Showing papers by "Robert L. Martuza published in 1995"
TL;DR: A double mutant of the herpes simplex virus type 1 (termed G207) with favourable properties for treating human malignant brain tumours: replication–competence in glioblastoma cells, attenuated neurovirulence, temperature sensitivity, ganciclovir hypersensitivity, and the presence of an easily detectable histochemical marker.
Abstract: We have created a double mutant of the herpes simplex virus (HSV) type 1 (termed G207) with favourable properties for treating human malignant brain tumours: replication–competence in glioblastoma cells (and other dividing cells), attenuated neurovirulence, temperature sensitivity, ganciclovir hypersensitivity, and the presence of an easily detectable histochemical marker. G207 has deletions at both γ34.5 (RL1) loci and a lacZ gene insertion inactivating the ICP6 gene (UL39). G207 kills human glioma cells in monolayer cultures. In nude mice harbouring subcutaneous or intracerebral U–87MG gliomas, intraneoplastic inoculation with G207 causes decreased tumour growth and/or prolonged survival. G207 is avirulent upon intracerebral inoculation of mice and HSV–sensitive non–human primates. These results suggest that G207 should be considered for clinical evaluation in the treatment of glioblastomas.
790 citations
TL;DR: The rate of clinical improvement was consistent with a previous retrospective study in the same setting, indicating that 25% to 30% of the patients who previously were unresponsive to medication and behavioral treatments are significantly improved after cingulotomy.
Abstract: Background: The purpose of this study was to assess prospectively long-term change in obsessive-compulsive disorder (OCD) symptoms in patients with an OCD diagnosis that was confirmed by structured interview and with documented unsuccessful trials of multiple medications and attempts at behavior therapy. Methods: We conducted an unblinded preoperative and follow-up assessment of comorbid diagnosis; OCD, depressive, and anxiety symptoms; and functional status in 18 patients who underwent cingulotomy. Results: At a mean follow-up of 26.8 months, five patients (28%) met conservative criteria for treatment responders, and three others (17%) were partial responders. The group improved significantly in mean functional status, and few serious adverse events were found. Improvement in OCD symptoms was strongly correlated with improvement in depressive and anxiety symptoms. Conclusions: The rate of clinical improvement was consistent with a previous retrospective study in the same setting, indicating that 25% to 30% of the patients who previously were unresponsive to medication and behavioral treatments are significantly improved after cingulotomy. Cingulotomy remains a last resort treatment for severely incapacitated patients who have not responded to all other state-of-the-art pharmacological and behavioral treatments for OCD and is not to be taken lightly.
215 citations
Journal Article•
TL;DR: It is demonstrated that replication-competent attenuated mutants of herpes simplex virus type 1 (HSV-1) have therapeutic potential for malignant gliomas and a recently described multiple mutant HSV (termed G207) has properties which may allow human clinical trials.
Abstract: We have demonstrated that replication-competent attenuated mutants of herpes simplex virus type 1 (HSV-1) have therapeutic potential for malignant gliomas. Moreover, a recently described multiple mutant HSV (termed G207) has properties which may allow human clinical trials. G207 is able to replicate within and kill cells from three human malignant meningiomas in cell culture. In nude mice harboring s.c. human malignant meningioma (F5), G207 can inhibit growth in a dose-dependent fashion. In nude mice harboring intracranial subdural human malignant meningioma (F5), one injection of G207 caused significantly decreased tumor growth and one apparent cure with neither neurological dysfunction nor pathological changes in the surrounding brain. These results suggest that G207 should be considered for therapeutic trials in the treatment of malignant meningioma refractory to currently available therapies.
155 citations
Patent•
23 Jun 1995TL;DR: A replication competent HSV vector with defective expression of the γ34.5 gene and the ribonucleotide reductase gene, specifically destroying tumor cells, is hypersensitive to anti-viral agents and yet is not neurovirulent as discussed by the authors.
Abstract: A method for killing malignant brain tumor cells in vivo entails providing replication competent herpes simplex virus vectors to tumor cells. A replication competent herpes simplex virus vector, with defective expression of the γ34.5 gene and the ribonucleotide reductase gene, specifically destroys tumor cells, is hypersensitive to anti-viral agents, and yet is not neurovirulent.
90 citations
TL;DR: Inhibition of tumor-induced angiogenesis by TNP-470 (previously termed AGM-1470), a synthetic analogue of fumagillin, was tested on the growth of human non-malignant and malignant meningiomas in nude mice and significantly inhibited tumor neovascularization and tumor growth.
Abstract: Meningiomas are relatively common (22%) vascular brain tumors. 3–11% of meningiomas are malignant, and defy currently available therapy. Inhibition of neovascularization is one potential strategy for treating these hypervascular tumors. Inhibition of tumor-induced angiogenesis by TNP-470 (previously termed AGM-1470), a synthetic analogue of fumagillin, was tested on the growth of human non-malignant and malignant meningiomas in nude mice. TNP-470 significantly inhibited tumor neovascularization and tumor growth of both non-malignant and malignant meningiomas. TNP-470 is now in human trial and should be tested for efficacy in treating malignant or recurrent aggressive meningiomas.
43 citations
01 Jan 1995
TL;DR: This chapter focuses on brain tumor therapy using genetically engineered replication-competent virus and discusses the potential safety problems related to the viral antitumor therapy, and other HSV mutants with decreased neurovirulence are explored.
Abstract: Publisher Summary This chapter focuses on brain tumor therapy using genetically engineered replication-competent virus. The most malignant and fastest growing tumor in the brain is glioblastoma multiforme. This tumor, even with modern technology using neurosurgical techniques, radiation, and chemotherapy, allows a patient a median survival of about one year after diagnosis. The proposed therapeutic mechanisms involve either direct cell killing by the virus or the production of new antigens on the tumor cell surface to induce immunologic rejection. Viruses are the most efficient means for getting foreign genes into cells. Various preliminary studies have suggested that the concept of viral tumor therapy is feasible because a virus can be genetically engineered to kill glioblastoma cells in situ with relative sparing of the surrounding brain. In glioblastoma multiforme, the tumor cells are rapidly proliferating, whereas the normal brain cells are quiescent and postmitotic. Therefore, the tumor cells provide a selected target for the mutated virus to replicate, lyse these cells, and spread to the surrounding proliferating tumor cells. Many steps are involved in viral antitumor therapy: distinguishing between the normal tissue and abnormal tumor cells .effective targeting and elimination of the abnormal cells by the virus and amplifying this effect to surrounding tumor cells. The discussion includes replication-incompetent and replication-competent vectors for gene transfer to tumors and the safety issues associated with it. To overcome the potential safety problems related to the viral antitumor therapy, other HSV mutants with decreased neurovirulence are also explored. Such mutant(s) would enable the administration of higher doses of virus, rendering treatment more effective, for example mutant RE6 and mutant R3616. Immune-mediated tumor therapy via gene delivery is an active area of research. Also, the viruses described in this chapter can be further engineered to produce cytokines to increase antitumor therapy.
14 citations
Journal Article•
3 citations
Patent•
05 Jun 1995
TL;DR: In this paper, compositions and methods for selective killing of neoplastic cells are described. But they do not specify the methods of selecting the specific genes to selectively express in the cells.
Abstract: The present invention discloses compositions and methods for selective killing neoplastic cells. Retroviral vectors are used to selectively express a gene in neoplastic cells. The gene or gene product targets the cells for selective killing.
1 citations
Patent•
05 Jun 1995
TL;DR: In this paper, compositions and methods for selectively killing neoplastic cells are described and described, where a gene or gene product targets the cells for selective killing, and the method is described.
Abstract: The present invention discloses compositions and methods for selectively killing neoplastic cells. Retroviral vectors are used to selectively express a gene in neoplastic cells. The gene or gene product targets the cells for selective killing.
1 citations
Patent•
23 Jun 1995
TL;DR: In this article, a procedure for tuer in vivo des cellules tumorales malignes du cerveau, consistant a mettre ces cellules en contact avec des vecteurs du virus de l'herpes simplex a competition de replication.
Abstract: Procede permettant de tuer in vivo des cellules tumorales malignes du cerveau, consistant a mettre ces cellules en contact avec des vecteurs du virus de l'herpes simplex a competition de replication. Un vecteur du virus de l'herpes simplex a competition de replication, presentant une expression defectueuse du gene η34.5 et du gene de ribonucleotide reductase, detruit specifiquement les cellules tumorales, et est hypersensible aux agents antiviraux sans etre neurovirulent.