Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody

A murine monoclonal antibody against a surface antigen of small-cell carcinoma of the lung (SM1 antibody) was investigated for its use in detecting bone marrow metastasis. Bone marrow cells of healthy volunteers and of patients with small-cell carcinoma of the lung (SCCL) were examined for reactivity with SM1 antibody and indirect immunofluorescence and the results compared to conventional histochemical staining (Wright-Giemsa stain of bone marrow aspirates and hematoxylin-eosin stains of bone marrow biopsies). No SM1 reactivity was found in marrow cells of eight healthy volunteers. Thirty-six samples from 33 patients with SCCL were examined; tumor involvement was found in 69% by SM1 antibody and in 16% by histochemical stains. All bone marrow samples from patients with SCCL that were unreactive with SM1 antibody also showed no evidence of tumor involvement by histochemical stains. Samples of 29 patients were investigated at initial staging; SM1 reactive cells were found in 50% of 16 patients with limited disease and in 77% of 13 patients with extensive disease. Overall, the proportion of patients recognized to have disseminated disease at diagnosis was increased from 45% to 72% by monoclonal antibody staining. Indirect immunofluorescence with SM1 antibody allows detection of bone marrow metastasis of SCCL that cannot be seen by conventional morphology and can identify disseminated disease in patients otherwise staged limited disease.     

Wnt signaling pathway: Implications for therapy in lung cancer and bone metastasis

Lung cancer remains a major worldwide health problem and patients have high rate of metastasis including bone. Although pathologic characteristics of this disease are clear and well established, much remains to be understood about this tumor, particularly at the molecular signaling level. Secreted signaling molecules of the Wnt family have been widely investigated and found to play a prominent role to induce human malignant diseases, such as breast and prostate cancer. A variety of studies have also demonstrated that the Wnt signaling pathway is closely associated with bone malignancies including osteosarcoma, multiple myeloma, and breast or prostate cancer induced bone metastasis. The aim of this review is to provide a summary regarding the role of the Wnt signaling pathway in lung cancer and bone metastasis, highlighting the aberrant activation of Wnt in this malignancy. We also discuss the potential therapeutic applications for the treatment of lung cancer and cancer induced bone metastasis targeting the Wnt pathway.     

非小细胞肺癌骨转移化疗后的骨髓抑制分析

目的：观察晚期非小细胞肺癌骨转移患者化疗后的骨髓抑制程度.方法：将247例晚期非小细胞肺癌患者分为两组,研究组为伴骨转移的患者132例,对照组为无骨转移的患者115例,化疗1周期,进行骨髓抑制和其他不良反应的比较.结果：研究组中化疗后Ⅲ-Ⅳ度白细胞、血小板、红细胞下降的患者比例分别是28.8％、31.1％和20.5％,对照组为15.7％、14.8％和13.0％,差异有统计学意义（P＜0.05）.研究组出现骨髓抑制最严重的平均时间为9天,对照组12天,差异有统计学意义（P＜0.05）.Ⅲ-Ⅳ度恶心、呕吐和流感样症状恶心、呕吐研究组为31.8％、8.3％,对照组为19.1％、1.7％,差异有统计学意义（P＜0.05）.结论：晚期非小细胞肺癌骨转移化疗后更易发生严重的骨髓抑制,且时间提前;恶心、呕吐及流感样症状程度较严重,应注意化疗剂量的调整.     

Wnt signaling through Snail1 and Zeb1 regulates bone metastasis in lung cancer

Wnt-β-catenin signaling participates in the epithelial-mesenchymal transition (EMT) in a variety of cancers; however, its role in lung cancer induced bone metastasis and the underlying mechanisms remain unclear. Here, we demonstrate that β-catenin, Snail1 and Zeb1 were significantly upregulated in bone metastasis tissues from human and mouse compared with the normal controls. E-cadherin expression is negatively regulated by Zeb1, Snail1 and β-catenin during bone metastasis tissues induced by lung cancer. Knocking down Zeb1 and Snail1 in lung cancer cell lines showed increased E-cadherin mRNA expression and less invasion compared with the original cell lines. In addition, β-catenin knockdown led to the increase of E-cadherin and the decrease of Zeb1 and Snail1, which in turn inhibited the invasive properties of lung cancer. Our results demonstrated that Wnt signaling through Snail1 and Zeb1 regulates bone metastasis in lung cancer.     

Management of bone metastasis originating from lung cancer

The preceding molecular target therapies have prolonged the life expectancy of many lung cancer patients, and some lung cancer patients have become long-term survivors. On the other hand, the proportion of patients who suffer from complications with bone metastasis and skeletal-related events(SRE)is increasing. Through management of bone metastasis, the preservation of quality of life and functional independence can be better maintained. Zoledronic acid and denosumab are usable in clinical practice; However, there are many problems in regard to treatments for bone metastasis. Lung cancer patients should be treated with bone metastasis with the coordinating cooperation between orthopedists, radiotherapists and dental surgeons.     

62例肺癌骨转移

报道62例肺癌骨转移。96．8％的患者有骨痛。63．3％的患者骨痛出现时间晚于呼吸道症状。肺癌骨转移的部位以胸骨最常见（占70．1％），其次为脊柱（69．3％）和骨盆（45．2％）。骨x线片对病灶的检出率为64．3％，且以单灶为多（68．6％），平均检出病灶数为1．6±0．2个。骨核素显像的检出率为100％，且能检出多灶（占59．1％），平均检出病灶数为2．8±0．1个。骨X线片和核素显像结合应用可提高骨转移灶的定性、定位诊断。     

Suppression of tumor metastasis by blockade of transforming growth factor beta signaling in bone marrow cells through a retroviral-mediated gene therapy in mice

Transforming growth factor B (TGF-beta) is a potent immunosuppressive cytokine that is frequently associated with mechanisms of tumor escape from immunosurveillance. We report that transplantation of murine bone marrow (BM) expressing a dominant-negative TGF-beta type II receptor (TbetaRIIDN) leads to the generation of mature leukocytes capable of a potent antitumor response in vivo. Hematopoietic precursors in murine BM from donor mice were rendered insensitive to TGF-beta via retroviral expression of the TbetaRIIDN construct and were transplanted in C57BL/6 mice before tumor challenge. After i.v. administration of 5 x 10(5) B16-F10 murine melanoma cells into TbetaRIIDN-BM transplanted recipients, survival of challenged mice at 45 days was 70% (7 of 10) versus 0% (0 of 10) for vector-control treated mice, and surviving TbetaRIIDN-BM mice showed a virtual absence of metastatic lesions in the lung. We also investigated the utility of the TGF-beta-targeted approach in a mouse metastatic model of prostate cancer, TRAMP-C2. Treatment of male C57BL/6 mice with TbetaRIIDN-BM resulted in the survival of 80% (4 of 5) of recipients versus 0% (0 of 5) in green fluorescent protein-BM recipients or wild-type controls. Cytolytic T-cell assays indicate that a specific T-cell response against B16-F10 cells was generated in the TbetaRIIDN-BM-treated mice, suggesting that a gene therapy approach to inducing TGF-beta insensitivity in transplanted BM cells may be a potent anticancer therapy.     

乳腺癌骨髓转移特点及治疗方法探讨

目的探讨乳腺癌患者骨髓转移临床表现的特殊性、转移规律及治疗策略。方法回顾性分析62例女性乳腺癌骨髓转移患者的临床及随访资料,包括乳腺癌骨髓转移发生时间、激素受体状况等及不同治疗策略对预后的影响。24例联合化疗,25例单药化疗,13例未接受化疗。生存率用Kaplan—Meier方法计算,用Log—rank方法进行生存曲线比较。结果62例患者中位年龄39岁（30～71岁）,中位病程21个月（1～49个月）。雌激素受体（ER）和（或）孕激素受体（PR）阳性患者30例（48．4％）,阴性19例（30．6％）。发热14例（22．6％）和（或）血象的一系或三系降低34例（62．9％）是乳腺癌骨髓转移的常见表现。联合化疗和单药化疗中位生存期分别为10个月和16个月（QPH=7．38,P=0．0335）,未接受化疗者中位生存期仅1个月。骨髓转移发生偏晚,一般有多处转移尤其是骨转移的背景。结论骨髓穿刺有利于早期发现骨髓转移;骨髓转移晚期体质较弱,单药化疗可能是有效的治疗策略之一,与联合化疗组的患者相比具有生存优势。     

The bone marrow stroma in hematological neoplasms--a guilty bystander

In the setting of hematological neoplasms, changes in the bone marrow (BM) stroma might arise from pressure exerted by the neoplastic clone in shaping a supportive microenvironment, or from chronic perturbation of the BM homeostasis. Under such conditions, alterations in the composition of the BM stroma can be profound, and could emerge as relevant prognostic factors. In this Review, we delineate the multifaceted contribution of the BM stroma to the pathobiology of several hematological neoplasms, and discuss the impact of stromal modifications on the natural course of these diseases. Specifically, we highlight the involvement of BM stromal components in lymphoid and myeloid malignancies, and present the most relevant processes responsible for remodeling the BM stroma. The role of bystander BM stromal elements in the setting of hematological neoplasms is discussed, strengthening the rationale for treatment strategies that target the BM stroma.     

PET-CT对肺癌骨转移诊断的研究进展

 正电子发射型计算机断层扫描仪 (PET)-CT对诊断肺癌骨转移有重要的作用,它可以反映肺癌骨转移病灶的病理生理变化及形态结构变化。PET-CT全身显像对肺癌骨转移诊断的敏感性、特异性及准确性均高于X线片、CT、磁共振成像（MRI）和单光子发射计算机断层（SPECT）等传统的肺癌骨转移临床诊断方法。     

Multidisciplinary strategy for lung cancer patients with bone metastasis

The fall of QOL by bone metastasis poses a problem with the increase in lung cancer. The examples of long-term survival of lung cancer are also increasing by progress of chemotherapy or molecular-targeted therapy. Now, in addition to the conventional radiotherapy, the multidisciplinary treatment including a newer bisphosphonates or an orthopedic operation has been needed to bone metastasis of lung cancer. We presented the lung cancer case who showed the symptoms in transcervical pathologic fracture and whose QOL was improved by orthopedic surgery, radiotherapy to bone metastasis, chemotherapy, gamma knife surgery, and treatment with zoledronic acid and gefitinib.     

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。     

胃癌骨髓转移的血液学特征和治疗方式探讨

目的 探讨胃癌骨髓转移患者的临床病理特征、治疗及预后.方法 回顾性分析9例胃癌骨髓转移患者的临床资料,总结其临床特点、诊断和治疗方法.结果 9例患者的年龄为18~68岁,中位年龄为51岁,病理均为低分化腺癌.患者均伴有其他部位转移,常见淋巴结和骨转移.骨痛、非感染性发热、红细胞和血小板二系下降、碱性磷酸酶和(或)乳酸脱氢酶不同程度升高、外周血涂片可见幼稚细胞是胃癌骨髓转移的常见表现.胃癌骨髓转移患者的中位生存期为34 d(11~266 d).结论 胃癌骨髓转移患者的预后差,熟悉胃癌骨髓转移的临床特点有利于早期诊断.     

Hedgehog信号通路与肿瘤转移

Hedgehog(Hh)信号通路在果蝇、多种脊椎动物及人类胚胎发育过程中对细胞分化和增生起重要作用.该通路中各信号分子的突变、异常激活和过表达都可能导致肿瘤的发生.最近研究表明,Hh信号通路与多种恶性肿瘤侵袭和转移有密切的关系,其机制与肿瘤干细胞、上皮细胞间质转化、自分泌/旁分泌途径、肿瘤新生血管和淋巴管等有关.对Hh...     

^153Sm—EDTMP治疗肺癌骨转移

探讨＾１５３Ｓｍ－ＥＤＴＭＰ治疗肺癌骨转移的临床效果。方法１１０例肺癌伴骨转移的患者接受该治疗。采用两次给药法,第一次先注射示踪剂量,分别计算尿排有摄取率,骨累积活性、红骨髓的吸收剂量,总用药量以后,再注射第二次剂理。结果疼痛完全缓解者３８例,中度缓者６０叫止痛有效率为８９．１％。     

肺癌骨转移相关分子的比较蛋白质组学研究

目的:分析比较人肺癌不同骨转移潜能细胞株的差异表达蛋白质图谱,筛选在肺癌骨转移中起重要作用的关键蛋白质分子。方法:利用双向凝胶电泳(2-DE)和基质辅助激光解析离子化-飞行时间-质谱技术,分析人肺癌骨转移细胞株SBC-5和非骨转移细胞株SBC-3/DOX蛋白质图谱的差异表达,查询数据库筛选肺癌骨转移相关蛋白质。结果:PDQuest 8.0软件分析3次相同条件下的2-DE图谱,结果显示重复性、匹配性较好。SBC-5检测到(1116±64)个蛋白点,平均匹配率为84%;SBC-3/DOX检测到(1132±72)个蛋白点,平均匹配率为82%;蛋白质点分布以PI 4-7、相对分子质量20 000-80 000范围内最多。两种细胞株16个差异蛋白质点胰酶胶内酶解,质谱分析获得14张肽质量指纹谱,鉴定出Annexin A1,CaN,IGFBP-1,ADAM32等8种胶内差异蛋白质。结论:人肺癌不同骨转移潜能细胞株SBC-5和SBC-3/DOX的2-DE蛋白质图谱具有明显的差异表达,多种差异表达蛋白可能与肺癌骨转移相关。     

Nasopharyngeal carcinoma with bone marrow metastasis

Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan.