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Screening for mt-DNA mutations in optic neuritis of unknown reason

Purpose To investigate mitochondrial DNA (mt-DNA) mutations in optic neuritis of unknow reason (ONUR) and to assess the pathogenic and differential diagnostic values of screening for mt-DNA mutations in ONUR. Method Thirty patients with ONUR were screened for mt-DNA mutations by using SSCP,mutation-specific primer PCR and sequencing. Results mt-DNA mutations were found in 12 out of the thirty patients.All of the mutations were at 11778 position,but no one at 3460 and 15257. Conclusions Quite a number of patients (12/30,40%) with ONUR were caused actually by mt-DNA mutation．Screening for mt-DNA mutation in these patients has a pathogenic and differential diagnostic significance. (Chin J Ocul Fundus Dis,2000,16:78-79) 

卵黄样黄斑营养不良基因三个新的点突变与散发性Best病表现型关系的分析

奥希替尼治疗肺腺癌双眼脉络膜转移1例

LncRNA MIR223HG regulates ATM expression affecting proliferation, migration and apoptosis of lung adenocarcinoma cells

Objective To investigate the molecular mechanisms by which the long non-coding RNA (lncRNA) MIR223HG affects the proliferation, migration and apoptosis of lung adenocarcinoma cells. MethodsDNA damaging agent Zeocin was used to treat human embryo lung cell (MRC-5) and lung cancer cell (A549 and H1299), and the expression of MIR223HG was tested by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, the ataxia-telangiectasia mutated (ATM) protein and ATM pathway downstream factor Cell cycle checkpoint kinase 2 (Chk2), p53 tumor suppressor protein (p53) in the lung cancer cell (A549 and H1299) with Zeocin were also tested by qRT-PCR. Cell transfection and Transwell migration assay, colony formation assays, apoptosis assays were performed to verify the role of ATM in the expression of MIR223HG in lung adenocarcinoma. ResultsThe expression of MIR223HG was reduced markedly in the lung cancer cells (A549 and H1299) compared with human embryo lung cell (MRC-5) after treated with Zeocin. ATM protein and its downstream factors Chk2, p53 involved in the process, and ATM regulated the expression of MIR223HG in the lung cancer cells with Zeocin. Futhermore, ATM joined in the processes that MIR223HG regulated the lung cancer cells proliferation, migration and apoptosis. Conclusions The expression of MIR223HG is related to the DNA damage response in the lung cancer, and MIR223HG regulates lung cancer cells proliferation, migration and apoptosis by ATM/Chk2/p53 pathway. MIR223HG may be a potential therapeutic target for lung adenocarcinoma treatment.

Research progress on KRAS mutation in pancreatic tumorigenesis and pancreatic cancer therapy

ObjectiveTo summarize the research progress of KRAS mutation in pancreatic tumorigenesis and therapy.MethodThe research progress of KRAS mutation in pancreatic tumorigenesis and therapy were summarized by reading the domestic and international literatures published in recent years.ResultsPancreatic cancer had the title of " king of cancer”. More than 90% of pancreatic cancer patients had KRAS mutation. KRAS had a complex relationship with pancreatic cancer through downstream signaling pathways, including Raf (rapidly accelerated fibrosarcoma)-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK), phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT), and RalGDS-Ral. Although basic research on pancreatic cancer was deepening, there was still a lack of effective molecular targeted drugs.ConclusionsKRASgene plays an important role in the occurrence of pancreatic cancer. The treatment associated with KRAS mutation provides a more effective prognostic possibility for pancreatic cancer patients.

Dynamic investigation on biological and molecular biological characteristics of SO-Rb50cloned cell strains

Objective To compare the differences of chromosome aberration and Rb 1 gene mutation among 3 cloned cells of SO-Rb50 cell line of retinoblastoma. Methods 1.Three cell cloned strains named MC2, MC3, MC4 were isolated from SO-Rb50. 2. Gbanding and karyotype analysis were performed on the llth passage cells of the 3 cell strains.3.All exons and the promoter region of the Rb gene were detected by PCR-SSCP analysis in tumor cell DNA extracted from the 3 cell strains. Results 1.Both numerical and structural chromosomal aberrations could be observed in these 3 cell strains.Several kinds of structural chromosomal aberrations were observed.The chromosome aberrations in the same passage of different cell strains were different.Aberration of chromosome 13 was rare and the aberration feature was different in the 3 cell strains.Five marker chromosomes were identified.M1,t(1;1)qter-p35∷q24-ter could befound in all cell strains.Two of them M4 and M5,have not been reported in SO-Rb50 cell line previously.2.SSCP analysis of exon　24 showed that MC411 and MC3138 had abnormal band. Conclusions The characteristics of heterogeneity of the original tumor cell line SO-Rb50are still kept during a long-term culture in vitro and the cloned strains had dynamic changes during this period.Aberration of chromosome 13 is not the only cause of RB;aberration of chromosome 1,a commom event in some neoplasias as well as in SO-Rb50, plays a meaningful role in the immortalization of this cell line. (Chin J Ocul Fundus Dis, 1999, 15: 146-148)

Primary mutation detection of mitochondrial DNA(mtDNA)in Leber′s hereditary optic neuropathy patients

Optic atrophy,hereditary／diagnosis; Polymerase chain reaction; DNA,mitochondrial; Point　mutation; Sequence analysis

Influence of EGFR co-mutation on efficacy of tyrosine kinase inhibitors in patients with non-small cell lung cancer

Tyrosine kinase inhibitors (TKIs) are the standard of care for non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutation. The efficacy of TKIs and prognosis of EGFR-mutated patients with compound EGFR mutation, oncogene mutation, suppresser gene mutation or other diver gene mutation are worse than those of patients with a single EGFR mutation. This article makes a review of related clinical researches aiming to provide references for clinical scenarios. To sum up, molecular alterations and clinical features should be correlated as accurately and dynamically as possible in the diagnostic and therapeutic process, and combined therapeutic strategies should be chosen flexibly and reasonably to improve patients’ survival and prognosis.

The major types and clinical manifestations of mitochondrial DNA mutations in Chinese patients with Leber′s hereditary optic neuropathy

Objective To investigate the major types and clinical manifestations of mitochondrial DNA (mtDNA)mutations in Chinese patients with Leber′s hereditary optic neuropathy(LHON). Methods A total of 119 patients with bilateral optic neuropathy from 117 pedigrees, including 37 with determinate diagnosis of LHON(group A) and 82 with suspected LHON(group B),were tested for mtDNA mutations by using single-strand conformational polymorphism, mutation-specific primer polymerase chain reaction and sequencing. Pertinent clinical data and history of the patients with the 11778 mutation were collected. Results Nucleotide positions(np)11778 mutation and np 14484 mutation was found in 33 (89.2%) and 3 (8.1%) patients respectively in group A, while np 11778 mutation was obtained in 26（31.7%）in group B. No 3460 mutation was found in group A or B. The clinical manifestations of 59 patients with np 11778 mutation were as follows: acute or chronic visual loss，no ophthalmalgia, the age of onset of 10-25, and either a central or paracentral scotoma in perimetry. The visual recovery rate was 8.6%～11.6%. Conclusion Chinese patients with LHON have a very high incidence of np 11778 mutation and the clinical manifestations of the patients with np 11778 mutation are similar to those of Caucasian patients. (Chin J Ocul Fundus Dis，2004，20：78-80)

Deletion and Mutation of p16/mts1 Gene in Human Gastric Cancer of Different Periods

ObjectiveTo determine the frequency and type of p16 gene homozygous deletion and mutation with the progression of human gastric carcinogenesis.MethodsPCR （polymerase chain reaction），SSCP (single strand conformation polymorphism) and DNA sequencing were performed on 50 operative tissues, which included 7 early gastric cancer and 43 advanced gastric cancer. In this group there were 36 male and 14 female patients aged 35 to 68,which included 30 welldifferetiated adenocarcinoma and 20 poordifferentiated carcinoma; 19 patients with lymph node metastases.ResultsTotal mutation frequency of p16 gene was 8.00%(4/50), including 14.29%(1/7) of early cancer and 7.00%(3/43) of advanced cancer，there was no significant difference between early and advanced cancer （P＞0.05）. In addition, p16 gene mutation was not related to site，location，grade of tumor differentiation and lymph node metastases, respectively. Total deletion frequency of p16 gene was 16.00%(8/50), of which 18.60%(8/43) was detected in advanced cancer, but no cases in early cancers. There was a significant difference between early and advanced cancer （P＜0.05）, and frequency p16 gene homozygous deletion was related to grade of tumor differentiation and lymph node metastases, respectively. Direct DNA sequencing displayed that 4 point mutations detected in 99,125,433,441 base, there were 3 missense mutation and 1 samesense mutation, no deletion or insertion was found. Conclusionp16 gene mutation is an early event in gastric carcinogenesis，it helps early diagnosis of human gastric carcinoma. p16 gene homozygous deletion is a late event in gastric carcinogenesis，it might relate to metastases and recurrence of gastric cancer.