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。     

Osteoblastic Factors in Prostate Cancer Bone Metastasis

Purpose of Review

Prostate cancer bone metastasis is the lethal progression of the disease. The disease frequently presents with osteoblastic lesions in bone. The tumor-induced bone can cause complications that significantly hamper the quality of life of patients. A better understanding of how prostate cancer induces aberrant bone formation and how the aberrant bone affects the progression and treatment of the disease may improve the therapies for this disease.

Recent Findings

Prostate cancer-induced bone was shown to enhance tumor growth and confer therapeutic resistance in bone metastasis. Clinically, Radium-223, an alpha emitter that selectively targets bone, was shown to improve overall survival in patients, supporting a role of tumor-induced bone in prostate cancer progression in bone. Recently, it was discovered that PCa-induced aberrant bone formation is due, in part, from tumor-associated endothelial cells that were converted into osteoblasts through endothelial-to-osteoblast (EC-to-OSB) conversion by tumor-secreted BMP4.

Summary

The unique bone-forming phenotype of prostate cancer bone metastasis plays a role in prostate cancer progression in bone and therapy resistance. Therapies that incorporate targeting the tumor-induced osteoblasts or EC-to-OSB conversion mechanism may reduce tumor-induced bone formation and improve therapy outcomes.

     

microRNA与乳腺癌浸润转移关系的研究进展

目的总结microRNA（miRNA）与乳腺癌浸润、转移关系的研究进展。方法检索并筛选近年来国内外发表的有关miRNA与乳腺癌浸润、转移关系的文献并对其进行综述。结果许多miRNA在乳腺癌发生、发展与浸润、转移过程中都起着关键作用,按其作用可分为促癌miRNA（miR-21、miR-10b等）和抑癌miRNA（miR-31、let-7等）两类。结论miRNA调控乳腺癌浸润及转移的具体过程还需要更多、更详细的实验研究。     

前列腺癌骨转移患者血清骨转换标志物的意义

目的:评价骨转换标志物在检测前列腺癌患者骨转移中的诊断准确性,并评价这些标志物作为预测前列腺癌患者死亡率指标的价值.     

雌二醇对唑来膦酸预防乳腺癌骨转移疗效的影响

目的探讨雌二醇（E2）对唑来膦酸预防骨转移疗效的影响。方法收集新疆医科大学第一附属医院2006年1月至2009年12月期间收治的乳腺浸润性导管或小叶癌行改良根治术、术后常规化疗后给予唑来膦酸预防骨转移的患者216例,根据2011年St．Gallen乳腺癌专家共识分型,其中luminalA型55例,luminalB型63例,HER-2阳性型50例,三阴型48例。根据血清E2水平分为2组：①E2低水平组,39例,化疗后均行药物卵巢去势;②E2正常组,177例,未行卵巢去势。2组均给予唑来膦酸预防骨转移,临床总观察时间为化疗后3～5年或直至病情进展（包括出现复发、骨转移或远处其他脏器转移等病情进展视为观察终点）。结果发生骨转移情况：E2低水平组共发生7例（17．95％）,E2正常组共发生105例（59．32％）,E2低水平组发生骨转移率明显低于E2正常组钟：21．91,P〈0．05）;其中luminalA型、luminalB型、HER-2阳性型及三阴型患者中E2低水平组骨转移发生率亦均明显低于E2正常组（1uminalA型：5．13％（2／39）比12．43％（22／177）,χ2=4．54,P〈0．05;luminalB型：7．69％（3／39）比13．56％（24／177）,χ2=6．04,P〈0．05;HER-2阳性型：2．56％（1／39）比15．25％（27／177）,χ2=3．95,P〈0．05;三阴型：2．56％（1／39）比18．08％（32／177）,P〈0．05]。E2低水平组各型乳腺癌患者骨转移发生率比较差异无统计学意义（χ2=0．55,P〉0．05）。结论从本组有限的数据初步总结,绝经前年轻乳腺癌患者去势后应用唑来膦酸预防骨转移有明显临床获益,并且这种获益在各型乳腺癌中无明显差异;未行去势且雌激素水平正常或升高的患者应用唑来膦酸临床获益不明显。     

Predictors of Survival in Patients With Bone Metastasis of Lung Cancer

The prognosis of patients with bone metastasis from lung cancer has not been well documented. We assessed the survival rates after bone metastasis and prognostic factors in 118 patients with bone metastases from lung cancer. The cumulative survival rates after bone metastasis from lung cancer were 59.9% at 6 months, 31.6% at 1 year, and 11.3% at 2 years. The mean survival was 9.7 months (median, 7.2 months; range, 0.1-74.5 months). A favorable prognosis was more likely in women and patients with adenocarcinoma, solitary bone metastasis, no metastases to the appendicular bone, no pathologic fractures, performance status 1 or less, use of systemic chemotherapy, and use of an epithelial growth factor receptor inhibitor. Analyses of single and multiple variables indicated better prognoses for patients with adenocarcinoma, no evidence of appendicular bone metastases, and treatment with an epithelial growth factor receptor inhibitor. The mean survival period was longer in a small group treated with an epithelial growth factor receptor inhibitor than in the larger untreated group. The data preliminarily suggest treatment with an epithelial growth factor receptor inhibitor may improve survival after bone metastasis.     

Radiotherapy of Bone Metastasis in Breast Cancer Patients - Current Approaches

Bone metastases (BM) represent the most frequent indication for palliative radiotherapy in patients with breast cancer. BM increase the risk of skeletal-related events defined as pathological fractures, spinal cord compression, and, most frequently, bone pain. The therapeutic goals of palliative radiotherapy for BM are pain relief, recalcification, and stabilization, reducing spinal cord compression and minimizing the risk of paraplegia. In advanced tumor stages radiotherapy may also be used to alleviate symptoms of generalized bone metastasis. This requires an individual approach including factors, such as life expectancy and tumor progression at different sites. Side effects of radiation therapy of the middle and lower spine may include nausea and emesis requiring adequate antiemetic prophylaxis. Irradiation of large bone marrow areas may cause myelotoxicity making monitoring of blood cell counts mandatory. Radiotherapy is an effective tool in palliation treatment of BM and is part of an interdisciplinary approach. Preferred technique, targeting, and different dose schedules are described in the guidelines of the German Society for Radiooncology (DEGRO) which are also integrated in 2012 recommendations of the Working Group Gynecologic Oncology (AGO).     

Prognostic Evaluation of Breast Cancer Patients with Evident Bone Marrow Metastasis

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty‐four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6–70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(?) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I–II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor‐positive, high‐grade, advanced‐stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor‐positive, multicentric, grade III, advanced‐stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single‐agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.     

MicroRNA and Colorectal Cancer

MicroRNAs are small 19 to 22 nucleotide sequences of RNA that participate in the regulation of cell differentiation, cell cycle progression, and apoptosis. MicroRNAs act much like small interfering RNA, annealing with RISC, to cleave messenger RNA, and microRNAs exert translational inhibition that is incompletely understood. They are important factors in tumorigenesis and have been the subject of research in many types of cancers, including colon cancer. MicroRNAs may be abnormally down-regulated or up-regulated in colon-cancer tissue. Artificial dysregulation of certain microRNAs will trigger tumorigenesis or apoptosis depending on which microRNA is manipulated. Although the natural mechanisms for the dysregulation of microRNAs is still largely unknown, one theory tested in colon cancers proposes that DNA hypermethylation leads to down-regulation of certain microRNAs. Specific microRNA expression patterns help characterize specific cancers and may be used as a prognostication factor and in following patient response to 5-fluorouracil chemotherapy. This article reviews the existing literature pertaining to the study of microRNA in colorectal cancer. This work was presented at the Molecular Surgeon Symposium on Personalized Genomic Medicine and Surgery at the Baylor College of Medicine, Houston, Texas, USA, on April 12, 2008.     

Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice

The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. © 2020 American Society for Bone and Mineral Research.     

前列腺癌患者10号染色体杂合性缺失与骨转移关系的初步研究

目的:探讨人前列腺癌特异性骨转移的细胞遗传学机制。方法:应用比较基因组杂交技术对18例前列腺癌患者进行染色体变异情况的初步分析,确定可能与骨转移密切相关的变异染色体。再应用PCR及微卫星多态性技术重点对10号染色体上的7个微卫星位点进行杂合性缺失(LOH)检测。结果:11例伴有远处骨转移的患者组织样本中,10号染色体的变异率为90.9%(10/11),显著高于其他染色体(P<0.01);进一步分析发现,7个微卫星位点的LOH现象中,骨转移患者的发生率最高,且以D10S1693～D10S587(10q24.2～q25.3)区的LOH发生率最高。结论:10号染色体上D10S1693～D10S587区(10q24.2～q25.3)是前列腺癌骨转移患者中一个高频的LOH区,此区可能与前列腺癌患者远处骨转移的发生密切相关。     

唑来膦酸预防乳腺癌骨转移的疗效研究

目的 探讨唑来膦酸预防乳腺癌骨转移的疗效。方法 回顾性收集2006年1月至2009年12月期间新疆医科大学第一附属医院确诊的418例浸润性乳腺导管癌患者,根据患者用药情况将其分为2组：预防组216例,接受唑来膦酸预防治疗;对照组202例,未接受唑来膦酸预防治疗。比较2组患者的骨转移及复发情况。结果 预防组患者发生骨转移37例（17.13%）,对照组发生骨转移73例（36.14%）,预防组的骨转移发生率较低（χ 2=19.45,P＜0.05）;不同分子分型乳腺癌患者中,均是预防组的骨转移发生率低于对照组（P＜0.05）。2组患者的肺转移、肝转移、其他部位转移和多脏器转移发生率,以及复发率比较差异均无统计学意义（P＞0.05）。结论 乳腺癌术后化疗后给予唑来膦酸预防治疗具有显著的临床获益,可减少乳腺癌骨转移的发生。     

Breast Cancer Metastasis to Bone: Mechanisms of Osteolysis and Implications for Therapy

The most common skeletal complication of breast cancer is osteolytic bone metastasis. Bone metastases are present in 80% of patients with advanced disease and cause significant morbidity. They are most often osteolytic, but can be osteoblastic or mixed. Tumor cells, osteoblasts, osteoclasts and bone matrix are the four components of a vicious cycle necessary for the initiation and development of bone metastases. Tumor cell gene expression is modified by interaction with bone-derived factors. For example, parathyroid hormone related protein (PTHrP), a tumor cell factor, is upregulated by bone-derived transforming growth factor β (TGFβ). Tumor cell factors, in turn, act upon bone cells to cause dysregulated bone destruction and formation. PTHrP increases osteoblast expression of RANK (receptor activator of NFκB) ligand which, in turn, activates osteoclasts. PTHrP-independent osteolytic factors, such as interleukin [IL]-11 and IL-8, also contribute to the vicious cycle. Other tumor-bone interactions, such as stimulation of tumor-homing through the CXCR4 chemokine receptor by its bone-derived ligand stromal-derived factor-1 (SDF-1), may be responsible for the site-specific predilection of breast cancer for bone. These factors and their roles in fueling the vicious cycle may identify novel targets for therapies to prevent metastasis.     

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。     

微小RNA在胰腺癌中的研究进展

目的总结微小RNA(microRNA,miRNA)与胰腺癌之间关系的研究现状,探讨其表达谱在胰腺癌诊断中的重要作用。方法应用PubMed及CNKI期刊全文数据库检索系统,以"microRNA、胰腺癌"等为关键词,检索2000～2012年的相关文献,共检索到英文文献60篇和中文文献15篇。纳入标准为:miRNA与胰腺癌的基础与临床研究以及miRNA在胰腺癌诊治中的前景。根据纳入标准,纳入31篇文献。结果研究发现,miRNA表达谱如miR-21、miR-34、miR-217、miR-196a、miR-10a、miR-155、miR-221、miR-222、miR-181a、miR-181b、miR-181d、miR-200、let-7等家族成员可作为肿瘤标志物用于胰腺癌与正常胰腺、慢性胰腺炎、胰腺内分泌肿瘤等的诊断和鉴别诊断,预测胰腺癌的预后等。结论胰腺癌中miRNA的表达谱不但与胰腺癌的诊断相关,也为胰腺癌的基因治疗提供了新的研究方向和方法。     

Tumor-Stromal Interactions in Bone Metastasis

The metastasis of tumor cells to distant organs is the primary cause of cancer-related mortality in most cancers. The interaction of tumor cells with local stroma at the metastatic site plays a critical role in metastatic dissemination and the establishment of metastases. These tumor-stromal interactions regulate several important steps including degradation of extracellular matrix, release of sequestered growth factors, and expression of chemokines, cytokines, and receptors on tumor cells and the interacting stromal cells. Breast, prostate, and lung cancers preferentially metastasize to bone. Tumor cell interactions with the bone microenvironment initiate a series of complex cellular interactions that promotes establishment of osteoclastic and/or osteoblastic metastasis. Understanding the interactions between tumor cells and the stroma is important to identify molecular targets to develop novel therapies aimed at reducing metastasis formation. In this article, we review the important mechanisms of tumor-stromal interaction in the development of bone metastasis.