Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/...Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.展开更多
BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in ...BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.展开更多
Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reve...Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.展开更多
An in situ hybridization technique with 35S labelled proto-oncogene probes (c-myc & c-fes) was used to detect their expression in bone marrow cells of 22 cases of leukemia of various types and immature granulocyte...An in situ hybridization technique with 35S labelled proto-oncogene probes (c-myc & c-fes) was used to detect their expression in bone marrow cells of 22 cases of leukemia of various types and immature granulocytes and erythroblasts of 16 nomal myelograms as controls. Both c-myc and c-fes were detectable in leukemic cells as well as in immature granulocytes and erythroblasts of normal bone marrow, but the expression extent varied in different cases. The levels of c-myc expression in leukemic cells were higher than those in controls (P<0.001). There was no difference of c-fes expression in two groups of bone marrow cells (P>0.05). This technique provides us a new method in studying variations of proto-oncogene expression in leukemic cells.展开更多
AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis(NF).METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of p...AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis(NF).METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of pathogenic mutations in RET protooncogene, von Hippel-Lindau(VHL) and succinate dehydrogenase complex subunits B(SDHB) genes were investigated. RET proto-oncogene mutation screening for exons 10, 11, 13, 14, 15, 16 were examined by polymerase chain reaction(PCR) and direct DNA sequencing in patient. Mutation screening for exons 1, 2, 3 of VHL gene was carried out. Both forward and reverse strandswere subjected to direct sequencing after PCR amplification. The entire coding sequence of SDHB gene was screened for the presence of pathogenic mutations by PCR-sequencing.RESULTS: A 45-year-old man presented with abdominal pain and hypertension over the previous year. The patient was a known case of neurofibromatosis type 1(NF1) who presented at the age of 15 years with hyperpigmented and hypopigmented lesions. After complete evaluation for hypertension, biochemical tests and imagings indicated a malignant pheochromocytoma of 120 mm × 70 mm in size. The patient underwent left adrenalectomy, nephrectomy and splenectomy. After surgery the symptoms improved and blood pressure was controlled. After 5 years he was admitted again for evaluation of hypertensive crisis. Biochemical tests were again consistent with pheochromocytoma and disease relapse. Imaging studies and liver biopsy confirmed metastatic pheochromocytoma to the liver and para-aortic area. 131 Iodine-metaiodobenzylguanidine therapy was carried out. Genetic screening of VHL(exons 1, 2, 3), RET proto-oncogene(exons 10, 11, 13, 14, 15, 16) and SDH complex subunits revealed no pathogenic mutation. CONCLUSION: We conclude that mutations in the NF1 gene are responsible for the patient's clinical findings. However, would be helpful to further examine somatic mutations for a more precise study of genotypephenotype correlation.展开更多
Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 ...Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.展开更多
Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectom...Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three展开更多
BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,fam...BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.展开更多
BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LN...BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LNM)remains controversial. Different surgical strategies may bring a bias in demonsstrating the association between them.In order to delineate a risk stratification to guide a tailored initial approach to tumors that express BRAF^V600E mutation,we performed this meta-analysis by using the articles in which total or near-total thyroidectomy plus bilateral central lymph node dissection was routinely performed to avoid the bias from the surgical strategy.We searched the Medline,Embase and CNKI database for eligible studies from January 2003 to May 2018.Meta-analysis was performed using the STATA 12.0 software.Odds ratios (ORs)and 95% confidence intervals (CIs)were calculated under fixed-effects or random-effects models.Fifteen clinical studies were included with a total of 4909 PTC patients. Our meta-analysis results reported that BRAF^V600E mutation was associated with LNM (OR=1.34;95% CI:1.09-1.65;P=0.005),as well as central LNM (OR=1.59;95% CI: 1.35-1.88;P<0.00001).Moreover,in patients with papillary thyroid microcarcinoma, we also confirmed the predictive value of BRAF^V600E mutation for LNM (OR=3.49;95% CI:2.02-6.02;P<0.00001).This meta-analysis demonstrates that BRAF^V600E mutation is closely related to LNM in PTC patients.The results suggest that BRAF^V600E mutation can be considered as a risk factor for LNM in PTC.Moreover,combining BRAF^V600E mutation with other risk factors to determine the initial surgical treatment may bring benefits for PTC patients.展开更多
Objective： To study the effect of Jinguo Weikang Capsule （金果暖康胶囊, JWC） on the gene expression of H-ras, epidermal growth factor receptor （EGFR）, P53 and C-myc of the gastric mucosa in rats with gastric prec...Objective： To study the effect of Jinguo Weikang Capsule （金果暖康胶囊, JWC） on the gene expression of H-ras, epidermal growth factor receptor （EGFR）, P53 and C-myc of the gastric mucosa in rats with gastric precancerous lesions, and to investigate the action mechanism of JWC on gastric precancerous lesions. Methods： A rat model with paratypical proliferation of the gastric epithelium mucosa was established by using ^60Co irradiation. Rats were divided into the normal group, model group, high-, medium-, low-dose JWC treatment groups, and the vitacoenzyme control group, and were treated for 30 days. The expression of H-ras, EGFR, P53 and C-myc genes of the gastric mucosa was detected by using immunohistochemical methods. Results： The expression and over-expression rates of H-ras, EGFR, P53 and C-myc gene in the high- and medium-dose JWC treatment groups were significantly lower （P〈0.05） as compared with those of the model group. Conclusion： JWC can inhibit the expression of the H-ras, EGFR, P53 and C-myc genes expression of the gastric mucosa in rats, which may be one of mechanisms involved in suppressing or reversing gastric carcinogenesis.展开更多
Summary： Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic （37-38℃） ischemia, mild hypotherm...Summary： Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic （37-38℃） ischemia, mild hypothermic （31 32℃） ischemia, hyperthermic （41-42℃） ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20omin ischemia. The expression of c-fos protein and the levels of malondialdehyde （MDA） and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-los protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion fol- lowing 20-min ischemia as compared with the sham-operated group （P〈0.01）. The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group （P〈0.01）. It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia.展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 30271110).
文摘Objective To study the effects of cadmium on hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats. Methods Cadmium chloride at the doses of 5, 10, and 20 μmol/kg was given to rats by i.p. and there were 5 male SD rats in each group. Hepatocellular DNA damage was measured by single cell gel electrophoresis （or comet assay）, while expression of proto-oncogenes c-myc, c-fos, and c-jun in rat hepatocytes were measured by Northern dot hybridization. C-Myc, c-Fos, and c-Jun were detected with immuno-histochemical method. Hepatocellular apoptosis was determined by TUNEL （TdT-mediated dUTP Nick End Labelling） and flow cytometry. Results At the doses of 5, 10, and 20 μmol/kg, cadmium chloride induced DNA damage in rat hepatocytes and the rates of comet cells were 50.20%, 88.40%, and 93.80%, respectively. Results also showed an obvious dose-response relationship between the rates of comet cells and the dose of cadmium chloride （r=0.9172, P〈0.01）. Cadmium chloride at the doses of 5, 10, and 20 μmol/kg induced expression of proto-oncogenes c-myc, c-fos, and c-jun. The positive brown-yellow signal for c-myc, c-fos, and c-jun was mainly located in the cytoplasm of hepatocytes with immunohistochemical method. TUNEL-positive cells were detected in cadmium-treated rat livers. Apoptotic rates （%） of cadmium-treated liver cells at the doses of 5, 10, and 20 μmol/kg were （17.24 ±2.98）, （20.58± 1.35）, and （24.06±1.77） respectively, being significantly higher than those in the control. The results also displayed an obvious dose-response relationship between apoptotic rates and the dose of cadmium chloride （r=0.8619, P〈0.05）. Conclusion Cadmium at 5-20 μmol/kg can induce hepatocellular DNA damage, expression of proto-oncogenes c-myc, c-fos, and c-jun as well as apoptosis in rats.
文摘BACKGROUND Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies.Different signaling pathways that participate in the progression of these tumors have been identified.B-raf proto-oncogene serine/threonine kinase(BRAF)is a protein involved in the behavior of ameloblastomas,and it is related to many cell mechanisms.BRAF gene mutations have been identified in ameloblastomas,of which the BRAF V600E(valine substituted by glutamic acid at amino acid 600)mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior.Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments.AIM To document the presence of BRAF V600E and additional mutations,their behavior,and targeted therapies in these tumors.METHODS An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE,Cochrane,EMBASE,and SpringerLink using the terms“ameloblastomas”,“BRAF V600E”,“additional mutations”,and“targeted therapies”.Ameloblastomas were classified according to WHO guidelines.Inclusion criteria were articles in English,published not more than 10 years ago,and studies with laboratory works related to BRAF V600E.Articles were evaluated by two independent reviewers and retrieved for full-text evaluation.The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies.Descriptive statistical analysis was performed.RESULTS Two independent reviewers,with a substantial concordance indicated by a kappa coefficient of k=0.76,evaluated a total of 19 articles that were included in this study.The analysis registered 521 conventional ameloblastomas(AM),81 unicystic ameloblastomas(UA),13 ameloblastic carcinomas(AC),three metastatic ameloblastomas(MA),and six peripheral ameloblastomas(PA),of which the histopathological type,anatomic location,laboratory tests,expression of BRAF mutation,and additional mutations were registered.The BRAF V600E mutation was found in 297 AM(57%),63 UA(77.7%),3 AC(23%),1 MA(50%),and 5 PA(83.3%).Follicular type predominated with a total of 116 cases(40%),followed by plexiform type with 63 cases(22.1%).Furthermore,both types presented additional mutations,in which alterations in JAK3 P132T,SMARCB1,PIK3CA,CTNNB1,SMO,and BRAF G606E genes were found.Four case reports were found with targeted therapy to BRAF V600E.CONCLUSION The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.
文摘Objective To investigate the expressions of estrogen receptor(ER)subtypes and c-met proto-oncogene in human endometrial carcinomas and to assess the clinical significance of ER and c-met in this carcinoma.Methods Reverse transcription PCR(RT-PCR)was used to detect the expressions of ERα,ERβ and c-met proto-oncogene mRNA in 30 samples of endometrial carcinoma and 11 samples of normal endometrium.Results The expression of ERα in endometrial carcinoma(0.70±0.40)was significantly reduced in comparison to that in normal endometrium(1.14±0.56,P<0.05).A similar finding was made for the expression of ERβ in carcinoma(0.24±0.18)versus normal tissues(0.48±0.20,P<0.05).In contrast,c-met mRNA expression was increased in endometrial carcinoma(1.45±0.72)compared to that in normal endometrium(0.42±0.31,P<0.01).A decrease tendency of the expression of ERα was also found from Stage Ⅰ(0.82±0.41)to a more severe Stag Ⅱ-Ⅲ of endometrial carcinoma(0.42±0.17,P<0.05).The analysis of ERα and ERβ mRNA revealed a decrease tendency from shallow to deep invasion of the uterine muscles(P<0.05).We found that the expressions of ERα and ERβ were negatively correlated with c-met proto-oncogene with a coefficient correlation of-0.63(P<0.01)and-0.32(P<0.05),respectively.Conclusion ERα and ERβ are both involved in mutagenic action of carcinogen.C-met proto-oncogene plays an important role in the carcinogenesis and development of endometrial carcinoma.C-met and ER expressions show a negative correlation in the development of endometrial carcinoma.
文摘An in situ hybridization technique with 35S labelled proto-oncogene probes (c-myc & c-fes) was used to detect their expression in bone marrow cells of 22 cases of leukemia of various types and immature granulocytes and erythroblasts of 16 nomal myelograms as controls. Both c-myc and c-fes were detectable in leukemic cells as well as in immature granulocytes and erythroblasts of normal bone marrow, but the expression extent varied in different cases. The levels of c-myc expression in leukemic cells were higher than those in controls (P<0.001). There was no difference of c-fes expression in two groups of bone marrow cells (P>0.05). This technique provides us a new method in studying variations of proto-oncogene expression in leukemic cells.
文摘AIM: To investigate pathogenic mutations related to malignant pheochromocytoma in neurofibromatosis(NF).METHODS: We present a patient with NF and metastatic pheochromocytoma in whom genetic screening for presence of pathogenic mutations in RET protooncogene, von Hippel-Lindau(VHL) and succinate dehydrogenase complex subunits B(SDHB) genes were investigated. RET proto-oncogene mutation screening for exons 10, 11, 13, 14, 15, 16 were examined by polymerase chain reaction(PCR) and direct DNA sequencing in patient. Mutation screening for exons 1, 2, 3 of VHL gene was carried out. Both forward and reverse strandswere subjected to direct sequencing after PCR amplification. The entire coding sequence of SDHB gene was screened for the presence of pathogenic mutations by PCR-sequencing.RESULTS: A 45-year-old man presented with abdominal pain and hypertension over the previous year. The patient was a known case of neurofibromatosis type 1(NF1) who presented at the age of 15 years with hyperpigmented and hypopigmented lesions. After complete evaluation for hypertension, biochemical tests and imagings indicated a malignant pheochromocytoma of 120 mm × 70 mm in size. The patient underwent left adrenalectomy, nephrectomy and splenectomy. After surgery the symptoms improved and blood pressure was controlled. After 5 years he was admitted again for evaluation of hypertensive crisis. Biochemical tests were again consistent with pheochromocytoma and disease relapse. Imaging studies and liver biopsy confirmed metastatic pheochromocytoma to the liver and para-aortic area. 131 Iodine-metaiodobenzylguanidine therapy was carried out. Genetic screening of VHL(exons 1, 2, 3), RET proto-oncogene(exons 10, 11, 13, 14, 15, 16) and SDH complex subunits revealed no pathogenic mutation. CONCLUSION: We conclude that mutations in the NF1 gene are responsible for the patient's clinical findings. However, would be helpful to further examine somatic mutations for a more precise study of genotypephenotype correlation.
文摘Objective:To study the effect of cisplatin-based concurrent radiochemotherapy on the malignant degree of advanced cervical cancer and the expression of proto-oncogene and tumor suppressor genes.Methods: A total of 82 patients with advanced cervical cancer who were treated in our hospital between July 2013 and December 2016 were collected and divided into control group and observation group according to random number table, with 41 cases in each group. The control group of patients received radiotherapy alone, while the observation group of patients received cisplatin-based concurrent radiochemotherapy. Tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were compared between two groups of patients before and after treatment.Results:Before treatment, differences in tumor marker levels in serum as well as proto-oncogene and tumor suppressor gene expression in tumor tissue were not statistically significant between two groups of patients. After treatment, serum tumor markers SCC, CA50, CA724 and CEA levels of observation group were significantly lower than those of control group;proto-oncogene DEK, c-myc and PIK3CA mRNA expression in tumor tissue were significantly lower than those of control group;tumor suppressor genes p53, SOCS-1, FHIT and PTEN mRNA expression in tumor tissue were significantly higher than those of control group.Conclusions:Cisplatin-based concurrent radiochemotherapy can effectively reduce the tumor malignancy and balance the proto-oncogene / tumor suppressor gene expression in patients with advanced cervical cancer.
文摘Objective To discuss clinical diagnosis and treatment of multiple endocrine neoplasia ( MEN) 2A,and report the mutation of RET proto-oncogene in a pedigree of three patients with MEN 2A. Methods Bilateral adrenalectomy was performed on two of the three
基金Supported by The Finance Bureau of Dongguan City,Guangdong Province.
文摘BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.
基金This study was supported by National Natural Science Foundation of China (No.81702650),Natural Science Foundation of Hubei Province (No.2016CFB323)and Innovation Foundation of Huazhong University of Science and Technology (No.2016YXMS229).
文摘BRAF^V600E mutation has been thought to be a valuable molecular marker that may predict a worse prognosis for papillary thyroid cancer (PTC).But whether BRAF^V600E mutation is associated with lymph node metastasis (LNM)remains controversial. Different surgical strategies may bring a bias in demonsstrating the association between them.In order to delineate a risk stratification to guide a tailored initial approach to tumors that express BRAF^V600E mutation,we performed this meta-analysis by using the articles in which total or near-total thyroidectomy plus bilateral central lymph node dissection was routinely performed to avoid the bias from the surgical strategy.We searched the Medline,Embase and CNKI database for eligible studies from January 2003 to May 2018.Meta-analysis was performed using the STATA 12.0 software.Odds ratios (ORs)and 95% confidence intervals (CIs)were calculated under fixed-effects or random-effects models.Fifteen clinical studies were included with a total of 4909 PTC patients. Our meta-analysis results reported that BRAF^V600E mutation was associated with LNM (OR=1.34;95% CI:1.09-1.65;P=0.005),as well as central LNM (OR=1.59;95% CI: 1.35-1.88;P<0.00001).Moreover,in patients with papillary thyroid microcarcinoma, we also confirmed the predictive value of BRAF^V600E mutation for LNM (OR=3.49;95% CI:2.02-6.02;P<0.00001).This meta-analysis demonstrates that BRAF^V600E mutation is closely related to LNM in PTC patients.The results suggest that BRAF^V600E mutation can be considered as a risk factor for LNM in PTC.Moreover,combining BRAF^V600E mutation with other risk factors to determine the initial surgical treatment may bring benefits for PTC patients.
基金the Bureau of Science and Techology of Shaanxi Province[No.2002K1I-G7(6)]
文摘Objective： To study the effect of Jinguo Weikang Capsule （金果暖康胶囊, JWC） on the gene expression of H-ras, epidermal growth factor receptor （EGFR）, P53 and C-myc of the gastric mucosa in rats with gastric precancerous lesions, and to investigate the action mechanism of JWC on gastric precancerous lesions. Methods： A rat model with paratypical proliferation of the gastric epithelium mucosa was established by using ^60Co irradiation. Rats were divided into the normal group, model group, high-, medium-, low-dose JWC treatment groups, and the vitacoenzyme control group, and were treated for 30 days. The expression of H-ras, EGFR, P53 and C-myc genes of the gastric mucosa was detected by using immunohistochemical methods. Results： The expression and over-expression rates of H-ras, EGFR, P53 and C-myc gene in the high- and medium-dose JWC treatment groups were significantly lower （P〈0.05） as compared with those of the model group. Conclusion： JWC can inhibit the expression of the H-ras, EGFR, P53 and C-myc genes expression of the gastric mucosa in rats, which may be one of mechanisms involved in suppressing or reversing gastric carcinogenesis.
基金supported by the Key Projects of Scientific Research Funds from Health Department of Hubei Province(No.JX5A04),China
文摘Summary： Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic （37-38℃） ischemia, mild hypothermic （31 32℃） ischemia, hyperthermic （41-42℃） ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20omin ischemia. The expression of c-fos protein and the levels of malondialdehyde （MDA） and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-los protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion fol- lowing 20-min ischemia as compared with the sham-operated group （P〈0.01）. The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group （P〈0.01）. It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia.
