乳腺癌溶骨性骨转移机制的研究进展

骨是乳腺癌最常见的远处转移部位之一。临床上骨转移大多为溶骨性转移,乳腺癌细胞、成骨细胞、破骨细胞和骨基质细胞共同参与这一病理过程。这些细胞分泌的细胞因子在骨转移启动和发展环节中起重要作用,并可能成为治疗骨转移新的靶点。     

乳腺癌骨转移动物模型的研究进展

乳腺癌骨转移动物模型的建立可分为自发性、化学诱导、转基因诱导和移植性四种,其中以移植性模型应用广泛,本文将综述该方面的研究进展。     

乳腺癌骨转移模型的建立

目的 介绍三类制作乳腺癌骨转移模型的方法及采用该模型所开展的研究现状。方法 综述国内外的进展。结果 经左心室注射制作的骨转移模型应用最广泛;经局部注射制备骨转移模型最简便,但与临床状况相差较大;经外科原位接种制作骨转移模型为骨转移机理及治疗方法的研究提供了较为理想的工具。结论 各种骨转移模型各有其应用价值,建立与人体乳腺癌骨转移过程完全相同的人乳腺癌动物模型是发展的方向。     

骨内微环境对乳腺癌骨转移的影响

骨骼是乳腺癌优先且最常见的转移部位之一。患者常先出现骨骼微转移(转移前龛影),进而发展为明显的转移灶,造成骨破坏。这一过程取决于骨微环境提供的生长支持和癌细胞对这一环境的适应能力,以及它们之间复杂的相互作用。骨微环境内细胞可产生多种因子,促进肿瘤细胞生长和骨转移进展,而乳腺癌细胞也会释放各种因子,影响骨髓微环境内细胞,加重骨破坏。乳腺癌骨转移的骨髓微环境内分子机制研究对于乳腺癌骨转移治疗有重要意义。     

乳腺癌骨转移106例临床分析

目的：探讨影响乳腺癌骨转移发生、发展的因素及治疗方法。方法：对106例乳腺癌骨转移患者的临床特点及近期疗效进行回顾性总结。结果：乳腺癌骨转移的发生及发生早晚与腋窝淋巴结的转移数目相关。治疗以全身治疗为主，包括化疗、内分泌治疗、放疗、放射性同位素内照射及二磷酸盐的综合治疗。结论：乳腺癌患者，特别是伴有较多数目腋窝淋巴结转移者，应进行同位素骨扫描检查，一旦出现骨转移，应积极进行全身治疗，转移局限者，可进行局部外放射治疗。     

骨转移瘤综合治疗

肿瘤患者严重并发症骨转移瘤的有效治疗可改善和提高患者生存状态、生活质量,减轻患者痛苦.综合应用化疗、内分泌治疗、放疗、放射性核素治疗、双膦酸盐治疗及手术治疗等是骨转移瘤治疗的有效手段,新药、分子靶向治疗等将进一步控制病情进展,延长生存期.该文就骨转移瘤综合治疗方面的研究作一综述.     

骨转移生化指标在乳腺癌诊治中的应用

目的：介绍骨生化指标在乳腺癌骨转移诊治中的应用及价值。方法：分析总结近8年来国、内外关于骨生化指标在乳腺癌骨转移诊治中的应用研究。结果：破骨型生化指标氮端肽(NTX)与骨转移的相关性最好，Ⅰ型胶原碳端肽(ICTP)在乳腺癌骨转移诊治中比NTX更有价值；成骨型生化指标在乳腺癌骨转移诊治中的价值不大。结论：骨生化指标尚不能取代影像学及骨活检在乳腺癌骨转移诊治中的地位。     

人源性乳腺癌骨转移小鼠模型的建立

目的 建立人乳腺癌细胞转移到人骨的"人源性"乳腺癌骨转移小鼠模型.方法 严重联合免疫缺陷(SCID/berg)雌小鼠50只,随机分为实验组(n=30)和对照组(n=20),其中实验组植入人骨后随机均分3组:A组(MDA-MB-231干细胞亚群,1×105个/只)、B组(同A组细胞,1 × 106个/只)和C组(MDA-MB-231亲代细胞,1×106个/只);对照组鼠随机均分2组:D组(阳性对照组,未植入人骨,MDA-MB-231亲代细胞,1×105个/只)、E组(阴性对照组,植入人骨,生理盐水).第4、7周行骨扫描,8周取人骨、鼠骨、肺等行HE染色及CK、CD34、CD105、SMA免疫组织化学检查.结果 骨扫描:第4周鼠植入的人骨均成活,第7周部分模型鼠出现可疑骨转移灶.HE染色及CK检查:B组人骨转移率最高77.8%(7/9),与C组人骨(20.0%)、D组鼠骨(20.0%)、E组鼠骨的骨转移率差异均有统计学意义(P《0.05);B组内人骨(77.8%)、鼠骨(0)、鼠肺(11.1%)转移差异有统计学意义(P《0.01).人骨表面结缔组织生长,骨内CD105、SMA、CD34均阳性的血管长入.结论 "人源性"乳腺癌骨转移小鼠模型骨转移发生率优于"非人源性"骨转移小鼠模型,能较好模拟人骨转移的血循环过程.     

肿瘤干细胞表型CD44和CD24在乳腺癌骨转移模型骨髓中的表达及意义

目的 探讨人乳腺癌细胞转移到人骨的乳腺癌骨转移小鼠模型中骨髓肿瘤干细胞表型CD44和CD24的表达及其意义.方法 50只SCID小鼠随机分成实验组和对照组,其中实验组鼠背部植入人骨后随机均分3亚组:A组(MDA-MB-231干细胞亚群1×105个/只)、B组(同A组细胞1×106个/只)和C组(MDA-MB-231亲代细胞1×106个/只);对照组设为D组(阳性对照,未植入人骨,同C组细胞直接注射)、E组(阴性对照,植入人骨,生理盐水注射).各组8周后取人骨、鼠骨等行常规HE染色及CK、CD44、CD24、CXCR4、OPN免疫组织化学标记.Real-time PCR检测CD44、CXCR4、OPN的mRNA水平.结果 B组骨转移率最高(77.8%,P＜0.05).B组中人骨转移灶CD44、CXCR4、OPN抗原表达高于C、D组骨中的表达(均有P＜0.05);CD24抗原则在A、B组人骨转移灶中低表达与C、D组骨中的高表达无统计学意义(P＞0.05).B组CD44mRNA表达水平是C组的15.2倍、D组的21.1倍;B组CXCR4mRNA表达水平是C组8.4倍、D组28.4倍;B组OPN-mRNA表达水平是C组4.8倍、D组11.6倍;而B组CD24的mRNA表达显著低于C、D组(均为30%).结论 利用MDA-MB-231肿瘤干细胞亚群(CD44+/CD24-)可制备高转移率的"人源性"乳腺癌骨转移模型,其机制可能与CD44高表达有关.骨转移相关基因CXCR4、OPN转录上调可能参与其过程.     

骨转移癌痛动物模型研究进展

一些人类肿瘤骨转移现象已在齿科动物复制成功.建立一完全反映人类骨转移癌痛的动物模型虽比较困难,但可依据不同实验目的选择相应的动物实验模型.目前接种性骨转移癌痛模型应用最多,近年随着转基因等分子技术在小鼠模型制作中成功应用,具有人类疾病特征的转基因性骨转移癌痛小鼠模型逐渐受到重视.该文就骨转移癌痛模型研究进展作一综述.     

乳腺癌器官亲嗜性转移的分子机制

乳腺癌是女性最常见的恶性肿瘤之一．虽其术后5年、10年生存率有了明显提高，但伴有远处转移的病人临床预后仍然较差。肿瘤转移有其特定的靶器官，称为靶向性转移。乳腺癌最常见的转移靶器官是骨髓、肺、肝、脑。肿瘤转移是一种多基因共同参与、多阶段演进的复杂的生物学过程。迄今为止，肿瘤转移的机制还不十分清楚。随着大量肿瘤转移相关基因的发现与功能研究的不断深入．转移     

Importance of the development time of isolated bone metastasis in breast cancer

Background and aims

To investigate whether isolated bone metastases at the time of diagnosis is a different entity than bone metastases after breast cancer surgery.

Patients and methods

One hundred thirty-nine patients were examined between June 2004 and January 2007. These patients were classified into synchronous (group I) and metachronous groups (group II) depending on time to development of bone metastases. Patients and tumor characteristics, treatment, clinical progression, and survival were compared for each group.

Results

There were 44 patients in group I and 95 patients in group II. The median follow-up time was 36?months. The two groups showed similar results when patients, tumor characteristics, and clinical progression were compared. In the groups, the median time to progression was 14 vs 13?months (p?=?0.70), and median overall survival was 47 vs 46?months (p = 0.96), respectively.

Conclusion

Development time of bone metastasis has no effect on clinical progression, time to progression, and overall survival in breast cancer.     

Therapeutic potential of hyaluronan oligosaccharides for bone metastasis of breast cancer

Hyaluronan (HA) oligosaccharides were reported to have suppressive effects on various malignant tumors via disruption of receptor HA interactions. However, no studies have focused on the effects of HA oligosaccharides on bone metastasis of breast cancer. In this study, we clarified the effective size of HA oligosaccharides required to inhibit cell growth in the highly invasive breast cancer cell line, MDA‐MB‐231 cells. Based on the results of cell growth assay, we subsequently analyzed the effects of HA tetrasaccharides, HA decasaccharides, and high molecular weight HA on the other breast cancer cell behaviors in vitro and breast cancer bone metastasis in vivo. HA decasaccharides significantly inhibited cell growth, motility, and invasion, whereas tetrasaccharides did not. HAS2 mRNA expression was altered after the treatment with both tetrasaccharides and decasaccharides. Phosphorylation of Akt was suppressed after 1 h treatment with HA decasaccharides, and the effect was partially reversed by anti‐CD44 monoclonal antibody. In vivo, local application of HA decasaccharides inhibited the expansion of osteolytic lesions in tibia on soft X‐rays using mouse bone metastasis model of breast cancer. Histological analysis revealed HA accumulation in bone metastatic lesions was perturbed by decasaccharides. These results suggest that HA oligosaccharides suppressed progression of bone metastasis in breast cancer via interruption of endogenous HA–CD44 interaction, and as such, can be a novel therapeutic candidate to limit bone metastasis of breast cancer. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:662–672, 2012     

前列腺癌淋巴结转移分子机制的研究进展

淋巴结转移是前列腺癌患者继骨转移之后最常见的转移模式,患者多表现为临床预后不良,因此阐明前列腺癌淋巴结转移的分子机制对了解前列腺癌恶性进展和制定治疗措施具有重要意义。淋巴管生成和肿瘤细胞的淋巴浸润是前列腺癌淋巴结转移的主要方式,瘤周淋巴管生成与淋巴结转移密切相关。血管内皮生长因子C/D-血管内皮生长因子受体-3轴(VEGF-C/D-VEGFR-3轴)和趋化因子配体21-趋化因子受体7轴(CCL21-CCR7轴)是淋巴管生成必不可少的重要分子轴,近年来又新提出了上皮间质转化、免疫逃逸、脂质代谢及缺氧适应性等过程也参与淋巴结转移,为今后研究指明了方向。通过对已知淋巴结转移分子机制以及淋巴管生成参与淋巴结转移的过程进行总结和综述,以期更好地预测前列腺癌的进展,为治疗提供参考。     

Choroidal metastasis in breast cancer

The commonest sites of metastatic carcinoma of the breast are lungs, bones and the brain. We report a rare case of intraocular metastasis from a breast primary to increase the awareness amongst frontline clinicians. We also discuss interventional options available as prompt treatment could be vision-saving for this group of patients despite its overall palliative intent.     

乳腺癌裸鼠骨转移模型的建立及评估

目的 建立乳腺癌骨转移动物模型并探讨对该转移模型的最佳评估方法.方法 将带GFP标记的人乳腺癌细胞MDA-MB-231注入裸鼠左心室,建立乳腺癌骨转移模型.6周后使用X线机、活体显像系统和病理学检查对裸鼠骨组织进行评估.结果 6周后病理学检查肿瘤细胞已扩散至裸鼠的脑、骨髓腔、肺等组织,X线影像清晰显示骨质破坏的位置及程度,活体显像系统可以观察到肿瘤细胞在裸鼠体内的分布.结论 X线、活体显像和组织学检查3种方法相结合是分析乳腺癌小鼠骨转移模型的最佳方法之一.     

Incidence and prognostic factors of Japanese breast cancer patients with bone metastasis

Background Few previous studies have analyzed the incidence of bone metastases in a defined population of Japanese breast cancer patients and their prognosis after chemotherapy. Methods This is a retrospective cohort study. We investigated 695 patients who underwent surgery for breast cancer. The strategy of adjuvant therapy was as follows. Patients with both estrogen receptors (ERs) and progesterone receptors (PgRs) had endocrine therapy as initial adjuvant therapy (n = 239). Patients with neither ERs nor PgRs had chemotherapy. When metastasis to other organs, including bone, was identified, patients received chemotherapy. The survival rates after surgery and after the onset of bone metastasis, as well as the incidence of bone metastasis, were calculated. We also evaluated the prognostic and predictive factors. Results Bone metastases developed in 148 of 695 patients. All 148 received chemotherapy, and 121 of them developed spinal metastases. The 5-year survival rate after bone metastases was 26.1%. Prognostic factors for bone metastases were visceral metastases and PgR status. Cord compression was observed in 17 of the 148 patients, with the thoracic spine being the most common. The 1-year survival rate for patients with bone metastases who received chemotherapy was 66.3%, whereas that of patients with paralysis after spinal metastases was 17.6%. Within 6 months of the development of spinal cord compression, 70.6% of the patients died. Conclusions We reported the incidence and prognostic factors for a defined population of Japanese breast cancer patients with bone and spinal metastases. Our results suggest that the expected survival time for patients with paralysis who received adequate endocrine therapy or chemotherapy is generally poor. However, to detect a predictive factor of long survival after paralysis and establish the indications for surgery, a comparative study among large groups of patients with paralysis and with different backgrounds is necessary.