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At least 127 records · Page 7Linked to original sources
PubMedDate not supplied

Retrovirus-mediated gene therapy of experimental brain neoplasms using the herpes simplex virus-thymidine kinase/ganciclovir paradigm.

Recent results in experimental brain tumors indicate that transfer of sensitizing genes to tumor cells in vivo with subsequent drug treatment can reduce tumor masses and prolong the survival of rodents. In the present study, the 9L rat gliosarcoma model was used to evaluate the therapeutic effectiveness of the herpes simplex virus-thymidine kinase (HSV-tk) gene, delivered by a retrovirus vector, against tumor cells in the rat brain after systemic application of the nucleoside analogue ganciclovir (GCV). The HSV-tk gene was inserted into a retroviral vector (pMFG), which was produced using the amphotropic packaging cell line CRIP-MFG-S-HSV-TK. Packaging cells were implanted into established 9L tumors in the brains of syngeneic rats to effect gene delivery to tumor cells, followed by intraperitoneal GCV injections. Treated animals survived significantly longer (more than twice as long) than did the control groups. Brains from GCV-treated and nontreated animals were examined immunohistochemically at different time intervals after grafting of CRIP-MFG-S-HSV-TK cells and GCV treatment. Tumors in GCV-treated animals were significantly smaller as compared with nontreated animals at all time points. Sections stained immunohistochemically for HSV-TK confirmed gene transfer to tumor cells, which could be distinguished from packaging cells by different morphology and immunohistochemical staining for the retroviral envelope protein gp70. Approximately 45% of the cells in tumors implanted with CRIP-MFG-S-HSV-TK cells, but not treated with GCV, showed immunocytochemical staining for HSV-TK, demonstrating a high-efficiency of retrovirus-mediated gene transfer. Tumors in rats treated with packaging cells and GCV showed only 9% HSV-TK-positive cells after treatment, indicating that most cells expressing the HSV-tk gene were killed. The success of this therapeutic modality in experimental animals depends in large parts on the high efficiency of gene delivery and on the immune response against tumor cells.

Animals↗
PubMedDate not supplied

[Value of isotope scintigraphy and angiography in the diagnosis of brain neoplasms].

The results of cerebral angiography and isotope scintigraphy were compared in 50 patients with brain tumours. The usefulness of each method for detection, localization and determination of the size of the tumour was evaluated. The overall detection rate of brain tumours was 92% in the case of angiography and 90% for scintigraphy, the possiblity of localization was 86% and 90% and size determination was 50% and 74% respectively. Scintigraphy often failed in the diagnosis of astrocytomas and tumours situated near the base of the brain, but this method was more reliable in evaluating the site and size of tumours than angiography.

Adolescent↗
PubMed1983

[New management of brain neoplasms. 2. Local injection of adriamycin].

This is the second paper on a trial treatment of malignant brain tumors by postoperative intracavity chemotherapy. In 34 patients with malignant brain tumors in cerebral hemispheres, 0.5 mg adriamycin (ADM) was injected through an Ommaya's device into the tumor-bed every other day after subtotal removal of tumor at craniotomy. Usual total doses of ADM were 5.0-10.0 mg. The patients were usually treated with 60Co-irradiation and immunotherapy after local injection of ADM. Twenty patients with malignant astrocytomas (Kernohan grade 3 or 4) of the cerebral hemisphere were treated with this local injection method of ADM. Clinical effect obtained was 65% and one-year survival rate was 55%. On the other hand, in 14 patients with other malignant brain tumors such as metastatic carcinoma, primary sarcoma, germinoma and medulloblastoma, clinical effect obtained was 36% and one-year survival rate was also 36%. In the autopsy cases of malignant brain tumors, the similar pathological findings were observed as obtained in the patients treated with local injection of bleomycin (BLM). Macroscopically there were extensive necrotic foci, small haemorrhages and increasing fibrin deposit. However, in the cases treated with ADM, the rate of increasing of fibrin debris and necrotic tissues in the tumor cavity were much less than those of in the cases with BLM. Comparative study was carried out on the estimation of the levels of concentration of ADM in the tumor tissues when ADM was injected locally and intravenously. The recurrent tumor tissues were used for the estimation of locally administered ADM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The risk of cancer in relatives of patients with brain neoplasm.

The family trees of 142 patients, suffering from histologically proven brain tumour, were compared to those of an equal number of sex and age matched controls. The results showed no statistically significant differences in the occurrence of malignant neoplasm between the two groups. These results indicate that the risk of cancer among relatives of patients with brain tumours does not exceed that of healthy controls.

Adult↗
PubMed1995

Selective uptake of viral and monocrystalline particles delivered intra-arterially to experimental brain neoplasms.

In this study we investigated the intra-arterial delivery of viral and nonviral particles to experimental brain tumors. A herpes simplex virus (HSV) vector and monocrystalline iron oxide nanoparticles (MION) were injected into the internal carotid artery of Fisher 344 rats harboring intracerebral 9L gliosarcomas, using bradykinin to disrupt the blood-tumor barrier. Brain and internal organs were stained both for virus-mediated gene expression and for iron. Quantitative comparisons of gene expression and MION uptake with and without blood-tumor barrier disruption were performed in the center and at the periphery of the tumor mass, as well as in normal brain. In addition, MION distribution was traced in vivo by MR imaging. Delivery of HSV into 9L gliosarcoma cells was greatly enhanced by intra-carotid bradykinin infusion. Virus-mediated expression of the HSV-thymidine kinase (TK) and beta-galactosidase gene products was highest at the tumor periphery as compared to the tumor center. Selective HSV infection of multiple tumor foci was achieved in both hemispheres without affecting normal brain. MION uptake was high at the tumor periphery even without blood-tumor barrier disruption. Bradykinin increased MION uptake predominantly in the center of the tumor with virtually no effect at the periphery. These findings show that selective blood-tumor barrier disruption by bradykinin can be used to enhance HSV-mediated gene delivery to tumor cells in the periphery of brain tumors. A crucial aspect in the treatment of malignant brain tumors is the eradication of tumor cells infiltrating the brain; bradykinin may facilitate access of vectors to these areas by selective disruption of their neovasculature.

Animals↗