106 results on '"Evan N. Cohen"'
Search Results
102. Treatment with Lenalidomide Has a Positive Immunomodulatory Effect in Patients with Chronic Lymphocytic Leukemia
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Evan N. Cohen, Stefan Faderl, James M. Reuben, Alessandra Ferrajoli, Susan O'Brien, Bang-Ning Lee, Hui Gao, William G. Wierda, Zeev Estrov, S Tin, and Michael J. Keating
- Subjects
medicine.medical_specialty ,business.industry ,Chronic lymphocytic leukemia ,Immunology ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Gastroenterology ,medicine.anatomical_structure ,Specimen collection ,Aldesleukin ,Internal medicine ,Medicine ,Cytotoxic T cell ,Sample collection ,Bone marrow ,business ,CD8 ,Lenalidomide ,medicine.drug - Abstract
Lenalidomide (Revlimid) is known to downregulate TNF-a, IL-6, IL-8, and VEGF, impair bone marrow microenviroment-neoplastic cell interaction, activate NK cells, and stimulate T-cell activity. Based on these properties, we sought to further evaluate the immumodulatory activity of treatment with lenalidomide in patients with previously untreated chronic lymphocytic leukemia age 65 and older. Nineteen patients enrolled in a phase II clinical trial were treated with lenalidomide, given orally at the dose of 5mg daily for 28 days followed by individual titration up of 5mg increments every 28 days to reach a maximum dose of 25mg daily. Patients were evaluated for response after 3 months and if an objective response or disease stability was obtained, the treatment was continued until obvious disease progression. Peripheral blood (15ml) was collected at baseline, after three months and every six months thereafter while on treatment in patients that agreed to optional correlative studies. Data at baseline and after three months of treatment are presented. Plasma cytokine levels were determined by Luminex Multiplex assay system. Percentages of CD3, CD4, and CD8 T cells and natural regulatory T cells (TR, CD4+CD25hiFoxP3+) cells, and the ability of anti-CD3 activated T cells to synthesize of IL-2, IFN-g, TNF-a, and IL-10 were measured by multi-color flow cytometry. Eleven patients had a partial response (responder, R) and 8 patients failed to respond (non-responder, NR) after 3 months of therapy. All patients had significantly higher percentages of CD3+ and CD4+ T-cells (P = 0.012) after three months of treatment respect to baseline, but only R patients had a significantly higher percentage of TR cells (P = 0.041). Both R (P = 0.016) and NR (P = 0.025) patients had higher percentages of IFN-g-producing CD8+ T cells after three months of therapy. Moreover in NR patients, the percentage of TR cells negatively correlated with the percentages of CD4+ T cells that produced IL-2 and TNF-a, and of CD8+ T cells that produced IFN-g and TNF-a. Following 3 months of therapy, plasma levels of IL-10 were significantly increased in both R (P =0.012) and NR (P = 0.05); IL-1b plasma level was elevated in NR (P = 0.012) but not in R; IL-17 plasma level was decreased in R (P = 0.006); neither R nor NR had changes in plasma levels of IL-1RA, IL-2, IL-6, TNF-a, TNF-R1, VEGF, and VEGF-R (R1, R2, R3). In conclusion treatment with lenalidomide increased the percentages of T-helper cells in both R and NR patients and of TR cells in R patients. Treatment with lenalidomide also increased the function of CD8+ T cells as exhibited by the synthesis of IFN-g in both R and NR patients. These preliminary data suggest that lenalidomide has a favorable immunomodulatory effect on patients with B-CLL. Sample collection is ongoing for further analyses.
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- 2008
103. IL-1β and IL-6 Levels and Sleep Patterns in HIV-Infected Children with Viremia
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Daniel G. Glaze, Shahriar Shahzeidi, Mary E. Paul, James M. Reuben, E.N. Ward, Gwendolyn B. Scott, W.T. Shearer, Evan N. Cohen, Steven E. Lipshultz, Beom-Chan Lee, Lynnette L. Harris, Pim Brouwers, C.D. Jackson, Claudia A. Kozinetz, L. Himic, J.E. Fehlis, Heidi Schwarzwald, Mark W. Kline, Daniel Armstrong, Samuel B. Foster, Deshratn Asthana, Andrew A. Colin, and Tracie L. Miller
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Sleep patterns ,biology ,business.industry ,Hiv infected ,Immunology ,medicine ,biology.protein ,Immunology and Allergy ,Viremia ,medicine.disease ,Interleukin 6 ,business ,Virology - Published
- 2008
104. Pro- and Anti-Sleep Cytokines Regulate Attention and Sleep Disorders in Older Children and Adolescents with Advanced HIV Disease
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James M. Reuben, Mark W. Kline, A.J. Loeb, Beom-Chan Lee, Daniel G. Glaze, Heidi Schwarzwald, Lynnette L. Harris, W.T. Shearer, C.D. Jackson, Claudia A. Kozinetz, Pim Brouwers, Mary E. Paul, P.R. Frerking, Stanley G. Cron, Samuel B. Foster, and Evan N. Cohen
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medicine.medical_specialty ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,business ,Psychiatry ,Sleep in non-human animals ,Hiv disease - Published
- 2006
105. Chemotherapy-induced peripheral neuropathy in multiple myeloma patients undergoing maintenance therapy
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Loretta A. Williams, Venus M Ilagan, Evan N. Cohen, Xin Shelley Wang, Charles S. Cleeland, Qiuling Shi, James M. Reuben, Mary L Sailors, and Tito R. Mendoza
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.disease ,Surgery ,Chemotherapy-induced peripheral neuropathy ,Maintenance therapy ,Internal medicine ,medicine ,Stem cell ,business ,Multiple myeloma - Abstract
9646 Background: After 3-months autologous stem cell transplant (AuSCT), a percentage of multiple myeloma (MM) patients during maintenance therapy continue to experience a complex of symptoms related to peripheral neuropathy. This longitudinal study examined these self-reported neuropathy symptoms and identified circulating inflammatory markers associated with high neuropathy-related symptoms. Methods: MM patients (N=51) rated symptom severity on 0-10 scale via the M. D. Anderson symptom Inventory (MDASI) weekly from 3 to 9 months post AuSCT during maintenance therapy. Patient also rated pain on hand or foot in routine clinic visit. A panel of pro- and anti-inflammatory cytokines, receptors, chemokines was evaluated on serum samples by Luminex. Mixed effect analysis was used to describe the changes on cytokines and symptom outcomes across time. Trajectory analysis identified patients that persistently reported higher or lower symptom severity overtime. Results: During the study period, there was no significant reduction on pain in general or on hand/foot, or change in neuropathic symptoms such as numbness/tingling and muscle weakness. Among a third (33%) of patients who was consistently in high pain (mean 5.5), MIP-1a (p=.001) and MCP-1 (p=.032) showed significant decrease. Approximately 40 % had persistently high numbness/tingling (mean 5.2) across the observation period. Compared to low symptom group patients, this high numbness group had significantly higher IL-6 (p=.019) and TNF-alpha (p=.006). High muscle weakness (mean 3.1) was for 69% of the sample. This group had significantly higher CRP (p=.005) and TNF-alpha (p=.001). Conclusions: This is the first longitudinal study that tracked persistent neuropathy-related symptoms for MM patients post AuSCT. Approximately one third reported painful neuropathy, either from induction therapy or ongoing maintenance therapy. High levels of these neuropathy symptoms were associated with higher levels of specific pro-inflammatory markers. This study provided rationale for examining the effectiveness of anti-inflammation as mechanism driven intervention on peripheral neuropathy in this cohort of MM patients.
106. High serum miR-19a levels are associated with inflammatory breast cancer and are predictive of favorable clinical outcome in patients with metastatic HER2+ inflammatory breast cancer.
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Simone Anfossi, Antonio Giordano, Hui Gao, Evan N Cohen, Sanda Tin, Qiong Wu, Raul J Garza, Bisrat G Debeb, Ricardo H Alvarez, Vicente Valero, Gabriel N Hortobagyi, George A Calin, Naoto T Ueno, Wendy A Woodward, and James M Reuben
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Medicine ,Science - Abstract
Altered serum microRNA (miRNA) levels may be correlated with a dysregulated expression pattern in parental tumor tissue and reflect the clinical evolution of disease. The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or -amplified [HER2(+)] and inflammatory breast cancer [IBC]).In this prospective study, we measured miR-21, miR-10b, and miR-19a levels using quantitative reverse transcriptase-polymerase chain reaction in the serum of 113 breast cancer patients and determined their association with clinicopathologic factors and clinical outcome. Thirty healthy donors with no history of cancer were enrolled as controls.Patients with non-metastatic HER2(+) breast cancer had higher serum miR-21 median levels than patients with non-metastatic HER2(-) disease (p = 0.044); whereas patients with metastatic HER2(+) breast cancer had higher serum miR-10b median levels than patients with metastatic HER2(-) disease (p = 0.0004). There were no significant differences in serum miR-19a median levels between HER2(+) and HER2(-) groups, regardless of the presence of metastases. High serum miR-19a levels were associated with IBC (p = 0.039). Patients with metastatic IBC had significantly higher serum miR-19a median levels than patients with metastatic non-IBC (p = 0.019). Finally, high serum miR-19a levels were associated with longer progression-free survival time (10.3 vs. 3.2 months; p = 0.022) and longer overall survival time (median not reached vs. 11.2 months; p = 0.003) in patients with metastatic HER2(+) IBC.High levels of miR-21 and miR-10b were present in the serum of patients with non-metastatic and metastatic HER2(+) breast cancer, respectively. High levels of serum miR-19a may represent a biomarker for IBC that is predictive for favorable clinical outcome in patients with metastatic HER2(+) IBC.
- Published
- 2014
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