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Compared with various malignant tumors, lung cancer has high incidence and the highest mortality worldwide. Non-small-cell lung cancer (NSCLC), the most common kind of lung cancer, is still a great threat to the world, including China. Surgery, platinum-based chemotherapy, and radiotherapy are still the primary treatments for NSCLC patients in the clinic, whereas immunotherapy and targeted therapy are gradually playing more important roles. A next-generation tyrosine kinase inhibitor (TKI), afatinib, was developed as a targeted reagent for epidermal growth factor receptor (EGFR). This targeted drug was effective in a series of trials. The US Food and Drug Administration then approved afatinib as a new first-line treatment for EGFR L858R and exon 19 deletion mutant patients in 2013. This review focused on current clinical studies of afatinib. Although this TKI was not widely available in China until recently, we aim to provide a reference for its future use in China. [ABSTRACT FROM AUTHOR]

Background. We aimed to investigate the distributive characteristics of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms and their influence on metformin efficacy in Chinese T2DM patients. Methods. The distributions of SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms were determined in 267 T2DM patients and 182 healthy subjects. Subsequently, 53 newly diagnosed patients who received metformin monotherapy were recruited to evaluate metformin efficacy. Results. No significant difference was found between T2DM patients and healthy subjects in SLC22A1 rs594709 and SLC47A1 rs2289669 allele frequencies and genotype frequencies. After metformin treatment, SLC22A1 rs594709 GG genotype patients showed a higher increase in FINS (p=0.015) and decrease in HOMA-IS (p=0.001) and QUICKI (p=0.002) than A allele carriers. SLC47A1 rs2289669 GG genotype patients had a higher decrease in TChol (p=0.030) and LDL-C (p=0.049) than A allele carriers. Among SLC22A1 rs594709 AA genotype, patients with SLC47A1 rs2289669 AA genotype showed a higher decrease in FBG (p=0.015), PINS (p=0.041), and HOMA-IR (p=0.014) than G allele carriers. However, among SLC22A1 rs594709 G allele carriers, SLC47A1 rs2289669 AA genotype patients showed a higher decrease in TChol (p=0.013) than G allele carriers. Conclusion. Our data suggest that SLC22A1 rs594709 and SLC47A1 rs2289669 polymorphisms may influence metformin efficacy together in Chinese T2DM patients. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association of genetic polymorphisms in high mobility group box 1 and 2 ( HMGB1 and HMGB2, respectively) with platinum-based chemotherapy responses in Chinese lung cancer patients. In total, 338 Chinese lung cancer patients (154 responders and 184 non-responders) were recruited to the study. All patients received at least two cycles of first-line platinum-based chemotherapy. Three tagging single nucleotide polymorphisms ( SNPs) of HMGB1 and two tagging SNPs of HMGB2 were detected in patients. We found that rs1412125 and rs2249825 of HMGB1 were significantly associated with the platinum-based chemotherapy response in both recessive and genotypic models. In addition, rs1412125 showed significant association with platinum-based chemotherapy response for the subgroup of patients aged >55 years in additive, recessive and genotypic models. No significant associations were detected between other SNPs and the platinum-based chemotherapy response. The HMGB1 SNPs (rs1412125 and rs2249825) were associated with platinum-based chemotherapy responses in Chinese lung cancer patients. In conclusion, HMGB1 SNPs may serve as potential biomarkers for predicting the efficacy of platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the influence of the nitric oxide synthase 3 ( NOS3) 894 G>T polymorphism on prognostic outcomes of anthracycline in Chinese patients with de novo intermediate-risk acute myeloid leukaemia (AML) and to examine the gene expression level in relation to genetic variation. In all, 225 Chinese patients with intermediate-risk AML (at the complete remission stage) treated with anthracycline were enrolled in the study. The 894 G>T polymorphism of the NOS3 gene was analysed by allele-specific matrix-assisted laser desorption ionization time-of-flight. Expression of NOS3 mRNA was tested in 72 patients of known genotype for NOS3 894 G>T. The clinical characteristics of these patients were obtained from medical records. Survival analysis showed that patients with AML (GG genotype) had a longer overall survival (OS; P = 0.006). After adjusting for age, gender, leucocyte count, haemoglobin level, platelet level, French, American and Britain (FAB) classification, lactate dehydrogenase levels, Eastern Cooperative Oncology Group Performance Status, nucleophosmin gene and fms-related tyrosine kinase 3 gene, multivariate survival analysis showed that the NOS3 894 G>T polymorphism appeared to be a predicting factor for OS ( P = 0.014; hazard ratio = 1.856). However, no significant associations between the NOS3 894 G>T polymorphism and relapse-free survival and relapse in patients with AML were observed. Gene expression levels were significantly higher in patients with the GG genotype than in patients with the GT and TT genotypes ( P = 0.033). The findings suggest that the NOS3 894 G>T variant may be a biomarker for the prediction of OS in Chinese patients with AML. [ABSTRACT FROM AUTHOR]

Aims The causes of genetic generalized epilepsies ( GGEs) are still uncertain now. Some studies found that the human potassium channel, subfamily T, member 1 ( KCNT1) is the candidate gene causing malignant migrating partial seizures of infancy and autosomal dominant nocturnal frontal lobe epilepsy which are all rare genetic generalized epilepsies. The aims of this study were going to evaluate the association between KCNT1 common variations and the susceptibility and drug resistance of genetic generalized epilepsies in Chinese population. Methods The allele-specific MALDI- TOF mass spectrometry method was used to assess 17 tag SNPs (tagged single-nucleotide polymorphisms) of KCNT1 in 284 healthy Chinese controls and 483 Chinese GGEs patients including 279 anti-epileptic drug-responsive patients and 204 drug-resistant patients. Results Genotype distributions of all the selected tag SNPs were consistent with Hardy-Weinberg equilibrium in GGEs and healthy controls. None of the all 17 tag SNPs alleles were found to be related with the susceptibility and drug resistance of genetic generalized epilepsies. The frequencies of haplotype 5 and haplotype 1 were significantly lower in GGEs than that in healthy controls (2% vs. 4%, OR = 0.47 [0.27-0.94], P = 0.03) and obviously higher in drug-resistant patients than that in drug-response patients (6% vs. 3%, OR = 2.56 [1.23-5.35], P = 0.01). However, after the correction of multiple comparisons with Bonferroni's method, we found that the above two haplotypes were not associated with the susceptibility and drug resistance in GGEs and healthy controls. Conclusion This gene-wide tagging study revealed no association between KCNT1 17 common variations and susceptibility of GGEs or AEDs (anti-epileptic drugs) efficacy of genetic generalized epilepsies in Chinese population. [ABSTRACT FROM AUTHOR]

SUMMARY Aims: Some study found that ATP-binding cassette (ABC) efflux transporters play an important role in antiepileptic drug resistance, especially ABCB1 and ABCC2. The aims of this study were to evaluate the relationship between the genetic polymorphisms of ABCC2 and ABCB1 and the therapeutic efficacy of antiepileptic drugs (AEDs) in Chinese epileptic patients. Methods: ABCB1 rs1045642 (3435C>T) and ABCC2 rs717620 (−24C>T), rs3740066 (3972C>T), and rs2273697 (1249G>A) polymorphisms loci in 537 Chinese epilepsy patients (217 drug resistant patients and 320 drug responders) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: ABCC2 rs717620 −24TT genotype was significantly associated with drug resistant epilepsy (odds ratio [OR]= 4.06 [1.79-9.20], P= 0.001). The OR values of ABCC2 rs717620 −24 CT+TT genotypes and ABCC2 rs3740066 (3972C>T) CT+TT genotypes were markedly higher in drug resistant patients (OR = 1.57 [1.08-2.29], P= 0.018; OR = 1.49 [1.02-2.18], P= 0.038, respectively) compared with responsive patients. ABCC2 rs2273697 (1249G>A) and ABCB1 rs1045642 (3435C>T) polymorphisms were not associated with drug resistant epilepsy. Linkage disequilibrium (LD) test showed that the ABCC2 rs717620 were in strong LD with rs2273697 (D'= 0.694) and rs3740066 (D'= 0.699). The frequencies of haplotypes TGT ( ABCC2 −24C>T/ ABCC2 1249G>A/ ABCC2 3972C>T) in resistant patients was significantly higher than those in responsive patients (21.0% vs. 14.2%, P < 0.05). Conclusion: ABCC2−24C>T, 3972C>T polymorphisms and one ABCC2 haplotype is associated with AED resistance; ABCC2 1249G>A and ABCB1 3435C>T polymorphisms are not associated with AED resistance in our study. These data suggest that ABCC2 polymorphisms and haplotype may affect the response of antiepileptic drugs. [ABSTRACT FROM AUTHOR]

SUMMARY Aims: To investigate the tolerability and efficacy of carbamazepine treatment in patients with partial-onset seizures and the association with polymorphisms in the sodium channel α-subunit type 1 ( SCN1A), and gamma-aminobutyric acid (GABA) receptor genes among the Chinese Han population. Methods: 448 patients were genotyped for single nucleotide polymorphisms selected of the SCN1A and GABA-receptor genes. Monotherapy with carbamazepine (CBZ) was administered to the patients. The effectiveness of CBZ treatment was evaluated with regard to efficacy by the decrease in seizures and tolerability by retention rates. Results: SCN1A rs3812718 A/G with CBZ tolerability ( P= 0.038) throughout 24 months of clinical follow-up and the GABRA1 rs2290732 A/G were significantly associated with CBZ tolerability ( P= 0.001). The maintenance dose and serum level of CBZ in AA genotype carriers of rs3812718 A/G were significantly higher than those of GG genotype carriers between 3 and 12 months of follow-up. The proportion of AA genotype carriers of rs2298771 A/G with seizure free was significantly higher than that of AG+GG genotype carriers from 3 months to 15 months of follow-up ( P < 0.05). Conclusion: rs3812718 A/G and rs2290732 A/G polymorphisms affected the tolerability of CBZ. rs2298771 A/G was associated with efficacy of CBZ treatment. [ABSTRACT FROM AUTHOR]

Objective ATP1A2 and ATP1A3 are genes that code for catalytic subunits of Na/K-ATPases, which play important roles in the basal electrophysiological states of nerve cells. The aim of this study was to investigate whether genetic polymorphisms of ATP1A2 and ATP1A3 influence susceptibility to genetic generalized epilepsies (GGEs) and the efficacy of anti-epileptic drugs in a Chinese population. Method Six ATP1A2 tagged single-nucleotide polymorphisms (tagSNPs) and two ATP1A3 tagSNPs were were genotyped by allele-specific MALDI–TOF mass spectrometry in 484 Chinese GGE patients (280 drug-responsive and 204 drug-resistant patients) and 284 healthy controls. Results Significant differences were found in the frequencies of the ATP1A3 rs8107107 C allele and the CC genotype between the GGEs and the healthy controls (11% vs. 15%, odds ratio (OR) = 0.807 (0.68–0.960), p = 0.021 and 0.4% vs. 3.2%, OR = 0.121 (0.026–0.565), p = 0.002, respectively). The frequency of the rs8107107 CT + CC genotype was significantly lower among the GGE patients than among the healthy controls (15% vs. 26.8%, OR = 0.327 (0.248–0.942), p = 0.001). No significant differences in the frequencies of six ATP1A2 tagSNPs or ATP1A2 haplotypes were found between the GGEs and the healthy controls. No tagSNPs were involved in anti-epileptic drug resistance. Conclusion Our findings demonstrated that common variants of ATP1A3 but not ATP1A2 were associated with the susceptibility to GGEs in a Chinese population, which indicates that the ATP1A3 gene plays a significant role in the pathophysiology of genetic generalized epilepsies. [ABSTRACT FROM AUTHOR]