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Guo L.P.,Shanghai Zhabei District Central Hospital
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi | Year: 2012

To investigate effects of low-dose cyclophosphamide and prednisone (CP) metronomic chemotherapy on microvessel density of bone marrow, serum vascular endothelial growth factor (VEGF) and platelet derived growth factor BB (PDGF-BB)in multiple myeloma (MM) patients. 54 refractory or relapsed MM patients were treated with CP metronomic chemotherapy consisted of oral cyclophosphamide (CTX, 50 mg/d) and prednisone (Pred, 15 mg/d). Bone marrow and peripheral blood of each patient were collected before and 2, 4, 6 months after treatment. Among the 37 assessable patients, 30 cases were responsive with the response rate of 81.08%. Another 17 cases were follow-uped less than 6 months or failure to obtain serum samples or lost to follow-up. Microvessel density of bone marrow was measured by immunohistochemistry and serum VEGF/PDGF-BB expression was analyzed by ELISA in the 37 assessable patients. 2, 4, 6 months following CP metronomic chemotherapy, microvessel densities of bone marrow in the responders were 33.1 ± 4.8/HP, 24.8 ± 3.7/HP, 19.7 ± 2.1/HP respectively; the expressions of VEGF were (394 ± 57) ng/L, (268 ± 32) ng/L and (217 ± 20) ng/L respectively; the expressions of PDGF-BB were (304 ± 31) ng/L, (274 ± 31) ng/L and (196 ± 22) ng/L respectively. After CP metronomic chemotherapy, there were significantly lower of microvessel density, VEGF and PDGF-BB levels than pretreatment \[MVD 48.5 ± 5.9/HP, VEGF (517 ± 60) ng/L, PDGF-BB (484 ± 60) ng/L\]in the responders (P < 0.01). While in the non-responders, after treated by CP metronomic chemotherapy for 2 months, microvessel density, the expression of VEGF and the expression of PDGF-BB were 32.5 ± 4.7/HP, 512 ± 39 ng/L and (452 ± 39) ng/L respectively. There were no significant changes of MVD, VEGF and PDGF-BB levels compared with pretreatment \[MVD 33.2 ± 5.6/HP,VEGF (498 ± 55) ng/L, PDGF-BB (488 ± 44) ng/L\] (P > 0.05). Our findings suggested that continuous low-dose CP metronomic chemotherapy could decrease microvessel density of bone marrow in MM patients. Furthermore, it down-regulated expression of serum VEGF and PDGF-BB to exert its anti-angiogenesis in MM. Source


Yingying L.,Shanghai Zhabei District Central Hospital | Jiangrong W.,Shanghai Public Health Clinical Center | Jing L.,Shanghai Public Health Clinical Center
Diagnostic Microbiology and Infectious Disease | Year: 2014

Objective: The objectives of the study are to characterize the cellular immune response in hepatitis C virus (HCV) genotype 1 and HIV co-infected patients with hemophilia in southern China during treatment with interferon and ribavirin and to study its correlation with the virologic response (VR). Thirty-six HCV genotype 1 and HIV co-infected patients with hemophilia in southern China were enrolled into the study. Using an ELISpot assay, HCV antigen-specific interferon (IFN) γ, interleukin (IL) 2, IL-4, and IL-10 secreting cells were measured in peripheral blood mononuclear cells. Single nucleotide polymorphisms of IL28B were determined, and immunological, virologic, and clinical variables were collected to identify factors associated with HCV-sustained VR (SVR) at week 72 after treatment. At baseline, there were no significant differences in IFN-γ and IL-2 mediated immune responses in subjects with VR versus non-responders. Higher IL-10 specific responses to NS3 were observed in VR patients. Subjects who had significant decreases in IL-10 responses at week 72 compared with baseline for NS3 and NS5 were more likely to be VR. In SVR, IL-2 production decreased moderately, and the levels of IL-4 were low throughout. The main correlation for SVR in genotype-l infected subjects was sustained HCV-specific IFN-γ responses through the whole 72-week period. In subjects with HIV and HCV co-infection combined with hemophilia, IL28B genotype CC, a decrease in HCV specific IL-l0 and IL-2 responses, and the maintenance of IFN-γ responses during treatment were associated with a 12- or 72-week VR. © 2014 Elsevier Inc. Source


Guo L.-P.,Shanghai Zhabei District Central Hospital
Journal of Leukemia and Lymphoma | Year: 2012

Objective To evaluate the efficacy and tolerability of continuous low-dose cyclophosphamide and prednisone treatment of relapsed and refractory multiple myeloma. Methods 84 relapsed and refractory multiple myeloma patients were enrolled, including 46 males and 38 females, the assess patients of 81 cases with average age of 69.7 (45-91) years. They were treated continuous with oral cyclophosphamide (50 mg/d) and prednisone (15 mg/d) and monthly follow-up. Results Average follow-up time were 23.5(1-71)months. The assessed patients were 81 cases, with 52 cases (64.2 %) responded. There were 2 cases(2.5 %)CR, 21 cases(25.9 %) of PR, 29 cases(35.8 %)MR, 19 cases(23.5 %)NC and 10 cases (12.3 %)PD. The median time to response was 2 months. In the patients who responded to the treatment, the median progression-free survival(PFS)and overall survival (OS) were 18(95 %CI 12.8-23.2-, 29(95 %CI 24.1-33.9)months. In the non-responding patients, the PFS and OS were 4(95 % CI 2.2-5.8) and 6(95 % CI 4.9- 7.1)months. Two groups were statistically significant(P<0.05). The most common toxicities included fatigue, nausea, neutropenia, hyperglycemia and lung infection. No patient withdrew from the study because of toxicity. Conclusions Continuous low-dose cyclophosphamide combined prednisone is a treatment options for relapsed and refractory MM patients. Source


Fan L.Y.,Tongji University | He D.Y.,Hua Medicine | Wang Q.,Shanghai Zhabei District Central Hospital | Wang Q.,Shanghai University | And 4 more authors.
Scandinavian Journal of Rheumatology | Year: 2012

Objectives: We aimed to investigate the possible effects of vimentin (Vim) and citrullinated Vim (cVim) on proliferation capacity, pro-inflammatory cytokine secretion, and the expression of peptidylarginine deiminase type 4 (PADI4) and receptor activator of nuclear factor kappa B ligand (RANKL) in cultured fibroblast-like synoviocytes (FLSs) from rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Method: Human native Vim was citrullinated with rabbit PAD in vitro and detected using a Western blot assay with antimodified citrulline antibody (anti-MC Ab). FLSs from RA or OA synovial samples were stimulated with Vim or cVim. Cell proliferation capacity was determined using the Celltiter 96 AQueous cell proliferation assay. The concentrations of tumour necrosis factor (TNF)-a, interleukin (IL)-1, and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The expression of PADI4 and RANKL was measured by real-time polymerase chain reaction (RT-PCR) and a Western blot assay. Results: Our Western blot assay with anti-MC Ab indicated that the amount of cVimincreased significantly after Vim had been incubated with rabbit PAD in vitro. The proliferation capacity and secretion of TNF-a and IL-1 were significantly enhanced in the FLSs of RA patients when treated with cVim. However, when treated with Vim, an inhibitory effect on the proliferation capacity was noted in the FLSs from RA and also from OA patients. cVim significantly increased the expression of PADI4 and RANKL in the FLSs from RA patients. Conclusion: cVim seems to have remarkable biological effects on RA as confirmed by the stimulation of proliferation capacity, pro-inflammatory cytokine secretion, and PADI4 and RANKL expression in the FLSs of RA patients. © 2012 Taylor & Francis on license from Scandinavian Rheumatology Research Foundation. Source


Fan L.,Shanghai University | Wang Q.,Shanghai Zhabei District Central Hospital | Liu R.,Ningxia Medical University | Zong M.,Shanghai University | And 4 more authors.
Arthritis Research and Therapy | Year: 2012

Introduction: Rheumatoid arthritis (RA) is characterized by synovial lining hyperplasia, in which there may be an imbalance between the growth and death of fibroblast-like synoviocytes (FLSs). Antibodies against citrullinated proteins are proposed to induce RA. This study aimed to investigate the pathogenic role of citrullinated fibronectin (cFn) in RA.Methods: The distribution of fibronectin (Fn) and cFn in synovial tissues from RA and osteoarthritis (OA) patients was examined by immunohistochemical and double immunofluorescence analysis. FLSs were isolated from RA and OA patients and treated with Fn or cFn. Apoptosis was detected by flow cytometry and TUNEL assay. The expression of survivin, caspase-3, cyclin-B1, Bcl-2 and Bax was detected by real-time PCR. The secretion of proinflammatory cytokines was measured by ELISA.Results: Fn formed extracellular aggregates that were specifically citrullinated in synovial tissues of RA patients, but no Fn deposits were observed in those of OA patients. Fn induced the apoptosis of RA and OA FLSs while cFn inhibited the apoptosis of RA and OA FLSs. Fn significantly increased the expression of caspase-3 and decreased the expression of survivin and cyclin-B1 in FLSs from RA and OA patients. cFn significantly increased the expression of survivin in RA FLSs. Furthermore, cFn increased the secretion of TNF-α and IL-1 by FLSs.Conclusions: cFn plays a potential pathophysiologic role in RA by inhibiting apoptosis and increasing proinflammatory cytokine secretion of FLSs. © 2012 Fan et al.; licensee BioMed Central Ltd. Source

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