National Medical Journal of China
Volume 88 · Issue 02 · 2008
Natl Med J China
The status and prospect of breast-conserving surgery in China
Breast cancer has become the main killer that seriously threatens women's physical and mental health worldwide, and the incidence rate is on the rise. It has ranked first and second among female malignant tumors in Beijing, Tianjin, Shanghai and other big cities in China. With the deepening of research on the biological characteristics of breast cancer, the development of prospective randomized trials and the successive reports of results, and the harvesting of a large number of retrospective research data, the development of clinical practice has been continuously promoted. "The difference of local treatment methods does not affect the survival rate of most breast cancer patients"-this new concept has been gradually accepted by people, and "effective minimum treatment" has gradually replaced "tolerable maximum treatment", which makes breast cancer treatment more humanized and individualized. Surgical treatment has become an important part of comprehensive treatment of breast cancer, and breast-conserving surgery has become the first choice for breast cancer surgery in stage I and II.
Influence of microencapsulated ovary cells modified with maspin gene on the microvessel density and lung metastasis of breast carcinoma
Objective To observe the inhibition of maspin on the angiogenesis in tumor and lung metastasis of breast carcinoma and the feasibility of treatment of tumor by microencapsulated transgene cells in vivo.Methods Microencapsulated Chinese hamster ovarian epithelial cells(CHO)modified with maspin gene,CHO/pcDNA3.1/maspin cells,were prepared.Twenty BALB/C nude rats underwent subcutaneous injection of breast carcinoma cells of the line Bcap37 to establish tumor-loaded animal models and then randomly divided into 2 groups:maspin group,undergoing subcutaneous injection of CHO/pcDNA3.1/maspin cells next to the transplanted tumor,and control group undergoing subcutaneous injection of microencapsulated CHO/pcDNA3.1 cells.One month later,the rats were killed and the size and microvessel density (MVD)of the transplanted tumor and metastatic tumor in lung were observed.Results The MVD of the transplanted tumor of the maspin group was 26±9,significantly lower than that of the control group(60±16,P<0.05).The lung metastatic rate of the maspin group was 15%,significantly lower than that of the control group(55%,P<0.05).Conclusion Maspin may inhibit the MVD in tumor and the occurrence of metastatic tumor in lung.It is feasible to use microencapsulated transgene cells as tumor-killer.
The relationship between lymphatic metastasis and serum vascular endothelial growth factor C and cyclooxygenase 2 expression in breast cancer
Objective To investigate the relationship among the serum vascular endothelial growth factor C(sVEGF-C),expression of cyclooxygenase 2(COX-2),and lymph vessel density(LMVD),and to discuss their role in tumor progression and lymphatic metastasis.Methods sVEGF-C level was detected by ELISA in 68 pre-operation breast cancer patients,35 breast benign disease patients,and 12 healthy women.Immunohistochemical method was used to detect the expression of COX-2 and lymphatic vessel endothelial hyaluronidase receptor(LYVE)-1 in the breast cancer tissues and benign disease tissues obtained during operation.Resuits (1)The sVEGF-C level of the pre-operation breast cancer group was (49±8)pg/ml,significantly higher than those of the begin tumor group[(8±4)pg/ml,P=0.045]and the healthy women[(5±3)pg/ml,P=0.003].(2)The COX-2 overexpression positive rate in the breast cancer tissues was 44.1%,significantly higher than that in the begin disease tissues(11.4%,P=0.002).Higher than that in the begin disease tissue;the LMVD overexpression in the breast cancer tissues was mainly located in the para-carcinoma tissue(8.7±4.7),significantly higher than that in the begin disease tissues(1.8±1.7,P=0.002).(3)The COX-2 overexpression rate of the patients with a high sVEGF-C level was significantly higher than that of the patients with a low sVEGF-C level(P=0.024).The LMVD level in the breast cancer of the sVEGF-C high level group was(8.7±3.9),significantly higher than that of the sVEGF-C normal group(5.6 ±3.3,P=0.039).(4)The LMVD in the COX-2 overexpression breast cancer group was 9.5±3.7,significantly higher than that in the COX-2 negative group(6.0±3.8,P=0.012).(5)The sVEGF-C level,COX-2,and LMVD expression in the breast cancer patients with lymphatie metastasis were significantly higher than those in the patients without lymphatic metastasis(P=0.025,0.022,and 0.002 respectively).Conclusion VEGF-C,COX-2,and LMVD play important roles in the lymphatie metastasis of breast cancer.They may be important prognostic factors in evaluating breast cancer lymphatic metastasis.
The clinical study on neoadjuvant chemotherapy with combination of Docetaxel and Pharmorubicin for locally advanced breast cancer
Objective To evaluate the clinical efficacy and toxicity of combination neoadjuvant chemotherapy with docetaxel and pharmorubicin in the treatment of locally advanced breast cancer.Methods From June 2005 to March 2007,94 breast cancer patients who have been pathologically confirmed by core needle biopsy were treated with neoadjuvant chemotherapy before operation.Docetaxel 75 mg/m2 plus pharmorubicin 80 mg/m2 were administered as intravenous infusion on the first day of each 3-week cycle.Accepted 2 to 4 cycles of the treatment,the patients were underwent surgery after 12 to 16 days.Results The overall response rate(RR)was 80%(76/94).The complete clinical response rate(CR)was 22%(21/94).The partial response rate(PR)was 58%(55/94).The stable disease(SD)rate was 17%(16/94).The progress disease(PD)rate was 2%(2/94).The pathological complete rate(pCR)was 3%(3/94).The major toxic reactions of the therapy were neutropenia,alopecia,nausea and vomit.76 patients (80%)suffered with grade 3 to 4 neutropenia.4 patients suffered with grade 3 to 4 thrombocytopenia.84 patients suffered with severe alopecia.90 patients(95%)accepted supportive treatment of G-CSF.Septicemia and death were not occurred in this study.Conclusion The combination neoadjuvant chemotherapy with docetaxel and pharmorubicin is an effective method to treat breast cancer and the toxicities are tolerable.
Role of ultrasound-guided needle biopsy of ultrasonographic abnormal axillary lymph nodes in patients with breast cancer
Objective To evaluate the utility of ultrasound(US)-guided needle biopsy of ultrasonographic abnormal axillary lymph nodes in the patients with breast cancer.Methods The pathological results of US-guided needle biopsy and clinical data of 395 primary breast cancer patients with ultrasonographic abnormal axillary nodes,all female,aged 24-83,were analyzed retrospectively.Results Node metastasis were detected in 277(70.1%)cases by mean of ultrasound-guided needle biopsy.Among 136 patients with clinical N0 breast cancer,65(47.8%)were proved node positive.Sixty-two patients were diagnosed as pathologically negative by needle biopsy and underwent sentinel lymph node biopsy or axillary lymph node clearance,and pathological examination showed negative axillary lymph node negative.The complete pathological complete remission rate of the metastatic lymph nodes after new adjuvant chemotherapy was 32.3%(62/192).Conclusion Ultrasonographic examination of axilla combined with ultrasoundguided needle biopsy of suspicious axillary node is valuable in primary breast cancer treatment.
Clinical characteristics and prognostic factors of female breast cancer patients with 10 or more positive lymph nodes:a report of 128 patients
Objective To analyze the clinical characteristics,survival,and prognosis of female breast cancer patients with 10 or more positive lymph nodes.Methods The data of 128 female breast cancer patients with 10 or more positive lymph nodes from JAN 1998 to Mar 2002 were retrospectively reviewed.The clinical characteristics,survival,and prognostic factors were analyzed by SPSS 10.0 statistic software.Results The 1-,3-,5,and 7-year overall survival(OS)rates were 91.4%,68.8%,53.1%,and 40.2%,and the disease free survival(DFS)rates were 80.9%,54.1%,44.7%,and 36.0%respectively.Log Rank test showed that tumor size was not related to prognosis:patients with more than 20 positive lymph nodes(P=0.029),positive lymph node ratio greater than 0.8(P=0.027),and infiltration of vessel(P=0.037)had a poorer DFS and shorter OS:patients with negative hormonal receptor had a poorer OS than those with positive hormonal receptor(P=0.019):radiotherapy improved DFS(P=0.000),and adjuvant chemotherapy for 4-6 cycles(P=0.000)or more than 6 cycles(P=0.004)and endocrine therapy(P=0.001)might improve DFS and OS;patients with multiple metastasis had a poorer survival than those with local recurrence(P=0.004)and single metastasis(P=0.058).COX proportional hazard model analysis showed that positive lymph node ratio and infiltration of vessel were independent prognostic factors for both DFS and OS;adiuvant endocrine therapy decreased relapse and death hazard ratio for 43%(RR=0.57,P=0.035)and 65%(RR=0.35,P=0.000)respectively;adjuvant radiotherapy decreased the relapse hazard ratio for 72%(RR=0.28,P=0.000):and adiuvant chemotherapy for more than 4 cycles decreased death hazard ratio for 51%(RR=0.49,P=0.001);patients with recurrence and/or metastasis had a higher death hazard ratio(RR=2.738,P=0.000),hormonal receptor was an independent prognostic factor,and active treatment might improve the survival.Conclusion Breast cancers with 10 or more positive lymph nodes have higher aggressively biologic characteristics;the prognosis of this subgroup has no relationship with tumor size and inverse correlation with the numbers of positive lymph nodes;Positive lymph node ratio and infiltration of vessel are important independent factors.Multidiscipline therapy including adjuvant radiotherapy, endocrine therapy, and at least 4 cycles chemotherapy increases the therapeutic effect,decreases relapse and death hazard ratio,and improves the survival.
Effect of pegylated interferon β-1a therapy on the liver fibrosis in chronic hepatitis C:a semi-quantitative analysis
Objective To access the effect of pegylated interferon(PEGIFN)β-1a on the reduction of liver fibrosis in chronic hepatitis C(HVC).Methods Twenty-one patients with chronic HVC were divided into two groups randomly and treated with recombinant human PEGIHN-β-1a(n=13)or PEGIHN-β-1a plus ribavirin(RBV)(n=8)for 24 weeks,and then followed up for another 24 weeks.The clinical manifestations were observed and the clinical effects were evaluated.Biopsy was conducted before and after the treatment to analyze the histological activity index(HAI)and staging of fibrosis according the modified Knodell scoring system.Immunohistochemical analysis was used to examine the levels of α-smooth muscle actin(α-SMA),marker of activation of hepatic stellate cells(HSCs),and collagen type Ⅲ in the HSCs.Resalts Sustained viral response(SVR)was achieved in 7 patients,and end-of-treatment virologic response(ETVR)was achieved in 9 patients.The HAI after treatment was 4.3±2.2,significantly lower than that before treatment(6.6±2.2,t=4.77,P<0.01).The fibrosis score after treatment was 1.1±1.1,significantly lower than that before treatment(1.7±1.2,t=1.92,P<0.05).The α-SMA score after treatment was 14±8,significantly lower than that before treatment(20±11,t=2.15,P<0.05).The integrated light density of collagen type Ⅲ after treratment was 10±10,significantly lower than that before treatment(16±12,t=1.83,P<0.05).The improvement levels of fibrosis,α-SMA score,and integrated light density of collagen type Ⅲ of the patients with SVR were all better than those of the patients without SVR:however,the differences were all not significant.The patients with combination therapy,female patients,and the patients with the HCV RNA<2×106 copies/ml before treatment all showed higher levels in histology response.HAI,α-SMA level,and collagen type Ⅲ values were all significantly correlated with the values of the semiquantitative indexes of fibrosis(all P<0.01).Conclusion Resisting hepatitis virus C and inhibiting and reversing the fibrotic progress,IFN-β-1a therapy improves the liver histology of chronic HVC regardless of the viral response.
Level of alpha-granulemembrane protein(CD62P)in coronary heart disease
Objective To investigate the role of alpha-granulemembrane protein(CD62P),marker of plate activation,in the patients with coronary heart disease(CHD)and to investigate the relationship between the severity of coronary artery stenosis and platelet activation.Methods Peripheral blood samples were collected from 70 patients with CHD,including 28 cases of stable angina pectoris(SAP),26 cases of unstable angina pectoris(UAP),and 16 cases of acute myocardial infarction(AMI),all of which underwent coronary arteriography,and 20 angiographically normal persons as no-CHD controls.The CD62P level was analyzed by flow cytometry(FCM).Resuits Coronary arteriography showed positivity in 70 of the 90 CHD patients.The CD62P positive rate of the UAP group was(28.3±20.1)%,significantly higher than those of the SAP group[(12.8 ±13.3)%]and no-CHD group[(9.9 ±6.4)%,both P<0.05].The CD62P positive rate of the double vessel disease group was(24.0 ±17.8)%,not significantly different from that of the three-vessel disease group[(22.6±20.4)%],but significantly higher than that of the single-vessel disease group[(11.1 ±8.5)%]and that of the no-CHD group[(9.9 ±6.4)%,both P<0.05].Condusion The platelet alpha-granulemembrane protein CD62P level is higher in the UAP patients.It is related to the pathophysiological process of UAP and the severity of coronary artery stenosis.
Prophylaxis and management of biliary complications after orthotopic liver transplantation
Objective To investigate the risk factors of biliary complications after orthotopic liver transplantation(OLTx)and the relevant prevention and management strategies.Methods The clinical data of 368 patients undergoing allograft orthotopic liver transplantation,282 males and 86 females,aged 47.5(8-73),were collected and analyzed retrospectively.Results Of the 368 OLTx patients,36(9.8%)experienced biliary complications,including simple anatomosis biliary leakage(7 cases),biliary leakage due to injury and omission of accessory hepatic duct(1 case),anastomosis stricture(5 cases),intrahepatic bile duct stricture(3 cases),bile duct stricture secondary to bile duct twist(1 case),calculus of intrahepatic duct(2 cases),bile duct stricture secondary to biliary leakage(2 cases),bile duct stricture combined with intrahepatic biloma(2 cases),bile duct stricture combined with biliary sludge(2 cases),biliary cast syndrome(5 cases),hemobilia(1 case),intrahepatic abscess(3 cases)and Oddi's sphincter dysfunction (2 cases).Among the 36 patients with biliary complications,23 were cured by nonsurgical therapies;and 13 patients needed abdominal surgical interventions,including retransplantation in 7 cases.Conclusion Biliary complications after OLT are difficult to treat.Most of these complications can be cured conservatively,such as radiological intervention and endoscopic treatment.When the patients are unresponsive to nonsurgical therapies,or when they suffer from hepatic arterial embolism or arterial stricture simultaneously,surgical interventions,even retransplantation should be considered.
Influence of pravastatin on blood lipids and serum high sensitive C-reactive protein in patients undergoing conventional coronary artery bypass grafting under on-pump:a clinical study of 81 cases
Objective To investigate the effect of pravastatin on blood lipids and serum high sensitive C-reactive protein(HsCRP)in patients undergoing conventional coronary artery bypass grafting under on-pump bypass(CCABG).Methods Eighty-one patients underwent CCABG.Among which 40 took orally pravastatin 20 mg once daily to at least 28 days after operation,and 41 were used as control group.The serum levels of total cholesterol(TC),triglyceride(TG),HDL-C cholesterol(HDL-C),LDI-C cholesterol(LDL-C),and HsCRP were monitored before and 24 h,72 h,7 days,10 days,14 days,and 28 days postoperatively.Results In the control group the levels of different blood lipids after operation remarkably decreased after operation compared with those before operation(all P<0.05),reached the lowest levels 24 h after operation,then gradually increased,however,still lower than those before operation (all P<0.05),and recovered to the baseline level 28 hours after operation;and the HsCRP level increased 24 h after operation and peaked 72 h after,then gradually decreased,and recovered to the baseline level 28 days after operation.In the pravastatin group the TC level reached its lowest level 24 h after operation,then graduallv increased,however,still lower than that before operation,and recovered to the baseline level 28 days after operation;and the TG level reached the lowest level 24 h after operation(P<0.05),and then gradually increased 3 d after operation(P>0.05).The TC,TG,and LDL-C levels 7,10,14,and 28 d after operation of the pravastatin group were all significantly lower than those of the control group(all P<0.05).The HsCRP levels at different time points of the pravastatin group were all significantly lower than those of the control group(all P<0.05).Conclusion The use of pravastatin in the early stage of CCABG is safe and can decrease systemic inflammatory reaction.
Detection of plasmid-mediated carbapenem-hydrolyzing β-lactamase KPC-2 in a strain of carbapenem-resistant Enterobacter cloacae
Objective To investigate the mechanism of carbapenem resistance in Enterobacter cloacae.Methods A carbapenem-resistant strain of E.cloacae (strain ZY1465)was isolated.Antibiotic susceptibilities were determined by agar dilution method.Conjugation experiments were carried out in mixed broth cultures.Plasmid DNA preparations were obtained by using an alkalinelysis technique and were digested by various endonucleases;The crude β-lactamase extracts of E.cloacae and E.coli transconjugant were subjected to analytical isoelectric focusing(IEF).Specific PCR amplification and DNA sequence analysis were preformed to confirm the β-lactamase type.Outer membrane proteins(OMPs)were isolated and examined by urea-sodium dodecyl sulfate-polyacrylamide gel electrophoresis.Results The E. cloacae isolate showed resistance against carbapenems.The MICs of imipenem and meropenem were both 32 μg/ml.The isolate was also resistant strongly against penicillins,cephalosporins,cefoxitin,aztreonam,quinolones,and aminoglycosides.Conjugation studies with E.coli resulted in the transfer of reduced carbapenem susceptibility from E.cloacae isolate.Plasmid restriction analysis showed identical restriction profiles between the transconjugants of E. cloacae ZY1465 and Serratia marcescens ZN008.Isoelectric focusing demonstrated six β-lactamases,with the isoelectrie points(pls)of5.4,6.7,7.3,7.8,7.9,and 8.6,in E.cloacae ZY1465.and only one β-lactamase with the pI of 6.7 in transconiugant.Specific PCR amplification and DNA sequence analysis confirmed that E.cloacae ZY1465 harbored TEM-1,KPC-2,DHA-1,CTX-M-14,CTX-M-3 and chromosomal AmpC(not detected in IEF)genes.Urea-SDS-PAGE analysis of OMPs showed that E. cloacae ZY1465 lacked an OMP of approximately 38 000 Da which was present in E. cloacae ATCC13047.Conclusion It is the first detection of plasmid-mediated carbapenemhydrolyzing β-lactamase KPC-2 in a clinical isolate of E.cloacae from China.Production of multiple β-lactamases,especially KPC-2 and loss of an OMP in E.cloacae ZY1465 result in resistance to carbapenems.
Regional gene delivery via the bile duct to damaged liver using peptide/DNA particles:experiment with rats
Objective To evaluate the efficacy of gene delivery to the fight lateral lobe of liver via a branch of the bile duct.Methods Twenty LEW rats underwent intraperitoneal injection of D-galactosamine to establish acute liver damage models and were randomly divided into 5 groups to undergo ligation of the common bile duct and left bile duct 4,5,6,or 7 days after the acute liver damage.Non-viral vector gene compound,polylysine-molossin/pGL3 containing firefly luciferin gene or CMVβ containing β-galactosidase of Escherichia coli/fusogenic)was injected in to the right lateral lobes 2 and 3 via the branch of right bile duct.Four rats without injection of D-galactosamine but undergoing injection of polylysine-molossin/pGL3 or CMVβ/fusogenic were used as normal controls.Twenty-four hours after the regional gene delivery the rats were killed.The expressions of luciferin and β-galactosidase in different lobes were detected.Pathological examination of liver was conducted.Results All rats survived after the operation.The expression levels of luciferin in the liver on the days 4,5,and 6 were all significantly higher than that of the normal control rats ( all P<0.05).The expression levels of luciferin in the liver on the day 7 was the highest compared with the normal control rats(P=0.01).However,the level of lucifefin in the liver on the day 9 was lower and not significantly different from that of the normal rats(P>0.05).Scattered distribution of β-galactosidase was seen in the lobe 2 of the rats with acute liver damage.The levels of alanine transaminase and aspartate aminotransferase were slightly increased and the albumin level was slightly decreased in the rats with acute liver damage on the days 4 and 7,however,these biochemical indexes were not significantly correlated with the gene expression.There was no obvious histological difference between the lobes 2 and 3 and lobe 1.Conclusion Gene delivery with peptide/DNA complexes shows a good expression in the acute damaged liver without aggravating the liver damage,thus providing a technical platform for the experimental research of liver gene therapy.
Effect of polygona-polysaccharose on atheromatous plaque:experiment with rabbits
Objective To study the effect of polygona-polysaccharose on the elimination of atheromatous plaque.Methods Thirty adult New Zealand rabbits were fed with high-fat and cholesterol forage for 8 weeks to establish hyperlipidemia animal models and then randomly divided into 3 equal groups:model group,simvastatin group receiving simvastatin orally,and polygona-polysaccharose group receiving polygona-polysaccharose orally.Ten rabbits were fed with normal food as control forage.At weeks 0,2,and 8 the levels of total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),and lipoprotein(a)[Lp(a)]were determined with enzyme method.At the end of the week 8,all rabbits were killed to observe the elimination of aorta atheromatous plaque by microscope.Results Before the experiment,there were no significant differences in the levels of serum lipids among all groups.At the end of week 2(before treatment),the levels of serum TC of the model group,simvastatin group,and polygona-polysaccharose group were(10.2 ±1.6)mmol/L,(11 ±1.8)mmol/L,and(11.2 ±1.9)mmol/L respectively,the LDL-C levels of the 3 groups were(9.85±1.65)mmol/L,(9.80 ±1.54)mmol/L,and(10.08±1.88)mmol/L respectively,the Lp(a)levels of the 3 groups were(656 ±106)mmol/L,(700 ±151)mmol/L,and(666±111)mmol/L respectively,all significantly higher than that of the control group[(1.3 ±0.3)mmol/L,(0.55 ±0.15)mmol/L,and(106 ±15)mg/L respectively,all P<0.01].At the end of week 8(after treatment),the levels of serum TC,LDL-C,and Lp(a)of the polygona-polysaccharose group were(6.0 ±2.0)mmol/L,(4.25 ±1.35)mmol/L,and(55 ±14)mg/Lrespectively,all significantly lower than that at the end of week 2 [(11.2±1.9)mmol/L,(10.08 ±1.88)mmol/L,and(666 ±111)mg/L respectively,all P<0.01].The aorta atheromatous plaques in the polygona-polysaccharose group were basically eliminated compared with that in the model group.Conclusion
16S rRNA gene sequencing for pathogen identification from clinical specimens
Objective To investigate the key point technique with 16S rRNA gene sequence for identifying the pathogens in clinical specimens,and to evaluate the feasibility and practicability as a routine tool for determining pathogens in clinical laboratory.Methods 117 clinical specimens from difierent sources underwent morphological examination,bacterium culture,and 16S rRNA gene PCR and sequencing.Two parts of 16S rRNA gene(BSF8-BSR534 and BAK11w-BAK2)were amplified by PCR,the products of PCR were purified by gel isolation,sequencing was conducted for the fragments,and then the sequence was put in GenBank BLAST to compare with data-base in NCBI.If the similarity of different original sequences was more than 99%,the bacterium could be considered as the homogeneous species.The sensitivity and specificity for pathogens identification were compared among different methods.Resuits The positive rates of bacterium culture and PCR test were 49%(57/117)and 72%(84/117)respectively.7 bacteria could be classified as the pathogens from the 60 cases negative by culture methods.The positive rate of direct smearing was 64%(75/117);similar to that of the PCR consequence,and the combination of both methods could provide inferential repots.The 16S rRNA gene was perfect relativity with bacterial evolution and phylogenesis,and it could be classified species by the sequencing.The first pair of primer of the 16S rRNA gene(amplification area:BSF8-BSR534)was suitable for the Gram positive bacterium,and second pair of primer(amplification area:BAK11w-BAK2)was suitable for the common pathogens in the clinical specimens.Conclusion By improving the extract DNA method,selecting suitable primer,developing the gene amplification and sequencing procedure,direct 16S rRNA gene sequencing can identify the pathogens from clinical specimens.
Mechanism of hepatic stellate cell migration during liver fibrosis
Objective To study the mechanism of migration of hepatic stellate cells(HSCs)within the Space of Disse microenvironment during liver fibrosis,and to explore the novel pathogenesis of liver fibrosis from the view of cell migration.Methods Human HSCs of the line LX2-HSC were cultured.A modified in vitro Boyden chamber system was used to partially mimic the microenvironment of Disse space of normal basement membrane like matrix or that in fibrosis.HSCs were put in the upper chamber,and transforming growth factor(TGF)-β1,plate-derived growth factor(PDGF)-BB,epidermal growth factor (EGF),vascular epithelial growth factor(VEGF),bfibroblast growth factor(bFGF),and collagen type Ⅰ or type Ⅳ were put into the lower chamber.Four hours later cell migration assay was conducted.HSCs were put into 6-well plate and then added with TGF-β1,PDGF-BB,EGF,VEGF,bFGF,and collagen type Ⅰ or type Ⅳ,zymography was used to examine the activity of matrix metalloproteinases 2 and 9.SDS-gel immunoblotting was used too.Resuits Stimulation of HSCs with PDGF-BB,TGF-β1,and/or EGF resulted in an increase in their migratory capacity and up-regulated MMP-2 activity.And the increase of MMP-2 could enhance Migration of HSC by 4.9-fold.The migration of HSCs(3.2-fold)was induced by type Ⅰ collagen and inhibited by type Ⅳ collagen(1.2-fold).Migration induced by PDGF-BB,TGF-β1,and collagen Ⅰ could be inhibited by α1-and/or α2-integrin blocking antibodies.Conclusion In liver fibrosis,alterations within the space of Disse microenvironment facilitate the migration of HSCs:the mechanism is associated with up-regulation of MMP-2 and with mediation of α1 β1 and α2β1 integrins.Extracellular matrix by it self shows feedback actions to migration of HSCs.
Role of progesterone in acylation stimulating protein-receptor C5L2 pathway in adipocytes and preadipocytes
Objective To evaluate the effects of progesterone on the mRNA expression of acylation stimulating protein(ASP)-receptor C5L2 in adipocytes and preadipocytes and the C5L2 protein expression on the cell surface.Methods Preadipocytes of the line 3T3-L1 were cultured and induced to differentiate.Progesterone of the doses 0-1×10-6 mol/L was added into the cultured fluid of the mature 3T3-L1 adipocytes and preadipocytes overnight.RT-PCR and flow cytometry were used to detect the mRNA and protein expression of ASP receptor C512.Both non-progesterone treated and progesterone-treated 3T3-L1 cells were cultured with 5.0 μmol/L ASP for 4 hours,then the cell protein was extracted and the expressions of G protein(including Gαq/11 and Gβ)and phosphated protein kinase C(including p-PKCα and PPKCζ)were measured by Western blotting.Results The C5L2 protein expression level of the mature adipocytes stimulated by progesterone 1 × 10-6 mol/L for 18 h was 36%± 15%,significantly downregulated compared with that of the adipocytes stimulated by progesterone 0 mol/L(46%±12%,P<0.01),with a inhibition rate of 22%.The C5L2 mRNA and protein expression levels of the preadipocytes stimulated by progesterone 1×10-6 mol/L for 18 h were 0.17±0.11 and 36%±16%respectively,both significantly lower than those of the preadipocytes stimulated by progesterone 0 mol/L (0.50±0.18 and 51%±20%respectively,P<0.01 and P<0.05)with the inhibition rates of 66%and 29%respectively.The ASPstimulated Gαq/11,Gβ,P-PKCα,and P-PKCζ expression levels of the mature adipocytes after overnight exposure to progesterone 1×10-8 and 1×10-6 mol/L were suppressed dose-dependently.For example,the ASP-stimulated Gαq/11,Gβ,and p-PKCα expression levels of the progesterone 1×10-6 mol/L group were significantly lower than those of the progesterone 0 mol/L group by 41%,63%,and 49%respectively(P<0.05 to P<0.01.In the preadipocytes the reduction of ASP-induced Gαq/11,Gβ,and p-PKCζ expression levels were observed at the concentration of progesterone as low as 1×10-8 mol/L,and all the four proteins were inhibited significantly at the 1×10-6 mol/L progesterone concentration.Conclusion Progesterone induces ASP resistance in adipocytes and preadipocytes.ASP resistance may contribute to the physiological abnormalities associated with insulin resistance induced by progesterone.
Molecular mechanism of the inhibitory effect of retinoic acid-induced gene G protein on tumor cell proliferation
Objective To investigate the molecular mechanisms of anti-proliferative effect of retinoic acid-induced gene G(RIG-G)protein on tumor cells.Methods HA-RIG-G expression plasmid and FLAG-Jun activating binding protein 1(JAB1)expression plasmid were construction and transfected into the African green monkey kidney cells of the line CDS-7 and mouse fibroblast cells of the line NIH3T3.Western blotting was used to detect the p27 expression in the cells.analysis,and Immunofluorescence staining was used to examine the distribution of JAB1 protein.Coimmunoprecipitation was used to analyze the interference of RIG-G on the function of JAB1 protein.Results Coimmunoprecipitation showed that when HA-RIG-G and FLAG-JAB1 were co-expressed,the RIG-G protein and JAB1 protein could be coprecipitated by the antibodies of the other side.RIG-G was able to interact with JAB1 and alter its intracellular localization and distribution.When JAB1 was transfected alone into the NIH3T3 cells,it dispersed in both nucleus and cytoplasm:however,when RIG-G and JAB1 were cotransfected,the nuclear JAB1 was markedly diminished and exhibited a partly co-localization with RIG-G in the cytoplasm.Western blotting showed that along with the increase of the dose of transfected JAB1 the amount of p27 in the cell;and along with the increase of co-transfected RIG-G gene expression plasmid the amount of p27 in the cells re-increased.Conclusion RIG-G interacts with JAB1,thus resulting in JAB1 sequestration in the cytoplasm,disturbing the JAB1 normal function,interfering the JAB1-mediated p27 degradation,maintaining p27 protein stability so as to prevent cells from entering the cycle and inhibiting cell proliferation.
Application of single nucleotide polymorphisms in predicting anticancer drug response and toxicity
Single nucleotide polymorphism (SNP), as one of the most common heritable variants, has important application value in disease risk assessment, prevention, early diagnosis, treatment response and prognosis assessment. Like all drugs, anticancer drugs play their role through absorption, metabolism, distribution and clearance in vivo, and through the direct attack of their active substances on therapeutic targets. The whole process requires the joint participation and synergistic action of multiple proteins/enzymes. If SNP changes the function and activity of any protein (including the therapeutic target itself), the efficacy and toxicity of anticancer drugs in specific individuals will be changed. To study the correlation between SNP and its gene expression products, we should reveal the correlation between the differences in genetic background and individual differences in drug response and toxicity, and make accurate prediction of therapeutic response, To realize the individualization of tumor drug therapy. The current status and progress of research on some SNPs related to the response and toxicity of anti-cancer drugs are reviewed.
Association between prostate-specific antigen concentration and obesity-related hemodilution in patients with prostate cancer
In the past 10 years, the incidence of obesity in the United States has increased sharply. Recent studies suggest that serum prostate specific antigen (PSA) concentrations in obese men are lower than those in non-obese men. Because men with higher body mass index (BMI) have larger circulating plasma volume, the low PSA concentrations in obese men may be related to hemodilution. In order to clarify the relationship between PSA concentrations and obesity-related hemodilution in prostate cancer patients, Lionel et al. from Duke University Medical Center in the United States conducted a retrospective study of prostate cancer patients undergoing radical prostatectomy from 1988 to 2006 using the equal access database shared by local cancer hospitals (n =1373), the Duke Prostate Research Center database (n =1974) and the Johns Hopkins Hospital database (n =10 287). The results were published in the November 21, 2007 issue of JAMA (JAMA, 2007, 298:2275-2280).
Relationship between lymph node examination rate and survival rate after tumor resection in patients with colon cancer
A number of studies have shown that patients with colon cancer who undergo more lymph node examination after colectomy have better survival. Recently, the American Quality Forum and other organizations have used ≥12 lymph nodes as one of the evaluation criteria for hospital diagnosis and treatment quality. In order to evaluate whether more lymph node examination after colectomy can improve the survival rate of patients, Sandra et al., who work at the University of Michigan, USA, conducted a retrospective cohort study on patients with non-metastatic colon cancer (n =30 625) who underwent colectomy with the help of the population surveillance, epidemiology and final results (SSER) database (1995-2005) linked with basic medical insurance data. The results were published in JAMA, Nov. 14, 2007 (JAMA, 2007, 298: 2149-2154).
The 3rd Annual Meeting of Chinese Dermatologists was held in Beijing
The 3rd Annual Conference of Chinese Dermatologists, sponsored by the Chinese Medical Doctor Association and the Dermatologist Branch of the Chinese Medical Doctor Association, co-organized by the Institute of Dermatology of Chinese Academy of Medical Sciences, the First Hospital of Peking University, the General Hospital of the Chinese People's Liberation Army and the Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences, was held in Beijing Jiuhua International Convention and Exhibition Center on December 5-8, 2007. The conference was chaired by Professor Sun Jianfang of the Institute of Dermatology of the Chinese Academy of Medical Sciences, Professor Wang Baoxi of the Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences as the chairman of the academic committee, and Professor Li Hengjin of the General Hospital of the Chinese People's Liberation Army as the secretary general of the conference. About 2500 dermatologists and scholars from affiliated hospitals of medical schools, provincial general hospitals and specialized hospitals all over the country attended the conference.
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A case of rhabdomyosarcoma of the nasal and paranasal sinuses
A 68-year-old female patient suffered from headache for 3 months and repeated epistaxis for 1 month. Physical examination showed that the right nasal cavity was filled with red new organisms, the surface was uneven, the texture was hard, and it was easy to bleed when touched, and a small amount of light blood exudate was found in the right nasal cavity. CT examination showed that the soft tissue mass was filled in the right nasal cavity, maxillary sinus, ethmoid sinus, frontal sinus and sphenoid sinus on both sides, and the density was uniform. The CT scan was about 44 HU (Figure 1), and the CT scan was about 91.6 HU (Figure 2), which indicated that the lesion was obviously enhanced, the involved sinus cavity was enlarged, the ethmoid sinus paper plate was destroyed, and the mass expanded and grew obviously, some of which crossed the midline and involved the left ethmoid sinus. The CT bone window showed that the skull base was destroyed, the bottom of the middle skull fossa was involved, and the mass grew backward from the posterior nostril, resulting in nasopharyngeal airway stenosis. The DSA of the right external carotid artery showed that the diameter of the right maxillary artery was thickened, with many small branches emanating from the main trunk and distributed in the area where the tumor was located. The blood vessels were twisted and the tumor area was slightly stained, but there were no obvious vascular lakes and malformed blood vessels. Some small branches of the facial artery emanated to supply
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