A De Novo Mouse Model of C11orf95-RELA Fusion-Driven Ependymoma Identifies Driver Functions in Addition to NF-κB.

The majority of supratentorial ependymomas (ST-ependymomas) have few mutations but frequently display chromothripsis of chromosome 11q that generates a fusion between C11orf95 and RELA (RELA). Neural stem cells transduced with RELAex vivo form ependymomas when implanted in the brain. These tumors display enhanced NF-κB signaling, suggesting that this aberrant signal is the principal mechanism of oncogenesis.

Corticosteroids compromise survival in glioblastoma.

Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects.

EDL-360: A Potential Novel Antiglioma Agent.

Glioma is a brain tumor that arises from glial cells or glial progenitor cells, and represents 80% of malignant brain tumor incidence in the United States. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor malignancy with fewer than 8% of patients with GBM surviving for more than 3 years. Over the past 10 years, despite improvement in diagnosis and therapies for cancer, the survival rate for high-grade glioma patients remains dismal.

Synthesis and in vitro evaluation of novel 1,2,3,4-tetrahydroisoquinoline derivatives as potent antiglioma agents.

Glioblastoma Multiforme (GBM) continues to demand improved chemotherapeutic solutions. In order to discover novel chemotherapeutic agents for GBM, we identified novel tetrahydroisoquinoline (THI) analogs as antiglioma agents. The present study reports the design, synthesis and in vitro evaluation of new THI derivatives in four established human glioma cell lines (T98, U87, LN18 and A172).

PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity.

Treatment-related toxicity can be life-threatening and is the primary cause of interruption or discontinuation of chemotherapy for acute lymphoblastic leukemia (ALL), leading to an increased risk of relapse. Mercaptopurine is an essential component of continuation therapy in all ALL treatment protocols worldwide. Genetic polymorphisms in thiopurine S-methyltransferase (TPMT) are known to have a marked effect on mercaptopurine metabolism and toxicity; however, some patients with wild-type TPMT develop toxicity during mercaptopurine treatment for reasons that are not well understood.

Animal models for glioma drug discovery.

Introduction: High-grade gliomas are among the most deadly of all cancer types and are also the most common malignant primary tumors of the CNS. Large-scale studies that have analyzed the transcriptional and translational expression patterns of glioma have found that the majority of these tumors can be categorized based on specific genomic anomalies. Genetically engineered mouse models (GEMMs) that represent the molecular subgroups of the human disease harbor a variety of molecular alterations that have been proven to drive gliomagenesis.

New substituted 4H-chromenes as anticancer agents.

As a continuation of our efforts to discover and develop small molecules as anticancer agents, we identified GRI-394837 as an initial hit from similarity search on RGD and its analogs. Based on GRI-394837, we designed and synthesized a focused set of novel chromenes (4a-e) in a single step using microwave method. All five compounds showed activity in the nanomolar range (IC(50): 7.

Dantrolene sodium for the treatment of aldesleukin-induced rigors in a melanoma patient.

Objective: To report the case of a 58-year-old male with melanoma who developed aldesleukin-induced rigors and was successfully treated with intravenous dantrolene sodium 20 mg and provide a review of the literature discussing other agents that have been used to treat drug-induced rigors.

Case Summary: A 58-year-old male was treated with 720,000 IU/kg of aldesleukin every 8 hours as part of his antimelanoma therapy. The patient developed rigors after aldesleukin administration and was successfully treated with 25 mg of meperidine.

Thiopurine methyltransferase predicts the extent of cytotoxicty and DNA damage in astroglial cells after thioguanine exposure.

Thiopurine methyltransferase (Tpmt) is the primary enzyme responsible for deactivating thiopurine drugs. Thiopurine drugs (i.e.

Molecular pathogenesis of malignant glial tumors.

Malignant glial tumors are the most aggressive and difficult to treat neoplasms arising in the brain. More than 22,000 people in the United States are diagnosed with a malignant glioma annually, and most will die within the first two years from diagnosis. Traditionally, gliomas have been categorized based solely on tumor histological features.

CRHR1 polymorphisms predict bone density in survivors of acute lymphoblastic leukemia.

Purpose: Corticosteroids are a critical component of therapy for acute lymphoblastic leukemia (ALL) but are associated with late effects, such as osteoporosis. Risk factors remain poorly defined. Because CRHR1 polymorphisms have been associated with other corticosteroid effects, our goal was to define whether CRHR1 polymorphisms predict which patients with ALL are likely to develop bone mineral deficits.