Clinical observation for NAPD regimen in the treatment of 67 cases of recurrent refractory non-Hodgkin's lymphoma / 中南大学学报(医学版)

To explore the clinical efficacy and toxicity of the NAPD regimen(vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory non-Hodgkin' s lymphoma.
 Methods: A total of 67 patients identified with recurrent refractory non-Hodgkin's lymphoma were enrolled for this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and side effects were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), 1, 2 or 4 years of OS and PFS rates were analyzed. The prognosis was evaluated with univariate and multivariate analysis.
 Results: The ORR was 53.8% after two cycles, including 5(7.5%) complete responses and 31(46.3%) partial responses. The clinical benefit rate (CBR) was 88.7% (59/67). The median OS was 22 (1.5-140.0) months. 1, 2 or 4 years of OS rates were 70.9%, 49.0%, and 35.0%, respectively. The median PFS was 14 (1.5-140.0) months; and 1, 2 or 4 years of PFS rates were 57.5%, 38.3%, and 29.8%, respectively. The main side effect was myelosuppression. The rates of Grade III/IV leukopenia and thrombocytopenia were 13.4% (9 cases) and 3.0% (2 cases), respectively. Gastrointestinal toxicity was at Grade I or II and 6% patients displayed gastrointestinal toxicity at Grade III/IV. No severe cardiac and hepatorenal functional toxicity was observed.
 Conclusion: The NAPD regimen for recurrent refractory non-Hodgkin's lymphoma is effective, and its toxicity is well tolerated. It is a salvage chemotherapy regimen and be of worth to be verified.

NAPD regimen for patients with recurrent refractory diffuse large B-cell lymphoma / 中南大学学报(医学版)

To investigate the clinical efficacy and toxicities for the NAPD regimen (vinorelbine, cytarabine, cisplatin, and dexamethasone) in the treatment of recurrent refractory diffuse large B-cell lymphoma.
 Methods: A total of 30 patients identified with recurrent refractory diffuse large B-cell lymphoma were enrolled in this retrospective study. The curative efficacy of NAPD regimen was evaluated after 2 consecutive cycles. The toxicities and adverse reaction were evaluated after 1 cycle. The objective response rate (ORR), overall survival (OS), progress free survival (PFS), and the rates of 1, 2, and 4-year OS and PFS were analyzed. The prognosis was evaluated with univariate analysis.
 Results: The ORR was 56.7% and clinical benefit rate (CBR) was 83.3% after 2 cycles. Five patients achieved complete remission, 12 achieved partial remission, and 8 achieved stable disease. The median OS was 22 (1.5-140) months. The 1, 2, and 4-year OS rates were 59.1%, 48.2%, and 40.2%, respectively. The median PFS was 14 (1.5-140) months. The 1, 2 and 4-year PFS rates were 56.3%, 42.2%, and 31.7%, respectively. The main adverse reaction was myelosuppression. Three patients suffered from grade III-IV leukopenia and 1 thrombocytopenia. Grade I-II gastrointestinal toxicity was 20%. No heart, liver, and kidney damages at grade III-IV were observed.
 Conclusion: The NAPD regimen is effective and its toxicity is well tolerated for the treatment of recurrent refractory diffuse large B-cell lymphoma. It is a salvage chemotherapy regimen worth to be verified.

Impact of diabetes mellitus on clinicopathological factors and relation with radiation pneumonitis in 332 patients with lung cancer / 中南大学学报(医学版)

OBJECTIVE@#To explore the relation between diabetes mellitus and clinicopathological factors and the incidence of radiation pneumonitis in patients with non-small cell lung cancer.@*METHODS@#The data of 332 patients with non-small cell lung cancer, who were admitted to the Department of Oncology of Third Xiangya Hospital of Central South University between January 2007 and August 2009, were collected retrospectively. The patients were divided into a diabetes mellitus (DM) group (n=45) and a non-diabetes mellitus (NDM) group (n=287). The clinicopathological factors were compared between the two groups. The patients who received radiotherapy were further divided into a diabetes mellitus (DMR) group (n=33) and a non-diabetes mellitus group (NDMR) group(n=287), and the incidence of radiation pneumonitis was compared.@*RESULTS@#A total of 45 patients (13.55%)developed diabetes mellitus. There was significant difference in the body-weight, age and hypertension (P0.05). No significant difference in the irradiation area was found between the DM group and the NDM group(P>0.05). The incidence of radiation pneumonitis in the DMR group was 42.42%(14 out of 33), while 21.31%(39 out of 183) in the NDMR group, with significant difference in the incidence of radiation pneumonitis between the DMR group and the NDMR group(P<0.05). The risk value in the DMR group was 2.721 folds (95%CI, 1.253-5.910) that in the NDMR group in patients with non-small cell lung cancer companied with diabetes mellitus.@*CONCLUSION@#Diabetes mellitus is the risk factor of radiation pneumonitis for patients with nonsmall cell lung cancer who receive radiotherapy.

Effect of different heating methods combined with neferine on the expressions of γH2AX and mdr-1/P-gp in MCF-7/Adr breast cancer cells / 中南大学学报(医学版)

OBJECTIVE@#To determine the effect of different heating Methods combined with neferine(Nef) on the proliferation and expressions of γH2AX and mdr-1/P-gp in MCF-7/Adr breast cancer cells.@*METHODS@#MTT assay was used to determine block heating, water submerged heating, medium heating, and oven heating combined with 10 μg/mL Nef on adriamycin cultured MCF-7/Adr cell proliferation. The mdr-1mRNA expression was detected by real-time quantitative PCR. γH2AX and P-gp expressions were detected by Western blot.@*RESULTS@#The absorbance values of MCF-7/Adr cells in different heating groups at 42 degree and 45 degree were significantly decreased, the mdr-1/P-gp expression was decreased, and γH2AX expression was upregulated compared with those of the 37 degree control group (all P<0.01). The absorbance values (P<0.01) and mdr-1/P-gp expression(P<0.05) were significantly lower and γH2AX expression(P<0.05) was significantly higher in the hyperthermia combined with 10 μg/mL Nef group than those of 10 μg/mL Nef group and hyperthermia group in MCF-7/Adr cells. The water submerged heating group had the lowest P-gp expression and the highest γH2AX expression among different heating groups at 42 degree and 45 degree in MCF-7/Adr cells (P<0.05).@*CONCLUSION@#Hyperthermia can increase the cell toxicity of adriamycin to multidrug resistant breast cancer cells. Hyperthermia significantly damages DNA of MCF-7/Adr cells and the higher temperature, the worse effect. Multidrug resistant breast cancer cells may respond differently to the different heating methods. Combined treatment of hyperthermia with Nef can increase the sensitivity in adriamycin chemotherapy.

Synergistic effect of hyperthermia and neferine on reverse multidrug resistance in adriamycin-resistant SGC7901/ADM gastric cancer cells / 华中科技大学学报（医学）（英德文版）

Multidrug resistance (MDR) plays a major obstacle to successful gastric cancer chemotherapy. The purpose of this study was to investigate the MDR reversal effect and mechanisms of hyperthermia in combination with neferine (Nef) in adriamycin (ADM) resistant human SGC7901/ADM gastric cancer cells. The MDR cells were heated at 42°C and 45°C for 30 min alone or combined with 10 μg/mL Nef. The cytotoxic effect of ADM was evaluated by MTT assay. Cellular plasma membrane lipid fluidity was detected by fluorescence polarization technique. Intracellular accumulation of ADM was monitored with high performance liquid chromatography. Mdr-1 mRNA, P-glycoprotein (P-gp), γH2AX expression and γH2AX foci formation were determined by real-time PCR, Western blot and immunocytochemical staining respectively. It was found that different heating methods induced different cytotoxic effects. Water submerged hyperthermia had the strongest cytotoxicity of ADM and Nef combined with hyperthermia had a synergistic cytotoxicity of ADM in the MDR cells. The water submerged hyperthermia increased the cell membrane fluidity. Both water submerged hyperthermia and Nef increased the intracellular accumulation of ADM. The water submerged hyperthermia and Nef down-regulated the expression of mdr-1 mRNA and P-gp. The water submerged hyperthermia could damage DNA and increase the γH2AX expression of SGC7901/ADM cells. The higher temperature was, the worse effect was. Our results show that combined treatment of hyperthermia with Nef can synergistically reverse MDR in human SGC7901/ADM gastric cancer cells.

Infection in patients with malignant tumors / 中南大学学报(医学版)

OBJECTIVE@#To investigate the characters of infection in patients with malignant tumors, especially the distribution, yearly change of pathogens, and pathogen resistance to common antibacterial agents.@*METHODS@#We respectively analyzed the characters of infection in 489 patients with malignant tumors.@*RESULTS@#The respiratory tract was the most frequent infection site (61.1%). The infection was mainly caused by opportunistic pathogens. The Gram-negative bacterias mainly consisted of Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii (46.3%). The Gram-positive bacteria mainly consisted of Staphylococcus aureus and Staphylococcus epidermidis (29.9%), and the rest 23.8% of the infection was caused by different fungi, mainly consisting of Candida albicans. The ratio of the Gram-negative bacteria resistance to antibiotics such as penicillins, cephalosporins (except ceftazidime), sulfanilamides, tetracyclines and quinolones was higher. The ratio of the Gram-positive bacteria resistance to antibiotics such as penicillins, macrolides and quinolones was higher. The ratio of fungus resistance to antibacterial agents such as fluconazol and itraconazole was higher. The infection caused by fungi obviously increased in the past 5 years.@*CONCLUSION@#The infection in patients with malignant tumors is mainly caused by opportunistic pathogens, and the pathogen resistance to antibacterial agents is serious. The infection caused by fungi is increasing.

Relation of promoter methylation of mdr-1 gene and histone acetylation status with multidrug resistance in MCF-7/Adr cells / 中南大学学报(医学版)

OBJECTIVE@#To analyze the mdr-1 gene promoter methylation and histone acetylation status in both MCF-7/Adr and MCF-7 cells and to preliminarily explore the epigenetic mechanism of multidrug resistance in breast cancer.@*METHODS@#mdr-1 gene promoter methylation status of the 2 cell lines was detected by methylation-sensitive PCR. mRNA expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) was detected by real-time quantitative PCR. Acetylation level of histone H3 and H4 was examined by optical density assay.@*RESULTS@#Promoter hypermethylation of mdr-1 gene was observed in MCF-7 cells whereas hypomethylation was found in MCF-7/Adr cells. Expression of DNMT1, DNMT3a, and DNMT3b mRNA in MCF-7/Adr cells significantly decreased compared with that of MCF-7 cells (P<0.05). H3 and H4 histone acetylation levels of MCF-7/Adr cells were obviously higher than those of the MCF-7 cells (P<0.01). Expression of HDAC1, HDAC2, HDAC7, and Sirtuin type 1 (SIRT1) mRNA in MCF-7/Adr cells was significantly reduced (P<0.05).@*CONCLUSION@#Hypomethylation of the promoter region of mdr-1 gene, high H3 and H4 histone acetylation, and low mRNA expression of DNMTs and HDACs may be important epigenetic factors for the development of MDR in MCF-7/ Adr cells.