Ovarian and uterine carcinosarcomas: a comparative analysis of prognostic variables and survival outcomes.
ABSTRACT Carcinosarcomas (malignant mixed Mullerian tumor) of the female genital tract are rare tumors associated with poor outcome. The objective of this study was to identify site-specific differences by comparing carcinosarcomas originating in the uterus and the ovaries.
Data on patients with uterine and ovarian carcinosarcomas were extracted from the Surveillance, Epidemiology, and End Results database between 1988 and 2005. Kaplan-Meier log rank and Cox proportional hazards models were used for survival analysis and for identification of possible predictors for survival.
The identified cohort included 3683 women of whom 2759 (75%) have uterine carcinosarcoma and 924 (25%) have ovarian carcinosarcomas. The patients with uterine carcinosarcoma were older than the patients with ovarian carcinosarcoma (median age, 67 vs 65 years; P < 0.001). The women with uterine carcinosarcoma compared with those with ovarian carcinosarcoma were more often African American (17.3% vs 6%; P < 0.001) and presented more often with localized disease (47% vs 10.8%; P < 0.001). Uterine carcinosarcoma compared with ovarian carcinosarcoma differed significantly with regard to the performance of lymphadenectomy (62.6% vs 41.2%; P < 0.001) and the administration of radiotherapy (38.2% vs 4.8%; P < 0.001). When controlled for the extent of disease spread, uterine carcinosarcoma had a more aggressive clinical course and shorter survival compared with ovarian carcinosarcoma. Although age (P < 0.001), race (P = 0.01), stage (P < 0.001), lymphadenectomy (P < 0.001), and radiation (P < 0.001) were all significant prognostic factors in uterine carcinosarcoma, only age (P < 0.001), stage (P < 0.001), and lymphadenectomy (P < 0.001) were significant predictors in ovarian carcinosarcoma.
Although uterine carcinosarcoma presents at an earlier stage than ovarian carcinosarcoma, it has a worse prognosis compared with ovarian carcinosarcoma, with a similar extent of disease spread. Improved survival observed in lymphadenectomy group lends support to its routine performance in patients with uterine and ovarian carcinosarcomas.
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ABSTRACT: Lumbrokinase (LK) is a group of serine proteases with strong fibrinolytic and thrombolytic activities. In clinical practice, LK can only be administered orally because of its antigenicity, immunogenicity and potential to produce anaphylactic reactions after injection. However, many useful drugs such as interferon, insulin, erythropoietin and interleukin have been modified with polyethylene glycol (PEG) to prepare injectable formulations. In this study, LK was modified with methoxy PEG succinimidyl carbonate (mPEG-SC) with molecular weights of 5000, 10,000 and 20,000 and the pegylated products were isolated and purified using the Akta protein purification system. The extent of pegylation was determined by HPLC. Fibrinolytic activities of pegylated and unmodified LK were measured both in vitro against urokinase on fibrin plates and in vivo using a mouse carageenan black tail model. Optimal pegylation was obtained using mPEG-SC5000 in a buffer pH 8.0 with a reaction time of 5 h, reaction temperature of 0 °C and LK:mPEG-SC molar ratio of 1:25. The results show that mPEG modified LK has strong fibrinolytic and thrombolytic activities both in vitro and in vivo. It is suggested that the pegylated LK is a promising injectable thrombolytic agent for the treatment of thrombotic diseases in clinical practice.Acta Pharmaceutica Sinica B. 04/2013; 3(2):123–129.
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ABSTRACT: The tubulins are significant players in maintaining microtubule dynamics and have important signaling and apoptotic functions. Alterations in microtubules as a result of changes in tubulin isotype content or polymerization affect the sensitivity of cell lines to tubulin-binding agents (e.g., taxol) in vitro. Epothilones, such as patupilone and ixabepilone, contain a 16-membered macrolide ring and act as competitive inhibitors of taxol. Class III β-tubulin overexpression has been linked to resistance to paclitaxel and correlated with poor survival in ovarian, breast, gastric, non-small-cell lung cancer and unknown primary tumors. Recent data suggest that class III β-tubulin may not only serve as a marker for sensitivity to epothilones, but also as a mediator of a bioaggressive tumor phenotype through activation of multiple cell survival pathways active under stress conditions.Expert Review of Anti-infective Therapy 01/2013; 13(1):63-74. · 2.07 Impact Factor
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ABSTRACT: OBJECTIVES: Uterine leiomyosarcoma (uLMS) was staged using the FIGO system for endometrial cancers. The new FIGO system takes into consideration tumor size disregarding myometrial and cervical involvement. We aimed to compare the two systems see which more accurately predicts overall survival (OS). METHODS: 86 patients with uLMS (1984-2010) were retrospectively staged using both FIGO systems. Mean OS rates were estimated using the Kaplan-Meier method. RESULTS: More patients had stage-I disease by the new FIGO system (42 versus 33). Five versus 18 and 27 versus 5 had old and new stage-II and III disease respectively. Five and 4 patients with old stage II and III uLMS respectively were downstaged to stage I while 18 with old stage III were downstaged to stage II. Median follow-up was 23.5 months with a median OS of 114 (95% CI, 61-166) months. Although patients with stage I tumors had a higher mean OS rate compared to those with higher stage disease by either system, patients with old stage II-IV disease showed similar mean OS rates, with stage III-IV patients having a slightly better mean OS and a similar trend was observed with the new system. Patients with new FIGO stage III had a higher mean OS rate than those with stage II or IV disease (37.6 versus 28.1 and 34.3 months). Nonetheless, no statistical significant differences were seen in OS according to stage using either system (p=0.786 and p=0.400 respectively). CONCLUSION: Neither FIGO staging system is ideal in classifying patients into four clinically significant stages.Gynecologic Oncology 11/2012; · 3.93 Impact Factor