Salmonella reduces tumor metastasis by downregulation C-X-C chemokine receptor type 4

Tumor metastasis is the main reason for the death of most cancer patients. C-X-C chemokine receptor type 4 (CXCR4) has been demonstrated to be overexpressed in numerous types of cancer. CXCR4 selectively binds with stromal cell-derived factor 1 (SDF1), also known as C-X-C family chemokine ligand 12 (CXCL12) (CXCL12/SDF-1), which induced tumor proliferation and metastasis. Recently, the use of conventional cancer treatments had some limitation; bacteria treatment for cancer becomes a trend that overcomes these limitations. Plenty of studies show that Salmonella has anti-tumor and anti-metastatic activity. The current study aimed to investigate Salmonella suppresses CXCR4 protein expression and tumor cell migration ability in B16F10 melanoma and LL2 lung carcinoma cells. Salmonella reduced CXCR4 protein expression through downregulating Protein Kinase-B (Akt)/Mammalian Target of Rapamycin (mTOR) signaling pathway. In cells transfected with constitutively active Akt plasmids, a reverse effect of Salmonella-induced inhibition of CXCR4 was observed. Tumor cells have chemotactic response to CXCL12 in migration assay, and we found that Salmonella reduced tumor chemotactic response after CXCL12 treatment. The C57BL/6 mice were intravenously injected with B16F10 and LL2 cells pre-incubated with or without Salmonella, the tumor size and lung weight of Salmonella group had obviously decreased, indicating anti-metastatic effect that confirmed the findings from the in vitro experiments.     

硼替佐米对多发性骨髓瘤细胞乙酰肝素酶表达及迁移能力的影响

目的: 研究硼替佐米对多发性骨髓瘤细胞株U266的乙酰肝素酶(HPA)表达及迁移能力的影响,并探讨其作用机制。方法: 体外培养U266细胞,以不同浓度的硼替佐米进行处理,采用CCK-8检测细胞活力,用RT-PCR方法检测HPA mRNA水平的变化,用Western blotting方法检测HPA蛋白及IκB表达水平的变化,以Transwell方法检测细胞迁移能力的变化。结果: U266细胞表达HPA,以0、3.125、12.5及50 nmol/L浓度的硼替佐米处理U266细胞48 h,HPA mRNA及蛋白的表达逐渐减少(P<0.01),而细胞迁移能力逐渐减弱(P<0.01)。同时,HPA的蛋白表达水平与IκB的表达水平呈负相关(P<0.01)。结论: 硼替佐米通过抑制HPA的表达抑制骨髓瘤细胞的迁移能力,其机制可能是通过NF-κB信号途径进行调控的。     

上皮细胞间质转型与肿瘤转移

皮细胞间质转型 (epithelial-mesenchymal transitions,EMT)是具有极性的上皮细胞转换成为具有活动能力的间质细胞并获得侵袭和迁移能力的过程,它存在于人体多个生理和病理过程中。EMT的发生涉及到多个信号转导通路和复杂的分子机制,与钙连接素、生长因子、转录因子、微环境等有关。EMT与肿瘤细胞的侵袭和转移关系密切。     

骨桥蛋白相关分子与肿瘤转移的关系

骨桥蛋白（OPN）及其相关分子与肿瘤转移的关系密切。通过转录因子与OPN启动子的应答元件（RAE序列、Tcf-4结合序列、AP-1结合序列、RE-1序列等）相互作用,调控OPN的表达。OPN通过促进肿瘤细胞黏附、激活生长因子受体、促进MMPs或uPA分泌、促进血管生成等多个环节参与肿瘤转移过程     

肿瘤微环境中的基质细胞在转移形成中的角色

传统观念认为癌症的进展仅仅是由癌细胞基因和表型变化的多个过程所致.但最近20年的研究显示肿瘤微环境(tumor microenvironment,TME)对于肿瘤行为的影响是同等重要的.TME的组成包括局部的基质细胞,如定植的成纤维细胞(cancer-associated fibroblasts,CAF)和巨噬细胞,远处招募的细胞如内皮细胞、免疫细胞包括髓系和淋巴系细胞、骨髓来源的前体细胞和循环中的血小板.TME能够分泌影响并调控肿瘤表型的分子,如能揭示成瘤细胞与微环境之间的关系,必定能够为肿瘤的发生发展及治疗等一系列难题提供全新的视角.     

己烯雌酚对肿瘤生长,转移的影响及机制探讨

目的：研究己烯雌酚（ＤＥＳ）对实验性肿瘤转移的影响。方法：利用自发性Ｌｅｗｉｓ肺癌（ＬＬＣ）及实验性Ｂ１６黑色素瘤（Ｂ１６Ｍ）转移模型研究ＤＥＳ对肿瘤生长、转移的影响。结果：发现预先用ＤＥＳ处理的小鼠对其移植的ＬＬＣ生长和自发性肺转移均有抑制作用，且ＤＥＳ剂量与肿瘤的生长、转移呈直线负相关（ｒ〉０．８０，Ｐ〈０．０１）；Ｂ１６Ｍ实验性肺转移也明显减少；小鼠接种ＬＬＣ后给予ＤＥＳ对ＬＬＣ也有抑制作用     

CD24与肿瘤侵袭转移的关系

CD24是一种黏蛋白样黏附分子。研究表明,CD24在卵巢癌、乳腺癌、子宫肿瘤、前列腺癌、肺癌等多种肿瘤组织中表达升高。CD24可能通过促进肿瘤细胞的增殖、侵袭和转移参与肿瘤的发生发展。CD24已成为某些恶性肿瘤的侵袭转移标志和预后指标。     

消化系统肿瘤转移相关蛋白质组学的研究进展

蛋白质组学已经成为当今研究肿瘤转移领域的核心技术之一，在筛选肿瘤转移相关蛋白方面中取得了许多进展。通过蛋白组学技术可以找到肿瘤转移相关蛋白，不仅有助于揭示肿瘤发生、发展的分子机制，为肿瘤转移诊断和预后预测提供生物学标志物，还可以为肿瘤治疗提供靶点。     

VEGF-C与VEGF-D比值变化与肿瘤淋巴道转移的研究进展

肿瘤侵袭周边原有淋巴管以及诱导组织内新生淋巴管的形成,是肿瘤淋巴道转移的必要条件。VEGF-C和VEGF-D是特异性淋巴管生长调节因子,与淋巴管的增生和分化密切相关。二者的比值升高可能是肿瘤淋巴道转移的早期事件和潜在评估指标。本文介绍VEGF-C和VEGF-D的结构、功能、比值变化以及二者与肿瘤淋巴道转移关系的研究进展。     

The negative prognostic impact of bone metastasis with a tumor mass

OBJECTIVE:

Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer.

METHODS:

Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001).

RESULTS:

According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11–1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression.

CONCLUSION:

Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients.     

Sarcomatoid intracardiac metastasis of a testicular germ cell tumor closely resembling primary cardiac sarcoma

This report describes a 40-year-old man with a remote history of testicular mixed nonseminomatous germ cell tumor (NSGCT) treated by surgery and chemotherapy. He presented 10 years later with shortness of breath and was found to have a mass occupying the right atrium, based high in the superior vena cava. He also had multiple pulmonary emboli. The sarcomatous and myxomatous histological appearance of the neoplasm closely resembled a primary cardiac sarcoma. However, immunohistochemical studies confirmed the diagnosis of metatstatic sarcomatoid germ cell tumor. Metastatic spindle cell tumors have been reported in patients with NSGCTs. These neoplasms are thought to arise from the spindle cell component of the yolk sac tumor that is resistant to chemotherapy.     

LASS2／TMSG-1基因与肿瘤转移关系的研究进展

人源性长寿保障基因2（homo sapiens longevity assurance homologue 2,LASS2）是一个与酵母长寿保障基因l（10ngevity assurance gene1,LAG1）高度同源的人类基因,又被称为肿瘤转移抑制相关基因1（tumor metastasis suppressor gene-1,TMSG-1）。目前研究发现LASS2／TMSG-1与神经酰胺合成密切相关,同时其与V-ATPase质子泵的相互作用被认为是抑制肿瘤转移的机制之一,多种肿瘤的转移都与此基因的表达相关。     

低氧对卵巢癌SKOV3细胞乙酰肝素酶表达及侵袭力的影响

目的：探讨低氧对卵巢癌细胞乙酰肝素酶(HPA)表达及侵袭力的影响。方法:将SKOV3细胞置于常氧(37 ℃，5％CO2，21％O2)和低氧(37 ℃，5％CO2，1％O2) 12、24、36 h条件下培养，采用RT-PCR及Western blotting方法对HPA表达进行检测，采用基质凝胶侵袭实验测定各组细胞侵袭力。结果:与常氧组比较，SKOV3细胞在低氧12、24、36 h HPA mRNA表达增高，以12h增加显著，蛋白表达则依次增加，各组比较差异显著(P<0.01)，而低氧各组间比较，HPA表达量亦不同(P<0.05)；常氧组侵袭细胞数与低氧12、24、36 h组比较差异显著(P<0.05)，且低氧引起的细胞侵袭力的提高呈时间依赖性，随着低氧时间延长，侵袭细胞数逐渐增多，组间比较有显著差异(P<0.05)；低氧时HPA蛋白表达的变化与细胞侵袭力变化呈正相关(r=0.8530，P<0.05)。结论:低氧可提高SKOV3细胞HPA的表达及细胞的侵袭力，且侵袭力的增加可能与HPA表达水平增高有关。     

局部麻醉药物在肿瘤转移和复发中作用的研究进展

围术期肿瘤治疗常需要使用麻醉药物.不同麻醉药物及麻醉方法的选择会影响肿瘤的增殖、转移复发及预后.围术期应用局部麻醉药物(简称局麻药)不仅能减少阿片类药物的用量,尚能通过阻滞肿瘤细胞钠通道、改变表观遗传学、减轻炎性反应和提高免疫功能等机制发挥抑制肿瘤转移和复发的作用.探讨局麻药在肿瘤转移复发中的作用机制,可为围术期肿瘤患...     

胃癌中肿瘤微环境转移的价值

目的研究胃癌中是否存在肿瘤微环境转移(tumor microenvironment of metastasis,TMEM)及其与胃癌血道转移的相关性。方法采用免疫组化双染法同时标记巨噬细胞和内皮细胞,计数26例远处转移及其配对26例无远处转移胃癌组织中TMEM密度。结果 (1)TMEM存在于胃癌组织中;(2)TMEM与分化程度、临床分期明显相关(P<0.001,P=0.006),与肿瘤大小、Lauren分型、淋巴结转移等其他临床病理特点无关(P均>0.05);(3)TMEM与有无远处转移呈正相关(P<0.001)。结论证实胃癌中存在TMEM,TMEM密度可以预测胃癌血道转移,有望成为评估胃癌血道转移危险性的新预测指标。     

The mechanisms of IL-17A on promoting tumor metastasis

In recent decades, extensive studies have indicated that IL-17A plays an important role in tumor progression and metastasis, but the underlying mechanisms are not immediately clear. In this review, we examined the literature from the recent years concerning the study of IL-17A in four kinds of tumor transfer paths, including hematogenous metastasis, lymphatic metastasis, local invasion and transcoelomic metastasis, to summarize the roles and underlying mechanisms of IL-17A on tumor metastasis.     

Evaluation of metastatic ability at specific times during primary tumor growth: a novel spontaneous metastasis assay

A transformed NIH 3T3 fibroblast cell line, CI-e, normally does not produce spontaneous metastasis from subcutaneous or footpad tumors in nude mice. However, pulmonary tumor nodules are formed when more than 1 × 10³ cells are injected intravenously into nude mice. Co-injection of 1 × 10⁶ heavily irradiated and inactivated cells increases the clonogenic ability of the viable cells in that tumor colonies then occur with as few as 1 × 10² viable cells. Utilizing the action of these inactivated cells to enhance the lung colonizing ability of a relatively small number of viable tumor cells, we have developed a novel experimental model of spontaneous metastasis. In this model, a footpad tumor of the nude mouse metastasizes to the lungs following intravenous injection of 1 × 10⁶ inactivated cells at a specific time of tumor growth and following tumor foot amputation, whereas no spontaneous metastasis develops without injection of inactivated cells. This model enables us to detect metastatic ability which would otherwise be too low to detect using other assays. In addition, it allows us to evaluate metastatic ability at a specific time point during primary tumor growth, since no metastases can develop during the periods before inactivated cell injection and after tumor amputation. Using this model, we have determined that the metastatic ability of CI-e tumors in the footpad is constant throughout the exponential and stationary growth phases, even though cells isolated from exponentially growing tumors possess a 3.3-fold greater lung colonizing ability following intravenous injection than those from stationary tumors. This new experimental model may be applicable to other tumor cell lines and to other analyses where metastatic ability during a defined interval of tumor growth is of importance.     

AXL在肿瘤转移和耐药中的作用及干预策略研究进展

AXL是酪氨酸激酶受体之一,在恶性肿瘤细胞中高表达,并通过多种信号传导途径,尤其是与EMT形成正向反馈循环,促进肿瘤转移和耐药,成为肿瘤治疗的一个新靶点。通过抑制AXL的表达可有效逆转EMT和肿瘤转移与耐药。