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Ovarian Carcinoma (ovarian + carcinoma)
Kinds of Ovarian Carcinoma Terms modified by Ovarian Carcinoma Selected AbstractsGranulocyte Colony-stimulating Factor Suppresses Autologous Tumor Killing Activity of the Peripheral Blood Lymphocytes in the Patients with Ovarian CarcinomaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2004Yoshiaki Ohta Problem:, Granulocyte colony-stimulating factor (G-CSF) is often administered to patients with chemotherapy-induced leukocytopenia. However, adequate attention has not been paid to its effects on cancer immunology. Reported by us and others, G-CSF often induces immunosuppression and down-regulation of response T helper (Th)2 directed immune reaction both in vivo and in vitro. In this study, we analyzed the effects of G-CSF on interferon (IFN)- , production and autologous tumor killing (ATK) activities of peripheral blood mononuclear cells (PBMCs). Methods of study:, In order to evaluate the cytokine-induced activation of peripheral T and natural killer (NK) cells, we analyzed IFN- , production by interleukin (IL)-2- and IL-12-stimulated PBMCs, using the ELISPOT assay. Specific killing of autologous tumor cells was evaluated by lactate dehydrogenase (LDH) release assay. Results:, The PBMC collected from both cancer-bearing patients and healthy subjects showed IL-2- and/or IL-12-induced IFN- , production. The frequency of IFN- , producing cells was significantly higher in the normal subjects compared with the patients with advanced ovarian carcinoma. The ATK activity was also enhanced in IL-2- and/or IL-12-stimulated PBMCs of patients with ovarian carcinoma. G-CSF almost completely abolished IFN- , production and ATK activity of PBMC stimulated with IL-2 and/or IL-12. Conclusions:, The G-CSF appears to be a suppressor of antitumor immunity. Routine administration of G-CSF to cancer patients may not be recommended, except for febrile neutropenia. [source] Increased MCL,1 Expression Is Associated with Poor Prognosis in Ovarian CarcinomasCANCER SCIENCE, Issue 5 2002Kazushi Shigemasa To investigate the potential role of the BCL,2 gene family (BAX, BCL,2, MCL,1, and BCL-XL) in ovarian cancer development and progression, mRNA expression levels of these genes were measured using semi-quantitative PCR in epithelial ovarian tumor tissues and normal ovaries. The immunohistochemical expression of MCL,1 in ovarian tumors was also examined. The expression levels of BAX and MCL,1 mRNA were significantly higher in ovarian cancers and in adenomas than in normal ovaries (P<0.05). In contrast, the BCL,2 mRNA expression level in ovarian cancers was significantly lower than in ovarian adenomas and in normal ovaries (P<0.05). Expression of BCL-XL mRNA was no different between normal ovaries and ovarian tumors. Log-rank testing showed that low BAX mRNA expression and high MCL,1 mRNA expression significantly correlate with poor survival for patients with stage III ovarian carcinomas (BAX, P=0.05; MCL,1, P=0.02). Immunohistochemical analysis showed that diffuse-positive expression of MCL,1 protein in mucinous carcinomas was significantly higher than in mucinous low malignant potential (LMP) tumors (P=0.03). In ovarian cancer cases, diffuse-positive expression of MCL,1 protein significantly correlates with advanced clinical stage, high histologic grade, and poor survival (stage, P<0.01; grade, P=0.01; survival, P=0.01). These results suggest that increased MCL,1 expression may play an important role in replacing the functions of increased BAX and decreased BCL,2 in ovarian carcinoma cells, thereby promoting cell survival, and resulting in a poor prognosis for patients with ovarian cancer. [source] Kallikrein 4 is expressed in malignant mesothelioma,Further evidence for the histogenetic link between mesothelial and epithelial cellsDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2007Ben Davidson M.D., Ph.D. Abstract The objective of this study was to analyze Kallikrein 4 protein (hK4) expression in effusions and solid tumors of patients diagnosed with malignant mesothelioma (MM) and compare hK4 expression in MM with that in breast and ovarian adenocarcinomas. Sections from 65 MM (21 effusions, 44 solid tumors) and 63 breast carcinomas (28 effusions, 35 solid tumors) were stained for hK4 using immunohistochemistry. Results were compared with our previously published data for 284 ovarian carcinomas (181 effusions, 103 solid tumors). Expression of hK4 was detected in 26/65 (40%) MM and 52/63 (83%) breast carcinomas. Ovarian carcinoma showed staining values that were comparable to those in breast carcinoma (expression of hK4 in 144/181; 80% effusions and 85/103; 83% solid tumors). As opposed to our previous findings in ovarian carcinoma, hK4 expression was higher in solid tumors when compared with to effusions in both MM (P = 0.013) and breast carcinoma (P = 0.002). Comparative analysis of the three tumor types showed significantly higher expression in ovarian and breast adenocarcinomas when compared with MM (P < 0.001). In conclusion, hK4 is frequently expressed in MM, with higher levels detected in solid tumors, although its expression is more limited than in gynecological adenocarcinomas. The presence of hK4 in MM, a non-hormonally regulated tumor, provides further support to the histogenetic link between mesothelial and epithelial cells. Diagn. Cytopathol. 2007;35:80,84. © 2007 Wiley-Liss, Inc. [source] Ovarian carcinoma screening in women at intermediate riskCANCER, Issue 2 2005Impact on quality of life, need for invasive follow-up Abstract BACKGROUND Women with family histories suggestive of an increased risk of ovarian carcinoma who have not had a deleterious BRCA1 or BRCA2 mutation identified are commonly suggested to consider ovarian carcinoma screening with transvaginal ultrasound and/or assessment of CA 125 levels. Limited information is available regarding the impact of this approach on either quality of life (QOL) or need for invasive follow-up in this group of women. METHODS From November 1999 to October 2002, 184 women at intermediate risk of ovarian carcinoma were enrolled in a prospective study. Participants were screened with twice yearly transvaginal ultrasound and CA 125 assessments. Impact on QOL was measured using the Mental Component Summary (MCS) score of the Medical Outcomes Studies Short Form-36. Need for invasive follow-up was determined by questionnaire and medical record review. RESULTS In the current study, 135 participants underwent , 1 follow-up assessment. During a mean of 19.8 months of follow-up, 12.9% of ultrasounds and 3.8% of CA 125 assessments were abnormal. The authors reported that 38.5% of participants had , 1 abnormal ovarian screen that required a short interval follow-up. Because of either abnormal bleeding or ultrasound abnormalities, 24% of participants underwent , 1 endometrial sampling. Controlling for a history of breast carcinoma and menopausal status, abnormal ovarian screening results were associated with a decrease in MCS score (P = 0.034), whereas the need for endometrial sampling was not (P = 0.87). CONCLUSIONS Ovarian carcinoma screening in women at intermediate risk was associated with a substantial rate of abnormal screen results, endometrial sampling, and in women with abnormal ovarian screening findings, a decrease in MCS scores. These findings may have important implications for women considering ovarian carcinoma screening and for the design of future ovarian carcinoma screening trials. Cancer 2005. © 2005 American Cancer Society. [source] A review of the cutaneous paraneoplastic associations and metastatic presentations of ovarian carcinomaCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2008N. Scheinfeld Summary Ovarian carcinoma possesses cutaneous and paraneoplastic associations. The aim of this study was to review the paraneoplastic associations and metastatic presentations of ovarian carcinoma. PubMed was searched through December 2006 for references to cutaneous metastatic ovarian carcinoma (CMOC). CMOC occurs in 2,7% of cases, manifests in advanced disease and indicates a poor prognosis. The paraneoplastic associations of ovarian carcinoma include acanthosis nigricans, Raynaud's phenomenon, scleroderma, dermatomyositis and palmar fasciitis with polyarthritis. Dermatomyositis, in particular, can precede the diagnosis of ovarian carcinoma. Ovarian carcinoma has many cutaneous paraneoplastic effects and metastatic presentations, all of which portend a poor prognosis. Dermatomyositis is sometimes the initial manifestation of ovarian cancer, thus women > 40 years of age with dermatomyositis should be checked for ovarian carcinoma. It is possible that paraneoplastic dermtomyosititis can be distinguished from nonparaneoplastic dermatomyostitis by the former's lack of (i) associated Raynaud's phenomenon, (ii) response to treatment, (iii) autoantibodies, (iv) overlap and association with other collagen vascular diseases and (v) the presence of the prodromal symptoms of ovarian carcinoma such as gastrointestinal symptoms, urinary symptoms and/or fatigue or malaise. [source] Expression of c-ABL, c-KIT, and platelet-derived growth factor receptor-, in ovarian serous carcinoma and normal ovarian surface epitheliumCANCER, Issue 4 2003Rosemarie E. Schmandt Ph.D. Abstract BACKGROUND Tyrosine kinases, such as c-KIT, c-ABL, and platelet-derived growth factor-beta (PDGFR-,), are important regulators of cell growth. Highly potent and selective inhibitors of tyrosine kinases are being investigated as alternatives to standard chemotherapy. One such inhibitor, imatinib mesylate, is being used to treat gastrointestinal stromal tumors and chronic myelogenous leukemia. Ovarian carcinomas frequently develop resistance to conventional chemotherapeutic agents. Immunohistochemical expression of c-ABL, PDGFR-,, and c-KIT was evaluated in ovarian carcinomas to determine whether treatment with imatinib mesylate might be feasible. METHODS The expression of c-ABL, c-KIT, and PDGFR-, in tumors was evaluated by immunohistochemical analysis of 52 ovarian serous carcinomas, including 21 low-grade (well differentiated) and 31 high-grade (poorly differentiated) tumors. Fourteen normal ovaries were also evaluated. RESULTS In normal ovarian surface epithelium, c-ABL was expressed universally. PDGFR-, was expressed in the majority (93%) of samples of normal ovarian epithelium, whereas the c-KIT protein was undetectable in normal ovarian surface epithelium. Overall, c-ABL was expressed in 71% of serous carcinomas. c-ABL was expressed more frequently in the low-grade serous carcinomas (81%) compared with the high-grade serous carcinomas (65%). PDGFR-, expression was observed in 81% of serous carcinomas overall and was observed more frequently in higher-grade tumors. c-KIT immunohistochemical staining was absent in low-grade tumors but was present in 26% of high-grade serous carcinomas. CONCLUSIONS The majority of ovarian serous carcinomas express one or more of the kinases targeted by the tyrosine kinase inhibitor, imatinib mesylate, suggesting the potential usefulness of this drug in the treatment of ovarian carcinoma. Cancer 2003;98:758,64. © 2003 American Cancer Society. DOI 10.1002/cncr.11561 [source] Primary small cell carcinoma of the lung initially presenting as a breast mass: A fine-needle aspiration diagnosisDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2009Wei Liu M.D. Abstract The incidence of metastases to the breast from extramammary sites is relatively low compared with the incidence of primary breast carcinoma. Primary sites which have a predilection for metastases to the breast include, in the order of decreasing frequency, malignant melanoma, lymphoma, lung carcinoma, ovarian carcinoma, and soft tissue sarcoma, followed by gastrointestinal and genitourinary primaries. Most lung primaries metastasizing to breast represent adenocarcinoma. Other types of lung carcinoma, including small cell carcinoma, are relatively rare. We report a case of lung small cell carcinoma metastasizing to the breast and initially presenting with a breast mass in a 50-year-old female. The tumor was first diagnosed on a fine-needle aspiration biopsy specimen (FNAB) from the breast lesion and subsequently supported by core biopsy. A discussion of the differential diagnoses to consider on FNAB follows. Because of the difference in treatment for primary small cell carcinoma of breast versus primary small cell carcinoma of the lung, as well as the difference in prognosis for both malignancies, determining the site of primary malignancy is crucial to adequate patient care. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Kallikrein 4 is expressed in malignant mesothelioma,Further evidence for the histogenetic link between mesothelial and epithelial cellsDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2007Ben Davidson M.D., Ph.D. Abstract The objective of this study was to analyze Kallikrein 4 protein (hK4) expression in effusions and solid tumors of patients diagnosed with malignant mesothelioma (MM) and compare hK4 expression in MM with that in breast and ovarian adenocarcinomas. Sections from 65 MM (21 effusions, 44 solid tumors) and 63 breast carcinomas (28 effusions, 35 solid tumors) were stained for hK4 using immunohistochemistry. Results were compared with our previously published data for 284 ovarian carcinomas (181 effusions, 103 solid tumors). Expression of hK4 was detected in 26/65 (40%) MM and 52/63 (83%) breast carcinomas. Ovarian carcinoma showed staining values that were comparable to those in breast carcinoma (expression of hK4 in 144/181; 80% effusions and 85/103; 83% solid tumors). As opposed to our previous findings in ovarian carcinoma, hK4 expression was higher in solid tumors when compared with to effusions in both MM (P = 0.013) and breast carcinoma (P = 0.002). Comparative analysis of the three tumor types showed significantly higher expression in ovarian and breast adenocarcinomas when compared with MM (P < 0.001). In conclusion, hK4 is frequently expressed in MM, with higher levels detected in solid tumors, although its expression is more limited than in gynecological adenocarcinomas. The presence of hK4 in MM, a non-hormonally regulated tumor, provides further support to the histogenetic link between mesothelial and epithelial cells. Diagn. Cytopathol. 2007;35:80,84. © 2007 Wiley-Liss, Inc. [source] Psammoma bodies in cervicovaginal smears: Incidence and significanceDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2002Vinita Parkash M.D. Abstract Psammoma bodies (PB) are seen in a wide variety of gynecologic conditions. However, only a few reports address the incidence or significance of PB in cervicovaginal smears (CVS). Twenty patients with PBs in CVS were identified over a 5-yr period during which time 82,840 CVS were screened. Nine cases were associated with malignancy: six uterine serous/clear cell carcinoma, two serous ovarian carcinoma, and one fallopian tube carcinoma. The remaining 11 were benign: one had an ovarian cystadenofibroma and one had PB associated with benign endometrium and endosalpingiosis. In the remaining nine cases, PB were not found on additional studies, although four gave a history of oral contraception and one each had chronic endometritis and IUD in place. The presence of atypical glandular cells diagnostic of carcinoma was the only single feature that predicted carcinoma (7/7). A combination of clinicopathologic features were helpful predictors of malignancy: postmenopausal bleeding (8/9 cases), age over 45 (9/9 cases), and abnormal clinical examination (5/9 cases). Conversely, benignancy was associated with postmenopausal bleeding in 1/11 cases, age over 45 in 3/11 cases and abnormal clinical examination in 2/11 cases. The incidence of PB in our series consecutively screened smears is 8 per 82,840 smears (0.009%). Unlike prior reports, we found that the presence of PB on CVS is not as ominous a finding as previously indicated, as only 12.5% (1/8) of patients with PB on their CVS harbor carcinoma. PB in a CVS in a young patient merits a thorough examination, but not surgical exploration in the absence of additional clinical findings or atypical cells on the CVS. Older patients (>45 yr) have a higher incidence of malignancy, even in the absence of clinical findings or atypical cells on CVS, and may warrant a surgical exploration. Diagn. Cytopathol. 2002;26:81,86; DOI 10.1002/dc.10058 © 2002 Wiley-Liss, Inc. [source] Lectin-based electrophoretic analysis of the expression of the 35,kDa inter-,-trypsin inhibitor heavy chain H4 fragment in sera of patients with five different malignanciesELECTROPHORESIS, Issue 12 2008Emida Mohamed Abstract A 35,kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n,=,12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O -glycosylated fragment of inter-,-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n,=,17), expression of the 35,kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n,=,10), epithelial ovarian carcinoma (n,=,10), and germ cell ovarian carcinoma (n,=,10) but not in patients with nasopharyngeal carcinoma (n,=,13) and osteosarcoma (n,=,7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression. [source] MiR-221 and MiR-222 alterations in sporadic ovarian carcinoma: Relationship to CDKN1B, CDKNIC and overall survivalGENES, CHROMOSOMES AND CANCER, Issue 7 2010Kaitlyn Wurz MicroRNAs are often aberrantly expressed in human neoplasms and are postulated to play a role in neoplastic initiation and progression. miR-221 and miR-222 negatively regulate expression of CDKN1B (p27) and CDKN1C (p57), two cell cycle regulators expressed in ovarian surface epithelium and down-regulated in ovarian carcinomas. We characterized miR-221 and miR-222 expression in 49 sporadic high grade ovarian carcinomas and determined whether somatic mutation or epigenetic alterations explained the differences in expression of these miRNAs. We correlated these findings with protein expression of CDKN1B and CDKN1C as assessed by immunohistochemistry. Expression of miR-221 and miR-222 were closely correlated with each other (P = 0.0001). Interestingly, a lower ratio of miR-221 to miR-222 expression was significantly correlated with worse overall survival (P = 0.01) and remained a significant predictor of overall survival in multivariate analysis using the covariate adequacy of surgical cytoreduction (P = 0.03). Higher miR-222 and miR-221 expression were significantly associated with decreased CDKN1C expression (P = 0.009 and 0.01). In contrast, CDKN1B expression was not associated with miR-221 or miR-222 expression. Neither somatic mutations nor methylation of the studied region explained the alterations in miR-221 and miR-222 expression in most carcinomas. © 2010 Wiley-Liss, Inc. [source] Analysis of chromosomal changes in serous ovarian carcinoma using high-resolution array comparative genomic hybridization: Potential predictive markers of chemoresistant diseaseGENES, CHROMOSOMES AND CANCER, Issue 1 2007Sang Wun Kim The mechanism of drug resistance in cancer is multifactorial, and the accumulation of multiple genetic changes may lead to drug-resistant phenotypes. This study sought to determine characteristic genetic changes in chemoresistant serous ovarian carcinomas using high-resolution array comparative genomic hybridization (aCGH), and identified genomic aberrations that could be used as predictive markers of chemoresistant disease. Seventeen primary ovarian tumors from optimally debulked stage IIIc serous ovarian carcinoma patients were analyzed using aCGH. Ten patients had chemoresistant disease (progression within 12 months of initial chemotherapy), whereas seven patients had chemosensitive disease (no recurrence for more than 36 months). Receiver operating characteristics curve analysis was used to select chromosomal aberrations that could help distinguish chemoresistant disease from chemosensitive disease. In 17 tumors, frequent increases in DNA copy number were seen on 1p36.33, 3q26.2, 8q24.3, 10q26.3, 12p11.21, 20q13.33, and 21q22.3, and frequent losses were observed on 4p12, 5q13.2, 7q11.21, 8p23.1, 14q32.33, Xq13.3, and Xq21.31. The gains on 5p15.33 and 14q11.2, and losses on 4q34.2, 4q35.2, 5q15, 8p21.1, 8p21.2, 11p15.5, 13q14.13, 13q14.2, 13q32.1, 13q34, 16q22.2, 17p11.2, 17p12, and 22q12.3 were more frequent in chemoresistant disease. The losses on 13q32.1 and 8p21.1 had the largest areas under the curve (AUC 0.90 and 0.85, respectively). The most reliable combination of chromosomal aberrations for detecting chemoresistant disease was the loss on 13q32.1 and 8p21.1 (AUC 0.950). Our findings suggest that these chromosomal aberrations are potential predictive markers of chemoresistant disease in patients with serous ovarian carcinomas. © 2006 Wiley-Liss, Inc. [source] Pyrrolizidine Alkaloids and Bisabolane Sesquiterpenes from the Roots of Ligularia cymbuliferaHELVETICA CHIMICA ACTA, Issue 2 2008Chun-Mei Liu Abstract The new pyrrolizidine alkaloid glycoside 1, and the three new highly oxygenated bisabolane sesquiterpenes 4,6, together with the two known pyrrolizidine alkaloids 2 and 3, were isolated from the roots of Ligularia cymbulifera (W.,W. Smith) Hand.- Mazz. Their structures were established on the basis of spectroscopic analysis, especially 1D- and 2D-NMR data. The cytotoxic activities of compounds 1, 2, and 4,6 were evaluated against hepatoma (BEL-7402), human leukemia (HL-60), human ovarian carcinoma (HO-8910), and nasopharyngeal carcinoma (KB) cell lines (Tables 1,3). Compound 6 showed weak cell-growth inhibition of BEL-7402 cell. [source] Expression of multidrug resistance-associated protein 1 in invasive ovarian carcinoma: implication for prognosisHISTOPATHOLOGY, Issue 6 2009Areeg Faggad Aims:, Multidrug resistance is a major impediment in chemotherapeutic treatment of ovarian carcinoma patients. The aim of this study was to investigate the expression of multidrug resistance-associated protein 1 (MRP1) and to assess the possible associations with clinicopathological variables and patient outcome in primary ovarian carcinoma. Methods and results:, Tumour specimens from 129 patients were obtained before chemotherapy and analysed by immunohistochemistry on tissue microarrays, and by real-time reverse transcriptase-polymerase chain reaction on RNA extracted from formalin-fixed paraffin-embedded tissue specimens using a new technique. Significantly increased MRP1 protein expression was observed in high-grade tumours (P = 0.005) and advanced International Federation of Gynaecology and Obstetrics stages (P = 0.036). On univariate Kaplan,Meier analysis, patients with higher expression of MRP1 protein had significantly decreased overall survival (P = 0.006). On multivariate Cox regression analysis, MRP1 protein expression retained its significance as an independent negative prognostic marker for overall survival (hazard ratio = 6.52, P = 0.003). Furthermore, MRP1 expression correlated with topoisomerase II, expression both at mRNA and protein level (P < 0.001 and P = 0.023, respectively). Conclusion:, In summary, in patients with primary ovarian cancer, overexpression of MRP1 is an adverse marker for patient outcome and cancer aggressiveness. Our data provide a translational basis for further clinical studies on the predictive value of MRP1 expression for response to chemotherapy. [source] Expression of leukaemia inhibitory factor in epithelial ovarian carcinoma: correlation with clinical characteristicsHISTOPATHOLOGY, Issue 2 2008First page of article [source] Type-specific roles of histone deacetylase (HDAC) overexpression in ovarian carcinoma: HDAC1 enhances cell proliferation and HDAC3 stimulates cell migration with downregulation of E-cadherinINTERNATIONAL JOURNAL OF CANCER, Issue 6 2010Akiko Hayashi Abstract Histone acetylation/deacetylation controls chromatin activity and subsequent gene transcription. Recent studies demonstrated the activation of histone deacetylases (HDACs) in various human malignancies; however, the expression and function of HDACs in ovarian tumors are not fully understood. In this study, we examined the immunohistochemical expression of HDAC1, HDAC2 and HDAC3 using tissues obtained from 115 cases of ovarian tumors and compared it with that of Ki-67 (a growth marker), p21, and E-cadherin and clinicopathological parameters. In addition, we analyzed the effect of specific siRNA for HDAC1, HDAC2 and HDAC3 on the expression of cell cycle-related molecules and E-cadherin to clarify the functional difference among the 3 HDACs. The results indicated that the immunohistochemical expression of nuclear HDAC1, HDAC2 and HDAC3 proteins increased stepwise in benign, borderline and malignant tumors. The expression of HDAC1 and HDAC2 was correlated with Ki-67 expression and that of HDAC3 was inversely correlated with E-cadherin expression. Among the HDACs examined, only HDAC1 was associated with a poor outcome, when overexpressed. Treatment with HDAC inhibitors suppressed the proliferation of ovarian cancer cells in association with apoptosis. A specific siRNA for HDAC1 significantly reduced the proliferation of ovarian carcinoma cells via downregulation of cyclin A expression, but siRNA for HDAC3 reduced the cell migration with elevated E-cadherin expression. Our results suggested that HDAC1 plays an important role in the proliferation of ovarian cancer cells, whereas HDAC3 functions in cell adhesion and migration. Therefore, specific therapeutic approaches should be considered according to the HDAC subtypes. [source] Bcl- XL and MCL-1 constitute pertinent targets in ovarian carcinoma and their concomitant inhibition is sufficient to induce apoptosisINTERNATIONAL JOURNAL OF CANCER, Issue 4 2010Emilie Brotin Abstract In ovarian carcinomas, recurrence and acquired chemoresistance are the first leading causes of therapeutic failure and are responsible for the poor overall survival rate. Cisplatin exposure of sensitive cells has been previously associated with a down-regulation of Bcl- XL expression and apoptosis, whereas recurrence was systematically observed when Bcl- XL expression was maintained. Bcl- XL down-regulation could thus constitute an interesting chemosensitizing strategy. We showed that a Bcl- XLtargeted RNA interference strategy efficiently sensitized chemoresistant ovarian carcinoma cells to cisplatin, but some of them were still able to re-proliferate. Considering the possible cooperation between Bcl- XLand MCL-1, we investigated the possibility to avoid recurrence in vitro using a multi-targeted RNAi strategy directed against these two anti-apoptotic proteins. We showed that their concomitant inhibition lead to massive apoptosis in absence of cisplatin, this multi-targeted RNAi approach being much more efficient than conventional chemotherapy. We thus demonstrated that Bcl- XL and MCL-1 cooperate to constitute together a strong molecular "bolt", which elimination could be sufficient to allow chemoresistant ovarian carcinoma cells apoptosis. Moreover, we demonstrated that in presence of a low concentration of cisplatin, the concomitant down-regulation of Bcl- XL and MCL-1 allowed a complete annihilation of tumour cells population thus avoiding subsequent recurrence in vitro in cell lines highly refractory to any type of conventional chemotherapy. Therefore, Bcl- XL and MCL-1 targeted strategies could constitute an efficient therapeutic tool for the treatment of chemoresistant ovarian carcinoma, in association with conventional chemotherapy. [source] Rapidly increasing incidence of papillary serous carcinoma of the peritoneum in the United States: Fact or artifact?,INTERNATIONAL JOURNAL OF CANCER, Issue 9 2009Marc T. Goodman Abstract Papillary serous carcinoma of the peritoneum (PSCP) has been recognized for almost 5 decades, but little is known about the etiology or pathogenesis of this uncommon malignancy. The objective of this analysis was to examine trends in the incidence of PSCP in the United States. Invasive PSCP cases (N = 4,389) were identified through 24 population-based registries in the United States during the period 1995-2004. Incidence rates were calculated per million population. PSCP is a disease of older women, with few cases diagnosed before the age of 40 years. The incidence of PSCP was 64% lower among black women and 47% lower among Asian-Pacific Islander women compared with white women. Rates among Hispanic women were 39% lower than among non-Hispanic women. The majority of PSCP (68%) was diagnosed at a distant stage, underscoring the difficulty of diagnosing this malignancy. The incidence of PSCP has increased dramatically during the past decade in the United States with the greatest rise (>13% per year) among non-Hispanic and white women. This trend was more pronounced among older women and women with early stage disease. The incidence of PSCP shows substantial racial and ethnic diversity. The increase in the rate of PSCP among all racial and ethnic groups during the 10-year observation period is cause for some alarm. Although the reason for this temporal trend is unknown, some of the increase may be attributable to reclassification of ovarian carcinoma to the peritoneum. © 2008 Wiley-Liss, Inc. [source] Angiogenesis in the female reproductive organs: pathological implicationsINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2002Lawrence P. Reynolds Summary. The female reproductive organs (ovary, uterus, and placenta) are some of the few adult tissues that exhibit regular intervals of rapid growth. They also are highly vascular and have high rates of blood flow. Angiogenesis, or vascular growth, is therefore an important component of the growth and function of these tissues. As with many other tissues, vascular endothelial growth factors (VEGFs) and fibroblast growth factors (FGFs) appear to be major angiogenic factors in the female reproductive organs. A variety of pathologies of the female reproductive organs are associated with disturbances of the angiogenic process, including dysfunctional uterine bleeding, endometrial hyperplasia and carcinoma, endometriosis, failed implantation and subnormal foetal growth, myometrial fibroids (uterine leiomyomas) and adenomyosis, ovarian hyperstimulation syndrome, ovarian carcinoma, and polycystic ovary syndrome. These pathologies are also associated with altered expression of VEGFs and/or FGFs. In the near future, angiogenic or antiangiogenic compounds may prove to be effective therapeutic agents for treating these pathologies. In addition, monitoring of angiogenesis or angiogenic factor expression may provide a means of assessing the efficacy of these therapies. [source] Spontaneous resolution of acquired factor V inhibitor associated with ovarian carcinomaINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2007E. O. MAUGHAN Summary A 74-year-old lady who presented initially with loin pain and haematuria, then melaena was found to have a prothrombin time ratio (PTR) > 10 and activated partial thromboplastin time ratio (APTTR) > 7. A factor V inhibitor was diagnosed. She was managed with supportive care and the FV inhibitor resolved. A few weeks later she developed abdominal swelling and ascites and was found to have an ovarian tumour. This is the first case, as far as we are aware, of a malignancy-associated FV antibody that has spontaneously remitted before overt presentation of the tumour and illustrates the value of adopting an expectant approach to the management of acquired FV inhibitors. [source] p27/Kip1 mediates retinoic acid-induced suppression of ovarian carcinoma cell growthJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004Scott Vuocolo We have investigated the mechanisms by which all-trans retinoic acid (ATRA) causes growth inhibition of ovarian carcinoma cells. As a model, we have studied the CAOV3 cell line, which is sensitive to ATRA, and the SKOV3 cell line, which is resistant. We have found that treatment of CAOV3 cells with ATRA causes a 5,10 fold increase in the protein level of the cyclin dependent kinase inhibitor p27/Kip1. p27/Kip1 protein upregulation is important in ovarian carcinoma as primary tumors are frequently found lacking this protein. The increase in p27/Kip1 is detected by day 3 of ATRA treatment of CAOV3 cells, and is maximal by day 5. Messenger RNA levels of p27/Kip1 do not change in CAOV3 cells following ATRA treatment, however, we have shown that p27/Kip1 mRNA is more stable in ATRA treated CAOV3 cells. Conversely, the ATRA resistant cell line SKOV3 fails to show p27/Kip1 accumulation. Interestingly, the SCF component protein SKP2 appears to be decreased in CAOV3 cells treated with ATRA. We have also shown that the ATRA dependent increase in p27/kip1 protein in CAOV3 cells leads to a decrease in the kinase activity of cyclin dependent kinase 4 (CDK4) following ATRA treatment. Finally, we found that CAOV3 cells stably transfected with a p27/kip1antisense construct, which express lower levels of p27/kip1 following ATRA treatment, and have a higher CDK4 kinase activity are less sensitive to ATRA induced growth suppression. Taken together our data suggest ATRA-induced growth inhibition in CAOV3 ovarian carcinoma cells involves modulation of the CDK inhibitor p27/kip1. J. Cell. Physiol. 199: 237,243, 2004© 2004 Wiley-Liss, Inc. [source] Debulking surgery for incompletely operated advanced epithelial ovarian carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2009Murat Gultekin MD Abstract Background and Objectives There is still no any data about the role of re-operation and re-debulking in previously incompletely operated advanced staged patients with epithelial ovarian carcinoma (EOC). In this study, the authors aimed to analyze the effect of an incomplete primary surgery on patient prognosis. Methods Clinicopathological variables of 317 advanced staged EOC patients were retrospectively collected. Results Twenty-nine patients had an initial incomplete surgery and referred to our center for debulking while remaining 288 had undergone primary debulking surgery at our institution. Comparison of the two groups with respect to clinicopathological variables could not reveal significant difference. Median survival was 3.24 years for re-operated patients while it was 2.07 years for patients who had undergone primary debulking surgery. Upon multivariate analysis, final optimal debulking, tumor grade and a history of an incomplete surgery before the final debulking were the significant prognosticators. A subgroup analysis of re-staged patients could not reveal a significant role for either the type or the time interval between the operations. Conclusion A history of an incomplete primary surgery does not seem to adversely affect patient prognosis and the optimal cytoreductive success achieved in final debulking surgery is still the most important prognostic factor. J. Surg. Oncol. 2009;100:258,260. © 2009 Wiley-Liss, Inc. [source] Cytoreductive surgery and intraoperative hyperthermic chemoperfusion for advanced ovarian carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 2 2005Trevor W. Reichman MD Abstract Background Optimal cytoreductive surgery combined with intraoperative hyperthermic chemoperfusion (IHCP) is a therapy that potentially could improve survival in a select group of patients with advanced ovarian cancer. The purpose of this study was to review the results of cytoreductive surgery and IHCP for advanced ovarian cancer and to identify factors that may predict which patients maximally benefit from this aggressive treatment. Methods Patients treated with cytoreduction followed by IHCP for ovarian cancer were identified from an IHCP database from 1/2001 through 3/2004. Several factors including resection status, peritoneal cancer index (PCI), and prior surgery were evaluated for their ability to predict survival in our cohort of patients. Results Thirteen patients with ovarian cancer treated with cytoreductive surgery followed by IHCP were identified. The 3-year overall survival rate for all thirteen patients was 55%. The median disease-free survival was 15.4 months (3-year disease-free survival, 11%). Several factors including PCI score (<6), ability to resect all gross disease, and previous surgical exploration appeared to impart an overall survival advantage. Conclusions The use of IHCP coupled with optimal cytoreduction is a safe and effective treatment for advanced ovarian carcinoma. However, the proper selection of patients who will benefit most from the therapy is essential for the success of the treatment. J. Surg. Oncol. 2005;90:51,56. © 2005 Wiley-Liss, Inc. [source] Umbilical metastasis from ovarian carcinoma: Sister Mary Joseph's noduleJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2002D Calista [source] Adenosarcoma of the uterine corpus associated with ovarian thecomaPATHOLOGY INTERNATIONAL, Issue 9 2001Kouichi Nomura We describe a case of adenosarcoma of the uterine corpus associated with ovarian thecoma in a 67-year-old woman. The patient underwent surgery under a diagnosis of ovarian carcinoma. The 110 × 70 mm-sized ovarian tumor was diagnosed as thecoma. The polypoid tumor of the uterine corpus which measured 30 × 15 mm was diagnosed as adenosarcoma. Cells of both epithelial and stromal elements of the adenosarcoma expressed estrogen receptors (determined by immunohistochemistry). These findings support the view that estrogen stimulation, including that by a pre-existing ovarian thecoma, may play a role in the development of mesenchymal and mixed epithelial / mesenchymal uterine tumors, including adenosarcoma. [source] Granulocyte Colony-stimulating Factor Suppresses Autologous Tumor Killing Activity of the Peripheral Blood Lymphocytes in the Patients with Ovarian CarcinomaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2004Yoshiaki Ohta Problem:, Granulocyte colony-stimulating factor (G-CSF) is often administered to patients with chemotherapy-induced leukocytopenia. However, adequate attention has not been paid to its effects on cancer immunology. Reported by us and others, G-CSF often induces immunosuppression and down-regulation of response T helper (Th)2 directed immune reaction both in vivo and in vitro. In this study, we analyzed the effects of G-CSF on interferon (IFN)- , production and autologous tumor killing (ATK) activities of peripheral blood mononuclear cells (PBMCs). Methods of study:, In order to evaluate the cytokine-induced activation of peripheral T and natural killer (NK) cells, we analyzed IFN- , production by interleukin (IL)-2- and IL-12-stimulated PBMCs, using the ELISPOT assay. Specific killing of autologous tumor cells was evaluated by lactate dehydrogenase (LDH) release assay. Results:, The PBMC collected from both cancer-bearing patients and healthy subjects showed IL-2- and/or IL-12-induced IFN- , production. The frequency of IFN- , producing cells was significantly higher in the normal subjects compared with the patients with advanced ovarian carcinoma. The ATK activity was also enhanced in IL-2- and/or IL-12-stimulated PBMCs of patients with ovarian carcinoma. G-CSF almost completely abolished IFN- , production and ATK activity of PBMC stimulated with IL-2 and/or IL-12. Conclusions:, The G-CSF appears to be a suppressor of antitumor immunity. Routine administration of G-CSF to cancer patients may not be recommended, except for febrile neutropenia. [source] Expression of heat-shock proteins hsp27, hsp70 and hsp90 in malignant epithelial tumour of the ovariesAPMIS, Issue 4 2003Correlation with clinicopathologic factors, survival Recently, considerable attention has been focused on the role of the small heat-shock protein group hsp27, hsp70 and hsp90 in the clinical outcome of several malignancies. However, conflicting data exist regarding the prognostic role of hsp27 expression in ovarian carcinoma, and the prognostic significance of hsp70 and hsp90 expression still remains unknown in these tumours. The purpose of this study was to investigate immunohistochemically whether hsp27, hsp70 and hsp90 expression was associated with clinicopathological parameters and survival in 52 epithelial ovarian carcinomas. Chi-square test, Kaplan-Meier and Cox regression analysis were used for statistical analysis. Among clinicopathological parameters, hsp27, hsp70 and hsp90 expression was only correlated with FIGO stage; hsp70 and hsp90 positivity failed to detect survival. However, the overall survival rate of patients with hsp27 expression was 13%, which was significantly worse than that of patients without hsp27 expression (47%) (p<0.01). The prognosis was also adversely affected by FIGO stage (p<0.01) and presence of ascites (p<0.01). In multivariate analysis, hsp27 expression and FIGO stage were independent prognostic variables. Our results indicate that hsp70 and hsp90 expression had no prognostic relevance in epithelial ovarian carcinomas. However, hsp27 expression and FIGO stage in these tumours could be reliable indicators of prognosis. [source] Indurated reticulate palmar erythema as a sign of paraneoplastic palmar fasciitis and polyarthritis syndromeAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2009Veronica A Preda ABSTRACT A 62-year-old woman presented with a 6-month history of polyarthritis. She had also noted a 2-month history of indurated palmar erythema and increasing bilateral hand swelling and stiffness. A biopsy from the area of palmar erythema showed interstitial fibroplasia within the dermis and subcutis representing a palmar fibromatosis. This presentation appears to belong to the spectrum of palmar fasciitis and polyarthritis syndrome. Rheumatologists have recognised this syndrome as a paraneoplastic disorder and subsequent investigations in our patient revealed an elevated cancer antigen 125 and an inoperable ovarian carcinoma. Indurated palmar erythema is a sign that is not widely recognised by dermatologists as a clue for this paraneoplastic syndrome, and skin biopsy demonstrating dermal and subcutaneous fibroplasia may help in diagnosis in the absence of advanced signs of palmar fasciitis. [source] A tale of two cancers: Collision presentation of ovarian carcinoma and lymphomaAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2009Nimit SINGHAL Synchronous malignancies are rare diagnostic and treatment challenges. Here we present three cases of synchronous ovarian cancer and lymphoma. Both malignancies were recognised in the same histopathology sections. This report discusses diagnosis and management dilemmas with a brief literature review. The simultaneous presentation of ovarian cancer and lymphoma has not previously been reported. [source] HuR expression in the nucleus correlates with high histological grade and poor disease-free survival in ovarian cancerAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2009Xiaofang YI Background: HuR, a nucleo-cytoplasmic shuttling protein, plays an important role in mRNA stability as well as cellular differentiation. Recently, HuR expression, particularly in the cytoplasm, was thought to be associated with the prognosis of several cancers including ovarian cancer. Aims: To study the clinical significance of nuclear HuR expression in ovarian cancer. Methods: Primary epithelial ovarian carcinomas (102) and ovarian low malignant potential tumours (11) were assessed for HuR protein expression by immunohistochemistry. HuR scoring accounted for both intensity and percentage of cells stained, and ranged from 0 to 300. Results: HuR was found to be present predominantly in the nucleus, where it was expressed in 85.8% of cases. Nuclear HuR was associated with the invasive cancers (P = 0.004), high grade (P < 0.0001), large residual disease (P = 0.045) and poor disease-free survival (P = 0.0009). Among those 91 specimens with high grade, 76.9% had a high nuclear HuR score, while in those 22 cases with low grade, only 31.8% had a high HuR score (P < 0.0001). Multivariate analysis showed that nuclear HuR intensity was an independent prognostic factor for poor disease-free survival (P = 0.0484). When the invasive cancers were analysed separately, only the association between nuclear HuR and high grade remained (P = 0.0089). Conclusions: Our results support the clinical significance of nuclear HuR in ovarian carcinoma and suggest that nuclear HuR may also play a role in the biology of ovarian cancer. These data suggest a more complex model for HuR in ovarian cancer than one limited to cytoplasmic localisation. [source] | |||||||||||||||||||||||||||||||