Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pyrrole-imidazole alkaloid rac-dibromophakellstatin displayed selective antitumor activity in vitro when tested in 36 cell lines in a cell survival and proliferation assay. The ovarian cancer cell line OVXF 899L proved to be most sensitive (0.60 microM, IC50), followed by the glioblastoma cell line CNXF 498NL (0.93 microM), the non-small lung cancer cell line LXF 529L (0.96 microM), and the uterus cancer cell line UXF 1138L (1.21 microM). The selectivity profile of rac-dibromophakellstatin may be indicative for a novel mechanism of action. Separation of the enantiomers on a chiral HPLC column revealed that only the naturally occurring (-)-dibromophakellstatin is antitumor active. Debromination of the pyrrole moiety leads to complete loss of activity.
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PMID:Antitumor activity of the marine natural product dibromophakellstatin in vitro. 1709 16

PARP inhibitors are a promising, novel class of anticancer agents. Iniparib (BSI-201) is an intravenously administered PARP1 inhibitor under development by BiPar Sciences Inc, a subsidiary of sanofi-aventis, under license from Octamer Inc, for the potential treatment of cancer. Iniparib, either alone or in combination with chemotherapy, had significant antitumor activity in preclinical studies in vitro and in vivo. Phase I clinical trials in patients with solid tumors demonstrated that treatment with iniparib was associated with minimal toxicity. Encouraging results were observed in a randomized phase II clinical trial, which demonstrated that the addition of iniparib to gemcitabine and carboplatin led to an improvement in clinical benefit rate, progression-free survival and overall survival in patients with metastatic triple-negative breast cancer (TNBC) compared with gemcitabine and carboplatin alone. A phase III clinical trial to test the survival benefit of iniparib in combination with gemcitabine and carboplatin in metastatic TNBC has completed accrual. Another phase III clinical trial will evaluate the overall survival of patients with newly diagnosed stage IV squamous NSCLC treated with gemcitabine and carboplatin with or without iniparib. Several phase II clinical trials of iniparib as a single agent or in combination with chemotherapy are ongoing in other tumor types, such as ovarian and uterine cancer, NSCLC and glioblastoma. These trials will clarify the role of iniparib in the treatment of cancer, including TNBC.
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PMID:Iniparib, a PARP1 inhibitor for the potential treatment of cancer, including triple-negative breast cancer. 2079 48

A 54-year-old woman with a past history of uterine cancer developed a tumor in her right cerebellum. Magnetic resonance imaging with contrast enhancement revealed a mass composed of two components, inside and outside, although both components resided in the same high-intensity area on T2-weighted imaging. Surgical resection removed the bulk of the tumor. Pathological examination revealed two distinct pathological features of the tumor-the inner major component had the features of glioblastoma whereas outer minor component had those of pilocytic astrocytoma (PA). These two components occurred with intercalating transitional areas. No genetic differences, including BRAF alteration or IDH mutations, were detected in either component. Activation of Akt, which is reported to be associated with clinically aggressive and anaplastic PA was found in the PA component of this tumor. The transitional area also stained positive, suggesting the continuity of both components. Consequently, the glioblastoma in this case was likely to have developed as a result of malignant transformation of PA. This case provides additional support for the concept of anaplastic transformation of PA.
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PMID:Transformation of adult cerebellar pilocytic astrocytoma to glioblastoma. 2388 31

Endocan, previously known as endothelial cell-specific molecule-1 (ESM-1), was cloned from the human umbilical vein endothelial cell cDNA library. Endocan is a novel ESM, and a 50 kDa soluble proteoglycan. Endocan is secreted into the blood as the soluble proteoglycan, which is the form in the presence of chondroitin sulfate. In normal tissues, chondroitin sulfate/dermatan sulfate proteoglycan is expressed by endothelial cells (such as lung and kidney) and is overexpressed in several carcinoma endothelial cells. There are studies that identified high endocan expression in lung cancer, uterine cancer, kidney cancer, liver cancer, brain glioblastoma, breast cancer and other tumors. Tumor prognosis, metastasis and angiogenesis were shown to be associated with endocan expression. The majority of investigators believe that endocan regulates the tumor by tumor-associated inflammation, angiogenesis, lymphangiogenesis, the tumor cells themselves and other aspects. Endocan may be a new target for cancer therapy.
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PMID:Endocan: A new marker for cancer and a target for cancer therapy. 2613 22

Germline mutations of the POLE gene are responsible for polymerase proofreading-associated polyposis syndrome (PPAP). These mutations were hypothesised to predispose to extra-gastrointestinal tumours (ovary, endometrium, brain), but this association has not been confirmed so far. We report a family with an autosomal dominant inheritance of PPAP due to a c.1089C>A; p.Asn363Lys mutation in the proofreading exonuclease domain of POLE. Ten patients presenting a history of colorectal tumours and three patients with polyposis are indexed in this family. Three carriers (including siblings and a distant cousin at 30, 45 and 52 respectively) and another member (at 37 not tested) presented glioblastoma. This is the second family reported to carry this mutation. Among the four glioblastomas in the family that we report, both show similar pathology: giant cell glioblastoma. These cases suggest that the c.1089C>A germline POLE mutation may confer an increased risk of brain cancer [incidence 17.4% (4/23) in mutation carriers combining the two families]. More observations are needed to support this hypothesis. It seems that not all mutations of POLE are equally associated with extra-gastrointestinal tumours. Although carriers of a mutation responsible for PPAP should benefit from screening for colorectal and uterine cancer, due to the rapid evolution of glioblastoma the value of neurological follow-up and brain imaging screening remains questionable. Nevertheless, considering the limitations of standard therapy for glioblastoma, mutation status could be useful for targeting therapy. The biological mechanism linking POLE mutation to glioblastoma remains to be determined.
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PMID:Germline mutation p.N363K in POLE is associated with an increased risk of colorectal cancer and giant cell glioblastoma. 3036 36