Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority o...Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.展开更多
胃肠道Cajal间质细胞(interstitial cells of Cajal,ICCs)是一类分布于消化道各个部位的特殊间质细胞,它和肠神经系统、平滑肌之间的特殊位置关系构成了"肠神经-ICCs-平滑肌细胞"的网络结构,其中ICCs是该网络重要的协调者,与...胃肠道Cajal间质细胞(interstitial cells of Cajal,ICCs)是一类分布于消化道各个部位的特殊间质细胞,它和肠神经系统、平滑肌之间的特殊位置关系构成了"肠神经-ICCs-平滑肌细胞"的网络结构,其中ICCs是该网络重要的协调者,与肠道慢波的形成密切相关。胃肠道ICCs的特异性受体c-kit,与其配体干细胞因子(stem cell factors,SCF)结合后启动的信号途径,在ICCs的生长、发育及表型维持中起着重要作用。因此,从SCF/c-kit信号系统入手,有望拉开治疗ICCs相关性胃肠运动功能障碍性疾病的新序幕。展开更多
Alterations of normal function of interstitial cells of Cajal (ICC) are reported in many intestinal disorders. Diagnosis of their involvement is rare (infrequent), but necessary to propose a specifi c treatment. This ...Alterations of normal function of interstitial cells of Cajal (ICC) are reported in many intestinal disorders. Diagnosis of their involvement is rare (infrequent), but necessary to propose a specifi c treatment. This article reviews the place of ICC in the pathogenesis of achalasia, gastroesophageal reflux disease, infantile hypertrophic pyloric stenosis, chronic intestinal pseudoobstruction and slow transit constipation. Moreover we discuss the role of the Cajal cells in the development of stromal tumors of the gastrointestinal tract.展开更多
BACKGROUND Constipation is one of the chronic gastrointestinal functional diseases.It seriously affects the quality of life.Cistanche deserticola(C.deserticola)can treat constipation obviously,but its mechanism has no...BACKGROUND Constipation is one of the chronic gastrointestinal functional diseases.It seriously affects the quality of life.Cistanche deserticola(C.deserticola)can treat constipation obviously,but its mechanism has not been clarified.We supposed that mechanism of it improved the intestinal motility by stimulating interstitial Cajal cells(ICC).Activation of the C-kit receptor on the surface of ICC is closely related to ICC function,and the stem cell factor(SCF)/C-kit signaling pathways plays an important role on it.To investigate the mechanism of how C.deserticola treats constipation,this study aimed to establish a constipation model in rats and explore the role of SCF/C-kit signaling pathway in the treatment.AIM To explore the SCF/C-kit signaling pathways in the role of C.deserticola for treatment of constipation by a constipation rat model.METHODS Forty-eight 8-mo-old Sprague–Dawley rats were divided into 4 groups by random weight method:Normal group(n=12),model group(n=12),C.deserticola group(n=12)and blocker group(n=12).The normal group received normal saline by gavage;the model group received loperamide by gavage;the blocker group received loperamide and C.deserticola by gavage,and STI571 was injected by intraperitoneally.During treatment,the weight,fecal granules and fecal quality were recorded every 10 d.On day 20 after model induction,the colon tissues of each group were removed.Hematoxylin and eosin staining was used to observe pathological changes.Expression levels of SCF,C-kit and Aquaporin genes were detected by immunohistochemistry,western blotting,and real-time-quantitative polymerase chain reaction.The colonic epithelial mitochondria and goblet cells were observed by transmission electron microscopy.RESULTS Compared with the normal group,as treatment progressed,the weight of rats in the model and blocker groups decreased significantly,the stool weight decreased,and the stool quality was dry(P<0.05).C.deserticola reversed the decrease in body weight and stool weight and improved stool quality.Histo展开更多
AIM: To explore the mechanisms of uncut Roux-en-Y gastrojejunostomy, which is used to decrease the occurrence of Roux stasis syndrome.METHODS: The changes of myoelectric activity, mechanic motility and interstitial ce...AIM: To explore the mechanisms of uncut Roux-en-Y gastrojejunostomy, which is used to decrease the occurrence of Roux stasis syndrome.METHODS: The changes of myoelectric activity, mechanic motility and interstitial cells of Cajal (ICC) of the Roux limb after cut or uncut Roux-en-Y gastrojejunostomy were observed. RESULTS: When compared with the cut group, the amplitude (1.15 ± 0.15 mV vs 0.48 ± 0.06 mV, P < 0.05) and frequency (14.4 ± 1.9 cpm vs 9.5 ± 1.1 cpm, P < 0.01) of slow waves and the incidence (98.2% ± 10.4% vs 56.6% ± 6.4%, P < 0.05) and amplitude (0.58 ± 0.08 mV vs 0.23 ± 0.06 mV, P < 0.01) of spike potential of the Roux limb in the uncut group were significantly higher. The migrating myoelectric complexes (MMC) phase Ⅲ duration in the uncut group was significantly prolonged (6.5 ± 1.1 min vs 4.4 ± 0.8 min, P < 0.05), while the MMC cycle obviously shortened (42.5 ± 6.8 vs 55.3 ± 8.2 min, P < 0.05). Both gastric emptying rate (65.5% ± 7.9% vs 49.3% ± 6.8%, P < 0.01) and intestinal impelling ratio (53.4% ± 7.4% vs 32.2% ± 5.4%, P < 0.01) in the uncut group were significantly increased. The contractile force index of the isolated jejunal segment in the uncut group was significantly higher (36.8 ± 5.1 vs 15.3 ± 2.2, P < 0.01), and the expression of c-kit mRNA was significantly increased in the uncut group (0.82 ± 0.11 vs 0.35 ± 0.06, P < 0.01). CONCLUSION: Uncut Roux-en-Y gastrojejunostomymay lessen the effects of operation on myoelectric activity such as slow waves, spike potential, and MMC, decrease the impairment of gastrointestinal motility, and remarkably increase the expression of c-kit mRNA.展开更多
AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unres...AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased. No signs of cell death were observed in the pacemaker region. CONCLUSION: These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.展开更多
AIM: To identify the cholecystokinin (CCK)-A receptors (CCK-AR) on the guniea pig gallbladder interstitial cells of cajal (ICC) and to study CCK-8 induced gallbladder muscle strip contractions through the CCK-AR. METH...AIM: To identify the cholecystokinin (CCK)-A receptors (CCK-AR) on the guniea pig gallbladder interstitial cells of cajal (ICC) and to study CCK-8 induced gallbladder muscle strip contractions through the CCK-AR. METHODS: The existence of CCK-AR was examined by immunohistofluorescence on sectioned tissue and cultured cells. In vitro contractile response of guinea pig gallbladder muscle strips and the strips with ICC removed were also studied with CCK-8 receptors added. RESULTS: In tissue sections, intensely CCKAR- immunoreactive interstitial cells were found mainly in the muscular layers. In cultured cell sections, distinctive double staining of C-kit and CCK-AR ICCs were found. When we removed the ICC of the gallbladder, CCK-8 induced muscle strip contraction dose response curve significantly shifted to the right. CONCLUSION: We proved that both the existence of CCK-AR on the guinea pig gallbladder ICC and CCK evoked contraction are mediated through direct action on CCK-AR on the gallbladder ICC.展开更多
文摘Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mes-enchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularlytargeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors.
文摘Alterations of normal function of interstitial cells of Cajal (ICC) are reported in many intestinal disorders. Diagnosis of their involvement is rare (infrequent), but necessary to propose a specifi c treatment. This article reviews the place of ICC in the pathogenesis of achalasia, gastroesophageal reflux disease, infantile hypertrophic pyloric stenosis, chronic intestinal pseudoobstruction and slow transit constipation. Moreover we discuss the role of the Cajal cells in the development of stromal tumors of the gastrointestinal tract.
基金Natural Science Foundation of Chongqing,No.cstc2017jcyjAX0306。
文摘BACKGROUND Constipation is one of the chronic gastrointestinal functional diseases.It seriously affects the quality of life.Cistanche deserticola(C.deserticola)can treat constipation obviously,but its mechanism has not been clarified.We supposed that mechanism of it improved the intestinal motility by stimulating interstitial Cajal cells(ICC).Activation of the C-kit receptor on the surface of ICC is closely related to ICC function,and the stem cell factor(SCF)/C-kit signaling pathways plays an important role on it.To investigate the mechanism of how C.deserticola treats constipation,this study aimed to establish a constipation model in rats and explore the role of SCF/C-kit signaling pathway in the treatment.AIM To explore the SCF/C-kit signaling pathways in the role of C.deserticola for treatment of constipation by a constipation rat model.METHODS Forty-eight 8-mo-old Sprague–Dawley rats were divided into 4 groups by random weight method:Normal group(n=12),model group(n=12),C.deserticola group(n=12)and blocker group(n=12).The normal group received normal saline by gavage;the model group received loperamide by gavage;the blocker group received loperamide and C.deserticola by gavage,and STI571 was injected by intraperitoneally.During treatment,the weight,fecal granules and fecal quality were recorded every 10 d.On day 20 after model induction,the colon tissues of each group were removed.Hematoxylin and eosin staining was used to observe pathological changes.Expression levels of SCF,C-kit and Aquaporin genes were detected by immunohistochemistry,western blotting,and real-time-quantitative polymerase chain reaction.The colonic epithelial mitochondria and goblet cells were observed by transmission electron microscopy.RESULTS Compared with the normal group,as treatment progressed,the weight of rats in the model and blocker groups decreased significantly,the stool weight decreased,and the stool quality was dry(P<0.05).C.deserticola reversed the decrease in body weight and stool weight and improved stool quality.Histo
文摘AIM: To explore the mechanisms of uncut Roux-en-Y gastrojejunostomy, which is used to decrease the occurrence of Roux stasis syndrome.METHODS: The changes of myoelectric activity, mechanic motility and interstitial cells of Cajal (ICC) of the Roux limb after cut or uncut Roux-en-Y gastrojejunostomy were observed. RESULTS: When compared with the cut group, the amplitude (1.15 ± 0.15 mV vs 0.48 ± 0.06 mV, P < 0.05) and frequency (14.4 ± 1.9 cpm vs 9.5 ± 1.1 cpm, P < 0.01) of slow waves and the incidence (98.2% ± 10.4% vs 56.6% ± 6.4%, P < 0.05) and amplitude (0.58 ± 0.08 mV vs 0.23 ± 0.06 mV, P < 0.01) of spike potential of the Roux limb in the uncut group were significantly higher. The migrating myoelectric complexes (MMC) phase Ⅲ duration in the uncut group was significantly prolonged (6.5 ± 1.1 min vs 4.4 ± 0.8 min, P < 0.05), while the MMC cycle obviously shortened (42.5 ± 6.8 vs 55.3 ± 8.2 min, P < 0.05). Both gastric emptying rate (65.5% ± 7.9% vs 49.3% ± 6.8%, P < 0.01) and intestinal impelling ratio (53.4% ± 7.4% vs 32.2% ± 5.4%, P < 0.01) in the uncut group were significantly increased. The contractile force index of the isolated jejunal segment in the uncut group was significantly higher (36.8 ± 5.1 vs 15.3 ± 2.2, P < 0.01), and the expression of c-kit mRNA was significantly increased in the uncut group (0.82 ± 0.11 vs 0.35 ± 0.06, P < 0.01). CONCLUSION: Uncut Roux-en-Y gastrojejunostomymay lessen the effects of operation on myoelectric activity such as slow waves, spike potential, and MMC, decrease the impairment of gastrointestinal motility, and remarkably increase the expression of c-kit mRNA.
基金Supported by a grant from MIUR (Roma,Italy) to G Emanuelli and partly by a grant from Regione Piemonte to G Bellone
文摘AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC). METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry. RESULTS: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased. No signs of cell death were observed in the pacemaker region. CONCLUSION: These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.
基金The Natural Science Foundation of Hubei Province, No.2006AA412c
文摘AIM: To identify the cholecystokinin (CCK)-A receptors (CCK-AR) on the guniea pig gallbladder interstitial cells of cajal (ICC) and to study CCK-8 induced gallbladder muscle strip contractions through the CCK-AR. METHODS: The existence of CCK-AR was examined by immunohistofluorescence on sectioned tissue and cultured cells. In vitro contractile response of guinea pig gallbladder muscle strips and the strips with ICC removed were also studied with CCK-8 receptors added. RESULTS: In tissue sections, intensely CCKAR- immunoreactive interstitial cells were found mainly in the muscular layers. In cultured cell sections, distinctive double staining of C-kit and CCK-AR ICCs were found. When we removed the ICC of the gallbladder, CCK-8 induced muscle strip contraction dose response curve significantly shifted to the right. CONCLUSION: We proved that both the existence of CCK-AR on the guinea pig gallbladder ICC and CCK evoked contraction are mediated through direct action on CCK-AR on the gallbladder ICC.
