转化生长因子β受体与肿瘤

许多恶性肿瘤细胞均有转化生长因子受体Ⅱ(transforming growth factor-β receptor typeⅡ,TGF-βⅡ)表达缺失或降低,从而使其逃脱TGFβ的生长控制而获得恶性增殖能力.在胃肠癌中,TGF-βRⅡ polyA序列的移码突变是造成受体表达异常的主要原因;头颈部癌中,TGF-βRⅡ点突变引起其蛋白产物磷酸化功能障碍;乳腺癌细胞TGF-βRⅡ表达缺失可能与其蛋白运输异常有关,基因及药物治疗可恢复TGF-βRⅡ表达,逆转肿瘤细胞恶性表型,为肿瘤治疗提供了新的发展方向.     

靶向 EphB4受体分子探针的研究进展

促红细胞生成素产生肝细胞受体（Eph）B 型受体4与肿瘤生长和肿瘤血管形成密切相关,并且在许多肿瘤中过量表达。EphB4靶向探针可提高肿瘤诊断的准确性和特异性。大量针对该靶点的分子探针已经被设计出来,有望为肿瘤的早期诊断和治疗提供新的方法。     

TGF-β／Smads信号转导与胰腺癌

TGF-β／Smads信号转导通路是由TGFIG超家族、TGF-β受体、Smads蛋白家族及其核内转录调节因子组成的肿瘤抑制通路。通路中任一元件的异常都可以引起TGF-β／Smads信号转导紊乱，从而导致肿瘤的发生。大多数胰腺癌都有TGF-β／Smads信号转导异常。其发生机制主要包括Smads家族突变(主要为Smad4)和表达异常(Smad6．7)，也涉及TGF—β超家族及其受体的改变。     

雌激素受体与乳腺癌内分泌治疗耐药的相关性研究

目的探讨雌激素受体β(ERβ)与乳腺癌内分泌治疗耐药的相关性。方法选取2010年1月至2015年6月间广东省惠州市中心人民医院收治的行乳腺癌改良根治术且接受他莫昔芬(TAM)内分泌治疗的100例早中期绝经后乳腺癌患者。检测乳腺癌患者ERβ表达情况,计算患者无肿瘤生存时间,比较不同ERβ表达患者间临床因素和预后的差异,分析ERβ表达差异与TAM内分泌治疗耐药的关系。结果 ERβ表达与原癌基因人类表皮生长因子受体2(HER-2)的表达相关,差异有统计学意义(P<0.05),与患者年龄、肿瘤大小、淋巴结转移、化疗及放疗无关,差异无统计学意义(P>0.05)。ERβ阳性表达患者无肿瘤生存率明显低于ERβ阴性表达患者,差异有统计学意义(P<0.05)。Cox多因素分析显示,ERβ阳性表达患者中,淋巴结转移是乳腺癌内分泌治疗预后不良的独立危险因素,差异有统计学意义(P<0.05)。结论 ERβ阳性表达在乳腺癌患者内分泌治疗耐药中具有重要作用,可能是导致患者预后不佳的危险因素之一。     

非小细胞肺癌中PDGF-BB及其受体PDG-FR-β的表达与淋巴管生成及淋巴道转移的关系

目的检测PDGF-BB及其受体PDGFR-β在NSCLC中的表达,探讨其表达与NSCLC淋巴管生成及淋巴道转移的关系。方法采用免疫组化SP法检测PDGF-BB及其受体PDGFR-β在113例NSCLC癌组织中的表达水平,分析它们的表达与临床病理参数之间的关系;应用D2-40进行淋巴管染色,计数NSCLC中微淋巴管密度（LMVD）;分析PDGF-BB及其受体与微淋巴管密度之间的关系,探讨其在NSCLC淋巴管生成及淋巴道转移中的作用。结果 PDGF-BB主要表达在NSCLC癌细胞的胞膜和胞浆中,其阳性表达率为63.7%（72/113）;PDGFR-β主要表达在NSCLC癌巢周围的间质细胞的细胞质中,阳性表达率为61.0%（69/113）;PDGF-BB在NSCLC癌细胞中的表达与间质中PDGFR-β的表达明显相关。PDGF-BB、PDGFR-β表达水平与患者的年龄、肿瘤大小、组织类型、分化程度均无关,而与TNM分期、淋巴结转移有关。PDGF-BB阳性表达组其LMVD显著高于阴性表达组（16.5817±5.4556对11.4689±5.5679,P〈0.05）;PDGFR-β阳性表达组其LMVD显著高于阴性表达组（15.7937±5.6383对11.6917±6.3862,P〈0.05）。结论 PDGF-BB及其受体PDGFR-β在NSCLC上的阳性表达可以促进肿瘤淋巴管的生成及淋巴转移,针对这些信号通路的抑制剂的研发将为抑制肿瘤淋巴转移带来新的治疗前景。     

Wnt/β-catenin信号通路相关长链非编码RNA在肿瘤进展中的功能与机制

长链非编码RNA（lncRNA）是一类长度大于200 nt、且不编码的RNA。lncRNA 已被证明与人类疾病紧密相关，尤其是肿瘤发生发展。研究表明，肿瘤中一些异常表达的lncRNA 可以通过不同的信号通路，如Wnt/β-catenin 信号通路，促进肿瘤进展过程。在不同肿瘤组织中具有特异性表达特征的lncRNA与Wnt/β-catenin 信号通路之间的相互作用显示出其作为新的生物标志物和治疗靶点的潜能。本文就Wnt/β-catenin 信号通路相关lncRNA 通过调控Wnt/β-catenin 信号转导，影响不同肿瘤类型发生发展的作用进行综述。本文结果或可为临床肿瘤诊断和治疗提供新的思路。     

血管内皮细胞生长因子及其受体与肿瘤血管形成

血管内皮细胞生长因子（ＶＥＧＦ）调控血管生长特异性高，作用强，许多肿瘤细胞均有表达；仅有极少正常组织，在特定的条件下，才量表达；也只有血管内皮细胞表达细胞表达ＶＥＧＦ特异性受体，因此，可通过干预ＶＥＧＦ及其受体，抑制肿瘤血管形成，达到预防和治疗肿瘤转移和复发的目的。     

mRNA疗法在肿瘤免疫治疗中的应用

mRNA疗法以mRNA为制剂治疗疾病，是一种新兴的基因疗法，既可通过功能性蛋白的表达治疗基因缺陷性疾病或组织修复，又可通过抗原或抗体或受体的表达应用于免疫治疗，具有极大的应用价值。在肿瘤免疫治疗中，编码肿瘤相关抗原、特异性抗原、抗体或受体的mRNA进入细胞质后翻译成蛋白质，进而诱导特定免疫反应，实现疾病的预防与治疗。随着免疫治疗技术和mRNA的技术发展，针对恶性肿瘤和传染性疾病等的mRNA免疫治疗已步入临床应用阶段。本文将就mRNA的合成、纯化及修饰，基于mRNA的肿瘤免疫疗法、临床试验结果及开发新药所遇到的关键性机遇与挑战进行综述。      

软组织肿瘤的凝集素组织化学

应用ABC免疫组化技术对134例软组织肿瘤进行12种凝集素受体的定位检测,了解其受体的分布特点,以判断肿瘤性质和组织起源,探讨其在软组织肿瘤诊断中的价值。结果发现不同组织源性及良、恶性软组织肿瘤凝集素受体表达不一.因此作者认为有些凝集素可作为软组织肿瘤诊断或鉴别诊断、良恶性区分的标志,(?)组织肿瘤的定性、定源提供了新的参数.     

生长抑素受体显像与肿瘤的诊断和治疗

受体和配体的结合具有高度的特异性和组织专一性,研究发现多种肿瘤组织表达高密度的生长抑素受体(SSTR),放射性核素标记的生长抑素可以与肿瘤细胞膜上的生长抑素受体特异性结合,通过放射性核素的介导作用对肿瘤进行定位和诊断.β射线可以直接杀伤相应的肿瘤细胞起内辐射的治疗作用.     

Release of serotonin from human carcinoid tumor cells in vitro and grown in the anterior eye chamber of the rat

Serotonin (5-HT)-producing human carcinoid tumors have been successfully transplanted to the anterior eye chamber of cyclosporine treated rats. Tumor transplants were rapidly vascularized and viable tumor cells could be demonstrated in transplants grown for 2 to 3 weeks in oculo. The release of 5-HT from carcinoid tumor cells grown in the anterior eye chamber and from tumor cells in suspension was studied after stimulation with various adrenoceptor agonists. A dose dependent release of 5-HT upon stimulation with isoprenaline was demonstrated for all viable carcinoid tumors in oculo. The isoprenaline-stimulated release of 5-HT from the tumor cells was further studied in vitro, and was efficiently antagonized by propranolol or nadolol, but not by phenoxybenzamine, indicating activation of beta-adrenoceptors on carcinoid tumor cells upon isoprenaline stimulation. Incubation of tumor cells with verapamil, a calcium channel inhibitor, also prevented the release of 5-HT upon isoprenaline stimulation. Thus, carcinoid tumors can be successfully transplanted to the anterior eye chamber of cyclosporine treated rats, offering new possibilities to study the pharmacologic and biologic features of this tumor. In the future, carcinoid tumors, as well as other endocrine tumors, may be grown in oculo in rats and receptor pharmacology and individual sensitivity to cytotoxic drugs can be studied, thus enabling optimal clinical treatment.     

骨肿瘤规范化治疗与研究展望

近30年来,骨与软组织肿瘤的治疗在整个骨科领域中所占的比重虽然不大,但其进步是非常显著的。随着化疗的引入,手术技术的提高,综合治疗和规范化治疗的倡导,骨与软组织肿瘤的诊治水平和策略有了长足的发展。对于常见的骨与软组织原发肿瘤,治疗的总体方案归结为以手术为主导,放化疗为辅助的综合治疗,患者的生存率较前大大提高,复发率明显降低,功能评定显著改善。在当前的总体治疗策略上,我们仍然一贯地推崇骨肿瘤的规范化治疗,并不遗余力地在全国进行推广。倡导规范化、推动规范化、推崇创新研究,是目前骨肿瘤学科的鲜明特点。     

肥大细胞与肿瘤血管生成

肥大细胞(MC)是起源于骨髓,定居于组织的免疫细胞.肿瘤可以通过干细胞因子(SCF)及其在肥大细胞上的受体c-kit来介导对MC的募集.MC在肿瘤部位的数量和分布与肿瘤的生长、血管新生密切相关.MC可以通过释放血管生成因子介导血管新生,促进肿瘤的进展.     

Targetable BRAF and RAF1 Alterations in Advanced Pediatric Cancers

RAF family protein kinases signal through the MAPK pathway to orchestrate cellular proliferation, survival, and transformation. Identifying BRAF alterations in pediatric cancers is critically important as therapeutic agents targeting BRAF or MEK may be incorporated into the clinical management of these patients. In this study, we performed comprehensive genomic profiling on 3,633 pediatric cancer samples and identified a cohort of 221 (6.1%) cases with known or novel alterations in BRAF or RAF1 detected in extracranial solid tumors, brain tumors, or hematological malignancies. Eighty percent (176/221) of these tumors had a known‐activating short variant (98, 55.7%), fusion (72, 40.9%), or insertion/deletion (6, 3.4%). Among BRAF altered cancers, the most common tumor types were brain tumors (74.4%), solid tumors (10.8%), hematological malignancies (9.1%), sarcomas (3.4%), and extracranial embryonal tumors (2.3%). RAF1 fusions containing intact RAF1 kinase domain (encoded by exons 10–17) were identified in seven tumors, including two novel fusions TMF1‐RAF1 and SOX6‐RAF1. Additionally, we highlight a subset of patients with brain tumor with positive clinical response to BRAF inhibitors, demonstrating the rationale for incorporating precision medicine into pediatric oncology.Implications for PracticePrecision medicine has not yet gained a strong foothold in pediatric cancers. This study describes the landscape of BRAF and RAF1 genomic alterations across a diverse spectrum of pediatric cancers, primarily brain tumors, but also encompassing melanoma, sarcoma, several types of hematologic malignancy, and others. Given the availability of multiple U.S. Food and Drug Administration‐approved BRAF inhibitors, identification of these alterations may assist with treatment decision making, as described here in three cases of pediatric cancer.     

Thrombin inhibition and cyclophosphamide synergistically block tumor progression and metastasis

Cancer is often associated with an increased risk of thrombotic events which are exacerbated by treatment with chemotherapeutics such as cyclosphosphamide (CP). Evidence suggests that thrombin can stimulate tumor progression via formation of fibrin and activation of protease-activated receptors (PARs) and platelets. We examined the effect of co-treatment with CP and dabigatran etexilate, a direct inhibitor of thrombin, using the murine orthotopic 4T1 tumor model. Mice receiving co-treatment with both low dose CP and dabigatran etexilate had significantly smaller mammary tumors and fewer lung metastases than mice treated with CP or dabigratran etexilate alone. Co-treatment with dabigatran etexilate and low dose CP also significantly decreased the number of arginase⁺Gr-1⁺CD11b⁺ myeloid derived suppressor cells as well as levels of TGF-β in spleens from tumor bearing mice. 4T1 tumors express procoagulant tissue factor (TF) and spontaneously release TF⁺ microparticles which are potent procoagulant factors that promote thrombin generation. Treatment with dabigatran etexilate alone prevented tumor-induced increases in circulating TF⁺ microparticles and also decreased the numbers of tumor-induced activated platelets by 40%. These results show that co-treatment with dabigatran etexilate and CP synergistically inhibits growth and metastasis of mammary tumors, suggesting that oral administration of the thrombin inhibitor dabigatran etexilate may be beneficial in not only preventing thrombotic events in cancer patients but also in treating malignant tumors themselves.     

HOXA5基因与肿瘤

HOXA5作为同源盒(HOX)基因家族的一员,在多器官中都有表达,具有调节基因表达、细胞分化和机体形态发生的功能,其结构和(或)功能异常与白血病、乳腺癌、脑血管瘤、肝细胞癌等肿瘤的发生密切相关.研究HOXA5与肿瘤的关系有助于肿瘤的诊断、治疗及预防.     

HOXA5基因与肿瘤

HOXA5作为同源盒（HOX）基因家族的一员，在多器官中都有表达，具有调节基因表达、细胞分化和机体形态发生的功能，其结构和（或）功能异常与白血病、乳腺癌、脑血管瘤、肝细胞癌等肿瘤的发生密切相关。研究HOXA5与肿瘤的关系有助于肿瘤的诊断、治疗及预防。     

胆固醇代谢与恶性肿瘤

已有研究证实胆固醇代谢在肿瘤发生、发展过程中发挥着重要的作用,同时也在预测恶性肿瘤预后中显示出重要的应用价值.胆固醇可以通过对恶性肿瘤患者进行恰当的风险分层,来提高肿瘤患者远期的生命质量和生存时间.     

基于DWMRI和增强CT勾画胰腺癌GTV对比研究

目的 通过对比研究增强CT及DWMRI在胰腺恶性肿瘤体积大小、肝脏及区域淋巴结转移瘤的差异,指导临床放疗实践。方法 计划入组40例胰腺癌患者,均行增强CT及DWMRI定位扫描,后依据不同图像进行靶区体积勾画、肿瘤最大截面长径测量、肝转移瘤及5~8 mm、>8 mm淋巴结转移瘤的测量。分别使用配对t检验或配对Wilcoxon秩和检验进行分析。结果 基于增强CT、DWMRI所勾画的GTV平均值分别为54.95、41.67 cm³(P=0.000),肿瘤最大界面长径平均值分别为4.18、3.94 cm (P=0.000),其中2例d_CT小于d_DWMRI。依据增强CT、DWMRI图像分别检出肝脏转移瘤83、112个,增强CT检出量占DWMRI检出的74%;>8 mm淋巴结转移瘤分别检出46、56个,5~8 mm淋巴结分别检出103、200个,增强CT检出量分别占DWMRI检出的82%、52%。结论 基于DWMRI测量的GTV及肿瘤最大界面长径较增强CT小,在肝脏及区域淋巴结转移瘤检出较增强CT敏感。然而还需要进一步参照病理对照试验证实。     

Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity

Streptococcus bovis (S. bovis) bacteria are associated with colorectal cancer and adenoma. S. bovis is currently named S. gallolyticus. 25 to 80% of patients with S. bovis/gallolyticus bacteremia have concomitant colorectal tumors. Colonic neoplasia may arise years after the presentation of bacteremia or infectious endocarditis of S. bovis/gallolyticus. The presence of S. bovis/gallolyticus bacteremia and/or endocarditis is also related to the presence of villous or tubular-villous adenomas in the large intestine. In addition, serological relationship of S. gallolyticus with colorectal tumors and direct colonization of S. gallolyticus in tissues of colorectal tumors were found. However, this association is still under controversy and has long been underestimated. Moreover, the etiological versus non-etiological nature of this associationis not settled yet. Therefore, by covering the most of up to date studies, this review attempts to clarify the nature and the core of S. bovis/gallolyicus association with colorectal tumors and analyze the possible underlying mechanisms.