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51.
52.
Alberti A Dattola A Parisi A Maccarone P Dattola P Celi S Basile M 《Annali italiani di chirurgia》2000,71(6):669-75; discussion 675-6
53.
Simona Soverini Giovanni Martinelli Gianantonio Rosti Simona Bassi Marilina Amabile Angela Poerio Barbara Giannini Elena Trabacchi Fausto Castagnetti Nicoletta Testoni Simona Luatti Antonio de Vivo Daniela Cilloni Barbara Izzo Milena Fava Elisabetta Abruzzese Daniele Alberti Fabrizio Pane Giuseppe Saglio Michele Baccarani 《Journal of clinical oncology》2005,23(18):4100-4109
PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered. 相似文献
54.
A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer. 总被引:4,自引:0,他引:4
Grace K Dy James P Thomas George Wilding Laura Bruzek Sumithra Mandrekar Charles Erlichman Dona Alberti Kim Binger Henry C Pitot Steven R Alberts Lorelei J Hanson Rebecca Marnocha Kendra Tutsch Scott H Kaufmann Alex A Adjei 《Clinical cancer research》2005,11(9):3410-3416
PURPOSE: To define the toxicities, pharmacodynamics, and clinical activity of the proteasome inhibitor, PS-341 (bortezomib), in patients with advanced malignancies. PATIENTS AND METHODS: Twenty-eight patients (14 male and 14 female) received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity necessitated dose omissions on this schedule, 16 additional patients (12 male and 4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of 20S proteasome activity in peripheral blood mononuclear cells (PBMC) and accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated as pharmacodynamic markers of PS-341 activity. RESULTS: The most common toxicity was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6 mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a patient in schedule I. Grade > or =3 toxicities for schedule I were constipation, fatigue, myalgia, and sensory neuropathy. Grade > or =3 toxicities for schedule II were dehydration resulting from diarrhea, nausea and vomiting, fatigue, hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both schedules. Reversible dose-dependent decreases in 20S proteasome activity in PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75% at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in tumor samples after treatment with PS-341. A patient with multiple myeloma had a partial response. CONCLUSION: PS-341 given 1.5 mg/m2 twice weekly for 2 of every 3 weeks is well tolerated and should be further studied. 相似文献
55.
Douglas G McNeel Jens Eickhoff Fred T Lee David M King Dona Alberti James P Thomas Andreas Friedl Jill Kolesar Rebecca Marnocha Jennifer Volkman Jianliang Zhang Luz Hammershaimb James A Zwiebel George Wilding 《Clinical cancer research》2005,11(21):7851-7860
At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on treatment. With this weekly schedule of administration, and in the doses studied, MEDI-522 seems to be without significant toxicity, may have effects on tumor perfusion, and may have clinical activity in renal cell cancer. These findings suggest the MEDI-522 could be further investigated as an antiangiogenic agent for the treatment of cancer. 相似文献
56.
Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis. 总被引:5,自引:0,他引:5
Dominique Arpin David Perol Jean-Yves Blay Lionel Falchero Line Claude Sylvie Vuillermoz-Blas Isabelle Martel-Lafay Chantal Ginestet Laurent Alberti Dimitri Nosov Bénédicte Etienne-Mastroianni Vincent Cottin Maurice Perol Jean-Claude Guerin Jean-Fran?ois Cordier Christian Carrie 《Journal of clinical oncology》2005,23(34):8748-8756
PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis. PATIENTS AND METHODS: Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses. RESULTS: Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFalpha, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011). CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication. 相似文献
57.
58.
59.
Fabián Matías Caro María Laura Alberti Federico Campins Juan Ignacio Enghelmayer Martín Eduardo Fernández Diana Lancellotti Tulio Papucci Javier Adrián Sebastiani Francisco Paulin 《Archivos de bronconeumologia》2019,55(2):75-80
Introduction
Pirfenidone was the first antifibrotic drug approved in Argentina for idiopathic pulmonary fibrosis (IPF). Outcomes in real life may differ from the results of clinical trials. The primary endpoint was to study the tolerance of pirfenidone in real life. Secondary endpoints were to analyze effectiveness and reasons for discontinuation.Materials and methods
Retrospective observational study conducted in four specialized centers in Argentina. We analyzed the medical records of patients with IPF who received pirfenidone between June 2013 and September 2016. Adverse events (AE) and the variables that could influence these results were analyzed. Forced vital capacity (FVC%) parameters were also compared between the pre-pirfenidone and post-pirfenidone periods.Results
Fifty patients were included, 38 (76%) men, with mean age (SD) 67.8 (8.36) years. Mean (SD) exposure to pirfenidone was 645.68 (428.19) days, with a mean daily dose (SD) of 2064.56 mg (301.49). Nineteen AEs in 15 patients (30%) were reported: nausea (14%), asthenia (10%) and skin rash (8%). A total of 18 patients (36%) interrupted treatment, only 1 definitively. The most frequent reason for discontinuation was failure of suppliers to provide the drug (9 subjects; 18%). We compared the evolution of FVC% between the pre-pirfenidone and post-pirfenidone periods, and found a mean (SD) FVC% decline of 4.03% (7.63) pre-pirfenidone and 2.64% (7.1) post-pirfenidone (P=.534).Conclusions
In our study, pirfenidone was well tolerated and associated with a reduction in FVC decline, although without reaching statistical significance. 相似文献60.
K. Molloy C. Jonak F.J.S.H. Woei-A-Jin E. Guenova A.M. Busschots A. Bervoets E. Hauben R. Knobler S. Porkert C. Fassnacht R. Cowan E. Papadavid M. Beylot-Barry E. Berti S. Alberti Violetti T. Estrach R. Matin O. Akilov L. Vakeva M. Prince A. Bates M. Bayne R. Wachsmuch U. Wehkamp M. Marschalko O. Servitje D. Turner S. Weatherhead M. Wobser J.A. Sanches P. McKay D. Klemke C. Peng A. Howles J. Yoo F. Evison J. Scarisbrick 《The British journal of dermatology》2020,182(3):770-779