mTOR通路在肿瘤骨转移中的作用

[摘要] 超过25%的实体瘤患者在晚期都会出现不同程度的骨转移。发生骨转移的肿瘤细胞与骨微环境内细胞相互作用,骨稳态被打破,建立起促进肿瘤生长、加速骨质破坏的恶性循环,进一步促进肿瘤细胞在骨髓腔中浸润,导致转移的级联反应。肿瘤骨转移是一个复杂的过程,大量分子和信号通路参与其中。研究证实,哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）信号通路活性的改变与肿瘤细胞的骨转移以及转移后骨质破坏密切相关。本文从肿瘤细胞的脱落、迁移、黏附和侵入等转移步骤以及骨代谢变化两方面对mTOR信号通路在肿瘤骨转移过程中的作用进行阐述,为肿瘤骨转移的预防和治疗提供新的方向。     

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。     

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。     

消化道肿瘤骨转移患者297例放射性骨显像分析

[目的]探讨核素骨显像对消化道肿瘤骨转移的临床诊断价值.[方法]分析605例消化道肿瘤患者中骨转移患者的全身骨显像结果.[结果] 605例肿瘤患者中,297例(49.09％)发生骨转移.多发骨转移(88.22％)多于单发骨转移(11.78％).转移灶的分布多为邻近转移,且躯干骨多于四肢骨和颅骨.69.36％患者有骨痛症状.[结论]核素骨显像对消化道肿瘤骨转移诊断具有诊断价值.消化道肿瘤患者在随访中应常规行核素骨显像.     

放射性核素全身骨显像诊断肺癌骨转移

采用~(99m)Tc—MDP对51例肺癌患者进行了全身骨显像,阳性者38例,占74.5％,检出病灶84个,同期X线检查异常者28例,占54.9％,检出病灶38个,两结果对照有显著性差异(P<0.01)。12例胸部放射治疗野内出现显像剂弥漫性增高,为非转移病变。阳性病灶在全身的分布以胸部、脊柱及骨盆为高,颅骨及四肢较少。本组病例分析,对多发性病灶可确认骨转移,对单发病灶的诊断应结合临床综合分析。     

核素骨显像联合血管内皮生长因子、瘦素检测对乳腺癌骨转移的诊断价值

目的 探讨乳腺癌患者核素骨显像联合血管内皮生长因子（VEGF）、瘦素（Leptin）检测对乳腺癌骨转移诊断价值.方法 应用酶联免疫吸附法和放射免疫分析法对40例乳腺癌患者进行手术前后血清VEGF和Leptin水平检测,并与50例乳腺良性疾病患者、60名健康对照比较.对乳腺癌患者手术治疗3个月后行核素骨显像.结果 乳腺癌患者术前VEGF和Leptin水平[（338±69）pg/ml、（1.71±0.30）ng/ml]显著高于乳腺良性病患者[（113±42）pg/ml、（1.16±0.27）ng/ml]和健康对照[（87±36）pg/ml、（1.01±0.16）ng/ml],差异有统计学意义（P＜0.05）.术后3个月无转移者与乳腺良性疾病者和健康对照比较差异无统计学意义（P＞0.05）,而伴骨转移者血清VEGF和Leptin水平明显升高,与乳腺癌无骨转移组比较差异有统计学意义（P＜0.05）.结论 核素骨显像对乳腺癌骨转移诊断有重要意义.检测血清VEGF和Leptin可用于乳腺癌患者疗效监测及预后评估;与核素骨显像联合应用,可用于监测乳腺癌骨转移.     

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。     

核素骨显像在肺癌骨转移诊断中的应用

目的: 观察肺癌患者的放射性核素骨显像的影像特征,评估骨显像在诊断肺癌骨转移中的临床价值.方法: 回顾性分析638例肺癌患者的临床资料和骨显像结果.结果: 肺癌骨转移率38.6%(246/638),其中腺癌48.1%(153/318),鳞癌24.8%(51/206),混合癌39.0%(23/59),未分化癌35.7%(15/42),未定型癌30.8%(4/13);肺癌骨转移部位胸部80.1%、脊柱56.1%、骨盆43.9%、四肢12.6%和颅骨6.1%;放射性     

全身骨扫描在肺癌骨转移临床诊断中的意义

目的 探讨全身骨扫描在肺癌骨转移临床诊断中的价值.方法 对256例确诊的肺癌患者进行99mTc-MDP骨显像检查,对骨转移的部位、数量、病理类型进行分析.结果 全组肺癌骨转移的发生率为39.45％,其中腺癌发生率50.66％,鳞癌发生率26.19％,小细胞癌发生率12.50％.101例肺癌骨转移中,多发病灶89例(88...     

The Chemokine CCL2 Increases Prostate Tumor Growth and Bone Metastasis through Macrophage and Osteoclast Recruitment

CC chemokine ligand 2 (CCL2, also known as monocyte chemoattractant protein-1) has been demonstrated to recruit monocytes to tumor sites. Monocytes are capable of being differentiated into tumor-associated macrophages (TAMs) and osteoclasts (OCs). TAMs have been shown to promote tumor growth in several cancer types. Osteoclasts have also been known to play an important role in cancer bone metastasis. To investigate the effects of CCL2 on tumorigenesis and its potential effects on bone metastasis of human prostate cancer, CCL2 was overexpressed into a luciferase-tagged human prostate cancer cell line PC-3. In vitro, the conditioned medium of CCL2 overexpressing PC-3luc cells (PC-3^lucCCL2) was a potent chemoattractant for mouse monocytes in comparison to a conditioned medium from PC-3^lucMock. In addition, CCL2 overexpression increased the growth of transplanted xenografts and increased the accumulation of macrophages in vivo. In a tumor dissemination model, PC-3^lucCCL2 enhanced the growth of bone metastasis, which was associated with more functional OCs. Neutralizing antibodies targeting both human and mouse CCL2 inhibited the growth of PC-3^luc, which was accompanied by a decrease in macrophage recruitment to the tumor. These findings suggest that CCL2 increases tumor growth and bone metastasis through recruitment of macrophages and OCs to the tumor site.     

108例恶性肿瘤骨转移的临床分析

目的 总结分析恶性肿瘤骨转移发病特点及临床表现,以提高骨转移瘤的诊治水平.方法 对108例恶性肿瘤骨转移的临床特点及近期疗效进行回顾性分析.结果 恶性肿瘤骨转移以40～80岁为发病高峰(78.7%),原发灶男性以肺癌,女性以乳腺癌最为多见.转移部位以脊柱、肋骨、骨盆等部位多见.多数患者(86.1%)表现为不同程度的疼痛,少数以局部肿块、功能障碍、病理性骨折甚至截瘫为主要临床表现,13.9%的患者仅以原发灶症状就诊时发.现骨转移.影像学以溶骨性多见(79.3%),16.7%的患者出现不同程度的碱性磷酸酶升高.治疗以全身治疗为主,采用化疗、内分泌治疗、生物治疗、双膦酸盐类药物、止痛药应用及放疗、姑息性手术等综合治疗手段.结论 恶性肿瘤骨转移发生率较高,临床表现复杂.应结合骨扫描、X线、CT等手段早期诊断、综合治疗,以提高生存质量,延长生存时间.     

超级增强子在肿瘤转移中的作用机制研究进展

超级增强子（SEs）是由基因启动子上游或下游附近的一大簇活性增强子组成,是维持肿瘤细胞特性所必需的。SEs的改变可引起肿瘤细胞转录程序的失调,导致肿瘤细胞高度依赖于SEs驱动的转录,形成“转录成瘾性”。肿瘤转移是肿瘤患者死亡的主要原因,已有研究表明SEs通过影响长链非编码RNA、肿瘤微环境、上皮-间质转化、肿瘤干细胞等调控肿瘤转移过程。本文总结了SEs的特点、功能及其与肿瘤转移的关系,以及针对SEs驱动的基因转录抑制剂,以期为SEs调控肿瘤转移的相关机制提供参考,为癌症转移患者的诊断、治疗提供新的视角。     

The Role of Tumor Suppressor Gene TIP30 in Tumorigenesis and Metastasis

Background: Malignant tumors are characterized by dysregulated growth control, the overcoming of replicative senescence, evasion of apoptosis, tissue invasion and metastasis, and sustained angiogenesis. Metastasis is the     

pH值调控肿瘤细胞生长转移的机制

实体瘤存在一个显著的特征是肿瘤胞内呈碱性和胞外呈酸性的微环境,这种酸性微环境能促进肿瘤细胞的生长、侵袭转移.调节肿瘤酸性微环境的主要因子是膜离子交换体,这些离子交换体如NHE和VHA不仅是肿瘤酸性微环境的主要调节者,而且能促进肿瘤细胞的生长转移.通过调节肿瘤胞内外pH值变化可以抑制肿瘤细胞生长转移,但pH值的变化对肿瘤细胞生长转移的调控机制尚不清楚.全文对肿瘤细胞转移的发生机制、肿瘤酸性微环境的形成和膜离子交换体对其调节作用以及三者的关系进行阐述.     

肿瘤微环境与前列腺癌骨转移研究进展

前列腺癌（prostate cancer, PCa）转移中大约80%是发生骨转移,是造成患者死亡的主要原因。前列腺癌骨转移主要呈现成骨和破骨混合性损伤。然而,诱发肿瘤细胞转移到骨以及引起混合样病变的机制仍不十分清楚。宿主微环境与前列腺癌细胞间的相互作用是其中一个重要原因。本文主要讨论宿主微环境如何影响前列腺癌骨转移各个阶段的发生及其中的机制,探讨多种细胞因子、分泌蛋白、微环境中的免疫细胞、成骨细胞、破骨细胞等分泌的因子在前列腺癌骨转移中的重要作用。     

Serum Tumor Markers for Detection of Bone Metastasis in Breast Cancer Patients

For the diagnosis of bone metastasis in breast cancer patients during systemic treatment serum tumor markers, including carbohydrate antigens 15-3 (CA 15-3) and 19-9 (CA 19-9), cancer antigen 125 (CA 125), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), beta-2 microglobulin (BMG), fer-ritin, and tissue polypeptide antigen (determined by the M3 monocolonal antibody, TPS) were measured in 22 patients with known bone metastases and in 30 patients without documented metastases. The most useful single marker was CA 15-3. By stepwise discriminant analysis, it was found that 90% of the patients could be diagnosed truly by using the markers CA 15-3, BMG and ferritin. It is concluded that monitoring with combinations of tumor markers at regular intervals increases the diagnostic efficiency.     

Circulating Tumor Cells are Associated with Bone Metastasis of Lung Cancer

Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bonemetastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer.