Cellular therapy is an emerging therapeutic modality with a great potential for the treatment of autism. Recent findings show that the major underlying pathogenetic mechanisms of autism are hypoperfusion and immune alterations in the brain. So conceptually, cellular therapy which facilitates counteractive processes of improving perfusion by angiogenesis and balancing inflammation by immune regulation would exhibit beneficial clinical effects in patients with autism. This is an open label proof of concept study of autologous bone marrow mononuclear cells (BMMNCs) intrathecal transplantation in 32 patients with autism followed by multidisciplinary therapies. All patients were followed up for 26 months (mean 12.7). Outcome measures used were ISAA, CGI, and FIM/Wee-FIM scales. Positron Emission Tomography-Computed Tomography (PET-CT) scan recorded objective changes. Out of 32 patients, a total of 29 (91%) patients improved on total ISAA scores and 20 patients (62%) showed decreased severity on CGI-I. The difference between pre- and postscores was statistically significant (P < 0.001) on Wilcoxon matched-pairs signed rank test. On CGI-II 96% of patients showed global improvement. The efficacy was measured on CGI-III efficacy index. Few adverse events including seizures in three patients were controlled with medications. The encouraging results of this leading clinical study provide future directions for application of cellular therapy in autism.

Prostate cancer is the most common solid malignancy in men, with 32,000 deaths annually. Piperine, a major alkaloid constituent of black pepper, has previously been reported to have anti-cancer activity in variety of cancer cell lines. The effect of piperine against prostate cancer is not currently known. Therefore, in this study, we investigated the anti-tumor mechanisms of piperine on androgen dependent and androgen independent prostate cancer cells. Here, we show that piperine inhibited the proliferation of LNCaP, PC-3, 22RV1 and DU-145 prostate cancer cells in a dose dependent manner. Furthermore, Annexin-V staining demonstrated that piperine treatment induced apoptosis in hormone dependent prostate cancer cells (LNCaP). Using global caspase activation assay, we show that piperine-induced apoptosis resulted in caspase activation in LNCaP and PC-3 cells. Further studies revealed that piperine treatment resulted in the activation of caspase-3 and cleavage of PARP-1 proteins in LNCaP, PC-3 and DU-145 prostate cancer cells. Piperine treatment also disrupted androgen receptor (AR) expression in LNCaP prostate cancer cells. Our evaluations further show that there is a significant reduction of Prostate Specific Antigen (PSA) levels following piperine treatment in LNCaP cells. NF-kB and STAT-3 transcription factors have previously been shown to play a role in angiogenesis and invasion of prostate cancer cells. Interestingly, treatment of LNCaP, PC-3 and DU-145 prostate cancer cells with piperine resulted in reduced expression of phosphorylated STAT-3 and Nuclear factor-κB (NF-kB) transcription factors. These results correlated with the results of Boyden chamber assay, wherein piperine treatment reduced the cell migration of LNCaP and PC-3 cells. Finally, we show that piperine treatment significantly reduced the androgen dependent and androgen independent tumor growth in nude mice model xenotransplanted with prostate cancer cells. Taken together, these results support further investigation of piperine as a potential therapeutic agent in the treatment of prostate cancer.

Background. Appendiceal adenocarcinomas (AAs) are rare and this has limited their molecular understanding. The purpose of our study was to characterize the molecular profile of AA and explore the role of targeted therapy against cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR). Patients and Methods. Weperformedaretrospectivereviewof 607 patients with AA at a single institution. A total of 149 patients underwent molecular testing for at least one of the following: activating mutations in KRAS, BRAF, cKIT, EGFR, or PI3K; protein expression of c-KIT or COX-2; or microsatellite instability (MSI) status by immunohistochemistry. Kaplan-Meier product limit method and log-rank test were used to estimate overall survival (OS)andtodetermineassociationsamongOS,COX-2expression, KRAS mutations, and other characteristics. Results. Age, grade, stage, signet ring cells, mucinous histology, and completeness of cytoreduction score correlated with survival outcomes. COX-2 expression, KRAS, PI3K, and BRAF mutations were seen in 61%, 55%, 17%, and 4% of patients, respectively. High MSI was seen in 6% of patients. KRAS mutation was strongly associated with well differentiated or moderately differentiated AA (p Ͻ .01). COX-2 expression (p ϭ .33) and the presence of KRAS mutation (p ϭ .91) had no impact on OS. The use of celecoxib in patients whose tumors expressed COX-2 (p ϭ .84) and the use of cetuximab or panitumumab in patients with KRAS wild-type tumors (p ϭ .83) also had no impact on OS. Conclusion.In this cohort, we demonstrated that COX-2 expression and KRAS mutations were frequently seen in AA, although neither exhibited any prognostic significance. MSI was infrequent in AA. Targeted therapy against COX-2 and EGFR appeared to provide no clinical benefit. Well and moderately differentiated AA were molecularly distinct from poorly differentiated AA. The Oncologist 2013;18:1270 -1277 Implications for Practice: Appendiceal adenocarcinomas (AAs) are rare, and current understanding of their molecular biology is poor. Surgical resection is the mainstay of therapy. Limited data exists to guide medical management, and the role of targeted therapy in AAs has not been studied. This study endeavors to define molecular alterations in AAs. Activating KRAS mutations represent the most common alteration, occurring in 55% cases. Interestingly, well and moderately differentiated tumors demonstrate similar high rates of KRAS mutation, contrary to the low rates seen in poorly differentiated tumors. These data link clinical behavior with molecular biology and suggest that moderately differentiated tumors resemble well-differentiated tumors and should be treated similarly. Further prospective trials are needed to evaluate the efficacy of targeted therapies such as antiepidermal growth factor receptor therapy in AAs, prior to their implementation in clinical practice. Constructing a molecular sketch of AAs is a necessary first step toward recognizing molecular pathways involved in their carcinogenesis and advancing the ro...

Cerebral palsy is a nonprogressive heterogeneous group of neurological disorders with a growing rate of prevalence. Recently, cellular therapy is emerging as a potential novel treatment strategy for cerebral palsy. The various mechanisms by which cellular therapy works include neuroprotection, immunomodulation, neurorestoration, and neurogenesis. We conducted an open label, nonrandomized study on 40 cases of cerebral palsy with an aim of evaluating the benefit of cellular therapy in combination with rehabilitation. These cases were administered autologous bone marrow mononuclear cells intrathecally. The follow-up was carried out at 1 week, 3 months, and 6 months after the intervention. Adverse events of the treatment were also monitored in this duration. Overall, at six months, 95% of patients showed improvements. The study population was further divided into diplegic, quadriplegic, and miscellaneous group of cerebral palsy. On statistical analysis, a significant association was established between the symptomatic improvements and cell therapy in diplegic and quadriplegic cerebral palsy. PET-CT scan done in 6 patients showed metabolic improvements in areas of the brain correlating to clinical improvements. The results of this study demonstrate that cellular therapy may accelerate the development, reduce disability, and improve the quality of life of patients with cerebral palsy.

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This is the first phase I, open-label study to assess the safety, pharmacokinetics, and antitumor activity of a novel immunotherapeutic regimen known as Folate Immune (EC90 vaccine administered with GPI-0100 adjuvant followed by EC17, a folate-targeted hapten immunotherapy that targets folate receptor expressing cancer cells), which is designed to convert poorly immunogenic tumors to highly immunogenic tumors in patients with metastatic renal cell carcinoma. Three to 6 patients were enrolled in each cohort. In the vaccination phase, patients were given once weekly vaccinations of 0.2 mg of EC90 plus 3.0 mg of GPI-0100 for 3-5 weeks. In the treatment phase, patients were treated with 0.031, 0.092, or 0.276 mg/kg of EC17, 5 d/wk, for weeks 3, 4, or 6. Forty-one patients were enrolled in the study of which 33 patients received ≥1 treatment of EC17. Two dose-limiting toxicities were observed including grade 4 anaphylaxis and grade 3 pancreatitis. During the vaccination phase, mild to moderate injection site reactions were the most frequently reported adverse events. During the treatment phase, transient hypersensitivity reactions were the most common adverse event. Partial response was noted in 4% (1/28) of patients, and stable disease was noted in 54% (15/28) of patients after cycle 1 and was maintained in the majority of patients entering the extension phase of the study. EC90 vaccine with GPI-0100 adjuvant followed by EC17 is safe and well tolerated. The recommended regimen for further studies is 4 weekly vaccinations with 0.2 mg of EC90 plus 3.0 mg GPI-0100 followed by treatment with 0.3 mg of EC17.

With the explosion of video content on the Internet, there is a need for research on methods for video analysis which take human cognition into account. One such cognitive measure is memorability, or the ability to recall visual content after watching it. Prior research has looked into image memorability and shown that it is intrinsic to visual content, but the problem of modeling video memorability has not been addressed sufficiently. In this work, we develop a prediction model for video memorability, including complexities of video content in it. Detailed feature analysis reveals that the proposed method correlates well with existing findings on memorability. We also describe a novel experiment of predicting video sub-shot memorability and show that our approach improves over current memorability methods in this task. Experiments on standard datasets demonstrate that the proposed metric can achieve results on par or better than the state-of-the art methods for video summarization.

Background Bone marrow necrosis (BMN) is characterized by infarction of the medullary stroma, leading to marrow necrosis with preserved cortical bone. In reported small series, BMN in hematological malignancies is associated with poor prognosis. We sought to find the impact of BMN on clinical outcome in a relatively larger cohort of patients with acute leukemias. Methods Overall we evaluated 1691 patients; 1051 with acute myeloid leukemia (AML) and 640 with acute lymphocytic leukemia referred to our institution between 2002 and 2013. Patients with AML and ALL were evaluated separately to determine the incidence of BMN, associated clinical features and its prognostic significance. Results At initial diagnosis; BMN was observed in 25 (2.4%) patients with AML and 20 (3.2%) patients with ALL. In AML, BMN was significantly associated with FAB AML M5 morphology (32% vs 10%, p = 0.002). The complete remission (CR) rate in AML with and without BMN was 32% and 59% respectively (p = 0.008). Likewise, CR rate in ALL with BMN was also inferior; 70% vs 92% (p = 0.005). The median overall survival (OS) in AML with BMN was significantly poorer; 3.7 months compared to 14 months without BMN (p= 0.003). Similarly, the median OS in ALL with and without BMN was 61.7 and 72 months respectively (p = 0.33). Conclusion BMN is not a rare entity in AML and ALL, but is infrequent. BMN in AML and in ALL is suggestive of inferior response and poor prognosis.