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

Eleven patients with recurrent malignant glioma were treated with single high doses of BCNU ranging from 600 to 1400 mg/sq m. To prevent the characteristic late myelosuppression observed after conventional doses of BCNU, autologous bone marrow harvested just before drug treatment was infused 24 to 36 hours after therapy. Higher doses of BCNU causes earlier and more profound myelosuppression; one patient died on pancytopenia, breakdown of the gut epithelium, and Clostridium septicemia 10 days after receiving 1400 mg/sq m of BCNU. All patients experienced transient emesis; four developed transient elevation of hepatic enzymes, two reversible interstitial pulmonary infiltrates, and two who received 1400 mg/sq m BCNU suffered irreversible cortical damage. Eight patients receiving 600 to 1200 mg/sq m demonstrated reconstitution of polymorphonuclear leukocytes an platelets within at least 30 days after treatment. With a follow-up time of up to 19 months, four patients improved, three stabilized, and three deteriorated and died. The median survival time was 7 months. Computerized tomography performed on patients receiving constant corticosteroids showed diminished contrast enhancement and mass effect in eight patients. High-dose BCNU at doses up to 1200 mg/sq m with marrow rescue is a feasible approach to the treatment of patients with glioblastoma.
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PMID:High-dose BCNU with autologous bone marrow rescue for recurrent glioblastoma multiforme. 625

Despite reported activity in many other solid tumors, high-dose ifosfamide produces few objective responses in recurrent pediatric brain tumors. Alkylating agents such as cyclophosphamide (CYCLO) possess good activity in many of solid tumors, including brain tumors. Although Ifosfamide (IFOS), a structural congener of CYCLO, has been suggested to have greater activity in several tumors, its activity in brain tumors is uncertain. We conducted a phase II trial of every-other day IFOS (3 gm/M2/qod x 3) in 87 recurrent pediatric brain tumors. Responses were evaluable in 71 patients. Partial responses occurred in 1/6 patients with low grade astrocytoma, 1/16 with malignant glioma, 1/16 with medulloblastoma, 1/3 with pineoblastoma and 1/12 patients with ependymoma. No responses occurred among 10 patients with brain stem gliomas or 8 patients with other brain tumors. Despite the poor objective response rate, 23/71 patients were clinically and imaging stable for periods of 8-62 weeks. There was no relationship between prior CYCLO treatment and subsequent response or failure with IFOS. The predominant toxicity was myelosuppression. Although generally reversible, prolonged suppression and sepsis were responsible for the deaths of 3 heavily pretreated patients. Renal toxicity was uncommon; 2 patients had grade III, and one grade IV renal tubular dysfunction. One patient had grade IV hematuria. Neurotoxicity was less common than in studies of daily ifosfamide; only 1 patient had grade IV neurotoxicity. Three patients had grade III or IV IFOS related hyponatremia. Despite the good stable disease rate, the poor rate of objective response suggests that IFOS monotherapy possesses little clinically meaningful activity in brain tumors.
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PMID:A phase II study of every other day high-dose ifosfamide in pediatric brain tumors: a Pediatric Oncology Group Study. 852 93

We evaluated the antitumor efficacy of and patient tolerance to a phase II study of concomitant-to-sequential use of etoposide and radiotherapy for newly diagnosed malignant gliomas. Fifty-two supratentorial malignant glioma patients were enrolled in this phase II study between May 1995 and May 1998. Standard cranial irradiation and six courses of etoposide (100 mg/m2 - xdays 1-3) were administered. The first course of etoposide was given on days 1 to 3 of radiotherapy and was resumed in the week following the end of radiotherapy. Treatment was consolidated by further courses of etoposide every 4 weeks. Fifty-one patients were assessable for toxicity, response, and survival. A complete surgical resection was only noted for 17 patients. Six patients had a confirmed complete response, and eight patients displayed a partial response. Six patients progressed within the first 3 months of starting treatment. The rate of objective response for assessable patients with residual tumor was 41.1%. Hematologic toxicity was mild; grade 3 or 4 neutropenia was noted in five patients, without sepsis. The overall median survival time (MST) was 12.5 months, and the mean survival of this population was 14.9 months. These results suggest a certain efficacy of this regimen testing a concomitant-to-sequential use of etoposide and radiotherapy for newly diagnosed malignant gliomas, and that continued evaluation of this combination is warranted, especially because this treatment is also well tolerated.
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PMID:Response to a phase II study of concomitant-to-sequential use of etoposide and radiation therapy in newly diagnosed malignant gliomas. 1279 12

Strongyloides stercoralis is an intestinal parasite that can cause fatal opportunistic infections in immunocompromised patients. Here we report an immunocompromised patient with glioblastoma who developed disseminated strongyloidiasis 6 weeks after completion of standard radiotherapy and concurrent temozolomide chemotherapy. She was effectively treated with albendazole and ivermectin. Strongyloidiasis should be considered in patients being treated for glioma who have lived or traveled to high risk areas and developed gram negative sepsis, along with gastrointestinal or respiratory symptoms, skin rash or SIADH.
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PMID:Disseminated strongyloidiasis complicating glioblastoma therapy: a case report. 1933 53

Congenital dacryocystocele is a uncommon type of nasolacrimal duct obstruction. Differential diagnosis for masses in the medial canthal region of a newborn include encephalocele, hemangioma, nasal glioma, and dermoid cyst. Because of the risk of becoming infected (acute dacryocystitis) and potentially lethal due to septicemia, aggressive management, including admission for intravenous antibiotics and surgical removal, is now advocated by many pediatric ophthalmologists if the cyst cannot be decompressed. Because of the commonly associated nasal cyst, infants with nasolacrimal dacryocyctocele may also experience respiratory distress especially when breast-feeding. The following case of dacryocystocele, which had progressed to dacryocystitis, was misdiagnosed as an infantile hemangioma. It is important to diagnose this entity quickly and refer for appropriate antibiotic and surgical management to avoid more serious sequelae of sepsis and possible death.
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PMID:Case report: Congenital dacryocystocele and dacryocystitis. 2127 64

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ.
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PMID:A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme. 2499 40

The presence of autoantibodies against neuronal cell surface or synaptic proteins and their relationship to autoimmune encephalitis have recently been characterized. These autoantibodies have been also reported in other pathologic conditions; however, their role during sepsis is not known. This study detected the presence of autoantibodies against neuronal cell surface or synaptic proteins in the serum of septic patients and determined their relationship to the occurrence of brain dysfunction and mortality. This prospective, observational cohort study was performed in four Brazilian intensive care units (ICUs). Sixty patients with community-acquired severe sepsis or septic shock admitted to the ICU were included. Blood samples were collected from patients within 24 h of ICU admission. Antibodies to six neuronal proteins were assessed, including glutamate receptors (types NMDA, AMPA1, and AMPA2); voltage-gated potassium channel complex (VGKC) proteins, leucine-rich glioma-inactivated protein 1 (LGI1), and contactin-associated protein-2 (Caspr2), as well as the GABAB1 receptor. There was no independent association between any of the measured autoantibodies and the occurrence of brain dysfunction (delirium or coma). However, there was an independent and significant relationship between anti-NMDAR fluorescence intensity and hospital mortality. In conclusion, anti-NMDAR was independently associated with hospital mortality but none of the measured antibodies were associated with brain dysfunction in septic patients.
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PMID:Anti-NMDA Receptor Autoantibody Is an Independent Predictor of Hospital Mortality but Not Brain Dysfunction in Septic Patients. 3093 Aug 37

MicroRNA-24 (miR-24) has been identified to be related to the development of glioma. However, the exact molecular mechanism of miR-24 in glioma progression remains vague. The aim of the present study was to investigate the role of miR-24 in sepsis and to reveal the associated mechanisms. Quantitative real-time polymerase chain reaction was used to compare the levels of miR-24 in glioma and normal tissue. The miR-24 inhibitor or miR-24 mimic was transfected into glioma cells, and then the effects of miR-24 on cell proliferation and apoptosis were detected using CCK-8 (Cell Counting Kit-8) assay and flow cytometry, respectively. Western blot was used to examine the levels of CDX1 (caudal-type homeobox 1), PI3K, p-PI3K, Akt, p-Akt, Cyclin D1, p27, proliferating cell nuclear antigen, Bcl-2, Bax, and Cleaved-casp3. Luciferase assay was used to identify the target gene of miR-24. An animal model was established in mice to detect the role of miR-24 in vivo. These results suggested that miR-24 was elevated in glioma, and miR-24 could promote glioma progression by facilitating cell proliferation and inducing cell apoptosis through CDX1/PI3K/Akt signaling pathway, indicating a novel pathway underlying progression in glioma cells and providing a potential target for glioma treatment.
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PMID:MiR-24 Promotes Cell Growth in Human Glioma by CDX1/PI3K/Akt Signaling Pathway. 3287

Non-enzymatic chitinase-3 like-protein-1 (CHI3L1) belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is regulated by extracellular matrix changes, cytokines, growth factors, drugs, and stress. CHI3L1 is synthesized and secreted by a multitude of cells including macrophages, neutrophils, synoviocytes, chondrocytes, fibroblast-like cells, smooth muscle cells, and tumor cells. It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses. CHI3L1 has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, and coronary artery disease. Moreover, following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line, CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models. To date, interleukin-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, chemo-attractant receptor-homologous 2, and CD44 have been identified as CHI3L1 receptors. CHI3L1 signaling plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4+ T cells. Interestingly, CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis. This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis, then posits investigational strategies for targeted therapies.
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PMID:Chitinase-3 like-protein-1 function and its role in diseases. 3292 74