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??Analysis of lymph node metastasis and clinicopathological characteristics in rectal cancer ZHAO Ze-liang, YANG Xin-hui, SUN Zhen-qiang, et al. Department of Abdomen Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi 830011, China
Corresponding author??WANG Hai-jiang, E-mail??wanghaijiang@medmail. com.cn
Abstract Objective To investigate the effect of clinicopathological characteristics on lymph node metastasis in rectal cancer. Methods The clinicopathological data of 210 patients with rectal cancer performed operation between January 2007 and December 2009 in Affiliated Tumor Hospital of Xinjiang Medical University were analyzed retrospectively. The risk factors of lymph node metastasis were evaluated. Results The rate of lymph node metastasis in all patients was 30.5%. The clearance rate of positive lymph nods was 14.5%. The statistical analysis showed that there was no correlation between rectal cancer lymph node metastasis and gender, nationality, age, infiltration degree, CEA level, vessel tumor embolus, tumor size or site (P>0.05). The univariate analysis revealed that infiltration depth, tissue type, general categories and cell differentiation degree were related to the lymph node metastasis of rectal cancer. The multivariate analysis demonstrated that infiltration depth, general categories and cell differentiation degree were independent factors predicting rectal cancer lymph node metastasis (P<0.05). The logistic regression analysis showed that in all the factors affecting on intensity of lymph node metastasis, cell differentiation degree was greater than infiltration depth, and there were significant differences between mass type and ulceration type as well as between mass type and infiltration type(P<0.05). Conclusion General categories, cell differentiation degree, tissue type and infiltration depth can be used to evaluate the biological behaviors and lymph node metastasis of rectal cancer. And general categories, cell differentiation degree and infiltration depth are independent factors predicting rectal cancer lymph node metastasis. In the general types of rectal cancer, the risks of lymph node metastases in the types of mass, ulceration and infiltration are increased in turn.     

表皮生长因子受体与乳酸脱氢酶在胰腺癌中的表达及意义的TIMER数据库分析

目的:应用生物信息学方法探讨表皮生长因子受体(EGFR)及乳酸脱氢酶(LDHA)在胰腺癌局部免疫微环境中的表达及意义。方法:运行TIMER(Tumor IMmune Estimation Resource)数据库,获取178例胰腺癌患者的临床信息,以及患者组织标本中EGFR、LDHA、胰腺癌相关信号分子的表达以及各亚群免疫细胞浸润数据,通过人类蛋白表达图谱,搜索EGFR、LDHA以及胰腺癌相关信号分子的蛋白表达丰度。采用Log-rank检验及Cox比例风险回归模型分析EGFR与LDHA表达以及各亚群免疫细胞与其他临床因素对患者预后的影响,并分析EGFR与LDHA与两者与胰腺癌相关信号分子的关系。结果:胰腺癌组织中EGFR与LDHA mRNA的表达水平均明显高于正常胰腺组织(均P0.05);在胰腺癌组织中,EGFR和LDHA mRNA呈正相关(P0.001)。EGFR mRNA高表达、LDHA mRNA高表达、低水平CD4~+T细胞的胰腺癌患者总体生存率较差(均P0.05)。LDHA是胰腺癌的独立预后因素(P0.001)。EGFR与胰腺癌相关信号分子P38、FOXM1、PD-L1、CSF1、CSF1R表达呈明显正相关,而LDHA与FOXM1、CSF1、CSF1R表达呈明显正相关(均P0.001)。EGFR、LDHA、P38、FOXM1和CSF1R蛋白在胰腺癌组织的表达丰度高于正常胰腺组织。结论:在胰腺癌组织中,EGFR与LDHA的表达升高,两者尤其是LDHA,可能通过对胰腺癌相关信号分子表达及局部免疫微环境的调控,从而影响患者预后。     

Growth Factors in Gliomas Revisited

Overexpression or untimely expression of wild-type or mutated protein growth factors and their receptors is associated with the biology of malignant gliomas and other types of cancer. It may result in unchecked tumour cell proliferation, migration/invasion into normal tissue, tumour angiogenesis, escape from immune surveillance, and decreased apoptotic cell death, i.e. after treatment with cytotoxic agents. This often involves activation of growth factor receptors either by simultaneous production of growth factors and corresponding receptors on the same or adjacent tumour cells or by constitutive receptor activation due to mutations. In several instances, the cellular genes encoding these growth factors and receptors are homologous to transforming genes/oncogenes from tumourigenic retroviruses and have thus been regarded as cellular proto-oncogenes. In recent years much progress has been made towards a better understanding of the function of these molecules and how they lead to the aggressive phenotype of malignant gliomas and its inherent resistance to adjuvant therapies. This, still insufficient, knowledge is a prerequisite for the development of novel therapies for this non-curable disease. The aim of this review is to address relevant growth factor receptor systems with emphasis on their particular role in glioma biology.     

血管内皮生长因子D和微淋巴管密度及微血管密度与直肠癌进展的关系

目的研究血管内皮生长因子D（VEGF—D）、微淋巴管密度（MLD）和微血管密度（MVD）在直肠癌中的表达情况及它们与直肠癌发展、转移的相关性。方法选取手术切除并经病理证实的中低位直肠癌标本80例、直肠息肉标本40例和正常直肠组织80例，应用免疫组织化学方法测定其VEGF—D的表达和MLD、MVD水平。结果（1）VEGF—D在直肠癌组织中的阳性率为55％（44／80），直肠息肉和正常直肠组织则均为0（P〈0．05）；MLD在直肠癌组织中为2．80±1．31，直肠息肉中为0．50±0．72，正常直肠组织中MLD为0．25±0．44，直肠癌组织中的MLD明显高于直肠息肉和正常直肠组织（P〈0．05）；MVD在直肠癌组织中为80．10±23．18，直肠息肉中为27．00±11．01，正常直肠组织中为10．45±5．34，直肠癌组织中的MVD明显高于直肠息肉和正常直肠组织（P〈0．05）。（2）直肠癌组织中的VEGF-D表达和MLD、MVD水平与淋巴结转移、术前远处转移有明显相关性（P〈0．01，P〈0．05）。（3）直肠癌组织中的MLD与VEGF—D呈正相关，随着VEGF—D表达的增高MLD明显增高（P〈0．01）。结论VEGF-D和MLD是反映直肠癌淋巴管生成的理想指标，同时也是反映直肠癌进展程度的重要指标，直肠癌淋巴管生成及血管生成可能具有协同作用。     

Multifaceted Roles of Integrins in Breast Cancer Metastasis

Malignant breast cancer can be a debilitating disease due to metastasis to tissues such as brain or bone. The metastatic process involves the invasion of tumor cells into the adjacent tissue, followed by systemic dissemination and colonization of secondary organs. These processes require interactions between tumor cells and a changing microenvironment, which drive cell proliferation, migration, invasion and colonization, as well as promoting cell survival. The integrin family of cell adhesion receptors has been shown to play a critical role in all of these processes, consistent with their extracellular matrix binding properties. Experiments in cultured epithelial cells and in vivo models have demonstrated that integrins can promote various stages of metastasis by modulating the effects of growth factor receptors, extracellular proteases and chemotactic molecules. Integrins may therefore play a pivotal role in multiple mechanisms of metastasis. As a result, they represent promising targets for effective treatment of metastatic breast cancer.     

The role of cell adhesion molecules and proteases in tumor invasion and metastasis

Summary Over the past 10 years it has become apparent that invasion and metastasis are extremely complex processes; neoplastic cells must escape from the primary tumor, degrade the extracellular matrix, migrate to distant sites, arrest in the capillaries, and migrate through the basement membrane and underlying connective tissue to the metastatic site. Therefore, tumor cells must exhibit considerable flexibility in their adhesive interactions, and this is reflected in a complex and dynamic expression pattern of cell adhesion molecules, proteases, protease inhibitors, motility factors, and growth factors. Despite the recent explosion of information regarding adhesion-related molecules, questions as to their possible roles in normal tissue architecture and as to how alterations in their expression or structure may be responsible for the progression from a single malignant cell to a lethal metastatic disease need further investigation. Moreover, efforts should be made to use the obtained knowledge to contribute to improvements in the clinical management of cancer. In this review the different classes of cell adhesion molecules and proteases are summarized, with special emphasis being placed on molecules that have been shown to correlate with invasion and metastasis. Furthermore, the role of E-cadherin in cell adhesion and invasive processes is discussed in more detail, since E-cadherin may be considered promising as a candidate among cell-adhesion-regulating molecules to be used as a biomarker for malignancy. We also elaborate on the role of the catenins, which associate with and are important for the functioning of E-cadherin.     

胃癌侵袭转移的影响因素分析及靶向治疗进展

肿瘤的侵袭和转移是决定疾病转归的关键因素,胃癌侵袭转移过程中影响因素包括生长因子及其受体、细胞黏附分子、基质降解酶和细胞周期调控等,研究这些影响因素的作用机制,不仅对胃癌侵袭转移的早期诊断具有重要的临床意义,而且对相关靶向治疗药物的研发有重要的社会价值.     

Association of increased immunostaining for inducible nitric oxide synthase and nitrotyrosine with fibroblast growth factor transformation in pancreatic cancer

BACKGROUND: Despite recognition of the devastating malignant potential of pancreatic cancer, the exact pathophysiological events contributing to tumor growth, vascular invasiveness, and hepatic metastasis remain to be elucidated. METHODS: Twelve human pancreatic adenocarcinomas were evaluated using immunohistochemical and in situ hybridization techniques for the appearance of the angiogenic and neurogenic growth factors, acidic fibroblast (FGF-1) and basic fibroblast growth factor (FGF-2), and their high-affinity receptors. Since FGF biological processes appear to be regulated by oxidant stress, tumors were examined further for the immunoappearance of inducible nitric oxide synthase (iNOS) and nitrotyrosine. RESULTS: Compared with normal human pancreatic tissue, tumor specimens exhibited varying levels of enhanced staining for FGF ligands and receptors. The increased appearance of FGF-1 and FGF-2 proteins was accompanied by increased detection of messenger RNA encoding each growth factor. In addition, these pancreatic tumors demonstrated the overexpression of iNOS and immunostaining of nitrotyrosine compared with normal pancreatic tissue. CONCLUSIONS: The enhanced expression of FGF and FGF receptors suggests that these polypeptide mitogens may serve as important mediators of growth and of angiogenic and metastatic responses associated with pancreatic tumors, not seen in normal pancreatic tissue. Furthermore, we provide the first indication of increased expression of iNOS and protein tyrosine nitration, thereby predicting the potential involvement of oxidant stress during development and progression of pancreatic adenocarcinoma.     

Smart drugs in prostate cancer

OBJECTIVES: Growth signaling is instrumental in tumor development. Insight into signaling pathways by molecular and cellular biology has changed the development of new anticancer agents. Outside the field of urology specifically targeted drugs such as imatinib mesylate and gefitinib showed impressive anticancer activity in chronic myeloid leukemia and non-small cell lung cancer, respectively. METHODS: Literature search of PubMed documented publications and abstracts from meetings. RESULTS: Preclinical data in prostate cancer shows upregulation of a wide variety of growth factors and their receptors such as PDGF, EGF, IGF, FGF, and VEGF suggesting efficacy of agents targeting these pathways. Here the preclinical evidence and first clinical data on the use of growth signal targeting in prostate cancer is reviewed. Although some anticancer efficacy of signal transduction inhibition monotherapy was reported, combination with chemotherapy and radiotherapy seemed most promising in prostate cancer. CONCLUSION: So-called smart drugs are small molecules targeted at specific growth signaling pathways. These new drugs will dominate clinical trials in the years to come either as single-drug modality, but more likely as combination treatment.     

GROWTH FACTORS AND CANCER

Recent advances in protein chemistry and genetic engineering have revealed new information about the molecular lesions involved in the induction and maintenance of cancer cells. It is now known that a single base change in the DNA of human cells leads to cancer. The normal pathway of proliferation and differentiation is perturbed by changes to molecules involved in the intracellular biochemical pathways controlled by growth factors. Some cancer cells appear to produce their own growth factor, others have higher concentrations of growth factor receptors on their surface and others have mutated versions of the intracellular proteins linked to the growth factor receptors. This increased understanding of growth control in normal and neoplastic cell populations is gradually providing a foundation for new approaches to cancer therapy.     

Growth factors and cancer

Recent advances in protein chemistry and genetic engineering have revealed new information about the molecular lesions involved in the induction and maintenance of cancer cells. It is now known that a single base change in the DNA of human cells leads to cancer. The normal pathway of proliferation and differentiation is perturbed by changes to molecules involved in the intracellular biochemical pathways controlled by growth factors. Some cancer cells appear to produce their own growth factor, others have higher concentrations of growth factor receptors on their surface and others have mutated versions of the intracellular proteins linked to the growth factor receptors. This increased understanding of growth control in normal and neoplastic cell populations is gradually providing a foundation for new approaches to cancer therapy.     

Seprase表达与人结直肠癌临床病理特征的关系

目的 探讨Seprase表达与结直肠癌临床病理特征间的关系。方法 分别采用免疫组织化学、免疫印迹及半定量免疫组织化学方法对50例结直肠癌患者肿瘤标本中Seprase的表达进行了检测，并对Seprase的表达与其临床病理特征的关系进行了分析。结果 Seprase在肿瘤细胞和邻近基质细胞中均有表达，Seprase蛋白在肿瘤组织中的表达明显高于正常结直肠组织（P〈0．01）．其表达与肿瘤Dukes分期及淋巴结转移有关。结论 Seprase在结直肠癌中高表达与肿瘤Dukes分期及淋巴结转移有关。     

MicroRNA在胃癌上皮-间质转化中的研究进展

上皮-间质转化不仅参与正常胚胎发育过程中器官和组织的生成,而且也有助于提高癌细胞的侵袭及转移.当上皮-间质转化受到刺激时,细胞和细胞之间黏附及极性由于黏附分子如E-钙黏蛋的消失而被打乱,导致细胞之间的相互作用发生改变,导致细胞发生间充质表型的改变,最终激活癌细胞的迁移和侵袭.研究证明部分转录因子、生长因子以及相关信号通路参与上皮-间质转化过程,而miRNA可通过调控癌基因或抑癌基因参与胃癌细胞的增殖、凋亡、侵袭及转移过程,其中也涉及上皮-间质转化的调控.本文就近年来miRNA在胃癌EMT过程中的具体调控机制予以综述.     

Association of interleukin-8 and plasminogen activator system in the progression of colorectal cancer

The aim of this study was to investigate the relationship of Interleukin-8 (IL-8) with vascular endothelial growth factor (VEGF) and plasminogen activator system (PA system) in the progression of colorectal cancer (CRC). In eighty-seven patients with CRC, the levels of IL-8, and VEGF as representative angiogenic factors and urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues. The levels of IL-8, VEGF, and PA system factors in tumor tissues were all significantly higher than those in normal tissues. The IL-8 level was significantly associated with tumor size, depth of infiltration, Dukes stage, and liver metastasis, and also significantly correlated with the levels of VEGF, uPAR, uPA, and PAI-1. The VEGF level was significantly associated with tumor size, vascular involvement. The levels of uPAR and PAI-1 were significantly associated with tumor size and depth of infiltration, and the uPAR level was associated with liver metastasis. The VEGF level was significantly correlated with the levels of uPAR and PAI-1. These results reveal that IL-8, VEGF, and PA system factors are contributed to tumor growth, invasion, and metastasis in CRC. Univariate analysis revealed that high levels of IL-8, VEGF, and uPAR were significantly associated with a shorter overall survival time; however, multivariate analysis identified only liver metastasis as an independent prognostic factor. In conclusion, IL-8 is responsible to tumor progression and liver metastasis of CRC, and the activation of PAS induced by IL-8 as well as VEGF may play an important role in the progression of CRC.     

The concept and significance of cancer stem cells

Functional heterogeneity occurs in tumor withs a hierarchy in which tumor growth is driven by a small subset of cancer stem cells (CSCs). Like normal tissue stem cells, which are capable of self-renewal and multi-differentiation, CSCs have the ability to reconstitute tumors. CSCs also have the ability to resist chemoradiotherapy and give rise to cancer metastasis and recurrence. Therefore, eradication of CSCs will lead to complete cancer cure. In the process of developing CSC-targeted therapy, it is necessary to identify CSC-specific molecules, for which it is essential to identify definitive CSC markers and isolate CSCs with high accuracy. Although the targeting and regulation of CSCs have not yet been fully established, some reports showed that it is possible to target CSCs using molecules on which they are highly dependent or using differentiation induction similar to the normal tissue differentiation mechanism. It is expected that novel therapeutic molecules with high specificity and effectiveness will be found in the near future. In addition, the CSC concept has itself been evolving. It is necessary to clarify the exact nature of CSCs to establish a treatment strategy against them.     

肿瘤相关巨噬细胞在结肠肿瘤中的浸润及意义

目的：了解结肠肿瘤组织中肿瘤相关巨噬细胞（TAMs）的浸润情况,并探讨其浸润程度的临床意义。方法：采用免疫组织化学染色的方法,用CD163标记巨噬细胞,光学显微镜下计数阳性染色细胞。结果：结肠癌组织中TAMs计数高于结肠腺瘤组织,结肠腺瘤组高于癌旁正常组织（P均〈0.05）,TAMs浸润程度与肿瘤的分化程度、浸润深度、淋巴结和远处转移等有关（P均〈0.05）。结论：TAMs在结肠癌组织中浸润较多,且在其发生发展中起重要作用,并促进其侵袭、转移,可作为临床评估结肠癌病情的新指标。     

突变型p53与Nampt在胃癌组织中的表达及其与预后的关系

目的：探讨突变型p53（mutp53）和尼克酰胺磷酸核糖转移酶（Nampt）在胃癌组织中的表达及其对患者预后的影响。方法：用免疫组化法检测68例胃癌患者胃癌组织及癌旁正常胃黏膜组织中p53（免疫组化检测到的p53主要为mutp53）与Nampt的表达,分析mutp53与Nampt表达与患者临床病理因素及预后的关系。 结果：胃癌组织中mutp53与Nampt的阳性表达率均明显高于癌旁正常胃黏膜组织（均P<0.05）;mutp53的高表达与肿瘤大小、浸润深度、淋巴结转移及TNM分期有关,而Nampt的高表达与肿瘤浸润深度、淋巴结转移及TNM分期有关（均P<0.05）。胃癌组织中,p53表达与Nampt表达呈明显正相关（r=0.982,P<0.05）。p53阳性表达患者的中位生存期明显短于阴性表达患者,且在p53阳性表达患者中,Nampt同时阳性患者的中位生存期明显短于Nampt阴性患者（均P<0.05）。结论：mutp53与Nampt的表达均与胃癌的恶性生物学行为相关,且两者存在一定的关联性,同时高表达患者预后差。

     

survivin在结直肠癌组织中的表达及其临床意义

目的探讨survivin在结直肠癌组织中的表达及其与肿瘤生物学特性及临床特性之间的相关性。方法应用RT-PCR方法检测60份结直肠癌组织及40例癌旁正常组织标本中survivin的表达,并分析其与肿瘤临床特性及生物学特性之间的相关性。结果 survivin在结直肠癌中的表达较癌旁正常组织明显升高(P<0.05)。在癌组织中,survivin的表达与患者的性别、肿瘤大小、部位及组织分化程度无明显相关性,但与Dukes分期及有无淋巴结转移密切相关。结论 survivin在结直肠癌组织中高表达,并与肿瘤Dukes分期及淋巴转移相关,提示检测survivin可以反应肿瘤的侵袭性,为评估肿瘤的预后提供参考。     

Inflammation and cancer

There is evidence supporting the hypothesis that inflammation participates in providing conditions that lead to cancer.An unresolved inflammation due to any failure in the precise control of the immune response can continue to perturb the cellular microenvironment, thereby leading to alterations in cancer-related genes and posttranslational modification in crucial cellular proteins involved in the cell cycle,DNA repair and apoptosis.In addition,there are data indicating that inflammatory cells and immunomodulatory mediators present in the tumor microenvironment influence tumor progression and metastasis.Historically,tumor-infiltrating leukocytes have been considered to be manifestations of an intrinsic defence mechanism against developing tumors.However,increasing evidence indicates that leukocyte infiltration can promote tumor phenotypes, such as angiogenesis,growth and invasion.This may be due to inflammatory cells that probably can influence cancer promotion by secreting cytokines,growth factors,chemokines and proteases,which stimulate proliferation and invasiveness of cancer cells.Conse-quently,events and molecules implicated in this cross talk between the tumor microenvironment and inflam- matory process may emerge as attractive targets in anticancer therapeutic interventions with significant clinical impact.     

Effect of aprotinin on metastasis of lewis lung tumor in mice

Kallikrein activity in human stomach tissue was measured and found to be about threefold higher in cancer tissue than in normal tissue. To clarify the physiological role of this tissue kallikrein, we investigated its effects on the spontaneous metastasis and tumor growth of Lewis tumors (3LL). Antiprotease, aprotinin, and gabexate mesilate (FOY) inhibited spontaneous metastasis but did not inhibit tumor growth, while tissue kallikrein and plasmin enhanced the spontaneous metastasis of 3LL. The results suggest that the inhibitory effects of aprotinin and FOY on metastasis are not only due to an inhibition of tumor cells released by tissue kallikrein, but that tissue kallikrein, a protease, also participates in metastasis. We thus conclude that aprotinin or FOY should be administered either before or immediately after operation to inhibit spontaneous metastasis.