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991.
Extravasations of oxaliplatin. 总被引:2,自引:0,他引:2
992.
Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma. 总被引:11,自引:0,他引:11
Roger K Strair Dale Schaar Daniel Medina Mary B Todd Joseph Aisner Robert S DiPaola Jacqueline Manago Beth Knox Amanda Jenkinson Rachelle Senzon Christina Baker Dudek Liesel Marie Ciardella Mercy Kuriyan Arnold Rubin Edmund C Lattime 《Journal of clinical oncology》2003,21(20):3785-3791
PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach. 相似文献
993.
Microglia cyclooxygenase-2 activity in experimental gliomas: possible role in cerebral edema formation. 总被引:9,自引:0,他引:9
994.
Adjuvant immunization of HLA-A2-positive melanoma patients with a modified gp100 peptide induces peptide-specific CD8+ T-cell responses. 总被引:3,自引:0,他引:3
John W Smith Edwin B Walker Bernard A Fox Daniel Haley Ketura P Wisner Teri Doran Brenda Fisher Lisa Justice William Wood John Vetto Holden Maecker Annemiek Dols Sybren Meijer Hong-Ming Hu Pedro Romero W Gregory Alvord Walter J Urba 《Journal of clinical oncology》2003,21(8):1562-1573
PURPOSE: To measure the CD8+ T-cell response to a melanoma peptide vaccine and to compare an every-2-weeks with an every-3-weeks vaccination schedule. PATIENTS AND METHODS: Thirty HLA-A2-positive patients with resected stage I to III melanoma were randomly assigned to receive vaccinations every 2 weeks (13 vaccines) or every 3 weeks (nine vaccines) for 6 months. The synthetic, modified gp100 peptide, g209-2M, and a control peptide, HPV16 E7, were mixed in incomplete Freund's adjuvant and injected subcutaneously. Peripheral blood mononuclear cells obtained before and after vaccination by leukapheresis were analyzed using a fluorescence-based HLA/peptide-tetramer binding assay and cytokine flow cytometry. RESULTS: Vaccination induced an increase in peptide-specific T cells in 28 of 29 patients. The median frequency of CD8+ T cells specific for the g209-2M peptide increased markedly from 0.02% before to 0.34% after vaccination (P <.0001). Eight patients (28%) exhibited peptide-specific CD8+ T-cell frequencies greater than 1%, including two patients with frequencies of 4.96% and 8.86%, respectively. Interferon alfa-2b-treated patients also had significant increases in tetramer-binding cells (P <.0001). No difference was observed between the every-2-weeks and the every-3-weeks vaccination schedules (P =.59). CONCLUSION: Flow cytometric analysis of HLA/peptide-tetramer binding cells was a reliable means of quantifying the CD8+ T-cell response to peptide immunization. This assay may be suitable for use in future trials to optimize different vaccination strategies. Concurrent interferon treatment did not inhibit the development of a peptide-specific immune response and vaccination every 2 weeks, and every 3 weeks produced similar results. 相似文献
995.
Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract 总被引:6,自引:0,他引:6
Engfer MB Stahl B Finke B Sawatzki G Daniel H 《The American journal of clinical nutrition》2000,71(6):1589-1596
BACKGROUND: Human milk oligosaccharides (HMOs) show a complexity and variety not found in milk of any other species. Although progress has been made in the past 3 decades with regard to identification and structural characterization of HMOs, not much is known about the physiologic functions of HMOs. OBJECTIVE: As a prerequisite for biological activity in infant metabolism, HMOs have to resist enzymatic hydrolysis in the gastrointestinal tract. To assess the extent to which selected HMOs are hydrolyzed, we carried out in vitro digestion studies using enzyme preparations of human and porcine pancreas and intestinal brush border membranes (BBMs). DESIGN: Fractions of HMOs, including structurally defined isolated oligosaccharides, were digested for up to 20 h with human pancreatic juice and BBMs prepared from human or porcine intestinal tissue samples. HMOs were incubated by using a porcine pancreatic homogenate and BBMs as enzyme sources. HMOs and digestion products were identified by mass spectrometry and anion-exchange chromatography. Additionally, free D-glucose, L-fucose, and N-acetylneuraminic acid were determined enzymatically. RESULTS: Whereas maltodextrin (control) was rapidly and completely hydrolyzed, neutral and acidic HMOs showed a profound resistance against pancreatic juice and BBM hydrolases. However, cleavage of most of the HMOs was achieved by using a pancreatic homogenate containing intracellular, including lysosomal, enzymes in addition to secreted enzymes. CONCLUSIONS: The results of this study strongly suggest that HMOs are not hydrolyzed by enzymes in the upper small intestine. Although intact HMOs may be absorbed, we postulate that a majority of HMOs reach the large intestine, where they serve as substrates for bacterial metabolism. Therefore, HMOs might be considered the soluble fiber fraction of human milk. 相似文献
996.
Richard B. Lock Bruce S. Thompson Daniel M. Sullivan Lolita Stribinskiene 《Cancer chemotherapy and pharmacology》1997,39(5):399-409
Protein kinase inhibitors have demonstrated potential for use in the therapy of human cancers, in particular leukemia. Staurosporine,
a protein kinase inhibitor with broad specificity, enhances the cytotoxic effects of various antitumor agents with different
modes of action. The topoisomerase II inhibitor, etoposide, has shown clinical activity against a wide range of tumor types.
Purpose: The purpose of this study was to assess the effects of staurosporine on etoposide-induced cell death processes in a human
tumor of epithelial origin. Methods: Modulation of etoposide-induced apoptosis by staurosporine in HeLa cells was assessed by cell morphology, extraction of
low molecular weight DNA, quantitation of DNA-protein complexes, and measurements of rates of DNA synthesis. The effects on
cellular genes implicated in apoptosis were determined by Northern and Western blotting, along with assays of cyclin-dependent
kinase activities. Results: Stauro- sporine exhibited a two- to three-fold potentiation of apoptosis caused by etoposide in HeLa cells when ap- plied
concurrently, or immediately following etoposide removal, but did not alter the quantity of DNA-protein complexes produced
by etoposide. Etoposide-induced apoptosis, and its potentiation by staurosporine, were associated with reduced c-myc expression, and a moderate increase in p21WAF1/CIP1 mRNA and protein levels. Inhibitors of cyclic AMP-dependent protein kinase and protein kinase C, which exhibit greater specificity
than staurosporine, were without effect on apoptosis caused by etoposide, whereas use of the tyrosine phosphatase inhibitor,
vanadate, resulted in its abrogation. The potentiation of etoposide-induced apoptosis by staurosporine was associated with
a significant increase in cyclin A-dependent kinase activity. In addition, etoposide caused substantial inhibition of DNA
synthesis. Conclusion: These results indicate that staurosporine potentiates apoptosis through events which occur downstream of DNA damage, and
implicate unscheduled activation of cyclin A-dependent kinase during inhibition of DNA synthesis as a possible cause.
Received: 28 November 1995/Accepted: 8 July 1996 相似文献
997.
Disentangling the Overlap between Tourette's Disorder and ADHD 总被引:11,自引:0,他引:11
Thomas Spencer Joseph Biederman Margaret Harding Deborah O'Donnell Timothy Wilens Stephen Faraone Barbara Coffey & Daniel Geller 《Journal of child psychology and psychiatry, and allied disciplines》1998,39(7):1037-1044
Objective : To identify similarities and differences in neuropsychiatric correlates in children with Tourette's syndrome (TS) and those with ADHD. Method : The sample consisted of children with Tourette's syndrome with ADHD( N = 79), children with Tourette's syndrome without ADHD ( N = 18), children with ADHD ( N = 563), psychiatrically referred children ( N = 212), and healthy controls ( N = 140). Results: Disorders specifically associated with Tourette's syndrome were obsessive compulsive disorder (OCD) and simple phobias. Rates of other disorders, including other disruptive behavioral, mood, and anxiety disorders, neuropsychologic correlates, and social and school functioning were indistinguishable in children with Tourette's and ADHD. However, children with Tourette's syndrome plus ADHD had more additional comorbid disorders overall and lower psychosocial function than children with ADHD. Conclusions: These findings confirm previously noted associations between Tourette's syndrome and OCD but suggest that disruptive behavioral, mood, and anxiety disorders as well as cognitive dysfunctions may be accounted for by comorbidity with ADHD. However, Tourette's syndrome plus ADHD appears to be a more severe condition than ADHD alone. 相似文献
998.
Objective: To determine if systemic neutrophil intrinsic 5-lipoxygenase (5-LO) inhibition correlates with decreased expression of surface adhesion molecules and attenuation of ischemia-reperfusion (i/r) injury in guinea pig island skin flaps. Methods: Eighty-one adult female Hartley guinea pigs were divided into one control group, three 2-hour ischemia groups, and four 10-hour ischemia groups. Island dorsal skin flaps were developed (except in the control group), and 2 hours before reperfusion, zileutin (a 5-LO inhibitor) or vehicle was administered orally. Postreperfusion systemic neutrophil receptor expression, neutrophil flap infiltration, and flap survival were measured. Neutrophils from whole blood were analyzed for CD 18 containing surface receptor expression using monoclonal antibodies and cell associated fluorescence. Neutrophil infiltration into a distal centimeter squared of flap tissue was assessed using myeloperoxidase antibodies, and flap survival was determined within 7 days postoperatively. Results: Flaps in the treated 2? and 10-hour ischemic groups survived totally intact, while the untreated 10-hour ischemic flaps underwent total necrosis. A significant main effect of the drug was detected using analysis of variance (ANOVA) (P =.0001). Surface receptor detection and neutrophil infiltration were significantly increased in the untreated animals. Conclusions: Zileuton, a 5-LO inhibitor, reduces adhesion receptor expression on systemic neutrophils and attenuates i/r injury. Systemic neutrophil intrinsic 5-LO activity and CD18 receptor expression are linked to reperfusion injury and may be fundamental events in its pathogenesis. 相似文献
999.
Alexandros Papanikolaou Qian-Shu Wang Don A. Delker Daniel W. Rosenberg 《Cancer letters》1998,130(1-2):29-34
Azoxymethane (AOM) is an organotropic colon carcinogen that is commonly used to induce colon tumors in rodents. Unlike its parent compound, 1,2-dimethylhydrazine (DMH), a tumor susceptibility phenotype in inbred mice with respect to AOM has not been established. Thus, this study was undertaken to determine whether genetic susceptibility extends to this carcinogen. SWR/J, A/J (both susceptible to DMH carcinogenesis) and AKR/J (resistant) mice were treated with 10 mg/kg AOM i.p. once a week for 8 weeks. Twenty-five weeks after the initial injection, tumor yield was determined. With a single exception, only SWR/J and A/J mice developed tumors, with a distribution that was limited to the distal colon (16.3±1.1 and 36.4±2.4, respectively). The formation of aberrant crypt foci (ACF), putative preneoplastic lesions, was also assessed in whole-mount colons using Methylene Blue staining. Consistent with tumor multiplicity, the total number of ACF was highest in A/J mice, followed by SWR/J mice. In addition, A/J mice had a significantly greater number of large ACF (five or more crypts per foci) than the other strains. Despite the absence of colon tumors, however, AKR/J mice did develop a significant number of ACF. This finding suggests that ACF in resistant mice are persistent but do not progress to tumors. 相似文献
1000.
Hellman Richard Neuberg Donna S. Wagner Henry Grunnet Margaret Robins H. Ian Karp Daniel Flynn Patrick Adams George 《Journal of neuro-oncology》1998,37(1):55-62
This study is a combined modality Phase II therapeutic trial to determine the efficacy of the novel combination of VP-16, Vincristine and Procarbazine in addition to postoperative radiation therapy in patients with high grade intracranial gliomas. Thirty three patients (median age 51 years) were entered (27 with glioblastoma multiforme, 6 with anaplastic astrocytoma). Toxicity was manageable with no lethal toxicities. Five of seven life threatening toxicities were hematologic. Median overall survival was 14.2 months. These data suggest this regimen is effective treatment for patients with high grade gliomas. 相似文献