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)

The management of patients with glioblastoma remains challenging with an average survival of 32-56 weeks. We report on a clinical trial of patients with recurrent glioblastoma treated with adenovirus/herpex simplex-thymidine kinase/ganciclovir (ADV/HSV-tk/GC). Entry criteria for this study included: recurrent malignant glioma after surgical resection and conventional radiation therapy. At the time of recurrence, computerized volumetric resection of the tumor was performed and the ADV/HSV-tk complex was injected in the tumor bed. GC was administered 24 h after surgery (10 mg/kg/day) for 7 days. Patients were divided into 3 ADV/HSV-tk dose-escalating cohorts. Adenoviral vector shedding, and local or systemic toxicity did not occur in this study. Magnetic resonance imaging showed lack of increased brain edema in the treated patients. Histological examination of the 5 patients that had repeated surgery after gene therapy treatment showed lack of tissue toxicity. Additionally, PCR for HSV-tk was negative in the brain 3 months after injection. The patients' Karnofsky score was maintained > or = 70 in 8/10 patients (80%) and 5/9 patients (55%) 3 and 6 months respectively, after gene therapy. Ten of 11 patients survived > or = 52 weeks from diagnosis with an average survival of 112.3 weeks. One patient is still alive 248 weeks from diagnosis. These data show that the ADV/HSV-tk/GC complex at the dose used in this study is safe. Additional dose escalation is currently in progress.
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PMID:Adenovirus/herpes simplex-thymidine kinase/ganciclovir complex: preliminary results of a phase I trial in patients with recurrent malignant gliomas. 1468 78

Brain tumors not uncommonly display a chronic course, with symptoms occurring insidiously. This case report describes a meningioma patient who presented sudden onset and rapidly progressing symptoms. She was 49 years old, a referred case from a nearby hospital, with severe headache and fever. This was also accompanied by unconsciousness and left hermiparesis which necessitated emergency brain CT and MRI scanning. A right temporal 5 cm ring enhancing lesion with massive surrounding edema was revealed. Despite osmotic diuretics to relieve brain edema, symptoms worsened, so decompressive right temporal craniotomy and total excision of the tumor was performed. This mass lesion was found to be extra axial, with histology revealing on atypical meningioma with massive necrosis. This rare case which is thought to be due to massive peritumoral edema, possibly from an ischemic occluded major feeder, conforms to glioma radiologically; while the clinical picture has a similarity to brain abscess. This case is presented as a reminder to neurosurgery practice that meningioma can also be a possibility when a ring enhancing cerebral mass in encountered and is accompanied by such a bizarre sudden and rapidly progressing neurologic condition.
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PMID:[A case of atypical meningioma associated with acute deterioration and cerebral herniation]. 1471 45

Although thrombin is a critical enzyme in the coagulation cascade, it has become apparent that it has many other effects. Thus, it may induce brain edema formation, angiogenesis and cell proliferation. Because of the importance of these three factors in the extremely poor prognosis of glioma patients, the present study examined the role of thrombin in that disease state. We found that thrombin activity is increased in a rat glioma model and thrombin positive cells were present in the tumor. Anti-thrombin treatment with argatroban reduced brain edema, tumor growth, and tumor-related neurological deficits. Our results suggest that thrombin is a new target for glioma treatment.
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PMID:A thrombin inhibitor reduces brain edema, glioma mass and neurological deficits in a rat glioma model. 1475 95

Vasogenic brain edema is a common diagnostic and management problem in brain tumor patients. Molecular mechanisms play a role in the pathophysiology, including abnormalities of tumor endothelium, vascular endothelial growth factor and leukotriene synthase. Edema diagnosis is facilitated by the development of neuroradiological imaging techniques, with diffusion-weighted imaging (DW-MRI) differentiating tumor grades or abscesses and tumors, and diffusion tensor imaging representing an advanced technique to potentially differentiate malignant glioma from metastasis or facilitate preoperative planning. Edema is a prognostic factor for meningioma and metastases but not for glioma. Therapy includes, amongst others, tumor-directed measures such as debulking surgery, radio- and chemotherapy. However, local therapeutic approaches might also induce or exacerbate edema formation. Peritumoral edema can usually be managed with corticosteroids. However, patients on corticosteroids are at greater risk of metabolic changes, Pneumocystis carinii pneumonia, and thromboembolism. More recently, inhibitors of cyclooxygenase-2 as well as boswellic acids have been explored as antiedema agents in patients with brain tumors.
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PMID:Brain edema in neurooncology: radiological assessment and management. 1524 15

Chemotherapy for the treatment of brain metastases arising from non-small cell lung cancer (NSCLC) has been limited by poor efficacy and high toxicity. Especially in heavily pretreated patients with brain metastases, further chemotherapy is known to be extraordinarily difficult. Expression of vascular endothelial growth factor is necessary but not sufficient for production and growth of brain metastasis. Most current preclinical experiments evaluate antiangiogenic drugs used singly or in combination with other antiangiogenic drugs and/ or cytotoxic drugs. Cerebral edema is responsible for significant morbidity and mortality in patients harboring malignant gliomas. In preclinical experiments, cyclooxygenase (COX) -2 plays an important role in the formation of brain edema. Glioma-infiltrating microglia are a major source of PGE2 production through the COX-2 pathway and support the use of COX-2 inhibitors as possible alternatives to glucocorticoids in the treatment of peritumoral edema in patients with malignant brain tumors. Here we report a case of lung cancer patient with brain metastases who had been treated with chemotherapy and whole-brain radiation therapy (WBRT). He was treated with thalidomide, celceoxib and gemcitabine, after which brain metastases have almost completely disappeared. He tolerated extremely well. This combination may play an important role for patients with NSCLC and brain metastases.
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PMID:[A case report of chemotherapy with thalidomide, celecoxib and gemcitabine in the treatment of patients with brain metastases from lung cancer]. 1622 82

Fluid filled cystic cavities are accompaniments of some cerebral gliomas. These tumoural cysts together with peritumoural vasogenic brain oedema add to the morbid effects of the gliomas in terms of mass effect and increased intracranial pressure. Although different mechanisms have been suggested as to the pathogenesis of glioma-associated cysts, it is still unclear why these cysts appear in only a limited number of cerebral gliomas while brain oedema, a probable precursor of glioma cysts, is a usual accompaniment of most gliomas. Here, the authors present a two-hit hypothesis of brain glioma cyst formation. We suggest that after the formation of vasogenic tumoural brain oedema, microvascular phenomena may lead to the formation of microcysts, which might later become confluent and grow to form macroscopic cysts. Progress in the understanding of pathogenesis of cerebral glioma cysts might set targets for treatment of brain edema and glioma cysts.
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PMID:Pathophysiology of glioma cyst formation. 1632 75

Our previous studies showed that intracerebral infusion of argatroban, a specific thrombin inhibitor, reduces brain edema and neurological deficits in a C6 glioma model. The present study investigated whether systemic argatroban administration can reduce glioma mass and neurological deficits and extend survival time in C6 and F98 gliomas. Rat C6 or F98 glioma cells were infused into the right caudate of adult male Fischer 344 rats. Osmotic minipump loaded with argatroban (0.3 mg/hour) or vehicle was implanted into abdomen immediately after glioma implantation. Tumor mass was determined at day 9. Over the period of the experiment, the animals underwent behavioral testing (forelimb placing and forelimb use asymmetry). In addition, survival time was tested in the F98 glioma model. In C6 glioma, argatroban reduced glioma mass (p < 0.05) and neurological deficits (p < 0.05) at day 9. In F98 glioma, agratroban prolonged the survival time (p < 0.05) and reduced the body weight loss (84 +/- 15 gram vs. 99 +/- 2 gram in the vehicle group, P < 0.05). In conclusion, systemic use of argatroban reduced tumor mass and neurological deficits, and prolonged survival time. These results suggest that thrombin plays a key role in glioma growth and thrombin inhibition with argatroban may be a novel treatment for gliomas.
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PMID:Systemic use of argatroban reduces tumor mass, attenuates neurological deficits and prolongs survival time in rat glioma models. 1646 90

Cerebral tissue acidosis following ischemia or traumatic brain injury contributes to cytotoxic brain edema formation. In vitro lactacidosis induces swelling of glial cells by intracellular Na+- and Cl--accumulation by the Na+/H+-antiporter, Cl-/HCO3--antiporters and the Na+-K+-2Cl--cotransport. The present study aimed to elucidate whether mechanisms of lactacidosis-induced glial swelling are dependent on intra- or extracellular Ca2+-ions. Therefore, C6 glioma cells were exposed to a lactacidosis of pH 6.2 in standard or calcium-free medium and following intracellular calcium chelation. Cell volume and intracellular pH were assessed by flow cytometry. Lactacidosis of pH 6.2 induced a prompt and sustained swelling of suspended C6 glioma cells reaching a maximum of 128% within 60 min. Omission of Ca2+ from the suspension medium strongly attenuated cell swelling while chelation of intracellular Ca2+ had no effects. Intracellular acidosis was not affected by either treatment. The present data show a strong dependency of lactacidosis-induced glial swelling upon extracellular Ca2+ while intracellular acidosis is not affected by omission of [Ca2+]e. Therefore, our data suggest that the Na+-K+-2Cl--cotransporter, the only so far known transporter involved in cell volume regulation but not in pHi regulation during lactacidosis, is activated in a [Ca2+]e-dependent manner.
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PMID:Lactacidosis-induced glial cell swelling depends on extracellular Ca2+. 1646 48

CEP-7055, a fully synthetic, orally active N,N-dimethylglycine ester of CEP-5214, a C3-(isopropylmethoxy)-fused pyrrolocarbazole with potent pan-vascular endothelial growth factor receptor (VEGFR) kinase inhibitory activity, has recently completed phase I clinical trials in cancer patients. These studies evaluated the antitumor efficacy of CEP-7055 using orthotopic models of glioblastoma and colon carcinoma in combination with temozolomide, and irinotecan and oxaliplatin, respectively, for their effects on primary and metastatic tumor burden and median survival. Chronic administration of CEP-7055 (23.8 mg/kg/dose) and temozolomide resulted in improvement of median survival of nude mice bearing orthotopic human glioblastoma xenografts compared with temozolomide alone (261 versus 192 days, respectively; P < or = 0.02). Reductions in neurologic dysfunction, brain edema, hemorrhage, and intratumoral microvessel density (CD34 staining) were observed in glioma-bearing mice receiving CEP-7055 alone, temozolomide alone, and the combination of CEP-7055 and temozolomide relative to vehicle and to temozolomide monotherapy. The administration of CEP-7055 in combination with irinotecan (20 mg/kg/dose i.p. x 5 days), and to a lesser degree with oxaliplatin (10 mg/kg/dose i.v.), showed reductions on primary colon carcinoma and hepatic metastatic burden in the CT-26 tumor model relative to that achieved by irinotecan and oxaliplatin monotherapy. These data show the significant efficacy and tolerability of optimal efficacious doses of CEP-7055 when given in combination with temozolomide and irinotecan relative to monotherapy with these cytotoxic agents in preclinical orthotopic glioma and colon carcinoma models and lend support for the use of these treatment regimens in a clinical setting in patients with glioblastoma and colon carcinoma.
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PMID:The effects of the oral, pan-VEGF-R kinase inhibitor CEP-7055 and chemotherapy in orthotopic models of glioblastoma and colon carcinoma in mice. 1689 60

A 29-year-old man developed a delayed postoperative extradural hematoma after the craniotomy to treat recurrent malignant glioma and hydrocephalus. The patient became alert on the day after the operation. Computed tomography (CT) 12 hours after the operation showed no intracranial hematoma and the subgaleal drainage catheter was removed 18 hours after the operation. The patient complained of headache and went into a coma 2 hours after removal of the drain. CT demonstrated massive acute extradural hematoma with marked midline shift. Emergency craniotomy revealed that the source of the hematoma was an injured scalp artery along the route of the drainage catheter. He died of acute brain edema 9 days later. Hemostasis should be confirmed at insertion and removal of the drainage catheter.
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PMID:Postoperative extradural hematoma after removal of a subgaleal drainage catheter--case report. 1765 18


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