抗粘附治疗在肿瘤转移中的研究与应用

细胞粘附与抗粘附治疗的研究越来越被人们重视 ,现综述粘附分子的种类与作用及抗粘附治疗在抗肿瘤侵袭转移中的研究进展     

细胞粘附分子、粘附蛋白与肿瘤转移

近年来随着细胞与细胞，细胞与细胞外基质粘附机制逐渐被阐明，参与、介导这一粘附机制的一类细胞粘附分子以及粘附蛋白正引起人们极大关注。已证明这些成分参与多细胞体包括生长发育、成形以及免疫应答、炎症反应、血液凝周等各种生命活动，也是肿瘤浸润转移的分子基础。已知肿瘤浸润转移是肿瘤致死眭的关键因素，而有选择性调节或阻断细胞粘附分子及粘附蛋白的粘附活性，可能会随着肿瘤转移机制不断被阐明而成为有效防治肿瘤转移的手段之一。本文就有关这方面研究工作进展作一探讨。     

视黄酸与肿瘤转移

癌转移是肿瘤细胞从原发部位进入体液循环,最后穿过管壁在靶器官定位,并在该处增殖成转移癌.已经发现癌转移是一个多步骤、多阶段、多基因的复杂过程,是癌症患者死亡的主要原因.因此如何控制癌转移是决定预后的关键因素.对癌转移机制研究也成为当今国内外的研究热点之一.     

细胞外间质与肿瘤浸润转移

一些细胞的增殖分化及功能发挥均依赖于细胞外环境中各种分子的作用。这些分子包括各种生物因子、分化因子、细胞粘附分子和细胞外间质 (extrace-llular matrix,ECM)成分 [1 ]。肿瘤细胞浸润转移是恶性肿瘤致死的主要原因。近十余年来 ,在 ECM与肿瘤细胞之间相互作用方面的研究取得了令人鼓舞的进展 ,尤其是 L iotta[2 ]提出的肿瘤细胞浸润转移三步假说 ,即粘附、降解、移动 ,不仅从理论上阐述了肿瘤细胞浸润转移的可能步骤 ,而且还发现了许多与此有关的细胞粘附分子、各种降解酶类和细胞移动因子 ;制备了相应的单克隆和多克隆抗体 ;合成…     

膀胱癌细胞—基底膜粘附力与肿瘤浸润转移关系初步研究

目的：分离高浸润转移能力的膀胱癌细胞亚系，探讨肿瘤细胞浸润能力与细胞粘附力之间的关系。方法：利用体内和体外两种方法，分离出具有高浸润转移能力的细胞亚系，并用微管吸吮系统直接测定细胞与人工基底膜间的粘附力。结果：成功从T24细胞系中分离出具有高淋巴结转移能力的细胞亚系Ts3L，发现肿瘤细胞与基底膜间的粘附力随浸润转移能力增高而逐渐降低。结论：高浸润转移能力细胞与基底膜粘附力减小，故更容易脱离基底膜形成转移。     

肿瘤转移干细胞与抗转移策略

肿瘤干细胞（cancer stem cell,CSC）能自我更新,分化形成异质性的肿瘤子代细胞群,是肿瘤复发与转移的主要原因。肿瘤转移干细胞（metastatic cancer stem cell,MCSC）具有CSC特性,同时伴有转移能力。肿瘤转移既发生于肿瘤晚期,也发生于早期。MCSC在起源、上皮-间质转变（epithelial-mesenchymal transition,EMT）、间质-上皮转变（mesenchymal-epithelial transition,MET）和靶器官小生境（niche）等方面与CSC不同,因而MCSC是肿瘤转移的基础。杀灭CSC、阻断EMT和MET、抑制MCSC微血管黏附和阻断MCSC依赖的小生境可构建抗肿瘤转移的治疗策略。本文主要介绍MCSC的可能来源,MCSC的生物学特性,MCSC近期研究中可能取得的突破,以及针对MCSC的抗转移策略,为肿瘤转移机制研究和抗转移研究提供参考。     

细胞粘附与耐药在血液系统肿瘤中的研究

细胞粘附介导的耐药(CAM-DR)使肿瘤细胞初始暴露于细胞毒药物时在肿瘤微环境中受到庇护，最终导致肿瘤细胞残留和经典耐药发生。造血微环境中的细胞外基质、骨髓基质细胞和细胞因子均参与血液系统肿瘤CAM-DR的发生，对疾病复发和耐药起重要作用。     

上皮钙粘附素与肿瘤分化、浸润及转移的关系

 近几年来，人们对细胞粘附分子(Cell Adhesion Molecules，CAMs)的研究发现胚胎的发育分化和正常组织结构的维持都离不开细胞与细胞之间、细胞与间质之间的相互作用，并清楚地表明在多种疾病包括肿瘤在内，细胞间相互作用被破坏。现已有100多种细胞粘附分子((CAMS)的基因被克隆化，结构和生化性质被阐明，而钙依赖性细胞粘 附分子大家族(Cadherin)是对细胞间连接诱导和维持起重要作用的一类粘附分子，其中钙粘附分子亚群—上皮钙粘附素(E-Cadherin，E-CD)是钙依赖性具有同种上皮亲合性的粘附分子，是维持正常上皮细胞形态完整性和极性的转膜糖蛋白。     

Loco-regional cancer therapy for hepatic metastasis

We undertook a clinical evaluation of chemotherapy for hepatic metastasis of gastric, colorectal and breast cancer. Between 1980 and 1989, chemotherapy for hepatic metastasis of gastric cancer was performed in 96 cases. Between 1973 and 1989, chemotherapy for hepatic metastasis of colorectal cancer and breast cancer was performed in 40 and 14 cases. Results: (1) In hepatic metastasis of gastric cancer, the 50% survival period was 149 days in local injection therapy, 132 days in arterial infusion therapy and 117 days with no chemotherapy. There was no significant difference in the survival period in gastric cancer. (2) In hepatic metastasis of colorectal cancer, the 50% survival period was 445 days in arterial infusion therapy, 206 days in local injection therapy and 96 days with no chemotherapy. The survival period with hepatic metastasis of colorectal cancer that had undergone chemotherapy was longer than for no chemotherapy. (3) In hepatic metastasis of breast cancer, arterial infusion therapy was more effective, and the survival period was prolonged significantly.     

Adhesion or anti-adhesion in cancer: what matters more?

Summary The regulation of adhesion processes between normal epithelial cells is an essential condition for the maintenance of appropriate tissular architecture and differentiation. Quantitative and qualitative alterations in these homotypic adhesions occur during the transformation of normal into malignant epithelium. How these complex alterations in various homotypic adhesions modify the ability of tumor cells to detach from the original neoplastic site, to grow and move as single or clumped cells, and to invade the stroma are current issues in tumor biology. This review contrasts tumor cell adhesion mediated by E-cadherin which is consistently decreased in carcinomas, with adhesion mediated by CD44 and CEA which are increased in the same tumors. A model proposing to resolve the apparent paradox of simultaneous adhesion and anti-adhesion mediated by the same protein is proposed.     

Emerging roles of radioresistance in prostate cancer metastasis and radiation therapy

Radiation therapy (RT) continues to be one of the most popular treatment options for localized prostate cancer (CaP). Local CaP recurrence after RT is a pattern of treatment failure attributable to radioresistance of cancer cells. One major obstacle to RT is that there is a limit to the amount of radiation that can be safely delivered to the target organ. Recent results indicate that phosphoinositide 3-kinase (PI3K)/Akt/phosphatase and tensin homolog (PTEN)/mammalian target of rapamycin (mTOR) signaling pathway, autophagy, epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) are involved in CaP metastasis and radioresistance. Emerging evidence also suggests that combining a radiosensitizer with RT increases the efficacy of CaP treatment. Understanding the mechanisms of radioresistance will help to overcome recurrence after RT in CaP patients and prevent metastasis. In this review, we discuss the novel findings of PI3K/Akt/PTEN/mTOR signaling pathway, autophagy, EMT and CSCs in the regulation of CaP metastasis and radioresistance, and focus on combination of radiosensitizers with RT in the treatment of CaP in preclinical studies to explore novel approaches for future clinical trials.     

Landscape of combination therapy trials in breast cancer brain metastasis

Combination therapy has become a cornerstone in cancer treatment to potentiate therapeutic effectiveness and overcome drug resistance and metastasis. In this work, we explore combination trials in breast cancer brain metastasis (BCBM), highlighting deficiencies in trial design and underlining promising combination strategies. On October 31, 2019, we examined ClinicalTrials.gov for interventional and therapeutic clinical trials involving combination therapy for BCBM, without limiting for date or location. Information on trial characteristics was collected. Combination therapies used in trials were analyzed and explored in line with evidence from the medical literature. Sixty-five combination therapy trials were selected (n = 65), constituting less than 0.7% of all breast cancer trials. Most trials (62%) combined ≥2 chemotherapeutic agents. Chemotherapy with radiation was main-stay in 23% of trials. Trastuzumab was mostly used in combination (31%), followed by lapatinib (20%) and capecitabine (15%). Common strategies involved combining tyrosine kinase inhibitors with thymidylate synthase inhibitors (6 trials), dual HER-dimerization inhibitors (3 trials), microtubule inhibitors and tyrosine kinase inhibitors (3 trials), and HER-dimerization inhibitors and tyrosine kinase inhibitors (3 trials). The combination of tucatinib and capecitabine yielded the highest objective response rate (83%) in early phase trials. The triple combination of trastuzumab, tucatinib and capecitabine lowered the risk of disease progression or death by 52% in patients with HER2-positive BCBM. Combining therapeutic agents based on biological mechanisms is necessary to increase the effectiveness of available anti-cancer regimens. Significant survival benefit has yet to be achieved in future combination therapy trials. Enhancing drug delivery through blood–brain barrier permeable agents may potentiate the overall therapeutic outcomes.     

复发转移性乳腺癌分子靶向药物治疗进展

化疗、内分泌治疗在复发转移性乳腺癌的治疗中起非常重要作用。随着对肿瘤发生、发展过程中分子机制的深入了解以及转化性研究的开展,针对乳腺癌复发转移病灶的靶向治疗取得很大进展。笔者将对复发转移性乳腺癌的靶向治疗进展进行综述。     

宫颈癌骨转移的研究进展

宫颈癌是最常见的女性生殖道恶性肿瘤.骨骼是宫颈癌少见的转移部位,一旦发生骨转移,常预示患者的生活质量下降和生存期缩短.针对骨转移采取多学科综合治疗模式制定个体化治疗,能有助于提高疾病控制率并延长患者的生存期.本文首先将介绍宫颈癌骨转移的临床特征和诊断要点,然后重点综述手术、放疗、化疗、靶向及免疫治疗、骨改良药物治疗及止...     

Chemo-endocrine therapy for prostate cancer with bone metastasis

We analyzed the clinical effects of initial chemoendocrine therapy on 31 prostate cancer patients with bone metastasis. These patients had been newly diagnosed between 1983 and 1991 and had received no previous therapy. As endocrine therapy, the patients received 1 mg ethynylestradiol daily with or without orchiectomy. In addition, they received three courses of chemotherapy consisting of 20 mg/m² cisplatin given on days 1, 3, and 5 and 20 mg/m² Adriamycin or 40 mg/m² epirubicin given on day 5. Subsequently, for maintenance therapy, the patients received 1 mg ethynylestradiol and 150 mg 5-fluorouracil [or 300 mg tegafur plus uracil (UFT)] daily. Patients given our regimen of chemoendocrine therapy had a significantly better prognosis than did the controls treated with endocrine therapy alone (P=0.05), although treatment was not randomized. The cause-specific survival rates at 5 years for the chemoendocrine-therapy patients and the control group were 65.4% and 37.4%, respectively. A multivariate analysis of possible prognostic factors, i.e., age, histological grade, prostatic acid phosphatase, tumorrelated pain, the extent of disease (EOD) on bone scan, and the type of initial treatment, confirmed that the initial treatment (P=0.03) and the EOD grade (P=0.05) had a significant effect on survival. On the basis of these results, it is necessary to carry out a randomized trial to compare our chemoendocrine regimen with endocrine therapy alone in untreated patients with advanced prostate cancer.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan