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Robert L. Martuza

Bio: Robert L. Martuza is an academic researcher from Harvard University. The author has contributed to research in topics: Oncolytic virus & Herpes simplex virus. The author has an hindex of 79, co-authored 263 publications receiving 27228 citations. Previous affiliations of Robert L. Martuza include Georgetown University Medical Center & House Ear Institute.


Papers
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Journal ArticleDOI
20 Jun 2014-Science
TL;DR: The genome sequence of single cells isolated from brain glioblastomas was examined, which revealed shared chromosomal changes but also extensive transcription variation, including genes related to signaling, which represent potential therapeutic targets.
Abstract: Human cancers are complex ecosystems composed of cells with distinct phenotypes, genotypes, and epigenetic states, but current models do not adequately reflect tumor composition in patients. We used single-cell RNA sequencing (RNA-seq) to profile 430 cells from five primary glioblastomas, which we found to be inherently variable in their expression of diverse transcriptional programs related to oncogenic signaling, proliferation, complement/immune response, and hypoxia. We also observed a continuum of stemness-related expression states that enabled us to identify putative regulators of stemness in vivo. Finally, we show that established glioblastoma subtype classifiers are variably expressed across individual cells within a tumor and demonstrate the potential prognostic implications of such intratumoral heterogeneity. Thus, we reveal previously unappreciated heterogeneity in diverse regulatory programs central to glioblastoma biology, prognosis, and therapy.

3,475 citations

Journal ArticleDOI
12 Mar 1993-Cell
TL;DR: A candidate gene for the NF2 tumor suppressor that has suffered nonoverlapping deletions in DNA from two independent NF2 families and alterations in meningiomas from two unrelated NF2 patients is identified.

1,268 citations

Journal ArticleDOI
10 May 1991-Science
TL;DR: A thymidine kinase-negative mutant of herpes simplex virus-1 (dlsptk) that is attenuated for neurovirulence was tested as a possible treatment for gliomas and merit further evaluation as novel antineoplastic agents.
Abstract: Malignant gliomas are the most common malignant brain tumors and are almost always fatal. A thymidine kinase-negative mutant of herpes simplex virus-1 (dlsptk) that is attenuated for neurovirulence was tested as a possible treatment for gliomas. In cell culture, dlsptk killed two long-term human glioma lines and three short-term human glioma cell populations. In nude mice with implanted subcutaneous and subrenal U87 human gliomas, intraneoplastic inoculation of dlsptk caused growth inhibition. In nude mice with intracranial U87 gliomas, intraneoplastic inoculation of dlsptk prolonged survival. Genetically engineered viruses such as dlsptk merit further evaluation as novel antineoplastic agents.

969 citations

Journal ArticleDOI
TL;DR: The rates of survival, tumor recurrence, and tumor progression were analyzed in 225 patients with meningioma who underwent surgery as the only treatment modality between 1962 and 1980, and there was no difference in the recurrence/progression rates according to the patients' age or sex, or the duration of symptoms.
Abstract: The rates of survival, tumor recurrence, and tumor progression were analyzed in 225 patients with meningioma who underwent surgery as the only treatment modality between 1962 and 1980. Patients were considered to have a recurrence if their studies verified a mass effect in spite of a complete surgical removal, whereas they were defined as having progression if, after a subtotal excision, there was clear radiological documentation of an increase in the size of their tumor. There were 168 females and 57 males (a ratio of 2.9:1), with a peak incidence of tumor occurrence in the fifth (23%), sixth (29%), and seventh (23%) decades of life. Anatomical locations were the convexity (21%), parasagittal area (17%), sphenoid ridge (16%), posterior fossa (14%), parasellar region (12%), olfactory groove (10%), spine (8%), and orbit (2%). The absolute 5-, 10-, and 15-year survival rates were 83%, 77%, and 69%, respectively. Following a total resection, the recurrence-free rate at 5, 10, and 15 years was 93%, 80%, and 68%, respectively, at all sites. In contrast, after a subtotal resection, the progression-free rate was only 63%, 45%, and 9% during the same period (p less than 0.0001). The probability of having a second operation following a total excision after 5, 10, and 15 years was 6%, 15%, and 20%, whereas after a subtotal excision the probability was 25%, 44%, and 84%, respectively (p less than 0.0001). Tumor sites associated with a high percentage of total excisions had a low recurrence/progression rate. For example, 96% of convexity meningiomas were removed in toto, and the recurrence/progression rate at 5 years was only 3%. Parasellar meningiomas, with a 57% total excision rate, had a 5-year probability of recurrence/progression of 19%. Only 28% of sphenoid ridge meningiomas a second resection, the probability of a third operation at 5 and 10 years was 42% and 56%, respectively. There was no difference in the recurrence/progression rates according to the patients' age or sex, or the duration of symptoms. Implications for the potential role of adjunctive medical therapy or radiation therapy for meningiomas are discussed.

967 citations

Journal ArticleDOI
TL;DR: Radiographic and neuropathologic evidence suggestive of anti-tumor activity and long-term presence of viral DNA in some cases is found, and no toxicity or serious adverse events could unequivocally be ascribed to G207.
Abstract: G207 is a conditionally replicating derivative of herpes simplex virus (HSV) type-1 strain F engineered with deletions of both γ134.5 loci and a lacZ insertion disabling the UL39 gene. We have demonstrated the efficacy of G207 in treating malignant glial tumors in athymic mice, as well as the safety of intracerebral G207 inoculation in mice and in Aotus nancymai. We sought to determine the safety of G207 inoculation into cerebral malignant glial tumors in humans. Criteria for inclusion into this dose-escalation study were the diagnosis of histologically proven malignant glioma, Karnofsky score ⩾70, recurrence despite surgery and radiation therapy, and an enhancing lesion greater than 1 cm in diameter. Serial magnetic resonance images were obtained for volumetric analysis. The trial commenced at a dose of 106 plaque forming units (p.f.u.) inoculated at a single enhancing site and was completed when the 21st patient was inoculated with 3 × 109 p.f.u. at five sites. While adverse events were noted in some patients, no toxicity or serious adverse events could unequivocally be ascribed to G207. No patient developed HSV encephalitis. We found radiographic and neuropathologic evidence suggestive of anti-tumor activity and long-term presence of viral DNA in some cases.

955 citations


Cited by
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Journal ArticleDOI
01 Jun 1990-Cell
TL;DR: A model for the genetic basis of colorectal neoplasia that includes the following salient features is presented, which may be applicable to other common epithelial neoplasms, in which tumors of varying stage are more difficult to study.

11,576 citations

Journal ArticleDOI
TL;DR: It is found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas, which are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumors.
Abstract: Because most colorectal carcinomas appear to arise from adenomas, studies of different stages of colorectal neoplasia may shed light on the genetic alterations involved in tumor progression. We looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 colorectal-tumor specimens representing various stages of neoplastic development. The specimens consisted of 40 predominantly early-stage adenomas from 7 patients with familial adenomatous polyposis, 40 adenomas (19 without associated foci of carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 92 carcinomas resected from 89 patients. We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial adenomatous polyposis were not lost in adenomas from the patients with polyposis but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from other patients. A specific region of chromosome 18 was deleted frequently in carcinomas (73 percent) and in advanced adenomas (47 percent) but only occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p sequences were usually lost only in carcinomas (75 percent). The four molecular alterations accumulated in a fashion that paralleled the clinical progression of tumors. These results are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumorigenesis.

6,309 citations

Journal ArticleDOI
TL;DR: The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of T MS in neuroimaging environments.

4,447 citations

Journal ArticleDOI
TL;DR: The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.
Abstract: The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

4,270 citations