ABSTRACT
Epithelial ovarian cancer (EOC) is the deadliest gynecologic cancer. Recently, the existence of ovarian cancer stem cells has been reported. Sox2, Nanog and Oct4 are key markers of "stemness". The objective of this study was to determine whether Sox2, Nanog, and Oct4 are associated with EOC and poor outcome. The expression of these markers was assessed by immunofluorescence staining and real-time RT-PCR in human EOC cell lines MDAH-2774 and SKOV-3, while the cancer genome atlas (TCGA) dataset was analyzed for associations with survival. Sox2, Nanog and Oct4 (POU5F1) were all detected by immunofluorescence staining and these results were confirmed by real-time RT-PCR. The TCGA dataset revealed a 26%, 9%, and 6% amplification of Sox2, Nanog and POU5F1, respectively. Additionally, K-M survival analyses showed a significant median overall survival difference (41 versus 48.3 months, P = .01) for Sox2 amplification, but not for Nanog (44.1 versus 36.2 months, P > .05) and POU5F1 (43.5 versus 45.0 months, P > .05). Our results suggest that Sox2 gene amplification significantly influences overall survival.
Subject(s)
Gene Amplification , Neoplasms, Glandular and Epithelial/genetics , Ovarian Neoplasms/genetics , SOXB1 Transcription Factors/genetics , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Databases, Genetic , Female , Fluorescent Antibody Technique , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Kaplan-Meier Estimate , Nanog Homeobox Protein , Neoplasms, Glandular and Epithelial/metabolism , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/therapy , Octamer Transcription Factor-3/genetics , Octamer Transcription Factor-3/metabolism , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/mortality , Ovarian Neoplasms/therapy , Prognosis , Proportional Hazards Models , Real-Time Polymerase Chain Reaction , SOXB1 Transcription Factors/metabolism , Time FactorsABSTRACT
Objective. To report a case of successful laparoscopic management of a left ruptured tubal pregnancy in the setting of an ipsilateral ectopic pelvic kidney. Method. Case report was prepared at Wayne State University/Detroit Medical Center. The patient is a young woman gravida 2 para 0 in her twenties who presented with severe abdominal pain and vaginal bleeding. She had a plateaued beta HCG and ultrasonographic findings suggestive of ectopic left tubal pregnancy along with an ectopic ipsilateral pelvic kidney. The IRB approval is not needed, as this is a case report. The informed consent could not be obtained, as the patient was not reachable. Result. Multiple intraperitoneal adhesions, left ruptured ampullary ectopic pregnancy and left retroperitoneal pelvic mass consistent with ipsilateral ectopic pelvic kidney. Conclusion. Laparoscopic management of tubal pregnancy can be safely performed in the setting of an ipsilateral ectopic pelvic kidney.
ABSTRACT
OBJECTIVE: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). METHODS: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 µmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. RESULTS: Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P < .01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). CONCLUSION: Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.
Subject(s)
Antineoplastic Agents/pharmacology , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism , Oxidative Stress/drug effects , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Glutathione Reductase/genetics , Glutathione Reductase/metabolism , Humans , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/pathology , Nitrates/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Nitrites/metabolism , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , RNA, Messenger/metabolismABSTRACT
Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.
Subject(s)
Brain/embryology , Brain/physiology , Neural Pathways , Female , Humans , Magnetic Resonance Imaging , PregnancyABSTRACT
BACKGROUND: Chemoradiation is an alternative to radical vulvectomy with en bloc node dissection for advanced vulvar cancer. We report a case of complete clinical and pathologic response with chemotherapy alone in a patient with advanced vulvar cancer. CASE: A middle-aged woman known to have had human immunodeficiency virus (HIV) for 10 years was newly diagnosed with advanced-stage squamous carcinoma of the vulva. She was treated with a total of nine cycles of platinum-based combination chemotherapy, with complete clinical and pathologic response. She remains in complete clinical remission without evidence of recurrent disease by noninvasive testing in the absence of any further therapy 24 months after her last chemotherapy treatment. CONCLUSION: Platinum-based combination chemotherapy may be used successfully for patients with advanced-stage squamous carcinoma of the vulva.
