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111.
Khuda D Khan Christos Emmanouilides Don M Benson Deborah Hurst Pablo Garcia Glenn Michelson Sandra Milan Amy K Ferketich Lawrence Piro John P Leonard Pierluigi Porcu Charles F Eisenbeis Amy L Banks Lei Chen John C Byrd Michael A Caligiuri 《Clinical cancer research》2006,12(23):7046-7053
PURPOSE: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)-bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted. EXPERIMENTAL DESIGN: The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting <6 months). I.V. rituximab was given at 375 mg/m(2) (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9). RESULTS: Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcgammaR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy. CONCLUSIONS: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL. 相似文献
112.
Steven J O'Day Peter D Boasberg Lawrence Piro Timothy S Kristedja He-Jing Wang Maureen Martin Regina Deck Patricia Ames Kelly Shinn Hannah Kim Patricia Fournier Guy Gammon 《Clinical cancer research》2002,8(9):2775-2781
PURPOSE: A prospective Phase II study of a novel maintenance biotherapy regimen after induction biochemotherapy was conducted in patients with metastatic melanoma in efforts to maintain responses and improve survival. EXPERIMENTAL DESIGN: Thirty-three patients with poor prognosis metastatic melanoma who achieved a partial response (PR) or stable disease (SD) to induction concurrent biochemotherapy were treated with chronic low-dose interleukin (IL)-2 and granulocyte macrophage-colony stimulating factor, and intermittent pulses of intermediate/high-dose decrescendo IL-2 over a 12-month period. The outcome of these patients was compared with a control group of patients at our institution who were treated recently with induction biochemotherapy and achieved a PR or SD. RESULTS: Five patients (15%) achieved a complete response, and 4 patients (12%) maintained SD for at least 6 months on maintenance biotherapy. The median progression-free survival (PFS) and overall survival (OS) were 8.1 months and 18.5 months, respectively, compared with historical controls, which were PFS 5.9 months (P = 0.0015) and OS 9.3 months (P = 0.0004). Administration of maintenance biotherapy was a significant predictor of PFS (P = 0.0008) and OS (P = 0.0001) in multivariate and matched-pair analyses (P = 0.002). The maintenance biotherapy regimen was well tolerated with no dose-limiting acute or cumulative toxicities. CONCLUSION: In this single institution study, maintenance biotherapy with IL-2 and granulocyte macrophage colony-stimulating factor in patients achieving PR or SD to induction biochemotherapy improved PFS and OS compared with historical controls. A larger multicenter Phase II trial has been initiated in an effort to confirm these results. 相似文献
113.
Is apoptosis a diagnostic marker of acute myocardial infarction? 总被引:1,自引:0,他引:1
Piro FR di Gioia CR Gallo P Giordano C d'Amati G 《Archives of pathology & laboratory medicine》2000,124(6):827-831
OBJECTIVE: To investigate and quantify the presence of apoptosis in early myocardial ischemia in humans. METHODS: Histologic sections from the left and right ventricles of 16 hearts with impending myocardial infarction were stained with terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick end labeling (TUNEL) method and with antibodies to p53, bcl-2, cpp32, FAS, FAS-L, and bax. DNA electrophoretic analysis was also performed. RESULTS: According to the inclusion criteria, all 16 cases showed morphologic changes consistent with ischemia and/or reperfusion. TUNEL results were positive in 14 of the 16 ischemic areas. Unexpectedly, they were also positive in "remote from ischemia" myocardium of both the left and right ventricles. DNA electrophoretic analysis confirmed the results of TUNEL. Immunohistochemistry was uniformly negative, probably because of autolysis phenomena. CONCLUSIONS: We showed that apoptosis precedes necrosis in humans, but the detection of apoptosis cannot be used as a diagnostic tool, since it can also be triggered by nonischemic events. 相似文献
114.
PURPOSE: Two thirds of patients with overactive bladder (OAB) are continent, but our knowledge on the treatment of the syndrome is largely based on studies with incontinent patients. Therefore, we have explored baseline symptoms and treatment responses to tolterodine in continent relative to incontinent OAB patients. MATERIALS AND METHODS: Data from an open-label, observational study involving 3824 patients with OAB symptoms were analyzed for baseline symptoms and alterations thereof upon a 9 months treatment with 4 mg q.d. tolterodine ER. RESULTS: Baseline symptoms (number of urgency episodes, total urination frequency, daytime frequency, nocturia, and three scales of OAB severity) were similar in 1147 continent and 2571 incontinent patients, the latter having 4.8+/-3.7 incontinence episodes per 24 h. Tolterodine ER-induced reduction of OAB symptoms was very similar in both groups of patients. CONCLUSIONS: The severity of OAB in continent patients can be similar to that in incontinent ones. Symptom improvement upon treatment with tolterodine ER is very similar in both groups. We propose that continent patients may similarly deserve treatment with a muscarinic receptor antagonist as incontinent ones. 相似文献
115.
116.
The Authors report a case of Zenker's diverticulum seen and treated at the University Department of Surgical Sciences of the University of Foggia. The treatment of this condition is invariably surgical and consists in a diverticulectomy combined with a lengthwise extramucosal myotomy. This latter technical adjunct, however, would not appear to be accepted by all Authors. Other techniques have been proposed for the treatment of this condition, but no confirmation of their efficacy exists in the literature. Mortality fluctuates in the various case series, from 0.45% to 8.1%, and the morbidity varies from 5.3% to 40%. The risk of postoperative complications is always present, but can be reduced if the patient undergoes a thorough preoperative investigation. 相似文献
117.
118.
Bahman Emami Watson G. Watring Won Tak Barrie Anderson Anthony T. Piro 《International journal of radiation oncology, biology, physics》1980,6(9):1237-1241
From 1970 until December, 1977, 36 patients with advanced carcinoma of the uterine cervix and with iliac or para-aortic nodes interpreted as un-equivocally positive on lymphangiography have received radiation therapy (4500–5000 rad) to the para-aortic area at the Department of Therapeutic Radiology at Tufts-New England Medical Center Hospital. Of 29 patients who received para-aortic area irradiation as part of their initial treatment, local control was achieved in 18 patients (62%). Of these, 11 patients are currently alive with no evidence of disease (NED); two died without evidence of tumor. The remaining 16 patients died of their tumor (11 with locally uncontrolled tumor and five with distant metastasis). Of seven patients in whom the para-aortic area was treated because of retroperitoneal nodal recurrence, only two are alive without disease and the rest succumbed to their tumor. Overall, four patients developed major complications requiring surgical intervention. Detailed results and our current pre-treatment evaluation policy including lymphangiography, percutaneous needle biopsy and selective extra-peritoneal lymph node biopsy will be discussed. 相似文献
119.
AIM: An investigation was made to reveal whether suspicion of occupational hearing loss can be satisfactorily determined by an otolaryngologist or workplace audiological measurement. These were compared with a formal audiometrical assessment at a university clinic. METHODS AND RESULTS: A retrospective study was made of 95 cases of noise induced hearing loss. A total of 78 individuals were investigated by an otolaryngologist and 70 by workplace audiometry. Using workplace audiometry, 27% of the tests showed a reduction in working capacity of at least 20%. In only five of these was a specialist opinion sought within a year. In 50%, this took longer than 5 years. A comparison of audiometric data from expert opinion revealed that there was conformity in only 47% with workplace audiometry and 48% with otolaryngologist testing. In some cases (27% workplace and 33% ENT practice), the measured hearing loss and calculation of disability exceeded that determined by the experts. CONCLUSIONS: The results of workplace audiometry demonstrated that hearing loss was frequently reported only after the workers had received a disability of at least 20%. Possible reasons for discrepancies in audiological testing might be the exaggeration of hearing loss by the worker, insufficient recovery time after noise exposure, or inexperienced audiologists. Our data show that audiometric testing in workplace audiometry, as well as in ENT practice, often reveal a higher disability rating compared to formal audiological (university) assessment, even if these discrepancies do not reach statistical significance. 相似文献
120.
BACKGROUND: A large proportion of older as well as younger patients do not use their hearing aids. Of the younger hearing impaired population, this occurs in the majority of those who do not benefit sufficiently from their hearing aids and, consequently, they face difficulties in their working and social life. SCIENTIFIC QUESTION: Our aim was to evaluate whether a classical hearing aid adjustment is of sufficient predictive value to determine whether adequate rehabilitation in everyday and professional life will occur. METHODS AND RESULTS: A questionnaire was returned by 197 adult hearing impaired patients. Only 108 were using their hearing aids all the time; 57 rarely and 32 never. The main reason for this low rehabilitation rate proved to be inadequate amplification. At the workplace, insufficient speech discrimination came into play. Another important factor was dysacusis induced by specific noise signals. There was an intolerable acoustic feedback in 40% which could not be sufficiently alleviated. Taking these results into account, only about a third of patients were sufficiently rehabilitated. CONCLUSIONS: Proof of effectiveness in a typical audiological testing situation is an important but not a fully reliable predictor for effectiveness in everyday life. Even when hearing aids are shown to be effective with such testing, their application in particular everyday or work situations may be insufficient of even impossible. 相似文献