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71.
Li Zhang Ming-Jie Wang Wei Wang Jing-Ya Zhao Jia-Liang Wu Yan-Pu Liu Hong Zhu Jie-Ming Qu Min Zhou 《International journal of cancer. Journal international du cancer》2020,146(1):103-114
Next-generation sequencing of cell-free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer-related genes. As results, log2-based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future. 相似文献
72.
Annemarie E. M. Post Johan Bussink Fred C. G. J. Sweep Paul N. Span 《Oncology research》2020,28(1):33-40
Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that
DNA damage repair or cell cycle genes are involved, and could therefore be targeted to preclude the occurrence
of cross-resistance. We aimed to characterize the observed cross-resistance by investigating gene expression
of DNA damage repair genes and cell cycle genes in estrogen receptor-positive MCF-7 breast cancer cells that
were cultured to tamoxifen resistance. RNA sequencing was performed, and expression of genes characteristic
for several DNA damage repair pathways was investigated, as well as expression of genes involved in different
phases of the cell cycle. The association of differentially expressed genes with outcome after radiotherapy was
assessed in silico in a large breast cancer cohort. None of the DNA damage repair pathways showed differential
gene expression in tamoxifen-resistant cells compared to wild-type cells. Two DNA damage repair genes were
more than two times upregulated (NEIL1 and EME2), and three DNA damage repair genes were more than two
times downregulated (PCNA, BRIP1, and BARD1). However, these were not associated with outcome after
radiotherapy in the TCGA breast cancer cohort. Genes involved in G1, G1/S, G2, and G2/M phases were lower
expressed in tamoxifen-resistant cells compared to wild-type cells. Individual genes that were more than two
times upregulated (MAPK13) or downregulated (E2F2, CKS2, GINS2, PCNA, MCM5, and EIF5A2) were not
associated with response to radiotherapy in the patient cohort investigated. We assessed the expression of DNA
damage repair genes and cell cycle genes in tamoxifen-resistant breast cancer cells. Though several genes in
both pathways were differentially expressed, these could not explain the cross-resistance for irradiation in these
cells, since no association to response to radiotherapy in the TCGA breast cancer cohort was found. 相似文献
73.
BackgroundAs an ongoing worldwide health issue, Coronavirus disease 2019 (COVID–19) has been causing serious complications, including pneumonia, acute respiratory distress syndrome (ARDS), and multi-organ failure. However, there is no decisive treatment approach available for this disorder, which is primarily attributed to the large amount of inflammatory cytokine production. We aimed to identify the effects of Nano-curcumin on the modulation of inflammatory cytokines in COVID-19 patients.MethodForty COVID-19 patients and 40 healthy controls were recruited and evaluated for inflammatory cytokine expression and secretion. Subsequently, COVID-19 patients were divided into two groups: 20 patients receiving Nano-curcumin and 20 patients as the placebo group. The mRNA expression and cytokine secretion levels of IL-1β, IL-6, TNF-α and IL‐18 were assessed by Real‐time PCR and ELISA, respectively.ResultOur primary results indicated that the mRNA expression and cytokine secretion of IL-1β, IL-6, TNF-α, and IL-18 were increased significantly in COVID-19 patients compared with healthy control group. After treatment with Nano-curcumin, a significant decrease in IL-6 expression and secretion in serum and in supernatant (P = 0.0003, 0.0038, and 0.0001, respectively) and IL-1β gene expression and secretion level in serum and supernatant (P = 0.0017, 0.0082, and 0.0041, respectively) was observed. However, IL-18 mRNA expression and TNF-α concentration were not influenced by Nano-curcumin.ConclusionNano-curcumin, as an anti-inflammatory herbal based agent, may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may cause an improvement in clinical manifestation and overall recovery. 相似文献
74.
《Drug metabolism and pharmacokinetics》2020,35(3):321-328
We performed a caffeine (N-3-methyl-13C) breath test (CafeBT) to determine whether it can be employed to identify caffeine metabolism-associated single nucleotide polymorphisms. The study included 130 healthy adults (mean age: 21.9 years). Saliva was collected using an Oragene®•DNA saliva collection kit. Breath samples were collected from the subjects. The subjects orally ingested 100 mg 13C-caffeine dissolved in distilled water. Subsequently, breath samples were collected in bags every 10 min for a total of 90 min. An analysis of 13CO2 in the expired breath was performed by infrared spectroscopy, and the sum of Δ13CO2 over 90 min (S90m) was calculated. DNA from saliva samples was genotyped using TaqMan® SNP Genotyping for the following genes: cytochrome P4501A2: rs762551, rs2472297, aryl-hydrocarbon receptor (rs4410790), and adenosine A2A receptor (rs5751876). All subjects had the genotype CC in rs2472297 alleles. No significant difference was observed in S90m among the genotypes of rs762551 and rs5751876; however, a significant difference was found in S90m among the genotypes of rs4410790 (C > T). Our findings suggest that the N-3 demethylation of caffeine is dependent on the rs4410790 allele and that CafeBT may be used to determine rs4410790 genotypes. 相似文献
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78.
Reham El-hoseny Mustafa Neamatallah Moheiddin Alghobary Adel Zalata Frank Comhaire Shimaa M. El-Beah 《Andrologia》2020,52(7):e13659
Male reproductive impairment is responsible for at least 50% of cases of couple infertility. Nuclear factor-kappa B (NF-κB) has been functionally linked to germ cell apoptosis, which may affect human fertility. The aim of this study was to determine the association between the rs28362491 SNP of the NF-κB1 gene and infertility in Egyptian men. In this case–control study, semen and blood samples of 247 infertile men, constituting the case group, and of 113 fertile healthy men as the control group were analysed. All study participants were genotyped for polymorphism of the NF-κB1 gene (rs28362491) by the polymerase chain reaction—restriction fragment length polymorphism (PCR-RFLP) technique. Heterozygous I/D genotype of the NF-κB1 rs28362491 polymorphism was associated with a significantly lower risk of poor semen quality, including asthenozoospermia, astheno–teratozoospermia, and oligo–astheno–teratozoospermia, when compared to I/I genotype (odds ratio = 0.25, 0.26, 0.18, p < .0005, <.0005, <.0005) respectively. Overall, the presence of the D allele was associated with a significantly decreased risk of poor sperm quality as compared to the I allele (odds ratio = 0.56, 0.64, 0.49, p = .050, .038, .001). In conclusion, these results suggest that heterozygosity of the NF-κB1 gene may play a protecting role against male infertility in Egyptians. 相似文献
79.
80.
背景与目的肺癌脑膜转移病死率极高。循环肿瘤DNA(circulating tumor DNA, ctDNA)已被证实含有肿瘤的基因组改变信息,并已被用于监测肿瘤的进展和对治疗的响应。对于存在脑膜转移瘤的患者,由于血脑屏障等因素的存在,外周血ctDNA不能反映脑部病灶的信息,此时脑脊液ctDNA作为检测样本能更好地体现颅内肿瘤的基因状态,指导临床对颅内病灶的靶向治疗。本研究旨在探究脑脊液ctNDA用于监测非小细胞肺癌(non-small cell lung cancer, NSCLC)脑膜转移的可行性以及脑脊液ctDNA检测对NSCLC脑膜转移的临床价值。方法入组NSCLC脑膜转移患者21例,通过二代基因测序技术对患者的脑脊液及外周血样本进行基因检测,并进行脑脊液细胞学病理学检测和头颅核磁共振增强检查。结果入组21例患者脑脊液中均检测到ctDNA。脑脊液ctDNA检测的灵敏性在脑膜转移诊断方面优于细胞学(P < 0.001)。脑脊液的基因突变检出率及基因突变丰度均高于血浆(P < 0.001)。脑脊液具有独特的基因谱。6例动态检测的患者中,脑脊液中ctDNA丰度变化均同时或早于临床疾病变化出现,可及时揭示耐药机制和监测复发趋势。结论脑脊液ctDNA检出率高于细胞学及影像学;脑脊液ctDNA检测可展现脑膜转移病灶特有的突变图谱;脑脊液ctDNA动态监测对肺癌患者临床疗效具有提示意义。 相似文献