Cellular immunotherapy for soft tissue sarcomas

Soft tissue sarcomas are rare neoplasms, with approximately 9000 new cases in the USA every year. Unfortunately, during the past two decades, there has been little progress in the treatment of metastatic soft tissue sarcomas beyond the standard approaches of surgery, chemotherapy and radiation. Immunotherapy is a modality complementary to conventional therapy. It is appealing because functional antitumor activity could affect both local-regional and systemic disease, and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies that are being developed, including several tumor vaccine, antigen vaccine and dendritic cell vaccine strategies.     

食管鳞癌组织VCAM-1和Survivin的表达及意义

目的探讨血管细胞黏附分子1（VCAM-1）和Survivin与食管鳞癌细胞发生、发展与转移的关系。方法采用免疫组化法检测24例正常食管黏膜、94例食管鳞癌组织中Survivin和VCAM-1的表达情况。结果VCAM-1和Survivin在癌组织中的表达率明显高于正常食管黏膜,其中VCAM-1表达与淋巴结转移、浸润深度和临床分期等因素有关（P均〈0．05）;Survivin表达与浸润深度有关（P〈0．01）;VCAM-1和Survivin在癌组织中的表达无相关性。结论VCAM-1和Survivin在食管鳞癌中高表达,二者在食管鳞癌的发生、发展过程中具有重要作用,可作为评价食管鳞癌生物学行为的指标。     

Cellular biology of the renin-angiotensin systems

The renin-angiotensin system is a major determinant of arterial pressure and intravascular volume in human beings. Recent evidence, however, suggests that renin can be synthesized at local tissue sites and that these local renin-angiotensin systems subserve important physiologic functions. In addition, it appears that there exist intracellular renin-angiotensin "systems" capable of generating angiotensin II intracellularly.     

Clinical significance of expression of apoptotic signal proteins in gastric carcinoma tissue

AIM: To evaluate the expressions of apoptotic signal proteins FADD, TRADD, FasL, Fas, and NFκB in gastric carcinoma tissues and their clinical significance. METHODS: Western blot immune trace method was adopted to detect the expressions of apoptotic signal proteins FADD, TRADD, FasL, Fas, and NFκB in 55 tissue specimens of gastric carcinoma. RESULTS: Five apoptotic signal proteins had different expressions in the gastric carcinoma samples and their expressions were not correlated to age (P= 0.085). Expressions of the FADD, FasL, Fas, and NFkB proteins reduced with increase of the volume of tumor with the exception of increased expression the TRADD protein (64.7-71.1%, P= 0.031). With gradual increase of the malignancy of gastric carcinoma tissues, expressions of the FADD, FasL, and Fas proteins decreased (78.6-28.0%, P= 0.008; 78.6-65.9%, P= 0.071; 100.0-46.3%, P= 0.014), while expressions of the TRADD and NFkB proteins increased (42.9-78.1%, P= 0.063; 78.6-79.1%, P= 0.134). With gradual increase of serum CEA, expression of the FADD protein decreased (62.5-34.0%, P = 0.073), but expressions of the TRADD, FasL, Fas, and NFκB proteins increased (0.0-80.8%, P=0.005; 62.5-70.2%, P= 0.093; 0.0-70.2%, P=0.003; 62.5-80.9%, P= 0.075). When compared to the tissues of gastric carcinoma without metastasis, the positive rate of expressions of the FADD and FasL proteins increased, whereas expressions of the TRADD, FADD, and NFkB proteins decreased. There was no significant difference between them (P= 0.095). CONCLUSION: Gastric carcinoma is endurable to Fas-related apoptosis and apoptotic signal proteins are differently expressed in gastric carcinoma.     

Cellular composition of stent-penetrating tissue

BACKGROUND: A surprisingly low number (< 20%) of relevant (> 75%) restenoses occur in exophytic lesions after treatment with uncovered metal stents. The goal of this study was to investigate whether radial stent forces can exert localized influence on tumor growth. PATIENTS AND METHODS: In 17 patients, intraluminal tumor tissue was histologically investigated before and 1 week after stent implantation. The amount of intact tumor cells (ITCs) was compared to necrotic and nontumor cells. The result in patency was proved by fiberoptic bronchoscopy. RESULTS: Initially, stenoses in all patients were > 75%. Before stent implantation, biopsy samples in seven patients showed > 67% ITCs, and five patients had 34 to 67% ITCs. Five patients had 1 to 33% ITCs, and no patients had 0% ITCs. One week after stent implantation, the cellular aspect of the biopsy samples had changed significantly (p < 0.03): two patients had > 67% ITCs, one patient had 34 to 67% ITCs, and seven patients had 1 to 33% ITCs. Seven patients had no ITCs at all. Endoscopically, patency increased significantly (prestent, 10 +/- 14.1%; poststent, 90.6 +/- 14.3% [mean +/- SD]; p < 0.0001). CONCLUSION: Pressure exerted by the stent on adjacent tumor tissue may cause a profound reduction in the amount of ITCs, most probably caused by radial and shear stress forces that compromise blood supply and nutrients of the tumor stroma.     

Cellular localization and trafficking of tissue factor

Tissue factor (TF) is the cellular receptor for clotting factor VIIa (FVIIa). The formation of TF-FVIIa complexes on cell surfaces triggers the activation of coagulation cascade and cell signaling. In the present study, we characterized the subcellular distribution of TF and its transport in fibroblasts by dual immunofluorescence confocal microscopy and biochemical methods. Our data show that a majority of TF resides in various intracellular compartments, predominantly in the Golgi. Tissue factor at the cell surface is localized in cholesterol-rich lipid rafts and extensively colocalized with caveolin-1. FVIIa binding to TF induces the internalization of TF. Of interest, we found that TF-FVIIa complex formation at the cell surface leads to TF mobilization from the Golgi with a resultant increase in TF expression at the cell surface. This process is dependent on FVIIa protease activity. Overall, the present data suggest a novel mechanism for TF expression at the cell surface by FVIIa. This mechanism could play an important role in hemostasis in response to vascular injury by increasing TF activity where and when it is needed.     

三种ED模型小鼠海绵体组织Cx43蛋白表达变化

目的 观察三种阴茎勃起功能障碍(ED)小鼠海绵体组织中连接蛋白(Cx)43表达变化.方法 将125只Wistar大鼠随机分为DM因素组35只、血管因素组31只、神经因素组28只及对照组31只,其中前三组分别通过腹腔注射链脲菌素(STZ)、结扎髂内动脉及游离并切断海绵体神经等方法建立ED模型.各组均于制模后3周进行阿朴吗啡试验,观察大鼠阴茎勃起情况;并分别于8、12、16周分批断颈处死,采用免疫组化法检测阴茎海绵体组织的Cx43.结果 DM因素组、血管因素组及神经因素组勃起比例及次数均明显低于对照组,阴茎海绵体组织Cx43蛋白表达显著低于对照组(P＜0.01),尤以DM因素组为著(P＜0.05).结论 三种ED小鼠海绵体组织中Cx43蛋白表达均下降,尤以DM性ED为著.     

Cellular senescence and tissue aging in vivo

A long-standing controversy concerns the relevance of cellular senescence, defined and observed as a cell culture phenomenon, to tissue aging in vivo. Here the evidence on this topic is reviewed. The main conclusions are as follows. First, telomere shortening, the principal known mediator of cellular senescence, occurs in many human tissues in aging. Second, it is not clear whether this results in cellular senescence or in some other cell fate (e.g., crisis). Third, rodents probably are not appropriate experimental models for these questions, because of important differences in telomere biology between rodent cells and cells from long-lived mammals (e.g., human or bovine cells). Fourth, better and more comprehensive observations on aging human tissues are needed to answer the question of the occurrence of senescent cells in tissues, and new experimental approaches are needed to elucidate the consequences of telomere shortening in tissues in aging.     

Cellular actions of the insulin-like growth factor binding proteins

In addition to their roles in IGF transport, the six IGF-binding proteins (IGFBPs) regulate cell activity in various ways. By sequestering IGFs away from the type I IGF receptor, they may inhibit mitogenesis, differentiation, survival, and other IGF-stimulated events. IGFBP proteolysis can reverse this inhibition or generate IGFBP fragments with novel bioactivity. Alternatively, IGFBP interaction with cell or matrix components may concentrate IGFs near their receptor, enhancing IGF activity. IGF receptor-independent IGFBP actions are also increasingly recognized. IGFBP-1 interacts with alpha(5)beta(1) integrin, influencing cell adhesion and migration. IGFBP-2, -3, -5, and -6 have heparin-binding domains and can bind glycosaminoglycans. IGFBP-3 and -5 have carboxyl-terminal basic motifs incorporating heparin-binding and additional basic residues that interact with the cell surface and matrix, the nuclear transporter importin-beta, and other proteins. Serine/threonine kinase receptors are proposed for IGFBP-3 and -5, but their signaling functions are poorly understood. Other cell surface IGFBP-interacting proteins are uncharacterized as functional receptors. However, IGFBP-3 binds and modulates the retinoid X receptor-alpha, interacts with TGFbeta signaling through Smad proteins, and influences other signaling pathways. These interactions can modulate cell cycle and apoptosis. Because IGFBPs regulate cell functions by diverse mechanisms, manipulation of IGFBP-regulated pathways is speculated to offer therapeutic opportunities in cancer and other diseases.     

Theory and models for planning and evaluating institutional influenza prevention and control programs

BACKGROUND: Low rates of staff influenza vaccine coverage occur in many health care facilities. Many programs do not offer vaccination to physicians or to volunteers, and some programs do not measure coverage or do so only for a subset of staff. The use of theory in planning and evaluation may prevent these problems and lead to more effective programs. METHOD: We discuss the use of theory in the planning and evaluation of health programs and demonstrate how it can be used for the evaluation and planning of a hospital or nursing home influenza control program. RESULTS: The application of theory required explicit statement of the goals of the program and examination of the assumptions underlying potential program activities. This indicated that staff should probably be considered as employees, volunteers, physicians, and contractors of the facility. It also directed attention to evidence-based strategies for increasing vaccination rates. CONCLUSION: The application of a program planning model to a problem of institutional influenza prevention may prevent planners from excluding important target populations and failing to monitor the important indicators of program success.     

利用组织芯片技术研究PTEN和VEGF在胃癌中的表达及意义

目的研究PTEN和血管内皮生长因子（vascular endothelial growth factor，VEGF）在胃癌中的表达及临床意义。方法应用组织微阵列仪制作97孔胃癌组织芯片（tissue microarray）。用免疫组织化学S—P法检测PTEN、VEGF在72例胃癌和25例正常胃黏膜中的表达。结果胃癌组织中PTEN蛋白阳性表达率显著低于正常胃黏膜（45．8％ VS 100％，P〈0．01）；VEGF的阳性表达率显著高于正常胃黏膜（75％VSl2％，P〈0．01），PTEN在胃癌中的表达与VEGF呈负相关（P〈0．01）。PTEN、VEGF的表达在中高分化腺癌分别为68．8％、62．5％（P〉0．05），在低分化及未分化腺癌分别为27．5％、85．0％（P〈0．05）；伴淋巴结转移者分别为31．6％、86．9％（P〈0．05），无淋巴结转移者分别为61．8％、61。8％（P〉0．05）；临床病理分期Ⅰ＋Ⅱ期分别为57．1％、61．9％（P〉0．05），Ⅲ＋Ⅳ期分别为30．0％、93．3％（P〈0．05）；与性别、年龄、肿瘤大小和组织分型无显著差异（P〉0．05）。结论PTEN失活或蛋白表达降低、VEGF的高表达与胃癌临床病理特征和生物学行为有密切关系。PTEN在低分化或未分化以及伴淋巴结转移和临床Ⅲ＋Ⅳ期胃癌中的表达与VEGF呈负相关。联合检测PTEN、VEGF对胃癌的恶性程度及预后判断具有一定的临床参考意义。应用组织芯片大规模高效检测临床组织样本是可行的，具有快速、准确、方便经济的特点。     

Comparison of four models for end-stage liver disease in evaluating the prognosis of cirrhosis

AIM： To investigate the prognostic value of the model for end-stage liver disease （MELD） and three new MELD-based models combination with serum sodium in decompensated cirrhosis patients-the MELD with the incorporation of serum sodium （MELD-Na）, the integrated MELD （iMELD）, and the MELD to sodium （MESO） index. METHODS： A total of 166 patients with decompensated cirrhosis were enrolled into the study. MELD, MELD- Na, iMELD and MESO scores were calculated for each patient following the original formula on the first day of admission. All patients were followed up at least 1 year. The predictive prognosis related with the four models was determined by the area under the receiver operating characteristic curve （AUC） of the four parameters. Kaplan-Meier survival curves were made using the cut-offs identified by means of receiver operating characteristic （ROC）. RESULTS： Out of 166 patients, 38 patients with significantly higher MELD-Na （28.84 ± 2.43 vs 14.72 ± 0.60）, iMELD （49.04 ± 1.72 vs 35.52 ± 0.67）, MESO scores （1.59 ± 0.82 vs 0.99 ± 0.42） compared to the survivors died within 3 mo （P 〈 0.001）. Of 166 patients, 75 with markedly higher MELD-Na （23.01 ± 1.51 vs 13.78 ± 0.69）, iMELD （44.06 ± 1.19 vs 34.12 ± 0.69）, MESO scores （1.37 ± 0.70 vs 0.93 ± 0.40） than the survivors died within 1 year （P 〈 0.001）. At 3 mo of enrollment, the iMELD had the highest AUC （0.841）, and was followed by the MELD-Na （0.766）, MESO （0.723）, all larger than MELD （0.773）; At year, the iMELD still had the highest AUC （0.783）, the difference between the iMELD and MELD was statistically significant （P 〈 0.05）. Survival curves showed that the three new models were all clearly discriminated the patients who survived or died in short-term as well as intermediate-term （P 〈 0.001）. CONCLUSION： Three new models, changed with serum sodium （MELD-Na, iMELD, MESO） can exactly predict the prognosis of patients with decompensated cirrhosis fo     

Cellular and molecular mechanisms of atherosclerosis with mouse models

Recently, there has been an explosion in the number of in vivo studies using genetically engineered mouse models. Atherosclerosis research using mice began with the invention of traditional atherosclerotic mice including low-density lipoprotein receptor knockout (LDLR(-/-)) and apolipoprotein E knockout (apoE(-/-)) mice, which provided tremendous progress in atherosclerosis research. Since then, a number of modified atherosclerotic mouse models have been reported to generate lesions that more closely characterize human atherosclerotic lesions. Those modifications include inflammation, hypertension, proteinases and extracellular matrix, glucose metabolism, and immune systems. This article focuses on various kinds of mouse models with atherosclerosis and their contributions to the current advances of research.