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)

26 patients with astrocytoma grade II-III, and 36 with malignant glioma (astrocytoma grade IV or glioblastoma) were submitted three days after surgery to a cycle of combination chemotherapy, including BCNU, VCR, PCZ (BVP). Eighteen days after surgery, patients received 40 Gy (astrocytoma grade II-III) or 45 Gy (malignant glioma) of megavoltage whole-brain irradiation, with an additional boost to the 'tumor' bed of 20 Gy, delivered in 6 weeks. Vincristine was injected weekly during radiotherapy. At the end of radiotherapy, patients received BVP every 6 weeks for at least 8 cycles or until a recurrence or progressive disease. Performance status of grade 1 or 2 was achieved in 15 (60%) and in 5 (20%), respectively, of patients with astrocytoma grade II-III after 6 months, and in 6 ps. (29%) and in 9 ps. (42%) after 12 months of follow-up. Only 2 (5.5%) and 18 (64%) patients with malignant glioma achieved a performance status of grade 1 or 2 after 6 months, and these proportions are 6% and 35%, respectively, after 12 months. After a 5-year follow-up, 59% of patients with astrocytoma are still alive, with a median survival time of 60+ months, whereas only 4% of patients with malignant glioma are alive, with a median of 11.2 months.
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PMID:Radiotherapy and combination chemotherapy with carmustine, vincristine, and procarbazine (BVP) in primary brain tumors. 298 23

In the first part of this paper, various chemotherapies were performed against oligodendrogliomas subcutaneously transplanted in to nude mice. Vincristine (VCR), adriamycin, and 1000 rads irradiation were effective against this tumors. Concerning these two drugs, dose response effect was observed. And the effect of 1 mg/kg injection of VCR roughly corresponded to that of five weekly injections of 0.2 mg/kg. In the second part of this experiment, single or combined effects of VCR and immunotherapeutic agents including OK-432 (OK), PSK, and recombinant leucocytic interferon (IFN) were examined. Two glioma lines including oligodendroglioma and glioblastoma were used. Following results were obtained from this experiment: 1) Effect of OK and VCR against oligodendrogliomas were as follows: control less than OK local injection (Local) less than OK intraperitoneal injection (IP); VCR; OK (IP X 2) less than VCR + OK(IP) less than VCR + OK (IP X 2). Effects of OK and VCR were expressed in order of their effects against glioblastomas: control less than VCR less than OK (IP); OK(IP X 2); OK(Local) less than VCR + OK (IP); VCR + OK (IP X 2). Effects of PSK and VCR against glioblastomas were as follows: control; PSK (Local) less than VCR less than VCR + PSK (Local) less than VCR + PSK (IP). Effects of IFN and VCR against oligodendrogliomas were as follows: control; IFN (IP) less than VCR less than IFN (Local) less than VCR + IFN (IP); VCR + IFN (Local). Effects of IFN and VCR against glioblastomas were as follows: control less than IFN (IP) less than VCR; IFN (Local); VCR + IFN (IP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunochemotherapy of human gliomas transplanted into nude mice]. 623 39

Topotecan and vincristine were evaluated alone or in combination against 13 independent xenografts and 1 vincristine-resistant derivative, representing childhood neuroblastoma (n = 6), rhabdomyosarcoma (n = 5), or brain tumors (n = 3). Topotecan was given by i.v. bolus on a schedule found previously to be optimal. Drug was administered daily for 5 days on 2 consecutive weeks with cycles repeated every 21 days over a period of 8 weeks. Doses of topotecan ranged from 0.16 to 1.5 mg/kg to simulate clinically achievable topotecan lactone plasma systemic exposures. Vincristine was administered i.v. every 7 days at a fixed dose of 1 mg/kg. Given as a single agent, vincristine induced complete responses (CRs) in all mice bearing two rhabdomyosarcomas (Rh28 and Rh30) and some CRs in Rh12-bearing mice (57%) but relatively few CRs (<29%) in other tumors. As a single agent, topotecan induced CR in a low proportion of tumor lines. A dose-response model with a logit link function was used to investigate whether the combination of topotecan and vincristine resulted in greater than expected responses compared with the activity of the agents when administered alone. Only CR was used to evaluate tumor responses. The combination resulted in significantly greater than expected CRs than individual agents in nine tumor lines (four neuroblastoma, three brain tumors, and two rhabdomyosarcomas). Similar event-free (failure) distributions were shown in SJ-GBM2 glioblastoma xenografts, whether vincristine was administered on day 1 or day 5 of each topotecan course. To determine whether the increased antitumor activity with the combination was attributable to a change in drug disposition, extensive pharmacokinetic studies were performed. However, little or no interaction between these two agents was determined. Toxicity of the combination was marked by prolonged thrombocytopenia and decreased hemoglobin. However, approximately 75 and 80% of the maximum tolerated dose of each single agent, topotecan (1.5 mg/kg) or vincristine (1 mg/kg), could be given in combination, resulting in a combination toxicity index of approximately 1.5. These results show that the therapeutic effect of combining topotecan with vincristine was greater than additive in most tumor models of childhood solid tumors, and toxicity data suggest that this can be administered to mice with only moderate reduction in the dose levels for each agent.
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PMID:Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts. 1058 79

We developed a new method of accelerated chemoimmunoradiotherapy for cerebral glioblastoma and evaluated the immediate effects. A single focal dose of 3Gy was administered once a day 5 times a week until the total focal dose of 51 Gy was reached. Chemoradiotherapy was followed by a course of biotherapy with recombinant interleukine-2 (roncoleukine). On administering a total dose of 10 million units, a course of chemoimmunotherapeutic support was given after a 2-week break. Vincristine 1 mg was injected on day 1 and nitrosourea preparations (lomustine 160 mg or carmustine 100 mg) on day 2. Later on, the same regimen of roncoleukine was used. Our method was followed by longer survival as compared with standard treatment (control) and use of incomplete course chemoimmunotherapy.
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PMID:[Postoperative chemoradiotherapy for cerebral glioblastoma]. 1894 2

The microtubule inhibitor vincristine is currently used to treat a variety of brain tumors, including low-grade glioma and anaplastic oligodendroglioma. Vincristine, however, does not penetrate well into brain tumor tissue, and moreover, it displays dose-limiting toxicities, including peripheral neuropathy. Mebendazole, a Food and Drug Administration-approved anthelmintic drug with a favorable safety profile, has recently been shown to display strong therapeutic efficacy in animal models of both glioma and medulloblastoma. Importantly, appropriate formulations of mebendazole yield therapeutically effective concentrations in the brain. Mebendazole has been shown to inhibit microtubule formation, but it is not known whether its potency against tumor cells is mediated by this inhibitory effect. To investigate this, we examined the effects of mebendazole on GL261 glioblastoma cell viability, microtubule polymerization and metaphase arrest, and found that the effective concentrations to inhibit these functions are very similar. In addition, using mebendazole as a seed for the National Cancer Institute (NCI) COMPARE program revealed that the top-scoring drugs were highly enriched in microtubule-targeting drugs. Taken together, these results indicate that the cell toxicity of mebendazole is indeed caused by inhibiting microtubule formation. We also compared the therapeutic efficacy of mebendazole and vincristine against GL261 orthotopic tumors. We found that mebendazole showed a significant increase in animal survival time, whereas vincristine, even at a dose close to its maximum tolerated dose, failed to show any efficacy. In conclusion, our results strongly support the clinical use of mebendazole as a replacement for vincristine for the treatment of brain tumors.
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PMID:Repurposing Mebendazole as a Replacement for Vincristine for the Treatment of Brain Tumors. 2838 21

Poor response to current treatments for glioblastoma has been attributed to the presence of glioblastoma stem-like cells (GSCs). GSCs are able to expel antitumor drugs to the extracellular medium using the multidrug resistance-associated protein 1 (MRP1) transporter. Tacrolimus (FK506) has been identified as an MRP1 regulator in differentiated glioblastoma (GBM) cells (non-GSCs); however, the effect of FK506 on GSCs is currently unknown. The objective of the following research is to evaluate the effect of FK506 on the MRP1-related chemo-resistant phenotype of GSCs. For this, U87MG and C6 glioma cell lines were used to generate non-GSCs and GSCs. mRNA and MRP1-positive cells were evaluated by RT-qPCR and flow cytometry, respectively. A Carboxyfluorescein Diacetate (CFDA)-retention assay was performed to evaluate the MRP1 activity. Apoptosis and MTT assays were employed to evaluate the cytotoxic effects of FK506 plus Vincristine (MRP1 substrate). GSC-derived subcutaneous tumors were generated to evaluate the in vivo effect of FK506/Vincristine treatment. No differences in transcript levels and positive cells for MRP1 were observed in FK506-treated cells. Lesser cell viability, increased apoptosis, and CFDA-retention in the FK506/Vincristine-treated cells were observed. In vivo, the FK506/Vincristine treatment decreased the tumor size as well as ki67, Glial Fibrillary Acidic Protein (GFAP), and nestin expression. We conclude that FK506 confers a chemo-sensitive phenotype to MRP1-drug substrate in GSCs.
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PMID:FK506 Attenuates the MRP1-Mediated Chemoresistant Phenotype in Glioblastoma Stem-Like Cells. 3020 61

Poor uptake of antitumor drugs by tumor cells is a critical challenge for anticancer therapeutics. Moreover, the deficiency of specific tumor selectivity for tumor sites may further limit the therapeutic efficacy and cause side effects in healthy regions of the body. Vincristine (VCR) is an effective antitumor drug; however, because of its severe nerve toxicity, short half-life, and fast metabolism, its clinical application is limited. Herein, novel anti-CD133 monoclonal antibody (CD133mAb)-targeted therapeutic immunomagnetic albumin microbeads (CD133mAb/TMAMbs) are smartly constructed for enhancing antiglioblastoma treatment. Superparamagnetic iron oxide nanoparticles (SPIO NPs) were first fabricated as nanocarrier cores, then encapsulated with human serum albumin (HSA), and loaded antitumor drug VCR. Then CD133mAb, which has specific affinity with the cell membrane CD133, was subsequently conjugated to form CD133mAb-decorated therapeutic immunomagnetic albumin microbeads (CD133mAb/TMAMbs). The influence of CD133mAb/TMAMbs on the viability, cell cycle, apoptosis, cell cytoskeleton, migration, and invasion of CD133-overexpressing U251 cells was explored. The CD133mAb-conjugated magnetic albumin microbeads exhibited a high drug loading capacity, stability and hemocompatibility, and active targeting ability by specific recognition of the CD133 surface antigen by the bioconjugation of CD133mAb. More importantly, the constructed therapeutic CD133mAb/TMAMbs have a specifically effective uptake via the CD133 transmembrane protein that is overexpressed in U251 glioblastoma cells and displayed an effective antitumor proliferation and invasive ability. Therefore, based on these results, the fabricated CD133mAb/TMAMbs demonstrate promising uses in brain cancer-targeted diagnosis and therapy.
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PMID:Anti-CD133 Antibody-Targeted Therapeutic Immunomagnetic Albumin Microbeads Loaded with Vincristine-Assisted to Enhance Anti-Glioblastoma Treatment. 3157 17