Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to improve local control and survival over those achieved with brain implant alone, a Phase I/II study of interstitial thermoradiotherapy was undertaken for recurrent malignant gliomas and recurrent solitary brain metastases. Between June 1987 and September 1990, 49 tumors in 48 patients were treated with thermoradiotherapy, including 26 glioblastoma multiforme (GM), 16 anaplastic astrocytomas (AA), 4 adenocarcinomas, and 3 melanomas. Patient age ranged from 18 to 71 years and Karnofsky Performance Status from 40 to 90. Stereotactically implanted catheters were used for both hyperthermia and brachytherapy. Hyperthermia was administered immediately before and after brachytherapy, heating as much of the tumor as possible to 42.5 degrees C for 30 min using helical coil microwave antennas. High-activity iodine-125 sources delivered tumor doses of 32.6 to 63.3 Gy. Complications included reversible neurologic changes in 13 patients, 9 seizures, 4 infections, 1 deep venous thrombosis with pulmonary embolus, and 1 scalp burn. Eighteen patients underwent reoperation for tumor and/or necrosis. Follow-up ranged from 9 to 166+ weeks. The median follow-up for living patients with GM and AA was 37 weeks and 92 weeks, respectively. Actuarial median survival was 47 weeks for patients with GM. For patients with AA, actuarial survival was 65% at 18 months and median survival has not yet been reached. Multivariate analysis showed a strong correlation between freedom from local tumor progression and "T90" temperature or minimum tumor temperature. Interstitial brain thermoradiotherapy is now being evaluated in a randomized Phase II trial for previously untreated GM.
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PMID:Thermoradiotherapy of recurrent malignant brain tumors. 131 81

Hypervascularity, focal necrosis, persistent cerebral edema, and rapid cellular proliferation are key histopathologic features of glioblastoma multiforme (GBM), the most common and malignant of human brain tumors. By immunoperoxidase and immunofluorescence, we definitively have demonstrated the presence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFr) in five out of five human glioma cell lines (U-251MG, U-105MG, D-65MG, D-54MG, and CH-235MG) and in eight human GBM tumor surgical specimens. In vitro experiments with glioma cell lines revealed a consistent and reliable relation between EGFr activation and VEGF production; namely, EGF (1-20 ng/ml) stimulation of glioma cells resulted in a 25-125% increase in secretion of bioactive VEGF. Conditioned media (CM) prepared from EGF-stimulated glioma cell lines produced significant increases in cytosolic free intracellular concentrations of Ca2+ ([Ca2+]i) in human umbilical vein endothelial cells (HUVECs). Neither EGF alone or CM from glioma cultures prepared in the absence of EGF induced [Ca2+]i increases in HUVECs. Preincubation of glioma CM with A4.6.1, a monoclonal antibody to VEGF, completely abolished VEGF-mediated [Ca2+]i transients in HUVECs. Likewise, induction by glioma-derived CM of von Willebrand factor release from HUVECs was completely blocked by A4.6.1 pretreatment. These observations provide a key link in understanding the basic cellular pathophysiology of GBM tumor angiogenesis, increased vascular permeability, and cellular proliferation. Specifically, EGF activation of EGFr expressed on glioma cells leads to enhanced secretion of VEGF by glioma cells. VEGF released by glioma cells in situ most likely accounts for pathognomonic histopathologic and clinical features of GBM tumors in patients, including striking tumor angiogenesis, increased cerebral edema and hypercoagulability manifesting as focal tumor necrosis, deep vein thrombosis, or pulmonary embolism.
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PMID:Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. 768 Feb 47

Previous work has demonstrated the importance of the Protein Kinase C (PKC) signal transduction system in regulating the growth rate of malignant gliomas in vitro. Tamoxifen inhibits PKC in a minority of malignant gliomas within the micromolar concentration range in vitro, a property distinct from its estrogen receptor blockade effect. Tamoxifen was administered orally in very high dosages to 11 patients (9 males:2 females, age range 26-73, mean 45 years) with malignant gliomas (anaplastic astrocytoma or glioblastoma multiforme) who had failed treatment with external beam radiation therapy (and additional chemotherapy in 2). The dosage administered was estimated to be that necessary to achieve tissue concentrations within the low micromolar range, shown necessary to inhibit PKC in these tumors in vitro, and is approximately 5 times that used for standard antiestrogen therapy. Tumor reduction on radiographic images (MRI and PET [18FdG uptake]) with clinical improvement occurred in 3 patients; halting of tumor progression clinically and radiographically occurred in an additional patient. Of the remaining seven patients, three patients had marked and rapid progression of their disease despite treatment (dead after 3, 4, and 6 months respectively). Complications of treatment included a deep venous thrombosis requiring anticoagulation in one patient, nausea in one patient, and "hot-flashes" in a third patient. Tumor biopsy and measurement of tamoxifen and its active metabolite within the tumor of one patient (non-responder) showed levels within the middle of the in vitro therapeutic range. Follow-up of alive patients ranges from 4-18 months (mean 10 months). These encouraging preliminary results in a minority of these patients suggests some potential for this type of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical and radiographic response in a minority of patients with recurrent malignant gliomas treated with high-dose tamoxifen. 838 28

From May 1990 to November 1994, 70 consecutive patients suffering from glioblastoma multiforme were treated following surgery with conventional radiotherapy and adjuvant IV BCNU administered alone or in combination with tamoxifen. Twenty-five patients received BCNU alone (control group A) while 24 patients also received 40 mg of tamoxifen (TMX) PO daily (group B) and 21 received 100 mg of TMX PO daily (group C). There were no significant differences between the 3 groups concerning age, type of resection and median post-operative Karnofsky performance status (KPS). Blood toxicity over grade II occurred in 33.5% of patients receiving TMX versus 12% of patients treated with BCNU alone (p < 0.05). Deep venous thrombosis complications were observed in 4 patients of each TMX group, whereas they were not observed in the control group (p < 0.04). Median time to tumor progression (MTTP) was 35 weeks in the control group and 27 weeks in both TMX groups B and C. Median survival time (MST) was 56, 66 and 51 weeks, respectively. These results suggest that the addition of TMX to standard treatment of glioblastomas does not affect the time to tumor progression and overall survival but may increase the risk of deep venous thrombosis or nitrosourea-induced blood toxicity.
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PMID:Treatment of supratentorial glioblastoma multiforme with radiotherapy and a combination of BCNU and tamoxifen: a phase II study. 1084 93

The purpose of this study was to determine the safety of tinzaparin for deep vein thrombosis prophylaxis in newly diagnosed grade III-IV malignant glioma patients. Patients were initiated on daily tinzaparin at a fixed dose of 4,500 IU subcutaneously between 48 h and 4 weeks post-operative for planned duration of 12 months. During chemotherapy cycles, blood counts were monitored weekly and tinzaparin was held if the platelet count decreased to <50,000 and was re-initiated at a platelet count >100,000. Forty patients were enrolled into the study, 35 with glioblastoma multiforme and 5 with anaplastic astrocytoma. Possible attributable toxicity was limited to two patients who developed CNS hemorrhages (one grade 1 and one grade 2) and one patient with an increase in liver enzymes (grade 3). There were no patients with a grade 4 or 5 CNS hemorrhages or systemic hemorrhages >or=grade 2. The median time on prophylactic tinzaparin was 161 days (range of 5 to 601 days). One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin. Tinzaparin at a fixed prophylactic dose is safe and may decrease the incidence of thromboembolic complications in brain tumor patients.
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PMID:Tinzaparin prophylaxis against venous thromboembolic complications in brain tumor patients. 1941 55

Patients with glioblastoma multiforme (GBM) are known to be at risk for hypercoagulable events. Tumoral intravascular thrombi likely contribute to the development of hypoxia and necrosis. The purpose of this study was to assess whether there is a relationship between the number of thrombi identified microscopically at the time of tumor resection and the subsequent development of extremity deep venous thrombosis (DVT). A retrospective review of 96 patients (53 men and 43 women; age range, 21-92 years; mean age, 60.2 years) with GBM (World Health Organization grade IV) was carried out. Thrombi were counted (number of thrombi/blood vessels evaluated/10 high-power fields) in nonnecrotic areas of the resected tumor and correlated with a variety of clinical and pathological parameters, including the development of postoperative DVT, as detected by extremity ultrasound. Thrombi were identified in the resected GBM in 66 (69%) patients. Of the tumors with thrombi, the percentage of blood vessels with thrombi ranged from 1.1% to 42.9% (mean, 10.7%). Deep venous thrombosis was discovered in 30 (31.3%) patients. There was no correlation between the number of microscopic thrombi and the development of DVT. Eighty-one patients died of tumor (survival, 1-66 months; mean, 11.0 months), 12 patients were alive at last known follow-up (mean, 23 months), and 3 patients were lost to follow-up. Of patients with DVT, 27 patients died of tumor (survival, 1-47 months; mean, 11.0 months), 3 patients were alive (18, 20, and 21 months), and 1 patient was lost to follow-up. There was no correlation between the number of microscopic thrombi and the percentage of resected tumor that was necrotic (range, <5%-90%), presence of palisaded necrosis (36.8% of tumors), presurgical (mean, 78.3) or postsurgical (mean, 75.5) Karnofsky performance scores, or survival (mean, 8.9 months in patients with no microscopic thrombi vs 11.5 months in patients with thrombi). Microscopic thrombi were identified in about two thirds (69%) of patients with GBM, and DVT developed in about one third (31.3%) of patients with GBM. There was no correlation between the number of microscopic thrombi and the subsequent development of DVT in patients with GBM. Patients who developed DVT did not appear to have a worse survival.
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PMID:Microscopic thrombi in glioblastoma multiforme do not predict the development of deep venous thrombosis. 1975 4

A 58-year-old woman presented with right supplementary motor area glioblastoma multiforme and deep venous thrombosis in her legs. The tumor was resected after temporary inferior vena cava filter placement, considering that increased thrombosis during and after the operation would cause fatal pulmonary embolism. After anticoagulation with unfractionated heparin, thrombocytopenia was aggravated, and computed tomography showed filter catheter-related thrombosis in the inferior vena cava. The diagnosis was heparin-induced thrombocytopenia, and argatroban and urokinase were administered. Thrombolysis with urokinase was completed and the temporary inferior vena cava filter catheter was removed without complication. The present case illustrates the possibility of heparin-induced thrombocytopenia associated with catheter-related thrombosis in neurosurgery.
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PMID:Heparin-induced thrombocytopenia in a glioblastoma multiforme patient with inferior vena cava filter placement for deep venous thrombosis. 2170 Nov 11

Previous evidence suggests that the humanized anti-VEGF antibody bevacizumab increases thrombosis risk in glioma patients. Here, we comprehensively assessed the risk of adverse vascular events in adult glioma patients receiving bevacizumab therapy. Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted to find prospective phase II/III clinical trials on adult bevacizumab-treated glioma patients and non-bevacizumab-treated controls that reported data on adverse vascular events. Four high-quality trials were finally included in the systematic review, scoring greater than or equal to 7/8 on the Newcastle-Ottawa Scale. Three trials provided sufficient data for four meta-analytical comparisons between bevacizumab-treated and control groups of newly diagnosed glioblastoma multiforme (GBM) patients: all-cause discontinuation, thrombocytopenia, deep vein thrombosis (DVT), and pulmonary embolism. None of these adverse outcomes were found to be significantly different between bevacizumab-treated and control groups (P > 0.05); however, there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism (P = 0.07). As there was a trend toward significance with regard to bevacizumab therapy and the risk of pulmonary embolism, anticoagulation may be advisable in certain newly diagnosed adult GBM patients who display a history of thromboembolism and/or more serious risk factors for thromboembolic events.
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PMID:Risk of Adverse Vascular Events in Newly Diagnosed Glioblastoma Multiforme Patients Treated with Bevacizumab: a Systematic Review and Meta-Analysis. 2642 13

A 37-year-old woman with known glioblastoma multiforme was admitted for treatment of new deep vein thrombosis. Anion gap and plasma lactate levels were found to be elevated. Magnetic resonance imaging of the brain showed a stable, advanced glioblastoma multiforme. All causes of lactic acidosis, including infections and medications, were ruled out. Aggressive tumors have been shown to produce lactate levels in minute quantities in their microenvironment, which helps them metastasize and evade immune response and even radiation.
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PMID:Lactate levels with glioblastoma multiforme. 2736 83