CD44v6和LYVE-1蛋白在卵巢上皮性肿瘤中的表达及意义

目的探讨CD44v6和LYVE-1蛋白在卵巢上皮性肿瘤中的表达及意义。方法应用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(SP)法检测CD44v6、和LYVE-1在63例卵巢上皮性癌、5例卵巢良性上皮性肿瘤和4例正常卵巢组织中的表达情况。结果正常卵巢组织、卵巢良性上皮性肿瘤和卵巢上皮性癌中CD44v6和LYVE-1蛋白的表达具有显著差异;CD44v6表达强度与卵巢癌临床分期和组织学分级呈正相关,LYVE-1的表达和卵巢癌的临床分期正相关,而不同组织学分级间差异无显著性;CD44v6和LYVE-1的表达强度与淋巴结有无转移显著相关;CD44v6和LYVE-1在卵巢癌中协同表达。结论CD44v6和LYVE-1在卵巢癌发生发展、和淋巴转移中起不同程度的作用,其检测可为卵巢肿瘤生物学行为判定提供参考依据。     

库肯勃瘤中CD44v6、VEGF、MMP-2、MMP-9的表达及相关性研究

目的:探讨CD44v6、VEGF、MMP-2、MMP-9在库肯勃瘤及卵巢原发上皮癌中的表达及相关性.方法:应用免疫组化SP法检测CD44v6、VEGF、MMP-2、MMP-9在20例正常卵巢组织、38例库肯勃瘤、45例卵巢原发上皮癌中的表达情况.结果:CD44v6、VEGF在卵巢原发上皮癌和库肯勃瘤组织中的表达显著高于正常卵巢组织(P＜0.05);MMP-2、MMP-9在正常卵巢组织中表达缺如;CD44v6、VEGF、MMP-2、MMP-9在库肯勃中阳性表达率明显高于卵巢原发上皮癌(P＜0.05).CD44v6、VEGF、MMP-2、MMP-9在卵巢原发上皮性癌、库肯勃瘤中,任意两指标阳性表达均有正相关性(P＜0.05).结论:CD44v6、VEGF、MMP-2、MMP-9均参与卵巢癌、胃癌、库肯勃瘤的发生、发展及演进过程,并可为卵巢上皮癌、胃癌及库肯勃瘤的鉴别诊断提供一定依据.     

人上皮性卵巢癌组织中PFTK1的表达及其对细胞迁移、侵袭及增殖能力的影响

目的:研究PFTAIRE蛋白激酶1（PFTAIRE protein kinase 1,PFTK1）在人上皮性卵巢癌（epithelial ovarian cancer,EOC）组织中的表达,以及PFTK1基因的沉默对人卵巢癌细胞迁移、侵袭及增殖能力的影响。方法: 随机选取我院2015年6月至2016年11月收治的25例EOC患者为研究对象,采用Western blot检测癌组织以及癌旁组织中PFTK1蛋白的表达情况。选取PFTK1高表达的人卵巢癌细胞株SKOV3为研究对象,转染PFTK1-siRNA后,采用流式细胞仪检测PFTK1基因的沉默对SKOV3细胞周期的影响,采用细胞迁移和侵袭实验（Transwell）检测SKOV3细胞迁移、侵袭能力的变化,采用平板克隆形成实验检测SKOV3细胞增殖能力的变化。结果:Western blot检测结果显示,EOC患者癌组织中的PFTK1蛋白表达量显著高于癌旁组织（P＜0.01）;流式细胞仪检测结果显示,PFTK1-siRNA组细胞出现明显的生长抑制,细胞多停滞在G0/G1期,与对照组相比差异显著（P＜0.01）;细胞迁移和侵袭实验（Transwell）结果显示,PFTK1-siRNA组细胞的迁移和侵袭能力与对照组比较显著下降,且差异均显著（P＜0.01）;平板克隆形成实验结果显示,PFTK1-siRNA组细胞增殖能力显著降低,与对照组相比差异显著（P＜0.01）。结论:PFTK1在人EOC癌组织中呈现高表达状态;PFTK1基因沉默后,EOC细胞株SKOV3的细胞迁移、侵袭及增殖能力均受到不同程度的抑制,这将为基因治疗人卵巢癌提供一定的理论依据。     

FN和CD44v6在肝胞癌中的表达及临床意义

目的:观察纤维连接蛋白(Fibronectin,FN)和CD44v6在肝细胞癌(Hepatocellular carcinoma,HCC)组织中的表达,探讨其与HCC侵袭转移的关系.方法:采用FN、CD44v6抗体,对39例HCC标本和10例正常肝组织进行SP免疫组化染色,对结果进行统计分析.结果:HCC组织中FN表达的阳性率为35.8%,而在正常肝细胞中全部表达,两者差异明显(P＜0.05).FN分布特征还与HCC分化程度及生长方式相关.CD44v6在HCC中表达的阳性率为69.2%,在正常肝组织中全部未表达,两者差异显著(P＜0.05).CD44v6的阳性表达率和表达程度与HCC的包膜、分化程度、临床分期和有否转移也有密切关系.结论:肝癌细胞FN表达的减少或消失和CD44v6的高表达与HCC的侵袭转移密切相关,两者在侵袭转移中的作用相反.FN和CD44v6可以作为HCC侵袭转移的观察指标.     

妇科

D卵巢原发癌与转移癌中survivin mRNA和caspase-3 mRNA的临床研究,乙酰肝素酶基因转染SKOV3细胞对细胞增殖、粘附、侵袭能力的影响,Kilon基因在卵巢上皮性肿瘤中的表达状况的探讨,抗HER-2工程抗体chA21和Herceptin对人卵巢癌SKOV3裸小鼠移值瘤的抑制作用,ERK信号转导通路蛋白在上皮性卵巢肿瘤组织中的表达及与肿瘤恶性程度的相关性研究,内皮抑素基因联合重组干扰素-α蛋白对卵巢癌抑制作用的研究,卵巢癌6811抗独特型微抗体诱导抗肿瘤免疫应答的体外实验,端粒酶抑制剂对顺铂不同敏感性卵巢癌细胞株的影响,     

雌激素对上皮性卵巢癌细胞转移相关蛋白OPN调控作用的机制研究

背景与目的:卵巢上皮性癌具有高度侵袭性,雌激素在女性卵巢癌发生、转移中所起的作用以及肿瘤的转移、侵袭的机制研究日益引起国内外关注,骨桥蛋白(osteopontin,OPN)是一个重要的趋化因子,能促进细胞趋化、粘附和迁移,增加肿瘤细胞转移、侵袭能力,研究发现雌激素能通过信号通路影响OPN表达。本实验旨在研究雌激素对上皮性卵巢癌细胞转移相关蛋白OPN的调控作用以及可能的机制。方法:17-β雌二醇作用于卵巢浆液性腺癌细胞株SKOV3细胞,采用Transwell穿膜小室体外侵袭实验观察肿瘤细胞侵袭能力的变化;采用蛋白印迹法(Western blot)检测SKOV3细胞HIF-1α、OPN蛋白表达;以CoCl2促进HIF-1α过表达,以西罗莫司抑制HIF-1α表达后,采用Western blot方法分别检测雌激素作用下OPN蛋白表达的变化。结果:Transwell小室培养细胞24 h,雌激素组穿过微孔膜的SKOV3细胞数为162±8个,对照组为121±6个,雌激素组明显多于对照组(P=0.001)。采用Western blot方法检测,17β雌二醇促进SKOV3细胞OPN蛋白及HIF-1α蛋白表达(P=0.002,P=0.001)。促进HIF-1α过表达后,雌激素对SKOV3细胞OPN蛋白表达升调节作用增强(P=0.005);西罗莫司抑制HIF-1α表达后,雌激素对SKOV3细胞OPN蛋白表达升调节作用减弱(P=0.011)。结论:雌激素通过HIF-1α调控上皮性卵巢癌细胞转移相关蛋白OPN的表达。     

CD44v6在乳腺癌患者化疗前后的表达及意义

背景与目的：CD44是粘附分子家族的成员,与肿瘤的形成及转移相关,尤其是变异型亚型CD44v6更是与多种肿瘤的侵袭和转移密切相关。本文旨在研究乳腺癌患者血、癌组织、淋巴结中CD44v6的表达及化疗对CD44v6表达的影响和意义。方法：用免疫组化方法检测癌组织CD44v6的表达,用流式细胞术检测血和淋巴结中CD44v6的表达。结果：乳腺癌组织中淋巴细胞（t=4.71,P＜0．05）和阳性淋巴结（t=5.11,P＜0．05）的CD44v6的表达与对照组相比显著增高,而患者外周血淋巴细胞CD44v6的表达也有所升高,但无统计学意义（t=0.98,P＞0．05）。乳腺癌细胞CD44v6的表达强阳性,且阳性率100％,而良性乳腺组织呈阴性表达。化疗后癌细胞CD44v6的表达仍是100％,血和淋巴结中淋巴细胞CD44v6的表达有所下降,但无意义,只有癌组织中淋巴细胞CD44v6的表达水平显著下降（t=4.13,P＜0．05）。结论：CD44v6的表达与乳腺癌患者的淋巴结转移和预后密切相关,化疗后癌组织中淋巴细胞CD44v6表达明显降低。     

TNF-α对人乳腺癌MCF-7细胞株CD44表达以及细胞侵袭性的影响

目的:检测TNF-α作用前后人乳腺癌细胞株MCF-7中CD44s、CD44v3和CD44v6的表达水平的变化,及对细胞侵袭能力的影响.方法:采用RT-PCR和Western blot方法检测TNF-α作用前后人乳腺癌细胞株MCF-7中CD44s、CD44v3和CD44v6的表达情况,了解TNF-α对CD44各亚型表达水平的影响;Transwell检测TNF-α作用前后人乳腺癌细胞株MCF-7侵袭力的变化情况.结果:TNF-α作用后,MCF-7细胞株CD44s mRNA表达下降,CD44v3 mRNA和CD44v6 mRNA的表达上升.相应蛋白表达与mRNA水平呈现一致性改变,其中CD44s蛋白表达下降,CD44v3蛋白和CD44v6蛋白表达上升;TNF-α作用后细胞侵袭力提高(P＜0.001).结论:在人乳腺癌细胞株MCF-7中,TNF-α可能通过影响CD44各亚型mRNA和蛋白表达水平,进而促进肿瘤细胞的侵袭能力.     

卵巢上皮性肿瘤中基质金属蛋白酶MMP-9及其组织抑制剂TIMP-1 mRNA的表达及意义

目的:探讨基质金属蛋白酶(MMP-9)及其组织抑制物(TIMP-1)mRNA与卵巢上皮性癌的发生、发展及侵袭、转移的关系.方法:采用RT-PCR技术检测38例卵巢上皮性癌、15例卵巢交界性上皮性肿瘤、16例卵巢良性上皮性肿瘤及11例正常卵巢组织中MMP-9及TIMP-1 mRNA的表达,并分析其与各临床病理参数的关系.结果:MMP-9 mRNA在卵巢上皮性癌及卵巢交界性上皮性肿瘤组织中的阳性表达率分别为76%、44%及表达水平(分别为154.14±4.42,96.87±3.04)均显著高于卵巢良性上皮性肿瘤及正常卵巢组织(分别为13%,9%和8.26±2.67,2.341.02;P均＜0.05);且MMP-9mRNA在晚期卵巢上皮性癌组织中的阳性表达率和表达水平明显高于早期(P＜0.05).TIMP-1 mRNA在卵巢上皮性癌及卵巢交界性上皮性肿瘤组织中的阳性表达率(分别为68%,38%)及表达水平(分别为126.35±3.81,90.62±5.54)均显著高于卵巢良性上皮性肿瘤及正常卵巢组织(分别为13%,9%和8.32±2.02,2.63±1.35;P均＜0.05);TIMP-1mRNA在卵巢上皮性癌组织中的阳性表达率和表达水平与各临床病理参数均无相关性(P＞0.05).结论:MMP-9mRNA的高表达及MMP-9/TIMP-1平衡的调节失衡导致卵巢上皮性肿瘤的发生、发展;MMP-9mRNA的高表达对卵巢上皮性癌的预后有意义.     

细胞黏附分子CD44v6对膀胱癌细胞增殖、凋亡及迁移的影响

目的:探讨细胞黏附分子CD44v6对膀胱癌T24细胞生物学行为的影响.方法:免疫细胞化学法检测正常膀胱移行上皮细胞和膀胱癌T24细胞中CD44v6蛋白的表达.用不同浓度的抗CD44v6单克隆抗体封闭细胞24、48和72 h后,MTT法检测细胞的生长抑制率.FCM检测封闭前后细胞凋亡率,并通过免疫细胞化学法检测细胞凋亡相关蛋白Bcl-2和Bax表达水平的变化;Transwell小室检测细胞迁移特性的变化.结果:膀胱癌T24细胞表达CD44v6蛋白,而正常膀胱移行上皮细胞几乎不表达.MTT法检测结果显示,抗CD44v6单克隆抗体可抑制T24细胞的生长(P＜0.01).抗CD44v6单克隆抗体能增加T24细胞的凋亡率(P＜0.01),并且Bcl-2蛋白表达降低,Bax蛋白表达增加(P＜0.01).抗CD44v6单克隆抗体封闭后T24细胞的迁移能力受到抑制,差异有统计学意义(P＜0.05).结论:抗CD44v6单克隆抗体封闭可以抑制膀胱癌细胞的增殖及迁移能力,同时诱导膀胱癌细胞凋亡,其机制可能与Bcl-2和Bax基因表达水平变化有关.     

Irinotecan and radiation in vitro and in vivo

Loss of chromosome sequences at 13q14 (Rbl) and 17p13 (p53) associated with squamous cell carcinoma of head and neck (SCCHN) was evaluated in 12 recurrent tumors and 51 primary tumors from 63 patients. The incidence of LOH at 17p13 was 19 of 50 (38%) tumors, and at 13q14 was 21 of 57 (37%). LOH affecting Rbl and/or p53 was observed in 30 of 63 (48%) SCCHN. Coincident LOH at Rbl and p53 was detected in 10 of 46 (22%) tumors. There were nine cases in which primary and metastatic tumors were obtained from the same patient. Of these, seven were informative and five of these (71%) manifested LOH at p53 in both primary and metastatic sites. Examination of Rbl in these same tumors showed LOH in six of the nine metastases, and of these six, only three revealed LOH in the primary tumor. LOH at p53 or Rbl alone showed no correlation with clinical outcome. However, tumors that manifested LOH at both loci were associated with poorer patient outcome and poorer histological differentiation.     

Daunorubicin and daunorubicinol pharmacokinetics in plasma and tissues in the rat

Recent evidence suggests that 13-hydroxy metabolites of anthracyclines may contribute to cardiotoxicity. This study was designed to determine the pharmacokinetics of daunorubicin and the 13-hydroxy metabolite daunorubicinol in plasma and tissues, including the heart. Fisher 344 rats received 5 mg kg^–1 daunorubicin i.v. by bolus injection. Rats were killed at selected intervals for up to 1 week after daunorubicin administration for determination of concentrations of daunorubicin and daunorubicinol in the plasma, heart, liver, kidney, lung, and skeletal muscle. Peak concentrations of daunorubicin were higher than those of daunorubicinol in the plasma (133±7 versus 36±2 ng ml^–1;P<0.05), heart (15.2±1.4 versus 3.4±0.4 g g^–1;P<0.05), and other tissues. However, the apparent elimination half-life of daunorubicinol was longer than that of daunorubicin in most tissues, including the plasma (23.1 versus 14.5 h) and heart (38.5 versus 19.3 h). In addition, areas under the concentration/time curves (AUC) obtained for daunorubicinol exceeded those found for daunorubicin in almost all tissues, with the ratios being 1.9 in plasma and 1.7 in the heart. The ratio of daunorubicinol to daunorubicin concentrations increased dramatically with time from <1 at up to 1 h to 87 at 168 h in cardiac tissue. Thus, following daunorubicin injection, cumulative exposure (AUC) to daunorubicinol was greater than that to daunorubicin in the plasma and heart. If daunorubicinol has equivalent or greater potency than daunorubicin in causing impairment of myocardial function, it may make an important contribution to the pathogenesis of cardiotoxicity.     

TCP and NTCP in preclinical and clinical research in Europe

European research in radiation oncology has a long and successful tradition. The aim of this research is to increase the therapeutic window of radiotherapy by increasing the tumor control probability (TCP) and/or by decreasing the normal tissue complication probability (NTCP). This paper summarizes the basic radiobiological concept underlying treatment optimization by TCP-NTCP data and discusses some of the limitations of currently used models. These are controversial in many aspects and cannot be recommended for clinical routine practice but should rather be considered as a research tool.     

Foscan and foslip based photodynamic therapy in osteosarcoma in vitro and in intratibial mouse models

Current osteosarcoma therapies cause severe treatment‐related side effects and chemoresistance, and have low success rates. Consequently, alternative treatment options are urgently needed. Photodynamic therapy (PDT) is a minimally invasive, local therapy with proven clinical efficacy for a variety of tumor types. PDT is cytotoxic, provokes anti‐vascular effects and stimulates tumor cell targeting mechanisms of the immune system and, consequently, has potential as a novel therapy for osteosarcoma patients. This study investigated the uptake and the dark‐ and phototoxicity and cytotoxic mechanisms of the photosensitizer (PS) 5,10,15,20‐tetrakis(meta‐hydroxyphenyl) chlorine (mTHPC, Foscan) and a liposomal mTHPC formulation (Foslip) in the human 143B and a mouse K7M2‐derived osteosaroma cell line (K7M2L2) in vitro. Second, the tumor‐ and metastasis‐suppressive efficacies of mTHPC formulations based PDT and associated mechanisms in intratibial, metastasizing osteosarcoma mouse models (143B/SCID and syngeneic K7M2L2/BALB/c) were studied. The uptake of Foscan and Foslip in vitro was time‐ and dose‐dependent and resulted in mTHPC and light dose‐dependent phototoxicity associated with apoptosis. In vivo, the uptake of both i.v. administered mTHPC formulations was higher in tumor than in healthy control tissue. PDT caused significant (Foscan p < 0.05, Foslip p < 0.001) tumor growth inhibition in both models. A significant (Foscan p < 0.001, Foslip p < 0.001) immune system‐dependent suppression of lung metastasis was only observed in the K7M2L2/BALB/c model and was associated with a marked infiltration of T‐lymphocytes at the primary tumor site. In conclusion, mTHPC‐based PDT is effective in clinically relevant experimental osteosarcoma and suppresses lung metastasis in immunocompetent mice with beneficial effects of the liposomal mTHPC formulation Foslip.     

Hyperthermia and platinum complexes: Time between treatments and synergy in vitro and in vivo

To investigate the greatest therapeutic efficacy, we investigated the effect of scheduling on the cytotoxic interaction between hyperthermia and seven different platinum complexes in vitro and in vivo using the FSaII murine fibrosarcoma cells. Hyperthermia treatment (43°C, 1 h) was administered at various times relative to exposure of the cells to the IC₉₀ (at 37°C, 1 h) of each platinum complex. Greater-than-additive killing of FSaII cells was obtained with cis-diamminedichloroplatinum (II) (CDDP) and hyperthermia when the drug and heat exposure were overlapping or simultaneous. The same cell killing effect with carboplatin and hyperthermia resulted from heat exposure up to 5 h prior to, simultaneous with, or immediately after the drug exposure. D-Tetraplatin and K₂PtCl₄ were synergistic with hyperthermia only if the drug and heat exposure were simultaneous. PtCl₄(Nile Blue)₂ and hyperthermia produced greater-than-additive cell killing if the heat and drug exposure occurred in immediate sequence, simultaneously, or with drug exposure up to 5 h prior to heat exposure. PtCl₄(Rh-123)₂ and hyperthermia produced greater-than-additive cell killing if the drug and heat occurred in immediate sequence, overlapping, or simultaneously. PtCl₄(Fast Black)₂ and hyperthermia were additive over a wide range of scheduling from heat exposure 2 h prior to 5 h after drug exposure. When animals bearing FSaIIC tumours were treated with single doses of CDDP (10 mg/kg), carboplatin/PtCl₄(Nile Blue)₂ (50 mg/kg), PtCl₄(Rh-123)₂/PtCl₄(Fast Black)₂ (100 mg/kg) under various combined schedules with hyperthermia treatment (43°C, 30 min), similar cytotoxicity patterns were observed. To administer hyperthermia at a time when the drug concentration in the tumour tissue is at peak level, careful scheduling of systemically administered anticancer drugs with hyperthermia is needed. Modelling studies can identify the stringency/flexibility of drug/heat scheduling to achieve synergistic tumour cell killing.     

Racial Differences in Oral and Pharyngeal Cancer Treatment and Survival in Florida

OBJECTIVE: This study examined racial differences in treatment and survival for blacks and whites in Florida diagnosed with oral or pharyngeal cancer. METHODS: Data for 21,481 malignancies of the oral cavity or pharynx diagnosed from 1988 to 1998 were derived from the Florida Cancer Data System. Type of cancer treatment was compared by race, stratified by anatomic site and summary stage at diagnosis. Kaplan-Meier survival curves were used to compare survival rates and Cox regression models were used to estimate hazard ratios for race. Covariates included age, sex, census tract income, and treatment. RESULTS: Stratifying by tumor site and stage, blacks consistently had poorer survival rates than whites. Across tumor stages, blacks with oral cavity cancer were consistently more likely than whites to have received only radiotherapy and less likely to have received cancer-directed surgery. Trends were similar for pharyngeal cancer, although statistically significant only for regional stages. Across site and stage, blacks consistently had elevated hazard ratios (range: 1.20-1.53) relative to whites. CONCLUSIONS: In Florida, there were racial differences in patient treatment for oral or pharyngeal cancer. Blacks had lower survival rates than whites, but differences in treatment did not entirely account for racial disparities in survival.     

Serum ghrelin and esophageal and gastric cancer in two cohorts in China

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case–cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case–control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR _Q1:Q4) for GNCA in NIT was 1.35 (95% CI: 0.89–2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02–2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR _Q1:Q4 = 2.00, 95% CI: 1.45–2.77; p-trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR _Q1:Q4 = 0.65, 95% CI: 0.45–0.92; p-trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.     

Synergistic anti-cancer effects of immunotoxin and cyclosporin in vitro and in vivo

Background:

The clinical use of immunotoxins (ITs) has been hampered by hepatotoxicity, and the induction of a strong human-anti-IT response. The human-anti-IT response results in neutralisation of the immunoconjugates, rendering repetitive treatment inefficacious.

Methods:

We evaluated the combination of cyclosporin A (CsA) with various Pseudomonas exotoxin A-based ITs in human breast, cervical, and prostate cancer cell lines measured by protein synthesis, cell viability, and TUNEL assay. Furthermore, expression of essential proteins were analysed by western blot. We used cervical cancer model in nude rats to evaluate the anti-metastatic effect of the combination. The anti-immunogenic response by the CsA treatment was investigated in immunocompetent rats.

Results:

The combination of CsA with ITs caused remarkable synergistic cytotoxicity, in several cancer cell lines, characterised by protein synthesis inhibition, decreased cell viability, and an increased apoptotic index. Furthermore, the combination strongly inhibited formation of metastases in a cervical cancer model in nude rats with a statistically significant increase in median survival time of the combination-treated animals, as compared with those receiving a suboptimal dose of IT alone. Notably, we found in immunocompetent rats that the anti-IT immunoresponse elicited by repeated administration of IT was efficiently abrogated by CsA; notably the antibody responds towards the highly immunogenic PE was shown to be prevented.

Conclusion:

The combination of ITs and CsA might constitute a significant improvement in the clinical potential of systemic IT treatment of cancer patients.     

Fibronectin and integrins in invasion and metastasis

Summary The adhesive glycoprotein fibronectin and integrin receptors appear to play important roles in the progression of metastatic disease. Fibronectin is a multifunctional extracellular glycoprotein that has at least two independent cell adhesion regions with different receptor specificities. The cell adhesive region in the central portion of fibronectin is comprised of at least two minimal amino acid sequences - an Arg-Gly-Asp (RGD) sequence and a Pro-His-Ser-Arg-Asn (PHSRN) sequence - which function in synergy. Another cell adhesive region is located near the carboxy-terminus in the alternatively spliced IIICS module. The critical minimal sequences for this region are Leu-Asp-Val (LDV) and Arg-Glu-Asp-Val (REDV) which function in an additive rather than synergistic fashion. Integrins are heterodimeric, transmembrane cell adhesion receptors for fibronectin and other extracellular matrix molecules. Several different integrins bind to fibronectin. The ₅₁ fibronectin-specific integrin binds to the central RGD/PHSRN site. The ₄₁ integrin binds to the IIICS site. Fibronectin-integrin interactions are important in tumor cell migration, invasion, and metastasis. In addition to promoting cell adhesion to the extracellular matrix, these proteins may also function in chemotaxis and control of proliferation. Peptide and antibody inhibitors of fibronectin and integrin functions have been shown to be effective inhibitors of metastasis, and are potentially important reagents for the study and control of cancer.