胃癌淋巴结转移诊断的研究进展

近10年,胃癌的发病率虽然有所下降,但它仍是与癌症相关的常见死亡原因之一~([1]).侵袭和淋巴结转移是导致胃癌患者复发和转移的重要途径,是影响患者预后的重要因素.     

T淋巴瘤侵袭转移诱导因子1反义核酸抑制胃癌细胞侵袭黏附的研究

T淋巴瘤侵袭转移诱导因子1（Tiam1）是与胃癌侵袭转移密切相关的细胞骨架调节因子。我们采用反义技术抑制胃癌高侵袭转移细胞株中Tiam 1的表达，并观察对其体外黏附和侵袭、移行能力的影响。[第一段]     

半乳糖凝集素-1与胃癌侵袭及转移关系的研究进展

目的探讨半乳糖凝集素-1(Gal-1)与胃癌侵袭及转移间的关系。方法对近年来国内外有关Gal-1与胃癌侵袭及转移关系研究的相关文献进行综述。结果胃癌组织中Gal-1的表达与肿瘤细胞的侵袭力、转移能力、免疫抑制、血管生成等密切相关,在胃癌的进展与演变过程中发挥重要作用;Gal-1表达越高,提示肿瘤的恶性程度越高,患者的预后越差。结论 Gal-1的表达可促进胃癌的侵袭和转移,但仍需进一步临床研究予以验证。     

UPA及CD34与胃癌侵袭和转移的关系及其相关性研究

目的 检测胃癌组织中尿激酶型纤溶酶原激活物(UPA)、血管标志物CD34的表达,并探讨其与胃癌侵袭和转移的关系及其相关性.方法 采用免疫组化染色(SP法),按各自显色情况,对UPA进行半定量测定,对CD34进行定量测定.结果 UPA及CD34在胃癌组织中高表达,并随病理分级的降低、淋巴转移的产生、远隔转移的发生、临床分期的提高而明显增高.胃癌中UPA与CD34的表达呈正相关.结论 UPA、CD34对胃癌的发生、发展、侵袭和转移起重要的促进作用.UPA与CD34在胃癌的发生、发展、侵袭和转移相互促进,相互协调,关系密切.     

RhoC与胃癌的相关性研究进展

Rho是具有GTP酶活性的小G蛋白超家族成员,在细胞的信号转导通路中起重要作用,RhoC对肿瘤转移的作用尤为突出,被称为肿瘤侵袭转移的分子开关。胃癌侵袭转移是多基因协调作用的结果,本文就近年来RhoC在胃癌组织中侵袭转移的相关性研究作一综述。     

趋化因子受体 CXCR4在胃癌组织中的表达及意义

目的探讨CXCR4在胃癌组织中的表达及意义。方法应用RT-PCR法和免疫组织化学方法检测30例正常胃组织、86例胃癌组织中CXCR4的表达,其中86例胃癌中包括60例淋巴结转移和8例腹膜转移。结果 CXCR4蛋白在胃正常组织未见表达,在86例胃癌组织中的阳性表达率高达66.2%（57/86）。CXCR4的表达与胃癌患者的年龄、性别、胃癌组织类型无关,而与临床转移有关。结论 CXCR4m RNA及蛋白在胃癌组织、胃癌转移淋巴组织和胃癌腹膜转移组织中的表达上调与胃癌侵袭转移的发生和淋巴结及腹膜转移有关,CXCR4很可能是协同胃癌进展、胃癌淋巴结转移,尤其是腹膜侵袭转移的一个重要分子。     

肿瘤相关成纤维细胞通过转化生长因子β调节胃癌细胞转移能力的研究

目的 :通过研究肿瘤相关成纤维细胞(cancer-associated fibroblast,CAF)促进胃癌细胞侵袭迁移的能力,探讨胃癌转移机制。方法:从胃癌组织分离CAF。通过transwell小室模型和Western印迹法检测CAF与胃癌细胞共培养对胃癌细胞侵袭迁移能力、上皮细胞间充质转化(epithelial mesenchymal transition,EMT)的影响。使用ELISA和定量PCR分别检测CAF转化生长因子β1(transforming growth factor-β1,TGF-β1)分泌水平和TGFB mRNA表达水平。进一步通过Western印迹法检测共培养后胃癌细胞中TGF-β信号通路标志物Smad2和磷酸化Smad2的表达水平。使用TGF-β拮抗剂阻断TGF-β信号通路,检测CAF对胃癌细胞EMT及侵袭迁移能力影响。结果:CAF促进MKN28侵袭迁移和发生EMT。CAF的TGF-β1分泌量较高于NF。与CAF共培养后,TGF-β信号通路活化。TGF-β拮抗剂抑制CAF诱导胃癌细胞发生EMT和CAF促胃癌细胞侵袭迁移的能力。结论:CAF通过分泌TGF-β诱导胃癌细胞发生EMT,从而促进了胃癌细胞侵袭能力,可能是胃癌转移的重要机制。     

CCDC与恶性肿瘤的研究进展

卷曲螺旋结构域（CCDC）蛋白具有许多重要生物学功能,并能调控恶性肿瘤细胞的侵袭和转移等多种生物学行为.目前已证实,CCDC蛋白在鼻咽癌、胃癌、前列腺癌、胰腺癌、乳腺癌、结直肠癌中的异常表达,且与肿瘤细胞迁移、侵袭和转移表型的获得有着直接的联系.CCDC蛋白的表达异常及其相关通路的抑制能明显影响肿瘤侵袭和转移,这为新型医药应用于肿瘤靶向治疗提供了理论依据.     

肿瘤相关巨噬细胞在胃癌中的作用研究进展

随着肿瘤相关巨噬细胞与恶性肿瘤关系的日益明晰,肿瘤相关巨噬细胞已成为癌症治疗的一个有前途的靶点。肿瘤相关巨噬细胞通常分为两种亚型：M1型和M2型。前者具有典型的抗肿瘤功能,后者可促进肿瘤细胞的发生、侵袭和转移等。本文就肿瘤相关巨噬细胞的起源、类型、生物学特点、对胃癌免疫逃逸、侵袭、转移的影响、胃癌靶向治疗策略、对胃癌耐药的影响以及其原代细胞获取方法等研究进展做一综述。     

计算机分析影响胃癌淋巴结转移的因素

目的:回顾性分析影响胃癌淋巴结转移的诸因素,为合理制定根治术式提供理论依据.方法:分析554例胃癌切除术患者的病史、手术记录和病理检测结果资料.应用BMDP软件包计算不同部位淋巴结转移者术后逐年生存率,采用单因素和Logistic回归多因素分析方法探讨胃癌临床病理特点与淋巴结转移的关系.结果:淋巴结转移者和无转移者5年生存率分别为31.04%和90.9%.单因素分析发现,大体类型、分化程度、浸润深度、原发部位及肿瘤大小均与淋巴结转移有关;多因素分析则发现肿瘤浸润深度及肿瘤大小为影响淋巴结转移的独立因素.结论:淋巴结转移是影响胃癌患者预后的重要因素,而胃癌的临床病理特点与淋巴结转移密切相关.     

Prognostic significance of CyclinD1 and E-Cadherin in patients with esophageal squamous cell carcinoma: multiinstitutional retrospective analysis

BACKGROUND:

Although many molecular biologic molecules have been analyzed for their prognostic influence on patients with esophageal cancer, previous studies have not been able to raise statistically significant prognostic factors.

STUDY DESIGN:

Immunohistochemical analysis of CyclinD1 expression and E-Cadherin expression was performed retrospectively in 416 esophageal squamous cell cancer patients who underwent curative resection of esophageal cancer at 10 major surgical departments in Japan, where more than 30 esophagectomies are performed in a year. The prognostic impact of these molecules and their relationship to clinicopathologic data of the patients were evaluated.

RESULTS:

Univariate analysis revealed that pN (pTNM), pT (pTNM), CyclinD1 expression, and E-Cadherin expression were significant prognostic factors, and multivariate analysis revealed that pN (risk ratio (RR) 2.19), pT (RR 3.35), CyclinD1 (RR 1.42), and E-Cadherin (RR 0.71) were significant prognostic factors. Combination analysis of these genes revealed that E-Cadherin-preserved and CyclinD1-negative patients had the best prognosis; E-Cadherin-reduced and CyclinD1-positive patients had the worst prognosis.

CONCLUSIONS:

Increased CyclinD1 expression and reduced E-Cadherin expression were significant prognostic factors in patients with esophageal squamous cell carcinoma.     

Cell surface molecules and their prognostic values in assessing colorectal carcinomas

OBJECTIVE: Carcinomas of the colon and rectum are the third leading cause of cancer-related deaths. Although advances in the surgical treatment of primary colorectal cancers have lead to improvements in patient survival at early tumor stages, treatment of more progressive cancers has not resulted in dramatic improvements in patient survival. However, the selection of patient subgroups based on their prognosis and other characteristics could result in improved outcomes from adjuvant therapies in patients with Dukes B and C carcinomas. METHODS: The authors reviewed the available data on the value of cell surface molecules in assessing the prognosis of colorectal carcinomas, paying specific attention to the evaluation of statistical analysis and multivariate procedures. RESULTS: Cell surface molecules have been identified on colorectal carcinoma cells whose expression appears to be related to malignant transformation, tumor progression, or patient prognosis. Among these cell surface molecules, various cell adhesion molecules, growth factor receptors, proteinases, and their receptors and inhibitors have been identified as potentially useful prognostic markers. CONCLUSIONS: Although data exist on the prognostic values of certain cell surface markers, the use of multivariate analysis for the identification of valuable prognostic factors remains uncommon. Using reproducible and standardized multivariate analysis procedures, new tumor markers should be carefully examined for their biologic and prognostic relevance before being considered as potentially useful in the management of colorectal cancers.     

Biomolecular prognostic factors in colorectal cancer

There is general agreement that staging of colorectal neoplasms based on classic anatomopathological parameters does not allow accurate selection of patients at higher risk of an adverse outcome. For this reason, identification of new prognostic factors is desirable. Such factors should be easily determined and expressed at an early stage of carcinogenesis. Moreover, it would be useful to identify factors predictive of response to radiotherapy and chemotherapy. Various molecules are involved in the carcinogenetic pathway and metastasis formation. The aim of this review is to analyse whether any of them are currently useful in clinical practice and which of them warrant further study. At present, apart from CEA, whose prognostic value has been known for some time, we do not have sufficient data to definitively incorporate any of the other biomarkers in clinical practice. The most promising factors would appear to be loss of heterozigosity of chromosome 18q21 (DCC) and microsatellite instability. However, other molecules warrant further in-depth study. In particular, growth factor receptors may play a role not only as prognostic factors but also in view of their therapeutic potential.     

Current status of prognostic factors in patients with metastatic renal cell carcinoma

In recent years, the induction of novel agents, including molecular‐targeted agents and immune checkpoint inhibitors, have dramatically changed therapeutic options and their outcomes for metastatic renal cell carcinoma. Several prognostic models based on the data of patients with metastatic renal cell carcinoma treated with targeted agents or cytokine therapy have been useful in real clinical practice. Serum or peripheral blood markers related to inflammatory response have been reported to be associated with their prognosis or therapeutic efficacy. In addition to them, investigation for novel predictive factors that represent the efficacy of agents, the risk of adverse events and the prognosis are required for the advance of therapeutic strategies. The present review discusses the conventional prognostic models and clinical factors, and recent advances of the identification of some of the most promising molecules as novel biomarkers for metastatic renal cell carcinoma.     

Molecular Prognostic Factors in Adenocarcinoma of the Esophagus and Gastroesophageal Junction

Objective This review describes genetic and molecular changes related to adenocarcinoma of the esophagus and gastroesophageal junction (GEJ) with emphasis on prognostic value and possibilities for targeted therapy in clinical setting. Summary background data Adenocarcinoma of the esophagus or GEJ is an aggressive disease with early lymphatic and hematogenous dissemination. Molecular pathology has revealed many molecular mechanisms of disease progression, which are related to prognosis. Some of these factors can be seen as prognostic factors per se. Better knowledge of molecular bases may lead to new paradigms, improved prognostication, early diagnosis and individually tailored therapeutic options. Methods A review of recent English literature (1990–October 2005) concerning esophageal adenocarcinoma was performed. This review focuses on genetic and molecular changes as prognosticators of adenocarcinoma of the esophagus and GEJ. Results A bewildering number of biomarkers have been described. Many genes and molecules have prognostic impact (cyclin D1, EGFR, Her-2/Neu, APC, TGF-β, Endoglin, CTGF, P53, Bcl-2, NF-κB, Cox-2, E-cadherin, β-catenin, uPA, MMP-1,3,7,9, TIMP, T _h 1/T _h 2 balance, CRP, PTHrP). Conclusions Adenocarcinomas of the esophagus and GEJ show multiple genetic alterations, which indicate that progression of cancer is a multistep complex process with many different alterations. Presumably, it is not one molecular factor that can predict the biological behavior of this cancer. The combination of diverse genetic alterations may better predict prognosis. In future, gene expression analysis with microarrays may reveal important prognostic information and the discovery of new genes and molecules associated with tumor progression and dissemination will enhance prognostication and offers adjuvant therapeutic options.     

Prognostic factors in upper urinary tract urothelial carcinomas: a comprehensive review of the current literature

Context

The heterogeneity of upper tract urothelial carcinoma (UTUC) biology and prognosis, as well as the presence of different treatment options, makes the clinical decision-making process extremely challenging.

Objective

Provide an overview of the currently available prognostic factors for UTUC, focusing on clinical and pathologic characteristics, as well as on molecular markers.

Evidence acquisition

A systematic literature search was conducted using the PubMed, Scopus, and Embase databases to identify original articles, review articles, and editorials regarding prognostic factors in patients with UTUC. Keywords included urothelial carcinoma, renal pelvis, ureter, upper urinary tract urothelial carcinoma, upper urinary tract transitional cell carcinoma, prognosis, prognostic factors, markers, and survival. Articles published between 2000 and 2011 were reviewed and selected with the consensus of all the authors.

Evidence synthesis

Prognostic factors can be divided into four different categories: preoperative/clinical factors, intraoperative/surgical factors, postoperative/pathologic factors, and molecular markers. Because of the rarity of the disease, only a small amount of level 1 evidence information from prospective randomized trials is available. Conversely, several single-institutional and multi-institutional studies have been published providing level 3 evidence information on various prognostic factors. Tumor stage and grade represent the best-established predictors of prognosis in patients with UTUC, but controversies still exist regarding the prognostic impact of tumor location and tumor necrosis. Several promising biomarkers have also been evaluated, but further studies evaluating their prognostic role are still needed. Finally, few prognostic models have been developed to provide clinicians with accurate estimates of the outcome of interest.

Conclusions

In the past few years, several prognostic factors have been identified to help clinicians dealing with patients with UTUC in the decision-making process. However, well-designed multi-institutional studies are still needed to provide stronger evidence and to promote the use of these prognostic factors in clinical practice.     

Prognostic Factors and Staging Systems for Renal Cell Carcinoma

ObjectivesPrimary tumour local extension, lymph-node status, and the presence of metastases have always been considered the most important prognostic factors in renal cell carcinoma (RCC). In recent years, many other clinical, pathological, and molecular factors able to independently predict survival in RCC have been proposed and discussed. The aim of this unsystematic literature review is to describe the most important advances in RCC prognostication.ResultsThe review provides updated information regarding the most important clinical (performance status, localized or systemic symptoms), pathological (Fuhrman nuclear grade, histological subtypes, sarcomatoid features, tumour necrosis), and molecular (molecules involved in the hypoxia-inducible pathway, proliferation, cell cycle regulation, or cell adhesion) prognostic factors. It also highlights the issues related to RCC staging systems, such as the debate about the ideal cut-off to stratify patients with localized disease into two categories with different survival as well as the different prognostic impact of perinephric fat invasion, ipsilateral adrenal gland involvement, venous axis neoplastic thrombosis, and the possible synergistic role of their association in locally advanced disease.ConclusionsThe ongoing development of integrated models combining different features improves the accuracy of survival prediction, thus allowing more detailed patient information, correct follow-up planning, and adequate recruitment and interpretation of clinical trials.     

Metastasis markers in bladder cancer: a review of the literature and clinical considerations

Cancer invasion and metastasis develop through a sequence of processes involving loss of cell-cell and cell-matrix adhesions, proteolysis and induction of angiogenesis. We reviewed the current literature on the molecules that have been shown to play a significant role in these three steps of metastatisation in bladder cancer (BC) cells and their host microenvironment. Particular emphasis was given to markers that are assessable through immunohistochemistry and for which an additional prognostic value over the TNM variables has been recognized, in order to identify a subset of tumour markers readily available for application in daily clinical practice. We conclude that markers such as E-cadherin, Sialosyl-LeX, laminin, collagen IV, TSP-1 and MVD are useful prognostic markers, alpha, beta, and gamma catenin, MMP-2 and -9, uPAR, PD-ECGF and Bfgf can be considered potentially useful, while research on CD44, MMP-1 and -3, uPA, cathepsin D and VEGF has proved inconclusive. Further research in this field should concentrate on the molecules listed in the first group.     

Prognostic factors in localised and regionally advanced renal cell carcinoma

In the last 10 years, several factors have been identified to confer a prognostic effect on renal cancer outcome. Pathologic stage, nuclear and histologic grade are the most frecuent studied and the most important at this moment. We evaluated those factors and introduced some others, looking for new parameters that could be useful. 96 cases of non methastatic renal cell cancer were included in our study. We found that as was mentioned by other authors pathologic and Furhman stage are the stronger prognostic factors but the presence of palpable tumor, pain and weight lost had significance too.     

Prognostic factors and risk classifications for patients with metastatic renal cell carcinoma

The introduction of molecular‐targeted therapy has made dramatical changes to treatment for metastatic renal cell carcinoma. Currently, there are four vascular endothelial growth factor receptor‐tyrosine kinase inhibitors and two mammalian target of rapamycin inhibitors in Japan. For the appropriate clinical use of these molecular‐targeted drugs, the identification of prognostic and/or predictive factors in patients who received these drugs is required. Although molecular biological and genetic factors that determine the prognosis of patients with metastatic renal cell carcinoma have been reported, most of these factors are problematic in that the number of patients analyzed was small. In contrast, clinicopathological prognostic factors, including the practice of cytoreductive nephrectomy, pathological findings, metastatic sites and metastasectomy, and abnormal inflammatory response, have been identified by analyzing a relatively large number of patients. Several prognostic classification models that were developed by combining these clinicopathological factors are widely used in not only clinical trials, but also routine clinical practice. However, the quality of these prognostic models is considered to be insufficient regarding prognostic prediction of metastatic renal cell carcinoma patients and, thus, requires further improvements. Recently, basic and clinical studies have been extensively carried out for the identification of promising informative markers and for understanding molecular mechanisms of resistance to molecular‐targeted drugs in metastatic renal cell carcinoma patients. The present review considers ongoing translational research efforts on clinicopathological, molecular biological, and genetic prognostic and/or predictive factors for metastatic renal cell carcinoma patients in the era of molecular‐targeted therapy, and discusses the clinical implications of these findings.