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Objective: To explore the sensitivity of Kit or PDGFRA mutants related to gastrointestinal stromal tumor (GIST) to Gleevec.Methods: The recombinant plasmids of KIT Del559-560, KIT Ins IPYD579, PDGFRA D842V and PDG-FRA L839P gene mutants were transiently transformed into the CHO cells by liposome methods.Western blot was used to detect the expression of the related protein and their phosphorylated forms after the cells were incubated with Gleevec for 90 min.At 72 hours after incubation with Gleevec, MTT was used to detect cell proliferation.Results: Western blot results showed that Gleevec at 0.1 μM can notably reduce phosphorylation of KIT Del559-560.Gleevec at 1μM completely blocked phosphorylation of KIT Ins IPYD579 and PDGFRA L839P, but did not affect PDGFRA D842V phosphorylation.MTT analy-sis indicated that growth of CHOPDGFRA L839P was inhibited by Gleevec at 1μM, however, CHOPDGFRA D842V was re-sistant to Gleevec at 5 μM.Conclusion: Gleevec can decrease the expression of phosphorylated protein CHOPDGFRA L839P and CHOKIT Ins IPYD579, and can remarkably inhibit the proliferation of cells containing PDGFRA L839P mutant.
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<p><b>OBJECTIVE</b>To investigate the effect of the expression and mutation of c-kit gene and its relationship with clinical pathology and prognosis of gastrointestinal stromal tumor (GIST).</p><p><b>METHODS</b>Immunohistochemical and PCR-SSCP techniques were used to detect c-kit protein expression and c-kit gene exon 11 mutation in 82 patients with GIST.</p><p><b>RESULTS</b>The positive c-kit protein expression and c-kit gene mutation rates were 97.6% (80/82) and 41.5% (34/82). Correlating the results of these two methods and clinicopathological factors, the c-kit expression and c-kit gene mutation rates were 95.0% (19/20) and 0 in benign GIST, and were 98.4% (61/62), 54.8% (34/62) in malignant GIST. Mutation positive GIST showed higher frequency of adjacent tissue invasion, metastasis and recurrence as compared with mutation negative ones.</p><p><b>CONCLUSION</b>c-kit protein is an important diagnostic marker of gastrointestinal stromal tumor. c-kit gene mutation may play a significant role in the pathogenesis of GIST and also may be a prognostic marker.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Gastrointestinal Neoplasms , Diagnosis , Genetics , Pathology , Mutation , Neoplasm Metastasis , Polymerase Chain Reaction , Polymorphism, Single-Stranded Conformational , Prognosis , Proto-Oncogene Proteins c-kit , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinicopathological and prognostic significance of the c-kit protein in gastrointestinal stromal tumor (GIST).</p><p><b>METHODS</b>Paraffin embedded materials from 53 benign GISTs, 13 potentially malignant and 55 malignant cases were analysed for c-kit expression by immunohistochemical method, while using leiomyomas and schwannomas as controls. Positive signals were shown in cytoplasma and cell membrane.</p><p><b>RESULTS</b>Of 122 GISTs, 118 (97%) were positive for c-kit. Localization of positive signals was accurate. The rate of c-kit protein in benign, potentially malignant and malignant cases was 98% (53/54), 93% (12/13), 96% (53/55) respectively. Compared with benign GIST, the positivity of c-kit in metastasis or recurrent cases decreased, but c-kit protein expression rate was not significantly different between the three patterns of GIST (chi(2) = 1.167, P > 0.05). Leiomyomas and schwannomas were typically c-kit negative.</p><p><b>CONCLUSION</b>As a sensitive and specific marker of GIST, c-kit seems to be a useful antibody in the diagnosis and differential diagnosis of GIST, but it may not be used as a prognostic index.</p>
Subject(s)
Humans , Biomarkers, Tumor , Genetics , Diagnosis, Differential , Gastrointestinal Neoplasms , Diagnosis , Metabolism , Immunohistochemistry , Mutation , Prognosis , Proto-Oncogene Proteins c-kit , GeneticsABSTRACT
Objective: To study the expression of CD15 mRNA,CD44v6 mRNA and nm23H1 mRNA in colon carcinoma and its relationship with clinical pathological parameters and prognosis of colon carcinoma. Methods: In situ hybridization was used to detect the expression of CD15 mRNA, CD44v6 mRNA and nm23H1 mRNA in 90 cases of colon carcinoma, and 53 cases were followed up for more than 5 years. Results: In 90 cases of colon carcinoma, the expression of CD15 mRNA,CD44v6 mRNA and nm23H1 mRNA were 84.4%,68.9%,66.7%, respectively. The high level expression of CD15 mRNA, CD44v6 mRNA and the low level expression of nm23H1 mRNA were positively corelated with the Dukes staging,serosa infiltration,lymph node and liver metastasis of colon carcinoma.The expression of CD15 mRNA in colon carcinoma was positively associated with that of CD44v6 mRNA and negatively with that of nm23H1 mRNA. Conclusion: CD15 mRNA,CD44v6 mRNA and nm23H1 mRNA play an up-regulation and a down-regulation role, respectively, and have a synergistic action in metastasis of colon carcinoma. CD15 mRNA can be used as a new biological index to predict the invasive potential of colon carcinoma and objectively evaluate the prognosis of patients.
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Objective: To observe the effect of coxsackie virus B3 on airway tract and lung morphology, and to study the relation between CVB infection and asthma. Methods: We established CVB3 infective model: 5 d neonatal rats inhaled CVB3 by ultrasonic brume. CVB3-IgM was examined 10 d after inoculating of CVB3, and LW/BW, airway tract and lung pathological change 10 d and 30 d after inoculation of CVB3 were observed. Results: Rats from the virus group had higher D of CVB3-IgM than control's (+2s ) and had higher LW/BW 10 d after inoculation of CVB3 than control (P<0.01). Neonatal rats had acute inflammatory changes 10 d after inoculation of CVB3 and persistent changes in morphology and cytology. Conclusion: Neonatal rats virus model is established. Respiratory infection by CVB3 in neonatal rats has persistent changes in airway tract inflammatory and morphology.
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0.05).The Nestin and C-kit expressions can be detected in all cases of GISTs by RT-PCR and Western Blot.Conclusion In conjunction with C-kit,Nestin may be a useful marker for diagnosis of GISTs but it cannot be used as a tumor differentiation index.
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Objective To investigate the significance of the mutation of c-kit gene in the development,(clinical) pathology and prognosis of gastrointestinal stromal tumors(GISTs).Methods The technique of(PCR-SSCP) was used to detect ckit gene mutation in 106 cases of GIST,and 57 of the cases were(followed-up).Results The c-kit gene mutation rate in the whole group was 45.3%(48/106),and(3.4)%(2/41) in benign GIST,and 70.8%(46/65) in malignant GIST.The 1-,3 and 5-year survival rates and median survival time of the mutation positive group were all markedlly lower than those of the(mutation) negative group.A comparison of the parameters that can differentiate the benign GISTs from malignant ones such as size,histological necrosis,aggressive grade,nucleus mitotic count and nuclear discrepancy,showed significant difference between the of postive and negative gene mutation(P
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Objective: To observe the effect of coxsackie virus B 3 on airway tract and lung morphology, and to study the relation between CVB infection and asthma. Methods: We established CVB 3 infective model: 5 d neonatal rats inhaled CVB 3 by ultrasonic brume. CVB 3 IgM was examined 10 d after inoculating of CVB 3, and LW/BW, airway tract and lung pathological change 10 d and 30 d after inoculation of CVB 3 were observed. Results: Rats from the virus group had higher D of CVB 3 IgM than control's ( +2s ) and had higher LW/BW 10 d after inoculation of CVB 3 than control ( P
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To study the clinicopathological and immunohistochemical characteristics of omental and mesenteric stromal tumor, 8 cases of stromal tumor were investigated, and followed up. The results showed that these tumors were solitary nodule, most were large. Histologically, cytoplasmic eosinophilia and perinuclear vacuolization were often seen in omental and mesenteric stromal tumor of spindle cell type. 3 cases showed epithelioid cytologic features. An immunohistochemical study showed that all the patients were C kit positive (100%),7 were CD34 positive, whereas 6 were SMA positive, positive expression of p53 and PCNA was found in 2 cases of malignant stromal tumor, Lower expression of PCNA was observed in 1 case of benign one.The results suggested that omental and mesenteric stromal tumors have distinct clinicopathological features, the expression of C kit and CD34 plays an important role in its diagnosis.
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Formalin-fixed paraffin-embedded biopsy specimens of the normal nasal mucosa,nasal polyps, inverted papillomas and papillary adenocarcinomas were analyzed by Avidin Biotin-Peroxidase Complextechnique for the demonstration of lectin receptors including peanut agglutinin (PNA), concanavalin ensifomis agglutinin (ConA),ulex europeaus agglutinin-I (UEA-1), sophora japonica agglutinin (SJA), wheat germ agglutinin (WGA), pisum sativum agglutinin (PSA), carcinoembryonic antigen (CEA) and keratin.lt was found that the distribution of PNA and UEA-I receptors was related to the degree of differentiation, dysplasia or malignant transformation of the nasal mucosa. The quantity of ConA receptors was increased with the degree of transformation of the nasal mucosal cells. There were many kinds of lectin receptors on the surface of one kind of cells. Lectin histochemistry was more economical, convenient, rapid and sensitive than immunohistochemistry. So, lectin histochemistry can be used to examine the degree of differentiation, dysplasia and malignant transformation of nasal neoplastic cells, providing objective index for clinical diagnosis, treatment and prognosis.