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排序方式: 共有371条查询结果,搜索用时 0 毫秒
1.
Christian J Streck Paxton V Dickson Catherine Y C Ng Junfang Zhou John T Gray Amit C Nathwani Andrew M Davidoff 《Clinical cancer research》2005,11(16):6020-6029
PURPOSE: Type I IFNs (IFN-alpha/beta) have shown significant antitumor activity in preclinical models but limited efficacy and significant toxicity in clinical trials. We hypothesized that the antitumor activity of type I IFNs could be enhanced by chronic, low-dose systemic delivery and sought to test this in murine neuroblastoma models. EXPERIMENTAL DESIGN: Continuous liver-generated expression of human IFN-beta (hINF-beta) was achieved through a gene therapy-mediated approach using adeno-associated virus vectors encoding hIFN-beta (AAV hINF-beta). Orthotopic localized retroperitoneal and disseminated models of neuroblastoma were established using three different xenografts. Immunohistochemical analysis and ELISA were used to evaluate the antiangiogenic effect of therapy. RESULTS: The development of both localized orthotopic (retroperitoneal) and disseminated neuroblastoma was prevented in all mice expressing hINF-beta. Continued growth of established retroperitoneal tumors, treated with AAV hINF-beta as monotherapy, was significantly restricted, and survival for mice with established, disseminated disease was significantly prolonged following administration of AAV hINF-beta. Analysis of treated tumors revealed a significant antiangiogenic effect. Mean intratumoral vessel density was diminished and expression of the angiogenic factors vascular endothelial growth factor and basic fibroblast growth factor were both decreased. Finally, combination therapy in which AAV hIFN-beta was used together with low-dose cyclophosphamide resulted in regression of both established retroperitoneal and disseminated disease. CONCLUSIONS: AAV-mediated delivery of hIFN-beta when used as monotherapy was able to restrict neuroblastoma growth due in part to inhibition of angiogenesis. When used in combination with conventional chemotherapy, AAV hIFN-beta was able to effect complete tumor regression. 相似文献
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Streptococcus pyogenes appears to have become an uncommon cause of pneumonia. In view of the recent increase in S. pyogenes infections this situation is likely to change. An intravenous drug user presented with acute onset of fever and chills. At presentation pleuritic chest pain was a prominent symptom, and later he developed pulmonary abscesses and an empyema. The patient had a good response to benzyl penicillin, and his pulmonary lesions resolved completely. Although his clinical picture was characteristic of S. pyogenes pneumonia, it could easily be mistaken for Staphylococcus aureus septicaemia. 相似文献
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Epstein-Barr viral (EBV) infections are associated with Hodgkin's disease (HD). To better characterize this relationship, fixed tissues of infectious mononucleosis, normal and reactive lymph nodes, lymph nodes with progressively transformed germinal centers, and biopsy specimens with the different subtypes of HD were analyzed by polymerase chain reaction (PCR). The presence or absence of EBV, the relative amounts of EBV, and the presence of multiple EBV genotypes as defined by amplification of a polymorphic EBV locus were determined for each specimen. Epstein-Barr virus could be detected from all specimens with infectious mononucleosis (eight of eight cases), generally in relatively large amounts, with multiple EBV genotypes evident in two cases. Epstein-Barr virus could not be detected from normal or reactive lymph nodes (none of 39 cases). Small amounts of EBV could be detected from a minority of cases with progressively transformed germinal centers (two of 16 cases), with multiple EBV genotypes evident in one case. Variable amounts of EBV could be detected from approximately half of the specimens with HD (26 of 50 cases). Epstein-Barr virus was most often detected in the subtypes of mixed cellularity (12 of 15 cases), nodular sclerosis (seven of 14 cases), and lymphocyte depletion (five of seven cases) compared with nodular lymphocyte predominance HD (two of 14 cases). In contrast to specimens with infectious mononucleosis and progressively transformed germinal centers, only one EBV genotype was evident in the specimens with HD. These findings are consistent with the hypothesis that some cases of HD may be directly associated with EBV. 相似文献
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B N Nathwani R C Griffith D R Kelly J J Shuster E Hvizdala M P Sullivan S B Murphy C W Berard 《Cancer》1987,59(6):1138-1142
Of 227 cases of pediatric non-Hodgkin's lymphoma with adequate histopathologic material for review, 72 (32%) were classified as diffuse "histiocytic" lymphoma (DHL). These cases were further divided into different morphologic subtypes according to the Lukes-Collins classification, and the National Cancer Institute Working Formulation, to ascertain whether there were any significant prognostic differences among the different subtypes. The results of our study showed that 40 patients were classified as immunoblastic lymphomas, and 32 were called large follicular center cell (FCC) tumors. Of the 40 patients with immunoblastic histology, 19 had morphologic features of the clear cell type and were interpreted as consistent with T-immunoblastic lymphomas; an additional two had polymorphous features also consistent with T-cell type: 17 had plasmacytoid features, and were morphologically classified as B-immunoblastic lymphomas; two could not be subtyped. Of the 32 patients with morphologic features of FCC lymphomas, 29 were classified as large noncleaved type, and three as large cleaved type. A clinicopathologic analysis showed that 90% of the patients obtained complete remission, and there were no significant differences in complete remission rate among the different morphologic subtypes of DHL. The estimated five year disease-free survival for all patients was over 70%, with no failure after the second year; and there were no significant differences in the disease-free survival among the different subtypes. The only clinical differences that we found, were that patients with lymphomas of FCC (large noncleaved) type were younger (P = 0.01); had less nodal involvement (P = 0.03); and had more organ involvement (P less than 0.01). We conclude that the morphologic subclassification of DHL in children currently has limited clinical prognostic significance. 相似文献
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Sam M. Mbulaiteye Sheeja T. Pullarkat Bharat N. Nathwani Lawrence M. Weiss Nagesh Rao Benjamin Emmanuel Charles F. Lynch Brenda Hernandez Vishala Neppalli Debra Hawes Myles G. Cockburn Andre Kim Makeda Williams Sean Altekruse Kishor Bhatia Marc T. Goodman Wendy Cozen 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2014,122(1):5-15
Burkitt lymphoma (BL) occurs at all ages, but the patterns of Epstein–Barr virus (EBV) positivity in relation to human immunodeficiency virus (HIV), immunoprofiles and age have not been fully explored. BL tissues from residual tissue repositories, and two academic centers in the United States were examined by expert hematopathologists for morphology, immunohistochemistry, MYC rearrangement, EBV‐encoded RNA (EBER), and diagnosed according to the 2008 WHO lymphoma classification. Analysis was done using frequency tables, Chi‐squared statistics, and Student's t‐test. Of 117 cases examined, 91 were confirmed as BL. The age distribution was 26%, 15%, 19%, and 29% for 0–19, 20–34, 35–59, 60+ years, and missing in 11%. MYC rearrangement was found in 89% and EBER positivity in 29% of 82 cases with results. EBER positivity varied with age (from 13% in age group 0–19 to 55% in age group 20–34, and fell to 25% in age group 60+ years, p = 0.08); with race (56% in Blacks/Hispanics vs 21% in Whites/Asians/Pacific Islanders, p = 0.006); and by HIV status (64% in HIV positive vs 22% in HIV negative cases, p = 0.03). EBER positivity was demonstrated in about one‐third of tumors and it was strongly associated with race and HIV status, and marginally with age‐group. 相似文献
10.
Nicole K. Paulk Katja Pekrun Erhua Zhu Sean Nygaard Bin Li Jianpeng Xu Kirk Chu Christian Leborgne Allison P. Dane Annelise Haft Yue Zhang Feijie Zhang Chris Morton Marcus B. Valentine Andrew M. Davidoff Amit C. Nathwani Federico Mingozzi Markus Grompe Mark A. Kay 《Molecular therapy》2018,26(1):289-303