骨存储生长因子在肿瘤骨转移中的作用

摘 要：骨存储生长因子又称骨源性生长因子,是大量存在于骨中的一系列生长因子。这些生长因子由存在于骨中的细胞分泌,正常情况下维持稳态,发生骨转移时,一方面癌细胞分泌骨存储生长因子,另一方面癌细胞影响骨中其他细胞分泌骨存储生长因子,都会造成骨存储生长因子分泌量失衡。其中一些骨存储生长因子失衡,如转化生长因子-β和胰岛素样生长因子分泌量增加,其可加速溶骨性损害。近年来,随着对肿瘤转移微环境研究的加深,骨存储生长因子成为研究热点,为了加深对这些生长因子作用机制的了解,本文就目前骨存储生长因子与肿瘤骨转移的研究进展作一综述。     

OPG RANKL和RANK在肿瘤骨转移中的作用

健康的骨骼依靠骨形成和骨吸收的动态平衡来维持完整性。     

前列腺癌骨转移后骨破坏相关信号通路的研究进展

骨转移是晚期前列腺癌患者常见的并发症之一,骨转移导致的疼痛等骨相关事件(SRE)治疗效果欠佳,预后差,严重影响患者的生命质量。因此,探究前列腺癌骨转移具有重要意义。目前,骨转移的相关机制尚不清楚,宿主微环境和前列腺癌细胞之间相互作用,形成恶性循环是一个重要原因。其中,RANK-RANKL信号通路的研究较为成熟。文章就前列腺癌骨转移相关信号通路的研究现状作一综述,并阐述同一信号分子在不同信号通路中的调控关系。     

肺癌骨转移后骨破坏相关信号通路的研究进展

[摘要] 晚期肺癌患者骨转移发病率高,骨折、神经压迫、骨痛等并发症多,不仅影响患者的生活质量,而且增加了患者的经济负担及心理压力。肺癌骨转移后,癌细胞和骨组织微环境间进行复杂的相互作用,有多种相关信号通路参与其中,通过复杂的机制最终形成成骨性骨破坏、溶骨性骨破坏及混合性骨破坏。尽管目前对相关信号通路的研究取得了一定的成果,但其在调控成骨/破骨细胞分化及骨形成/骨溶解方面的确切分子机制及相互作用方式仍未阐明。随着研究的进一步深入,将会揭开肺癌骨转移后骨破坏过程的完整机制,为临床有效防治肺癌骨转移提供新的理论依据与治疗靶点。本文从溶骨性骨破坏、成骨性骨破坏和混合性骨破坏3个方面阐述近年来对肺癌骨转移后骨破坏相关信号通路的研究进展。     

GDF15在肿瘤骨转移中的作用及机制的研究进展

恶性肿瘤患者常常死于肿瘤转移所造成的并发症而非原发灶,在我国,居民防癌意识不强,大量的患者在就诊时已处于肿瘤的晚期阶段,因此恶性肿瘤的死亡率持续升高。肿瘤常转移到骨组织,一旦发生骨转移,SREs等并发症将严重降低患者生活质量。然而,现阶段对于肿瘤骨转移的诊疗水平却十分有限,其相关机制更是知之甚少。GDF15在肿瘤中的作用被我们逐渐认识,而它同时又在包括骨转移在内的几种骨相关疾病中被报道,因此GDF15极有可能在肿瘤骨转移中扮演重要角色。本文将对GDF15在肿瘤骨转移及相关疾病中的争议作用和机制作一综述。     

骨膦在肿瘤性骨转移综合治疗中的作用

我院１９９３．２－１９９５．１０用骨膦治疗骨转移癌３２例，以评价骨膦在肿瘤骨转移综合治疗中的作用。其中肺癌１７例，乳腺癌１１例，鼻咽癌３例，肝癌１例。３２例经骨膦治疗后止痛总的有效率为８１．２５％，其中ＣＲ８例（２５％），ＰＲ１０例（３１．２５％），ＭＲ８例（２５％）。与治疗前相比，有明显疗效。有效患者的Ｋａｒｎｏｆｓｋｙ状况分级法分别提高２０－４０分，由于治疗后患者疼痛减轻，症状缓解，生存质量得到明显提高。我们认为骨膦联合放疗对控制广泛骨转移性骨痛，提高晚期肿瘤患者生存质量有实际意义。     

骨转换指标与肿瘤骨转移的相关性研究进展

骨转移是恶性肿瘤的常见并发症,乳腺癌、前列腺癌、肺癌、肾癌等实体肿瘤均好发骨转移。约70％的进展期乳腺癌或前列腺癌病人会发生骨转移。肿瘤骨转移打破了破骨细胞介导的骨吸收和成骨细胞介导的骨形成之间的动态平衡,导致胸腰椎压缩性骨折和其他病理性骨折发生危险增加。随着肿瘤诊治水平不断提高,病人生存时间明显延长,预防和治疗肿瘤骨转移相关的不良事件对改善病人的生活质量具有重要意义。     

Notch信号通路在肿瘤微环境中的调控作用

摘 要：肿瘤细胞与肿瘤微环境（tumor microenvironment,TME）之间通过多种信号通路相互作用,其中Notch信号被认为是重要的信号通路之一。现已证实Notch信号与TME之间的相互作用参与调节肿瘤的血管生成、肿瘤干细胞干性的维持、免疫细胞的浸润和对治疗的抗性。此外,Notch信号还介导许多分子的分泌,影响TME中的细胞功能。大量研究表明,Notch信号在TME中的作用与不同肿瘤中Notch的促癌和抑癌特性有关。该综述讨论了Notch信号在调节TME不同组分之间的相互作用中发挥的重要作用,还从治疗的角度讨论了Notch―TME相互作用的结果。     

赖氨酰氧化酶在肿瘤骨转移中的作用及其抑制剂研究进展

靶向药物在许多恶性肿瘤原发灶的治疗中显示出良好的疗效,但目前缺乏针对恶性肿瘤骨转移靶点的相关研究。赖氨酰氧化酶（LOX）家族是一组分泌型铜依赖性胺氧化酶,包括LOX和赖氨酰氧化酶样（LOXL）1～LOXL4 5个成员,其主要功能是催化细胞外基质（ECM）中胶原蛋白、弹性蛋白的共价交联。LOX主要通过影响骨转移灶局部肿瘤微环境的稳态、重塑骨转移灶ECM、促进上皮-间充质转化促进肿瘤骨转移。β-氨基丙腈（β-APN）、铜螯合剂、PXS复合物是目前LOX家族的主要抑制剂,在动物实验及早期临床试验中显示出了抑制恶性肿瘤骨转移较好的结果。本文对肿瘤骨转移过程中LOX的作用及其抑制剂的研究进展进行综述。     

骨代谢指标在乳腺癌骨转移的临床应用

乳腺癌骨转移在复发转移乳腺癌中的发生率为65%～75%。骨痛、骨损伤、骨相关事件(skeletal related event,SRE)的发生及生活质量的降低是乳腺癌骨转移的常见并发症,其将进一步降低癌症患者的生活质量并缩短生存期。随着疗效的增加,生存期的延长,骨转移在临床上出现的频率亦在增加,因此,乳腺癌骨转移的诊治日益成为乳腺癌治疗的     

mTOR信号通路与非小细胞肺癌放疗敏感性的关系

目的:研究mTOR信号通路与非小细胞肺癌放疗敏感性的关系。方法:采用不同剂量的雷帕霉素抑制非小细胞肺癌细胞系A549中的mTOR信号通路;Western blot检测雷帕霉素作用后下游信号分子的表达;将A549细胞分为空白对照组及雷帕霉素作用的实验组,将对照组和实验组经不同剂量射线作用;用MTT实验（噻唑蓝）及克隆形成能力检测细胞增殖能力,流式细胞仪检测细胞凋亡的变化。结果:雷帕霉素药物作用抑制了mTOR信号通路及下游分子的表达,经不同剂量射线照射后细胞的增殖能力和克隆形成能力显著低于对照组,凋亡显著高于对照组。结论:抑制mTOR信号通路可以增加非小细胞肺癌对放疗的敏感性。     

Management of bone metastases from breast cancer

Bone is the most common of breast cancer metastasis. Bone metastasis causes skeletal-related events(SREs), including pain, bone fractures, spinal cord compression, and hypercalcemia. SREs significantly impair patients' quality of life. The main purpose of treatment for bone metastasis is to prevent or delay SREs and to improve patients' quality of life. Accurate diagnosis of bone metastases is important in order to choose an appropriate treatment. Treatment of bone metastasis requires a multidisciplinary approach. Analgesic medication with NSAIDs and opioids is the first choice for pain control. In addition to bisphosphonate, the receptor activator of the nuclear factor κB ligand(RANKL)inhibitor, denosumab is a novel bone-targeting agent effective in preventing SREs. Prophylactic stabilization of impending fractures provides several advantages compared with fixation of an acute fracture, in terms of short hospitalization and a quick return to baseline. In general, radiation therapy is indicated for patients for whom surgery is suitable. Radiation therapy to palliate pain from bone metastasis can reduce the intake of analgesic medications. Local radiation therapy is indicated for a limited number of bone metastases, and systemic radionuclide therapy is appropriate for multiple lesions. In summary, treatment using these modalities for bone metastasis from breast cancer should be stratified, considering the symptoms, site of bone metastasis, and patients' life expectancy and performance status.     

Radiotherapy of bone metastases from cervical cancer

The authors have investigated 6 cases of bone metastases from cervical cancer out of a total of 90 cases of metastatic bone tumors that were irradiated for relief of associated pain at the Department of Radiology, Nagasaki University Hospital from April 1977 to March 1987. In 2 of the 6 cases, a rare, delayed recurrence with paraaortic lymph node metastases was seen. An invasion to the psoas major muscle, ilio major muscle was demonstrated by Computed Tomography after the initiation of therapy, so that the size of the field was modified. Computed Tomography was found useful to determine the exact field size for radiotherapy of metastatic bone tumor.     

Radiation therapy in bone metastases from lung cancer

The record of 73 patients with 153 sites of bone metastases from a lung cancer treated by radiation have been reviewed to evaluate the effectiveness of pain relief. Radiation therapy for bone metastases was found to be very effective. Sufficient symptomatic improvement was achieved in 94% of all patients, while 63% obtained almost complete pain relief that was sustained until death. Onset of a symptomatic response to radiotherapy was within less than 20 Gy in total dose in more than 80% of all patients. There were no significant differences in the frequency of pain relief among the various histological types of primary lung tumors.     

乳腺癌骨转移的治疗现状与展望

目的:总结乳腺癌骨转移痛变治疗的新进展.方法:应用Medline及CNKI期刊全文数据库检索系统,以"乳腺癌、骨转移瘤和治疗"等为关键词,检索2004-2009年的相关文献,共检索到731条,纳入标准:1)骨转移瘤的特点和表现;2)骨转移肿瘤的核素治疗、放疗、手术治疗和化疗治疗;根据纳入标准,精选分析25篇文献.结果:乳腺癌患者病程中常见骨转移,治疗有双磷酸盐药物,化疗、放疗、放射性核素治疗和手术等,CT引导下的射频治疗是相对新的治疗方法,也有联合放疗和靶向药物治疗的实验研究在开展中.结论:针对乳腺癌骨转移瘤患者,长期、持续、有效的治疗方法是根据患者情况,选择性采用不同治疗措施的综合治疗.     

哺乳动物雷帕霉素靶蛋白信号通路与大肠癌

哺乳动物雷帕霉素靶蛋白(mTOR)信号通路作为细胞内重要信号转导通路之一,通过影响下游多种效应分子的活化状态,调节细胞存活、增殖、转分化、迁移和细胞周期.mTOR这些调节机制的异常与大肠癌的发生和发展密切相关.目前mTOR抑制剂治疗大肠癌已处于临床试验中,并取得了一定的进展.     

Pathogenesis of osteoblastic bone metastases from prostate cancer

Prostate cancer is the second leading cause of cancer‐related death in men. A typical feature of this disease is its ability to metastasize to bone. It is mainly osteosclerotic, and is caused by a relative excess of osteoblast activity, leading to an abnormal bone formation. Bone metastases are the result of a complex series of steps that are not yet fully understood and depend on dynamic crosstalk between metastatic cancer cells, cellular components of the bone marrow microenvironment, and bone matrix (osteoblasts and osteoclasts). Prostate cancer cells from primary tissue undergo an epithelial‐mesenchymal transition to disseminate and acquire a bone‐like phenotype to metastasize in bone tissue. This review discusses the biological processes and the molecules involved in the progression of bone metastases. Here we focus on the routes of osteoblast differentiation and activation, the crosstalk between bone cells and tumor cells, and the molecules involved in these processes that are expressed by both osteoblasts and tumor cells. Furthermore, this review deals with the recently elucidated role of osteoclasts in prostate cancer bone metastases. Certainly, to better understand the underlying mechanisms of bone metastasis and so improve targeted bone therapies, further studies are warranted to shed light on the probable role of the premetastatic niche and the involvement of cancer stem cells. Cancer 2010. © 2010 American Cancer Society.     

哺乳动物雷帕霉素靶蛋白及其信号通路在胃癌中的研究进展

哺乳动物雷帕霉素靶蛋白(mTOR)及其信号通路控制着蛋白质合成、细胞的生长和代谢以及血管的生成等.其信号通路在胃癌中常被高度激活,与胃癌进展及预后密切相关.雷帕霉素及其衍生物可通过阻断mTOR通路的信号传递,抑制胃癌细胞生长,促进肿瘤坏死,并能与其他化疗药物产生协同作用,有望为胃癌预防和治疗提供有效的方法.     

mTOR pathway in colorectal cancer: an update

The mammalian target of rapamycin (mTOR) has emerged as a potential target for drug development, particularly due to the fact that it plays such a crucial role in cancer biology. In addition, next-generation mTOR inhibitors have become available, marking an exciting new phase in mTOR-based therapy. However, the verdict on their therapeutic efectiveness remains unclear. Here we review phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling as one of the primary mechanisms for sustaining tumor outgrowth and metastasis, recent advances in the development of mTOR inhibitors, and current studies addressing mTOR activation/inhibition in colorectal cancer (CRC). We will also discuss our recent comparative study of diferent mTOR inhibitors in a population of colon cancer stem cells (CSCs), and current major challenges for achieving individualized drug therapy using kinase inhibitors.     

哺乳动物雷帕霉素靶蛋白及其信号通路在胃癌中的研究进展

哺乳动物雷帕霉素靶蛋白(mTOR)及其信号通路控制着蛋白质合成、细胞的生长和代谢以及血管的生成等.其信号通路在胃癌中常被高度激活,与胃癌进展及预后密切相关.雷帕霉素及其衍生物可通过阻断mTOR通路的信号传递,抑制胃癌细胞生长,促进肿瘤坏死,并能与其他化疗药物产生协同作用,有望为胃癌预防和治疗提供有效的方法.