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Yun H.,Tianjin Medical University | Yun H.,Sino Us Center For Lymphoma And Leukemia | Yun H.,Tianjin Key Laboratory of Cancer Prevention and Therapy | Zhang H.,Tianjin Medical University | And 5 more authors.
Medical Oncology | Year: 2015

This study was conducted to evaluate the efficacy and safety of rituximab and Bortezomib in relapsed or refractory indolent B cell non-Hodgkin’s lymphoma (NHL). Treatments consisted of rituximab 375 mg/m2, i.v. on days 1, 8, 15, and 22 of cycle 1 and on day one of cycles 2–5, bortezomib 1.6 mg/m2, given by intravenous injection (3-s to 5-s bolus) on days 1, 8, 15, and 22 of a maximum of five cycles. The primary end points were the overall survival (OS) and progression-free survival (PFS). Secondary endpoints included response rate (ORR; CR) and toxicities. From January 2008 to December 2010, 60 successive patients at Tianjin cancer hospital lymphoma department were enrolled in this study. All patients were recurrent or refractory indolent B cell NHL, including follicular lymphoma grades 1–2 (n = 35), small lymphocytic lymphoma/chronic lymphocytic leukemia (LL/CLL; n = 16) and marginal zone lymphoma (n = 9). The median follow-up time was 30 months (range 12–48). The overall response rate was 70.0 %, with a CR/CRu rate of 31.7 %. The 2-year OS and PFS of all patients were 75.0 and 41.0 %, respectively. Grade 3–4 neutropenia and thrombocytopenia occurred in 10 and 3.3 % of patients, respectively. Higher IPI and refractory disease were independently associated with worse survival and PFS. RB chemotherapy in patients with refractory or relapsed indolent B cell NHL was effective with low toxicity. © 2014, Springer Science+Business Media New York. Source


Hou Y.,Tianjin Medical University | Hou Y.,Sino Us Center For Lymphoma And Leukemia | Hou Y.,Tianjin Key Laboratory of Cancer Prevention and Therapy | Wang H.-Q.,Tianjin Medical University | And 4 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012

Background The cell division cycle 7 (CDC7) is a serine- threonine kinase, which is required for DNA replication and is high expressed in diffuse large B cell lymphoma (DLBCL). Methods In this study, we targeted CDC7 in human DLBCL-ABC subtype cells (ly3) and examined the subsequent alterations in cellular apoptosis. The expression of CDC7 was silenced with small interfering RNA (siRNA)- expressing plasmid. CDC7 gene silencing cells were then incubated with or without rituximab for 24 h. Following treatment, Annexin V/propidium iodide staining followed by flow cytometry was used to examine cellular apoptosis. Furthermore, the expression of caspase 3, Bax, and Bcl-2 protein was analyzed by Western blotting. The expression of Bax and Bcl-2 mRNA was analyzed by quantitative realtime PCR. Results Compared to non-treated or control siRNAtransfected cells, significantly higher levels of apoptosis were detected in siCDC7-transfected cells and rituximabtreated cells (P<0.05), which was further enhanced in CDC7-targeted cells with rituximab treatment (P<0.05). The pro-apoptotic effects were accompanied with up-regulation of caspase 3 and Bax, meanwhile down-regulation of Bcl-2. Conclusion Combined treatments using rituximab and CDC7 gene silencing significantly increases apoptosis in ly3 cells and plays synergistic effect. CDC7 is a novel therapeutic target in DLBCL patients. CDC7 inhibitors combined with rituximab will be the new therapy for the ABC-DLBCL patients. © Springer-Verlag 2012. Source


Hou Y.,Tianjin Medical University | Hou Y.,Sino Us Center For Lymphoma And Leukemia | Hou Y.,Tianjin Key Laboratory of Cancer Prevention and Therapy | Wang H.-Q.,Tianjin Medical University | And 4 more authors.
Medical Oncology | Year: 2012

This study was conducted to evaluate the efficacy and safety of Rituximab, Gemcitabine, Cisplatin, and Dexamethasone (R-GDP) in relapsed or refractory aggressive B-Cell Non-Hodgkin's Lymphoma (NHL). Treatments consisted of rituximab 375 mg/m2, i.v. on day 1; gemcitabine 1,000 mg/m 2, i.v. on days 1 and 8, dexamethasone 40 mg i.v. on days 1-4, and cisplatin 25 mg/m2 i.v. on days 1-3, every 21 days. The primary end-points were the overall survival (OS) and progression-free survival (PFS). Secondary endpoints included response rate (ORR; CR) and toxicities. Eligible patients could then proceed to high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or receive up to six treatment cycles. From January 2005 to December 2010, 50 successive patients at Tianjin cancer hospital lymphoma department were enrolled in this study. All patients were recurrent or refractory aggressive B-cell NHL, including diffuse large B-cell lymphoma (n = 30) and follicular lymphoma grade 3b (n = 20). The median follow-up time was 42 months (range, 12-70). After two cycles, the overall response rate was 72.0 %, with a CR/CRu rate of 56 %. The 2-year OS and PFS of all patients were 70.0 and 48.0 %, respectively. Grade III-IV neutropenia and thrombocytopenia occurred in 34 and 40 % of patients, respectively. Twenty-one patients (42 %) proceeded to ASCT. Higher International Prognostic Index and refractory disease were independently associated with worse survival and progression-free survival. R-GDP chemotherapy in patients with refractory or relapsed aggressive B-Cell NHL was effective as a salvage therapy and helpful for HDC/ASCT. © 2012 Springer Science+Business Media, LLC. Source


Hou Y.,Tianjin Medical University | Hou Y.,Sino Us Center For Lymphoma And Leukemia | Hou Y.,Tianjin Key Laboratory of Cancer Prevention and Therapy | Wang H.-Q.,Tianjin Medical University | And 4 more authors.
Medical Oncology | Year: 2012

Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma. According to the clinical risk factors and biological heterogeneity, clinical outcome of DLBCL is extremely various, with 5-year survival rates between 30 and 80 %. Although the International Prognostic Index (IPI) remains the primary clinical tool used to predict outcome for patients with DLBCL, notable variability in outcome is still observed within the same IPI score. The cell division cycle 7 (CDC7) is a serine-threonine kinase, which is required to initiate DNA replication. Study showed that high expression of CDC7 was correlated with poor prognosis in patients with DLBCL. Whether CDC7 is an independent prognostic factor for DLBCL remains debatable. We studied the expression of CDC7 protein in 60 Chinese DLBCL patients with immunohistochemical analysis, 34 patients (56.7 %) categorized as low CDC7 expression and 26 patients (43.3 %) as high CDC7 expression. The median survival time of patients with low CDC7 expression was not achieved and that of high expression was 9 months (P = 0.027). A multivariate analysis showed that IPI score and Ann Arbor stage were independent prognostic factors in relation to patients' OS (P < 0.05). Pearson correlation analysis showed that CDC7 expression level was positively correlated with IPI score and Ann Arbor stage (P < 0.001). The results suggest that CDC7 expression level in combination with IPI score and Ann Arbor stage can be specific prognostic factors for DLBCL patients. CDC7 could also be a potential therapeutic target in DLBCL, especially for ABC-DLBCL. © 2012 Springer Science+Business Media, LLC. Source


Hou Y.,Tianjin Medical University | Hou Y.,Sino Us Center For Lymphoma And Leukemia | Hou Y.,Tianjin Key Laboratory of Cancer Prevention and Therapy | Wang H.-Q.,Tianjin Medical University | And 4 more authors.
Medical Oncology | Year: 2012

To compare the efficacy and safety of RFT (retuximab, fludarabine, pirarubicin) with RCTVP (retuximab, cyclophophamide, pirarubicin, vindesine and prednisone) in 248 indolent B-cell non-Hodgkin's lymphoma (NHL) patients. Two hundred and forty-eight patients with indolent B-cell NHL were treated with combined chemotherapy, including RFT and RCTVP, from January 2002 to December 2010 in Tianjin Cancer Hospital. The rate of response, toxicity and long-term survival for the two regimens were analyzed retrospectively. For the previously untreated patients, overall response rate for RFT arm and RCTVP arm was 71.7 and 70.6%, and complete response rate was 47.5 and 54.9%, respectively (P > 0.05). For the refractory and relapsed patients, overall response (OR) rate and complete response (CR) rate were significantly improved in the RFT arm versus the RCTVP arm (P < 0.05). There were no statistically significant differences in overall survival (OS) between treatment groups. Comparing with RCTVP regimen, fludarabine-based treatment was associated with superior PFS both in previously untreated, refractory and relapsed patients. WHO grades 3 and 4 hematological adverse events were more common in the RFT arm. Neurotoxicity was more common in the RCTVP arm. For the previously untreated patients, there was no difference between RFT arm and RCTVP arm on OR and CR rates. For the refractory and relapsed indolent B-cell NHL patients who received RFT regimen achieved higher OR and CR rates compared with RCTVP-treated patients. No differences in OS were noted. RFT regimen was associated with superior PFS both in previously untreated, refractory and relapsed patients. RFT regimen is effective and well tolerated for patients with untreated, refractory and relapsed indolent B-cell NHL. © 2012 Springer Science+Business Media, LLC. Source

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