Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and o...Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.展开更多
The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapi...The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.展开更多
AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa a...AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113cases of gastric cancers were studied for the expression of PTEN and Caspase-3 andmicrovessel density (MVD)by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9% vs89.4%; P=0.000, χ2=33.474). PTEN expression was significantly associated with invasive depth (P=0.003,rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren′s classification (P=0.000,rs=0.345), and histological classification (P=0.005, rs=0.262)of tumors, but not with tumor size (P=0.639, rs=0.045),Borrmann′s classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020,F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 % vs 50.4 %; P=0.007,χ2=7.286).Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, χ2=15.266).CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth,differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.展开更多
Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases...Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.展开更多
AIM To investigate the effect of Boschniakiarossica(BR)extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory ac...AIM To investigate the effect of Boschniakiarossica(BR)extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase(GST-P),p53 and p21<sup>ras</sup>proteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H<sub>2</sub>O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver(GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05)andthe expression of mutant p53 and p21<sup>ras</sup>proteinwas lower than that of hepatic preneoplasticlesions(33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup).Both CH<sub>2</sub>Cl<sub>2</sub> and H<sub>2</sub>O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema(inhibitory rateswere 26%-29% and 35%-59%,respectively). BR-H<sub>2</sub>O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH<sub>2</sub>CI<sub>2</sub> and H<sub>2</sub>O extracts from BR exerted anti-inflammatory effect in rats and mice.展开更多
There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessar...There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.展开更多
AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).METHODS: The rat model of liver fibro...AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).METHODS: The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin α-SMA staining as well as Sirius-red and HE staining.RESULTS: The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with lie and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 Iobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of α-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of α-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P〈0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen.CONCLUSION: The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.展开更多
基金Acknowledgments We thank Drs Fengyong Liu and Sheng Luan at UC Berkeley, USA, for their discussion and help with the writing of the manuscript. This work was supported by grants from the National Natural Science Foundation of China (no. 30225037, 30471991, 30570731), National Basic Research Program of China (973 Program) (no. 2006CB503909, 2004CB518603), the "111" Project, and the Natural Science Foundation of Jiangsu Province (no. BK2004082, BK2006714).
文摘Dysregulated expression of microRNAs (miRNAs) in various tissues has been associated with a variety of diseases, including cancers. Here we demonstrate that miRNAs are present in the serum and plasma of humans and other animals such as mice, rats, bovine fetuses, calves, and horses. The levels of miRNAs in serum are stable, reproducible, and consistent among individuals of the same species. Employing Solexa, we sequenced all serum miRNAs of healthy Chinese subjects and found over 100 and 91 serum miRNAs in male and female subjects, respectively. We also identified specific expression patterns of serum miRNAs for lung cancer, colorectal cancer, and diabetes, providing evidence that serum miRNAs contain fingerprints for various diseases. Two non-small cell lung cancer-specific serum miRNAs obtained by Solexa were further validated in an independent trial of 75 healthy donors and 152 cancer patients, using quantitative reverse transcription polymerase chain reaction assays. Through these analyses, we conclude that serum miRNAs can serve as potential biomarkers for the detection of various cancers and other diseases.
基金supported by the Program for Changjiang Scholars and Innovative Research Team in University scheme of the Ministry of Education of China(NO.IRT1111)the National Basic Research Program of China(2012CB518300)+2 种基金the National Natural Science Foundation of China(81101946)the Shanghai Pujiang Program(12PJD008)Prostate Cancer Foundation Young Investigator Award,Shanghai Municipal Health and Family Planning Commission Outstanding Young Investigator(XYQ2013077).
文摘The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.
文摘AIM: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.METHODS: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113cases of gastric cancers were studied for the expression of PTEN and Caspase-3 andmicrovessel density (MVD)by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.RESULTS: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9% vs89.4%; P=0.000, χ2=33.474). PTEN expression was significantly associated with invasive depth (P=0.003,rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren′s classification (P=0.000,rs=0.345), and histological classification (P=0.005, rs=0.262)of tumors, but not with tumor size (P=0.639, rs=0.045),Borrmann′s classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020,F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 % vs 50.4 %; P=0.007,χ2=7.286).Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, χ2=15.266).CONCLUSION: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth,differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.
文摘Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.
基金the National Natural Science Foundation of China,No.39660021
文摘AIM To investigate the effect of Boschniakiarossica(BR)extract on expression of GST-P,p53 and p21<sup>ras</sup>proteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase(GST-P),p53 and p21<sup>ras</sup>proteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H<sub>2</sub>O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver(GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05)andthe expression of mutant p53 and p21<sup>ras</sup>proteinwas lower than that of hepatic preneoplasticlesions(33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup).Both CH<sub>2</sub>Cl<sub>2</sub> and H<sub>2</sub>O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema(inhibitory rateswere 26%-29% and 35%-59%,respectively). BR-H<sub>2</sub>O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH<sub>2</sub>CI<sub>2</sub> and H<sub>2</sub>O extracts from BR exerted anti-inflammatory effect in rats and mice.
基金The study was supported by National Key Research and Development Program(2018YFA0704100,2018YFA0704104)National Natural Science Foundation of China(81827805,82130060)Jiangsu Provincial Special Program of Medical Science(BE2019750).The funding sources had no role in the writing of the report,or decision to submit the paper for publication.
文摘There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.
文摘AIM: To study the morphological and serum hyaluronic acid (HA), laminin (LN), and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine (DMN).METHODS: The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin α-SMA staining as well as Sirius-red and HE staining.RESULTS: The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 (P = 0.043). The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with lie and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 Iobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of α-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of α-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group (P〈0.05) on different d (7, 14, and 28). The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen.CONCLUSION: The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.