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Objective To investigate the value of serum lactate dehydrogenase (LDH) in advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI).Methods Pretreatment LDH level,pathological characteristic,tumor staging and treatment situation of 190 advanced NSCLC patients with EGFR sensitive mutation confirmed by pathology were retrospectively collected in Zhuhai People's Hospital of Guangdong Provice from July 2011 to July 2015.All the patients were divided into LDH normal group (LDH ≤252 U/L,n =78) and elevated group (LDH ＞ 252 U/L,n =112) according to pretreatment LDH level.Inaging evaluations of the patients were performed regularly,and the progression-free survival (PFS) and overall survival (OS) were recorded.The survival curves were plotted by Kaplan-Meier method and survival difference between patients with different LDH level was compared by logrank test.Cox regression analysis was used to analyze prognostic factors for mortality.Results The objective response rate of the LDH normal group was 76.9％ (60/78),and the elevated group was 71.4％ (80/112),with no statistically significant difference (x2 =0.716,P =0.398).The disease control rate of the LDH normal group was 89.7％ (70/78),and the elevated group was 85.7％ (96/112),with no statistically significant difference (x2 =0.676,P =0.411).The median PFS of the LDH normal group was 11.5 months,and the elevated group was 9.7 months (x2 =5.92,P =0.015).The median OS was 31.0 months in the LDH normal group,and 26.1 months in the elevated LDH group (x2 =4.79,P =0.029).Both PFS and OS of patients with elevated LDH were shorter than those of patients with normal LDH.Cox multivariate regression analysis showed that tumor staging (HR =1.652,95％ CI:1.386-2.259,P =0.018),PS score (HR =2.248,95％ CI:1.507-3.846,P ＜ 0.001),carcino-embryonic antigen (CEA) level (HR =1.250,95％ CI:1.066-1.703,P =0.037) and LDH level (HR =1.771,95 ％ CI:1.324-1.947,P =0.015) were independent prognostic factors in patients with advanced NSCLC.Conclusion Pretreatment serum LDH can not affect the objective response rate and disease control rate of EGFR-TKI in the treatment of advanced NSCLC,but can affect the PFS and OS of patients.Pretreatment serum LDH is an independent prognostic factor.
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Objective To evaluate the efficacy and adverse effect caused by capecitabine compared with S-1 as maintenance treatment of patients with advanced gastric cancer (AGC). Methods A total of 123 AGC patients who did not suffer disease progression after first-line chemotherapy were randomized into three groups. The capecitabine group(Cap)received maintenance chemotherapy with capecitabine(1000 mg/m2 twice daily for 14 days,21 days/cycle),and the S-1 group(S1)received S-1(40,50,or 60 mg according to the body surface area and orally administered twice a day for 14 days ,21 days/cycle). The observation group was given the support-ive treatment. Patients kept this chemotherapy regimens until disease progressed or with intolerant toxicity. Re-sults The disease control rate was 70.7%in the Cap group and 80.5%in the S1 group(P=0.304). The median time of progression was 8.3 months in the Cap group and 8.5 months in the S1 group(P = 0.448). Maintenance chemotherapy groups showed better responses in the treatment group than the observation group ,which demonstrat-ed a median progression of 6.7 months(P<0.001). The median overall survival time was 15.3 months in the Cap group and 15.7 months in the S1 group(P = 0.637). Maintenance chemotherapy groups showed better responses than the observation group ,which demonstrated a median survival of 12.8 months (P < 0.05). The main side effects included hyperpigmentation,bone marrow suppression,nausea and vomiting and hand-foot syndrome. No death occurred in relation to the therapy. Conclusion The effectiveness of capecitabine and S-1 as maintenance chemotherapy in AGC patients after the first-line chemotherapy are similar,and both can prolong the time of overall survival. And the adverse reactions can be tolerated.
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Objective To study the FMS-like tyrosine kinase-3 (FLT3) gene, NPM1 gene and c-kit gene mutations in acute myeloid leukemia (AML) by extracting DNA from the storage of bone marrow slides, and to investigate the relationship between the three gene mutations and clinical features in AML. Methods The bone marrow slides of 55 patients diagnosed with AML were enrolled in this study. The PCR, DNA sequencing and molecular cloning were used to detect and analyse the FLT3-ITD, NPM1 and c-kit gene mutations. Patients' remission, progression and survival time were also recorded. Results The DNA was successfully extracted from the bone marrow slides with -20 ℃ frozen storage without Wright stained, chemically fixed, and room temperature storage Wright stained discoloured by phenol ∶ chloroform ∶ isoamyl alcohol method, which can be used in PCR, direct sequencing and molecular cloning sequencing analysis. 10 of the 55 cases (18.2 %) were FLT3-ITD positive, including 9 cases with heterozygous mutations and 1 case with homozygous mutation. FLT3-ITD positive group had lower complete remission (CR) rate, shorter event-free survival (EFS) time and overall survival (OS) time than the negative group (P< 0.05). 9 of the 55 cases (16.4 %) had NPM1 heterozygous gene mutations, all belonging to type A. The EFS rate of the patients with NPM1 mutation was higher in 10 months and the OS rate was higher in 19 months (P< 0.05). 3 of 9 NPM1 mutations patients were FLT3-ITD positive. The CR rates of the four groups after initial remission induction therapy in order were NPM1+FLT3-ITD-, NPM1-FLT3-ITD-, NPM1-FLT3-ITD+, NPM1+FLT3-ITD+(P<0.05). Besides, NPM1-FLT3-ITD+was a risk factor affecting the OS (RR=1.250, P=0.005). 2 of the 55 cases (3.6 %) had c-kit gene mutations, namely mutant D816H and mutant D816V. The c-kit gene mutations were not found in patients with FLT3-ITD and NPM1 mutations. Conclusions The FLT3-ITD mutation is a poor prognosis molecular marker in AML, and NPM1 mutation is a good factor for the prognosis. NPM1-FLT3-ITD+is a risk factor affecting OS. The rate of c-kit gene mutation is low in AML, without the overlap of FLT3 and NPM1 mutations.
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Objective To analyze the association between β2-AK 27 locus genetic polymorphisms and asthma, and the protective effect in airway hyperreactivity. Methods The allel polymerase chain reaction were used to determine β2-AR 27 locus genetic polymorphisms in 149 patients with cough variant asthma who have the airway hyperreactivity. To observe these people for two years in order to know the proportion of changed to typical asthma. And compare with 90 people in healthy group. Results (1) The distribution frequency of β2-AR 27 locus genetic polymorphisms is major in heterozygote (57 % ) , and the Glu/Glu homozygote has the least ( 20% ) , (2) There was a significant decrease in the frequency of Glu/Glu genotype in asthmatics compared with healthy group(9% VS 20% ) ,OR = 0.4(P<0.05) ,95% CI (0.2 ～0. 9) ,but there was no significant difference in the allele frequency of asthmatics compared with healthy group,(3)The frequency of Glu/Glu genotype in severe asthma was lower than stable asthma group(P<0. 05). Conclusion These results suggesteded that β2-AR 27 locus genetic polymorphisms is correlated with asthma,and the Glu27 could have the protective effect to the airway.
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Objective To determine the allele and genotype frequencies of two single nucleotide polymor-phisms (SNPs) 677C/T,1298A/C in the methylenetetrahydrofolate reductase(MTHFR) gene in Chinese Southern Han individuals, and to assess whether there are differences in alleles frequencies among rheumatoid arthritis(RA) patients and normal controls. Methods 187 subjects(101 normal controls and 86 RA patients) were analyzed. The slide frequencies were carried out with polymerase chain reaction-restriction fragment langth polymorphism (PCR-RFLP). The two MTHFR SNPs Hardy-Weinberg equilibrium, linkage disequilibrium were analyzed with population genetics methods. Results The allele distribution of SNPs was in good unity with Hardy-Weinberg eqilibrium. The genotype frequencies of 677CC, CT, TT were 36.0%, 51.2%, 12.8%, respectively, in RA group, and 42.6%, 44.6% ,12.9%, respectively, in controls. The genotype frequencies of 1298AA,AC、CC were 60.5%、32.6%、 7.0%, respectively, in RA group, and 49.5% ,46.5% ,4.0% ,respectively, in controls. The frequencies of rarely allele 677T were 38. 4% and 35.1% in RA and controls. The 1298C were 23.3% and 27.2% in RA and controls. Allele frequencies were similar between RA group and controls, and there is no linkage between two SNPs and RA. The relationship between 677C/T and 1298A/C was strong linkage disequilibrium. Conclusions The research pro-vided Chinese southern Han population genetics data on MTHFR gene. The relationship between 677C/T and 1298A/C was strong linkage disequilibrium.