Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is...Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.展开更多
In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue rem...In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.展开更多
AIM: To investigate the role of artifi cial neural networks in predicting the presence of thyroid disease in atrophic body gastritis patients. METHODS: A dataset of 29 input variables of 253 atrophic body gastritis pa...AIM: To investigate the role of artifi cial neural networks in predicting the presence of thyroid disease in atrophic body gastritis patients. METHODS: A dataset of 29 input variables of 253 atrophic body gastritis patients was applied to artifi cial neural networks (ANNs) using a data optimisation procedure (standard ANNs,T&T-IS protocol,TWIST protocol). The target variable was the presence of thyroid disease. RESULTS: Standard ANNs obtained a mean accuracy of 64.4% with a sensitivity of 69% and a specifi city of 59.8% in recognizing atrophic body gastritis patients with thyroid disease. The optimization procedures (T&T-IS and TWIST protocol) improved the performance of the recognition task yielding a mean accuracy,sensitivity and specifi city of 74.7% and 75.8%,78.8% and 81.8%,and 70.5% and 69.9%,respectively. The increase of sensitivity of the TWIST protocol was statistically signifi cant compared to T&T-IS. CONCLUSION: This study suggests that artificial neural networks may be taken into consideration as a potential clinical decision-support tool for identifying ABG patients at risk for harbouring an unknown thyroid disease and thus requiring diagnostic work-up of their thyroid status.展开更多
NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with n...NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.展开更多
基金Supported by Grants (No. S0801035, to Naito Z) from the Ministry of Education, Culture, Sports, Science, and Technol-ogy (MEXT), JapanGrant-in-Aid for Young Scientists (A, No. 22689038 to Matsuda Y)
文摘Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.
基金Supported by Wellcome Trust Clinical Research Training Fellowship to MDB
文摘In addition to regulating acid secretion, the gastric antral hormone gastrin regulates several important cellular processes in the gastric epithelium including proliferation, apoptosis, migration, invasion, tissue remodelling and angiogenesis. Elevated serum concentrations of this hormone are caused by many conditions, particularly hypochlorhydria (as a result of autoimmune or Helicobacter pylori (H pylori)-induced chronic atrophic gastritis or acid suppressing drugs) and gastrin producing tumors (gastrinomas). There is now accumulating evidence that altered local and plasma concentrations of gastrin may play a role during the development of various gastric tumors. In the absence of H pylori infection, marked hypergastrinemia frequently results in the development of gastric enterochromaffi n cell-like neuroendocrine tumors and surgery to remove the cause of hypergastrinemia may lead to tumor resolution in this condition. In animal models such as transgenic INS-GAS mice, hypergastrinemia has also been shown to act as a cofactor with Helicobacter infection during gastric adenocarcinoma development. However, it is currently unclear as to what extent gastrin also modulates human gastric adenocarcinoma development. Therapeutic approaches targeting hypergastrinemia,such as immunization with G17DT, have been evaluated for the treatment of gastric adenocarcinoma, with some promising results. Although the mild hypergastrinemia associated with proton pump inhibitor drug use has been shown to cause ECL-cell hyperplasia and to increase H pylori-induced gastric atrophy, there is currently no convincing evidence that this class of agents contributes towards the development of gastric neuroendocrine tumors or gastric adenocarcinomas in human subjects.
基金funds from MIUR 2005 (Italian Ministry for University and Research) and University Sapienza Roma
文摘AIM: To investigate the role of artifi cial neural networks in predicting the presence of thyroid disease in atrophic body gastritis patients. METHODS: A dataset of 29 input variables of 253 atrophic body gastritis patients was applied to artifi cial neural networks (ANNs) using a data optimisation procedure (standard ANNs,T&T-IS protocol,TWIST protocol). The target variable was the presence of thyroid disease. RESULTS: Standard ANNs obtained a mean accuracy of 64.4% with a sensitivity of 69% and a specifi city of 59.8% in recognizing atrophic body gastritis patients with thyroid disease. The optimization procedures (T&T-IS and TWIST protocol) improved the performance of the recognition task yielding a mean accuracy,sensitivity and specifi city of 74.7% and 75.8%,78.8% and 81.8%,and 70.5% and 69.9%,respectively. The increase of sensitivity of the TWIST protocol was statistically signifi cant compared to T&T-IS. CONCLUSION: This study suggests that artificial neural networks may be taken into consideration as a potential clinical decision-support tool for identifying ABG patients at risk for harbouring an unknown thyroid disease and thus requiring diagnostic work-up of their thyroid status.
基金Supported by National Natural Science Foundation of China, No.81025015,30921006,91129301
文摘NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.
