Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mxi1 is thought to negatively regulate Myc function and may therefore be a potential tumor suppressor gene. Little effort has yet been made to find alterations involving this gene in human solid tumors. We screened 31 human gastric cancers, 7 esophageal cancers, 85 bone and soft tissue tumors of various types, including 4 neurofibrosarcomas. We also examined 29 human tumor cell lines consisting of 12 esophageal cancers, 7 glioma/glioblastomas and 10 others for Mxi1 mutations in exons 1, 2, 4 (HLH domain), 5 and 6. Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and subsequent sequencing revealed three distinct polymorphisms in the intron-exon boundary upstream from exon 6. We discovered a missense mutation, GCA to GTA (Ala 54 Val), in exon 2 in a neurofibrosarcoma patient (case 1), two missense mutations, AAA to CAA (Lys 118 Gln) and GAA to GGA (Glu 154 Gly) in exon 5 of another neurofibrosarcoma patient (case 2), and 3 amino acid substitutions, GTG to GCG (Val 179 Ala), GTT to GCT (Val 181 Ala) and TTC to CTC (Phe 186 Leu), in a third neurofibrosarcoma patient (case 3). In case 3, loss of heterozygosity was also demonstrated by informative (TTC)3/(TTC)2 polymorphism. Our data demonstrate that mutations occur in the Mxi1 gene in neurofibrosarcoma. Missense mutations in the functional domain of Mxi1 in these cases may be involved in the pathogenesis of neurofibrosarcoma.
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PMID:Mxi1 mutations in human neurofibrosarcomas. 1047 Feb 86

Anthracyclines are effective in breast cancer and have in vitro cytotoxicity in glioma. In patients with glioma anthracyclines are not effective possibly because the hydrophilic drugs do not reach cytotoxic levels in tumor tissue. Idarubicin is more lipophilic than the other anthracyclines and is more cytotoxic in glioma cell lines. The uptake of idarubicin and its major metabolite idarubicinol in brain tumor tissue were measured in a patient with a brain metastasis from breast cancer and in 4 patients with malignant glioma after an oral dose of idarubicin (45 mg/m2 in 1 patient; 25 mg/m2 in 4 patients), given 15-24 h before brain tumor resection. The concentrations of idarubicin and of idarubicinol in tumor tissue exceeded the concurrent plasma concentrations as well as the peak plasma concentrations in all cases. The median tumor:concurrent plasma ratio of idarubicinol was 5.7 (range 1.7-18). The concentration of idarubicinol in the marginal zone between brain and tumor tissue was lower than in central tumor tissue, but was still higher than the plasma concentration in 2 of the 3 examined cases. Bone marrow suppression (platelets CTC grade 2, granulocytes CTC grade 4) occurred after a single dose of 45 ml/m2. No toxicity was seen at a dose of 25 mg/m2. These results, the in vitro activity of idarubicin in glioma, the convenience of oral administration, and its toxicity profile make clinical studies with idarubicin in malignant glioma, and perhaps also in brain metastases from breast cancer worthwhile.
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PMID:Penetration of idarubicin into malignant brain tumor tissue. 1058 71

Temozolomide (TMZ) has demonstrated activity and acceptable toxicity for the treatment of recurrent malignant gliomas in carious prospective phase II studies. No information is, however, available on TMZ treatment for recurrent malignant glioma in Japanese patients. We report Hokkaido University Hospital experience on 35 adult patients with a recurrent malignant glioma, including 13 glioblastomas, 9 anaplastic astrocytomas, and 13 anaplastic oligondendroglial tumors. The median age was 52 years. The starting dose of TMZ was 150 mg/m2/day for 5 days. When no remarkable toxicity was observed, the dose was increased to 200 mg/m2 for subsequent cycles, every 4 week. In the 35 patients, the overall objective response rate (partial response) was 12% and 74% of the patients achieved disease stabilization. The median progression-free survival was 28 weeks and the median overall survival was 43 weeks. Although hematological toxicity was the most frequent adverse event (CTC grade 3 or 4 in 6 patients), overall toxicity was generally mild. Four patients required hospitalization due to the toxicity, but 28 patients had been treated with TMZ at our outpatient clinic. These results suggested that the reported efficacy and toxicity profile of TMZ for the treatment of Japanese patients with recurrent malignant glioma is reproducible from the setting of clinical trials in the western countries.
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PMID:[Temozolomide in the treatment of recurrent malignant glioma]. 1715 70

Temozolomide (TMZ) is the standard of care for patients with newly diagnosed glioblastoma (GBM) as well as those with recurrent anaplastic glioma (AG) and GBM. It has become common practice to re-expose patients to TMZ who had been previously treated with TMZ, or to switch patients to alternative dosing regimens of TMZ when there are signs of relapse or progress on standard TMZ therapeutic regimens. To date, however, there is a scarcity of data on the efficacy of this therapeutic strategy, currently referred to as TMZ rechallenge. We have conducted a retrospective review of patients with recurrent glioma rechallenged with TMZ. Patients experiencing progressive disease (PD) during TMZ therapy who were rechallenged with alternative TMZ regimens and patients rechallenged after stable disease in a TMZ-free interval were evaluated separately. A total of 90 rechallenges were identified in 80 patients. The progression-free survival at 6 months (PFS-6) was 48% in patients with AG (12/25) and 27.7% in those with GBM (14/47). The PFS-6 was 16.7% in AG and 26.3% in GBM for patients switched during TMZ and 57.9 and 28.6% in patients rechallenged after a TMZ-free interval of at least 8 weeks. Relevant hematological toxicity (NCI-CTC grade 3-5) was observed in 22 of 90 rechallenges, and relevant non-hematological in ten of 90 rechallenges. Temozolomide was well tolerated and generated promising PFS-6 in patients who had previously failed TMZ, regardless if they progressed during TMZ treatment, or if they were rechallenged after a TMZ-free interval. These results suggest that the TMZ rechallenge strategy warrants further investigation in a prospective randomized trial.
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PMID:Rechallenge with temozolomide in patients with recurrent gliomas. 1924 Sep 62

The study aimed to examine the tolerability of the combination of radiotherapy and tamoxifen and the effect on median and event free survival as well as collecting data on the use of steroids in this population. 31 patients with diffuse intrinsic pontine glioma, diagnosed on clinical and radiological criteria, were treated with high-dose oral tamoxifen (120 mg/m(2)/day) given concomitantly with standard dose radiotherapy (54 Gy in 1.8 Gy fractions over 6 weeks). Results Tamoxifen was well tolerated with no grade 3 or 4 CTC toxicity reported. At 1 year, the progression free and event free survival were 3.2% (95% CI: 0.2-14.1%), and at 6 months 19.4% (CI: 7.9% to 34.6%). The overall survival at 1 year was 16.1% (CI: 5.9-30.9%) with median survival 6.32 months. In this study, in which tamoxifen was used in conjunction with radiotherapy, progression free survival was shown to be less good when compared with historical data HR = 3.1 (CI: 1.7-5.7). There was no significant reduction in overall survival. The addition of high-dose tamoxifen, although well tolerated, confers no clinical benefit to patients treated with diffuse intrinsic pontine glioma treated with standard radiotherapy.
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PMID:The addition of high-dose tamoxifen to standard radiotherapy does not improve the survival of patients with diffuse intrinsic pontine glioma. 2023 35

Temozolomide (TMZ) as a concomitant and adjuvant chemotherapy to radiotherapy following maximal surgical resection is the established standard therapy for patients with newly diagnosed high-grade glioma. However, detailed analysis of chemotherapy-induced nausea and vomiting (CINV) associated with concomitant TMZ has not been sufficiently described. We prospectively analyzed the profile of CINV associated with concomitant TMZ. Eighteen consecutive patients with newly diagnosed high-grade glioma treated with concomitant chemoradiotherapy including TMZ were enrolled. CINV was recorded using a daily diary including nausea assessment, emetic episodes, degree of appetite suppression, and antiemetic medication use. The observed incidence rates of all grade nausea, moderate/severe (CTC grade 2, 3) nausea, emetic episodes, and appetite suppression for the overall period were 89%, 39%, 39%, and 83%, respectively. Moderate/severe nausea and severe (CTC grade 3) appetite suppression were frequently observed during the delayed phase of the treatment. Emetic episodes and moderate/severe nausea were significantly correlated with female gender. Moderate/severe nausea and severe appetite suppression were significantly correlated with low lymphocyte counts before chemoradiotherapy. For CINV associated with concomitant TMZ, enhanced antiemetic therapy focused on the delayed phase of the treatment will likely be beneficial, especially in female patients with a low lymphocyte count before chemoradiotherapy.
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PMID:Profile Analysis of Chemotherapy-induced Nausea and Vomiting in Patients Treated with Concomitant Temozolomide and Radiotherapy: Results of a Prospective Study. 2634 64

Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326 blood samples from patients with 6 different solid organ carcinomas and lymphomas. Significantly, CTC-positive rates increased remarkably with tumor progression from N0M0, N+M0 to M1 in each of 5 tested cancers (lung, colon, liver, gastric and pancreatic cancer, and glioma). Among 21 non-small cell lung cancer cases in which CTC values were consecutively monitored, 81% showed treatment-related decreases, which was also found after treatments in the other solid tumors. Moreover, monitoring CTC values provided an efficient treatment response indicator in hematological malignancies. Compared to CellSearch, our method detected significantly higher positive rates in 40 NSCLC in all stages, including N0M0, N+M0 and M1, and was less affected by chemotherapy. This simple, robust and clinically-applicable technology detects viable CTCs from solid and hematopoietic malignancies in early to late stages, and significantly improves clinical detection and treatment prognostication.
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PMID:Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells. 2720 95