The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP. The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a 3-year OS of 76% versus 89% (P<0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte-monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared with healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD-1 axis inhibitors.

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.

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 ¼ .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.

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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 mmol/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.

Platinum-based combination chemotherapy may be used successfully for patients with advanced-stage squamous carcinoma of the vulva.

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 were used. Total RNA was extracted and subjected to real-time RT-PCR to evaluate the expression of inducible nitric oxide synthase (iNOS) and glutathione reductase (GSR) in all cells. Nitrate/nitrite levels and GSR activity were also measured using colorimetric and ELISA assays respectively. Cell proliferation was assessed using Ki-67 immunostaining in all cells. Unpaired t-tests were used for statistical analysis at p-value &lt;0.05 for significance. Results: Both EOC cisplatin sensitive cells manifested significant increase in the expression and activity of GSR as compared to their resistant counterparts (p&lt;0.05). On the other hand, EOC sensitive cells manifested a decrease in iNOS expression as compared to their resistant counterparts (p&lt;0.05). Nitrate/nitrite levels were significantly decreased in EOC sensitive cells as compared to their resistant counterparts (p&lt;0.05). Ki-67 immunofluorescence staining revealed increased proliferation in cisplatin resistant cells compared to controls for the MDAH-277a and SKOV-3 cell lines. Conclusion: Our data suggests that the development of cisplatin resistance heighten the prooxidant state in EOC leading to a further increase in cell proliferation. Citation Format: Jimmy Belotte, Nicole Fletcher, Awoniyi Awonuga, Mitchell Alexis, Husam Abu-soud, Michael Diamond, Mohammed Saed, Ghassan Saed. The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B49.

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.