Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy.However,the relation between the...Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy.However,the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear.Through comprehensive bioinformatic analyses,we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy.Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant.Mechanistically,activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance.Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors.Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance,which holds important clinical implications for improving SCLC treatment.展开更多
Objective： Hepatocellular carcinoma （HCC） is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, wh...Objective： Hepatocellular carcinoma （HCC） is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of micreRNA-718 （miR-718） in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods： Here we first used a methylthiazolyldiphenyl- tetrazolium bromide （MTT） assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein （GFP） reporter assay, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR） to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results： We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 （EGR3） is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the via- bility and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions： miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic 07） found that overexpreget for HCC.展开更多
AIM:To compare the clinicopathological characteristics of human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative Barrett's adenocarcinoma in Japan. METHODS:We performed immunohistochemical anal...AIM:To compare the clinicopathological characteristics of human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative Barrett's adenocarcinoma in Japan. METHODS:We performed immunohistochemical analysis of HER2 in 30 samples taken from patients with Barrett's adenocarcinoma and dual color in situ hybridization in cases showing 2+ reactions. We compared the clinicopathological characteristics of HER2-positive and HER2-negative patients.RESULTS:HER2 positivity was identified in 8 (27%) carcinoma samples. We found that HER2 expression was associated with p53 overexpression (100% vs 52.6% in pT1 tumor; 100% vs 54.5% in all stage tumor, P < 0.05) and protruding lesions at the early disease stage. There was no association between the mucin phenotype of the carcinomas and prognosis. HER2 expression and low clinical stage were unexpectedly different between Barrett's adenocarcinoma patients and gastric cancer patients, but the macroscopic features may be associated with earlier diagnosis in these patients. CONCLUSION:Our results suggest that HER2-positive Barrett's adenocarcinomas are associated with p53 overexpression and lesion protrusion at the early disease stage.展开更多
The purpose of this work is to illustrate the relationship between genotype and phenotype in the complex cellular network of saccharomyces cerevisiae. As a structure-oriented method, using elementary flux mode(EFM) an...The purpose of this work is to illustrate the relationship between genotype and phenotype in the complex cellular network of saccharomyces cerevisiae. As a structure-oriented method, using elementary flux mode(EFM) analysis can obtain its popularity in analysis of the robustness of the central metabolism, as well as network function of some organisms. However, this method has not been widely used for modeling gene deletion phenotype. By enumerating all the metabolic pathways, the EFM analysis presented herein can be used to identify the functional features and predict the growth phenotype of the S.cerevisiae. In comparison with the flux balance analysis(FBA), the performance of EFM analysis was superior to FBA in prediction of gene deletion phenotype. EFM analysis is demonstrated to be an effective tool for bridging the gap between metabolic network and growth phenotype.展开更多
Objective: To study the genetic and non-genetic factors and their interactions affecting growth rate and body weights at birth, weaning and at 6 months of age in Saudi Ardi, Damascus goats and their crosses. Methods: ...Objective: To study the genetic and non-genetic factors and their interactions affecting growth rate and body weights at birth, weaning and at 6 months of age in Saudi Ardi, Damascus goats and their crosses. Methods: Crossbreeding program between Saudi Ardi(A) goats with Damascus(D) was carried out to improve the meat productivity of Ardi goats through crossbreeding. The pedigree records of the body weights were obtained from 754 kids (397 males and 357 females) produced from 46 Sires and 279 Dams. Birth weight, weaning weigh and 6 months weight as well as average daily gain during different growth stages from birth to weaning (D1), weaning to 6 months (D2) and from birth to 6 months of age (D3) were recorded during winter/autumn and summer/spring. Data were classified according to breed, generation, sex, season, year, and type of birth. Data were analyzed using GLM procedure for the least-squares means of the fixed factors. Heritability and genetic parameters were estimated with derivative-free restricted maximum likelihood procedures using the MTDFREML program. Results: The percentages of variations were moderate for body weights and high for daily gains. Genetic groups had a highly significant (P<0.01) effect on the body weights traits. Damascus goats had higher (P<0.01) birth and weaning weights, but ?D?A group kids had a higher (P<0.01) body weight at 6 months. The genetic groups had a significant effects on the daily weight gains for D1 (P<0.01) and D3 (P<0.05) periods, whereas, it had no effects on D2 period. The fixed effects of sex, season, year and type of birth were significant differences for body weights. Male kids were heavier (P<0.01) than females for different growth stages. Body weights and daily gains during winter/autumn were significantly higher (P<0.01) than summer/spring. Kids born and raised as singles were significantly (P<0.01) heavier than those were born as twins or triplets. The genetic and phenotypic correlations between birth and weaning weights were positive for both Damascus and Ar展开更多
基金supported by the National Natural Science Foundation of China(82030083 to H.J.,81871875 to L.H.)the National Basic Research Program of China(2017YFA0505501 to H.J.+8 种基金2020YFA0803300 to H.J.)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19020201 to H.J.)the National Natural Science Foundation of China(81872312 to H.J.,82011540007 to H.J.,31621003 to H.J.,81402371 to Y.J.,81802279 to H.H.,81902326 to X.W.,81602443 to X.L.)the Basic Frontier Scientific Research Program of Chinese Academy of Science(ZDBSLY-SM006 to H.J.)the International Cooperation Project of Chinese Academy of Sciences(153D31KYSB20190035 to H.J.)the Youth Innovation Promotion Association CAS(Y919S31371 to X.W.)the Natural Science Foundation of Hunan Province,China(2019JJ50550 to X.L.)Clinical Medical Technology Innovation Guide Project of Hunan(2020SK51827 to X.L.)Project of Scientific Research Plan of Hunan Provincial Health Commission(202103100127 to X.L.)。
文摘Small cell lung cancer(SCLC)is a phenotypically heterogeneous disease with an extremely poor prognosis,which is mainly attributed to the rapid development of resistance to chemotherapy.However,the relation between the growth phenotypes and chemo-resistance of SCLC remains largely unclear.Through comprehensive bioinformatic analyses,we found that the heterogeneity of SCLC phenotype was significantly associated with different sensitivity to chemotherapy.Adherent or semiadherent SCLC cells were enriched with activation of the PI3K/Akt/mTOR pathway and were highly chemoresistant.Mechanistically,activation of the PI3K/Akt/mTOR pathway promotes the phenotypic transition from suspension to adhesion growth pattern and confers SCLC cells with chemo-resistance.Such chemo-resistance could be largely overcome by combining chemotherapy with PI3K/Akt/mTOR pathway inhibitors.Our findings support that the PI3K/Akt/mTOR pathway plays an important role in SCLC phenotype transition and chemo-resistance,which holds important clinical implications for improving SCLC treatment.
基金Project supported by the Science and Technology Project of Higher Education of Shandong Province(No.J12LK07),China
文摘Objective： Hepatocellular carcinoma （HCC） is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of micreRNA-718 （miR-718） in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods： Here we first used a methylthiazolyldiphenyl- tetrazolium bromide （MTT） assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein （GFP） reporter assay, Western blot, and quantitative real-time polymerase chain reaction （qRT-PCR） to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results： We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 （EGR3） is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the via- bility and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions： miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic 07） found that overexpreget for HCC.
文摘AIM:To compare the clinicopathological characteristics of human epidermal growth factor receptor 2 (HER2)-positive and HER2-negative Barrett's adenocarcinoma in Japan. METHODS:We performed immunohistochemical analysis of HER2 in 30 samples taken from patients with Barrett's adenocarcinoma and dual color in situ hybridization in cases showing 2+ reactions. We compared the clinicopathological characteristics of HER2-positive and HER2-negative patients.RESULTS:HER2 positivity was identified in 8 (27%) carcinoma samples. We found that HER2 expression was associated with p53 overexpression (100% vs 52.6% in pT1 tumor; 100% vs 54.5% in all stage tumor, P < 0.05) and protruding lesions at the early disease stage. There was no association between the mucin phenotype of the carcinomas and prognosis. HER2 expression and low clinical stage were unexpectedly different between Barrett's adenocarcinoma patients and gastric cancer patients, but the macroscopic features may be associated with earlier diagnosis in these patients. CONCLUSION:Our results suggest that HER2-positive Barrett's adenocarcinomas are associated with p53 overexpression and lesion protrusion at the early disease stage.
文摘The purpose of this work is to illustrate the relationship between genotype and phenotype in the complex cellular network of saccharomyces cerevisiae. As a structure-oriented method, using elementary flux mode(EFM) analysis can obtain its popularity in analysis of the robustness of the central metabolism, as well as network function of some organisms. However, this method has not been widely used for modeling gene deletion phenotype. By enumerating all the metabolic pathways, the EFM analysis presented herein can be used to identify the functional features and predict the growth phenotype of the S.cerevisiae. In comparison with the flux balance analysis(FBA), the performance of EFM analysis was superior to FBA in prediction of gene deletion phenotype. EFM analysis is demonstrated to be an effective tool for bridging the gap between metabolic network and growth phenotype.
文摘Objective: To study the genetic and non-genetic factors and their interactions affecting growth rate and body weights at birth, weaning and at 6 months of age in Saudi Ardi, Damascus goats and their crosses. Methods: Crossbreeding program between Saudi Ardi(A) goats with Damascus(D) was carried out to improve the meat productivity of Ardi goats through crossbreeding. The pedigree records of the body weights were obtained from 754 kids (397 males and 357 females) produced from 46 Sires and 279 Dams. Birth weight, weaning weigh and 6 months weight as well as average daily gain during different growth stages from birth to weaning (D1), weaning to 6 months (D2) and from birth to 6 months of age (D3) were recorded during winter/autumn and summer/spring. Data were classified according to breed, generation, sex, season, year, and type of birth. Data were analyzed using GLM procedure for the least-squares means of the fixed factors. Heritability and genetic parameters were estimated with derivative-free restricted maximum likelihood procedures using the MTDFREML program. Results: The percentages of variations were moderate for body weights and high for daily gains. Genetic groups had a highly significant (P<0.01) effect on the body weights traits. Damascus goats had higher (P<0.01) birth and weaning weights, but ?D?A group kids had a higher (P<0.01) body weight at 6 months. The genetic groups had a significant effects on the daily weight gains for D1 (P<0.01) and D3 (P<0.05) periods, whereas, it had no effects on D2 period. The fixed effects of sex, season, year and type of birth were significant differences for body weights. Male kids were heavier (P<0.01) than females for different growth stages. Body weights and daily gains during winter/autumn were significantly higher (P<0.01) than summer/spring. Kids born and raised as singles were significantly (P<0.01) heavier than those were born as twins or triplets. The genetic and phenotypic correlations between birth and weaning weights were positive for both Damascus and Ar
