Particulate drug carriers offer unique opportunities to improve tumor therapy through several different mechanisms. Liposomes may (1) assist in formulation of poorly-soluble therapeutic agents, (2) provide a slow-release vehicle to achieve pharmacokinetic profiles that maximize the therapeutic index, or (3) behave as long-circulating nano-particulates that can extravasate in the hyperpermeable regions of tumor vasculature. For paclitaxel, liposomes provide an aid to formulation.
International Journal of Radiation Oncology, Biology, Physics
PURPOSE: We investigated the effects of fractionated radiation treatments on the life spans of athymic rats bearing intracerebral brain tumors. METHODS AND MATERIALS: U-251 MG or U-87 MG human glioblastoma cells were implanted into the brains of athymic rats, and the resulting tumors were irradiated once daily with various doses of ionizing radiation for 5 consecutive days or for 10 days with a 2-day break after Day 5. RESULTS: Five daily doses of 1 and 1.5 Gy, and 10 doses of 0.75 and 1 Gy, cured some U-251 MG tumors.
BACKGROUND: Glioma, including anaplastic astrocytoma and glioblastoma multiforme (GBM) are among the most commonly diagnosed malignant adult brain tumors. GBM is a highly invasive and angiogenic tumor, resulting in a 12 to 15 months median survival. The treatment of GBM is multimodal and includes surgical resection, followed by adjuvant radio-and chemotherapy. We have previously reported that short-term starvation (STS) enhances the therapeutic index of chemo-treatments by differentially protecting normal cells against and/or sensitizing tumor cells to chemotoxicity.
Regardless of their cell type of origin, all aggressive brain tumors, such as malignant gliomas and metastatic tumors produce brain edema, which is an important cause of patient morbidity and mortality. Caloric restriction (CR) has long been recognized as a natural therapy that improves health, promotes longevity, and significantly reduces both the incidence and growth of many tumor types. The aim of present work was to investigate the effect of CR on edema and survival in the mice implanted with U87 gliomas.
Glutamate is the major excitatory neurotransmitter in the CNS that is cleared from the extracellular space by a family of high-affinity glutamate transporters. The astroglial glutamate transporter EAAT2 is thought to carry out the uptake of the vast quantity of glutamate, and dysregulation of EAAT2 expression is involved in the pathogenesis of neurological disorders with marked excitotoxic components. Here, we present a novel epigenetic mechanism by which the human EAAT2 gene is kept in a silent state. Sequence inspection identified a classical CpG island at the EAAT2 promoter.
Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM).
There is an urgent need to identify novel therapies for glioblastoma (GBM) as most therapies are ineffective. A first step in this process is to identify and validate targets for therapeutic intervention. Epigenetic modulators have emerged as attractive drug targets in several cancers including GBM. These epigenetic regulators affect gene expression without changing the DNA sequence. Recent studies suggest that epigenetic regulators interact with drivers of GBM cell and stem-like cell proliferation. These drivers include components of the Notch, Hedgehog, and Wingless (WNT) pathways.
BACKGROUND: Regulatory T cells (Tregs) are potentially prognostic indicators in patients with glioblastoma. If differences in frequency of Tregs in tumor or blood account for substantial variation in patient survival, then reliably measuring Tregs may enhance treatment selection and improve outcomes. METHODS: We measured Tregs and CD3+ T cells in tumors and blood from 25 patients with newly diagnosed glioblastoma.
Proceedings of the National Academy of Sciences of the United States of America
Bromodomain and extraterminal (BET) domain proteins have emerged as promising therapeutic targets in glioblastoma and many other cancers. Small molecule inhibitors of BET bromodomain proteins reduce expression of several oncogenes required for Glioblastoma Multiforme (GBM) progression. However, the mechanism through which BET protein inhibition reduces GBM growth is not completely understood.