinomas), patients with ALK(+) adenocarcinoma presented at a younger age; and there was no correlation noted with sex or smoking status. The most common histological pattern in SP was papillary/micropapillary. Mucinous features were associated with ALK rearrangement in SP specimens. Signet ring cells and psammoma bodies were evident in and significantly associated with ALK(+) SP and CP specimens. However, psammoma bodies were observed in rare adenocarcinomas with an EGFR mutation. Both the ALK(+) and ALK(-) groups had mostly high nuclear grade. Salient features, including signet ring cells and psammoma bodies, were found to be significantly associated with ALK(+) lung adenocarcinomas and are identifiable on CP specimens. Recognizing these may be especially helpful in the molecular triage of scant CP samples. © 2014 American Cancer Society.

Heterogeneous Cadherin Expression and Multicellular Aggregate Dynamics in Ovarian Cancer Dissemination.

PubMed

Klymenko, Yuliya; Johnson, Jeffrey; Bos, Brandi; Lombard, Rachel; Campbell, Leigh; Loughran, Elizabeth; Stack, M Sharon

2017-07-01

Epithelial ovarian carcinoma spreads via shedding of cells and multicellular aggregates (MCAs) from the primary tumor into peritoneal cavity, with subsequent intraperitoneal tumor cell:mesothelial cell adhesion as a key early event in metastatic seeding. Evaluation of human tumor extracts and tissues confirms that well-differentiated ovarian tumors express abundant E-cadherin (Ecad), whereas advanced lesions exhibit upregulated N-cadherin (Ncad). Two expression patterns are observed: "mixed cadherin," in which distinct cells within the same tumor express either E- or Ncad, and "hybrid cadherin," wherein single tumor cell(s) simultaneously expresses both cadherins. We demonstrate striking cadherin-dependent differences in cell-cell interactions, MCA formation, and aggregate ultrastructure. Mesenchymal-type Ncad+ cells formed stable, highly cohesive solid spheroids, whereas Ecad+ epithelial-type cells generated loosely adhesive cell clusters covered by uniform microvilli. Generation of "mixed cadherin" MCAs using fluorescently tagged cell populations revealed preferential sorting into cadherin-dependent clusters, whereas mixing of cell lines with common cadherin profiles generated homogeneous aggregates. Recapitulation of the "hybrid cadherin" Ecad+/Ncad+ phenotype, via insertion of the CDH2 gene into Ecad+ cells, resulted in the ability to form heterogeneous clusters with Ncad+ cells, significantly enhanced adhesion to organotypic mesomimetic cultures and peritoneal explants, and increased both migration and matrix invasion. Alternatively, insertion of CDH1 gene into Ncad+ cells greatly reduced cell-to-collagen, cell-to-mesothelium, and cell-to-peritoneum adhesion. Acquisition of the hybrid cadherin phenotype resulted in altered MCA surface morphology with increased surface projections and increased cell proliferation. Overall, these findings support the hypothesis that MCA cadherin composition impacts intraperitoneal cell and MCA dynamics and thereby affects

Enhanced p53 gene transfer to human ovarian cancer cells using the cationic nonviral vector, DDC.

PubMed

Kim, Chong-Kook; Choi, Eun-Jeong; Choi, Sung-Hee; Park, Jeong-Sook; Haider, Khawaja Hasnain; Ahn, Woong Shick

2003-08-01

Previously we have formulated a new cationic liposome, DDC, composed of dioleoyltrimethylamino propane (DOTAP), 1,2-dioeoyl-3-phosphophatidylethanolamine (DOPE), and cholesterol (Chol), and it efficiently delivered plasmid DNA into ovarian cancer cells. Mutations in the p53 tumor suppressor gene are the most common molecular genetic abnormalities to be described in ovarian cancer. However, there has been so far no report of nonviral vector-mediated p53 gene deliveries in ovarian cancer. In this study, wild-type p53 DNA was transfected into the ovarian cancer cells, using the DDC as a nonviral vector and the expression and activity of p53 gene were evaluated both in vitro and in vivo. DDC liposomes were prepared by mixing DOTAP:DOPE:Chol in a 1:0.7:0.3 molar ratio using the extrusion method. Plasmid DNA (pp53-EGFP) and DDC complexes were transfected into ovarian carcinoma cells (OVCAR-3 cells) and gene expression was determined by reverse transcription-polymerase chain reaction and Western blot analysis. The cellular growth inhibition and apoptosis of DDC-mediated p53 transfection were assessed by trypan blue exclusion assay and annexin-V staining, respectively. The OVCAR-3 cells treated with DDC/pp53-EGFP complexes were inoculated into female balb/c nude mice and tumor growth was observed. The transfection of liposome-complexed p53 gene resulted in a high level of wild-type p53 mRNA and protein expressions in OVCAR-3 cells. In vitro cell growth assay showed growth inhibition of cancer cells transfected with DDC/pp53-EGFP complexes compared with the control cells. The reestablishment of wild-type p53 function in ovarian cancer cells restored the apoptotic pathway. Following the inoculation of DDC/pp53-EGFP complexes, the volumes of tumors in nude mice were significantly reduced more than 60% compared to the control group. The DDC-mediated p53 DNA delivery may have the potential for clinical application as nonviral vector-mediated ovarian cancer therapy due to its

Live birth after ovarian tissue transplant

NASA Astrophysics Data System (ADS)

Lee, D. M.; Yeoman, R. R.; Battaglia, D. E.; Stouffer, R. L.; Zelinski-Wooten, M. B.; Fanton, J. W.; Wolf, D. P.

2004-03-01

Radiation and high-dose chemotherapy may render women with cancer prematurely sterile, a side-effect that would be avoided if ovarian tissue that had been removed before treatment could be made to function afterwards. Live offspring have been produced from transplanted ovarian tissue in mice and sheep but not in monkeys or humans, although sex steroid hormones are still secreted. Here we describe the successful transplantation of fresh ovarian tissue to a different site in a monkey, which has led to the birth of a healthy female after oocyte production, fertilization and transfer to a surrogate mother. The ectopically grafted tissue functions without surgical connection to major blood vessels and sets the stage for the transplantation of cryopreserved ovarian tissue in humans.

Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung.

PubMed

Haneda, Hiroshi; Sasaki, Hidefumi; Shimizu, Shigeki; Endo, Katsuhiko; Suzuki, Eriko; Yukiue, Haruhiro; Kobayashi, Yoshihiro; Yano, Motoki; Fujii, Yoshitaka

2006-04-01

Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.

Anti-Mullerian Hormone: A Marker of Ovarian Reserve and its Association with Polycystic Ovarian Syndrome.

PubMed

Verma, Anil Kumar; Rajbhar, Sarita; Mishra, Jyoti; Gupta, Mayank; Sharma, Mratunjai; Deshmukh, Geeta; Ali, Wahid

2016-12-01

Anti-Mullerian Hormone (AMH) is a useful endocrine marker for assessing the ovarian reserve. AMH serum level reflects the number of follicles that have made the transition from the primordial pool into the growing follicle pool, and it is not controlled by gonadotropins. The present study was conducted to correlate serum AMH levels with Polycystic Ovarian Syndrome (PCOS) and type of treatment protocol. Serum AMH levels were performed in the early follicular phase (on 2 nd day of menstrual cycle) both in infertile females including PCOS and control women. The results were analyzed in relation to age, Body Mass Index (BMI), ovarian volume, serum Follicle Stimulating Hormone (FSH) levels, Antral Follicle Count (AFC), type of treatment protocols and also in association with PCOS patients. The serum levels of AMH were measured in all the participants on 2 nd day of menstrual cycle using ultra sensitive Enzyme Linked Immunosorbent Assay (ELISA). The plasma AMH levels were significantly higher in women with polycystic ovarian syndrome. The significant association was seen between FSH and AFC with AMH. However, no significant association was observed between AMH levels with age, BMI, ovarian volume and type of treatment protocols. The serum AMH measurement was significantly higher in PCOS patients. No association with type of treatment protocol was obtained.

Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case Report.

PubMed

Zhang, Geng-Yuan; Mao, Jie; Zhao, Bin; Long, Bo; Zhan, Hao; Zhang, Jun-Qiang; Zhou, Hui-Nian; Guo, Ling-Yun; Jiao, Zuo-Yi

2017-01-01

Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary tract which has a low incidence rate and nonspecific symptoms. It is difficult to diagnose early, and the misdiagnosis rate is high. CT, MRI, upper gastrointestinal endoscopy, and other advanced imaging modalities should be combined to make a comprehensive evaluation. The diagnostic confirmation of this tumor type mainly depends on the pathological examination. The combination of surgery with other treatment modalities is effective. A review of reports on duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990. However, there are few reports on neoadjuvant chemotherapy for the disease. In this report, preoperative S-1 in combination with oxaliplatin neoadjuvant chemotherapy achieved a complete pathological response in the treatment of duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to be further verified. © 2017 S. Karger AG, Basel.

AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma

NASA Astrophysics Data System (ADS)

Rita, R.; Delyuzar; Laksmi, L. I.

2018-03-01

Benign prostatic hyperplasia and prostatic adenocarcinoma were common diseases and usually occurred after the 5th decade of life. The problem in diagnosing using Hematoxylin and Eosin staining was how to differentiate whether it is benign or malignant zone. Therefore, proliferating markers, such as AgNOR, could be helping to over this difficulty. A descriptive study using consecutive sampling as the method of sample recruiting was conducted to describe AgNOR histochemical expression in benign prostatic hyperplasia and prostatic adenocarcinoma. AgNOR staining was done in 13 benign prostatic hyperplasia samples and 7 prostatic adenocarcinoma samples, which have been confirmed using p63 immunohistochemical staining before. Benign prostatic hyperplasia usually showed lower AgNOR proliferating activity while all of theprostatic adenocarcinoma (100%) had high AgNOR proliferating activity.

Nasal and paranasal adenocarcinomas with neuroendocrine differentiation in dogs.

PubMed

Ninomiya, F; Suzuki, S; Tanaka, H; Hayashi, S; Ozaki, K; Narama, I

2008-03-01

Tumors of the nasal cavity or paranasal sinuses of 18 dogs were examined histopathologically, immunohistochemically, and histochemically. The tumors were classified histologically as 13 adenocarcinomas, 3 transitional carcinomas, 1 squamous cell carcinoma, and 1 adenosquamous carcinoma. Tumor cells were strongly immunoreactive for broad-spectrum cytokeratins in all cases, for cytokeratin 8/18 in 16 cases, and for cytokeratin 19 in 17 cases. None of the 18 carcinomas had cytologic or histologic features indicative of neuroendocrine differentiation, yet tumor cells in 5 of the 13 adenocarcinomas were argyrophilic and immunohistochemically positive for synaptophysin and chromogranin A. Results of this study indicate that neuroendocrine markers may be detected immunohistochemically and histochemically in canine nasal or paranasal adenocarcinomas despite the lack of typical histologic features of neuroendocrine differentiation.

Human epididymis protein 4 immunostaining of malignant ascites differentiates cancer of Müllerian origin from gastrointestinal cancer.

PubMed

Stiekema, Anna; Van de Vijver, Koen K; Boot, Henk; Broeks, Annegien; Korse, Catharina M; van Driel, Willemien J; Kenter, Gemma G; Lok, Christianne A R

2017-03-01

An accurate diagnosis of cancer of Müllerian origin is required before the initiation of treatment. An overlap in clinical presentation and cytological, histological, or imaging studies with other nongynecological tumors does occur. Therefore, immunocytochemistry markers are used to determine tumor origin. Human epididymis protein 4 (HE4) is overexpressed in tissue of epithelial ovarian cancer (EOC). It has shown to be a sensitive and specific serum marker for EOC and to be of value for the differentiation between EOC and ovarian metastases of gastrointestinal origin. The objective of the current study was to evaluate HE4 immunocytochemistry in malignant ascites for differentiation between cancer of Müllerian origin, including EOC, and adenocarcinomas of the gastrointestinal tract. Cytological specimens of 115 different adenocarcinomas (45 EOCs, 46 cases of gastric cancer, and 24 cases of colorectal cancer) were stained for HE4, paired box 8 (PAX8), and other specific markers. 91% of the ascites samples from patients with EOC stained for both HE4 and PAX8. The 4 samples without HE4 staining were a clear cell carcinoma, a low-grade serous adenocarcinoma, an undifferentiated adenocarcinoma, and a neuroendocrine carcinoma. All high-grade serous adenocarcinomas (n = 37, 100%) stained with HE4, compared with 94% that stained positively for PAX8. In cases of gastric or colorectal cancer, 25% and 21% of cases, respectively, stained positive for HE4. No PAX8 staining was observed in colorectal or gastric adenocarcinomas. HE4 staining in ascites is feasible and appears to have a high sensitivity for high-grade serous ovarian cancer. HE4 is a useful addition to the current panel of immunocytochemistry markers for the diagnosis of EOC and for differentiation with gastrointestinal adenocarcinomas. Cancer Cytopathol 2017;125:197-204. © 2016 American Cancer Society. © 2017 American Cancer Society.

Clinicopathologic features of ovarian neoplasms with emphasis on borderline ovarian tumors: an institutional perspective.

PubMed

Hashmi, Atif Ali; Hussain, Zubaida Fida; Bhagwani, Aneel Roy; Edhi, Muhammad Muzzammil; Faridi, Naveen; Hussain, Syed Danish; Khan, Mehmood

2016-04-06

Ovarian cancer is the most lethal gynecologic malignancy and it represents third most common malignancy in Karachi (after breast and oral cancer). Due to lack of well established cancer registry in our country, changing trends of ovarian tumors has not been determined. Therefore we aimed to establish the current trends and classification of ovarian tumors in our setup according to latest WHO guidelines. We retrospectively analyzed 162 cases of ovarian tumors that underwent surgical resection from January 2009 till December 2014. Specimens were received in histopathology department, Liaquat National hospital and cases were examined by senior histopathologists and classified according to latest WHO guidelines. Various histopathologic parameters including capsular invasion, omental and lymph node meatstasis along with uterine and fallopian tube involvement were determined apart from tumor type and grade. Mean age at diagnosis was 35.8 years (± 15.5). surface epithelial tumors were most common, 109 cases (67.2%) followed by germ cell tumors, 44 cases (27.1%) and sex cord stromal tumors, 8 cases (4.9%). Serous tumors were most common surface epithelial tumors with 90% benign morphology. On the other hand, mucinous tumors showed a higher percentage of borderline and malignant features (16.7 and 14.6% respectively). Higher incidence of capsular invasion and omental metastasis was noted in endometroid and serous carcinoma compared to mucinous tumors. We noted a higher frequency of young age ovarian cancers in our set up. Serous and endometroid carcinomas were found to be associated with adverse prognostic factors like capsular invasion and omental metastasis. Moreover a significantly higher proportion of ovarian tumors constitute mucinous histology including borderline tumors. Whether this represents a changing trend towards biology of these tumors in this part of the world needs to be uncovered by further studies.

Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium.

PubMed

Olsen, Catherine M; Nagle, Christina M; Whiteman, David C; Ness, Roberta; Pearce, Celeste Leigh; Pike, Malcolm C; Rossing, Mary Anne; Terry, Kathryn L; Wu, Anna H; Risch, Harvey A; Yu, Herbert; Doherty, Jennifer A; Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Wang-Gohrke, Shan; Goodman, Marc T; Carney, Michael E; Matsuno, Rayna K; Lurie, Galina; Moysich, Kirsten; Kjaer, Susanne K; Jensen, Allan; Hogdall, Estrid; Goode, Ellen L; Fridley, Brooke L; Vierkant, Robert A; Larson, Melissa C; Schildkraut, Joellen; Hoyo, Cathrine; Moorman, Patricia; Weber, Rachel P; Cramer, Daniel W; Vitonis, Allison F; Bandera, Elisa V; Olson, Sara H; Rodriguez-Rodriguez, Lorna; King, Melony; Brinton, Louise A; Yang, Hannah; Garcia-Closas, Montserrat; Lissowska, Jolanta; Anton-Culver, Hoda; Ziogas, Argyrios; Gayther, Simon A; Ramus, Susan J; Menon, Usha; Gentry-Maharaj, Aleksandra; Webb, Penelope M

2013-04-01

Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case-control studies (13 548 cases and 17 913 controls). We combined study-specific adjusted odds ratios (ORs) using a random-effects model. We further examined the associations by histological subtype, menopausal status and post-menopausal hormone use. High BMI (all time-points) was associated with increased risk. This was most pronounced for borderline serous (recent BMI: pooled OR=1.24 per 5 kg/m(2); 95% CI 1.18-1.30), invasive endometrioid (1.17; 1.11-1.23) and invasive mucinous (1.19; 1.06-1.32) tumours. There was no association with serous invasive cancer overall (0.98; 0.94-1.02), but increased risks for low-grade serous invasive tumours (1.13, 1.03-1.25) and in pre-menopausal women (1.11; 1.04-1.18). Among post-menopausal women, the associations did not differ between hormone replacement therapy users and non-users. Whilst obesity appears to increase risk of the less common histological subtypes of ovarian cancer, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.

Computed tomographic features of adenocarcinoma compared to malignant lymphoma of the stomach.

PubMed

Chamadol, Nittaya; Wongwiwatchai, Jitraporn; Wachirakowit, Tharinee; Pairojkul, Chawalit

2011-11-01

To compare the CT findings of adenocarcinoma and malignant lymphoma of the stomach. The authors retrospectively reviewed the computed tomographic images of 21 patients who received a definite pathologic diagnosis of adenocarcinoma or malignant lymphoma of the stomach. The images were taken at Srinagarind Hospital between January 2006 and February 2009. Seventeen patients with gastric adenocarcinoma and four with malignant gastric lymphoma were included in the present study. The pattern of involvement, the location of lesion, the perigastric fat plane, the perigastric lymphadenopathy and the extension of disease on CT images were evaluated and analyzed by Chi-square and Fisher exact tests. There was a statistically significant difference between gastric adenocarcinoma and malignant gastric lymphoma in the pattern of involvement of disease (p = 0.010), the perigastric fat plane (p = 0.002) and the location of disease (p = 0.008). By contrast, there was no respective statistically significant difference in the perigastric lymphadenopathy (p = 0.950) and the extension of disease (p = 0.175) in between gastric adenocarcinoma and malignant gastric lymphoma. The CT findings helpful for differentiating gastric adenocarcinoma from malignant gastric lymphoma are the pattern of involvement, the perigastric fat plane, and the location of lesion. Localized involvement of the lesion, abnormal perigastric fat plane and location involving one region of the stomach tend to indicate gastric adenocarcinoma; while diffused involvement of the lesion, preserved perigastric fat plane and location involving more than one region of the stomach tend to indicate malignant gastric lymphoma.

Comparison of the effects of letrozole and cabergoline on vascular permeability, ovarian diameter, ovarian tissue VEGF levels, and blood PEDF levels, in a rat model of ovarian hyperstimulation syndrome.

PubMed

Şahin, Nur; Apaydın, Nesin; Töz, Emrah; Sivrikoz, Oya Nermin; Genç, Mine; Turan, Gülüzar Arzu; Cengiz, Hakan; Eskicioğlu, Fatma

2016-05-01

To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS). In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels. The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues. Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

PubMed

De Bellis, Annamaria; Bellastella, Giuseppe; Falorni, Alberto; Aitella, Ernesto; Barrasso, Mariluce; Maiorino, Maria Ida; Bizzarro, Elio; Bellastella, Antonio; Giugliano, Dario; Esposito, Katherine

2017-10-01

Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages. © 2017 European Society of Endocrinology.

Stages of Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer

MedlinePlus

... of Ovarian Germ Cell Tumors Ovarian Low Malignant Potential Tumors Symptoms, Tests, Prognosis, & Stages Treatment of Ovarian Low Malignant Potential Tumors Prevention of Ovarian, Fallopian Tube, & Primary Peritoneal ...

Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations.

PubMed

Zheng, Difan; Wang, Rui; Zhang, Yang; Pan, Yunjian; Cheng, Xinghua; Cheng, Chao; Zheng, Shanbo; Li, Hang; Gong, Ranxia; Li, Yuan; Shen, Xuxia; Sun, Yihua; Chen, Haiquan

2016-04-01

We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.

Laparoscopic ovarian cystectomy of endometriomas does not affect the ovarian response to gonadotropin stimulation.

PubMed

Marconi, Guillermo; Vilela, Martín; Quintana, Ramiro; Sueldo, Carlos

2002-10-01

To evaluate the ovarian response cycles of IVF-ET in patients who previously underwent laparoscopic cystectomy for endometriomas. Retrospective study with prospective selection of participants and controls. Instituto de Ginecología y Fertilidad Buenos Aires, Argentina. Thirty-nine patients underwent an operation for ovarian endometriomas by atraumatic removal of the pseudocapsule with minimal bipolar cauterization of small bleeders and an IVF-ET cycle (group A) and 39 control patients of similar age underwent an IVF-ET cycle for tubal factor infertility (group B). Laparoscopic endometrioma cystectomy, IVF-ET cycle. E(2) levels, number of gonadotropin ampoules, follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate. There were no differences in all the parameters studied (E(2) levels, number of follicles, oocytes retrieved, number and quality of embryos transferred, and clinical pregnancy rate) except for the number of gonadotropin ampoules needed for ovarian hyperstimulation, which was significantly higher in group A than in group B. Our results indicate that laparoscopic cystectomy for endometriomas is an appropriate treatment since it did not negatively affect the ovarian response for IVF-ET.

Ethnicity as a determinant of ovarian reserve: differences in ovarian aging between Spanish and Indian women.

PubMed

Iglesias, Carlos; Banker, Manish; Mahajan, Nalini; Herrero, Leyre; Meseguer, Marcos; Garcia-Velasco, Juan A

2014-07-01

To investigate differences in ovarian reserve markers (antimüllerian hormone [AMH] and antral follicle count [AFC]) in Indian and Spanish women. Cross-sectional study. In vitro fertilization (IVF) clinics. Infertile Spanish (n=229) and Indian (n=236) women who underwent controlled ovarian stimulation for IVF from January to October 2012. None. Data on ovarian reserve markers and results after ovarian stimulation were collected. The mean age of women undergoing their first or second IVF cycle was significantly higher in Spanish than in Indian women (37.5±3.3 years vs. 31.5±3.8 years). Despite this 6-year age gap, AFCs were similar (9.5±4.7 vs. 9.9±4.6), as were day 3 FSH levels (7.5±4.5 IU/L vs. 6.9±2.3 IU/L). AMH levels were slightly lower in Spanish women (1.6±1.7 ng/mL vs. 2.5±1.6 ng/mL). Multivariate regression analysis showed that being Indian decreased AFC by 2.3, such that AFC in Indian women was similar to that in Spanish women 6.3 years older (95% confidence interval 3.39-1.10). Similar ovarian reserve markers and ovarian response were observed in women with a 6-year age difference in favor of the Spanish, suggesting ethnic differences in ovarian aging. Further research is needed to understand whether these differences are genetically induced or are caused by other variables, such as nutrition. Our results may help clinicians to counsel infertile women when discussing assisted reproductive technology outcomes according to age and ethnic background. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Human Adenocarcinoma Cell Line Sensitivity to Essential Oil Phytocomplexes from Pistacia Species: a Multivariate Approach.

PubMed

Buriani, Alessandro; Fortinguerra, Stefano; Sorrenti, Vincenzo; Dall'Acqua, Stefano; Innocenti, Gabbriella; Montopoli, Monica; Gabbia, Daniela; Carrara, Maria

2017-08-11

Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus , P. lentiscus var. chia (mastic gum), P. terebinthus , P. vera , and P. integerrima , was screened on three human adenocarcinoma cell lines: MCF-7 (breast), 2008 (ovarian), and LoVo (colon). The results indicate that all the Pistacia phytocomplexes, with the exception of mastic gum oil, induce cytotoxic effects on one or more of the three cell lines. PCA highlighted the presence of different cooperating clusters of bioactive molecules. Cluster variability among species, and even within the same species, could explain some of the differences seen among samples suggesting the presence of both common and species-specific mechanisms. Single molecules from one of the most significant clusters were tested, but only bornyl-acetate presented cytotoxic activity, although at much higher concentrations (IC 50 = 138.5 µg/mL) than those present in the essential oils, indicating that understanding of the full biological effect requires a holistic vision of the phytocomplexes with all its constituents.

Gallbladder adenoma with focal adenocarcinoma.

PubMed

Ciurea, S; Matei, E; Petrisor, P; Luca, L; Boros, Mirela; Herlea, V; Popescu, I

2008-01-01

The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

ERIC Educational Resources Information Center

Jaffe, J. S.; Chambers, J. T.

2005-01-01

Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

Primary Papillary Mucinous Adenocarcinoma of the Ureter Mimicking Genitourinary Tuberculosis

PubMed Central

Gulwani, Hanni; Jain, Aruna

2010-01-01

Primary adenocarcinomas of the renal pelvis and ureter are rare and account for less than 1% of all malignancies at this site. We report a case of primary papillary mucinous adenocarcinoma of the ureter that clinically mimicked genitourinary tuberculosis. Early diagnosis is important for the better outcome. PMID:21151719

Metastatic ovarian tumors: a clinicopathologic study of 150 cases.

PubMed

Alvarado-Cabrero, Isabel; Rodríguez-Gómez, Adriana; Castelan-Pedraza, Jorge; Valencia-Cedillo, Raquel

2013-10-01

To determine the frequency of metastatic ovarian tumors and to identify their clinicopathologic features. A total of 150 patients with pathologically confirmed metastatic ovarian carcinoma who were treated between 1995 and 2011 at the Mexican Oncology Hospital were identified by retrospective review. Clinicopathologic data were analyzed. Metastatic ovarian carcinoma accounted for 15.7% of all ovarian malignancies. The primary sites of nongynecologic tumors were the colon (30%), stomach (16%), appendix (13%), breast (13%), pancreas (12%), biliary tract (15%), and liver (4%). Gynecologic primary sites were the uterine cervix (4%) and the uterine body (23%). Primary malignancies were detected first in 66 patients (44%) and simultaneously with ovarian metastasis in 53 patients (35.3%). An ovarian mass was the first manifestation of disease in 20.6% of the cases. The patients ranged in age from 26 to 72 years (mean, 51). Krukenberg tumors were found in 35 patients (23%). The cut surfaces of the ovaries were solid in 68 patients, solid-cystic in 38, and multicystic in 44. Metastatic ovarian carcinomas are an important group of ovarian neoplasms, constituting 15.7% of all ovarian malignancies. Most of them arise from the gastrointestinal tract.

Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study.

PubMed

Eng, Kevin H; Szender, J Brian; Etter, John Lewis; Kaur, Jasmine; Poblete, Samantha; Huang, Ruea-Yea; Zhu, Qianqian; Grzesik, Katherine A; Battaglia, Sebastiano; Cannioto, Rikki; Krolewski, John J; Zsiros, Emese; Frederick, Peter J; Lele, Shashikant B; Moysich, Kirsten B; Odunsi, Kunle O

2018-02-01

Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89) and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001). Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12-2.25) independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034). Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005). We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in MAGEC3) reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75-4.65) advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families.

Paternal lineage early onset hereditary ovarian cancers: A Familial Ovarian Cancer Registry study

PubMed Central

Eng, Kevin H.; Szender, J. Brian; Etter, John Lewis; Kaur, Jasmine; Poblete, Samantha; Huang, Ruea-Yea; Zhu, Qianqian; Battaglia, Sebastiano; Cannioto, Rikki; Krolewski, John J.; Zsiros, Emese; Frederick, Peter J.; Lele, Shashikant B.; Moysich, Kirsten B.; Odunsi, Kunle O.

2018-01-01

Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89) and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001). Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12–2.25) independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034). Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005). We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in MAGEC3) reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75–4.65) advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families. PMID:29447163

Polymorphisms in the FGF2 gene and risk of serous ovarian cancer: results from the Ovarian Cancer Association Consortium

PubMed Central

Johnatty, Sharon E.; Beesley, Jonathan; Chen, Xiaoqing; Spurdle, Amanda B.; deFazio, Anna; Webb, Penelope M; Goode, Ellen L.; Rider, David N.; Vierkant, Robert A.; Anderson, Stephanie; Wu, Anna H.; Pike, Malcolm; Van Den Berg, David; Moysich, Kirsten; Ness, Roberta; Doherty, Jennifer; Rossing, Mary-Anne; Pearce, Celeste Leigh; Chenevix-Trench, Georgia

2009-01-01

Fibroblast growth factor (FGF)-2 (basic) is a potent angiogenic molecule involved in tumour progression, and is one of several growth factors with a central role in ovarian carcinogenesis. We hypothesised that common single nucleotide polymorphisms (SNPs) in the FGF2 gene may alter angiogenic potential and thereby susceptibility to ovarian cancer. We analysed 25 FGF2 tgSNPs using five independent study populations from the United States and Australia. Analysis was restricted to non-Hispanic White women with serous ovarian carcinoma (1269 cases and 2829 controls). There were no statistically significant associations between any FGF2 SNPs and ovarian cancer risk. There were two nominally statistically significant associations between heterozygosity for two FGF2 SNPs (rs308379 and rs308447; p<0.05) and serous ovarian cancer risk in the combined dataset, but rare homozygous estimates did not achieve statistical significance, nor were they consistent with the log additive model of inheritance. Overall genetic variation in FGF2 does not appear to play a role in susceptibility to ovarian cancer. PMID:19456219

Neonatal ovarian cysts: ultrasound assessment and differential diagnosis.

PubMed

Llorens Salvador, R; Sangüesa Nebot, C; Pacheco Usmayo, A; Picó Aliaga, S; Garcés Iñigo, E

Ovarian cysts are the most common abdominal cysts in female fetuses and newborn girls. Ultrasonography is the imaging technique of choice for diagnosing ovarian cysts because it makes it possible to differentiate them from other cystic lesions. Although most neonatal ovarian cysts regress in the first few months after birth, complications can occur during gestation or after birth. The manifestations of ovarian cysts on ultrasonography will depend on the complications. The management is controversial, although the current trend favors watchful waiting. We describe the different presentations of neonatal ovarian cysts with their complications and their patterns of findings on ultrasonography. We also discuss the differential diagnosis with other cystic abdominal lesions, and finally we discuss the therapeutic management of neonatal ovarian cysts. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

ClinicalTrials.gov

2016-03-17

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

Association of lipid metabolism with ovarian cancer.

PubMed

Tania, M; Khan, M A; Song, Y

2010-10-01

Defects in lipid metabolism have been found to be linked to several diseases, among which atherosclerosis, hypertension, obesity, and diabetes are the most important. Although cancer is chiefly a genetic disease, dietary lipid intake and metabolism are related to some cancer risks, including the risk for ovarian cancer. Higher intake of dietary lipids, systemic lipid metabolism malfunction, and abnormal serum lipid levels are somehow related to ovarian cancer. Overexpression of some lipid metabolic enzymes are also found in ovarian cancer. In this review article, we summarize the relationships between lipid intake, lipid metabolism, and ovarian cancer.

Association of lipid metabolism with ovarian cancer

PubMed Central

Tania, M.; Khan, M.A.; Song, Y.

2010-01-01

Defects in lipid metabolism have been found to be linked to several diseases, among which atherosclerosis, hypertension, obesity, and diabetes are the most important. Although cancer is chiefly a genetic disease, dietary lipid intake and metabolism are related to some cancer risks, including the risk for ovarian cancer. Higher intake of dietary lipids, systemic lipid metabolism malfunction, and abnormal serum lipid levels are somehow related to ovarian cancer. Overexpression of some lipid metabolic enzymes are also found in ovarian cancer. In this review article, we summarize the relationships between lipid intake, lipid metabolism, and ovarian cancer. PMID:20975872

Genetic zygosity of mature ovarian teratomas, struma ovarii, and ovarian carcinoids.

PubMed

Kato, Noriko; Sakamoto, Kazuhiro; Murakami, Koutaro; Iwasaki, Yuri; Kamataki, Akihisa; Kurose, Akira

2018-02-17

Although ovarian monodermal teratomas, including struma ovarii and carcinoids, are closely associated with mature teratomas, their genetic basis is poorly understood. A series of mature and monodermal ovarian teratomas were analyzed by short tandem repeat genotyping to evaluate their genetic zygosity and its associations. Informative DNA genotyping data were obtained for ten mature teratomas, six struma ovarii, and three carcinoids (one insular, one trabecular, and one mucinous). A homozygous genotype was present in five of the ten (50%) mature teratomas, three of the six (50%) struma ovarii, and one of the three (33%) ovarian carcinoids. There was no significant difference in genetic zygosity between mature and monodermal teratomas. Patients' age was not correlated with the genetic zygosity: the youngest age in the homozygous tumor group of patients was 4 years. It is suggested that an oocyte after meiosis I, which has escaped from meiotic arrest, is a significant cause of these tumors. Although one mature teratoma was a rare case with lactating adenoma-like breast tissue, its genetic zygosity was concordant with that of the surrounding teratomatous tissue. In one ovarian carcinoid, the carcinoid and accompanying teratomatous components showed matching zygosity at all but one locus: the carcinoid was heterozygous but teratoma was homozygous at one pericentromeric locus. This suggests that not all carcinoids are secondary neoplasms arising from a fully developed mature teratoma: some are neoplasms deviating from a developing mature teratoma.

Poor outcome of oesophageal adenocarcinoma after prior antireflux surgery.

PubMed

Mitchell, E M; Pal, N; Kalyan, J P; Rhodes, M; Lewis, M P N

2009-12-01

Gastro-oesophageal reflux disease is an important risk factor for oesophageal adenocarcinoma, but abolishing reflux through surgery has not been shown to reduce this risk. The purpose of this study is to report on adenocarcinomas occurring after previous antireflux surgery and their long-term outcome. Six hundred and forty three patients underwent surgical resection in our unit for oesophagogastric adenocarcinoma between 2000 and 2009. Nine of these had antireflux surgery a median of 6.9 (mean of 9.3) years previously. Clinical and pathological characteristics and outcome (in terms of survival) are described for this patient group. The patients who had prior antireflux surgery were compared to matched control patients for disease free survival. Disease free survival in our antireflux patients was 25.1% as compared to 72.1% in controls at 3 years. (Log rank test p=0.004). Patients who have undergone antireflux surgery for chronic gastro-oesophageal reflux disease can develop adenocarcinoma and need to be monitored closely. The outcome following surgery appears greatly worse for patients with previous antireflux surgery than age/sex/stage/treatment matched controls in this small study.

No compelling positive association between ovarian hormones and wearing red clothing when using multinomial analyses.

PubMed

Blake, Khandis R; Dixson, Barnaby J W; O'Dean, Siobhan M; Denson, Thomas F

2017-04-01

Several studies report that wearing red clothing enhances women's attractiveness and signals sexual proceptivity to men. The associated hypothesis that women will choose to wear red clothing when fertility is highest, however, has received mixed support from empirical studies. One possible cause of these mixed findings may be methodological. The current study aimed to replicate recent findings suggesting a positive association between hormonal profiles associated with high fertility (high estradiol to progesterone ratios) and the likelihood of wearing red. We compared the effect of the estradiol to progesterone ratio on the probability of wearing: red versus non-red (binary logistic regression); red versus neutral, black, blue, green, orange, multi-color, and gray (multinomial logistic regression); and each of these same colors in separate binary models (e.g., green versus non-green). Red versus non-red analyses showed a positive trend between a high estradiol to progesterone ratio and wearing red, but the effect only arose for younger women and was not robust across samples. We found no compelling evidence for ovarian hormones increasing the probability of wearing red in the other analyses. However, we did find that the probability of wearing neutral was positively associated with the estradiol to progesterone ratio, though the effect did not reach conventional levels of statistical significance. Findings suggest that although ovarian hormones may affect younger women's preference for red clothing under some conditions, the effect is not robust when differentiating amongst other colors of clothing. In addition, the effect of ovarian hormones on clothing color preference may not be specific to the color red. Copyright © 2017 Elsevier Inc. All rights reserved.

Incidence trends of adenocarcinoma of the cervix in 13 European countries.

PubMed

Bray, Freddie; Carstensen, Bendix; Møller, Henrik; Zappa, Marco; Zakelj, Maja Primic; Lawrence, Gill; Hakama, Matti; Weiderpass, Elisabete

2005-09-01

Rapid increases in cervical adenocarcinoma incidence have been observed in Western countries in recent decades. Postulated explanations include an increasing specificity of subtype-the capability to diagnose the disease, an inability of cytologic screening to reduce adenocarcinoma, and heterogeneity in cofactors related to persistent human papillomavirus infection. This study examines the possible contribution of these factors in relation with trends observed in Europe. Age-period-cohort models were fitted to cervical adenocarcinoma incidence trends in women ages <75 in 13 European countries. Age-adjusted adenocarcinoma incidence rates increased throughout Europe, the rate of increase ranging from around 0.5% per annum in Denmark, Sweden, and Switzerland to >/=3% in Finland, Slovakia, and Slovenia. The increases first affected generations born in the early 1930s through the mid-1940s, with risk invariably higher in women born in the mid-1960s relative to those born 20 years earlier. The magnitude of this risk ratio varied considerably from around 7 in Slovenia to almost unity in France. Declines in period-specific risk were observed in United Kingdom, Denmark, and Sweden, primarily among women ages >30. Whereas increasing specificity of subtype with time may be responsible for some of the increases in several countries, the changing distribution and prevalence of persistent infection with high-risk human papillomavirus types, alongside an inability to detect cervical adenocarcinoma within screening programs, would accord with the temporal profile observed in Europe. The homogeneity of trends in adenocarcinoma and squamous cell carcinoma in birth cohort is consistent with the notion that they share a similar etiology irrespective of the differential capability of screen detection. Screening may have had at least some impact in reducing cervical adenocarcinoma incidence in several countries during the 1990s.

Reduced ovarian glyoxalase-I activity by dietary glycotoxins and androgen excess: a causative link to polycystic ovarian syndrome.

PubMed

Kandaraki, Eleni; Chatzigeorgiou, Antonis; Piperi, Christina; Palioura, Eleni; Palimeri, Sotiria; Korkolopoulou, Penelope; Koutsilieris, Michael; Papavassiliou, Athanasios G

2012-10-24

Glyoxalase detoxification system composed of glyoxalase (GLO)-I and GLO-II is ubiquitously expressed and implicated in the protection against cellular damage because of cytotoxic metabolites such as advanced glycation end products (AGEs). Recently, ovarian tissue has emerged as a new target of excessive AGE deposition and has been associated with either a high AGE diet in experimental animals or hyperandrogenic disorders such as polycystic ovarian syndrome (PCOS) in humans. This study was designed to investigate the impact of dietary AGEs and androgens in rat ovarian GLO-I activity of normal nonandrogenized (NAN, group A, n = 18) and androgenized prepubertal (AN) rats (group B, n = 29). Both groups were further randomly assigned, either to a high-AGE (HA) or low-AGE (LA) diet for 3 months. The activity of ovarian GLO-I was significantly reduced in normal NAN animals fed an HA diet compared with an LA diet (p = 0.006). Furthermore, GLO-I activity was markedly reduced in AN animals compared with NAN (p ≤ 0.001) when fed with the corresponding diet type. In addition, ovarian GLO-I activity was positively correlated with the body weight gain (r(s) = 0.533, p < 0.001), estradiol (r(s) = 0.326, p = 0.033) and progesterone levels (r(s) = 0.500, p < 0.001). A negative correlation was observed between GLO-I activity and AGE expression in the ovarian granulosa cell layer of all groups with marginal statistical significance (r(s) = -0.263, p = 0.07). The present data demonstrate that ovarian GLO-I activity may be regulated by dietary composition and androgen levels. Modification of ovarian GLO-I activity, observed for the first time in this androgenized prepubertal rat model, may present a contributing factor to the reproductive dysfunction characterizing PCOS.

Apatinib in the treatment of advanced lung adenocarcinoma with KRAS mutation.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Huang, Jian-An; Jiang, Jun-Hong

2017-01-01

Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment.

Development of a Mouse Model of Menopausal Ovarian Cancer

PubMed Central

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

2014-01-01

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

Clear cell carcinoma of the ovary: molecular insights and future therapeutic perspectives

PubMed Central

2016-01-01

Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to chemotherapeutic agents and to be associated with a worse prognosis than the more common serous adenocarcinoma or endometrioid adenocarcinoma. To improve the survival of patients with ovarian CCC, the deeper understanding of the mechanism of CCC carcinogenesis as well as the efforts to develop novel treatment strategies in the setting of both front-line treatment and salvage treatment for recurrent disease are needed. In this presentation, we first summarize the mechanism responsible for carcinogenesis. Then, we highlight the promising therapeutic targets in ovarian CCC and provide information on the novel agents which inhibit these molecular targets. Moreover, we discuss on the cytotoxic anti-cancer agents that can be best combined with targeted agents in the treatment of ovarian CCC. PMID:27029752

Comparison of the effects of laparoscopic bipolar electrocoagulation and intracorporeal suture application to ovarian reserve in benign ovarian cysts.

PubMed

Özgönen, Hakan; Erdemoglu, Evrim; Günyeli, Ilker; Güney, Mehmet; Mungan, Tamer

2013-04-01

Aim of the present study is to determine the effects of bipolar electrocoagulation and intracorporeal suture on the ovarian reserve after ovarian cystectomy. Sixty patients aged 18-42 years old and with a persistent adnexal mass were recruited to the study. Patients were randomized into suture hemostasis group or bipolar hemostasis group. Laparoscopic ovarian cystectomy was performed to all patients. Hemostasis was obtained by bipolar coagulation in 30 patients and by intracorporeal sutures in 30 patients. Serum levels of FSH, LH, estradiol, inhibin B and ultrasonographic measurements (antral follicle count and ovarian volume) were analyzed and recorded at day 3 of menstrual cycle, 1 and 3 months after the surgery. Basal FSH level measurement at the postoperative third month was significantly increased to 6.96 ± 1.86 mIU/ml (p < 0.05) in the bipolar electrocoagulation group. However, the decreased ovarian volume and antral follicle count was restored at the postoperative third month in the bipolar electrocoagulation group. Preoperative and postoperative FSH, LH, estradiol and inhibin B levels and ultrasonographic measurements were similar in the intracorporeal suture group. The unwanted effect of bipolar electrocoagulation on ovarian reserve is probably transient and causes minimal damage to ovary. FSH levels may be slightly elevated. Gentle use of bipolar electrocoagulation or intracorporeal are not found to effect ovarian reserve.

Body mass index and risk of ovarian cancer.

PubMed

Leitzmann, Michael F; Koebnick, Corinna; Danforth, Kim N; Brinton, Louise A; Moore, Steven C; Hollenbeck, Albert R; Schatzkin, Arthur; Lacey, James V

2009-02-15

Convincing epidemiologic evidence links excess body mass to increased risks of endometrial and postmenopausal breast cancers, but the relation between body mass index (BMI) and ovarian cancer risk remains inconclusive. Potential similarities regarding a hormonal mechanism in the etiology of female cancers highlight the importance of investigating associations according to menopausal hormone therapy (MHT) use. However, to the authors' knowledge, data addressing whether the relation between BMI and ovarian cancer differs by MHT use are very sparse. The authors prospectively investigated the association between BMI and ovarian cancer among 94,525 US women who were followed between 1996 through 1997 to December 31, 2003. During 7 years of follow-up, 303 epithelial ovarian cancer cases were documented. Compared with normal weight women (BMI of 18.5-24.9 kg/m(2)), the multivariate relative risk (MVRR) of ovarian cancer for obese women (BMI of >or=30 kg/m(2)) in the cohort as a whole was 1.26 (95% confidence interval [95% CI], 0.94-1.68). Among women who never used MHT, the MVRR for obese versus normal weight women was 1.83 (95% CI, 1.18-2.84). In contrast, no relation between BMI and ovarian cancer was apparent among women who ever used MHT (MVRR = 0.96; 95% CI, 0.65-1.43; P interaction = 0.02). Exploratory analyses also suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer (MVRR comparing obese vs normal weight women = 1.36; 95% CI, 1.00-1.86), but no relation with BMI was apparent among women with a positive family history of ovarian cancer (MVRR = 0.74; 95% CI, 0.34-1.62 [P interaction = .02]). Based on the results of the current study, the authors suspect that obesity is associated with enhanced ovarian cancer risk through a hormonal mechanism.

Monoclonal antibody against human ovarian tumor-associated antigens.

PubMed

Poels, L G; Peters, D; van Megen, Y; Vooijs, G P; Verheyen, R N; Willemen, A; van Niekerk, C C; Jap, P H; Mungyer, G; Kenemans, P

1986-05-01

Mouse monoclonal antibodies (OV-TL 3) were raised against human ovarian tumor-associated antigens for diagnostic purposes. A cloned hybridoma cell line was obtained by fusion of murine myeloma cells with spleen lymphocytes from BALB/c mice immunized with a tumor cell suspension prepared from an ovarian endometrioid carcinoma. The antibodies were initially screened for their ability to bind on frozen sections of human ovarian carcinoma tissue and a negative reaction on gastric carcinoma tissue by indirect immunofluorescence. The reactivity of the selected OV-TL 3 clone (IgG1 subclass) was studied on normal and neoplastic tissues as well as on a cell line derived from the original tumor cell suspension used for immunization. OV-TL 3 antibodies stained frozen sections of human ovarian carcinomas of the following histological types: serous, mucinous, endometrioid, and clear cell. No reaction was found with breast cancers or other nongynecological tumors. No differences in staining pattern were observed between primary and metastatic ovarian carcinomas. OV-TL 3 antibodies brightly stained ovarian carcinoma cell clusters in ascitic fluids and left unstained mesothelial cells and peripheral blood cells. The OV-TL 3-defined antigen also remained strongly expressed on a cell line derived from the endometrioid ovarian carcinoma originally used for generation of OV-TL 3 clone. Reactivity was weak and irregular in a few ovarian cysts, while traces of fluorescence were sometimes detected in epithelial cells lining the female genital tract. In only 3 specimens of 15 endometrium carcinomas was weak focal reactivity with OV-TL 3 antibodies observed. The results of the immunofluorescence study were confirmed by the more sensitive avidin-biotin method and by 125I-labeled OV-TL 3 antibodies. Thus OV-TL 3 recognizes a common antigen for most ovarian carcinomas and may be a useful tool for rapid diagnosis of ovarian carcinomas.

Spontaneous Rupture of Adenocarcinoma of Meckel’s Diverticulum- A Rare Entity

PubMed Central

2015-01-01

Meckel’s diverticulum is a true diverticulum from remnant of vitelline duct. It is most common congenital anomaly of intestine. It is associated with intestinal atresia and anorectal anomalies. It contains heterotrophic epithelium. Most common heterotrophic mucosa is gastric followed by pancreatic tissue. Adenocarcinoma arising from Meckel’s diverticulum is very rare. Spontaneous perforation of adenocarcinoma rarely reported. Most of perforation reported in Meckel’s diverticulum diagnosed during intraoperative period. This is a case report of spontaneous rupture of adenocarcinoma of Meckel’s diverticulum, which was managed with primary resection and ileostomy. PMID:26672729