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991.
目的 探讨不同冻存条件下细胞因子诱导的杀伤细胞(CIK)细胞表型的变化及对K562细胞杀伤活性的影响.方法 收集培养12 d的CIK细胞,分别冻存于-80℃冰箱及液氮中,于冻存后4、12、24周复苏,通过流式细胞仪检测CIK细胞表型变化,CCK-8法测定其对K562细胞的杀伤活性,并与未冻存CIK细胞进行比较.结果 液氮冻存4、12、24周及-80℃冻存4周后复苏培养的CIK细胞增殖、细胞存活率、免疫细胞表型及对K562的杀伤活性与未冻存组比较差异无统计学意义(P>0.05).-80℃冻存12周及24后复苏培养的CIK细胞与未冻存组比较,细胞增殖明显抑制,细胞存活率低,CD3+、CD3 +/CD4+、CD3 +/CD8+、CD3 +/CD56+细胞比例显著降低,对K562细胞杀伤活性显著抑制(P<0.05).结论 临床治疗中CIK细胞应尽量冻存于液氮中,如冻存于-80℃时冻存时间应≤4周. 相似文献
992.
Neuromedin U alters bioenergetics and expands the cancer stem cell phenotype in HER2‐positive breast cancer 下载免费PDF全文
Vanesa G. Martinez John Crown Richard K. Porter Lorraine O'Driscoll 《International journal of cancer. Journal international du cancer》2017,140(12):2771-2784
Neuromedin U (NmU) is a neuropeptide belonging to the neuromedin family. Recently, we reported a significant association between NmU and breast cancer, particularly correlating with increased aggressiveness, resistance to HER2‐targeted therapies and overall significantly poorer outcome for patients, although the mechanism through which it exerts this effect remained unexplained. Investigating this, here we found that ectopic over‐expression of NmU in HER2‐positive breast cancer cells induced aberrant metabolism, with increased glycolysis, likely due to enhanced pyruvate dehydrogenase kinase activity. Similar results were observed in HER2‐targeted drug‐resistant cell variants, which we had previously shown to display increased levels of NmU. Overexpression of NmU also resulted in upregulation of epithelial‐mesenchymal transition markers and increased IL‐6 secretion which, together with aberrant metabolism, have all been associated with the cancer stem cell (CSC) phenotype. Flow cytometry experiments confirmed that NmU‐overexpressing and HER2‐targeted drug‐resistant cells showed an increased proportion of cells with CSC phenotype (CD44+/CD24–). Taken together, our results report a new mechanism of action for NmU in HER2‐overexpressing breast cancer that enhances resistance to HER2‐targeted drugs through conferring CSC characteristics and expansion of the CSC phenotype. 相似文献
993.
994.
Microsatellite instability—a useful diagnostic tool to select patients at high risk for hereditary non-polyposis colorectal cancer: a study in different groups of patients with colorectal cancer 总被引:7,自引:0,他引:7 下载免费PDF全文
C Lamberti R Kruse C Ruelfs R Caspari Y Wang M Jungck M Mathiak H Malayeri W Friedl T Sauerbruch P Propping 《Gut》1999,44(6):839-843
BACKGROUND: Clinical diagnosis of hereditary non-polyposis colorectal cancer (HNPCC) is based on a typical family history. As molecular genetic testing is predominantly restricted to these families, gene carriers not meeting the clinical criteria may be missed. AIMS: To examine the value of microsatellite instability (MSI) as a tool to increase the likelihood for uncovering a mismatch repair germline mutation in patients with colorectal cancer and to identify a genotype-phenotype relation in families with verified mutations. METHODS: Systematic search for germline mutations (hMSH2 and hMLH1 genes) was performed in 96 patients: 57 fulfilled the Amsterdam criteria (group 1) and 12 the looser HNPCC criteria (group 2). Seventeen patients showed familial clustering of cancers (group 3) and 10 patients under 50 years had sporadic cancer (group 4), the latter of whom all exhibited MSI+ tumours. RESULTS: A similar proportion of germline mutations was found in patients who fulfilled the clinical criteria of HNPCC and had MSI+ tumours (groups 1 and 2; 15/39) compared with patients who did not meet these clinical criteria but who had MSI+ tumours (groups 3 and 4; 8/27 patients). Affected relatives of patients with hMLH1 mutations showed a significantly higher frequency of colorectal cancer but a lower frequency of endometrium cancer than those with hMSH2 mutations. CONCLUSIONS: MSI in tumour tissue is a useful criterion for selecting patients who should be tested for germline mutations in the mismatch repair genes hMSH2 and hMLH1 irrespective of their family history. Among carriers of hMSH2 mutations the tumour spectrum was broader than among carriers of hMLH1 mutations. 相似文献
995.
Alper SARI Erdal BODAK Berkan ARMAAN Hasan SATI Nuh ATA Nazife Sule YAAR BLGE Reyhan BLC SALMAN Gzde Kübra YARDIMCI Hakan BABAOLU Levent KILI Mehmet Akif
ZTÜRK eminur HAZNEDAROLU Berna G
KER Umut KALYONCU Timuin KAFOLU Abdurrahman TUFAN 《Turkish Journal of Medical Sciences》2021,51(4):1695
Background/aimFamilial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia.Materials and methodsAll patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively.ResultsAmong 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively).ConclusionOur findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant. 相似文献
996.
Shujia Chen Xiaofei Li Jiachen Zhang Li Li Xueqiu Wang Yinghui Zhu Lianyi Guo Jiwei Wang 《Journal of gastrointestinal oncology.》2021,12(5):2157
BackgroundColon adenocarcinoma (COAD) is one of the most common malignancies worldwide. Genomic instability is one of the hallmarks of colon cancer and is associated with prognosis. Nevertheless, the impact of genome instability-associated long non-coding RNAs (lncRNAs) along with their clinical significance in cancers has remained mostly unexplored.MethodsIn this study, a mutator hypothesis-derived computational frame integrating the somatic mutation profiles and lncRNA expression profiles in a tumor genome was developed, which enabled the identification of 137 novel genomic instability-associated lncRNAs in colon cancer. Subsequently, a genome instability-derived lncRNA signature (GILncSig) segregated the patients into low- and high-risk groups with prominent differences in outcomes.ResultsCombined with the overall survival data, we established 6 six lncRNA-based signature to predict prognosis, which were LINC00896, AC007996.1, NKILA, , MIRLET7BHG, and AC009237.14. We found that the expression level of PD-L1 (CD274) and somatic mutations in the high-risk group were higher than those in the low-risk group. This suggests that high-risk patients may be sensitive to immunotherapy. We further found that the prognosis of patients in the high-risk group was significantly lower than that of patients in the low-risk group, and that patients’ prognosis was likely to be worse as the patient’s risk score increased.ConclusionsIn conclusion, this study explores the role of lncRNAs in genomic instability and cancer prognosis and provides a new idea for the prognostic prediction of colon cancer. AP003555.2相似文献
997.
Kenichi Miyata Yoshinori Imai Satoshi Hori Mika Nishio Tze Mun Loo Ryo Okada Liying Yang Tomoyoshi Nakadai Reo Maruyama Risa Fujii Koji Ueda Li Jiang Hao Zheng Shinya Toyokuni Toyonori Sakata Katsuhiko Shirahige Ryosuke Kojima Mizuho Nakayama Masanobu Oshima Satoshi Nagayama Hiroyuki Seimiya Toru Hirota Hideyuki Saya Eiji Hara Akiko Takahashi 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(35)
998.
Allison M. Brennan Richard M. Pauli 《American journal of medical genetics. Part A》2001,100(4):292-310
Hajdu‐Cheney syndrome is a rare, autosomal dominant disorder comprising acroosteolysis of the distal phalanges with associated digital abnormalities, distinctive craniofacial and skull changes, dental anomalies, and proportionate short stature. The clinical and radiologic characteristics of Hajdu‐Cheney syndrome develop and progress with age. Many of the medical problems that arise in this syndrome cluster in specific age ranges. Case reports of six affected individuals in two additional families and a summary of the English literature is presented with emphasis on the changing physical findings and medical sequelae over time. © 2001 Wiley‐Liss, Inc. 相似文献
999.
1000.
目的 建立子宫结合带干细胞(uJZSCs)的分离培养及鉴定方法.方法 将手术中无菌取得的子宫内肌层即子宫结合带用胰酶和胶原酶Ⅰ进行消化、培养、扩增.采用倒置显微镜观察细胞形态,流式细胞仪进行表型分析及存活率判断,CCK-8法判断其生长特性,并在体外诱导其成脂、成骨、成软骨分化.结果 所获细胞传代后能迅速贴壁,呈长梭形;流式细胞仪检测结果显示,表面标志物CD90、CD73、CD105、CD29、CD44、CD13、CD166、HLA-ABC呈阳性表达,而CD34、CD45、CD14、HLA-DR、CD19呈阴性表达.CCK-8生长曲线呈S形.诱导分化实验结果显不,uJZSCs具有成脂、成骨和成软骨的分化能力.结论 uJZSCs具有很强的增殖扩增能力,可作为间充质干细胞的来源. 相似文献