3-磷酸甘油酸脱氢酶在宫颈鳞状细胞癌中高表达

目的:检测宫颈鳞状细胞癌组织和细胞中3-磷酸甘油酸脱氢酶(3-phosphoglycerate dehydrogen-ase,PHGDH)的表达水平,探讨其在肿瘤发生发展中的作用.方法:使用实时荧光定量PCR法和免疫组织化学法检测宫颈鳞状细胞癌和正常宫颈组织中PHGDH mRNA转录水平和蛋白翻译水平;利用实时荧光定量...     

丙酮酸脱氢酶与肿瘤

丙酮酸脱氢酶是丙酮酸生成乙酰辅酶A的关键酶,而乙酰辅酶A是葡萄糖进入三羧酸循环有氧氧化的首要原料。丙酮酸脱氢酶激酶可以抑制丙酮酸脱氢酶的活性。肿瘤细胞的总体丙酮酸脱氢酶激酶表达增加,造成丙酮酸脱氢酶活性降低,导致肿瘤细胞主要通过糖酵解的方式获取能量。恶性肿瘤糖酵解活跃能促进细胞增殖和抑制细胞凋亡,而形成肿瘤细胞糖酵解的微环境可保护肿瘤细胞逃避宿主免疫杀伤并减轻化疗药物损伤,还有利于肿瘤细胞的侵袭和转移。因此,丙酮酸脱氢酶在肿瘤的发生发展过程中起作用。事实上胚胎干细胞以及成体干细胞也主要是以糖酵解的方式获取能量。由此推断,丙酮酸脱氢酶的活性可能与肿瘤细胞的干性相关。     

三磷酸腺苷-柠檬酸裂解酶在肿瘤中的研究进展

癌细胞最重要的代谢特征之一是脂肪酸从头合成的增多。脂肪酸是所有生物膜脂的重要组成部分,是能量代谢的重要底物。三磷酸腺苷-柠檬酸裂解酶(adenosine triphosphatecitrate lyase,ACLY)主要存在于细胞质,是糖代谢与脂肪酸从头合成之间的桥梁。ACLY在多数肿瘤细胞中高表达,通过促进脂肪酸从头合成,或者参与不同的调控通路,从而影响肿瘤的发生、转移及耐药等生物学过程。ACLY受到多种基因、转录因子以及翻译后修饰调节,抑制ACLY能够抑制肿瘤细胞的增殖、侵袭、转移。目前越来越多的ACLY抑制剂及其在肿瘤中的应用正在被发掘研究。全文将对ACLY在多种肿瘤中的相关调控机制及其研究现状进行综述。     

Tbx3基因在肿瘤进展中的机制

Tbx3(T-box3)基因作为T-box家族的成员之一,广泛存在于人体的多种组织和器官中,参与了胚胎时期乳腺、四肢、心脏、眼、肺、胰腺的发育调控,并且在维持胚胎干细胞的发育中发挥了重要作用.最新研究表明,Tbx3可以作为转录因子通过上皮间质转化、肿瘤干细胞和甲基化等多种途径参与肿瘤的发生和发展.更好地了解Tbx3将为肿瘤的基因诊断和靶向治疗提供新的思路.     

乳酸脱氢酶与肿瘤免疫代谢研究进展

不同免疫细胞亚群的代谢特征有所不同,抗肿瘤免疫细胞主要以有氧酵解和谷氨酰胺分解代谢提供代谢的物质与能量,而促进肿瘤发生和进展的抑制性免疫细胞亚群可利用肿瘤细胞代谢产物通过脂肪酸代谢等途径获取能量及中间产物。乳酸作为糖酵解途径的重要产物,直接或间接地影响肿瘤生物学行为,参与肿瘤免疫微环境调控。乳酸代谢的关键酶乳酸脱氢酶（LDH）常在肿瘤组织中高表达,是肿瘤微环境中连接各种免疫细胞代谢的关键酶之一,可激活某些信号传导途径和调控免疫应答参与肿瘤发生、发展。LDH水平升高主要由于肿瘤糖酵解活性增加和肿瘤缺氧坏死引起,其为免疫抑制性微环境的重要驱动者,LDH水平在一定程度上反映并可用于肿瘤糖酵解活性和免疫代谢状态的评估。本文对LDH与T淋巴细胞、巨噬细胞、树突状细胞等免疫细胞的代谢相关研究进行综述,旨在探究其在恶性肿瘤预后评估、抗肿瘤治疗尤其是免疫治疗疗效预测及监测中的可能应用。     

肝细胞再生磷酸酶-3在肿瘤中的研究进展

肝细胞再生磷酸酶-3（PRL-3）属于蛋白酪氨酸磷酸酶家族的成员,自2001年研究者通过SAGE技术首先发现其在结肠癌肝转移患者中存在高表达后,又进一步在乳腺癌、前列腺癌、肝癌、胃癌、肺癌、肾癌等肿瘤中检测出PRL-3高表达.文章就PRL-3与肿瘤发生及转移的相关性作一综述.     

丙酮酸脱氢酶激酶在恶性肿瘤中的研究进展

正常细胞能量代谢以线粒体的氧化磷酸化为主,而癌细胞则以有氧糖酵解为主。这种代谢特征的偏移与丙酮酸脱氢酶激酶及其相关蛋白密切相关。因此本文通过介绍该激酶功能及相关蛋白、抑制剂研究等以阐述其在恶性肿瘤发生发展等方面的研究进展,进一步深入了解其在临床中的应用价值。     

B7-H3、葡萄糖6-磷酸脱氢酶及SET8蛋白在肾透明细胞癌中的表达及与预后的关系分析

目的 分析B7-H3、葡萄糖6-磷酸脱氢酶(G6PD)及SET8蛋白在肾透明细胞癌中的表达及与预后的关系.方法 收集81例肾透明细胞癌患者的肾透明细胞癌组织及正常组织,比较不同组织中B7-H3、G6PD及SET8蛋白阳性表达情况,随访2年分析肾透明细胞癌预后的影响因素.结果 肾透明细胞癌组织中B7-H3、G6PD及SE...     

Tbx3基因在肿瘤进展中的机制研究

 Tbx3(T-box3)基因作为T-box家族的成员之一,广泛存在于人体的多种组织和器官中,参与了胚胎时期乳腺、四肢、心脏、眼、肺、胰腺的发育调控,并且在维持胚胎干细胞的发育中发挥了重要作用。最新研究表明,Tbx3可以作为转录因子通过上皮间质转化、肿瘤干细胞和甲基化等多种途径参与肿瘤的发生和发展。更好地了解Tbx3将为肿瘤的基因诊断和靶向治疗提供新的思路。     

Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis

Background:

Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated with prostate cancer (PC) remains unclear.

Methods:

ALDH3A1 expression was analysed in various PC cell lines. Xenograft tumours and 54 primary and metastatic PC tumours were stained using immunohistochemistry for ALDH3A1 expression.

Results:

In comparison with the non-stem counterparts, a robust upregulation of ALDH3A1 was observed in DU145-derived PC stem cells (PCSCs). As DU145 PCSCs produced xenograft tumours with more advanced features compared with those derived from DU145 cells, higher levels of ALDH3A1 were detected in the former; a dramatic elevation of ALDH3A1 occurred in DU145 cell-derived lung metastasis compared with local xenograft tumours. Furthermore, while ALDH3A1 was not observed in prostate glands, ALDH3A1 was clearly present in PIN, and further increased in carcinomas. In comparison with the paired local carcinomas, ALDH3A1 was upregulated in lymph node metastatic tumours; the presence of ALDH3A1 in bone metastatic PC was also demonstrated.

Conclusions:

We report here the association of ALDH3A1 with PC progression.     

乳酸脱氢酶及肿瘤标记物对胰腺癌的预后影响

目的:观察胰腺癌患者乳酸脱氢酶(LDH)及肿瘤标记物对预后影响.方法:收集LDH及肿瘤标记物,对病理诊断明确且回访到生存期的胰腺癌患者分析预后.结果:297例胰腺癌患者中位生存期5.0月,1年、2年、3年生存率分别为27.3％,10.1％,2.0％.肿瘤最大径大及分期晚的患者1年、2年、3年生存率降低(P＜0.05).胰体尾癌及全胰腺癌较胰头癌生存期短,分期晚、LDH、CEA、CA19-9、CA125升高的患者生存期短(P＜0.05)；LDH高于300U/L患者较轻度升高者生存期短(P ＜0.05):CA125、CA15-3高于100L/ml患者较轻度升高者生存期短(P＜0.05).多因素Cox比例风险回归分析显示肿瘤分期及CA19-9是独立预后因素.结论:肿瘤原发部位、分期、LDH、CEA、CA19-9、CA125是胰腺癌的独立预后因素.     

PI3K/Akt信号传导通路在肿瘤发生发展及治疗中的作用

在许多恶性肿瘤中PI3K/Akt信号通路的表达出现异常,影响多个靶标分子的功能,在肿瘤发生、发展过程中起着关键作用,与肿瘤细胞治疗抗拒、增殖凋亡、周期调控、侵袭转移及血管形成等过程密切相关。抑制该通路的方案已成为肿瘤治疗的研究热点,其中以通路中关键分子为靶点的靶向治疗有了长足发展。我们就PI3K/Akt信号通路的组成功能、调节及其对肿瘤形成和治疗的关系进行整理,希望为广大医务工作者提供参考。     

p53/Lactate dehydrogenase A axis negatively regulates aerobic glycolysis and tumor progression in breast cancer expressing wild‐type p53

Tumor suppressor p53 is a master regulator of apoptosis and plays key roles in cell cycle checkpoints. p53 responds to metabolic changes and alters metabolism through several mechanisms in cancer. Lactate dehydrogenase A (LDHA), a key enzyme in glycolysis, is highly expressed in a variety of tumors and catalyzes pyruvate to lactate. In the present study, we first analyzed the association and clinical significance of p53 and LDHA in breast cancer expressing wild‐type p53 (wt‐p53) and found that LDHA mRNA levels are negatively correlated with wt‐p53 but not with mutation p53 mRNA levels, and low p53 and high LDHA expression are significantly associated with poor overall survival rates. Furthermore, p53 negatively regulates LDHA expression by directly binding its promoter region. Moreover, a series of LDHA gain‐of‐function and rescore experiments were carried out in breast cancer MCF7 cells expressing endogenous wt‐p53, showing that ectopic expression of p53 decreases aerobic glycolysis, cell proliferation, migration, invasion and tumor formation of breast cancer cells and that restoration of the expression of LDHA in p53‐overexpressing cells could abolish the suppressive effect of p53 on aerobic glycolysis and other malignant phenotypes. In conclusion, our findings showed that repression of LDHA induced by wt‐p53 blocks tumor growth and invasion through downregulation of aerobic glycolysis in breast cancer, providing new insights into the mechanism by which p53 contributes to the development and progression of breast cancer.     

Role of thymidine phosphorylase and dihydropyrimidine dehydrogenase in tumour progression and sensitivity to doxifluridine in gastric cancer patients

This study was designed to investigate the role of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) on tumour progression and sensitivity to 5′-deoxy-5-fluorouridine (5′-DFUR). Tumour tissue was obtained from surgically resected samples from 93 patients with primary gastric cancer. Tumour TP and DPD expression levels were determined by the enzyme-linked immunosorbent assay (ELISA) system and compared with several clinicopathological factors and in vitro sensitivity to 5′-DFUR. DPD showed no correlation with any clinicopathological factors. However, the TP level was significantly correlated with the depth of tumour, lymphatic invasion and venous invasion. In comparison with 5′-DFUR sensitivity, there was a weak inverse correlation between the DPD level and the sensitivity to 5′-DFUR (r_s=−0.361). Furthermore, the TP/DPD ratio showed a significant correlation with 5′-DFUR sensitivity (r_s=0.634). In a subgroup of patients with postoperative 5′-DFUR administration, the survival rate was significantly better in patients with a high TP/DPD ratio (n=8) than in those with low TP/DPD ratio (n=14) (P=0.0140). These results suggest that sensitivity to 5′-DFUR is predictable by measurement of both TP and DPD levels.     

Upregulation of REG Iα accelerates tumor progression in pancreatic cancer with diabetes

Diabetes is now generally accepted as a crucial event in the process of pancreatic cancer (PaC). However, molecular mechanisms underlying the relationship between diabetes and PaC are not fully understood. Regenerating gene (REG) Iα is a growth factor affecting pancreatic islet beta cells, and it has been shown to be involved in the carcinogenesis in gastrointestinal tract. It is rational to speculate that REG Iα plays a potential role in the pathogenesis of PaC with diabetes. The aim of this study was to evaluate the REG Iα protein expression profile in PaC with and without diabetes, and define the contribution of REG Iα on PaC development. We found that REG Iα protein preferentially expressed in cancerous tissues of PaC patients with diabetes by Western blot. REG Iα positive cancer cells in PaC with diabetes (n = 38) was significantly higher than that in subjects without diabetes (n = 42, p < 0.05) by immunohistochemical analysis. Furthermore, we found that overexpression of REG Iα protein in PaC cell lines resulted in accelerated cell proliferation and consequently tumor growth, both in vitro and in vivo. The findings suggest that REG Iα may act as one of the tumor promoter and contribute to the aggressive nature of PaC, especially in the subpopulation with diabetes. This study would shed new insights for understanding the molecular mechanisms underlying the link between diabetes and PaC.