Although there are many antihypertensive drugs available for hypertensive patients at present, about 10% of patients who receive standardized antihypertensive therapy still have blood pressure that can't reach the standard [1]. Such patients often have many cardiovascular complications and poor prognosis. Clinically, this type of hypertension is called intractable hypertension, which is generally defined as taking three kinds of antihypertensive drugs with different mechanisms of action regularly on the basis of lifestyle improvement, one of which is diuretic, but blood pressure still can't reach the standard [1]. Therefore, new treatment methods have been searched in clinic, hoping to control intractable hypertension simply, safely and effectively.
Although CT has been widely accepted and applied in clinic, it still has great limitations in qualitative diagnosis. The images obtained by PET can more truly reflect the physiological and pathological conditions of organs and tissues, and PET/CT combined with CT has the advantages of both. PET/CT has been used in lymphoma for 10 years, and can more sensitively and specifically find the affected lesions of lymphoma and judge the curative effect. Therefore, PET/CT has been introduced into the Ann Arbor staging of lymphoma, and it is expected that more accurate staging can further improve the curative effect of lymphoma; It is also used as one of the methods to evaluate the efficacy of lymphoma, and the evaluation standard of efficacy is revised [1]. Despite this, the clinical practical application value of PET/CT is still controversial.
PING Ling-yan, ZHENG Wen, WANG Xiao-pei, XIE Yan, LIN Ning-jing, TU Mei-feng, YING Zhi-tao, ZHANG Chen, LIU Wei-ping, DENG Li-juan, et al.
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.006
Abstract
Objective To analyze the safety and adverse event profiling of pegylated L-asparaginase (PEG-asp) combined chemotherapy in the treatment of lymphoma patients.Methods The clinical data of 32 lymphoma patients on PEG-asp-based chemotherapy from January 2008 to March 2012 were retrospectively collected and analyzed.Results There were 22 males and 10 females with a median age of 40 years.They were diagnosed as NK/T cell lymphoma (n =22) and lymphoblastic lymphoma (n =10).The overall response rate was 71.9% (23/32).And complete remission was 40.6% (13/32) and partial remission 31.3% (10/32).Myelosuppression was the most common adverse event at an incidence of 81.2%(26/32).Other adverse events included a low level of fibrinogen (n =13,40.6%),hypoalbuminemia (n =8,25%) and hyperlipidemia (n =9,28.1%).No instance of anaphylaxis,acute pancreatitis and thrombosis occurred.Conclusion PEG-asp is both effective and safe in the treatment of lymphoma and it is well-tolerated.
LI Zeng-jun, XU Yan, ZHANG Pei-hong, LIU Wei, YI Shu-hua, ZOU De-hui, QI Jun-yuan, ZHAO Yao-zhong, QIU Lu-gui
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.005
Abstract
Objective To summarize the clinical characteristics of Richter syndrome and explore the methods of successful treatment and timely diagnosis.Methods Five patients with Richter syndrome in the last three years (from January 2009 to December 2011) were analyzed retrospectively at our hospital,including their clinical features and therapy before and after transformation.Results There were 4 males and 1 female with a median age on a diagnosis of chronic lymphocytic leukemia (CLL) at 47 (44-68) years.The median duration from a diagnosis of CLL to transformation was 52 (5-90) months.As for cytogenetic abnormalities,3/4 patients had 17p deletion by fluorescence in situ hybridization (FISH).The clinical manifestations on transformation included regional enlargement of lymph node (n =2) and systemic enlargement of lymph nodes (n =3).All diagnoses were confirmed by lymph node biopsy and all transformed into diffuse large B cell lymphoma (classical transformation).The subgroups were germinal center B-cell like (GCB) (n =3) and non-GCB (n =1).After transformation,one patient underwent sibling allo-stem cell transplantation and survived 24 months until April 2012.Another patient with auto-stem cell transplantation relapsed and died 12 months later.One patient lost the treatment opportunity due to worsening condition.Another 2 patients gained partial remission after therapy and survived 20 and 8 months respectively.Conclusions Richter syndrome may occur during a late stage of CLL Such a high-risk cytogenetic abnormality as del17p may be correlated with transformation.Early identification and optimal therapy may extend the survival of Richter syndrome.Allo-stem cell transplantation remains a curable option.
ZHANG Yan-ru, WANG Yan-ying, LI Zeng-jun, YI Shu-hua, FENG Xiao-yan, LIU Wei, QI Jun-yuan, ZOU De-hui, ZHAO Yao-zhong, QIU Lu-gui
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.004
Abstract
Objective To explore the clinical and laboratory characteristics and survival of Chinese patients with hairy cell leukemia (HCL).Methods A total of 30 HCL patients from August 1990 to March 2012 were retrospectively analyzed.Results There were 22 cases with classical HCL (HCL-C) and 8 with variant HCL (HCL-V).Splenomegaly was the most common physical finding.Leukocytosis was found in all cases of HCL-V.But pancytopenia only accounted for 36.4% (8/22) in HCL-C.And 3/5 of HCL-V had abnormal chromosome karyotypes.Ribosomal-lamellae complexes (RLC) were found only in about 3/12 of HCL cases.Chemotherapy regimens including purine nucleoside analogues achieved a better complete remission (CR) rate than other regimens (3/4 vs 1/18,P =0.012) in HCL-C.The median follow-up period was 27(1-142) months.There was no follow-up loss.Eleven cases progressed and 6 died.The median overall survival (OS) was not reached.And the 1,3,6-year OS rates were 84%,78% and 58% respectively.The median progression-free survival (PFS) was (63 ±24) months and the 1,2,5-year PFS rates were 86%,72% and 44% respectively.The median PFS of HCL-V was significant shorter than HCL-C ((23 ±3) vs (78 ±12) months,P=0.014).In HCL-C group,fever (P=0.038) and anemia (P=O.000) at diagnosis were poor prognostic factors.But purine nucleoside analogues made no significant difference in PFS.Conclusions Pancytopenia is infrequent in Chinese HCL patients.And classical RLC is rare under electron microscope.Purine nucleoside analogues may achieve a better CR rate,but fail to improve PFS rate.As compared with HCL-C,HCL-V is common with genetic abnormalities and has a worse prognosis with a shorter PFS.
YING Zhi-tao, SONG Yu-qin, ZHENG Wen, WANG Xiao-pei, XIE Yan, LIN Ning-jing, TU Mei-feng, PING Ling-yan, LIU Wei-ping, DENG Li-juan, et al.
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.003
Abstract
Objective To evaluate the prognostic value of maximum standard uptake (SUVmax) on pretreatment 18F-fluoro-2-deoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) scan in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL).Methods The clinical data of 39 DLBCL patients undergoing a PET/CT scan at pre-treatment from December 2009 to October 2011 were analyzed retrospectively.SUVmax on PET/CT was evaluated by SPSS 13.0 for the associations with patient characteristics,prognostic factors,treatment efficacy and survival time.Results The median SUVmax was higher in non-germinal center B cell-like (non-GCB) patients than that in GCB ones (18.0(2.2-40.5) vs 11.6 (5.3-18.7),P =0.039).No difference of SUVmax was observed between the patients with and without bulky disease (P =0.539).SUVmax was not associated with such patient characteristics as international protein index,age,stage,Eastern Cooperative Oncology Group performance status,lactate dehydrogenase,number of extranodal invovlement and Ki-67 (all P >0.05).No significant difference in median SUVmax existed between complete remission (CR) and non-CR patients (P=0.312).The difference of SUVmax was insignificant for the patients with efficacy and no efficacy (P =0.243).With the cut-off values of 10,15,20,the CR rate,response rate,2-year progression-free survival (PFS) rate and 2-year overall survival (OS) rate were not different between the patients with SUVmax below and above cut-off value (all P > 0.05).Conclusions The prognostic value of SUVmax on PET/CT is indeterminate.And it can not be used to predict the patient prognosis.
HE Ying-jian, LI Jin-feng, WANG Tian-feng, XIE Yun-tao, FAN Zhao-qing, OUYANG Tao
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.013
Abstract
Objective To explore the diagnostic value and health economic evaluation of ultrasound-combined fine-needle aspiration cytology for axillary lymph node status in breast cancer.Methods We reviewed retrospectively collected the data from 2503 cases of biopsy-proved breast cancer (T0-2) at our breast center between May 2005 and June 2010.The diagnostic fees of ultrasound-combined fine-needle aspiration cytology and clinical examination were calculated and assessed with cost-minimization analysis.Results Ultrasound-combined fine-needle aspiration cytology prevented 10.9 percent of the patients with positive clinical findings from unnecessary sentinel lymph node biopsy and achieved a saving of 155.55 RMB per patient.However,only 29.4 percent of the cases were diagnosed with ultrasonographic abnormal axillary nodes.Conclusions Ultrasound-combined fine-needle aspiration cytology has great application values.The ultrasonic diagnostic criteria of abnormal axillary nodes should be loosened.
GONG Zhi-yun, GAO Chang-qing, LI Bo-jun, JIANG Sheng-li, XIAO Cang-song, WANG Rong, WU Yang, LI Feng
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.012
Abstract
Objective To explore the occurrence of acute kidney injury (AKI) in early stage after cardiac surgery under cardiopulmonary bypass (CPB) and discuss the perioperative risk factors and its impact on clinical outcome.Methods Retrospective analysis was performed among 1472 adult patients undergoing cardiac surgery with CPB between January 2008 and April 2011.The postoperative occurrence of AKI following cardiac surgery was stratified according to the RIFLE criteria.And the perioperative risk factors of AKI and its impact on clinical outcome were analyzed.Results AKI occurred in 437 patients (29.7%) within 72 hours postoperation.Of these,292 (19.8%) fulfilled AKI-Risk,110 (7.5%) AKI-Injury and 35 (2.4%) AKI-Failure.Logistic regression analysis showed that age,hypertension,chronic renal insufficiency,reoperation,aortic surgery,CPB duration,intraoperative transfused erythrocyte volume and perioperative use of intra-aortic balloon pump were independent risk factors for AKI.A postoperative elevation of AKI level was associated with a prolonged duration of mechanical ventilation,intensive care unit stay,postoperative hospital stay,delayed extubation,extubation failure and death.Receiver operator characteristic (ROC) curve showed that AKI classification was a postoperative predictor of delayed extubation,extubation failure and death.Conclusion As a common complication after cardiac surgery,AKI is associated with many perioperative risk factors.And the AKI classification is predicator of delayed extubation,extubation failure and death.
DING Xiao-yan, FAN Ying, MA Fei, LI Qing, WANG Jia-yu, YUAN Peng, ZHANG Pin, XU Bing-he
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.011
Abstract
Objective To explore the therapeutic outcomes of various first-line regimens and prognostic factors for hormone receptor positive (HR +) breast cancer (BrCa) patients with bone-only metastases.Methods A total of 139 HR + BrCa patients with bone-only metastases between January 1,2005 and October 31,2010 were retrospectively reviewed.Their clinicopathologic characteristics,various treatment regimens and clinical survival factors were analyzed.Furthermore,the effects of various therapeutic regimens on skeletal-related events (SREs) were explored.Results In this cohort,99 patients received first-line chemotherapeutic regimens and 40 had first-line endocrine drugs.Their median overall survival time was 61 months.No significant difference was noted in 5-year overall survival rate between first-line chemotherapy group (49.4%) and first-line endocrine group (44.3%) (hazard ratio (HR) 0.687,95% confidence interval (CI) 0.307-1.539,P =0.362).Furthermore,interval of disease-free survival >3 years and number of positive lymph nodes < 10 were favorable prognostic factors by univariate analyses (HR =0.333,95% CI 0.138-0.803,P =0.014; HR =0.239,95% CI 0.102-0.562,P=0.001) ; they were also independent favorable prognostic factors by multivariate Cox-regression analyses.The proportion of patients with SREs decreased in the first-line chemotherapy group compared with the first-line endocrine group (45/99 (45.4%) vs 25/40 (62.5%)).Nonetheless,the difference was insignificant (P =0.092).Conclusion Interval of disease-free survival > 3 years and number of positive lymph nodes <10 are independent favorable prognostic factors.The overall survival of HR + BrCa patients with bone-only metastases is not significantly different between two groups.First-line chemotherapy may lower the incidence of SREs.Both endocrine therapy and chemotherapy are effective for HR + BrCa patients with bone-only metastases and they should be individualized.
XU Wei-guo, CHEN Yuan-shui, DONG Hong-chao, LIU Yun
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.010
Abstract
Objective To explore the relationship between neuropilin 2 (NRP-2) and lymphangiogenesis and lymphatic metastasis of human colorectal carcinoma (CRC),as well as the expression of NRP-2 in CRC tissues.Methods A total of 55 cases of CRC,adjacent and normal tissues of surgical resection were randomly selected at our hospital from March 2010 to January 2012.All pathological findings were confirmed by histopathology.The expression of NRP-2 was detected with reverse transcription (RT)-PCR and immunohistochemistry in parenchymatous and surrounding malignant tissues.Then lymphangiogenesis was marked with D2-40 monoclonal antibody and microlymphatic density (MLD) counted.Results Significant differences of MLD existed between those of tumor region(39 ± 19) and tumor margin(53 ± 26,P <0.01).Both the number and shape of lymphangiogenesis were different between the parenchymatous and surrounding tissues.The expression of NRP-2 had a positive correlation with MLD both at the protein level(r =0.325,P < 0.05)and at the gene level (r =0.545,P =0.000).And it was also correlated with the differentiation degree,infiltrative degree,lymphovascular invasion,lymph node metastasis and Dukes tumor staging (all P < 0.05).Conclusion The expression of NRP-2 may regulate lymphangiogenesis and it may play an important role in the incidence and development of CRC.
Objective To explore the function and clinicopathological significance of miR-135b in the occurrence and development of gastric cancer.Methods Seventy-two pairs of fresh gastric cancer tissues and corresponding normal gastric epithelium were collected at our department from September 2007 to March 2011.Six of them were randomly selected and miRNA microarray was applied to study the miRNA expression profiles of gastric cancer.Quantitative real-time PCR was used to validate the reliability of microarray and detect miR-135b expression in the above clinical samples,as well as cell lines GES-1,BGC-823 and SGC-7901.The methods of cell transfection,thiazolyl blue tetrazolium bromide (MTT) and flow cytometry were used to study the impact of miR-135 on cell proliferation,cell cycle and apoptosis of gastric cancer cells.Real-time quantitative PCR and Western blot were used to explore the relationship between miR-135b and adenomatous polyposis coli (APC).Results Compared with normal gastric tissues,7 miRNA were significantly up-regulated and 9 miRNA significantly down-regulated for over 2 folds in gastric cancer tissues (P <0.05).The results of microarray were verified by quantitative real-time PCR.MiR-135b expression was up-regulated in most clinical samples compared with their corresponding epithelium (n =66,91.67%).The average expression level of miR-135b in gastric cancer tissues was significantly higher than normal epithelium (3.42 ±2.62 vs 1.00 ±0.07,P <0.05).MiR-135b was related to Laurén classification,tumor differentiation,invasion and pathologic tumor-node-metastasis (pTNM) stage of gastric cancer (all P <0.05).The worse differentiation degree of gastric cell lines,the higher miR-135b expression level (P <0.05).MiR-135b promoted gastric cancer cell proliferation,inhibited its apoptosis and directly regulated the expression of APC in gastric cancer cell.Conclusions Special miRNA expression profiles of gastric cancer are found.MiR-135b is closely correlated with the biological behavior of human gastric cancer.And its regulation of APC may be one of the pathogenic mechanisms of gastric cancer.
JIANG Xiong-jing, LIANG Tuo, DONG Hui, PENG Meng, MA Wen-jun, GUAN Ting, ZHANG Hui-min, BIAN Jin, XU Bo, GAO Run-lin
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.008
Abstract
Objective Transcatheter renal sympathetic denervation (RDN) is a novel technology/therapy in treating resistant hypertension.The present study aims to evaluate the safety and short-term efficacy of RDN for the treatment of resistant hypertension in a Chinese population.Methods This prospective single-center pilot study was the first one conducted in China with Medtronic Ardian Symplicity Catheter System.Eight patients (6 males and 2 females) with resistant hypertension underwent RDN at our hospital from February to April 2012.All patients were followed up at one month and three months postRDN.Blood pressure,use of antihypertensive medications,renal function and complications were recorded and analyzed.Results At one month and three months post-RDN,24-hour ambulatory blood pressure monitoring showed mean systolic blood pressure and diastolic blood pressure decreased 10 (0-18) 13 (3-19) and 8(-2-15),9(2-16) mm Hg throughout 24 hours respectively (P <0.05,vs baseline).The number of drugs decreased from 4.3 ± 0.5 to 2.8 ± 0.9 and 2.5 ± 0.7 post-RSD respectively (P < 0.01).There was no significant change of renal function (P > 0.05).No complications were observed.Conclusion The preliminary results revealed that RDN was safe and effective for the treatment of resistant hypertension in the Chinese population during a 3-month follow-up.Further large and long-term studies are warranted.
LI Zhen-nan, HE Jian-guo, LIU Zhi-hong, GU Qing, NI Xin-hai, CHENG Xian-sheng, XIONG Chang-ming
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.007
Abstract
Objective To explore the relationship between serum uric acid levels and patient conditions and prognosis in idiopathic pulmonary arterial hypertension (IPAH).Methods A total of 76 IPAH patients confirmed by right heart catheterization were enrolled consecutively and followed up until the endpoint of all-cause death.Their baseline data were recorded and analyzed by Spearman's rank test and independent t-test.And the follow-up outcomes were analyzed with Kaplan-Meier plots.Results There were 27 males and 49 females with a mean age of 29.7 ± 9.7 years.They were classified into World Health Organization functional class (WHO-FC) Ⅱ (n =28),class Ⅲ (n =45) and class Ⅳ (n =3).Their baseline mean pulmonary artery pressure was (65 ± 16) mm Hg,pulmonary vascular resistance (1677 ±669) dyn· s-1 · cm-5,pulmonary capillary wedge pressure (9.6 ± 5.0) mm Hg,mean right atrial pressure (9.8 ±6.1) mm Hg,cardiac index (2.07 ±0.57) L · min-1 · m-2 and serum uric acid (391 ±103) μmol/L.The correlation analysis indicated that the serum level of uric acid correlated positively with right ventricular diameter (r =0.28,P =0.018) and negatively with CI (r =-0.34,P =0.003).Independent t-test results indicated that the patients with a higher level of uric acid were apt to have a worse WHO-FC,and the higher level uric acid group (serum uric acid >416.5 μmol/L) had a relative higher level of WHO-FC,NT-proBNP and endothelin-1.A lower level of CI denoted more severe conditions and prognosis.Survival analysis indicated that the serum level of uric acid could strongly predict survival in IPAH patients with over time and those with a high level of uric acid had a worse prognosis.Conclusion The serum level of uric acid correlates significantly with patient conditions and prognosis in IPAH.And a higher serum level of uric acid predicts worse conditions and prognosis.
HAN Shu-guang, ZHAO Hong-qing, L(U) Lei, WANG Xin-hua, WANG Xun
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.017
Abstract
Objective To explore the effects of H2 relaxin on the expression of exchange protein directly activated by cyclic adenosine monophosphate (Epac) in a murine model of chronic asthma and the roles in the management of airway remodelling.Methods Thirty-two BALB/c mice were randomly divided into 4 groups of normal control,asthma,vehicle control and relaxin treatment (n =8 each).They were sensitized and challenged with ovalbumin to establish a chronic asthmatic model.The vehicle control and relaxin treatment groups were subcutaneously injected with saline and relaxin (0.25 mg · kg-1 · d-1) respectively.Alteration of airway inflammation was observed by hematoxylin-eosin (HE) staining.The airway expressions of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were evaluated by immunohistochemistry.The protein expression of Epac and phosphorylated extracellular signal regulated kinasesl/2 (p-ERK1/2) were detected by Western blot.Results Compared to those in the normal control group,massive infiltration of inflammatory cells,airway stenosis,bronchial smooth muscle hypertrophy were present in the asthmatic and vehicle control groups.The above-mentioned changes were significantly ameliorated in the relaxin treatment group.The percentage of PCNA positive cells (34.8% ±6.1%,33.5% ±6.6%) and the expression of α-SMA ((1.70 ±0.25),(1.54 ±0.24) μm2/μm) in the asthmatic and vehicle control groups were significantly higher than those in the normal control group (9.9% ±2.6%,(0.51±0.16) μm2/μm) (all P <0.05) while administration of relaxin decreased the airway expression levels of PCNA and α-SMA (22.9% ±5.2%,(1.06 ±0.25) μm2/μm) (all P <0.05).The results of Western blot showed that the expression levels of Epac in the asthmatic and vehicle groups (0.62 ±0.12,0.68 ± 0.11) were lower than those in the control group (1.50 ± 0.17) (all P < 0.05) while it significantly increased in the relaxin group (1.08 ±0.15) (all P < 0.05).The levels of phosphorylation of ERK1/2 in the asthmatic and vehicle groups (1.45 ± 0.13,1.36 ± 0.09) were higher than those in the control group (0.38 ±0.17) (all P < 0.05) while it decreased in the relaxin treatment group (0.72 ±0.06) (all P < 0.05).No differences existed in all parameters between the asthmatic and vehicle groups (P>0.05).Conclusion Relaxin alleviates the airway inflammation and airway smooth muscle cell proliferation in a murine model of chronic asthma probably through activating Epac and inhibiting the phosohorylation of ERK1/2.
LIU Shi-ping, HE Li-ning, XIAO Yang, LI Xin-ying, ZHOU Zhi-guang
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.016
Abstract
Objective To investigate the potential role of adipocytes fatty acid binding protein (A-FABP) inhibitor to prevent pancreatic islet cells from cytotoxic injury by inflammatory cytokines released from macrophage.Methods Co-culture system for RAW264.7 macrophage and MIN6 insulinoma cells was established through transwell combined with A-FABP inhibitor BMS309403 treatment for 48 h.Meanwhile,cultured RAW264.7 and MIN6 respectively were set up as controls.In the inhibitor group,BMS309403 preprocessing (5 μmol/L) was performed 2 h before co-culture.The expression of toll-like receptors(TLR) 4 and A-FABP in RAW264.7 macrophages was detected by RT-PCR and Western blotting,interleukin(IL)-1β and tumor necrosis factor(TNF)-α levels in the supernatant were detected by ELISA,Glucose-stimulated insulin level was detected by insulin radioimmuno-assay kits for the function of islets.Results (1) The mRNA and protein levels of both TLR4 and A-FABP in RAW264.7 macrophages as well as the concentrations of IL-1β and TNF-α in the supernatant were significantly higher in co-culture group than in macrophages control group(P < 0.05).(2) Insulin secretion stimulated by high glucose was obviously decreased in co-culture group when compared with insulinoma cells control group [(16.0 ± 2.2) vs (41.1 ±6.6) ng/ml,P <0.05].After the treatment with A-FABP inhibitor,the mRNA and protein levels of both TLR4 and A-FABP as well as the concentrations of IL-1β and TNF-α in the supernatant were significantly lower than in co-culture control (P < 0.05).However,insulin secretion stimulated by high glucose was significantly enhanced when compared with insulinoma cells control group [(31.4 ± 3.3) vs (16.0 ± 2.2) ng/ml,P < 0.05].Conclusions This study demonstrated that co-culture of macrophage and islet cells can activate inflammation pathway,stimulate inflammatory cytokine release and decrease insulin secretion from islet cells.A-FABP inhibitor can protect islet cells from macrophage-mediated cytotoxicity and preserve its insulin secretory function.
SUN Yan-lin, GAO Peng, ZHANG Xiao-fang, ZHOU Geng-yin
National Medical Journal of ChinaVol.92,No.462012
DOI: 10.3760/cma.j.issn.0376-2491.2012.46.015
Abstract
Objective To explore the inhibitory effects on glucosylceramide synthase (GCS) expression and drug sensitivity in breast cancer cells by transfecting artificial microRNA targeting GCS.Methods Two microRNA expression vectors targeting GCS were constructed and transfected into MCF-7/ADR cells via Lipofectamine 2000.The levels of GCS mRNA and protein were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.Methyl thiazolyl tetrazolium (MTT) assay was used to assess the chemosensitivity of MCF-7/ADR cells to adriamycin (ADM) and vincristine.Results After transfection of two microRNA expression vectors,the expression of GCSmRNA in MCF-7/ADR cells was 0.098 ± 0.005 and 0.143 ± 0.007 respectively.Compared with the control cells (0.875 ± 0.008),the difference was significant (P < 0.01).The expression of GCS protein (0.127 ±0.004,0.165 ±0.008) in MCF-7/ADR cells was lower than that in the control cells (0.765 ±0.007 ; P <0.01).Furthermore,in comparison with the control cells,the resistance factor to adriamycin significantly dropped to 4.06 and 6.06 while the drug resistance to vincristine decreased to 8.30 and 12.67 respectively (P <0.01).Conclusion Artificial microRNA targeting GCS inhibits the GCS expression and restores significantly the sensitivity of breast cancer cells to anticancer drugs.These findings may provide a novel strategy of enhancing the chemotherapy sensitivity of breast cancer.
Objective To explore the variation of small ubiquitin-related modification (SUMO) level of glucocorticoid receptors (GRs) exposed to acrolein stimulation as well as the influence of the variation on mucus hypersecretion.Methods The recombinant plasmid was constructed by inserting small ubiquitin-like modifier 1 (SUMO1) cDNA into eukaryotic expression plasmid pcDNA3.1-EGFP with a flag sequence marker.The recombinant plasmid pcDNA3.1-EGFP-flag-SUMO1 was identified by enzyme digestion analysis.The 16HBE cells were cultured and randomized divided into 9 following groups:A.control; B.acrolein stimulated; C.dexamethasone incubated; D.acrolein stimulated and dexamethasone incubated; E.SUMO1 transfected; F.pcDNA3.1-EGFP vector transfected; G.SUMO1 transfected and acrolein stimulated; H.SUMO1 transfected,acrolein stimulated and dexamethasone incubated; Ⅰ.pcDNA3.1-EGFP vector transfected,acrolein stimulated and dexamethasone incubated.Each group consisted of 5 parallel wells and experiments were repeated for 4 times for statistical analysis.The transfection efficiency was evaluated by the expression of enhanced green fluorescent protein (EGFP) via fluorescence microscope.The SUMO modification level of GRs was measured with co-immunoprecipitation and Western blot.The transcription level of mucin (MUC) 5AC was evaluated with reverse transcriptionpolymerase chain reaction (RT-PCR).The MUC5AC secreted in supernatant was measured by enzymelinked immunosorbent assay (ELISA).Results The SUMO modification level was much lower in group B (0.079 ± 0.023) than that in group A (0.446 ± 0.068) (t =-23.13,P =0.000) and in group D (0.574 ±0.018) than that in group C (0.843 ±0.028) (t =-36.34,P =0.000).The transcription level of MUC5AC was significantly lower in group H (0.330 ±0.063) than group D (0.617 ± 0.190) (q =-7.80,P =0.000).Through ELISA,there was no significance between groups G and B in the term of secretion level of MUC5AC.While the secretion level of MUC5AC was much lower in group H ((0.416 ±0.092) μg/L) than group D ((0.663 ±0.104) μg/L) and group G ((0.740±0.343) μg/L) (q=-7.31,-9.59 ; P =0.001,0.000).Conclusion Acrolein decreases the SUMO modification of GRs and reduces the inhibitory effect of dexamethasone on the transcription of MUC5AC.
lenalidomide (LEN, C5013, Revlimid) is a derivative of glutamate and belongs to the immunomodulatory class of drugs [1-2]. It mainly plays a role through immunomodulation and inhibition of vascular endothelial growth factor, thus inhibiting tumor neovascularization and directly inhibiting tumor cell proliferation [3-5]. It is a second-generation derivative of thalidomide. Its amino group at C4 position on the phthaloyl ring makes it more chemically stable than thalidomide, has stronger angiogenesis inhibition and immunomodulatory effects, and has lower neurotoxicity, especially its reduction of teratogenic rate, which has aroused widespread attention. The US Food and Drug Administration (FDA) approved this drug for the treatment of myelodysplasia syndrome (MDS) on December 27, 2005, and it was approved for the treatment of multiple myeloma (MM) on June 29, 2006. In recent years, it has been shown that oral administration of ralidomide alone or combined with chemotherapy can make some patients with newly treated lymphoma get better curative effect, and some patients with relapsed and refractory treatment get remission again, and the adverse reactions are mild.