The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal me...The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal metaplastic mucosa and exhibit structurally altered tumor suppressor genes, typified by p53, which is inactivated via the classic two-hit mechanism, i.e. loss of heterozygosity （LOH） and mutation of the remaining allele. LOH at certain chromosomal loci accumulates during tumor progression. Approximately 20% of differentiated carcinomas show evidence of mutator pathway tumorigenesis due to hMLH1 inactivation via hypermethylation of promoter CpG islands, and exhibit high-frequency microsatellite instability. In contrast, undifferentiated carcinomas rarely exhibit structurally altered tumor suppressor genes. For instance, while methylation of E-cadherin is often observed in undifferentiated carcinomas, mutation of this gene is generally associated with the progression from differentiated to undifferentiated carcinomas. Hypermethylation of tumor suppressor and tumor-related genes, including APC, CHFR, DAP- kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3, and TSLC1, can be detected in both differentiated and undifferentiated carcinomas at varying frequencies. However, the significance of the hypermethylation varies according to the analyzed genomic region, and hypermethylation of these genes can also be present in non-neoplastic gastric epithelia. Promoter demethylation of specific genes, such as MAGE and synudein y, can occur during the progressive stages of both histological types, and is associated with patient prognosis. Thus, while the molecular pathways of gastric carcinogenesis are dependent on histological background, specific genetic alterations can still be used for risk assessment, diagnosis, and prognosis.展开更多
AIM： TO study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS： Paraffin-embedded tissue samples of 25 patients （18 males and 7 females） with hepatoc...AIM： TO study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS： Paraffin-embedded tissue samples of 25 patients （18 males and 7 females） with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method （avidin-biotin-peroxidase） for detection of p53, cyclinD1, RB1, c-los and N-ras proteins. RESULTS： Six （24%）, 5 （20%）, 12 （48%） and 2 samples （8%） were positive for p53, cyclinDl, C-los and N-ras expression, respectively. Twenty-two （88%） samples had alterations in the （31 cell-cycle checkpoint protein expression （RBI or cyclinD1）. P53 positive samples showed a higher （9 times） risk of being positive for RBI protein than p53 negative samples. Loss of expression of RBI in association with p53 over-expression was observed in 4 （66.7%） of 6 samples. Loss of expression of RBI was seen in all cyclinD1 positive, 20 （90.9%） N-ras negative, and ii （50%） C-fos positive samples, respectively. CyclinD1 positive samples showed a higher （2.85 and 4.75 times） risk of being positive for c-los and N-ras expression than cyclinD1 negative samples. CONCLUSION： The expression of p53, RB1 and c-los genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma.展开更多
Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival...Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway.This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.展开更多
AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, silenced tumor suppressor gene promoter in human gastric cancer cell lines and to elucidate whether al...AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, silenced tumor suppressor gene promoter in human gastric cancer cell lines and to elucidate whether alteration of DNA methylation could affect histone modification. METHODS： We used chromatin immunoprecipitation （CHIP） assay to assess the status of histone acetylation and methylation in promoter regions of the p16 and rnutL homolog 1 （MLH1） genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation- specific PCR （MSP） to evaluate the effect of 5-Aza-2＇- deoxycytidine （5-Aza-dC）, trichostatin A （TSA） or their combination treatment on DNA methylation status. We used RT-PCR to determine whether alterations of histone modification status after 5-Aza-dC and TSA treatment are reflected in gene expression. RESULTS： For thep16 and MLH1 genes in two cell lines, silenced loci associated with DNA hypermethylation were characterized by histone H3-K9 hypoacetylation and hypermethylation and histone H3-K4 hypomethylation. Treatment with TSA resulted in moderately increased histone H3-K9 acetylation at the silenced loci with no effect on histone H3-K9 methylation and minimal effects on gene expression. In contrast, treatment with 5-Aza- dC rapidly reduced histone H3-K9 methylation at the silenced loci and resulted in reactivation of the two genes. Combined treatment with 5-Aza-dC and TSA was synergistic in reactivating gene expression at the loci showing DNA hypermethylation. Similarly, histone H3-K4 methylation was not affected alter TSA treatment, andincreased moderately at the silenced loci after 5-Aza-dC treatment. CONCLUSION： Hypermethylation of DNA in promoter CpG islands is related to transcriptional silencing of tumor suppressor genes. Histone H3-K9 methylation in different regions of the promoters studied correlates with DNA methylation status of each gene in gastric cancer cells. However, histone H3-K9 acetylation and H3-K4 methylation inversely correlate 展开更多
AIM： To examine how High-mobility group box I （HMGB1） regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin （GL）, a known HMGB1 inhibitor, prevents HMGBl-induced hepatocyte apoptosis.
文摘The development and progression of gastric cancer involves a number of genetic and epigenetic alterations of tumor suppressor and tumor-related genes. The majority of differentiated carcinomas arise from intestinal metaplastic mucosa and exhibit structurally altered tumor suppressor genes, typified by p53, which is inactivated via the classic two-hit mechanism, i.e. loss of heterozygosity （LOH） and mutation of the remaining allele. LOH at certain chromosomal loci accumulates during tumor progression. Approximately 20% of differentiated carcinomas show evidence of mutator pathway tumorigenesis due to hMLH1 inactivation via hypermethylation of promoter CpG islands, and exhibit high-frequency microsatellite instability. In contrast, undifferentiated carcinomas rarely exhibit structurally altered tumor suppressor genes. For instance, while methylation of E-cadherin is often observed in undifferentiated carcinomas, mutation of this gene is generally associated with the progression from differentiated to undifferentiated carcinomas. Hypermethylation of tumor suppressor and tumor-related genes, including APC, CHFR, DAP- kinase, DCC, E-cadherin, GSTP1, hMLH1, p16, PTEN, RASSF1A, RUNX3, and TSLC1, can be detected in both differentiated and undifferentiated carcinomas at varying frequencies. However, the significance of the hypermethylation varies according to the analyzed genomic region, and hypermethylation of these genes can also be present in non-neoplastic gastric epithelia. Promoter demethylation of specific genes, such as MAGE and synudein y, can occur during the progressive stages of both histological types, and is associated with patient prognosis. Thus, while the molecular pathways of gastric carcinogenesis are dependent on histological background, specific genetic alterations can still be used for risk assessment, diagnosis, and prognosis.
文摘AIM： TO study the effect of some genes especially those involved in cell cycle regulation on hepatocellular carcinoma. METHODS： Paraffin-embedded tissue samples of 25 patients （18 males and 7 females） with hepatocellular carcinoma were collected from 22 pathology centers in Tehran during 2000-2001, and stained using immunohistochemistry method （avidin-biotin-peroxidase） for detection of p53, cyclinD1, RB1, c-los and N-ras proteins. RESULTS： Six （24%）, 5 （20%）, 12 （48%） and 2 samples （8%） were positive for p53, cyclinDl, C-los and N-ras expression, respectively. Twenty-two （88%） samples had alterations in the （31 cell-cycle checkpoint protein expression （RBI or cyclinD1）. P53 positive samples showed a higher （9 times） risk of being positive for RBI protein than p53 negative samples. Loss of expression of RBI in association with p53 over-expression was observed in 4 （66.7%） of 6 samples. Loss of expression of RBI was seen in all cyclinD1 positive, 20 （90.9%） N-ras negative, and ii （50%） C-fos positive samples, respectively. CyclinD1 positive samples showed a higher （2.85 and 4.75 times） risk of being positive for c-los and N-ras expression than cyclinD1 negative samples. CONCLUSION： The expression of p53, RB1 and c-los genes appears to have a key role in the pathogenesis of hepatocellular carcinoma in Iran. Simultaneous overexpression of these genes is significantly associated with their loss of expression during development of hepatocellular carcinoma.
文摘Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway.This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.
基金National Natural Science Foundation of China,No.30271477,No.30572162
文摘AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, silenced tumor suppressor gene promoter in human gastric cancer cell lines and to elucidate whether alteration of DNA methylation could affect histone modification. METHODS： We used chromatin immunoprecipitation （CHIP） assay to assess the status of histone acetylation and methylation in promoter regions of the p16 and rnutL homolog 1 （MLH1） genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation- specific PCR （MSP） to evaluate the effect of 5-Aza-2＇- deoxycytidine （5-Aza-dC）, trichostatin A （TSA） or their combination treatment on DNA methylation status. We used RT-PCR to determine whether alterations of histone modification status after 5-Aza-dC and TSA treatment are reflected in gene expression. RESULTS： For thep16 and MLH1 genes in two cell lines, silenced loci associated with DNA hypermethylation were characterized by histone H3-K9 hypoacetylation and hypermethylation and histone H3-K4 hypomethylation. Treatment with TSA resulted in moderately increased histone H3-K9 acetylation at the silenced loci with no effect on histone H3-K9 methylation and minimal effects on gene expression. In contrast, treatment with 5-Aza- dC rapidly reduced histone H3-K9 methylation at the silenced loci and resulted in reactivation of the two genes. Combined treatment with 5-Aza-dC and TSA was synergistic in reactivating gene expression at the loci showing DNA hypermethylation. Similarly, histone H3-K4 methylation was not affected alter TSA treatment, andincreased moderately at the silenced loci after 5-Aza-dC treatment. CONCLUSION： Hypermethylation of DNA in promoter CpG islands is related to transcriptional silencing of tumor suppressor genes. Histone H3-K9 methylation in different regions of the promoters studied correlates with DNA methylation status of each gene in gastric cancer cells. However, histone H3-K9 acetylation and H3-K4 methylation inversely correlate
基金Supported by Samsung Biomedical Research Institute grant,No.SBRI C-A8-219-1
文摘AIM： To examine how High-mobility group box I （HMGB1） regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin （GL）, a known HMGB1 inhibitor, prevents HMGBl-induced hepatocyte apoptosis.
