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)

Tumour angiogenesis is essential for progression of solid tumours and constitutes an interesting target for therapy. However, impaired tumour blood supply may also be an important obstacle for treatment by radiotherapy and chemotherapy. Estramustine has been shown to increase tumour blood flow and potentiate the effect of radiotherapy in experimental glioma. This study investigated the effects of fractionated radiotherapy and estramustine on angiogenesis in malignant glioma. The intracerebral BT4C rat glioma model was used and the animals were given whole brain radiotherapy 4 Gy x 5 days alone or in combination with estramustine 20 mg kg(-1) i.p. daily. Tumour microvascular density (MVD) was assessed by manual and computerized morphometrical analysis. Expression of vascular endothelial growth factor (VEGF) was studied by in situ hybridization. Radiotherapy decreased MVD to 157 vessels per mm2 compared to 217 vessels per mm2 in controls. Estramustine counteracted this anti-angiogenic effect and potentiated the anti-tumoural effect of radiotherapy. In addition, vessel size increased after estramustine treatment. Five days after completion of radiotherapy the expression of VEGF was increased in the centre of the tumours. In conclusion, fractionated radiotherapy decreases microvascular density in experimental malignant glioma. This effect was abolished by estramustine. The anti-vascular effect of irradiation is important to recognize when combining radiotherapy with cytotoxic drugs.
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PMID:Effects of radiotherapy and estramustine on the microvasculature in malignant glioma. 1038 90

Estramustine (EM), a conjugate of nornitrogen mustard and estradiol, is a antimicrotubule drug currently in use for the treatment of advanced prostatic carcinoma. Experimental data are accumulating concerning the antitumor effect of EM in other malignancies, and clinical studies in other malignancies are ongoing. This review summarizes the information available to date concerning the effects of EM and the development of drug resistance. EM depolymerizes microtubules by binding to microtubule-associated proteins (MAPs) as well as tubulin. Because of the radiosensitizing effect of this drug there has been a recent increase in interest concerning estramustine and its clinical use. Recently, it was proposed that EM induces an apoptotic cell death in glioma cells in vitro and in a rat model. EM resistance is distinct from MDR phenotype; it has been used in combination with antimitotic agents which are part of the MDR phenotype. Observations made with estramustine-resistant cell lines show the acquisition of estramustine resistance is a function of multiple adaptation by changes at tubulin expression pattern, and is also associated with changes in tau expression and phosphorylation.
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PMID:Estramustine resistance. 1046 48

Estramustine is a chemotherapeutic drug, used in the treatment of prostatic carcinoma. In the prostate, it binds specifically to a 46 kDa glycoprotein called estramustine-binding protein (EMBP), which consists of three polypeptide components; C1, C2, and C3, each coded for by a specific gene. Expression of EMBP and binding of estramustine has also been detected in malignant glioma in both rats and humans. Elevated levels of this protein in astrocytoma have proved to correlate with poor prognosis. In the present work, expression of all three polypeptide components of EMBP was confirmed in an orthotopic rat glioma model with nested reverse transcriptase PCR and Western blot (molecular weights of 8, 10, and 12 kDa). Specific binding of estramustine with a Kd of 40 for male and 50 for female rats, and a total number of binding sites of 0.7 and 0.4 pmol/mg proteins for male and female rats respectively, was demonstrated with Scatchard plot analysis. These binding characteristics are similar to those of prostatic EMBP. Further studies to elucidate how EMBP expression affects the effect of estramustine treatment, and its putative prognostic value is of special clinical interest. The confirmation of BMBP expression in BT4C rat glioma demonstrates its suitability as a model system for such studies.
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PMID:Estramustine-binding protein in malignant glioma in rat. 1113 83

Patients with high grade glioma generally have poor prognoses. Addition of radiosensitizing agents might improve the response to irradiation. The chemotherapeutic agent estramustine sensitizes experimental gliomas to radiation. Gliomas express estramustine binding proteins, and cytotoxic concentrations of estramustine metabolites are found in gliomas after oral administration. Twenty three patients, aged 25-78, with new or recurrent high grade glioma were treated with estramustine and radiosurgery and/or radiotherapy. Patients with recurrent tumors were treated with estramustine and Gamma Knife stereotactic radiosurgery; eligible tumors were limited to 4 cm maximal diameter. Patients with newly diagnosed tumors were treated with estramustine and fractionated radiotherapy, with radiosurgery also performed if the tumor was less than 4 cm maximal diameter. Estramustine (16 mg/kg per day orally) was started three days prior to radiosurgery, or, if only radiotherapy was performed, on the first day of radiotherapy. Estramustine was continued until the completion of radiosurgery and/or radiotherapy (72 Gy, 60 fractions, 1.2 Gy bid over 6 weeks). Of the 13 patients treated for newly diagnosed glioblastoma, median survival was 16 months with 38% 2-year survival. Of five patients treated for recurrent glioblastoma, survival was 3, 8, 9, 15, and 23 + months. Two patients with recurrent anaplastic astrocytoma survived for 24 and 48+ months. One patient with recurrent anaplastic mixed glioma survived 5+ months. Two patients with newly diagnosed anaplastic oligodendroglioma survived 20 and 42+ months. Four of the new glioblastoma patients developed deep vein thrombosis. The results of this pilot study indicate some benefit, and further investigation incorporating estramustine into clinical trials is suggested.
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PMID:Pilot study of estramustine added to radiosurgery and radiotherapy for treatment of high grade glioma. 1507 70

Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22-87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for the estramustine + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.
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PMID:High-grade astrocytoma treated concomitantly with estramustine and radiotherapy. 1659 26


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