TFF1在胃肠道肿瘤中的研究

TFF1（三叶因子1）是一种具有特定三叶结构域的胃肠道激素,它在肿瘤发生发展中发挥重要作用,但其具体机制尚不清楚。近来研究表明它干扰关键的生物学过程：如细胞增殖、分化、凋亡和血管生成。TFF1的功能及其参与的信号转导途径的研究也已取得了显著进展。本文对TFF1在胃肠道肿瘤中的研究归纳如下。     

肿瘤生物标志物的临床应用

本文介绍了一些肿瘤生物标志物有一些可用于有症状的肿瘤患者检测的标志，大部分标志物对癌症患者的监控有价值。由于有抗肿瘤生物标志物的抗体，在肿瘤的治疗或定位中可用这些标志作为靶目标，有助于肿瘤诊断，治疗及预后的判断。     

胃泌素及其受体拮抗剂对人胃癌细胞株MKN45增殖及TFF1、TFF3表达的影响

探讨17肽胃泌素（Gas-17）及其受体拮抗剂对人胃癌细胞株MKN45增殖及三叶因子1（TTF1）、三叶因子3（TFF3）表达的影响,并分析TTF1、TFF3在胃癌病变过程中的作用。方法 培养人胃癌细胞株MKN45后按药物干预分组：第1组：17肽胃泌素组,培养液中Gas-17终浓度为1~1000 nmo1/L;第2组：丙谷胺（PGL）组,培养液中PGL终浓度为0.1~10 mmol/L;第3组：17肽胃泌素+丙谷胺组（联合用药组）,培养液中Gas-17终浓度为100 nmo1/L 、PGL终浓度为1~10 mmol/L;以不加药培养液为对照组。采用四甲基偶氮唑盐（MTT）比色法观察各组细胞增殖活力。蛋白免疫印迹法(Western blot)测定17肽胃泌素组（培养液中Gas-17终浓度为1~100 nmo1/L）,丙谷胺组（PGL终浓度为10mmol/L）,联合用药组（Gas-17终浓度为100 nmo1/L、PGL终浓度为10 mmol/L）及不加药对照组中TFF1和TFF3蛋白的表达变化。结果 MTT结果显示：Gas-17在1~1000 nmo1/L时具有明显的促MKN45细胞增殖作用（P<0.05）;PGL在1~10 mmol/L时有显著的抑制MKN45细胞增殖作用(P<0.05);Gas-17+PGL组中,PGL（1~10 mmol/L）能阻断并抑制Gas-17对胃癌细胞MKN45的促增殖作用（P<0.05）。Western blot结果显示：在Gas-17组中TFF1蛋白表达减弱（P<0.05）,而TFF3蛋白表达增强（P<0.05）;PGL组中TFF1蛋白表达增强而TFF3蛋白表达减弱;Gas-17+PGL组中,PGL能阻断Gas-17诱导的TFF1蛋白表达下调（P<0.05）,阻断Gas-17诱导的TFF3蛋白表达上调（P<0.05）。结论 Gas-17可诱导人胃癌细胞MKN45增殖,其受体抑制剂PGL能阻断并抑制这一作用。胃癌细胞株MKN45中有TFF1和TTF3蛋白的表达,Gas-17促进TFF1蛋白表达下调,而促进TFF3蛋白表达上调,这可能是胃泌素诱导胃癌发生发展的的机制之一。     

hSTC-1作为肿瘤标志物的研究

斯钙素(stanniocalcin,STC)是一种首先在硬骨鱼中发现的糖蛋白激素,该激素由鱼类独有的内分泌腺斯坦尼氏小体所分泌。近年来发现人和其它哺乳动物也存在STC,有STC-1和STC-2两种。有研究探讨了hSTC-1作为肿瘤标志物的可行性,本文主要就hSTC-1作为肿瘤标志物的研究作一综述。     

hSTC-1作为肿瘤标志物的研究

斯钙素（stanniocalcin,STC）是一种首先在硬骨鱼中发现的糖蛋白激素,该激素由鱼类独有的内分泌腺斯坦尼氏小体所分泌。近年来发现人和其它哺乳动物也存在STC,有STC-1和STC-2两种。有研究探讨了hSTC-1作为肿瘤标志物的可行性,本文主要就hSTC-1作为肿瘤标志物的研究作一综述。     

食管癌疗效相关肿瘤生物标志物的研究进展

食管癌的传统治疗已进入平台期,基于生物标志物检测的个体化治疗逐渐成为一种趋势.全文就食管癌各种标志物(包括化疗药物相关标志物以及靶向药物相关标志物)的研究进展作一综述,初步介绍这些标志物的表达或突变对药物治疗疗效的影响.     

eIF3各亚基和肿瘤相关性的研究进展

摘 要：真核细胞起始因子3（eukaryotic translation initiation factor 3,eIF3）是相对分子量最大和最复杂的一个真核细胞翻译起始因子。eIF3在真核细胞翻译起始进程中起着核心作用。最近的国内外研究也发现,eIF3的多个亚基在各种肿瘤中的表达有增高或降低等异常现象,从相关研究来看,eIF3的多个亚基与肿瘤的发生、进展、预后是密切相关的。文章主要对eIF3各亚基和肿瘤相关性研究进行综述。     

2023年度肿瘤蛋白生物标志物研究进展盘点

抗肿瘤治疗已进入靶向治疗和免疫治疗的精准治疗时代,这对指导抗肿瘤治疗和监测肿瘤治疗反应的生物标志物提出了更高的要求。本文对2023年取得较大进展的肿瘤蛋白生物标志物进行盘点,按照蛋白的细胞内定位进行综述,同时提出本领域仍面临的挑战和未来探索的方向,以供进一步研究及实践借鉴。     

microRNA作为电离辐射生物标志物的研究现状

为了更好地应对辐射突发事件,寻找快速、简便、适合大范围人群应用的新型分子水平生物标志物成为目前电离辐射研究的热点。微小RNA(microRNA,miRNA)是一类长度为21～23个核苷酸的单链非编码小RNA,通过与mRNA的3'UTR结合而介导翻译水平的调控,也可通过mRNA翻译区结合而直接引起mRNA的切割。越来越多的证据表明,microRNA与氧化应激特别是辐射生物效应相关,microRNA有可能成为电离辐射生物标志物的潜在新靶点。本文着重概述与电离辐射相关的microRNA的研究现状。     

TFF1和TFF3在结直肠癌中的表达与临床病理特点及预后的关系

  目的  检测三叶因子1（trefoil factor,TFF1）和三叶因子3（TFF3）在结直肠癌组织、癌旁组织及转移淋巴结中的表达,评价其与肿瘤发生、转移和预后的关系。  方法  采用免疫组织化学SP法检测65例结直肠癌、30例癌旁组织、25例转移淋巴结中TFF1和TFF3的表达,分析二者表达的差异及其与临床病理特征和预后的关系。  结果  TFF1在癌旁组织、癌组织和转移淋巴结中表达逐渐增高（26.7%,70.8%,96%,两两比较均P < 0.05）。癌组织和转移淋巴结与癌旁组织比较,TFF3表达率均有降低（100% vs. 84.6%或80%,均P < 0.05）,癌组织和转移淋巴结之间差异无统计学意义（P>0.05）。TFF1在结直肠癌中的表达仅与肿瘤分化程度相关（P < 0.05）;TFF3表达与淋巴结转移及TNM分期有关（均P < 0.05）。TFF1在结直肠癌中的表达与TFF3呈负相关（P=0.014,r=-0.291）。TFF1表达水平与总生存率无相关性（P=0.639）,而TFF3表达水平与总生存率有关（P=0.045）。Cox比例风险模型单因素分析显示,浸润深度、淋巴结转移、远处转移、TNM分期等为影响预后的相关因素。多因素分析显示,淋巴结转移、远处转移、TNM分期和TFF3为预后的影响因素。  结论  TFF1和TFF3表达率与结直肠癌的发生、转移和预后密切相关。两者可能在结直肠癌的侵袭、转移中存在共同作用,相互影响。      

肿瘤细胞中HER2与脂肪酸合酶的关系

脂肪酸代谢和机体的能量平衡与肿瘤发生发展密切相关。脂肪酸合成酶（fatty acid synthase, FASN）作为一个代谢性癌基因,是能量链中的核心分子。近年来不少研究发现FASN和人表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）之间存在双向分子联系,共同促进癌细胞转化、增殖、侵袭、转移、耐药等。本文对肿瘤细胞中二者相互作用作一综述。     

Aberrant Promoter Hypermethylation of RASSF1a and BRCA1 in Circulating Cell-Free Tumor DNA Serves as a Biomarker of Ovarian Carcinoma

Objective: Ovarian cancer is one of the leading causes of cancer deaths in women. Ovarian cancer is diagnosed at the late stages and generally relapses within 12-14 months of cytoreductive surgery. This is attributed to lack of precise molecular detection methodologies to detect and track the disease. Epigenetic alteration such as aberrant promoter hypermethylation is an important early event that occurs during cancer development and progression. This study focuses on development of a minimally invasive methylation marker that could be used for detection and prognosis of ovarian cancer patients. Methods: Aberrant promoter hypermethylation of RASSF1a and BRCA1 was assessed in circulating DNA of 72 EOC patients using methylation-specific PCR. The findings were correlated with various clinicopathological parameters. Statistical analysis was done using the Fisher exact test and chi-square test. Results: The aberrant methylation patterns of RASSF1a and BRCA1 was identified to be present in the cancerous samples. A total of 31.9 % and 56.9% methylation was observed for RASSF1a and BRCA1 respectively. A striking 50% methylation of BRCA1 was identified in the benign sample cohort, which marks the significance of assessing the hypermethylation pattern to detect cancer at its early stages. Methylation of the two tumor suppressor genes was evident across various stages and grades of ovarian tumors suggesting that this could also help as a prognostic marker. Conclusion: The results of the current study hold significance since the hypermethylation patterns can be identified in the cell-free circulating tumor DNA from a small volume of blood plasma and is a simple and minimally-invasive method. Assessment of hypermethylation patterns of a panel of TSG along with the existing screening markers could aid in better diagnosis and management of the disease. It could also aid in designing specifically tailored treatment strategies to fight the disease.     

干细胞因子Nanog在肿瘤中的研究进展

Nanog是维持胚胎干细胞自我更新和多能性的关键转录因子。Nanog在分化的细胞中表达逐渐降低或缺失。研究发现肿瘤细胞中Nanog异常激活,并且与肿瘤发生、发展和转移密切相关。Nanog通过调控肿瘤细胞增殖、迁移和侵袭、肿瘤干性以及肿瘤免疫逃逸等多种机制参与肿瘤生长、转移和耐药。临床研究证据提示Nanog在肿瘤患者中异常高表达,可作为预后评估的独立指标。本文就Nanog在肿瘤中的作用、分子机制和临床应用的研究进展作一综述。     

表皮生长因子受体靶向肿瘤生物治疗

表皮生长因子受体(epidermal growth factor receptor,EGFR)的异常高表达可见于多种恶性肿瘤,并与肿瘤细胞的恶性生物学行为以及肿瘤患者的不良预后密切相关。EGFR已成为阳性表达肿瘤的重要治疗靶标。以EGFR为靶点的治疗主要有单克隆抗体以及小分子化合物激酶拮抗剂两种方式,目前已进行了广泛的实验与临床研究,其抗肿瘤的主要作用机制包括：(1)细胞周期阻滞;(2)促凋亡;(3)抗肿瘤浸润与转移;(4)抗新生血管生成;(5)放化疗细胞毒增敏。此外,本实验室曾以异种同源分子免疫的策略打破了机体对自身EGFR的免疫耐受,发现以人EGFR为免疫原在小鼠体内可以激发特异的免疫反应,该反应能交叉反应于鼠同源EGFR,进而达到治疗EGFR阳性表达肿瘤的目的。迄今,EGFR靶向治疗均很少观察到显著的EGFR相关的毒副作用,这可能与正常细胞EGFR显著的调控性低表达以及对EGFR通路信号的相对不依赖性相关。     

Tumor Necrosis Factor-β and Hypercalcemia

Hypercalcemia in hematological malignancy is frequently encountered in lymphoid malignancies such as adult T-cell leukemia (ATL) and multiple myeloma and is difficult to manage. As a causative agent of hypercalcemia in ATL, tumor necrosis factor-β (TNF-β), previously known as lymphotoxin, has been carefully studied and reviewed here. Bone resorption studies showed the presence of activity in culture supernatants of HTLV-I infected cells. Enzyme linked immunosorbent assays (ELISA) for TNF-β detected elevated TNF-β in the sera of ATL patients with hypercalcemia. Immunostaining by monoclonal anti-TNF-β antibody demonstrated the presence of TNF-β in both HTLV-I infected cell lines and freshly isolated ATL cells. Furthermore biological TNF-β activity assay including inhibition of anti-TNF-β antibody confirmed the conventional documentation of TNF-β activity in the sera and culture supernatants of HTLV-I infected cell lines. These studies showed that the TNF-β secreted from ATL cells might be one of the factors contributing to the hypercalcemia in patients with ATL functioning as an osteoclast activating factor (OAF).     

Tumor necrosis factor-α alters protein metabolism and cell-cycle kinetics in malignant tumor

The effects of tumor necrosis factor-α (TNF) on protein metabolism and cell-cycle kinetics were investigated in malignant tumor. Sprague-Dawley rats, subcutaneously inoculated with Walker 256 carcinosarcoma, were injected intraperitoneally with recombinant human TNF at a dose of 4.75×10⁶ U/kg for 3 consecutive days. Tumor protein metabolism and cell-cycle kinetics were analyzed. The results showed a significant decrease in tumor volume and weight in comparison with control. TNF resulted in significant decrease in tumor protein fractional synthesis rate, protein synthesis and fractional growth rate, but no change of tumor protein fractional degradation rate. TNF also resulted in remarkable decline in labelling index and G1 phase increase of tumor cells, 6 hours after bromodeoxyuridine injection, by cytometry. The results indicated that TNF inhibits tumor growth as a result of decreases in tumor cell DNA and protein syntheses.