In Vitro Anti-tumor Immune Response Induced by Dendritic Cells Transfected with Recombinant Adenovirus Carrying Mutant K-ras Genes

Summary： The specific anti-tumor immune response induced by mouse bone marrow dendritic cells （DCs） lransfected with recombinant adenovirus carrying mutant k-ras genes was investighted. DCs were generated from mouse bone marrow in the presence of rmGM-CSF （3.3 ng/mL） and rmIL-4 （1.3 ng/mL） and detected by FACS, and then transfecled with the recombinant adenovirus encoding mutant k ras gene. The efficacy of transfection and T cell stimulating activity of DCs were detected. CTL activity of the mice vaccinated with DCs was observed. The resuhs showed thai DCs had dendritic veiled morphology. BmDCs highly expressed B7-1（80%）, B7-2（77%）, MHC Ⅱ （70%）, CDllc （65%）, CD40 （70%） and CD54 （96%） with FACS, and no significant difference in the expression was observed before and after the transfection （P〈0.05）. The DCs transfeeled by mutant k-ras gene could significantly stimulate lymphoeytes proliferation as compared with those transfeeted by Ad e or non-modified DCs （P〈0.05）. DC vaccine transfected by mutant k-ras gene could induce CTL activity against Lewis lung cancer, but not against B16. The specific eytotoxicity against Lewis lung cancer in Ad-k-ras/12-transdueed DC group was signifieantly higher than those in the control, vector and non transfeeted DCs groups （P〈0.05）. It was concluded that special antitumor response could be induced by DCs transfected with recombinant adenovirus carrying mutant k-ras genes.

APC and K-ras gene mutation in aberrant crypt foci of human colon

AIM To study the genetic alteration in ACF andto define the possibility that ACF may be a veryearly morphological lesion with molecularchanges, and to explore the relationshipbetween ACF and colorectal adenoma evencarcinoma.METHODS DNA from 35 CRC, 15 adenomas, 34ACF and 10 normal mucus was isolated by meansof microdissection. Direct gene sequencing of K-ras gene including codon 12, 13 and 61 as well asthe mutation cluster region (MCR) of APC genewas performed.RESULTS K-ras gene mutation frequency inACF, adenoma and carcinoma was 17.6% (6/34), 13.3% (2/ 15), and 14.3% (5/ 35)respectively, showing no difference ( P > 0.05)in K-fas gene mutation among three pathologicprocedures. The K-ras gene mutation inadenoma, carcinoma and 4 ACF restricted incodon 12 (GGT→GAT), but the other 2 mutationsfrom ACF located in codon 13 (GGC→GAC). K-res gene mutation was found more frequently inolder patients and patients with polypoidcancer. No mutation in codon 61 was found in thethree tissue types. Mutation rate of APO gene inadenoma and carcinoma was 22.9% (8/35) and26.7% (4/ 15), which was higher than ACF(2.9%) (P < 0.05). APC gene mutation incarcinoma was not correlated with age ofpatients, location, size and differentiation oftumor.CONCLUSION ACF might be a very earlymorphological lesion in the tumorogenesis ofcolorectal tumor. The morphological feature andgene mutation status was different in ACF andadenoma. ACF is possibly putative'microadenoma' that might be the precursor ofadenoma. In addition, the development of asubgroup of colorectal carcinomas mightundergo a way of 'normal epithelium→ ACF→carcinomas'.

Detection of k-ras gene point mutation in fine needle aspiration and pancreatic juice by sequence special primer method and its clinical significance

INTRODUCTIONThe point mutation rate of k-ras gene at codon 12 inpancreatic adenocarcinoma is reported to be as highas 90%,and with no mutations in normalpancreas tissues or other pancreatic disorders.Wehave detected the presence of k-ras gene

K-ras gene mutation in the diagnosis of ultrasound guided fine-needle biopsy of pancreatic masses

AIM: To investigate the utility of K-ras mutation analysis ofultrasound guided fine-needle aspirate biopsy of pancreaticmasses.METHODS: Sixty-six ultrasound guided fine-needle biopsieswere evaluated by cytology, histology and k-ras mutation.The mutation at codon 12 of the k-ras oncogene wasdetected by artificial restriction fragment lengthpolymorphisms using Bst NI approach.RESULTS: The presence of malignant cells was reported in40 of 54 pancreatic carcinomas and K-ras mutations weredetected in 45 of the 54 FNABs of pancreatic carcinomas. Thesensitivity of cytology and k-ras mutation were 74 % and 83%, respectively. The speciality of cytology and k-ras mutationwere both 100 %. The sensitivity and speciality of k-ras mutationcombined with cytology were 83 % and 100 %, respectively.CONCLUSION: High diagnostic accuracy with acceptablediscomfort of FNAB make it useful in diagnosis of pancreaticcarcinoma. Ultrasound guided fine-needle biopsy is a safeand feasible method for diagnosing pancreatic cancer.Pancreatic carcinoma has the highest K-ras mutation rateamong all solid tumors. The mutation rate of k-ras is about80-100 %. The usage of mutation of codon 12 of k-rasoncogene combined with cytology is a good alternative forevaluation of pancreatic masses.

Detection of K-ras gene mutation in fecal samples from elderly large intestinal cancer patients and its diagnostic significance

AIM:To study the diagnostic significance of K-ras gene mutations in fecal samples from elderly patients with large intestinal cancer.METHODS: DNA was extracted in the fecal and tissue samples from 23 large intestinal cancer patients, 20 colonic adenomatoid polypus patients and 20 healthy subjects. The K-ras gene mutations at the first and second bases of codon 12 were detected by the allele specific mismatch method.RESULTS: The K-ras gene mutation was 56.52%(13/23) in the large intestinal cancer patients, which was notably higher than that in the normal subjects whose K-ras gene mutation was 5%(1/20) (x^2=12.93, P<0.001). There was no significant difference in comparison with that of colonic adenomatoid polypus patients whose K-ras gene mutation was 30%(6/12)(x^2=3.05, P>0.05). The K-ras gene mutation at the second base of codon 12 was 92.13%(12/13) in the large intestinal cancer patients. There was no significant difference between the detection rate of K-ras gene mutation in the fecal and tissue samples (X^2=9.35, P<0.01).CONCLUSION:Our results indicate that detection of the K-ras gene mutations in fecal samples provides a non-invasive diagnostic method for the elderly large intestinal cancer patients. Its significance in the early diagnosis of large intestinal cancer awaits further studies.

Detection of K-ras gene mutation at codon 12 by pancreatic duct brushing for pancreatic cancer

OBJECTIVE: To assess the diagnostic value of endoscopic pancreatic duct brushing in detecting mutation of the K-ras gene at codon 12 in cytologic specimens from patients with pancreatic cancer. METHODS: Thirty-five patients treated at Changhai Hospital, Shanghai between 1999 and 2001 were enrolled. Their cells obtained by pancreatic duct brushing during endoscopic retrograde tholangiopancreatography (ERCP) were suspended with phosphate buffer solution (PBS). DNA of the cells was extracted and mutation of the K-ras gene at codon 12 detected by means of PCR-SSCP. RESULTS: The K-ras gene mutation rate of pancreatic cancer was 70%, which was higher than that of chronic pancreatitis (14%, P<0.05). K-ras gene mutation was not found in patients with pancreatic cystorcarcinoma and duodenum carcinoma. As to the location of pancreatic cancer, no significant difference was observed between the head, the body and tail. The sensitivity, specificity, accuracy of pancreatic duct brushing in detecting pancreatic cancer was 70%, 94%, and 83%, respectively. CONCLUSION: K-ras analysis of pancreatic brushing samples is helpful in the diagnosis of patients with early pancreatic cancer.

Study of mutations of p53, APC and K-ras genes in 47 cases of intestinalmetaplasia of gastric mucosa

Objective:To study the role of the mutations of p53, APC and K-ras genes in 47 cases of 3 types of intestinal metaplasia (IM) of gastric mucosa. Methods:In 47 cases of IM, exons 5- 8 of p53 and exons 15 of APC were examined with PCR-SSCP and codon 12 of K-ras with PCR-RFLP to detect the existence of any mutations of these structures. Results:Muta- tions of p53, APC and K-ras were found in 29.8% (14/47),6.4% (3/47) and 6.4% (3/47) respectively in our series of patients who consisted of 33 with types I and II and 14 with type III of IM. The mutation rate of p53 was far higher in patients with type III IM (57.1%,8/14) than in those with types I and II IM(18.2%,6/33)(P <0.05). Though the mutation rate of APC and K-ras was also higher in the patients with type III IM than in those with types I and II IM, it was of no statistical significance (P >0.05). In one case of type III IM, mutation of both p53 and K-ras was found. Conclusion: The molecular changes of 3 types of IM are different. The mutation of p53 may be closely related to carcinogenesis in cases of type III IM and it serve as a sign for the early diagnosis of gastric carcinoma.

INHIBITION OF ACTIVATED K-RAS GENE BY SIRNA EXPRESSION CASSETTES IN HUMAN PANCREATIC CARCINOMA CELL LINE MIAPACA-2

Objective: To construct the small interfering RNA(siRNA) expression cassettes (SECs) targeting activated K-ras gene sequence and investigate the effects of SECs on K-ras gene in human pancreatic cancer cell line MIAPaCa-2. Methods: Three different sites of SECs were constructed by PCR. The K1/siRNA, K2/siRNA and K3/siRNA were located at the site 194, 491 and 327, respectively. They were transfected into MiaPaCa-2 cells by liposome to inhibit the expression of activated K-ras. In the interfering groups of site 194,491, we observed the cytopathic effect of confluent MiaPaCa-2 cells after they were incubated for 48 hours, and detected the apoptosis in cells by FACS, then we tested the alternation of K-ras gene in confluent MiaPaCa-2 cells by RT-PCR,immunofluorescence and western blot, respectively. Results: Introductions of the K1/siRNA and K2/siRNA against K-ras into MiaPaCa-2 cells led to cytopathic effect, slower proliferation and increased apoptosis, while the appearances of control MiaPaCa-2 cells remained well. The number of apoptotic cells increased compared with control cells. RT-PCR,immunofluorescence and western blot showed the effects of inhibited expression of activated K-ras gene by RNA interference in the K1/siRNA and K2/siRNA groups. We also found that the introduction of K3/siRNA had no effect on MiaPaCa-2 cells. Conclusion: K1/siRNA and K2/siRNA can inhibit the expression of activated K-ras and decrease the growth of MiaPaCa-2 cells, while K3/siRNA has no such effect, demonstrating that the suppression of tumor growth by siRNA is sequence-specific. We conclude that K-ras is involved in maintenance of tumor growth of human pancreatic cancer, and SECs against K-ras expression may be a powerful tool to be used therapeutically against human pancreatic cancer.

Rapid Detection ofK-ras Gene Point Mutation at Codon 12 by PCR-SSPin Pancreatic Adenocarcinom a

To evaluate the feasibility and clinical significance of the PCR SSP technique in detecting K ras gene mutation at codon 12 in pancreatic adenocarcinoma tissues. 80 specimens of surgical resection or biopsy samples were tested at our hospital from January 1994 to September 1995. Three different special sequence primers (SSP) synthesized according to mutation styles of CGT, GTT, GAT were respectively prepared. Three amplification reactions were performed for each sample. The amplification products were analyzed by conventional polyacrylamide gel electrophoresis, stained with ethidium bromide and observed under UV transillumination. Results: All of the 34 pancreatic adenocarcinoma samples had positive PCR results with the mutation rate 100%. 7 cases were CGT mutation, 18 GGT and 17 GAT mutation, in which 2 types of mutation existed in 8 cases. No mutation appeared in 13 normal pancreatic tissues, 6 insulinomas, 6 chronic pancreatitis, 5 benign pancreatic cysts, 7 bile duct carcinoma, 5 ampulla carcinoma and 4 carcinomas of duodenal papilla. Conclusion: Pancreatic adenocarcinoma is one of the commonly encounted tumors and is still very difficult to diagnose at the early stage and to distinguish from other lesions preoperatively. Our study indicates that PCR SSP is an ideal assay in comparison with other methods to detect K ras gene mutation. It is simple, rapid, specific, sensitive and easily generalized for clinical application on preoperative diagnosis.

Detection of K-ras Gene Point Mutation＇s Style in Human Pancreatic Cancer Cell Line PANC-1 by PCR-SSP

客观：在人的胰腺的癌症房间线 PANC-1 检测 K 地岬基因点变化的风格；确定地岬目标位置的 bp 顺序由 RNA 介入了。方法：为关于变化式样的聚合酶链反应(PCR ) 的三种特殊顺序教材(SSP )(GAT，法国总工会；GGT ) 在 12 K 地岬上的鳕鱼被用来学习人的胰腺的癌症房间线 PANC-1。扩大产品与 polyacrylamine 胶化电气泳动被学习检测点变化的风格。结果：在 12 上的鳕鱼的 K 地岬基因点变化的风格是在人的胰腺的癌症房间线的 GAT。结论：PCR-SSP 是快速的，方便；高特定。结果为胰腺的癌症由 RNA 干扰为进一步的基因治疗提供一个基础。

ERCC1、K-ras、TP-73在替雷利珠单抗联合TP化疗方案治疗非小细胞肺癌中的评估价值

目的研究探讨核苷酸切除修复交叉互补基因1(ERCC1)、Kirsten-Rous肉瘤病毒蛋白(K-ras)、肿瘤蛋白P73(TP73)在替雷利珠单抗结合紫杉醇+顺铂(TP)化疗方案治疗NSCLC中的评估价值。方法选取2020年1月至2021年12月本院收治的126例NSCLC肺癌患者为研究对象,按随机抽签法分为对照组、观察组,各63例。对照组以TP化疗方案治疗,观察组增加替雷利珠单抗治疗。评估组间临床疗效、肿瘤标记蛋白、免疫指标、生存周期、不良反应。结果观察组患者的客观缓解率为69.84%(44/63)高于对照组患者为52.38%(33/63),观察组疾病控制率为82.54%(52/63),高于对照组患者为66.67%(42/63)(P<0.05)。化疗1周期、化疗3周期、化疗6周期时,观察组ERCC1、K-ras、TP-73水平均低于对照组(P<0.05)。治疗后观察组免疫功能补体C3、补体C4、CD40细胞低于对照组,NK细胞高于对照组(P<0.05)。观察组患者的TTP、PFS、总生存期均高于对照组(P<0.05)。观察组不良反应发生率为19.05%(12/63),对照组为12.70%(8/63),组间比较差异无统计学意义(P>0.05)。结论替雷利珠单抗联合TP化疗方案治疗肺癌有良好的治疗效果,能够改善患者免疫功能,延长患者生存周期,治疗安全性较好,且ERCC1、K-ras、TP-73水平变化可反映替雷利珠单抗联合TP化疗方案在肺癌治疗中的效果,在综合疗效评估中有较高的应用价值。

K-ras基因突变与胃癌组织病理特征及预后的相关性分析

目的 探讨与分析K-ras基因突变与胃癌组织病理特征及预后的相关性。方法 选取100例胃癌患者作为胃癌组,选择同期在本院体检的健康人群100例作为对照组,检测所有对象的外周血K-ras基因突变情况。调查胃癌患者的组织病理特征,随访患者的预后并进行相关性分析。结果 胃癌组的K-ras基因突变率显著高于对照组,差异有统计学意义(P<0.05)。在胃癌组中,不同胃癌组织病理特征(病灶直径、组织学分化、临床分期、淋巴结转移)患者的K-ras基因突变率对比差异均有统计学意义(P<0.05)。胃癌患者平均随访时间(35.59±1.19)月,其中死亡18例,死亡患者的K-ras基因突变率显著高于生存患者,差异有统计学意义(P<0.05)。在胃癌组中,Spearman分析显示K-ras基因突变率与病灶直径、组织学分化、临床分期、淋巴结转移、预后死亡等存在正相关性(P<0.05)。结论 胃癌患者多伴随有血清K-ras基因突变,与患者的临床病理特征与预后死亡存在相关性,K-ras基因突变具有重要的临床应用价值。

K-Ras、BRAF、PIK3CA基因突变与直肠癌新辅助放化疗疗效及预后的关系

目的:探讨K-Ras、BRAF、PIK3CA基因突变与直肠癌新辅助放化疗(nCRT)疗效及预后的关系。方法:选取2015年03月至2020年03月于医院接受nCRT并行根治手术的直肠癌患者182例作为研究对象。所有患者术前接受卡培他滨化疗,同时采用长程分割疗法进行放疗,共治疗5周,nCRT结束后5~12周,根据肿瘤位置及nCRT情况行手术治疗,出院后进行为期1年的随访。以肿瘤退缩分级(TRG)评价直肠癌nCRT疗效,TRG 1-3级纳入nCRT有效组,TRG 4-5级纳入nCRT无效组。nCRT前经肠镜取肿瘤组织,检测K-Ras、BRAF、PIK3CA基因突变状态,分析K-Ras、BRAF、PIK3CA基因突变与直肠癌nCRT疗效及预后的关系。结果:在182例直肠癌患者中,K-Ras、BRAF、PIK3CA基因突变率分别为34.07%、6.59%、13.19%,nCRT治疗有效率为60.44%。nCRT有效组K-Ras、BRAF及PIK3CA基因突变率显著低于nCRT无效组(P<0.05)。K-Ras、BRAF、PIK3CA基因突变状态预测直肠癌nCRT疗效的敏感度分别为68.45%、65.38%、57.76%,特异度分别为72.39%、69.23%、63.12%,AUC分别为0.626、0.573、0.532。Logistic回归分析结果显示K-Ras、BRAF、PIK3CA基因突变与直肠癌nCRT疗效显著相关(P<0.05)。K-Ras、BRAF、PIK3CA基因突变患者平均生存时间均分别短于K-Ras、BRAF、PIK3CA无突变者,差异有统计学意义(P<0.05)。多变量COX回归分析结果显示K-Ras、BRAF及PIK3CA基因突变患者死亡风险分别是K-Ras、BRAF、PIK3CA无突变者的1.639倍、1.811倍、1.432倍(P<0.05)。结论:K-Ras、BRAF、PIK3CA基因突变与直肠癌患者nCRT疗效和预后相关,可作为nCRT疗效和预后的预测指标。

1889例结直肠癌MSI、K-ras、N-ras和B-raf基因状态以及临床病理特征分析

目的通过对1889例结直肠癌微卫星不稳定(MSI)、K-ras、N-ras和B-raf基因检测,分析其基因状态与临床病理特征之间的关联性。方法收集东部战区总医院病理科结直肠癌患者手术切除大标本共计1889例,通过PCR荧光法联合毛细管电泳法对1889例结直肠癌进行MSI、K-ras、N-ras和B-raf检测,分析其基因状态与临床病理特征之间的关系,以及MSI与K-ras、N-ras和B-raf之间的关联性分析,并且对MSI自身位点的相关性分析。结果1889例结直肠癌患者中,微卫星高度不稳定(MSI-H)更易发生于右侧结肠(16.4%)、黏液腺癌(14.9%)、分化程度较低(18.7%)、年龄偏低(8.3%)、淋巴结未转移(9.1%)以及B-raf突变(5.2%)的患者中,K-ras突变更易发生于右侧结肠(50.7%)、黏液腺癌(50.7%)、分化程度较高(52.1%)、微卫星低度不稳定或稳定型(42.2%)的患者中,而B-raf突变更易发生在MSI-H(6.9%)的患者中,而N-ras基因则与临床病特征关联性不强。结论结直肠癌患者的MSI、K-ras和B-raf基因状态与临床病理特征存在着高度的关联性,因此通过分析其基因状态与临床病理特征之间的关系可以为临床靶向治疗以及预后提供更加可靠的依据。

曲美替尼对K-ras突变直肠癌细胞恶性行为、耐药蛋白及巨噬细胞极化的作用机制的研究

目的探讨曲美替尼对K-ras突变直肠癌细胞恶性行为、耐药蛋白及巨噬细胞极化的作用机制。方法取K-ras突变直肠癌细胞HCT116,将其随机分为HCT116组(HC组)、西妥昔单抗+HCT116组(CE组)、低剂量曲美替尼+HCT116组(LT组)、中剂量曲美替尼+HCT116组(MT组)、高剂量曲美替尼+HCT116组(HT组),Transwell实验及划痕实验检测细胞恶性行为,MTT法检测药物敏感性,RT-PCR法检测耐药蛋白表达,免疫印迹法检测巨噬细胞极化相关指标。结果与HC组相比,其余四组细胞侵袭、迁移及GST-π、P-gp、TopoⅡ、CD163表达显著降低(P<0.05),CD40蛋白表达显著升高(P<0.05);与LT组相比,MT组、HT组细胞侵袭、迁移及GST-π、P-gp、TopoⅡ、CD163表达显著降低(P<0.05),CD40蛋白表达显著升高(P<0.05),且HT组比MT组变化明显(P<0.05);HCT116细胞对西妥昔单抗与曲美替尼均敏感,但与西妥昔单抗相比,曲美替尼的IC_(50)明显更低(P<0.05)。结论曲美替尼对K-ras突变直肠癌细胞具有显著疗效,可显著改善其恶性行为,抑制耐药蛋白表达,抑制巨噬细胞M2极化。

Values of mutations of K-ras oncogene at codon 12 in detection of pancreatic cancer:15-year experience

AIM:To summarize progress in the study of K-ras gene studies in pancreatic cancer and its potential clinical significance in screening test for early detection of pancreatic cancer,and to differentiate pancreatic cancer from chronic pancreatitis in recent decade.METHODS:Literature search (MEDLINE 1986-2003) was performed using the key words K-ras gene, pancreatic cancer, chronic pancreatitis, and diagnosis. Two kind of opposite points of view on the significance of K-ras gene in detection early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis were investigated.The presence of a K-ras gene mutation at codon 12 has been seen in 75-100% of pancreatic cancers, and is not rare in patients with chronic pancreatitis, and represents an increased risk of developing pancreatic cancer. However,the significance of the detection of this mutation in specimens obtained by needle aspiration from pure pancreatic juice and from stools for its utilization for the detection of early pancreatic cancer, and differentiation pancreatic cancer from chronic pancreatitis remains controversial.CONCLUSION:The value of K-ras gene mutation for the detection of early pancreatic cancer and differentiation pancreatic cancer from chronic pancreatitis remains uncertains in clinical pratice. Nevertheless, K-ras mutation screening may increase the sensitivity of FNA and ERP cytology and may be useful in identifying pancreatitis patients at high risk for developing cancer, and as a adjunct with cytology to differentiate pancreatic cancer from chronic pancreatitis.

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Noncoding RNAs instruct the Cas9 nuclease to site speifillyl cleave DNA in the CRISPR/Cas9 system.Despite the high incidence of hepatocellular carcinoma(HCC),the patient's outcome is poor.As a result of the emergence of therapeutic resistance in HCC patients,dlinicians have faced difficulties in treating such tumor.In addition,CRISPR/Cas9 screens were used to identify genes that improve the dlinical response of HCC patients.It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer,with a particular emphasis on HCC as part of the current state of knowledge.Thus,in order to locate recent developments in oncology research,we examined both the Scopus database and the PubMed database.The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs.Drug resistance can be overcome with the help of the CRISPR/Cas9 system.HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening although this method is not without limitations.It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy.CRISPR and its applications to tumor research,particularly in HCC,are examined in this study through a review of the literature.

Wilm′s tumor gene1肽疫苗Galinpepimut-S在肿瘤免疫治疗中的应用

目的为Wilm′s tumor gene1(WT1)肽疫苗Galinpepimut-S(GPS)用于肿瘤免疫治疗的后续研究提供参考。方法采用计算机检索中国知网、PubMed等数据库自建库起至2022年12月的肿瘤免疫治疗相关文献,总结GPS在肿瘤免疫治疗中的应用现状。结果GPS能激发自身免疫系统,对WT1抗原产生强烈免疫反应而发挥抗肿瘤作用,在卵巢癌、恶性胸膜间皮瘤、急性髓系白血病、多发性骨髓瘤的治疗中均显示出较好的疗效。结论以GPS为代表的肿瘤疫苗是未来肿瘤治疗的重要方向,需进一步进行临床研究,以获取更多数据。

AMME chromosomal region gene 1基因变异矮小相关综合征一例及文献复习

目的探讨1例身材矮小、面中部发育不全患儿的病因,以提高临床医师对特殊矮小综合征的认识。方法收集1例身材矮小、面中部发育不全患儿的临床资料,对患儿及父母行基因检测,并给予患儿常规治疗、随访。结果结合患儿特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征,结合文献复习总结AMMECR1基因变异矮小相关综合征特点。结论AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,临床主要表现为身材矮小、运动语言落后、肌张力减低、听力损失、面中部发育不全,部分存在心脏改变、腭裂、骨骼改变及椭圆形红细胞增多症、智力落后和肾钙质沉着症。该文报道1例AMMECR1基因新变异引起身材矮小、面中部发育不全患儿的病例资料,结合特殊面容及基因检测,诊断为AMMECR1基因变异矮小相关综合征。AMMECR1基因变异矮小相关综合征是一种罕见的X连锁遗传性疾病,本文初步概括其特点,并结合文献进行分析,以提高临床医师对AMMECR1基因变异矮小相关综合征的诊治。

Genetic and epigenetic targets of natural dietary compounds as anti-Alzheimer's agents

Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.