肿瘤干细胞对恶性肿瘤诊治的意义

恶性肿瘤严重地威胁着人类的健康.多药耐药现象增加了其治疗难度,局部复发和远处转移最终导致了治疗失败,然而遗憾的是机制尚不清楚.研究发现在肿瘤组织中有一个具有自我更新及分化潜能的的细胞亚群,是复发及转移的根源.这部分细胞被称为肿瘤干细胞.随后,人们相继从血液系统肿瘤及多种实体瘤中分离、鉴定了肿瘤干细胞.随着肿瘤干细胞学说的提出及确认,人们对肿瘤的复发、转移及多药耐药现象有了新的认识,从而为恶性肿瘤的治疗及复发转移的预防提供了一个全新的线索.本文就此进行综述.     

肿瘤细胞浸润和血管生成在胃癌肝转移中的机制研究

胃癌血行转移最常见的部位是肝脏,其预后差,是胃癌患者常见的死亡原因.近年来,随着分子生物学的进展,人们对肿瘤转移机制的认识也逐渐深入.肿瘤转移是一个多步骤且复杂的过程,首要条件是细胞自原发灶脱落,并局部转移进入肿瘤新生血管.本文就肿瘤细胞浸润和血管生成在胃癌肝转移中的相关机制作一综述.     

肿瘤标志物联合检测判断大肠癌复发转移的研究进展

大肠癌的转移是一个多因素多基因共同作用的结果,术后复发转移是其预后不良的重要原因.由于肿瘤发展是一个动态的过程,不同阶段肿瘤标志物的浓度随肿瘤的发展而变化,而且目前尚未发现任何一种肿瘤标志物为某一类型大肠癌所特有,因此单项肿瘤标志物的敏感性和特异性均不理想,较佳的肿瘤标志物组合可以提高临床早期诊断率,具有单项检测不具有的优势.采用多种标志物联合检测,有利于提高诊断的阳性率.     

肿瘤干细胞和肿瘤

肿瘤干细胞(cancer stem cell,CSC)近几年来成为肿瘤研究的新的热点,尽管越来越多的肿瘤干细胞亚群被鉴定出来,但是肿瘤干细胞的细胞表面标记物并不唯一,这町能是因为肿瘤干细胞的来源不一造成的.肿瘤干细胞在肿瘤迁移中扮演着重要角色.肿瘤干细胞发生上皮细胞间质转化(epithelial-mesenchymal-transition,EMT)后获取较强的迁移能力,随着血液循环在转移灶停留,并与组织细胞和骨髓源间质细胞-同形成适应肿瘤转移灶形成的微环境,最终形成肿瘤转移.     

肿瘤干细胞和肿瘤

肿瘤干细胞(cancer stem cell,CSC)近几年来成为肿瘤研究的新的热点,尽管越来越多的肿瘤干细胞亚群被鉴定出来,但是肿瘤干细胞的细胞表面标记物并不唯一,这町能是因为肿瘤干细胞的来源不一造成的.肿瘤干细胞在肿瘤迁移中扮演着重要角色.肿瘤干细胞发生上皮细胞间质转化(epithelial-mesenchymal-transition,EMT)后获取较强的迁移能力,随着血液循环在转移灶停留,并与组织细胞和骨髓源间质细胞-同形成适应肿瘤转移灶形成的微环境,最终形成肿瘤转移.     

肝原发性与转移性神经内分泌肿瘤的临床病理分析

目的 探讨原发性和转移性肝神经内分泌肿瘤的临床病理特征以及两者的鉴别要点.方法 收集35例肝原发性神经内分泌肿瘤(原发组)和35例肝转移性神经内分泌肿瘤(转移组).对两组患者性别、肿瘤大小、肿瘤个数、发生部位、肿瘤分化程度、生长方式、坏死(有/无)、瘤栓(有/无)以及核分级和核分裂相10个指标进行对照分析,评估各项指标在两组间的分布差异.结果 原发组有明显的男性发病优势(25比15;P＜0.05).在肿瘤发生个数和大小的比较上原发组多为单发(n=30)并且肿块较大(平均直径8.4 cm),转移组多个肿块多见(n=11)并且肿块较小(平均直径5.4 cm)(P＜0.05).原发组与转移组肿瘤,肝左右叶的分布无差异(P＞0.05),原发组肿瘤多位于单叶,转移组肿瘤多双叶同时发生(P＜0.05).两组肿瘤组织病理形态学(肿瘤分化程度、生长方式、坏死、瘤栓、核分级及核分裂相)无显著差异(P＞0.05).结论 患者性别、肿瘤大小、发生部位、肿瘤个数这4项指标对于区别肝神经内分泌肿瘤是原发性还是转移性具有一定参考价值.     

肿瘤转移前微环境假说及其研究进展

肿瘤的侵袭转移是恶性肿瘤患者治疗失败和死亡的主要原因.肿瘤转移的机制至今未明,而肿瘤的转移前微环境假说为认识肿瘤的转移机制提供了新的思路.在该假说中,骨髓源性细胞、微泡、外分泌体、CD44等多种因素在前微环境的形成过程中都发挥了重要作用.对肿瘤转移前微环境假说的深入研究有助于我们理解肿瘤转移的本质,为肿瘤的临床诊断和靶向治疗提供新的策略.     

癌胚抗原与大肠癌复发转移的关系

提高结直肠癌病人的预后,主要寄希望于早期检测期能发现复发与转移。转移是一多步骤过程,涉及一系列宿主－肿瘤之间的相互作用。Ｌｉｏｔｔａ将肿瘤的转移过程概括为：粘附、降解和移动。肿瘤细胞转移过程首先是粘附和去粘附交替过程。在粘附过程中有一系列粘附分子在起作用。癌胚抗原（ＣＥＡ）是大肠癌细胞去分过程中表达的一个重要标志,是最有价值的肿瘤标志物之一,在大肠癌诊断和治疗中的作提高结直肠癌病人的预后,主要寄希望于早期检测期能发现复发与转移。转移是一多步骤过程,涉及一系列宿主－肿瘤之间的相互作用。Ｌｉｏｔｔａ…     

乳腺癌骨转移机制的研究进展

前言乳腺癌是女性最常见的恶性肿瘤之一,死亡率仅次于肺癌,居第二位。乳腺癌也是最常见的转移性肿瘤之一,乳腺癌术后的远处转移以骨、肺、肝多见;有数据表明,骨骼是其最常见的转移部位。肿瘤转移是一个复杂的多步骤的过程,任何转移部位都有典型环境障碍.     

结肠癌根治术后转移复发的特点及预后分析

目的 探讨结肠癌根治术后肿瘤转移复发的特点和影响预后的因素。方法回顾性分析310例结肠癌患者根治术后转移复发的特点，并对预后进行单因素及多因素分析。结果本组患者结肠癌行根治术后转移复发率为23．2％（72例），其中3年内转移复发者占76．4％（55例）。肝转移28例（38．9％），多脏器转移16例（22．2％）。X^2检验显示，肿瘤大体类型、分化程度、有无淋巴结转移、Stage分期与转移复发相关。本组5年生存率64．6％。单因素分析显示，肿瘤大体类型、组织学类型、分化程度、淋巴结转移、脉管瘤栓、Stage分期、有无化疗和门脉化疗与预后相关；多因素分析显示，肿瘤大体类型、淋巴结转移、术后有无化疗和门脉化疗为影响预后最重要的因素。结论结肠癌患者根治术后转移复发多在3年内，肝脏是最常见的转移部位。肿瘤大体类型、淋巴结转移、有无化疗和门脉化疗是结肠癌术后影响预后的重要因素。     

肝癌复发和转移的新理念

Cancer metastasis is considered as a complex process involving a series of sequential steps and a variety of molecalar signal transduction pathways.Tumor recurrence and metastasis are major obstacles for long-term survival of Liver cancer patients.Although the prognosis after recurrence and metastasis is dismal,the advancement of molecular researches of metastasis of liver cancer seems promising.In studies of origins of metastasis of liver cancer,the primary cancer cell and corresponding metastatic liver cancer cells share similar gene signature,which indicates that genes favoring metastasis progression are initiated in the primary tumors.The metastasis of liver cancer may be an early event in hepatic carcinogenesis and progression.Some molecular signatures have been developed to classify the metastatic potential of liver cancer.Furthermore,a variety of studies demonstrate that the tumor microenvironment instead of tumor cells plays a more important role in liver cancer metastasis.The pre-metastatic niche composed of non-tumoral cells may promote the cancer cell sedimentation and progression.The theory of cancer stem cell speculates that cancer stem cells were the real source of recurrent or metastatic tumors.Cancer stem cells will be one of the main targets of liver cancer treatment.The prevention and treatment of liver cancer recurrence or metastasis are quite difficult because liver cancer is resistant to traditional chemotherapy.Targeting the molecules involved in the metastasis of liver cancer WOuld be promising to cure those diseases.     

MicroRNA Exert Macro Effects on Cancer Bone Metastasis

Bone metastasis is a deadly complication of cancers arising from many different primary tumor locations. Cross talk between cancer and bone cells is a well-established driver of bone metastasis, and recent work reveals microRNA (miRNA) as key players in this communication. Functional significance of miRNA was first demonstrated in cancer cells and has now also been documented in bone cell differentiation and skeletal remodeling. Review of recent literature highlights how different miRNAs can impact each step of the metastatic process by acting in both tumor and the metastatic niche to exert pleiotropic effects. Additionally, whether a miRNA is ultimately pro- or anti-metastatic dependents on the context—varied or even opposite outcomes can be conferred by the same miRNA in different cancer/cell types. In spite of this complexity, emerging research has provided a wealth of knowledge to uncover the exciting potential of miRNA as new diagnostic tools and therapeutic treatments for cancer bone metastasis.     

低分子肝素抑制肿瘤转移的研究进展

肿瘤转移是一个复杂的过程,而针对转移治疗一直是研究的热点.低分子肝素通过抑制肝素酶对基底膜的降解、降低血液黏稠度等作用,对肿瘤细胞转移有明显的干预作用.本文就低分子肝素(LMWH)对肿瘤转移过程影响和作用机制做一综述,讨论其抗肿瘤转移的临床应用价值.     

Metastasis Suppressors and Their Roles in Breast Carcinoma

Metastasis remains the most deadly aspect of cancer and still evades direct treatment. Clinically and experimentally, primary tumor development and metastasis are distinct processes—locally growing tumors can progress without the development of metastases. The discovery of endogenous molecules that exclusively inhibit metastasis suggests that metastasis is an amenable therapeutic target. By definition, metastasis suppressors inhibit metastasis without inhibiting tumorigenicity and are thus distinct from tumor suppressors. As the biology underlying functional mechanisms of metastasis suppressors becomes clearer, it is evident that metastasis suppressors could be harnessed as direct drug targets, prognostic markers, and to understand the fundamental biology of the metastatic process. Metastasis suppressors vary widely in their cellular localization: they are found in every cellular compartment and some are secreted. In general, metastasis suppressors appear to regulate selectively how cells respond to exogenous signals, by affecting signaling cascades which regulate downstream gene expression. This review briefly summarizes current functional and biochemical data on metastasis suppressors implicated in breast cancer. We also present a schematic integrating known mechanisms for these metastasis suppressors highlighting potential targets for therapeutic intervention.     

The Multifaceted Roles of Autophagy in Tumors—Implications for Breast Cancer

Autophagy is an evolutionarily conserved lysosomal degradation process that is crucial for adaptation to stress as well as in cellular homeostasis. In cancer, our current understanding has uncovered multifaceted roles for autophagy in tumor initiation and progression. Although genetic evidence corroborates a critical role for autophagy as a tumor suppressor mechanism, autophagy can also promote the survival and fitness of advanced tumors subject to stress, which has important implications during breast cancer progression and metastasis. Here, I discuss the mechanisms and the evidence underlying these diverse roles for autophagy in cancer and speculate on specific circumstances in which autophagy can be most effectively targeted for breast cancer treatment.     

LIMK与结直肠癌关系的研究进展

目的了解LIM激酶(LIMK)与结直肠癌的关系,为结直肠癌的转移、侵袭及靶向治疗提供研究依据。方法复习近年来国内外关于LIMK的结构功能以及其与结直肠癌关系研究进展的相关文献并加以综述。结果 LIMK及其主要通路ROCK/LIMK/cofilin及PAK/LIMK/cofilin上下游因子均参与了肿瘤细胞周期进展、肿瘤细胞侵袭、迁移、增殖等多种细胞生物学行为,如p21活化蛋白激酶4(PAK4)通过PAK4/LIMK1/cofilin信号通路参与细胞骨架动力学调节癌细胞迁移和侵袭,cofilin经过Rho/ROCK/LIMK1/cofilin通路影响肿瘤细胞运动和形态的变化,从而参与肿瘤细胞的侵袭和迁移;两种肿瘤转移相关蛋白MYH9和ACTN4为LIMK1的直接靶标,此三者相互作用可以促进结肠癌进展。LIMK家族的另一成员LIMK2可通过限制上皮间充质转化过程抑制细胞转移的能力,并与β-连环蛋白的核可激活Wnt信号传导途径,从而导致结肠癌进展和转移。二烯丙基二硫可以下调结肠癌细胞SW480中LIMK1的表达,抑制LIMK1/cofilin信号通路,阻碍血管生成和上皮间充质转化,抑制结肠癌的迁移和侵袭,而其他LIMK抑制剂暂未在结直肠癌中得到验证。结论结直肠癌及其转移的分子机制尚未完全阐明,通过对结直肠癌及其转移机制与LIMK关系的深入研究,可为结直肠癌及转移提供分子靶向治疗突破点,并有助于为探究结直肠癌的诊断、判断复发、预后及转移情况提供更多帮助。     

A case of duodenal intramural metastasis from gastric cancer

INTRODUCTIONHere, we report a case of duodenal intramural metastasis from gastric cancer, which is extremely rare.PRESENTATION OF CASEA 72-year-old man was admitted to our hospital with a chief complaint of lack of appetite in 2010. An endoscopic evaluation detected a Borrmann type 2 tumor occupying the lesser curvature of the gastric body and antrum, and pyloric stenosis. The patient underwent total gastrectomy. In an examination of the resected specimen, a type 2 tumor was identified in the middle gastric body and antrum, and a submucosal tumor was detected in the duodenal bulb. A histopathological examination demonstrated that the gastric tumor was not contiguous with the duodenal submucosal tumor. A microscopic examination demonstrated that the gastric tumor was a moderately to poorly differentiated adenocarcinoma and displayed lymphatic permeation. The duodenal submucosal tumor was also found to be an adenocarcinoma and was similar to the gastric tumor; therefore, we diagnosed the duodenal tumor as an intramural metastasis from gastric cancer.DISCUSSIONThe most common route of metastasis from gastric cancer involves hematogenous metastasis, lymph node metastasis, and peritoneal metastasis. Intramural metastasis from gastric cancer is rare and has been reported to be a variant of lymphogenic metastasis. The clinicopathological features of patients with duodenal intramural metastasis from gastric cancer are unclear because only one case of the condition has been reported.CONCLUSIONDuodenal intramural metastasis from gastric cancer is an advanced form of cancer, and we suggest that it should be treated with surgical resection followed by adjuvant therapy.     

A Methodological Approach to Unravel Organ-Specific Breast Cancer Metastasis

Breast cancer is the most commonly diagnosed and the second highest cause of cancer-related mortality. Although major breakthroughs have emerged during the past decades concerning the characterization of major malignant tumors hallmarks, little is known about the molecular process that sustains the most deadly feature of cancer: metastasis to distant organs. In fact, this colonization of tumor cells to secondary sites is not random but rather orientated, and depends on several signalling events that are not fully elucidated yet. Understanding the precise molecular and cellular mechanisms accountable for the specific invasion of tissues by breast cancer cells is likely to be important for developing new therapeutic strategies to effectively prevent metastasis in patients diagnosed with early cancer lesions. Here, we briefly describe a multidisciplinary approach based on the molecular profiling of breast cancer metastases, the elaboration of prognostic gene signatures, the clinical validation and the experimental confirmation using cell and animal models to better address breast cancer metastasis. This methodology can be considered as a useful workflow to identify and validate the genes that trigger and support organ tropism of breast cancer cells during metastasis.     

胰腺星形细胞在胰腺癌中的作用

胰腺癌是常见的消化道恶性肿瘤之一,因早期诊断困难,恶性程度高,手术切除率低,并对化放疗均不敏感,故预后极差.其病理特征之一是肿瘤中有大量的结缔组织形成反应.而胰腺星形细胞(PSCs)在这一反应中起重要作用,并通过与胰腺癌细胞的相互作用,对胰腺癌细胞的增生、侵袭和转移有重要作用.本文就PSCs在胰腺癌发展中的作用及机制作一综述.     

胃癌淋巴结转移相关危险因素及其临床预测价值分析

背景与目的:淋巴结转移与胃癌患者预后之间密切关联,且淋巴结转移与否及淋巴结转移程度对患者治疗方案的选择至关重要,但目前术前淋巴结转移预测方法仍有一定局限性。本研究旨在探讨胃癌患者淋巴结转移现象的相关危险因素,为术前预测淋巴结转移提供一定途径。方法:回顾2014年1月-2015年4月收治的380例胃癌患者的临床与随访资料,分析淋巴结转移与患者相关临床病理因素的关系,从中寻找出胃癌淋巴结转移危险因素,并进一步用ROC曲线分析危险因素对胃癌淋巴结转移的预测能力,用Kaplan-Meier法分析危险因素对患者预后的影响。结果:380例患者中,241例(63.42%)发生淋巴结转移。单因素分析结果显示,BMI、肿瘤浸润深度、分化程度、Lauren’s分型、肿瘤直径以及肿瘤标志物CA125与胃癌淋巴结转移明显有关(均P<0.05);多因素分析结果显示,BMI(OR=4.175,P=0.041)和肿瘤浸润深度(OR=16.444,P<0.000 1)是胃癌淋巴结转移的独立危险因素;相关性分析结果显示,淋巴结转移阳性率与BMI值呈明显正相关(r=1.95,P=0.007)。BMI(以24 kg/m^2为临界值)与肿瘤浸润深度分级(以T4期为标准)预测是否有淋巴结转移的敏感度均为63.16%,特异度分别为76.84%、53.68%;两者联合应用特异度增高至88.36%,ROC曲线下面积达75.76%。生存分析结果显示,高BMI值患者的3年总生存率明显低于低BMI值患者(51.09% vs.53.13%,P<0.05)。结论:BMI与肿瘤浸润深度是胃癌患者淋巴结转移的独立危险因素,患者BMI值越高淋巴结转移的可能性越大,结合肿瘤浸润深度情况分析,对术前预测淋巴结转移有一定的临床实用价值。