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Sonego M.,Italian National Cancer Institute | Schiappacassi M.,Italian National Cancer Institute | Lovisa S.,Italian National Cancer Institute | Dall'Acqua A.,Italian National Cancer Institute | And 21 more authors.
EMBO Molecular Medicine | Year: 2013

Stathmin is a p53-target gene, frequently overexpressed in late stages of human cancer progression. Type II High Grade Epithelial Ovarian Carcinomas (HG-EOC) represents the only clear exception to this observation. Here, we show that stathmin expression is necessary for the survival of HG-EOC cells carrying a p53 mutant (p53MUT) gene. At molecular level, stathmin favours the binding and the phosphorylation of p53MUT by DNA-PKCS, eventually modulating p53MUT stability and transcriptional activity. Inhibition of stathmin or DNA-PKCS impaired p53MUT-dependent transcription of several M phase regulators, resulting in M phase failure and EOC cell death, both in vitro and in vivo. In primary human EOC a strong correlation exists between stathmin, DNA-PKCS, p53MUT overexpression and its transcriptional targets, further strengthening the relevance of the new pathway here described. Overall our data support the hypothesis that the expression of stathmin and p53 could be useful for the identification of high risk patients that will benefit from a therapy specifically acting on mitotic cancer cells. © 2013. Source

Abdullah F.,Morzak Clinic | Abdullah F.,Anderson Cancer Center Houston | Rashid R.M.,Morzak Center | Rashid R.M.,Anderson Cancer Center Houston
Journal of Drugs in Dermatology | Year: 2010

The use of herbal medications in dermatologic disease has become common practice among consumers. In this paper, the authors review and discuss the existing evidence-based botanical modalities in the peer-reviewed literature with a particular focus on various presentations of alopecia. To maximize potential clinical application, this review has been limited human studies. The goal of the study was to provide a thorough evaluation of the current understanding of the use of non-pharmaceutical botanical products in the management of hair loss. Copyright © 2010 Journal of Drugs in Dermatology. Source

Trpkov K.,University of Calgary | Grignon D.J.,Indiana University | Amin M.B.,Cedars Sinai Medical Center | Billis A.,University of Campinas | And 8 more authors.
American Journal of Surgical Pathology | Year: 2013

The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a Z65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was needed to confirm the gross impression. Other recommendations were that the renal vein margin be considered positive only when there is adherent tumor visible microscopically at the actual margin. When a specimen is submitted separately as "caval thrombus, "the recommended sampling strategy is to take 2 or more sections to look for the adherent caval wall tissue. It was also recommended that uninvolved renal parenchyma be sampled by including normal parenchyma with tumor and normal parenchyma distant from the tumor. There was consensus that radical nephrectomy specimens should be examined for the purpose of identifying lymph nodes by dissection/palpation of the fat in the hilar area only; however, it was acknowledged that lymph nodes are found in <10% of radical nephrectomy specimens. Copyright © 2013 by Lippincott Williams & Wilkins. Source

Anderson P.M.,Anderson Cancer Center Houston | Bielack S.S.,Klinikum Stuttgart Olgahospital Stuttgart Germany | Gorlick R.G.,Montefiore Medical Center | Skubitz K.,University of Minnesota | And 14 more authors.
Pediatric Blood and Cancer | Year: 2016

Background: Robatumumab (19D12; MK-7454 otherwise known as SCH717454) is a fully human antibody that binds to and inhibits insulin-like growth factor receptor-1 (IGF-1R). This multiinstitutional study (P04720) determined the safety and clinical efficacy of robatumumab in three separate patient groups with resectable osteosarcoma metastases (Group 1), unresectable osteosarcoma metastases (Group 2), and Ewing sarcoma metastases (Group 3). Procedure: Robatumumab infusions were administered every 2 weeks and were well tolerated with minimal toxicity. Centrally reviewed response data were available for 144 patients. Results: Low disease burden was important for osteosarcoma response: three of 31 patients had complete response or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) in resectable patients (Group 1) versus zero of 29 in unresectable patients (Group 2); median overall survival was 20 months in Group 1 versus 8.2 months in Group 2. In centrally reviewed patients with Ewing sarcoma with PET-CT data (N = 84/115), there were six PR, 23 stable disease, and 55 progression of disease by RECIST at 2 months. Patients with Ewing sarcoma had a median overall survival of 6.9 months. However, responding patients with Ewing sarcoma were allowed to continue on treatment after study closure. A minority of patients with metastatic Ewing sarcoma showed clinical responses and have remained healthy after receiving 25-115 doses of robatumumab with remissions of >4 years duration (N = 6). Conclusions: These findings show that although the IGF-1R remains an attractive treatment target, additional research is needed to identify responders and/or means to achieve durable remissions in order to successfully exploit IGF-1R signal blockade in Ewing sarcoma (clinicaltrials.gov: NCT00617890). © 2016 Wiley Periodicals, Inc. Source

Smitha S.,Cochin University of Science and Technology | Haseena V.S.,Cochin University of Science and Technology | Narayanan T.N.,Rice University | Reena Mary A.P.,Cochin University of Science and Technology | And 8 more authors.
Materials Express | Year: 2012

Multimodal imaging agents that combine magnetic and fluorescent imaging capabilities are desirable for the high spatial and temporal resolution. In the present work, we report the synthesis of multifunctional fluorescent ferrofluids using iron oxide as the magnetic core and rhodamine B as fluorochrome shell. The core-shell structure was designed in such a way that fluorescence quenching due to the inner magnetic core was minimized by an intermediate layer of silica. The intermediate passive layer of silica was realized by a novel method which involves the esterification reaction between the epoxy group of prehydrolysed 3-Glyidoxypropyltrimethoxysilane and the surfactant over iron oxide. The as-synthesized ferrofluids have a high saturation magnetization in the range of 62-65 emu/g and were found to emit light of wavelength 640 nm (λexcitation = 446 nm). Time resolved life time decay analysis showed a bi-exponential decay pattern with an increase in the decay life time in the presence of intermediate silica layer. Cytotoxicity studies confirmed the cell viability of these materials. The in vitro MRI imaging illustrated a high contrast when these multimodal nano probes were employed and the R2 relaxivity of these sample was found to be 334 mM-1s-1 which reveals its high potential as a T2 contrast enhancing agent. © 2012 by American Scientific Publishers. All rights reserved. Source

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