Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Comparison of Cell Deaths Induced by Transmembrane and Secretory TNF-α

Our previous study showed that transmembrane TNF-α （TM-TNF-α） had broader tumoricidal spectrum than secretory TNF-α （s-TNF-α）. This study examined the difference between the two kinds of TNF-α in inducing cells and the relationship between the apoptosis induced by TM-TNF-α and the cell cycle. Bioassay was employed to compare the cytotoxic effect of two kinds of TNF-α on cell lines L-929 and HepG2. TUNEL was used to detect apoptosis and the TdT and PI co-staining were used for determining the phase of apoptotic cells. Our results showed that TM-TNF-α could kill not only s-TNF-sensitive L929 cells but also s-TNF-tolerant HepG2 cells. TM-TNF-α predominantly induced apoptosis while s-TNF could induce both apoptosis and necrosis. The apoptosis of L-929 cells induced by TM-TNF-α mainly occurred in S phase and the apoptosis of HepG2 predominantly took place in G1 phase. It is concluded that the cytotoxic effects of the two TNF differ substantially. Since TM-TNF-α works locally, mainly induces apoptosis and has broader anti-tumor spectrum, it may be more effective for the treatment of tumor than s-TNF.

Effect of rhTNF-α on Mitochondrial Transmembrane Potential and Motility of Human Sperm in vitro by Flow Cytometry and Computer Aided of Semen Analysis

To evaluate effect of recombined human tumor necrosis factor （rhTNF- α） on mitochondrial transmembrane potential and motility of human sperm in vitro Methods Semen samples for study were obtained from 40 health men （average age 26 ± 1.2 years） with normal semen analysis. Sperm suspension with computer aided of semen analysis （CASA） technique; 2） were stained in the presence of 10 μg/ml Rh123 and PI, mitochondrial transmembrane potential of those was analyzed by flow cytometry （FCM）. Results Significant differences were found between experimental groups and control groups on viability, straight line velocity, curvilinear velocity, average path velocity, progressive motility of human sperm and number of sperm with normal mitochondrial transmembrane potential （P〈0.01） expect final concentration 30 pg/ml group （P〉0. 05）. Sperm motility lowed with increasing rhTNF-α concentration and incubating time （P〈0. 01）. Number of sperm with normal mitochondrial transmembrane potential decreased with increasing rhTNF-α concentration and incubating time （P〈0.01）. Conclusion rh TNF-α can decrease human sperm motility function in vitro, which can interfere the function of human sperm mitochondrial transmembrane potential and may inhibit sperm mitochondrial enzymatic activities.

Transmembrane serine protease 4 expression in the prognosis of radical resection for biliary tract cancer

BACKGROUND Recent advancements in biliary tract cancer(BTC)treatment have expanded beyond surgery to include adjuvant therapy,yet the prognosis remains poor.Identifying prognostic biomarkers could enhance the assessment of patients who have undergone radical resection for BTC.AIM To determine transmembrane serine protease 4(TMPRSS4)utility as a prognostic biomarker of radical resection for BTC.METHODS Medical records of patients who underwent radical resection for BTC,excluding intrahepatic cholangiocarcinoma,were retrospectively reviewed.The associations between TMPRSS4 expression and clinicopathological factors,overall survival,and recurrence-free survival were analyzed.RESULTS Among the 85 patients undergoing radical resection for BTC,46(54%)were TMPRSS4-positive.The TMPRSS4-positive group exhibited significantly higher preoperative carbohydrate antigen 19-9(CA19-9)values and greater lymphatic invasion than the TMPRSS4-negative group(P=0.019 and 0.039,respectively).Postoperative overall survival and recurrence-free survival were significantly worse in the TMPRSS4-positive group(median survival time:25.3 months vs not reached,P<0.001;median survival time:28.7 months vs not reached,P=0.043,respectively).Multivariate overall survival analysis indicated TMPRSS4 positivity,pT3/T4,and resection status R1 were independently associated with poor prognosis(P=0.032,0.035 and 0.030,respectively).TMPRSS4 positivity correlated with preoperative CA19-9 values≥37 U/mL and pathological tumor size≥30 mm(P=0.016 and 0.038,respectively).CONCLUSION TMPRSS4 is a potential prognostic biomarker of radical resection for BTC.

Potential role of transmembrane 9 superfamily member 1 as a biomarker in urothelial cancer

Bladder cancer is a urological tumor with high rates of recurrence despite recent advances in novel therapies.Many proteins involved in the molecular mechanisms are currently an enigma,especially the transmembrane 9 superfamily member 1 which has an unclear function.Wei et al published the function and mechanism of this protein,and showed that it could participate in the proliferation,migration and invasion of tumor cells in bladder cancer,therefore treatments directed against this protein may be beneficial in avoiding this condition.

Six transmembrane epithelial antigens of the prostate to illustrate inflammatory response in gastrointestinal cancers

Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe^(3+),Cu^(2+) reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

Understanding the role of transmembrane 9 superfamily member 1 in bladder cancer pathogenesis

In this editorial we comment on the article by Wei et al,published in the recent issue of the World Journal of Clinical Oncology.The authors investigated the role of Transmembrane 9 superfamily member 1(TM9SF1)protein in bladder cancer(BC)carcinogenesis.Lentiviral vectors were used to achieve silencing or overexpression of TM9SF1 gene in three BC cell lines.These cell lines were then subject to cell counting kit 8,wound-healing assay,transwell assay,and flow cytometry.Proliferation,migration,and invasion of BC cells were increased in cell lines subjected to TM9SF1 overexpression.TM9SF1 silencing inhibited proliferation,migration and invasion of BC cells.The authors conclude that TM9SF1 may be an oncogene in bladder cancer pathogenesis.

Low Level of Cystic Fibrosis Transmembrane Conductance Regulator Is Associated with Human Sperm Autophagy and Vitality

Low sperm motility is one of the main causes of male infertility. Cystic fibrosis transmembrane conductance regulator (CFTR, an anion channel protein) is related to the progressive motility of sperm. CFTR disruptor CFTRinh-172 or forskolin (FSK) in this study were used to treat human sperm separately, and the rates of sperm autophagy and progressive motility, mitochondrial membrane potential (MMP) and ATP concentration, and the expression levels of related factors were detected to explore their relationship. It was showed that sperms treated with CFTRinh-172 or FSK reduced the levels of cAMP, CFTR and PKA, but increased sperm autophagy rate, expression levels of AMPK and LC3B. However, reactive oxygen species content had no significant difference. It was indicated that low level of CFTR performed with cAMP and its downstream effectors such as PKA and AMPK to regulate mitochondrial structure and function, leading to increased autophagy rate and reduced vitality of sperm.

Correlation of Cytotoxic Effect of Transmembrane and Secretory TNF-α to Cell Cycle

This study was aimed to examine the correlation of the cytotoxic effects induced by two types of TNF-α to cell cycle. Hoechst 33342 and PI were used to detect the morphological changes in the cell death induced by the two types of TNF-α. TdT and PI co-staining was performed to determine the phase of cell cycle of apoptotic cells. L929 cells in different phases of cell cycle were further synchronized and their sensitivity to the two types of TNF-α was observed. Our results showed that the apoptosis of HepG2 cells triggered by tm-TNF-α mainly occurred in G1 phase while in HL-60, Raji and K562 cell lines it mainly took place in S phase. The apoptosis of L929 cells induced by tm-TNF-α mainly occurred in S phase while the apoptosis induced by s-TNF-α mainly appeared in G1 phase. L929 cells were sensitive to s-TNF-α when synchronized in G1 phase (cytotoxicity 49.8%) while their sensi-tivity to tm-TNF-α was highest in S phase (45.7%) and G1/S phase (cytotoxicity 40.6%). It was concluded that tm-TNF-α-induced apoptosis of different target cells took place in different phases of cell cycle. The apoptosis of the specific cell line induced by the two types of TNF-α occurred in different phases of cell cycle. The sensitivity of the specific cell line to the two types of TNF-α was correlated with the phase of cell cycle.

大黄素对大鼠腹腔巨噬细胞产生的TNF_α、IL-1、IL-6及细胞[Ca^(2+)]_i的影响

目的 研究中药大黄有效成分大黄素对不同状态下的巨噬细胞分泌 TNFα、IL- 1、IL- 6和 [Ca2 + ]i 的影响。方法 利用脂多糖 (lipopolysacchride,L PS)刺激的大鼠腹腔巨噬细胞作为过度炎症反应的体外模型 ,用生物学方法和荧光分光光度法测定巨噬细胞合成分泌的 TNFα、IL- 1、IL- 6和 [Ca2 + ]i。结果 大黄素对 TNFα 的分泌和[Ca2 + ]i 有双向调节作用。结论 大黄素可能具有免疫双向调节功能。

板蓝根有效部位对脂多糖致小鼠血清中TNF_α和NO的影响

目的 探讨板蓝根有效部位小鼠体内对脂多糖刺激产生 TNFα和 NO的影响。方法 从板蓝根中提取分离出有效部位并配制成 2 % ,1% ,0 .5 %三种浓度的样品液 ;将用卡介苗致敏的小鼠随机分为 5组 ,实验组分别 ig2 % ,1% ,0 .5 %样品液各 0 .4 m L ,对照组和模型组给予相同量生理氯化钠溶液 ;0 .5 h后 ,实验和模型组分别尾 iv脂多糖 80 0 ng/ 2 0 g,9h后眼眶取血 ,制备血清 ,用 EL ISA法测 TNFα,用 Griess法测 NO浓度。结果 板蓝根有效部位高、中、低 3种样品液对脂多糖刺激小鼠释放 TNFα和 NO均有抑制作用 ,抑制率分别为 83.5 9% ,6 7.92 % ,2 1.6 1% ,对 NO抑制率分别为 98.6 6 % ,70 .77% ,2 0 .33%。结论 板蓝根有效部位对脂多糖刺激小鼠体内释放TNFα和 NO有抑制作用 ,且有剂量依赖性。

丝瓜叶成分L-6a对BALB/C鼠产生IL-1、TNF_α及IL-2的影响

目的 :研究丝瓜叶成分L 6a对BALB/C小鼠产生IL 1、TNFα 及IL 2的影响。方法 :IL 1采用胸腺细胞生物法测定 ;TNFα 采用L92 9细胞生物法测定 ;IL 2采用CTLL细胞生物法测定。结果 :丝瓜叶成分L 6a对LPS刺激BALB/C小鼠PM产生IL 1及TNFα。 2～ 5 0 μg·ml 1范围内 ,促进IL 1及TNFα 的产生 ,促进IL 1作用在 10 μg·ml 1时达高峰 (P <0 0 1) ;L 6a在 0 2～ 5 0 μg·ml 1范围内 ,对于PHA刺激BALB/C小鼠脾细胞产生IL 2有促进作用 ,在 2 μg·ml 1时达高峰 (P <0 0 1)。结论 :L 6a在体外对BALB/C小鼠产生IL 1、TNFα 及IL

槲皮素对TNF_α诱导的内皮细胞与中性粒细胞粘附的抑制作用

目的：研究槲皮素对ＴＮＦα诱导的内皮细胞与中性粒细胞粘附的抑制作用及作用机制。方法：用髓过氧化酶法测定中性粒细胞与内皮细胞的粘附，ＥＬＩＳＡ法测定内皮细胞粘附分子的表达。结果：ＴＮＦα通过增加／诱导内皮细胞ＩＣＡＭ１，ＶＣＡＭ１及Ｅｓｅｌｅｃｔｉｎ的表达而剂量、时间依赖性地增加内皮细胞与中性粒细胞的粘附。槲皮素可剂量依赖性地抑制上述粘附，其作用机制为抑制ＴＮＦα诱导内皮细胞上述３种粘附分子的表达。结论：槲皮素通过抑制ＩＣＡＭ１，ＶＣＡＭ１及Ｅｓｅｌｅｃｔｉｎ的表达而降低ＴＮＦα诱导的内皮细胞与中性粒细胞的粘附。

肺缺血再灌注损伤后TNF_α、IL-6和IL-8的变化及其意义

为探讨炎性细胞因子在肺缺血再灌注损伤发病机制中的作用，采用大鼠在体温缺血再灌注模型，动态测定了肺组织和血浆肿瘤坏死因子α（ＴＮＦ_α）、白介素-６（ＩＬ－６）和白介素－８（ＩＬ－８）含量的变化。结果表明，肺缺血再灌注损伤早期肺组织ＴＮＦ_α、ＩＬ－６、ＩＬ－８相继释放增加，上述因子的血浆变化滞后于肺组织变化。提示炎性细胞因子参与了肺缺血再灌注损伤的发生和发展过程。

Study on the Knockout and the Soluble Prokaryotic Expression of VP5 Protein Transmembrane Region of IBDV

[Objective] The research aimed to construct the prokaryotic expression vector of VP5 protein of IBDV.The transmembrane region sequence of VP5 protein was knocked out.Moreover,the expression,separation and purification of objective protein were carried out.[Method] PCR technology was used to respectively amplify the extracellular and intracellular fragments of VP5 gene of IBDV.Then,the two fragments were simultaneously linked to pET-28b（＋）,and it was the vector-intracellular fragment-extracellular fragment-vector.The recombinant expression plasmid pET-VP5-FC and the improved pET-VP5-SC of VP5 whose transmembrane region gene fragment was knocked out were constructed.Then,the expression plasmid was transformed into BL21（DE3）.After IPTG induction,the recombinant protein was purified by Ni affinity chromatography and the gel filtration chromatography.[Result] The soluble expressed VP5 of IBDV was obtained.[Conclusion] The research laid the foundation for further studying the structure and function of VP5 protein.

大黄素对内毒素刺激下的大鼠腹腔巨噬细胞分泌TNF_α及NO的影响

目的 :研究大黄素抗炎作用机理。方法:利用脂多糖 (Lipopolysacchride ,LPS)刺激的大鼠腹腔巨噬细胞(PMΦ)作为人体过度炎症反应的体外模型 ,用MTT法和荧光法测定了大黄素对不同状态下的巨噬细胞分泌TN Fα、NO的影响。结果:大黄素可通过抑制LPS刺激的大鼠腹腔巨噬细胞分泌TNFα ,抑制过度的炎症反应 ;而对于未经LPS刺激的大鼠腹腔巨噬细胞 ,大黄素可促进TNFα的分泌。大黄素能抑制炎症反应中的NO的大量合成与释放。结论:大黄素对机体的免疫功能可能具有双向的调节作用。

BCAA对大鼠LDH、TNF_α、Ca^(2+)-ATPase的影响初探

目的 :初步探讨BCAA对大鼠LDH、Ca2 + ATPase、TNFα 的影响。方法 :Wistar鼠 ,随机分为正常对照组、BCAA实验组。正常对照组摄食普通酪蛋白饲料 ,BCAA实验组饲料添加BCAA ,5周后处死动物取标本待测。结果 :BCAA显著增加血中TNFα 水平 ,明显增加骨骼肌LDH活力 ,显著增强心肌和骨骼肌中Ca2 + ATPase活性 ,但不影响血乳酸、肌中LDH活力和心肌及骨骼肌中糖原含量。结论 :BCAA具有调节LDH、Ca2 + ATPase活力 ,促进TNFα

Effect of Quercetin on the Proliferation and Mitochondrial Transmembrane Potential of CBRH-7919 Cells

[Objective] To investigate the effect of quercetin on the proliferation and mitochondrial transmembrane potential of CBRH-7919 cells. [Method] The CBRH-7919 cells of hepatocarcinoma were cultured in vitro. After treated with different concentrations of quercetin, the OD405 nm of CBRH-7919 cells was detected by using the acid phosphatase assy （APA）; morphologic changes of the cells were observed under inverted microscope; the mitochondrial transmembrane potential （△ψm） intensity changes of CBRH-7919 cells were analyzed by flow cytometry after stained with Rhodamine 123. [Result] Quercetin inhibited the proliferation of CBRH-7919 cells significantly, and the growth inhibitory effect presented time- and dose-dependent relationship. Typical decrease of cell density was observed by optical microscopy on the quercetin-treated cells. With the effect of 10 μg/ml quercetin on CBRH-7919 cells for 12, 24 and 48 h, the percentage of Rhodamine 123 stained hypofluorescence cells increased, while the mitochondrial transmembrane potential（△ψm） intensity of CBRH-7919 cells decreased. [Conclusion] Quercetin could inhibit the proliferation of CBRH-7919 cells in vitro, causing the decrease in mitochondrial transmembrane potential.

黄芪对慢性肾功不全患者的TNF_α红细胞免疫效应及改善肾功能的观察

目的观察黄芪对慢性肾功能不全患者提高红细胞免疫功能及改善肾功能的情况方法将68 例慢性肾功能不全患者随机分为实验组和对照组两组均给予抗凝降压和对症治疗实验组在此基础上给予黄芪观察指标红细胞C 3 b 受体花环率RCR 红细胞免疫复合物花环率RICR 采用酵母菌玫瑰花环试验法循环免疫复合物C IC 采用P EG 紫外线分光比色法肿瘤坏死因子T NF