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

Radiotherapy combined with chemotherapy is the treatment of choice for glioblastoma and locally advanced lung cancer, but radioresistance of these two types of cancer remains a significant therapeutic hindrance. To identify molecular target(s) for radiosensitization, we screened a small interfering RNA (siRNA) library targeting all protein kinases and E3 ubiquitin ligases in the human genome and identified tumor necrosis factor receptor-associated factor 2 (TRAF2). Silencing of TRAF2 using siRNA caused a significant growth suppression of glioblastoma U251 cells and moderately sensitized these radioresistant cells to radiation. Overexpression of a really interesting new gene (RING)-deleted dominant-negative TRAF2 mutant also conferred radiosensitivity, whereas overexpression of wild-type (WT) TRAF2 significantly protected cells from radiation-induced killing. Likewise, siRNA silencing of TRAF2 in radioresistant lung cancer H1299 cells caused growth suppression and radiosensitization, whereas overexpression of WT TRAF2 enhanced radioresistance in a RING ligase-dependent manner. Moreover, siRNA silencing of TRAF2 in UM-SCC-1 head and neck cancer cells also conferred radiosensitization. Further support for the role of TRAF2 in cancer comes from the observations that TRAF2 is overexpressed in both lung adenocarcinoma tissues and multiple lung cancer cell lines. Importantly, TRAF2 expression was very low in normal bronchial epithelial NL20 cells, and TRAF2 silencing had a minimal effect on NL20 growth and radiation sensitivity. Mechanistically, TRAF2 silencing blocks the activation of the nuclear factor-kappaB signaling pathway and down-regulates several G(2)-M cell cycle control proteins, resulting in enhanced G(2)-M arrest, growth suppression, and radiosensitization. Our studies suggest that TRAF2 is an attractive drug target for anticancer therapy and radiosensitization.
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PMID:Growth inhibition and radiosensitization of glioblastoma and lung cancer cells by small interfering RNA silencing of tumor necrosis factor receptor-associated factor 2. 1879 45

Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). Previously, we reported on the development of an anti-AM antibody that potently inhibits tumor cell proliferation in vitro and tumor growth in vivo. Here, we report the effect of anti-AM receptor antibodies (alphaAMRs) on angiogenesis and tumor growth. We demonstrate that alphaAMRs decrease in a dose-dependent manner the growth of U87 glioblastoma cells and HT-29 colorectal cancer cells, but not A549 lung cancer cells, in vitro. In vivo, AM in Matrigel plugs induces angiogenesis by promoting recruitment of endothelial cells, pericytes, myeloid precursor cells, and macrophages and by promoting channel formation. Remarkably, systemic administration of alphaAMRs every 3 d markedly reduced neovascularization of Matrigel plugs in a dose-dependent fashion, as demonstrated by reduced numbers of the recruited cells and vessel structures. Several human tumor xenografts in athymic mice were used to examine the effect of alphaAMR treatment on tumor angiogenesis and growth. AlphaAMR treatment significantly suppressed the growth of glioblastoma, lung, and colon tumors. Histological examination of alphaAMR-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial and pericyte cells, and increased tumor cell apoptosis. These findings support the conclusion that alphaAMR treatment inhibits tumor growth by suppression of angiogenesis and tumor growth and suggest that AMRs may be useful therapeutic targets.
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PMID:Targeting adrenomedullin receptors with systemic delivery of neutralizing antibodies inhibits tumor angiogenesis and suppresses growth of human tumor xenografts in mice. 1954 5

We newly cloned the gene encoding the human aspartyl (asparaginyl) beta-hydroxylase (HAAH) from the surgical tissue of a patient with hepatocellular carcinoma. This study was designed to generate HAAH-specific monoclonal antibody (MAb) for further exploration of its structure and function. Mice were co-immunized with naked plasmid DNA containing N-terminal domain of encoding HAAH gene and recombinant HAAH polypeptide. Hybridomas were developed by the electrofusion of the splenocytes from mice immunized with plasmid DNA to Sp2/0 myeloma cells in vitro. Three hybridoma cell lines (designated G3, G9, and F11, respectively) stably secreting HAAH-specific MAbs were obtained. The specificity and sensitivity of MAbs were assessed by indirect enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Results showed that the three MAbs belong to IgG1 kappa isotype, the titer of MAbs reached was 5 x 10(4) - 1 x 10(5), and the affinity constant (k(aff)) of MAbs ranged between 2.5 x 10(8) - 1.1 x 10(9). MAb G3 was preliminarily applied to detection expression of HAAH for seven tumor tissues, including hepatocellular carcinoma, lung cancer, kidney cancer, cholangiocarcinoma, prostate cancer, breast cancer, and glioblastoma by immunohistochemical stain. Our studies demonstrated that co-immunization of naked DNA containing encoding gene of target antigen and recombinant target protein, and combined with in vitro electrofusion, is an effective and simple method to raise MAbs.
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PMID:Monoclonal antibodies against human aspartyl (asparaginyl) beta-hydroxylase developed by DNA immunization. 1966 97

Vitespen is a heat shock protein (gp96)-peptide complex purified from resected autologous tumors, developed as a means of capturing the antigenic 'fingerprint' of a specific cancer for use as a patient-specific vaccine. Vitespen has been extensively assessed in animal models, and clinically in a range of cancers, including Phase I and II trials in colorectal cancer, glioblastoma, lung cancer, melanoma and renal cell carcinoma, and two Phase III studies in melanoma and renal cell carcinoma. Vitespen has shown itself capable of inducing major histocompatibility class I-restricted immune responses in a range of tumor types, and clinical responses in patients with earlier-stage disease, in line with previously published data on cancer vaccines. Vitespen is almost devoid of side effects aside from minor injection-site reactions.
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PMID:Vitespen: a preclinical and clinical review. 1966 26

Methylation of the CpG island in the MGMT promoter region is a frequent event in several cancer types including colorectal cancer, lung cancer, lymphoma, and glioblastoma. A correlation between methylation and the T allele of the rs16906252 single nucleotide polymorphism (SNP) in colorectal carcinomas has previously been reported. As aberrant MGMT methylation can be an early event in tumor development, we tested the hypothesis that normal individuals possessing the T allele may be predisposed to somatic methylation at the MGMT promoter. Peripheral blood monononuclear cell DNA from 89 normal, healthy individuals was genotyped at rs1690625 and assessed for the methylation status of the MGMT promoter region using independent quantitative methodologies capable of detecting low-level methylation: MethyLight and Sensitive Melting Analysis after Real-time Methylation-Specific PCR (SMART-MSP). There was a strong association between presence of the T allele and detectable methylation (P = 0.00005) in the peripheral blood DNA. Furthermore, when a MSP assay flanking the SNP was used to amplify methylated sequences in heterozygotes, only the T allele was methylated. Thus, detectable somatic methylation of the MGMT promoter in normal individuals is strongly associated with the T allele of the rs16906252 MGMT promoter SNP.
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PMID:Detection of MGMT promoter methylation in normal individuals is strongly associated with the T allele of the rs16906252 MGMT promoter single nucleotide polymorphism. 1978 93

Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent. Fenretinide shows biological activity against numerous cancer types in vitro and in preclinical studies. Clinical trials have shown that fenretinide induces a significant reduction of second breast cancer in premenopausal women. Several studies on different neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma, glioblastoma, head and neck and skin cancers and others. It has minimal side effects in humans, so that trials in young women at high-risk of breast cancer and ovarian and for the prevention of other tumor types such as lung cancer could be envisaged. Here we review some ongoing clinical trials and evaluate the possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In particular we report basic and translational data on the anti-angiogenic "angiopreventive" properties of fenretinide, its anti-invasive activity, its ability to induce apoptosis and to generate or enhance production of reactive oxygen species as possible molecular bases for a chemopreventive action in patients.
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PMID:Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies. 2003 9

Vascular endothelial growth factor (VEGF) targeted therapy, either alone or in combination with chemotherapy, has become the standard of care in several solid tumours, including colorectal cancer, renal-cell carcinoma, breast cancer, non-small-cell lung cancer, and glioblastoma. VEGF is crucial in the process of angiogenesis and wound healing and, thus, its inhibition has the potential to affect wound healing in patients undergoing surgery. In this review, we summarise the data available on the use of VEGF-targeted therapies, and their effect on perioperative wound complications. Surgery in patients receiving VEGF-targeted therapies seems to be safe when an appropriate interval of time is allowed between surgical procedures and treatment. Recommendations regarding this interval are provided in a disease and agent site-specific manner. We also discuss complications arising from the use of VEGF-directed therapies that might require surgical intervention and the considerations important in their management. At this juncture, safety data on the use of VEGF-targeted therapies in the perioperative period are sparse, and investigators are urged to continue to study this issue prospectively in current and future clinical trials to establish firm guidelines.
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PMID:Vascular endothelial growth factor targeted therapy in the perioperative setting: implications for patient care. 2017 Nov 41

MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in regulation of eukaryotic gene expression. Aberrant expression and structural alternation of miRNAs are considered to participate in tumorigenesis and cancer development. Recently, different genotypes of miR-196a polymorphisms (SNP, rs11614913) were found to be associated with the survival of patients with lung cancer and increased risk of breast cancer. To further investigate whether this polymorphism may influence glioma risk or not, we examined the SNP allele frequency in Chinese population. Our data shows the genotype CC of miR-196a (rs11614913) polymorphism is associated with decreased risk of glioma in the Chinese population (OR = 0.74, 95% CI:0.56-0.98). Furthermore, a significant association was observed between this genotype and glioma risk in the subgroups of adult glioma (OR = 0.73, 95% CI:0.55-0.98), male glioma (OR = 0.69, 95% CI:0.48-0.99) and patients with glioblastoma (OR = 0.58, 95% CI:0.37-0.91). This was the first study investigating the association between the miR-196a rs11614913 and glioma risk. Compared with the results from previous studies in lung cancer and breast cancer, our data suggest a different genotype association in glioma. This may be related to the diversity on the tissue origin, tumor type, tumorigenesis, and developing process.
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PMID:A polymorphism of microRNA196a genome region was associated with decreased risk of glioma in Chinese population. 2022 73

Y-box binding protein-1 (YB-1) is a member of the cold shock protein family and functions in transcription and translation. Many reports indicate that YB-1 is highly expressed in tumor cells and is a marker for tumor aggressiveness and clinical prognosis. Here, we show clear evidence that YB-1 is expressed in the angiogenic endothelial cells of various tumors, such as glioblastoma, esophageal cancer, gastric cancer, colon cancer, and lung cancer, as well as in tumor cells. YB-1 was highly expressed in glomeruloid microvascular endothelial cells of brain tumors and microvessels in the desmoplastic region around multiple solid tumors. On the other hand, no or low YB-1 expression was observed in normal angiogenic endothelial cells from fetal kidney, newborn lung, and placenta. The endothelial cells in inflammatory regions of granulomas were also weakly labeled. Knockdown of YB-1 expression by small-interfering RNA induced G1 cell cycle arrest and inhibited the growth of human umbilical vein endothelial cells stimulated by growth factors. Taken together, YB-1 plays an important role in the growth of not only tumor cells but also tumor-associated endothelial cells, suggesting that YB-1 is a promising target for cancer therapy.
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PMID:Y-box binding protein-1 is a novel molecular target for tumor vessels. 2039 58

Lung cancer is the leading cause of cancer death for both men and women in the United States, and similar trends are seen world wide. The lack of early diagnosis is one of the primary reasons for the high mortality rate. A number of biomarkers have been evaluated in lung cancer patients, however, their specificity and early stage diagnostic values are limited. Using traditional protein chemistry and proteomics tool we have demonstrated higher serum haptoglobin levels in small cell lung cancer (SCLC). Similar findings have been reported for other cancers including ovarian cancer and glioblastoma. Haptoglobin is an acute phase protein with at least six possible phenotypes. The six phenotypes, in combination with two post translational modifications, glycosylation and deamidation, lead to large numbers of possible haptoglobin isoforms. Recent studies indicate a possible correlation between specific haptoglobin glycosylation and particular disease conditions. In our current study, we have fractionated control and SCLC patient serum by 2-D gel electrophoresis to identify differentially expressed haptoglobin isoforms in SCLC serum samples.
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PMID:DIFFERENTIAL SERUM LEVEL OF SPECIFIC HAPTOGLOBIN ISOFORMS IN SMALL CELL LUNG CANCER. 2052 21


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