乳腺癌骨转移过程中的分子机制

乳腺癌患者易发生骨转移。乳腺癌骨转移依赖多种细胞因子及蛋白的参与,是癌细胞与骨微环境相互作用的结果。骨转移患者常见骨痛、病理性骨折等骨相关事件(skeletal related event,SRE),严重影响患者生活质量及预后。了解乳腺癌骨转移的分子机制有助于对乳腺癌骨转移患者的诊断及治疗。作者就参与乳腺癌骨转移相关因子及分子机制进行了综述。     

来曲唑联合唑来磷酸治疗乳腺癌骨转移

目的:观察来曲唑联合唑来磷酸治疗乳腺癌骨转移的临床疗效及不良反应.方法:使用来曲唑联合唑来磷酸静脉注射治疗32例绝经后妇女乳腺癌骨转移伴有不同程度骨痛患者,观察其镇痛效果、骨转移灶的变化及不良反应.结果:32例患者接受治疗后,止痛的总有效率93.75%;骨转移灶有明显缩小,临床获益率90.62%;所有患者均未发现严重的不良反应.结论:来曲唑联合唑来磷酸对绝经后妇女乳腺癌骨转移骨痛的临床止痛疗效明显,对乳腺癌骨转移是一种有效的治疗方法.     

唑来膦酸联合放疗治疗骨转移性疼痛的临床观察

骨转移是晚期恶性肿瘤患者常见的并发症之一,特别是乳腺癌、前列腺癌、肺癌、甲状腺癌和肾癌等最易出现骨转移.骨转移可表现为骨痛、高钙血症、病理性骨折等.骨转移以40岁～60岁患者居多,多为溶骨性破坏.因此抑制骨破坏,减轻骨痛,提高患者的生存质量,是晚期肿瘤治疗的重要内容.     

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     

乳腺癌骨转移和骨相关疾病临床诊疗专家共识(2008版)

乳腺癌骨转移在复发转移乳腺癌中的发生率为65%～75%.乳腺癌远处转移中,首发症状为骨转移者占27%～50%.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.SHE是指在临床试验中表明双膦酸盐类药物治疗失败的研究观察终点,一般定义为骨痛加剧或出现新的骨痛、病理性骨折、椎体压缩或变形、脊髓压迫、骨放疗、骨转移病灶进展及高钙血症等事件,是影响患者自主活动能力和生活质量的主要因素[1-3].     

120例乳腺癌骨转移核素显像特点分析

目的探讨乳腺癌骨转移患者骨显像的特点及规律.方法 120例乳腺癌患者做全身骨核素显像.结果 120例乳腺癌患者中有58例骨显像异常,结合临床及X线检查诊断为骨转移,骨转移发生率为48.3%.其中27例年龄≤40岁乳腺癌患者骨转移8例,骨转移发生率为29.6%;93例年龄>40岁乳腺癌患者骨转移50例,骨转移发生率为53.8%,年龄>40岁的乳腺癌患者骨转移发生率明显增加(P<0.05).58例骨转移患者中49例为多发病灶(占84.5%),9例为单发病灶(占15.5%),每例患者的平均病灶数为4.83个.骨转移的部位以胸部为多见,其余依次为脊柱、骨盆、肢体和颅骨.结论乳腺癌骨转移发生率很高,骨转移的发生有一定的规律及特点,核素全身骨显像对于临床诊断分期及治疗决策有一定的意义.     

乳腺癌骨转移患者骨代谢指标PICP、β-CTx与治疗效果的关系

目的 探讨骨代谢指标Ⅰ型胶原羧基端前肽(carboxyl-terminal propeptide of type 1 procollagen,PICP)、β胶原降解产物(beta collagen degradation products,β-CTx)与乳腺癌骨转移患者治疗反应的关系.方法 测定56例乳腺癌骨转移患者治疗前后骨代谢指标PICP和β-CTx,比较治疗前后骨代谢指标与治疗效果的关系,并进行随访.结果 56例乳腺癌骨转移患者中,临床获益组36例,治疗3月后PICP和β-CTx明显下降(P=0.016,P=0.001);病情进展组20例,治疗3月后PICP和β-CTx有所升高(P=0.008,P=0.042).临床获益组中20例患者骨代谢指标先于影像学检查提示临床治疗有效.结论 PICP和β-CTx可作为乳腺癌骨转移患者评价疗效的辅助指标.     

骨唾液蛋白诊断乳腺癌骨转移的临床意义

文献报道,约80%的乳腺癌患者尸检发现有骨转移,而且在Ⅰ期乳腺癌患者中就检出23%临床骨转移隐匿病变.临床中这些乳腺癌骨转移患者在发病早期大多无骨痛症状,X线亦无骨破坏征象,一旦发现多数已属晚期,治疗很困难.有文献报道,骨唾液蛋白(bone sialoprotein BSP)主要来源于肿瘤细胞,而且在转移瘤细胞靶向转移至骨的过程中发挥了重要作用,故在众多乳腺癌骨转移标志物中,显示了较高的灵敏性及特异性.     

唑来膦酸联合放疗治疗骨转移性疼痛的临床观察

骨转移是晚期恶性肿瘤患者常见的并发症之一，特别是乳腺癌、前列腺癌、肺癌、甲状腺癌和肾癌等最易出现骨转移。骨转移可表现为骨痛、高钙血症、病理性骨折等。骨转移以40岁．60岁患者居多，多为溶骨性破坏。因此抑制骨破坏，减轻骨痛，提高患者的生存质量，是晚期肿瘤治疗的重要内容。     

NF-κB通过调节GM-CSF促进乳腺癌的溶骨性骨转移

骨骼转移是乳腺癌最常见的并发症，也是造成晚期患者高病死率的主要原因。与前列腺癌骨转移灶以病理性骨增生为主不同，乳腺癌的骨转移呈现一个溶骨的特征。其中破骨细胞和肿瘤细胞之间存在的一个相互促进的恶性循环，被认为是导致溶骨主要作用环节，但是具体的分子机制一直不明。[第一段]     

Bone metastases in breast cancer

Opinion statement Patients with advanced breast cancer who develop bone metastases suffer from longterm skeletal morbidity. Complications of bone metastases include pain, pathologic fractures, and spinal cord compression, which have a significant impact on the quality of life of patients. Treatment options for patients with bone metastases include surgery, radiation, and analgesics to reduce bone pain and to prevent or repair fractures. Intravenous bisphosphonates can delay the onset of bone metastasis and reduce the percentage of patients who experience skeletal complications of bone metastasis, thus reducing skeletal morbidity. For the past 6 years, pamidronate disodium (90 mg administered by 2-hour intravenous infusion) has been the treatment of choice for the prevention of skeletal complications of bone metastases in patients with breast cancer. However, a more potent bisphosphonate, zoledronic acid (4 mg administered by 15-minute intravenous infusion), was approved for use and has improved efficacy in patients with bone metastases. Because of the increased efficacy and more convenient infusion time, zoledronic acid may become the new standard of care for the treatment and prevention of skeletal complications secondary to bone metastases in patients with breast cancer. Phase III clinical trials have shown that patients with an existing skeletal complication are more likely to develop subsequent complications compared with patients who have not experienced a complication. Therefore, zoledronic acid therapy should be initiated when the patient is diagnosed with bone metastasis.     

肿瘤标志物与乳腺癌骨转移的诊治

 骨转移是乳腺癌远处转移的最常见部位，及时和准确的诊断和治疗对提高患者生活质量、延长生存期具有重要意义。近年来，肿瘤标志物在乳腺癌骨转移中的作用日益受到重视。对部分肿瘤标志物在乳腺癌骨转移诊断、治疗以及疗效监测等方面研究进展进行了综述。     

Implications of bone metastases and the benefits of bone-targeted therapy

Several cancers, including those originating in the breast, prostate, and lung, exhibit a propensity to metastasize to bone, resulting in debilitating skeletal complications. These sequelae, such as intractable pain, pathologic fractures, spinal compression, and hypercalcemia, greatly erode the patients' quality of life. Bisphosphonates, a class of antiresorptive drugs, are now the mainstay of the treatment of skeletal-related events in myeloma bone disease and many solid cancers with bone metastases. Current evidence indicates that newer-generation nitrogen-containing bisphosphonates, particularly zoledronic acid, are potent inhibitors of bone resorption. In addition, increased understanding of the pathogenesis of bone metastasis has resulted in the development of several bone-targeted therapies including a monoclonal antibody targeting the receptor activator of nuclear factor (NF)-κB ligand (RANKL). In this review, clinical evidence regarding the efficacy and safety of currently available bone-targeted therapies including bisphosphonates and anti-RANKL monoclonal antibody in the treatment of bone metastasis due to breast cancer, prostate cancer, lung cancer, and multiple myeloma bone disease will be summarized.     

前列腺癌骨转移治疗的研究进展

前列腺癌是常见的男性泌尿系恶性肿瘤之一，而骨转移是前列腺癌常见的并发症之一。骨转移后出现严重的骨痛、病理性骨折、神经压迫等各种并发症，严重影响患者的生活质量，更决定患者的生存时间。目前关于前列腺癌骨转移治疗的文献较多，但还没有宏观上分析各种治疗方法的应用时机，未形成一个大家都认同的标准化治疗方案。本文就通过前列腺癌骨转移的分类来制定治疗方案作一综述。     

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。     

数字机器人在乳腺癌骨转移活检中应用

目的 探讨数字机器人在乳腺癌骨转移灶活检诊疗中的应用价值.方法 初步分析了2018年5月至2021年5月江苏省人民医院收治的符合选择标准的12例乳腺癌骨转移患者临床资料,其中,2例在机器人辅助下行骨转移病灶穿刺活检术,10例行经皮徒手活检术.活检标本送病理科行组织病理学检查.应用SPSS26.0统计软件对数据进行分析....     

ABCC5 supports osteoclast formation and promotes breast cancer metastasis to bone

Introduction

Bone is the most common site of breast cancer metastasis, and complications associated with bone metastases can lead to a significantly decreased patient quality of life. Thus, it is essential to gain a better understanding of the molecular mechanisms that underlie the emergence and growth of breast cancer skeletal metastases.

Methods

To search for novel molecular mediators that influence breast cancer bone metastasis, we generated gene-expression profiles from laser-capture microdissected trephine biopsies of both breast cancer bone metastases and independent primary breast tumors that metastasized to bone. Bioinformatics analysis identified genes that are differentially expressed in breast cancer bone metastases compared with primary, bone-metastatic breast tumors.

Results

ABCC5, an ATP-dependent transporter, was found to be overexpressed in breast cancer osseous metastases relative to primary breast tumors. In addition, ABCC5 was significantly upregulated in human and mouse breast cancer cell lines with high bone-metastatic potential. Stable knockdown of ABCC5 substantially reduced bone metastatic burden and osteolytic bone destruction in mice. The decrease in osteolysis was further associated with diminished osteoclast numbers in vivo. Finally, conditioned media from breast cancer cells with reduced ABCC5 expression failed to induce in vitro osteoclastogenesis to the same extent as conditioned media from breast cancer cells expressing ABCC5.

Conclusions

Our data suggest that ABCC5 functions as a mediator of breast cancer skeletal metastasis. ABCC5 expression in breast cancer cells is important for efficient osteoclast-mediated bone resorption. Hence, ABCC5 may be a potential therapeutic target for breast cancer bone metastasis.     

乳腺癌骨转移机制与靶向治疗进展

乳腺癌骨转移是晚期乳腺癌常见的症状,乳腺癌细胞通过局部浸润、渗入血管和或淋巴管、随循环系统转移到骨、移出血管和或淋巴管、在骨定居并增殖引起溶骨性骨损伤。乳腺癌骨转移的发生发展取决于乳腺癌细胞与骨局部微环境之间相互作用,最后形成骨的结构破坏及功能受损。本文主要从分子水平阐述乳腺癌骨转移机制,并且综述针对乳腺癌骨转移关键靶点的抗骨转移药物的临床应用。     

放疗在乳腺癌骨转移中的临床应用进展

骨转移是晚期乳腺癌最常见的远处转移,多伴有局部疼痛、肢体功能障碍等症状,常导致患者的生存质量下降。由骨转移引起的病理性骨折等骨相关事件(skeletal-related events,SREs)会显著增加乳腺癌患者的死亡风险。积极有效的骨转移治疗有重要的临床意义,放疗是重要的局部治疗手段。本文就放疗在乳腺癌骨转移中的临床应用进展进行综述,着重阐述放疗实施手段及综合治疗模式的循证医学证据。