BACKGROUND: Nerve growth factor (NGF) attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) promotes neuronal ...BACKGROUND: Nerve growth factor (NGF) attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) promotes neuronal apoptosis. However, effects of PTEN in NGF-mediated neuroprotection against glutamate excitotoxicity remain poorly understood. OBJECTIVE: To investigate the relationship between NGF inhibition of glutamate-induced injury and PTEN. DESIGN, TIME AND SETTING: The randomized, controlled, in vitro study was performed at the Department of Pathophysiology, Medical School of Nantong University, China from October 2007 to March 2008. MATERIALS: Glutamate, NGF, 4, 6-diamidino-2-phenyl-indolediacetate, 3-[4, 5-dimethylthiazol-2-yl]- 2, 5-diphenyl tetrazoliumbromide (MTT), and lactate dehydrogenase kit (Sigma, USA), fluorescence microscope and inverted phase contrast microscope (Olympus, Japan) were used in this study. METHODS: Hippocampal neurons were obtained from newborn (< 24 hours) Sprague Dawley rats and cultured for 7 days. The control group was not treated with any intervention factor, the glutamate group was treated with glutamate (0.2 mmol/L), and NGF groups were treated with NGF (10, 50, 100, and 200 μg/L, respectively) prior to glutamate treatment. MAIN OUTCOME MEASURES: The MTT and lactate dehydrogenase assays were applied to evaluate viability of hippocampal neurons. Morphological changes in hippocampal neurons were observed using an inverted phase-contrast microscope, and neuronal apoptosis was detected by 4, 6-diamidino-2-phenyl-indolediacetate staining. PTEN mRNA and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. RESULTS: Glutamate (0.2 mmol/L) induced significantly decreased neuronal viability and greater lactate dehydrogenase efflux compared with the control group (P < 0.01). However, compared with the glutamate group, cell viability significantly increased and lactate dehydrogenase efflux decreased in the NGF group with increasing NGF concentrations (P < 0.05 or P < 0.01). The apoptotic ratio and PTEN mRNA and protein expression decreased in the NGF group compared with the glutamate group (P < 0.01). CONCLUSION: Pretreatment with NGF exerted neuroprotective effects against glutamate-induced injury, partially through inhibition of PTEN expression and neuronal apoptosis.展开更多
To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein express...To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.展开更多
AIM: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD). METHODS: ...AIM: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD). METHODS: Forty eight male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 48 athymic mice were distributed randomly into 4 groups: A, B, C, D, each group had 12 athymic mice. Group A were were treated by intragastric administration with FT207 (Tegafur) for 4 wk. Group B, C and D were treated by intragastric administration with FJD (complex prescription of Chinese crude drug) that had been delegated into 3 kinds of density as the low, middle, and high for 4 wk. At last, athymic mice were put to death, live time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry.RESULTS: Four weeks later, the total survival rate in treatment group (A + B + C) was 50% and higher than the control group (0%) treated by FT207, (P < 0.01). The survival rate in group A, B, C was higher than in group D, and except group A with D, there was significant differentces (Fisher's Exact Test P = 0.05 or 0.01). And no differences were observed between the treatment groups and the control group in volume of tumors and exponent of tumors (P > 0.05). Tumor metastasis in livers of the treatment group was less than the controls (Fisher's Exact Test, P = 0.021). The result of immunohistochemistry showed that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue (Kruskal-Wallis test, χ2 = 60.67, P = 0.000). It also showed that the intensity of PTEN in treatment groups (A, B, C) was higher than the control group (D) (F = 5.90, P = 0.002 in hepatic tissue and F = 15.99, P = 0.000 in latero-cancer tissue and χ2 = 26.08, P = 0.000 in cancer tissue), and group B is the highest in the treatment groups (P < 0.05, r = 0.01. respectively). However, there was no significant statistic difference between group A and group C (P > 0.05).CONCLUSION: FJD can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Mechanisms of FJD healing HCC may partially be explained by enhancing the expression of PTEN in liver.展开更多
Recent studies have shown that phosphatase and tensin homolog-deleted on chromosome ten(PTEN) gene plays an important role in ischemic brain damage and synaptic plasticity.The AdEasy system,which has been widely used,...Recent studies have shown that phosphatase and tensin homolog-deleted on chromosome ten(PTEN) gene plays an important role in ischemic brain damage and synaptic plasticity.The AdEasy system,which has been widely used,greatly simplifies preparation of recombinant adenovirus.Therefore,recombinant defective adenovirus vector carrying human PTEN tumor suppressor gene(Ad-PTEN) was constructed using the AdEasy-1 system and was transfected into HEK293 cells for packaging and amplification.Infection efficiency and expression intensity were observed in primary cultured rat hippocampal neurons infected with Ad-PTEN in vitro.Results revealed a cytopathic effect in green fluorescent protein expression,which increased with prolonged time.After three cycles of amplification,the adenovirus titer was increased to an adequate titer for infecting hippocampal neurons.The entire process typically requires 4-5 weeks for completion.Results suggested that recombinant defective adenovirus vector carrying the PTEN gene was successfully and rapidly constructed using the AdEasy system.展开更多
Phosphatase and tensin homolog deleted on chromosome 10(PTEN) and the proliferating antigen Ki67 have been widely studied in several tumors.However,their role as indicator in non-small cell lung cancer(NSCLC)remains u...Phosphatase and tensin homolog deleted on chromosome 10(PTEN) and the proliferating antigen Ki67 have been widely studied in several tumors.However,their role as indicator in non-small cell lung cancer(NSCLC)remains unknown.Here,we investigated the expression of PTEN and Ki67 in NSCLC tissues and paired normal lung tissues to identify whether these proteins are associated with lung cancer development and survival.Immunohistochemistry for PTEN and Ki67 was performed on 67 lung cancer tissues and 41 paired adjacent normal lung tissues to detect the expression of these two proteins.The expression of PTEN in NSCLC tissues(32.8%) was significantly lower than that in normal tissues(82.9%,P < 0.05).In contrast,the expression of Ki67 in NSCLC tissues(76.1%) was significantly higher than that in normal tissues(27.3%,P < 0.05).Expression of both PTEN and Ki67 were strongly associated with tumor histology,clinical stage,lymph node metastasis,differentiation and4-year postoperative survival rate(P < 0.05).However,PTEN expression was negatively correlated with Ki67 expression(r =-0.279,P < 0.05).In conclusion,low PTEN expression and Ki67 overexpression are associated with malignant invasion and lymph node metastasis of NSCLC.These proteins may serve as diagnostic and prognostic biomarkers of NSCLC.展开更多
This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury.Experimental and clinical studies indicate that gastric mucosa of aging individuals-"agin...This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury.Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa.Some of these abnormalities include a partial atrophy of gastric glands,impaired mucosal defense(reduced bicarbonate and prostaglandin generation,decreased sensory innervation),increased susceptibility to injury by a variety of damaging agents such as ethanol,aspirin and other non-steroidal anti-inflammatory drugs(NSAIDs),impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs.Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa:reduced mucosal blood flow and impaired oxygen delivery cause hypoxia,which leads to activation of the early growth response-1(egr-1)transcription factor.Activation of egr-1,in turn,upregulates the dual specificity phosphatase,phosphatase and tensin homologue deleted on chromosome ten(PTEN)resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein,survivin.The imbalance between pro-and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury.This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals.Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity,increase in replicative cellular senescence,and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus.Aging gastropathy is an important and clinically relevant issue because of:(1)an aging world population due to prolonged life span;(2)older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications(e.g.,NSAIDs-induced gastric injury)than younger patients;and(3)increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically.展开更多
Recently,phosphatase and tensin homolog deleted on chromosome 10(PTEN) is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of...Recently,phosphatase and tensin homolog deleted on chromosome 10(PTEN) is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells(HKC) were treated with transforming growth factor-beta 1(TGF-β1),or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase(PI3K) inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition(EMT) and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of DJ-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.展开更多
To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carci...To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expres-sions and the tumor’s invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor’s clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinoma-tous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarci-nomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively re-lated to the progression of the pathological differentiation and invasion of tumor, whereas the expres-sions of VEGF and MVD were positively related. Moreover, there was a negative relationship be-tween the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression proba-bly induces abnormal hyperexpression of VEGF may play an important role in the invasion and me-tastasis of HCC.展开更多
AIM:To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten(PTEN)hamartoma tumor syndrome(PHTS)and to perform a systematic literature review regarding...AIM:To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten(PTEN)hamartoma tumor syndrome(PHTS)and to perform a systematic literature review regarding the same.METHODS:This study was approved by the appropriate institutional review board prior to initiation.A clinical genetics database was searched for patients with PHTS or a component syndrome that received gastrointestinal endoscopy or pathology interpretation at our center.These patient’s records were retrospectively reviewed for clinical characteristics(including family history and genetic testing),endoscopy results and pathology findings.We also performed a systematic review of the literature for case series of PHTS or component syndromes that reported gastrointestinal manifestations and investigations published after consensus diagnostic criteria were established in 1996.These results were compiled and reported.RESULTS:Eight patients from our institution met initial inclusion criteria.Of these,5 patients underwent4.2 colonoscopies at mean age 45.8±10.8 years.All were found to have colon polyps during their clinical course and polyp histology included adenoma,hyperplastic,ganglioneuroma and juvenile.No malignant lesions were identified.Two had multiple histologic types.One patient underwent colectomy due to innumerable polyps and concern for future malignant potential.Systematic literature review of PHTS patients undergoing endoscopy revealed 107 patients receiving colonoscopy at mean age 37.4 years.Colon polyps were noted in92.5%and multiple colon polyp histologies were reported in 53.6%.Common polyp histologies included hyperplastic(43.6%),adenoma(40.4%),hamartoma(38.3%),ganglioneuroma(33%)and inflammatory(24.5%)polyps.Twelve(11.2%)patients had colorectal cancer at mean age 46.7 years(range 35-62).Clinical outcomes secondary to colon polyposis and malignancy were not commonly reported.CONCLUSION:PHTS has a high prevalence of colon polyposis with multiple histologic types.It should be considered a mixed polyposis syndrome.Systematic review found an increased prevalence of colorectal cancer and we recommend initiating colonoscopy for colorectal cancer surveillance at age 35 years.展开更多
目的探讨Y染色体性别决定区相关高迁移率组盒蛋白6(SOX6)、第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)在急性心肌梗死(AMI)患者血清中的表达及临床意义。方法选取2021年1月至2022年3月淄博市第一医院和淄博市中心医院收治的AMI...目的探讨Y染色体性别决定区相关高迁移率组盒蛋白6(SOX6)、第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)在急性心肌梗死(AMI)患者血清中的表达及临床意义。方法选取2021年1月至2022年3月淄博市第一医院和淄博市中心医院收治的AMI患者100例为研究组,根据主要不良心血管事件(MACE)发生情况将患者分为MACE组52例和非MACE组48例,选取同期于淄博市第一医院和淄博市中心医院进行健康体检的志愿者110例为对照组。检测血清PTEN和SOX6水平,用Pearson相关性分析AMI患者血清PTEN和SOX6与临床指标的相关性,用ROC曲线分析PTEN和SOX6水平对AMI及预后的诊断价值。结果与对照组比较,研究组血清SOX6 mRNA水平显著降低(0.69±0.14 vs 1.03±0.16,P<0.01),血清PTEN mRNA水平显著升高(1.56±0.15 vs 1.05±0.08,P<0.01)。与非MACE组比较,MACE组血清SOX6 mRNA水平显著降低(0.61±0.15 vs 0.78±0.13,P<0.01),血清PTEN mRNA水平显著升高(1.74±0.18 vs 1.37±0.12,P<0.01)。Pearson相关性分析显示,AMI患者血清PTEN水平与cTnI、CK-MB、Gensini评分呈正相关,血清SOX6水平与cTnI、CK-MB、Gensini评分呈负相关(P<0.01)。ROC曲线分析显示,血清SOX6和PTEN联合诊断AMI的曲线下面积为0.932(95%CI:0.889~0.962),二者联合预测AMI患者发生MACE的曲线下面积为0.933(95%CI:0.866~0.974)。结论AMI患者血清中SOX6水平下调,PTEN水平上调,二者联合检测有助于诊断AMI及预测MACE。展开更多
基金the Natural Science Foundation of Jiangsu Province, No. BK2004048the Social Development and Technology Plan of Nantong City, No. K2008009
文摘BACKGROUND: Nerve growth factor (NGF) attenuates glutamate-induced injury to hippocampal neurons, and the human tumor suppressor gene phosphatase and tensin homologue deleted on chromosome 10 (PTEN) promotes neuronal apoptosis. However, effects of PTEN in NGF-mediated neuroprotection against glutamate excitotoxicity remain poorly understood. OBJECTIVE: To investigate the relationship between NGF inhibition of glutamate-induced injury and PTEN. DESIGN, TIME AND SETTING: The randomized, controlled, in vitro study was performed at the Department of Pathophysiology, Medical School of Nantong University, China from October 2007 to March 2008. MATERIALS: Glutamate, NGF, 4, 6-diamidino-2-phenyl-indolediacetate, 3-[4, 5-dimethylthiazol-2-yl]- 2, 5-diphenyl tetrazoliumbromide (MTT), and lactate dehydrogenase kit (Sigma, USA), fluorescence microscope and inverted phase contrast microscope (Olympus, Japan) were used in this study. METHODS: Hippocampal neurons were obtained from newborn (< 24 hours) Sprague Dawley rats and cultured for 7 days. The control group was not treated with any intervention factor, the glutamate group was treated with glutamate (0.2 mmol/L), and NGF groups were treated with NGF (10, 50, 100, and 200 μg/L, respectively) prior to glutamate treatment. MAIN OUTCOME MEASURES: The MTT and lactate dehydrogenase assays were applied to evaluate viability of hippocampal neurons. Morphological changes in hippocampal neurons were observed using an inverted phase-contrast microscope, and neuronal apoptosis was detected by 4, 6-diamidino-2-phenyl-indolediacetate staining. PTEN mRNA and protein expression were measured by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. RESULTS: Glutamate (0.2 mmol/L) induced significantly decreased neuronal viability and greater lactate dehydrogenase efflux compared with the control group (P < 0.01). However, compared with the glutamate group, cell viability significantly increased and lactate dehydrogenase efflux decreased in the NGF group with increasing NGF concentrations (P < 0.05 or P < 0.01). The apoptotic ratio and PTEN mRNA and protein expression decreased in the NGF group compared with the glutamate group (P < 0.01). CONCLUSION: Pretreatment with NGF exerted neuroprotective effects against glutamate-induced injury, partially through inhibition of PTEN expression and neuronal apoptosis.
文摘To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.
基金Supported by the Technological Planning Program of Guangdong Province China, No. 2005B33001040 Programs of Bureau of Traditional Chinese Medicine of Guangdong Province, No. 1040056 and 301014
文摘AIM: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) in liver of athymic mice with hepatocellular carcinoma (HCC) and the effect of Fuzheng Jiedu Decoction (FJD). METHODS: Forty eight male BALB/c athymic mice models were built by Bel-7402 with an indirect method. After 24 h of postoperation, the 48 athymic mice were distributed randomly into 4 groups: A, B, C, D, each group had 12 athymic mice. Group A were were treated by intragastric administration with FT207 (Tegafur) for 4 wk. Group B, C and D were treated by intragastric administration with FJD (complex prescription of Chinese crude drug) that had been delegated into 3 kinds of density as the low, middle, and high for 4 wk. At last, athymic mice were put to death, live time, volume of tumors, exponent of tumors and the tumor metastasis in livers were observed; and PTEN was detected in hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry.RESULTS: Four weeks later, the total survival rate in treatment group (A + B + C) was 50% and higher than the control group (0%) treated by FT207, (P < 0.01). The survival rate in group A, B, C was higher than in group D, and except group A with D, there was significant differentces (Fisher's Exact Test P = 0.05 or 0.01). And no differences were observed between the treatment groups and the control group in volume of tumors and exponent of tumors (P > 0.05). Tumor metastasis in livers of the treatment group was less than the controls (Fisher's Exact Test, P = 0.021). The result of immunohistochemistry showed that the intensity of PTEN in latero-cancer tissue was the highest, and then the hepatic tissue, the lowest was cancer tissue (Kruskal-Wallis test, χ2 = 60.67, P = 0.000). It also showed that the intensity of PTEN in treatment groups (A, B, C) was higher than the control group (D) (F = 5.90, P = 0.002 in hepatic tissue and F = 15.99, P = 0.000 in latero-cancer tissue and χ2 = 26.08, P = 0.000 in cancer tissue), and group B is the highest in the treatment groups (P < 0.05, r = 0.01. respectively). However, there was no significant statistic difference between group A and group C (P > 0.05).CONCLUSION: FJD can prolong the survival time and decrease tumor metastasis in livers of these experimental mice. Mechanisms of FJD healing HCC may partially be explained by enhancing the expression of PTEN in liver.
文摘Recent studies have shown that phosphatase and tensin homolog-deleted on chromosome ten(PTEN) gene plays an important role in ischemic brain damage and synaptic plasticity.The AdEasy system,which has been widely used,greatly simplifies preparation of recombinant adenovirus.Therefore,recombinant defective adenovirus vector carrying human PTEN tumor suppressor gene(Ad-PTEN) was constructed using the AdEasy-1 system and was transfected into HEK293 cells for packaging and amplification.Infection efficiency and expression intensity were observed in primary cultured rat hippocampal neurons infected with Ad-PTEN in vitro.Results revealed a cytopathic effect in green fluorescent protein expression,which increased with prolonged time.After three cycles of amplification,the adenovirus titer was increased to an adequate titer for infecting hippocampal neurons.The entire process typically requires 4-5 weeks for completion.Results suggested that recombinant defective adenovirus vector carrying the PTEN gene was successfully and rapidly constructed using the AdEasy system.
基金supported by Nanjing Medical University Focus Development and Natural Science Foundation of China
文摘Phosphatase and tensin homolog deleted on chromosome 10(PTEN) and the proliferating antigen Ki67 have been widely studied in several tumors.However,their role as indicator in non-small cell lung cancer(NSCLC)remains unknown.Here,we investigated the expression of PTEN and Ki67 in NSCLC tissues and paired normal lung tissues to identify whether these proteins are associated with lung cancer development and survival.Immunohistochemistry for PTEN and Ki67 was performed on 67 lung cancer tissues and 41 paired adjacent normal lung tissues to detect the expression of these two proteins.The expression of PTEN in NSCLC tissues(32.8%) was significantly lower than that in normal tissues(82.9%,P < 0.05).In contrast,the expression of Ki67 in NSCLC tissues(76.1%) was significantly higher than that in normal tissues(27.3%,P < 0.05).Expression of both PTEN and Ki67 were strongly associated with tumor histology,clinical stage,lymph node metastasis,differentiation and4-year postoperative survival rate(P < 0.05).However,PTEN expression was negatively correlated with Ki67 expression(r =-0.279,P < 0.05).In conclusion,low PTEN expression and Ki67 overexpression are associated with malignant invasion and lymph node metastasis of NSCLC.These proteins may serve as diagnostic and prognostic biomarkers of NSCLC.
基金Supported by VA Merit Review grant to Tarnawski AS
文摘This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury.Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa.Some of these abnormalities include a partial atrophy of gastric glands,impaired mucosal defense(reduced bicarbonate and prostaglandin generation,decreased sensory innervation),increased susceptibility to injury by a variety of damaging agents such as ethanol,aspirin and other non-steroidal anti-inflammatory drugs(NSAIDs),impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs.Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa:reduced mucosal blood flow and impaired oxygen delivery cause hypoxia,which leads to activation of the early growth response-1(egr-1)transcription factor.Activation of egr-1,in turn,upregulates the dual specificity phosphatase,phosphatase and tensin homologue deleted on chromosome ten(PTEN)resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein,survivin.The imbalance between pro-and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury.This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals.Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity,increase in replicative cellular senescence,and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus.Aging gastropathy is an important and clinically relevant issue because of:(1)an aging world population due to prolonged life span;(2)older patients have much greater risk of gastroduodenal ulcers and gastrointestinal complications(e.g.,NSAIDs-induced gastric injury)than younger patients;and(3)increased susceptibility of aging gastric mucosa to injury can be potentially reduced or reversed pharmacologically.
基金supported by a grant from National Natural Sciences Foundation of China (No. 30800525)
文摘Recently,phosphatase and tensin homolog deleted on chromosome 10(PTEN) is suggested as a new agent in the fighting against fibrogenesis.In tumor,DJ-1 is identified as a negative regulator of PTEN.But the expression of DJ-1 and the regulation of PTEN in fibrosis are unclear.Renal fibrosis was induced in 5/6 subtotal nephrectomy rat model.Human proximal tubular epithelial cells(HKC) were treated with transforming growth factor-beta 1(TGF-β1),or transfected with DJ-1 or PTEN.Confocal microscope was used to investigate the localization of DJ-1 and PTEN.The selective phosphoinositide-3 kinase(PI3K) inhibitor,LY294002,was administered to inhibit PI3K pathway.The DJ-1 and PTEN expression,markers of epithelial-mesenchymal transition(EMT) and Akt phosphorylation were measured by RT-PCR,Western blotting or immunocytochemistry.In vitro,after HKC cells were stimulated with 10 ng/mL TGF-β1 for 72 h,the expression of DJ-1 was increased,and that of PTEN was decreased.In vivo,the same results were identified in 5/6-nephrectomized rats.In normal HKC cells,most of DJ-1 protein localized in cytoplasm,and little in nucleus.TGF-β1 upregulated DJ-1 expression in both cytoplasma and nuclei.In contrary,TGF-β1 emptied cytoplasmic PTEN protein into nucleus.Overexpression of DJ-1 decreased the expression of PTEN,promoted the activation of Akt and the expression of vimentin,and also led to the loss of cytoplasmic PTEN.Contrarily,overexpression of PTEN protected HKC cells from TGF-β1-induced EMT.In conclusion,DJ-1 is upregulated in renal fibrosis and DJ-1 mediates EMT by suppressing cytoplasmic PTEN expression and Akt activation.
文摘To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expres-sions and the tumor’s invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor’s clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinoma-tous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarci-nomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively re-lated to the progression of the pathological differentiation and invasion of tumor, whereas the expres-sions of VEGF and MVD were positively related. Moreover, there was a negative relationship be-tween the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression proba-bly induces abnormal hyperexpression of VEGF may play an important role in the invasion and me-tastasis of HCC.
文摘AIM:To investigate our clinical experience with the colonic manifestations of phosphatase and tensin homolog on chromosome ten(PTEN)hamartoma tumor syndrome(PHTS)and to perform a systematic literature review regarding the same.METHODS:This study was approved by the appropriate institutional review board prior to initiation.A clinical genetics database was searched for patients with PHTS or a component syndrome that received gastrointestinal endoscopy or pathology interpretation at our center.These patient’s records were retrospectively reviewed for clinical characteristics(including family history and genetic testing),endoscopy results and pathology findings.We also performed a systematic review of the literature for case series of PHTS or component syndromes that reported gastrointestinal manifestations and investigations published after consensus diagnostic criteria were established in 1996.These results were compiled and reported.RESULTS:Eight patients from our institution met initial inclusion criteria.Of these,5 patients underwent4.2 colonoscopies at mean age 45.8±10.8 years.All were found to have colon polyps during their clinical course and polyp histology included adenoma,hyperplastic,ganglioneuroma and juvenile.No malignant lesions were identified.Two had multiple histologic types.One patient underwent colectomy due to innumerable polyps and concern for future malignant potential.Systematic literature review of PHTS patients undergoing endoscopy revealed 107 patients receiving colonoscopy at mean age 37.4 years.Colon polyps were noted in92.5%and multiple colon polyp histologies were reported in 53.6%.Common polyp histologies included hyperplastic(43.6%),adenoma(40.4%),hamartoma(38.3%),ganglioneuroma(33%)and inflammatory(24.5%)polyps.Twelve(11.2%)patients had colorectal cancer at mean age 46.7 years(range 35-62).Clinical outcomes secondary to colon polyposis and malignancy were not commonly reported.CONCLUSION:PHTS has a high prevalence of colon polyposis with multiple histologic types.It should be considered a mixed polyposis syndrome.Systematic review found an increased prevalence of colorectal cancer and we recommend initiating colonoscopy for colorectal cancer surveillance at age 35 years.
文摘目的探讨Y染色体性别决定区相关高迁移率组盒蛋白6(SOX6)、第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN)在急性心肌梗死(AMI)患者血清中的表达及临床意义。方法选取2021年1月至2022年3月淄博市第一医院和淄博市中心医院收治的AMI患者100例为研究组,根据主要不良心血管事件(MACE)发生情况将患者分为MACE组52例和非MACE组48例,选取同期于淄博市第一医院和淄博市中心医院进行健康体检的志愿者110例为对照组。检测血清PTEN和SOX6水平,用Pearson相关性分析AMI患者血清PTEN和SOX6与临床指标的相关性,用ROC曲线分析PTEN和SOX6水平对AMI及预后的诊断价值。结果与对照组比较,研究组血清SOX6 mRNA水平显著降低(0.69±0.14 vs 1.03±0.16,P<0.01),血清PTEN mRNA水平显著升高(1.56±0.15 vs 1.05±0.08,P<0.01)。与非MACE组比较,MACE组血清SOX6 mRNA水平显著降低(0.61±0.15 vs 0.78±0.13,P<0.01),血清PTEN mRNA水平显著升高(1.74±0.18 vs 1.37±0.12,P<0.01)。Pearson相关性分析显示,AMI患者血清PTEN水平与cTnI、CK-MB、Gensini评分呈正相关,血清SOX6水平与cTnI、CK-MB、Gensini评分呈负相关(P<0.01)。ROC曲线分析显示,血清SOX6和PTEN联合诊断AMI的曲线下面积为0.932(95%CI:0.889~0.962),二者联合预测AMI患者发生MACE的曲线下面积为0.933(95%CI:0.866~0.974)。结论AMI患者血清中SOX6水平下调,PTEN水平上调,二者联合检测有助于诊断AMI及预测MACE。