Search

Your search keyword '"Lebwohl D"' showing total 172 results
Start Over Author "Lebwohl D"
172 results on '"Lebwohl D"'

4. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

Author

Maude, S, Laetsch, T, Buechner, J, Rives, S, Boyer, M, Bittencourt, H, Bader, P, Verneris, M, Stefanski, H, Myers, G, Qayed, M, De Moerloose, B, Hiramatsu, H, Schlis, K, Davis, K, Martin, P, Nemecek, E, Yanik, G, Peters, C, Baruchel, A, Boissel, N, Mechinaud, F, Balduzzi, A, Krueger, J, June, C, Levine, B, Wood, P, Taran, T, Leung, M, Mueller, K, Zhang, Y, Sen, K, Lebwohl, D, Pulsipher, M, Grupp, S, Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, Grupp SA, Maude, S, Laetsch, T, Buechner, J, Rives, S, Boyer, M, Bittencourt, H, Bader, P, Verneris, M, Stefanski, H, Myers, G, Qayed, M, De Moerloose, B, Hiramatsu, H, Schlis, K, Davis, K, Martin, P, Nemecek, E, Yanik, G, Peters, C, Baruchel, A, Boissel, N, Mechinaud, F, Balduzzi, A, Krueger, J, June, C, Levine, B, Wood, P, Taran, T, Leung, M, Mueller, K, Zhang, Y, Sen, K, Lebwohl, D, Pulsipher, M, Grupp, S, Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H, Bader P, Verneris MR, Stefanski HE, Myers GD, Qayed M, De Moerloose B, Hiramatsu H, Schlis K, Davis KL, Martin PL, Nemecek ER, Yanik GA, Peters C, Baruchel A, Boissel N, Mechinaud F, Balduzzi A, Krueger J, June CH, Levine BL, Wood P, Taran T, Leung M, Mueller KT, Zhang Y, Sen K, Lebwohl D, Pulsipher MA, and Grupp SA

Abstract

BACKGROUND In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects.

Published
2018

5. Soluble markers for the assessment of biological activity with PTK787/ZK 222584 (PTK/ZK), a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor in patients with advanced colorectal cancer from two phase I trials

Author

Drevs, J., Zirrgiebel, U., Schmidt-Gersbach, C.I.M., Mross, K., Medinger, M., Lee, L., Pinheiro, J., Wood, J., Thomas, A.L., Unger, C., Henry, A., Steward, W.P., Laurent, D., Lebwohl, D., Dugan, M., and Marmé, D.

Published
2005
Full Text
View/download PDF

8. TS and ERCC-1 mRNA expressions and clinical outcome in patients with metastatic colon cancer in CONFIRM-1 and-2 clinical trials

Author

Grimminger, P. P., Shi, M., Barrett, C., Lebwohl, D., Danenberg, K. D., Brabender, J., Vigen, C. L. P., Danenberg, P. V., Winder, T., Lenz, H-J, Grimminger, P. P., Shi, M., Barrett, C., Lebwohl, D., Danenberg, K. D., Brabender, J., Vigen, C. L. P., Danenberg, P. V., Winder, T., and Lenz, H-J

Abstract

To validate established cutoff levels of thymidylate synthase (TS) and excision repair cross-complementing (ERCC-1) intratumoral mRNA expressions in tumor samples from metastatic colorectal cancer (mCRC) patients treated with PTK787/ZK222584 (PTK/ZK). From 122 samples of patients with mCRC enrolled in CONFIRM-1 (Colorectal Oral Novel Therapy for the Inhibition of Angiogenesis and Retarding of Metastases) or CONFIRM-2, mRNA was isolated of microdissected formalin-fixed paraffin-embedded samples and quantitated using TaqMan-based technology. Existing TS and ERCC-1 cutoff levels were tested for their prognostic value in first-line and second-line therapy. TS expression was associated with overall survival (OS) in first-line, but not second-line therapy. ERCC-1 was associated with OS in patients treated with first-line and second-line FOLFOX4. In first-line FOLFOX4, combination of high TS and/or high ERCC-1 was associated with shorter OS. A correlation was observed between ERCC-1 expression and benefit from PTK/ZK_FOLFOX4 treatment. TS and ERCC-1 expression is associated with clinical outcome in mCRC. Baseline TS and ERCC-1 levels may allow the selection of patients who benefit from FOLFOX4 chemotherapy. The Pharmacogenomics Journal (2012) 12, 404-411; doi:10.1038/tpj.2011.29; published online 26 July 2011

Published
2012

10. Intratumoral expression profiling of genes involved in angiogenesis in colorectal cancer patients treated with chemotherapy plus the VEGFR inhibitor PTK787/ZK 222584 (vatalanib)

Author

Wilson, P M, primary, Yang, D, additional, Azuma, M, additional, Shi, M M, additional, Danenberg, K D, additional, Lebwohl, D, additional, Sherrod, A, additional, Ladner, R D, additional, Zhang, W, additional, Danenberg, P V, additional, Trarbach, T, additional, Folprecht, G, additional, Meinhardt, G, additional, and Lenz, H-J, additional

Published
2012
Full Text
View/download PDF

13. Overall survival (OS) of metastatic renal cell carcinoma (mRCC) patients corrected for crossover using inverse probability of censoring weights (IPCW) and rank preserving structural failure time (RPSFT) models: Two analyses from the RECORD-1 trial.

Author

Korhonen, P., primary, Malangone, E., additional, Sherman, S., additional, Casciano, R., additional, Motzer, R. J., additional, Baladi, J., additional, Haas, T., additional, Zuber, E., additional, Kay, A. C., additional, and Lebwohl, D. E., additional

Published
2010
Full Text
View/download PDF

17. 97 EVEROLIMUS (EVE) IN RECORD-1 ELDERLY PATIENTS (PTS) WITH METASTATIC RENAL CELL CARCINOMA (MRCC) AND MANAGEMENT OF RELATED ADVERSE EVENTS (AES)

Author

Calvo, E., primary, Porta, C., additional, Escudier, B., additional, Ravaud, A., additional, Oudard, S., additional, Osanto, S., additional, Bracarda, S., additional, Grünwald, V., additional, Vaishampayan, U., additional, Climent, M.A., additional, Berg, W.J., additional, Lebwohl, D., additional, and Motzer, R.J., additional

Published
2010
Full Text
View/download PDF

22. Phase III Trial of Satraplatin, an Oral Platinum plus Prednisone vs. Prednisone alone in Patients with Hormone-Refractory Prostate Cancer

Author

Sternberg, C.N., primary, Whelan, P., additional, Hetherington, J., additional, Paluchowska, B., additional, Slee, P.H.Th.J., additional, Vekemans, K., additional, van Erps, P., additional, Theodore, C., additional, Koriakine, O., additional, Oliver, T., additional, Lebwohl, D., additional, Debois, M., additional, Zurlo, A., additional, and Collette, L., additional

Published
2005
Full Text
View/download PDF

24. Expanded phase I/II study of PTK787/ZK 222584 (PTK/ZK), a novel, oral angiogenesis inhibitor, in combination with FOLFOX-4 as first-line treatment for patients with metastatic colorectal cancer

Author

Steward, W. P., primary, Thomas, A., additional, Morgan, B., additional, Wiedenmann, B., additional, Bartel, C., additional, Vanhoefer, U., additional, Trarbach, T., additional, Junker, U., additional, Laurent, D., additional, and Lebwohl, D., additional

Published
2004
Full Text
View/download PDF

28. 5-Year Results of Dose-Intensive Sequential Adjuvant Chemotherapy for Women With High-Risk Node-Positive Breast Cancer: A Phase II Study

Author

Hudis, C., primary, Fornier, M., additional, Riccio, L., additional, Lebwohl, D., additional, Crown, J., additional, Gilewski, T., additional, Surbone, A., additional, Currie, V., additional, Seidman, A., additional, Reichman, B., additional, Moynahan, M., additional, Raptis, G., additional, Sklarin, N., additional, Theodoulou, M., additional, Weiselberg, L., additional, Salvaggio, R., additional, Panageas, K.S., additional, Yao, T.J., additional, and Norton, L., additional

Published
1999
Full Text
View/download PDF

29. Sequential Dose-Dense Doxorubicin, Paclitaxel, and Cyclophosphamide for Resectable High-Risk Breast Cancer: Feasibility and Efficacy

Author

Hudis, C., primary, Seidman, A., additional, Baselga, J., additional, Raptis, G., additional, Lebwohl, D., additional, Gilewski, T., additional, Moynahan, M., additional, Sklarin, N., additional, Fennelly, D., additional, Crown, J. P.A., additional, Surbone, A., additional, Uhlenhopp, M., additional, Riedel, E., additional, Yao, T. J., additional, and Norton, L., additional

Published
1999
Full Text
View/download PDF

32. Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer.

Author

Hudis, C A, primary, Seidman, A D, additional, Crown, J P, additional, Balmaceda, C, additional, Freilich, R, additional, Gilewski, T A, additional, Hakes, T B, additional, Currie, V, additional, Lebwohl, D E, additional, Baselga, J, additional, Raptis, G, additional, Gollub, M, additional, Robles, M, additional, Bruno, R, additional, and Norton, L, additional

Published
1996
Full Text
View/download PDF

34. Vascular density analysis in colorectal cancer patients treated with vatalanib (PTK787/ZK222584) in the randomised CONFIRM trials.

Author

Giatromanolaki, A, Koukourakis, M I, Sivridis, E, Gatter, K C, Trarbach, T, Folprecht, G, Shi, M M, Lebwohl, D, Jalava, T, Laurent, D, Meinhardt, G, and Harris, A L

Subjects
COLON cancer treatment, PROTEIN kinases, VASCULAR endothelial growth factors, IMMUNOHISTOCHEMISTRY, GENE expression, RANDOMIZED controlled trials
Abstract

Background:Pharmacological inhibitors of vascular endothelial growth factor (VEGF) receptors, like vatalanib, have been tested in randomised trials (CONFIRM (Colorectal Oral Novel therapy For the Inhibition of Angiogenesis and Retarding of Metastases) 1 and 2) in colorectal cancer showing activity in a subgroup of patients with high serum LDH expression. In the current study, we assessed the predictive role of vascular density (VD) in patients treated in the above trials.Methods:Paraffin-embedded materials from 141 patients were analysed with immunohistochemistry for the expression of the CD31 (pan-endothelial cell marker) and of phosphorylated pVEGFR2/KDR on endothelial cells. The VD was correlated with response to therapy and with progression-free (PFS) and overall survival (OS).Results:A significant association of pVEGFR2/KDR+ VD with poor response in the placebo group was noted (response rates (RRs) 15% (3/20) when high VD vs 52% (26/50) when low VD; P=0.006). The RR increased from 15 (3/20) to 50% (11/22) in tumours with high VD when vatalanib was added to chemotherapy (P=0.02). A significantly improved PFS was noted in patients with high pVEGFR2/KDR+ VD when treated with vatalanib (P=0.002). A similar effect was also noted in patients with high CD31+ VD (P=0.07). Overall survival was marginally improved (P=0.07).Conclusion:Assessment of the activated vessel density may allow the stratification of patients recruited in randomised trials with VEGFR-targeting anti-angiogenic agents, unmasking their therapeutic potential and enabling their introduction in the clinical practice for the benefit of specific patient subgroups, at the same time reducing the cost of therapy. [ABSTRACT FROM AUTHOR]

Published
2012
Full Text
View/download PDF

37. Progression-free survival: gaining an overall survival as a gold standard and accelerating drug development.

Author

Lebwohl D, Kay A, Berg W, Baladi JF, and Zheng J

Abstract

In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS. [ABSTRACT FROM AUTHOR]

Published
2009
Full Text
View/download PDF

45. Herbimycin A induces the 20 S proteasome- and ubiquitin-dependent degradation of receptor tyrosine kinases.

Author

Sepp-Lorenzino, L, Ma, Z, Lebwohl, D E, Vinitsky, A, and Rosen, N

Abstract

Herbimycin A is an ansamycin antibiotic isolated as an agent that reverses morphological transformation induced by v-src. Although herbimycin A is widely used as a tool for inhibiting multiple tyrosine protein kinases and tyrosine kinase-activated signal transduction, its mechanism of action is not well defined and includes a decrease in both tyrosine kinase protein levels and activity (Uehara, Y., Murakami, Y., Sugimoto, Y., and Mizuno, S. (1989) Cancer Res. 49, 780-785). We now show that herbimycin A induces a profound decrease in the total cellular activity of transmembrane tyrosine kinase receptors, such as insulin-like growth factor, insulin, and epidermal growth factor receptors. A substantial proportion of the in vivo inhibition could be explained by an increase in the rate of degradation. The enhanced degradation of insulin-like growth factor-insulin receptor was prevented by inhibitors of the 20S proteasome, whereas neither lysosomotropic agents nor general serine- and cysteine-protease inhibitors were active in preventing receptor degradation induced by herbimycin A. Moreover, in a temperature-sensitive mutant cell line defective in the E1-catalyzed activation of ubiquitin, herbimycin A treatment at the restrictive temperature did not result in the degradation of insulin receptor. These results suggest that herbimycin A represents a novel class of drug that targets the degradation of tyrosine kinases by the 20S proteasome. The ubiquitin dependence of this process indicates that this degradation of tyrosine kinases might involve the 20S proteasome as the proteolytic core of the ubiquitin-dependent 26S protease.

Published
1995

46. Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin.

Author

Chou, C K, Dull, T J, Russell, D S, Gherzi, R, Lebwohl, D, Ullrich, A, and Rosen, O M

Abstract

Transfected Chinese hamster ovary cell lines were developed that expressed equivalent numbers of either normal human receptor or receptor that had alanine substituted for Lys-1018 in the ATP-binding domain of the beta subunit. The mutated receptor was processed into subunits and bound insulin but lacked protein tyrosine kinase activity. Five effects of insulin were assayed: deoxyglucose uptake, S6 kinase activity, endogenous protein-tyrosine phosphorylation, glycogen synthesis, and thymidine uptake. In each case, cells bearing normal human receptors were 10-100-fold more sensitive to insulin than the parental cells. Cells with the mutant receptor behaved like the parental cells with respect to S6 kinase activation, endogenous substrate phosphorylation, glycogen synthesis, and thymidine uptake, but their deoxyglucose uptake was significantly depressed and relatively insensitive to insulin. The analyses led to the following conclusions: substitution of alanine for lysine at amino acid 1018 inactivates the kinase activity of the receptor; a kinase-negative receptor can be properly processed and bind insulin; insulin-dependent deoxyglucose uptake, S6 kinase activation, endogenous substrate phosphorylation, glycogen synthesis, and thymidine incorporation into DNA are mediated by the normal but not by the kinase-deficient human receptor.

Published
1987
Full Text
View/download PDF

47. Synthesis, purification, and characterization of the cytoplasmic domain of the human insulin receptor using a baculovirus expression system.

Author

Herrera, R, Lebwohl, D, Garcia de Herreros, A, Kallen, R G, and Rosen, O M

Abstract

The cytoplasmic domain of the beta subunit of the human insulin receptor has been overexpressed in insect cells using the baculovirus expression system. A recombinant baculovirus (BIR-2) was constructed by inserting the human insulin proreceptor cDNA fragment that encodes the cytoplasmic domain of the receptor into the genome of Autographa californica nuclear polyhedrosis virus adjacent to the strong polyhedrin promoter. Synthesis of the protein (baculovirus insulin receptor kinase (BIRK), Mr 48,000) in BIR-2-infected Spodoptera frugiperda (Sf9) cells was detected 24 h after infection and maximal accumulation (2-3% of the cytosolic protein) was achieved 48-72 h post-infection. The expressed protein is active as a soluble protein tyrosine kinase, both in Sf9 cells and in vitro. Rapid purification to near homogeneity was accomplished by sequential chromatography on Fast-Q-Sepharose and phenyl-Superose with an overall yield of 35% and a specific activity with histone as substrate of 20 nmol/min/mg protein. Autophosphorylation activated the intrinsic kinase activity of BIRK and decreased its mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Using a combination of tryptic digestion and immunoprecipitation with specific antipeptide antisera, it was ascertained that 30-40% of the 32P incorporated into BIRK by autophosphorylation is in the carboxyl-terminal domain (that includes tyrosyl residues 1316 and 1322 of the human proreceptor). Of the remaining radioactivity, 75% is in the amino-terminal domain (that includes tyrosyl residues 953, 960, 972, 999, and 1075) and 25% is in the conserved autophosphorylation domain (including tyrosyl residues 1146, 1150, and 1151). Limited digestion of BIRK with trypsin yielded a fragment, Mr 38,000, that lacks the carboxyl-terminal domain. This fragment exhibits protein tyrosine kinase activity that is stimulated by autophosphorylation. The properties of the soluble, monomeric BIRK are similar to those of the intact, activated, oligomeric insulin receptor kinase with respect to specificity, immunoreactivity, divalent cation requirements, and specific activity. These observations coupled with the ease of producing 0.4 mg of purified enzyme from 100 ml of suspension culture suggest that BIRK will be useful for biochemical and biophysical analysis of the insulin receptor protein tyrosine kinase.

Published
1988
Full Text
View/download PDF

50. Phase III study of N, N-Diethyl-2-[4-(Phenylmethyl) Phenoxyl] Ethanamine (BMS-2173801-01) combined with doxorubicin versus doxorubicin alone in metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA-19.

Author

Reyno, L., Seymour, L., Tu, D., Dent, S., Gelmon, K., Walley, B., Pluzanska, A., Gorbunova, V., Garin, A., Jassem, J., Pienkowski, T., Dancey, J., Pearce, L., MacNeil, M., Marlin, S., Lebwohl, D., Voi, M., Pritchard, K., Marx, Gavin M., and Rutovitz, Josie J.

Subjects
BREAST cancer, CANCER treatment, DOXORUBICIN, ANTHRACYCLINES, CANCER chemotherapy
Abstract

Presents the results of a study on the efficacy of the combination of N,N-diethyl-2-[4-(phenylmethyl) phenoxyl ]ethanamine (BMS-2173801-01)(DPPE) with doxorubicin in women with metastatic breast cancer. Role of DPPE in anthracycline cytotoxicity; Association of the combined treatment with gastrointestinal and neurologic symptoms; Rate of progression free survival of patients who received the combined treatment.

Published
2004
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results