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Muscal, jodi

Mari Kogiso, Lin Qi, Frank K Braun, Sarah G Injac, Linna Zhang, Yuchen Du, Huiyuan Zhang, Frank Y Lin, Sibo Zhao, Holly Lindsay, Jack M Su, Patricia A Baxter, Adekunle M Adesina, Debra Liao, Mark G Qian, Stacey Berg, Jodi A Muscal, Xiao-Nan Li
Purpose: Pediatric glioblastoma multiforme (pGBM) is a highly aggressive tumor in need of novel therapies. Our objective was to demonstrate the therapeutic efficacy of MLN8237 (alisertib), an orally available selective inhibitor of Aurora A kinase (AURKA), and to evaluate which in vitro model system (monolayer or neurosphere) can predict therapeutic efficacy in vivo Experimental Design: AURKA mRNA expressions were screened with qRT-PCR. In vitro antitumor effects were examined in three matching pairs of monolayer and neurosphere lines established from patient-derived orthotopic xenograft (PDOX) models of the untreated (IC-4687GBM), recurrent (IC-3752GBM), and terminal (IC-R0315GBM) tumors, and in vivo therapeutic efficacy through log rank analysis of survival times in two models (IC-4687GBM and IC-R0315GBM) following MLN8237 treatment (30 mg/kg/day, orally, 12 days)...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Adam J Esbenshade, Christopher R Pierson, Amanda L Thompson, Damon Reed, Abha Gupta, Adam Levy, Lisa S Kahalley, Paul Harker-Murray, Reuven Schore, Jodi A Muscal, Leanne Embry, Kelly Maloney, Terzah Horton, Patrick Zweidler-Mckay, Girish Dhall
BACKGROUND: Mentorship of junior faculty is an integral component of career development. The Children's Oncology Group (COG) Young Investigator (YI) Committee designed a mentorship program in 2004 whose purpose was to pair YIs (faculty ≤10 years of first academic appointment) with a senior mentor to assist with career development and involvement in COG research activities. This study reports on the committee's ability to achieve these goals. PROCEDURE: An online survey was sent to YIs who were registered with the program from 2004 to2015, assessing three major domains: (1) overall experience with the mentor pairing, (2) satisfaction with the program, and (3) academic accomplishments of the mentees...
March 2018: Pediatric Blood & Cancer
Krista J Childress, Ninad Mohan Patil, Jodi A Muscal, Jennifer E Dietrich, Rajkumar Venkatramani
STUDY OBJECTIVE: To determine the diagnosis, management, and outcome for children and adolescents with borderline ovarian tumor (BOT), and to provide a review of the literature on BOT in children and adolescents. DESIGN: A retrospective cohort study of female adolescents younger than age 21 years diagnosed with BOT between January 2001 and May 2016. SETTING: Texas Children's Hospital, Houston, Texas. PARTICIPANTS: Fourteen patients (ages 12 to 18 years) diagnosed with BOT...
February 2018: Journal of Pediatric and Adolescent Gynecology
Jiaxiong Lu, Shan Guan, Yanling Zhao, Yang Yu, Sarah E Woodfield, Huiyuan Zhang, Kristine L Yang, Shayahati Bieerkehazhi, Lin Qi, Xiaonan Li, Jerry Gu, Xin Xu, Jingling Jin, Jodi A Muscal, Tianshu Yang, Guo-Tong Xu, Jianhua Yang
Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling...
August 1, 2017: Cancer Letters
Shayahati Bieerkehazhi, Zhenghu Chen, Yanling Zhao, Yang Yu, Huiyuan Zhang, Sanjeev A Vasudevan, Sarah E Woodfield, Ling Tao, Joanna S Yi, Jodi A Muscal, Jonathan C Pang, Shan Guan, Hong Zhang, Jed G Nuchtern, Hui Li, Huiwu Li, Jianhua Yang
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Aberrant activation of the non-receptor tyrosine kinases Src and c-Abl contributes to the progression of NB. Thus, targeting these kinases could be a promising strategy for NB therapy. In this paper, we report that the potent dual Src/Abl inhibitor bosutinib exerts anti-tumor effects on NB. Bosutinib inhibited NB cell proliferation in a dose-dependent manner and suppressed colony formation ability of NB cells. Mechanistically, bosutinib effectively decreased the activity of Src/Abl and PI3K/AKT/mTOR, MAPK/ERK, and JAK/STAT3 signaling pathways...
January 3, 2017: Oncotarget
Sergio Jaramillo, Yesenia Rojas, Bethany J Slater, Michael L Baker, M John Hicks, Jodi A Muscal, Timothy J Vece, David E Wesson, Jed G Nuchtern
Tracheobronchial mucoepidermoid carcinomas (MEC) are rare in the pediatric population with literature limited primarily to case reports. Here we present our institutional experience treating MEC in three patients and review the literature of 142 pediatric cases previously published from 1968 to 2013. Although rare, tracheobronchial MEC should be included in the differential diagnosis in a child with recurrent respiratory symptoms. Conservative surgical management is often sufficient to achieve complete resection and good outcomes...
April 2016: Pediatric Surgery International
Yongfeng Wang, Long Wang, Shan Guan, Wenming Cao, Hao Wang, Zhenghu Chen, Yanling Zhao, Yang Yu, Huiyuan Zhang, Jonathan C Pang, Sophia L Huang, Yo Akiyama, Yifan Yang, Wenjing Sun, Xin Xu, Yan Shi, Hong Zhang, Eugene S Kim, Jodi A Muscal, Fengmin Lu, Jianhua Yang
ALK receptor tyrosine kinase has been shown to be a therapeutic target in neuroblastoma. Germline ALK activating mutations are responsible for the majority of hereditary neuroblastoma and somatic ALK activating mutations are also frequently observed in sporadic cases of advanced NB. Crizotinib, a first-line therapy in the treatment of advanced non-small cell lung cancer (NSCLC) harboring ALK rearrangements, demonstrates striking efficacy against ALK-rearranged NB. However, crizotinib fails to effectively inhibit the activity of ALK when activating mutations are present within its kinase domain, as with the F1174L mutation...
January 20, 2016: Scientific Reports
Piti Techavichit, M John Hicks, Dolores H López-Terrada, Norma M Quintanilla, R Paul Guillerman, Stephen F Sarabia, Hadi Sayeed, Jed G Nuchtern, Arnold C Paulino, Jodi A Muscal, M Fatih Okcu, Murali Chintagumpala
PURPOSE AND OBJECTIVE: To determine the clinicopathologic and molecular features and outcome of children with mucoepidermoid carcinoma (MEC). METHODS: A retrospective analysis of clinical and histopathologic findings was performed in patients with MEC diagnosed at Texas Children's Cancer Center between 2000 and 2014. RESULTS: Ten female and four male patients with median age 12 years (range 7-19 years) were included in the study. Tumors involved major salivary glands, minor salivary glands of the palate, and the tracheobronchial tree...
January 2016: Pediatric Blood & Cancer
Robin E Norris, Suzanne Shusterman, Lia Gore, Jodi A Muscal, Margaret E Macy, Elizabeth Fox, Noah Berkowitz, Aby Buchbinder, Rochelle Bagatell
BACKGROUND: EZN-2208 is a water-soluble PEGylated conjugate of the topoisomerase inhibitor SN38, the active metabolite of irinotecan. Compared to irinotecan, EZN-2208 has a prolonged half-life permitting extended exposure to SN38. EZN-2208 has demonstrated clinical tolerability and antitumor activity in adults with advanced solid tumors. This Phase 1 study evaluated the safety, pharmacokinetics, and preliminary antitumor activity of EZN-2208 in children with relapsed or refractory solid tumors...
October 2014: Pediatric Blood & Cancer
Patrick A Thompson, Rachid Drissi, Jodi A Muscal, Eshini Panditharatna, Maryam Fouladi, Ashish M Ingle, Charlotte H Ahern, Joel M Reid, Tong Lin, Brenda J Weigel, Susan M Blaney
PURPOSE: Imetelstat is a covalently-lipidated 13-mer thiophosphoramidate oligonucleotide that acts as a potent specific inhibitor of telomerase. It binds with high affinity to the template region of the RNA component of human telomerase (hTERC) and is a competitive inhibitor of telomerase enzymatic activity. The purpose of this study was to determine the recommended phase II dose of imetelstat in children with recurrent or refractory solid tumors. EXPERIMENTAL DESIGN: Imetelstat was administered intravenously more than two hours on days 1 and 8, every 21 days...
December 1, 2013: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Jodi A Muscal, Patrick A Thompson, Terzah M Horton, Ashish M Ingle, Charlotte H Ahern, Renee M McGovern, Joel M Reid, Matthew M Ames, Igor Espinoza-Delgado, Brenda J Weigel, Susan M Blaney
BACKGROUND: A pediatric Phase I trial was performed to determine the maximum-tolerated dose, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of vorinostat and bortezomib, in patients with solid tumors. PROCEDURE: Oral vorinostat was administered on days 1-5 and 8-12 of a 21-day cycle (starting dose 180 mg/m(2) /day with dose escalations to 230 and 300 mg/m(2) /day). Bortezomib (1.3 mg/m(2) i.v.) was administered on days 1, 4, 8, and 11 of the same cycle...
March 2013: Pediatric Blood & Cancer
Jodi A Muscal, Kathleen A Scorsone, Linna Zhang, Jeffrey A Ecsedy, Stacey L Berg
PURPOSE: Histone deacetylase (HDAC) inhibitors, such as vorinostat, decrease Aurora kinase activity by a variety of mechanisms. Vorinostat and MLN8237, a selective Aurora A kinase inhibitor, disrupt the spindle assembly and the mitotic checkpoint at different points, suggesting that the combination could have increased antitumor activity. The purpose of this study was to determine the cytotoxicity of vorinostat and MLN8237 in pediatric tumor cell lines. METHODS: Cell survival was measured after 72 h of drug treatment using a modified methyl tetrazolium assay...
February 2013: Investigational New Drugs
Jodi A Muscal, Yongkai Sun, Jed G Nuchtern, Robert C Dauser, Leticia H McGuffey, Brian W Gibson, Stacey L Berg
PURPOSE: Thalidomide, originally developed as a sedative, was subsequently identified to have antiangiogenic properties. Lenalidomide is an antiangiogenic and immunomodulatory agent that has been utilized in the treatment of patients with brain tumors. We studied the pharmacokinetics and cerebrospinal fluid (CSF) penetration of thalidomide and lenalidomide in a nonhuman primate model. METHODS: A dose of 50 mg of thalidomide or 20 mg of lenalidomide was administered once orally to each of three rhesus monkeys...
April 2012: Cancer Chemotherapy and Pharmacology
Jodi A Muscal, Patrick A Thompson, Vincent L Giranda, Brian D Dayton, Joy Bauch, Terzah Horton, Leticia McGuffey, Jed G Nuchtern, Robert C Dauser, Brian W Gibson, Susan M Blaney, Jack M Su
PURPOSE: ABT-888 inhibits poly(ADP-ribose) polymerase (PARP) and may enhance the efficacy of chemotherapy and radiation in CNS tumors. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration. METHODS: ABT-888, 5 mg/kg, was administered orally to three NHPs. Serial blood and CSF samples were obtained. Plasma and CSF concentrations of ABT-888 were measured using LC/MS/MS, and the resulting concentration versus time data were evaluated using non-compartmental and compartmental PK methods...
February 2010: Cancer Chemotherapy and Pharmacology
Jodi A Muscal, Jeremy Y Jones, Arnold C Paulino, Alison A Bertuch, Jack Su, Shiao Y Woo, Donald H Mahoney, Murali Chintagumpala
PURPOSE: Acute and late changes in magnetic resonance imaging of the pediatric brain have been described after radiotherapy (RT). We report the post-RT neuroimaging changes in the posterior fossa after intensity-modulated RT (IMRT) in children with medulloblastoma and contrast them with those of leptomeningeal disease. METHODS AND MATERIALS: We performed a retrospective review of 53 consecutive children with medulloblastoma who were treated with craniospinal RT followed by IMRT to the posterior fossa and chemotherapy between 1997 and 2006...
January 1, 2009: International Journal of Radiation Oncology, Biology, Physics
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