AIM:To investigate the effects of nilotinib in a rat model of trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Twenty-one Wistar albino female rats obtained from Dokuz Eylul University Department of Laborat...AIM:To investigate the effects of nilotinib in a rat model of trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Twenty-one Wistar albino female rats obtained from Dokuz Eylul University Department of Laboratory Animal Science were categorized into a control(n=7),TNBS(n=7)and nilotinib group(n=7).Saline was administered orally for 14 d to the control and the TNBS group.The TNBS group received rectal TNBS on the first day while saline was administered to the control group.The nilotinib group received 20mg/kg nilotinib for 14 d in 2 divided doses,starting the same day as TNBS administration.For 14 d,the rats were fed a standard diet,and their weights were recorded daily.After sacrifice,colon tissue samples from each group were scored for macroscopic and microscopic pathology.Apoptotic indices were determined by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method.Platelet-derived growth factor receptor(PDGFR)alpha and beta levels were assessed through immunohistochemistry staining scores and compared among the groups.Tissue and serum tumor necrosis factor(TNF)alpha levels were determined by enzyme-linked immunosorbent assay.RESULTS:Between days 1 and 14,the nilotinib group rats lost significantly less weight than the TNBS group rats(-0.7 g vs-14.0 g,P=0.047).The difference in weight between the control and nilotinib groups was also statistically significant(+8.3 gvs-0.7 g,P=0.031).From day 7 to day 14,the weight differences of the control group vs the TNBS group,the TNBS group vs the nilotinib group,and the control group vs the nilotinib group were all statistically significant(+8.0 g vs-11.1 g,P=0.007;-11.1 g vs+2.9 g,P=0.015;+8.0g vs+2.9 g,P=0.042,respectively).Macroscopic and microscopic scores were significantly lower in the nilotinib group than in the TNBS group(0.00±0.00 vs 1.43±0.65,P=0.009;2.86±0.55 vs 7.71±1.48,P=0.030,respectively).However,these scores were similar between the nilotinib and control groups.While no significant difference for the nilotinib vs 展开更多
Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative staining.If the tumor is negative for KIT,but is positive for CD34,a histological diagno...Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative staining.If the tumor is negative for KIT,but is positive for CD34,a histological diagnosis is possible.However,if the tumor is negative for KIT,CD34,S-100,and SMA,a definitive diagnosis is often challenging.Recently,Discovered on GIST-1(DOG1)has received considerable attention as a useful molecule for the diagnosis of GIST.DOG1,a membrane channel protein,is known to be overexpressed in GIST.Because the sensitivity and specificity of DOG1 are higher than those of KIT,positive staining for DOG1has been reported,even in KIT-negative GISTs.KITnegative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically.We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia.Our findings suggest that immunohistochemical staining for DOG1,in addition to gene analysis,is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.展开更多
Mazur and Clark introduced the term ＂gastrointestinal stromal tumor＂ （GIST）. These tumors are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal. Activation ...Mazur and Clark introduced the term ＂gastrointestinal stromal tumor＂ （GIST）. These tumors are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal. Activation of c-kit or platelet-derived growth factor receptor alpha （PDGFRA） gene mutation has been shown to be a major force in GIST pathogenesis leading to down-stream phosphorylation of substrate proteins and subsequently activation of networks of signal transduction pathways that regulate cell proliferation,survival, apoptosis, motility and other important cell functions. Immunohistochemically, a great majority of GISTs show strong, diffuse c-kit expression. The diagnosis of GIST is currently based on morphologic features and immunohistochemical demonstration of c-kit （CD117）. However, in some cases c-kit immunoreactivity is weak or undetectable.展开更多
Gastrointestinal(GI)stromal tumor is the most common mesenchymal neoplasm of the GI tract but also occurs with a lower frequency in extragastrointestinal regions and is called extragastrointestinal stromal tumor(EGIST...Gastrointestinal(GI)stromal tumor is the most common mesenchymal neoplasm of the GI tract but also occurs with a lower frequency in extragastrointestinal regions and is called extragastrointestinal stromal tumor(EGIST).We report an unusual case of EGIST presenting as a vaginal mass.A 41-year-old woman presented with a gradually enlarging vaginal mass for the last2 years.Physical examination revealed an elliptical,non-tender mass about 7.5 cm×7 cm in size in the posterior vaginal wall and was resected completely.Under histological examination,the tumor showed a spindle cell type with coagulation necrosis,hemorrhage and high mitotic count.Immunohistochemical analysis revealed tumor cells were positive for DOG1,CD117,CD34 and p53 protein.Ki-67 labeling was 8%.Genetic analysis showed a deletion of exon 11 of the c-kit gene at codons 557-558.EGISTs should be kept in mind in the differential diagnosis in patients presenting with solid mass of the vaginal wall.展开更多
Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the ho...Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the homologous platelet-derived growth factor receptor alpha(PDGFRA) kinase.Most GISTs(90%-95%) are KIT-positive.About 5% of GISTs are truly negative for KIT expression.GISTs have been documented to resistant conventional chemotherapeutics.Due to the KIT activation that occurs in the majority of the cases,KIT inhibition is the primary treatment approach in the adjuvant treatment of metastatic GISTs.Imatinib mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase,and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase Ⅱ and Ⅲ trials.The presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic disease.Molecular analysis in phaseⅠ-Ⅱ trials revealed significant differences in objective response,progression-free survival,and overall survival between GISTs with different kinase mutations.The aim of this letter is to touch on the need for exon mutation analysis for adjuvant treatment with imatinib in GIST patients.展开更多
Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whet...Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.展开更多
Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen disease.In the current case,we report a 27-year-old woman with NF1,who presented wi...Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen disease.In the current case,we report a 27-year-old woman with NF1,who presented with a lower abdominal mass,symptomatic anaemia,and significant weight loss.We employed multiple approaches to assess the tumor behavior,including computed tomography(CT)scan,surgical tumor resection,histological and immunohistochemical analysis and gene sequencing.Additionally,the patient was given Imatinib mesylate(Gleevec)as adjuvant therapy.CT scan delineated a large thick wall cavity lesion connecting to the small bowel segment.Resection of the tumor yielded a mass of 17 cm×13 cm with achievement of safety margins.The diagnosis was GIST,confirmed by immunohistochemical expression of CD117,CD34,and Bcl-2.Sequencing revealed no mutations in either KIT or platelet-derived growth factor receptor-alpha,genes which are mutated in over 85%of sporadic GIST cases.Further,there was no evidence of recurrence,metastasis or metachronous GIST for over three years in our patient.From our analyses,we believe selective genotyping is advisable for high risk patients to predict potential tumor behavior.展开更多
基金Supported by Dokuz Eylul University Research Committee,grant number 42/2010
文摘AIM:To investigate the effects of nilotinib in a rat model of trinitrobenzene sulfonic acid(TNBS)-induced colitis.METHODS:Twenty-one Wistar albino female rats obtained from Dokuz Eylul University Department of Laboratory Animal Science were categorized into a control(n=7),TNBS(n=7)and nilotinib group(n=7).Saline was administered orally for 14 d to the control and the TNBS group.The TNBS group received rectal TNBS on the first day while saline was administered to the control group.The nilotinib group received 20mg/kg nilotinib for 14 d in 2 divided doses,starting the same day as TNBS administration.For 14 d,the rats were fed a standard diet,and their weights were recorded daily.After sacrifice,colon tissue samples from each group were scored for macroscopic and microscopic pathology.Apoptotic indices were determined by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method.Platelet-derived growth factor receptor(PDGFR)alpha and beta levels were assessed through immunohistochemistry staining scores and compared among the groups.Tissue and serum tumor necrosis factor(TNF)alpha levels were determined by enzyme-linked immunosorbent assay.RESULTS:Between days 1 and 14,the nilotinib group rats lost significantly less weight than the TNBS group rats(-0.7 g vs-14.0 g,P=0.047).The difference in weight between the control and nilotinib groups was also statistically significant(+8.3 gvs-0.7 g,P=0.031).From day 7 to day 14,the weight differences of the control group vs the TNBS group,the TNBS group vs the nilotinib group,and the control group vs the nilotinib group were all statistically significant(+8.0 g vs-11.1 g,P=0.007;-11.1 g vs+2.9 g,P=0.015;+8.0g vs+2.9 g,P=0.042,respectively).Macroscopic and microscopic scores were significantly lower in the nilotinib group than in the TNBS group(0.00±0.00 vs 1.43±0.65,P=0.009;2.86±0.55 vs 7.71±1.48,P=0.030,respectively).However,these scores were similar between the nilotinib and control groups.While no significant difference for the nilotinib vs
文摘Approximately 80%-95%of gastrointestinal stromal tumors(GISTs)show positive staining for KIT,while the other 5%-20%show negative staining.If the tumor is negative for KIT,but is positive for CD34,a histological diagnosis is possible.However,if the tumor is negative for KIT,CD34,S-100,and SMA,a definitive diagnosis is often challenging.Recently,Discovered on GIST-1(DOG1)has received considerable attention as a useful molecule for the diagnosis of GIST.DOG1,a membrane channel protein,is known to be overexpressed in GIST.Because the sensitivity and specificity of DOG1 are higher than those of KIT,positive staining for DOG1has been reported,even in KIT-negative GISTs.KITnegative GISTs most commonly arise in the stomach and are mainly characterized by epithelioid features histologically.We describe our experience with a rare case of a KIT-negative GIST of the stomach that was diagnosed by positive immunohistochemical staining for DOG1 in a patient who presented with severe anemia.Our findings suggest that immunohistochemical staining for DOG1,in addition to gene analysis,is useful for the diagnosis of KIT-negative tumors that are suspected to be GISTs.
文摘Mazur and Clark introduced the term ＂gastrointestinal stromal tumor＂ （GIST）. These tumors are thought to originate from mesenchymal stem cells that differentiate toward the interstitial cells of Cajal. Activation of c-kit or platelet-derived growth factor receptor alpha （PDGFRA） gene mutation has been shown to be a major force in GIST pathogenesis leading to down-stream phosphorylation of substrate proteins and subsequently activation of networks of signal transduction pathways that regulate cell proliferation,survival, apoptosis, motility and other important cell functions. Immunohistochemically, a great majority of GISTs show strong, diffuse c-kit expression. The diagnosis of GIST is currently based on morphologic features and immunohistochemical demonstration of c-kit （CD117）. However, in some cases c-kit immunoreactivity is weak or undetectable.
文摘Gastrointestinal(GI)stromal tumor is the most common mesenchymal neoplasm of the GI tract but also occurs with a lower frequency in extragastrointestinal regions and is called extragastrointestinal stromal tumor(EGIST).We report an unusual case of EGIST presenting as a vaginal mass.A 41-year-old woman presented with a gradually enlarging vaginal mass for the last2 years.Physical examination revealed an elliptical,non-tender mass about 7.5 cm×7 cm in size in the posterior vaginal wall and was resected completely.Under histological examination,the tumor showed a spindle cell type with coagulation necrosis,hemorrhage and high mitotic count.Immunohistochemical analysis revealed tumor cells were positive for DOG1,CD117,CD34 and p53 protein.Ki-67 labeling was 8%.Genetic analysis showed a deletion of exon 11 of the c-kit gene at codons 557-558.EGISTs should be kept in mind in the differential diagnosis in patients presenting with solid mass of the vaginal wall.
文摘Gastrointestinal stromal tumors(GISTs) are the most common soft tissue sarcoma of the gastrointestinal tract,resulting from an activating mutation of stem cell factor receptor(KIT),and an activating mutation of the homologous platelet-derived growth factor receptor alpha(PDGFRA) kinase.Most GISTs(90%-95%) are KIT-positive.About 5% of GISTs are truly negative for KIT expression.GISTs have been documented to resistant conventional chemotherapeutics.Due to the KIT activation that occurs in the majority of the cases,KIT inhibition is the primary treatment approach in the adjuvant treatment of metastatic GISTs.Imatinib mesylate is an oral agent that is a selective protein tyrosine kinase inhibitor of the KIT protein tyrosine kinase,and it has demonstrated clinical benefit and objective tumor responses in most GIST patients in phase Ⅱ and Ⅲ trials.The presence and the type of KIT or PDGFRA mutation are predictive of response to imatinib therapy in patients with advanced and metastatic disease.Molecular analysis in phaseⅠ-Ⅱ trials revealed significant differences in objective response,progression-free survival,and overall survival between GISTs with different kinase mutations.The aim of this letter is to touch on the need for exon mutation analysis for adjuvant treatment with imatinib in GIST patients.
基金supported by grants from the National Natural Science Foundation of China,No.31100769
文摘Platelet-derived growth factor receptor alpha （PDGFRct） is a marker of oligodendrocyte precursor cells in the central nervous system. NG2 is also considered a marker of oligodendrocyte precursor cells. However, whether there are differences in the distribution and morphol- ogy of oligodendrocyte precursor cells labeled by NG2 or PDGFRa in the developing neonatal rat brain remains unclear. In this study, by immunohistochemical staining, NG2 positive （NG2＋） cells were ubiquitous in the molecular layer, external pyramidal layer, internal pyramidal layer, and polymorphic layer of the cerebral cortex, and corpus callosum, external capsule, piriform cortex, and medial septal nucleus. NG2~ cells were stellate or fusiform in shape with long processes that were progressively decreased and shortened over the course of brain development. The distribution and morphology of PDGFRct positive （PDGFRa＋） cells were coincident with NG2＋ cells. The co- localization of NG2 and PDGFRu in the cell bodies and processes of some cells was confirmed by double immunofluorescence labeling. Moreover, cells double-labeled for NG2 and PDGFRa were predominantly in the early postnatal stage of development. The numbers of NG2＋/PDGFRa＋ cells and PDGFRa＋ cells decreased, but the number of NG2＋ cells increased from postnatal days 3 to 14 in the developing brain. In addition, amoeboid microglial cells of the corpus callosum, newborn brain macrophages in the normal developing brain, did not express NG2 or PDGFRu, but NG2 expression was detected in amoeboid microglia after hypoxia. The present results suggest that NG2 and PDGFRct are specific markers of oligodendrocyte precursor cells at different stages during early development. Additionally, the NG2 protein is involved in inflammatory and pathological processes of amoeboid microglial cells.
文摘Gastrointestinal stromal tumors(GISTs)represent a malignant gastrointestinal tumor of neurofibromatosis type 1(NF1)Von Recklinghausen disease.In the current case,we report a 27-year-old woman with NF1,who presented with a lower abdominal mass,symptomatic anaemia,and significant weight loss.We employed multiple approaches to assess the tumor behavior,including computed tomography(CT)scan,surgical tumor resection,histological and immunohistochemical analysis and gene sequencing.Additionally,the patient was given Imatinib mesylate(Gleevec)as adjuvant therapy.CT scan delineated a large thick wall cavity lesion connecting to the small bowel segment.Resection of the tumor yielded a mass of 17 cm×13 cm with achievement of safety margins.The diagnosis was GIST,confirmed by immunohistochemical expression of CD117,CD34,and Bcl-2.Sequencing revealed no mutations in either KIT or platelet-derived growth factor receptor-alpha,genes which are mutated in over 85%of sporadic GIST cases.Further,there was no evidence of recurrence,metastasis or metachronous GIST for over three years in our patient.From our analyses,we believe selective genotyping is advisable for high risk patients to predict potential tumor behavior.
