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排序方式: 共有722条查询结果,搜索用时 15 毫秒
1.
Marlene L Hauck Susan M LaRue William P Petros Jean M Poulson Daohai Yu Ivan Spasojevic Amy F Pruitt Allison Klein Beth Case Donald E Thrall David Needham Mark W Dewhirst 《Clinical cancer research》2006,12(13):4004-4010
PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted. 相似文献
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Identification of widespread Helicobacter hepaticus infection in feces in commercial mouse colonies by culture and PCR assay. 总被引:10,自引:1,他引:9 下载免费PDF全文
B Shames J G Fox F Dewhirst L Yan Z Shen N S Taylor 《Journal of clinical microbiology》1995,33(11):2968-2972
The identification of a new murine pathogen, Helicobacter hepaticus, and its association with chronic active hepatitis and liver tumors prompted an evaluation of the prevalence of H. hepaticus in commercially available mice. Of the 28 different strains or stocks, totaling 160 mice from four major commercial vendors, cultured for H. hepaticus, 100% of mice from two outbred strains from one vendor were infected with H. hepaticus, whereas 9 of 13 inbred mouse strains from another vendor were infected. This high prevalence of H. hepaticus established a need for a rapid and reproducible, noninvasive assay for the screening of colony-maintained mice being used for biomedical research. The culturing of fecal material by using 0.45-microns-pore- size filtration for H. hepaticus consistently yielded reproducible results but required extended periods of time. (1 to 3 weeks) to obtain a definitive answer. Although it is rapid, the use of a direct PCR-based detection assay with fecal specimens is restricted by inhibitory agents. to circumvent these inhibitory agents and to augment our H. hepaticus culture technique, we have developed a novel PCR system in which the bacteria are isolated from fecal material in the presence of polyvinylpyropyrollidone and lysed by treatment with Chelex 100. The PCR is performed with Tth polymerase supplemented with a polymerase enhancer. By this PCR method, 24 H. hepaticus culture-positive and 30 H. hepaticus culture-negative fecal samples were correctly identified. Moreover, two samples which were PCR positive and culture negative initially were positive by both methods upon retesting of fresh material. Southern blot hybridizations and sequencing of PCR products showed them to be H. hepaticus specific. A comparison of results obtained under identical conditions indicated a 100-fold increase in sensitivity with Tth polymerase over Taq polymerase. This PCR method can be used as a noninvasive means of rapidly screening large numbers of colony mice for H. hepaticus. 相似文献
5.
Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma 总被引:1,自引:0,他引:1
Hsu SC; Obeid OE; Collins M; Iqbal M; Chargelegue D; Steward MW 《International immunology》1998,10(10):1441-1447
Plasmid DNA vectors have been constructed with minigenes encoding a single
cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of
respiratory syncytial virus (RSV) or from the nucleoprotein of measles
virus (MV) with or without a signal sequence (also called secretory or
leader sequence). Following intradermal immunization, plasmids in which the
CTL epitopes were expressed in-frame with the signal sequence were more
effective at inducing peptide- and virus- specific CTL responses than
plasmids expressing CTL epitopes without the signal sequence. This
immunization resulted in protection against MV-induced encephalitis and a
significant reduction in viral load following RSV challenge. The reduction
of viral load following RSV challenge was abrogated by prior injection with
anti-IFN-gamma antibodies. These results highlight the ability of
epitope-based DNA immunization to induce protective immune responses to
well-defined epitopes and indicate the potential of this approach for the
development of vaccines against infectious diseases.
相似文献
6.
Flaherty JD Levett PN Dewhirst FE Troe TE Warren JR Johnson S 《Journal of clinical microbiology》2003,41(5):2237-2239
This is the first reported case of endocarditis due to the Lactobacillus-like vancomycin-resistant gram-positive bacillus Weissella confusa. Full identification and susceptibility testing of Lactobacillus-like organisms recovered in blood culture should be performed for patients with clinical presentations that suggest endocarditis. 相似文献
7.
MW Lieberman R Barrios G Kala SV Kala ED Lykissa CN Ou 《Environmental health perspectives》1999,107(9):A444-A445
Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165 相似文献
8.
A variety of techniques for measuring oxygen in normal and tumor tissue has been developed over the years in response to the realization that hypoxia is important in a number of pathophysiological conditions in normal tissues and in the response of tumors to radiation treatment. A review of the techniques for measuring tissue oxygenation is presented with an emphasis on clinical results. Histomorphometry, DNA strand break analysis (comet assay), oxygen microelectrodes and hypoxia markers are highlighted. Comparison among techniques is touched on and a short discussion of the possibility that hypoxia is not an independent variable in determining the outcome of radiation therapy is presented. 相似文献
9.
Ellen L Jones Leonard R Prosnitz Mark W Dewhirst P Kelly Marcom Patricia H Hardenbergh Lawrence B Marks David M Brizel Zeljko Vujaskovic 《Clinical cancer research》2004,10(13):4287-4293
PURPOSE: The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO(2)) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy. EXPERIMENTAL DESIGN: Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment. RESULTS: Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2 mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses. CONCLUSIONS: This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation. 相似文献
10.
Omar I Abdel-Wahab Elizabeth Grubbs Benjamin L Viglianti Tsung-Yen Cheng Tomio Ueno SaeHee Ko Zahid Rabbani Simon Curtis Scott K Pruitt Mark W Dewhirst Doug S Tyler 《Clinical cancer research》2004,10(17):5919-5929
The role of hyperthermia during regional alkylating agent chemotherapy is controversial. The aim of this study was to determine the exact contribution of hyperthermia to tumor response during isolated limb infusion with l-phenylalanine mustard. Rats bearing rodent fibrosarcoma on the hindlimb underwent isolated limb infusion with saline, saline plus heat, l-phenylalanine mustard, l-phenylalanine mustard under conditions of normothermia, or l-phenylalanine mustard plus hyperthermia. Heat was administered locally using an in-line hot water circulation loop. Treatment with l-phenylalanine mustard at a concentration of 15 or 50 micrograms/mL was ineffective at producing tumor growth delay (P = 0.24 and 0.41, respectively). Furthermore, thermal enhancement of l-phenylalanine mustard activity was not seen at 15 micrograms/mL. However, administration of high-dose l-phenylalanine mustard, 50 micrograms/mL, with increasing amounts of heat yielded increasing tumor growth delay, increased regressions, and decreased proliferative index. Although l-phenylalanine mustard infusion under normothermia yielded a tumor growth delay of 7.1 days, combination l-phenylalanine mustard + hyperthermia treatment produced tumor growth delay of 27.0 days (P < 0.01; with two of five animals showing a complete response). Four hours after isolated limb infusion, 50.9% of cells in tumor treated with l-phenylalanine mustard + hyperthermia experienced apoptosis, whereas only 18.1, 16, and 4.4% of cells underwent apoptosis after treatment with l-phenylalanine mustard, saline + hyperthermia, or saline. The mean concentration of l-phenylalanine mustard within tumor relative to perfusate following isolated limb infusion was found to be similar among all groups at 0.023, 0.025, and 0.032 in animals undergoing isolated limb infusion with l-phenylalanine mustard, l-phenylalanine mustard + normothermia, and l-phenylalanine mustard + hyperthermia, respectively. These data indicate a synergistic cytotoxic effect of l-phenylalanine mustard + hyperthermia in isolated limb infusion, which is not attributable to enhanced tumor drug uptake. 相似文献