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OBJECTIVE:To investigate the relationship of Cytochrome P450 (CYP)3A4* 18 gene polymorphism with therapeutic efficacy and ADR of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients receiving primary treatment.METHODS:A total of 46 advanced NSCLC patients receiving primary EGFR-TKI (gefitinib or edotinib) treatment until disease progression or intolerance were selected from our hospital during Jan.2013-Mar.2016,and (gefitinib of erlotinib) treatment until disease progression or intolerance.CYP3A4*18 genotype was detected by PCR and direct sequencing.Clinical efficacies,progression-free survival (PFS) and the occurrence of ADR were compared among differ ent genotypes.RESULTS:Among 46 patients,there were 17 cases of CYP3A4*18 wild-type and 29 cases of CYP3A4*18 mutation-type,with mutation frequency of 63.0％.The objective response rate (ORR) of CYP3A4*18 wild-type patients was 23.5％,and disease control rate (DCR) of them was 70.6％.For CYP3A4*18 mutation-type patients,ORR and DCR were 27.6％ and 69.0％.There was no statistical significance in the proportion of patients with partial response,stable disease or progressive dis ease,ORR or DCR among different genotypes (P＞0.05).PFS of female patients were significantly longer than male patients;those of patients without smoking history were significantly longer than those with smoking history,with statistical significance (P＜0.05).There was no correlation between patients' age,therapy drugs,Eastern Oncology Collaboration scores,EGFR mutation types,CYP3A4*18 genotypes and PFS (P＞0.05).Patients'gender and smoking history were independent prognostic factors for PFS [odds ratios were 3.438,0.205,95％ CI were(1.393,8.488),(0.088,0.481)].Among CYP3A4* 18 wild-type patients,6 patients suffered from rash (35.3％) and 3 diarrhea (17.6％).Among mutation-type patients,26 patients suffered from rash (89.7％) and 15 diarrhea (51.7％),with statistical significance (P＜0.05).There was no statistical significance in the incidence of liver function injury and interstitial dermatitis among different genotypes (P＞0.05).CONCLUSIONS:CYP3A4*18 gene polymorphism may be not associated with therapeutic efficacy of EGFR-TKI in advanced NSCLC patients receiving primary treatment,but it is correlated with the occurrence of ADR.Mutation type patients are more likely to suffered from rash,diarrhea and other ADR.
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OBJECTIVE:To investigate the correlation between ribonucleotide reductase M1 subunit (RRM1) single nucleo-tide polymorphisms (SNPs) and chemotherapy sensitivity of patients with non-small cell lung cancer (NSCLC) for gemcitabine. METHODS:A total of 96 NSCLC patients receiving primary treatment selected from our hospital during Aug. 2014-Jul. 2016 were all accepted gemcitabine-based two-drug chemotherapy plan,with continuous treatment for at least 2 cycles(28 d as a cycle). Che-motherapy sensitivity rate was calculated by using the ratio of the sum of patients with complete response and partial response to the sum of test patients. RRM1 genotype was tested by PCR and direct sequencing. The correlation between different genotypes and chemotherapy sensitivity was analyzed. RESULTS:Distribution frequency of RRM1-37C>A CC, CA, AA genotype were 35.42％,52.08％,12.50％,respectively;distribution frequency of-524C>T CC,CT,TT genotype were 18.75％,37.50％, 43.75％,respectively. The frequency of each genotype was in the line with Hardy-Weinberg equilibrium(P>0.05). Chemotherapy sensitivity rate of 96 NSCLC patients was 37.50％. The patient's age,sex,ethnicity,smoking or not,TNM stage,pathological type,chemotherapy plan,and the Eastern American Oncology Collaboration score were not associated with chemotherapy sensitivi-ty (P>0.05). Chemotherapy sensitivity rates of RRM1(-37CA)+(-524CT)genotype and (-37CC)+(-524TT) genotype patients (57.14％,39.39％) were significantly higher than those of other genotype patients (10.71％),with statistical significance (P<0.05). There was no statistical significance in chemotherapy sensitivity rate between RRM1(-37CA)+(-524CT) and (-37CC)+(-524TT)genotype patients. CONCLUSIONS:In NSCLC patients,the SNPs of RRM1 can be used as predictive factor for the sen-sitivity of gemcitabine chemotherapy,and RRM1(-37CA)+(-524CT)and(-37CC)+(-524TT)genotype patients have higher sensi-tivity to this type of chemotherapy.
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Background and purpose: Solid papillary carcinoma (SPC) is an uncommon histological pattern accounting for <1% of breast carcinomas. It is a distinctive form of papillary carcinoma characterized by closely apposed expansile, cellar nodules. The present study aimed to investigate the clinicopathologic features, immunophenotype and prognosis of SPC of breast. Methods:We retrieved the data of 32 cases of SPC of the breast from pathology files, and determined the expressions of ER, PR, C-erbB-2, p63, Calponin, CK5/6, Ki-67, Syn and CgA by pathohistological observation and immunohistochemical examination. Results:All the patients were females with a mean age of 67.3 years. The clinical features were a palpable mass or bloody nipple discharge. The tumor was observed as a whitish-grey or yellowish-brown, lfeshy ifrm or soft, nodular circumscribed mass on gross examination. Microscopy showed solid and papillary area inside the capsule wall and that fine delicate fibrovascular septa were discovered amid the solid proliferation. The tumor cells were oval, polygonal, spindled or signet ring-like with abundant eosinophilic cytoplasm and contained mildly to moderately pleomorphic nuclei. Immunohistochemically, all tumor cells were strongly positive for ER and PR (++-+++), negative for C-erbB-2 and all cases were negative for CK5/6, p63 and Calponin in the cellular nodules. The positive expression rates of Syn and CgA were 68.8%and 78.2%, respectively. The average positive rate of Ki-67 in tumor cells was 7.5%(2%-20%). Twenty-seven patients were available for follow-up examination from 6 to 84 months and 25 patients were alive and disease free. One patient had tumor recurrence, and was alive after reoperation. Another patient died of the tumor metastasis. Conclusion:SPC is predominantly found in elderly females with distinctive pathological features and immunophenotype. SPC often carries an indolent clinical behavior, and even if accompanied by inifltration, very rare cases have recurrence and metastasis after resection, so its prognosis is better.
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Objective To evaluate expression and significance of TLR4 and NF-κB on inflammatory injure after intracerebral hemorrhage in rats .Methods 60 Sprague Dawley maleness rats were randomly divided into Sham group ,12 h ,24 h ,72 h and 7 d af-ter ICH group(12 s) .The ICH was induced by injection of autologous blood in rats .The behavioral changes were detected by neu-rologic deficit score .The water content of the brain was used to evaluate brain edema changes .Number of TLR4 and NF-κB positive cells by Nissl staining and the expression of protein determined by immunohistochemistry and Western blot .Results After ICH 12 h ,expression of TLR4 and NF-κB positive cells around the hematoma were expressed ,with the extension of the time ,expression was gradually increasing ,and after ICH 72 h the expression of protein were the highest .Cerebral edema and severe neurological damage occurred .Western blot shows the amount of TLR4 expression and NF-κB were in line with the result .Conclusion After in-tracerebral hemorrhage in rat causing inflammatory injure of brain tissue around the hematoma .TLR4 may activate the expression of NF-κB involved in the secondary inflammatory injure after intracerebral hemorrhage in rats .