Publications by authors named "Jodi A Muscal"

Olaratumab is a monoclonal antibody that specifically binds to platelet-derived growth factor receptor alpha (PDGFRα) and blocks receptor activation. We conducted a phase 1 trial to evaluate the safety of olaratumab and determine a recommended dose in combination with three different chemotherapy regimens in children. Patients <18 years with relapsed/refractory solid or central nervous system tumors were enrolled to two dose levels of olaratumab.

View Article and Find Full Text PDF

Background: Aromatase inhibitors (AIs) are used for estrogen-modulated conditions. Some borderline ovarian tumors (BOT) express estrogen receptors. We present 2 cases of progression from mucinous cystadenoma to mucinous BOT (mBOT) after prior cystectomies in whom an AI was used with recurrence prevention.

View Article and Find Full Text PDF

Clear cell sarcoma of the kidney (CCSK) is the second most common malignant pediatric renal tumor. Two of the recurrent somatic alterations reported in CCSK are BCL-6 corepressor (BCOR) internal tandem duplication (ITD) and YWHAE-NUTM2B/E gene fusion. A minority of patients with CCSKs have other rare somatic alterations.

View Article and Find Full Text PDF

Pediatric germ cell tumors (GCTs) are neoplasms that originate from primordial germ cells and, according to their site of presentation, are classified as gonadal or extragonadal. The most common site of extragonadal GCTs in children is the sacrococcygeal region, and the standard management is multimodal with a focus on chemotherapy. In selected instances, sacrococcygeal resection is performed.

View Article and Find Full Text PDF

Background: Identification and development of young investigators (YI) is critical to the long-term success of research organizations. In 2004, the Children's Oncology Group (COG) created a mentorship program to foster the career development of YIs (faculty <10 years from initial appointment). This study sought to assess mentors' long-term assessment of this program.

View Article and Find Full Text PDF

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 model system (monolayer or neurosphere) can predict therapeutic efficacy AURKA mRNA expressions were screened with qRT-PCR. 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 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).

View Article and Find Full Text PDF

Neuroblastoma (NB), the most common extracranial pediatric solid tumor, continues to cause significant cancer-related morbidity and mortality in children. Dysregulation of oncogenic receptor tyrosine kinases (RTKs) has been shown to contribute to tumorigenesis in various human cancers and targeting these RTKs has had therapeutic benefit. RET is an RTK which is commonly expressed in NB, and high expression of RET correlates with poor outcomes in patients with NB.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF
Article Synopsis
  • Imetelstat is a specialized oligonucleotide that inhibits telomerase, which may help treat recurrent or refractory solid tumors in children.
  • The study evaluated different doses of imetelstat in a trial involving 20 young patients, assessing safety and effectiveness.
  • The recommended phase II dose for imetelstat is 285 mg/m², with notable toxicities like neutropenia, and some patients showed partial tumor responses.
View Article and Find Full Text PDF
Article Synopsis
  • A Phase I trial was conducted to assess the maximum-tolerated dose and side effects of vorinostat combined with bortezomib in pediatric patients with solid tumors.
  • The trial involved administering vorinostat orally at escalating doses over a 21-day cycle and bortezomib intravenously on specific days.
  • Results showed dose-limiting toxicities in some patients, but no objective responses were observed; the recommended Phase II dosing for vorinostat and bortezomib was established for further testing in children with recurrent solid tumors.
View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

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.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: