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)

The cytotoxic activity of sodium 5,6-benzylidene-L-ascorbate (SBA) against eight human cancer cell lines and three human normal cells was investigated, SBA showed slightly higher cytotoxicity against human tumor cell lines, as compared with normal cells, with a tumor-specificity index of 2.0. The human myelogenous leukemia cell lines (HL-60, ML-1, KG-1) were the most sensitive to SBA, followed by human oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4) and human glioblastoma (T98G, U87MG). Human oral normal cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast) were the most resistant. In contrast to actinomycin D, SBA induced little or no activation of caspase-3, caspase-8 and caspase-9 in the HSC-2, HSC-4, T98G and HL-60 cells, regardless of incubation time (either 6 or 24 h). SBA induced little or no internucleosomal DNA fragmentation after 6 h in all of these cells. However, prolonged treatment with SBA (24 h) induced a smear pattern of DNA fragmentation in the HSC-2, HSC-4 and T98G cells and a low level of internucleosomal DNA fragmentation in the HL-60 cells. Electron microscopy demonstrated the destruction of mitochondrial structure and autophagocytosis of broken organelles by SBA in the HSC-2, HSC-4 and HL-60 cells. At higher concentrations of SBA, necrotic cell death was observed in the HSC-2 cells, but not in the T98G cells, where the production of acidic organelles (detected by acridine orange staining) was much lower than that attained by nutritional starvation, a well-defined method of inducing autophagy. The present study suggests that SBA induces various degrees of autophagic cell death, followed by either necrosis or apoptosis at laters stage, depending on the cell type.
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PMID:Tumor-specific cytotoxicity and type of cell death induced by sodium 5,6-benzylidene-L-ascorbate. 1903 81

The insulin-like growth factor 1 receptor (IGF-1R) and its associated signalling system has provoked considerable interest over recent years as a novel therapeutic target in cancer. A brief outline of the IGF-1R signalling system and the rationale for its use in cancer medicine is given. This is followed by a discussion of the different possible targets within the IGF-1R system, and drugs developed to interact at each target. A systems-based approach is then used to review the in vitro and in vivo data in the published literature of the following compounds targeting IGF-1R components using specific examples: growth hormone releasing hormone antagonists (e.g. JV-1-38), growth hormone receptor antagonists (e.g. pegvisomant), IGF-1R antibodies (e.g. CP-751,871, AVE1642/EM164, IMC-A12, SCH-717454, BIIB022, AMG 479, MK-0646/h7C10), and IGF-1R tyrosine kinase inhibitors (e.g. BMS-536942, BMS-554417, NVP-AEW541, NVP-ADW742, AG1024, potent quinolinyl-derived imidazo (1,5-a)pyrazine PQIP, picropodophyllin PPP, Nordihydroguaiaretic acid Insm-18/NDGA). The following tumour types are specifically discussed: lung, breast, colorectal, pancreatic, NETs, sarcoma, prostate, leukaemia, multiple myeloma. Other tumour types are mentioned briefly: squamous cell carcinoma of the head and neck, melanoma, glioblastoma, ovary, gastric and mesothelioma. Results of early stage clinical trials, involving recently patented drugs. are included where appropriate. We then outline the current understanding of toxicity related to IGF-1R targeted therapy, and finally outline areas for further research.
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PMID:Insulin-like growth factor 1 receptor targeted therapeutics: novel compounds and novel treatment strategies for cancer medicine. 1914 88

Mastic is a resinous exudate obtained from the stem and the main leaves of Pistacia lentiscus. We have reported the antiplaque effect of mastic-containing chewing gum on the oral cavity. We hypothesize that mastic may be a multifunctional food which has some beneficial pharmaceutical properties. The aim of this study was to assess the biological activity of solid and liquid types of mastic by cytotoxicity against fibroblasts, radical-scavenging activities and inhibitory effect on cell death of oral polymorphonuclear leukocytes (OPMNs). Mastic showed selective antibacterial action against Porphyromonas gingivalis and Prevotella melaninogenica, but no anti-HIV activity. Among a total of thirteen human cell types, promyelocytic leukemia HL-60 was the most sensitive to the cytotoxicity of mastic, followed by myeloblastic leukemia (ML-1, KG-1), erythroleukemia (K-562), oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4), hepatocellular carcinoma (HepG2), glioblastoma (T98G, U87MG) and normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast, most resistant). Mastic did not induce the differentiation of myelogenous leukemic cells into maturing cells with higher nitroblue tetrazolium-reducing activity, but induced apoptotic cell death, characterized by internucleosomal DNA fragmentation, caspase-3 activation and a decline in the intracellular concentration of putrescine. The cytotoxicity of mastic against leukemic cells did not diminish during its storage. On the other hand, mastic inhibited the spontaneous apoptosis of OPMNs. Mastic showed hydroxyl radical-scavenging activity. The selective antibacterial and apoptosis-modulating activity of mastic suggests its possible beneficial effects on oral health.
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PMID:Selective antibacterial and apoptosis-modulating activities of mastic. 1941 6

The therapeutic potential of tocotrienol, an extract of vitamin E with anti-cancer properties, is hampered by its failure to specifically reach tumors after intravenous administration, without secondary effects on normal tissues. We hypothesize that the encapsulation of tocotrienol-rich fraction (TRF) within vesicles bearing transferrin, whose receptors are overexpressed on many cancer cells, could result in a selective delivery to tumors after intravenous administration. The objectives of this study are therefore to prepare and characterize transferrin-targeted vesicles encapsulating TRF, and to evaluate their therapeutic efficacy in vitro and in vivo. The entrapment of TRF in transferrin-bearing vesicles led to a 3-fold higher TRF uptake and more than 100-fold improved cytotoxicity in A431 (epidermoid carcinoma), T98G (glioblastoma) and A2780 (ovarian carcinoma) cell lines compared to TRF solution. The intravenous administration of TRF encapsulated in transferrin-bearing vesicles led to tumor regression and improvement of animal survival in a murine xenograft model, contrary to that observed with controls. The treatment was well tolerated by the animals. This work corresponds to the first preparation of a tumor-targeted delivery system able to encapsulate tocotrienol. Our findings show that TRF encapsulated in transferrin-bearing vesicles is a highly promising therapeutic system, leading to tumor regression after intravenous administration without visible toxicity.
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PMID:Tumor regression after systemic administration of tocotrienol entrapped in tumor-targeted vesicles. 1970 37

Tumor angiogenesis is controlled by the integrated action of physicochemical and biological cues; however, the individual contributions of these cues are not well understood. We have designed alginate-based microscale tumor models to define the distinct importance of oxygen concentration, culture dimensionality, and cell-extracellular matrix interactions on the angiogenic capability of oral squamous cell carcinoma, and have verified the relevance of our findings with U87 glioblastoma cells. Our results revealed qualitative differences in the microenvironmental regulation of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) secretion in three-dimensional (3D) culture. Specifically, IL-8 secretion was highest under ambient conditions, whereas VEGF secretion was highest in hypoxic cultures. Additionally, 3D integrin engagement by RGD-modified alginate matrices increased IL-8 secretion independently of oxygen, whereas VEGF secretion was only moderately affected by cell-extracellular matrix interactions. Using two-dimensional migration assays and a new 3D tumor angiogenesis model, we demonstrated that the resulting angiogenic signaling promotes tumor angiogenesis by increasing endothelial cell migration and invasion. Collectively, tissue-engineered tumor models improve our understanding of tumor angiogenesis, which may ultimately advance anticancer therapies.
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PMID:Oxygen-controlled three-dimensional cultures to analyze tumor angiogenesis. 2021 69

One minute downward pressure on the tip of any one of the front 3 teeth (1st incisor, 2nd incisor, and canine) at the right and left sides of the upper and lower jaw by a wooden toothpick induced temporary disappearance (20 min approximately 4 hours) of abnormally increased pain parameters (pain grading, Substance P, & TXB2), and cancer parameters (Telomere, Integrin alpha5beta1, Oncogene C-fos Ab2, etc. of Astrocytoma, Glioblastoma, squamous cell carcinoma of esophagus, adenocarcinoma of lung, breast cancer, adenocarcinoma of colon, prostate cancer). The effect included temporary disappearance of headache, toothache, chest and abdominal pain, and backache, often with improved memory & concentration. Since these beneficial changes resembled the effects of giving one optimal dose of DHEA, increase of DHEA was measured. Above mechanical stimulation of one of these front teeth increased abnormally reduced DHEA levels of less than 10 ng to norm1 100 approximately 130 ng BDORT units and normal cell (NC) telomeres from markedly reduced values to near normal values, and improved acetylcholine in the Hippocampus. Large organ representation areas for the Adrenal gland & Hippocampus may exist at these front teeth. This method can be used for emergency pain control and can explain the beneficial effect of bruxism and tooth brushing, through the increase of DHEA levels and activities of the Hippocampus by increasing Acetylcholine. Increasing NC telomere to optimally high level resulted in disappearance of pain and improvement or significant reduction of malignant tumor. Repeated daily press needle stimulation of True ST. 36 increased NC telomere 450-700 ng BDORT units. One optimal dose of DHEA increased NC telomere 525 ng DBORT units and eliminated the pain and abnormally increased cancer parameters; effect of one optimal dose lasted 0.5-11 months. One optimal dose of Boswellia Serrata or Astragalus not only increased NC telomere 650 ng BDORT units, eliminating pain and cancer parameters, but also reduced the size of the Astrocytoma grade I by 10-20% and the Glioblastoma by 15-90% in less than 2-6 months in some patients, as long as high NC telomere is maintained.
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PMID:Temporary anti-cancer & anti-pain effects of mechanical stimulation of any one of 3 front teeth (1st incisor, 2nd incisor, & canine) of right & left side of upper & lower jaws and their possible mechanism, & relatively long term disappearance of pain & cancer parameters by one optimal dose of DHEA, Astragalus, Boswellia Serrata, often with press needle stimulation of True ST. 36. 2034 85

Vesicular Over-expressed in cancer Prosurvival Protein 1 (VOPP1), also known as Glioblastoma Amplified and Secreted Protein and EGFR-Coamplified and Over-expressed Protein has been previously shown to be over-expressed in human glioblastoma multiforme and squamous cell carcinoma. Additionally, previous experimental work suggests that it confers a prosurvival cellular phenotype. A query of a public database of gene expression profiling data (Oncomine) shows that the VOPP1 transcript is also highly expressed in several other common human cancers, including breast carcinoma, pancreatic carcinoma, and lymphoma. Analysis of VOPP1 sequence structure shows both a signal sequence and a transmembrane domain, and examination of a public microarray dataset for endoplasmic reticulum (ER)-bound mRNA transcripts is consistent with the VOPP1 protein product being synthesized into the ER. Immunoblot analysis of cell culture and conditioned media confirms that the protein product is not secreted and is retained intracellularly. VOPP1 protein tagged with a fluorescence reporter, as well as antibody-mediated visualization of recombinant and native forms of the protein reveals an intracellular vesicular pattern of localization. Co-localization experiments reveal that VOPP1 vesicles do not co-localize with mitochondria or peroxisomes, but show partial co-localization with perinuclear lysosomes. Additionally, markers of endocytosis and autophagy show partial perinuclear co-localization, suggesting that VOPP1-containing vesicles enter final common pathways of the lysosomal system. These findings throw into doubt the hypothesis that VOPP1 interacts directly with cytoplasmic mediators of the NF kappa B pathway, and suggest that the prosurvival phenotype conferred by this gene product is mediated by other mechanisms.
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PMID:Intracellular localization of GASP/ECOP/VOPP1. 2057 87

We have previously reported that sodium 5,6-benzylidene-L-ascorbate (SBA) induced dramatic antitumor activity in inoperable cancer patients, but induced only marginal tumor specificity in vitro. Here the tumor specificity and type of cell death induced by benzaldehyde (BA), a degradation product of SBA, was investigated, using human tumor cell lines (oral squamous cell carcinoma [OSCC], glioblastoma, myelogenous leukemia) and human normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast). BA showed much higher tumor-specific cytotoxicity than SBA. BA induced the formation of autophagosomes, the destruction of mitochondrial structure and digestion of broken organelles, without any apparent induction of internucleosomal DNA fragmentation and caspase activation in an OSCC cell line HSC-2, in a similar manner to SBA. However, pretreatment with 3-methyladenine or bafilomycin A(1), autophagy inhibitors, did not completely rescue the cells from the cytotoxicity induced by BA. The study suggests that BA may play an important role in the induction of antitumor activity of SBA in vivo, although the autophagic phenotypes induced by BA may be involved in both cell death and survival.
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PMID:Tumor-specific cytotoxicity and type of cell death induced by benzaldehyde. 2118 92

A series of curcumin analogues with different substituents at the 4-position of the phenyl group were synthesized and screened for in vitro cytotoxicity against a panel of human cancer cell lines. Several novel curcumin analogues, especially 32 and 34, exhibited selective and potent cytotoxic activity against human epidermoid carcinoma cell line A-431 and human glioblastoma cell line U-251, implying their specific potential in the chemoprevention and chemotherapy of skin cancer and glioma. The preliminary SAR information extracted from the results suggested that introduction of appropriate substituents to the 4'-positions could be a promising approach for the development of new cytotoxic curcumin analogues with special selectivity for A-431 and U-251 cell lines.
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PMID:Synthesis and preliminary evaluation of curcumin analogues as cytotoxic agents. 2121 29

A review of 905 consecutive cases of pathologically confirmed brain tumour yielded 25 cases in which the initial presentation strongly suggested the diagnosis of occlusive cerebrovascular disease. Most of these 25 patients were admitted through the emergency department of our hospital and referred to the general medical service for investigation. Nineteen cases of transient ischemic attack and six cases of completed stroke were found in 12 cases of glioblastoma, seven of meningioma, two of metastatic renal cell carcinoma, and one case each of malignant astrocytoma, low-grade astrocytoma, oligodendroglioma, and metastatic squamous cell carcinoma. We document the clinical overlap between neoplastic and vascular syndromes, and stress the need for "tumour awareness" in the work-up of patients presenting to non-neurological practitioners with the clinical picture of occlusive cerebrovascular disease.
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PMID:Brain tumours presenting with tias and strokes. 2125 45


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