The future of clinical cancer genomics

The current and future applications of genomics to the practice of preventive oncology are being impacted by a number of challenges. These include rapid advances in genomic science and technology that allow massively parallel sequencing of both tumors and the germline, a diminishing of intellectual property restrictions on diagnostic genetic applications, rapid expansion of access to the internet which includes mobile access to both genomic data and tools to communicate and interpret genetic data in a medical context, the expansion of for-profit diagnostic companies seeking to monetize genetic information, and a simultaneous effort to depict medical professionals as barriers to rather than facilitators of understanding one’s genome. Addressing each of these issues will be required to bring “personalized” germline genomics to cancer prevention and care. A profound future challenge will be whether clinical cancer genomics will be “de-medicalized” by commercial interests and their advocates, or whether the future course of this field can be modulated in a responsible way that protects the public health while implementing powerful new medical tools for cancer prevention and early detection.     

Genetic variation and risk of chronic lymphocytic leukaemia

Chronic lymphocytic leukaemia (CLL) is the most common form of lymphoid malignancy in Western countries, accounting for around a quarter of all leukaemias.Evidence from epidemiological and family studies have provided evidence for familial clustering of CLL compatible with inherited genetic predisposition to CLL. Direct evidence for genetic susceptibility has been provided by a recent genome wide association study of CLL which has identified common variants at 10 different loci which influence CLL risk. Here we review the current knowledge regarding the allelic architecture of susceptibility to CLL and what the currently identified risk loci are telling us regarding disease aetiology.     

Current status of familial gastrointestinal polyposis syndromes

Because of the rarity of familial gastrointestinal cancer-predisposing syndromes, their exploration in literature is not extensive. In this review, an update of the clinicopathological and molecular criteria of gastrointestinal familial polyposis syndromes with potential malignant transformation is performed. In addition, a guide for screening and surveillance was synthesized and a distribution of gene mutations according to the specific syndromes and geographic distribution was included. The following inherited polyposes syndromes were analyzed: familial adenomatous polyposis, the hamartomatous familial polyposes (Juvenile polyposis, Peutz-Jeghers syndrome, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, hereditary mixed polyposis syndrome, Gorlin syndrome, Birt-Hogg-Dube syndrome, neurofibromatosis type I and multiple endocrine neoplasia syndrome 2B), Li-Fraumeni syndrome, and MUTYH-associated adenomatous polyposis. For proper medical care, subspecialization of gastroenterologists, pathologists, and genticists in the field of familial diseases should be introduced in the medical curriculum.     

Platelets promote osteosarcoma cell growth through activation of the platelet‐derived growth factor receptor‐Akt signaling axis

The interactions of tumor cells with platelets contribute to the progression of tumor malignancy, and the expression levels of platelet aggregation‐inducing factors positively correlate with the metastatic potential of osteosarcoma cells. However, it is unclear how tumor‐platelet interaction contributes to the proliferation of osteosarcomas. We report here that osteosarcoma‐platelet interactions induce the release of platelet‐derived growth factor (PDGF) from platelets, which promotes the proliferation of osteosarcomas. Co‐culture of platelets with MG63 or HOS osteosarcoma cells, which could induce platelet aggregation, enhanced the proliferation of each cell line in vitro. Analysis of phospho‐antibody arrays revealed that co‐culture of MG63 cells with platelets induced the phosphorylation of platelet derived growth factor receptor (PDGFR) and Akt. The addition of supernatants of osteosarcoma‐platelet reactants also increased the growth of MG63 and HOS cells as well as the level of phosphorylated‐PDGFR and ‐Akt. Sunitinib or LY294002, but not erlotinib, significantly inhibited the platelet‐induced proliferation of osteosarcoma cells, indicating that PDGF released from platelets plays an important role in the proliferation of osteosarcomas by activating the PDGFR and then Akt. Our results suggest that inhibitors that specifically target osteosarcoma‐platelet interactions may eradicate osteosarcomas.     

Elevated Mean Platelet Volume is Associated with Presence of Colon Cancer

Background: Colon cancer is the second most common cancer in developed countries. Activated plateletsplay a key role in inflammation and atherothrombosis, with mean platelet volume (MPV) is an early markerof platelet activation. The aim of the study was to clarify the relevance of MPV in patients with colon cancer.Materials and Methods: We measured MPV levels in 128 patients with colon cancer before and after surgery,and 128 controls matched for age, gender, body mass index (BMI) and smoking status. The odds ratios (ORs) and95% confidence intervals (CIs) for colon cancer were calculated using multivariate logistic regression analysesacross MPV quartiles. Results: Patients with colon cancer had higher MPV compared with controls. Surgicaltumor resection resulted in a significant decrease in MPV levels (11.4 fL vs 10.7 fL; p<0.001). A positive correlationbetween MPV and tumor-nodule-metastases (TNM) stage was found. Furthermore, after adjusting for other riskfactors, the ORs (95%CIs) for colon cancer according to MPV quartiles were 1.000, 2.238 (1.014-4.943), 3.410(1.528-7.613), and 5.379 (2.372-12.198), respectively. Conclusions: The findings show that patients with coloncancer have higher MPV levels compared with controls, and these are reduced after surgery. In addition, MPVwas found to be independently associated with the presence of colon cancer. Further studies are warranted toassess the utility of MPV as a novel diagnostic screening tool for colon cancer.     

家族性脑肿瘤多学科诊疗进展

中枢神经系统肿瘤指起源于中枢神经系统内的组织或结构的一组良恶性疾病。常见的中枢神经系统肿瘤为散发性的，但也有少数出现家族性发病。相比散发性脑肿瘤，家族性脑肿瘤的临床症状、诊断思路和随诊复查计划更复杂。多学科诊疗（MDT）模式，通常指针对某种涉及多器官、多系统的病例进行讨论，在综合各学科意见的基础上为患者制定出最佳的治疗方案的治疗模式。由于家族性脑肿瘤常涉及多器官、多学科、多系统，并且发病率较低，神经外科医生对其临床经验较少，所以MDT模式更有利于高效率诊治、管理家族性脑肿瘤。本文将详细阐述以神经外科医生为主导的MDT模式，以常见的家族性脑肿瘤为引导，针对关于家族性脑肿瘤的流行病学、遗传特点、临床表现、诊断思路和多学科管理办法方面进行综述并对最新研究加以介绍。     

Evaluation of Platelet Indices in Lung Cancer Patients

Background: In this study, we aimed to determine platelet indices such as platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), Plateletcrit (PCT) platelet count (PLT) in lung cancer cases, and evaluate any relationships between these parameters and stage or histologic types. Materials and Methods: This retrospective study covered 44 lung cancer patients and 47 healthy subjects. Platelet indices including PLT, PCT, MPV, PDW were estimated and compared with normal subjects. The results were evaluated statistically. Results: The PDW value was significantly higher in the cancer group compared to the control group; however, the values for PCT and MPV were lower. Conclusions: We suggest potential use of platelet indices in diagnosis of lung cancer.     

血小板相关参数对恶性肿瘤合并静脉血栓栓塞的诊断价值

目的：探讨血小板相关参数对恶性肿瘤合并静脉血栓栓塞的诊断价值。方法：恶性肿瘤118例,其中血栓组58例,非血栓组60例,60例门诊健康体检者作为正常对照组,比较各组外周血血小板参数特点。结果：入院时检测血栓组血小板平均体积（MPV）及血小板分布宽度（PDW）分别为（8．7±1．0）fl、（12．6±1．4）％,非血栓组MPV及PDW分别为（8．8±1．3）fl、（12．8±1．4）％,正常对照组MPV及PDW分别为（8．0±1．1）fl、（11．5±1．9）％,血栓组及非血栓组外周血MPV及PDW水平要显著高于正常对照组（P＜0．05）。血栓组于血栓检出时检测MPV及PDW分别为（10±1．6）fl、（14．1±1．8）％,同期检测非血栓组MPV及PDW分别为（9．28±1．6）fl、（13．3±1．6）％,血栓组MPV及PDW要显著高于非血栓组（P＜0．05）,两次检测血栓组外周血MPV及PDW变化的百分比要显著高于非血栓组（P＜0．05）。结论：血栓组患者外周血MPV、PDW及其变化百分比明显增高,提示这些指标对早期预测恶性肿瘤并发血栓形成有重要作用。     

上皮性卵巢癌中血小板计数与聚集功能的变化及临床意义

  目的  探讨上皮性卵巢癌（epithelial ovarian cancer, EOC）中血小板聚集功能与计数的变化及其对卵巢癌早期诊断、病情监测和预后评估的临床意义。  方法  选取天津医科大学总医院妇科2010年1月至2012年6月收治的61例上皮性卵巢癌患者（EOC组）, 57例卵巢良性肿瘤患者（良性肿瘤组）和80例健康查体患者（健康对照组）, 应用血小板聚集测量仪以二磷酸腺苷（ADP）为诱导剂, 比浊法检测血小板最大聚集率（maximum aggregation rate, MAR）及聚集曲线坡度（Platelet Aggregation Slope, PtS）, 全血细胞自动检测分析仪检测血小板计数及血红蛋白浓度, 并与卵巢癌临床病理因素进行相关性分析。  结果  24.59% EOC患者伴有血小板增多症, EOC组平均血小板计数及MAR显著高于良性肿瘤组和健康对照组（P < 0.05）; EOC组PtS显著高于健康对照组（P < 0.05）。EOC患者血小板增多及MAR水平升高与组织学高分级、FIGO分期晚期、术后残余灶≥1 cm及术前CA125升高显著相关（P < 0.05）, 与病理类型无关（P>0.05）。PtS与EOC患者临床病理特征无明显相关性（P>0.05）。  结论  卵巢癌患者外周血血小板数量与聚集功能均明显增强, 并且血小板计数增多及MAR水平升高与组织学分级、FIGO分期、术后残余灶以及CA125水平等卵巢癌不良预后因素密切相关。      

Platelet response during the second cycle of decitabine treatment predicts response and survival for myelodysplastic syndrome patients

Despite the efficacy of decitabine to myelodysplastic syndrome (MDS), there is a wide range of responses, and no definite predictive marker has been identified. This study aimed to describe the efficacy of decitabine and to identify potential predictors of response and survival in patients with MDS. We retrospectively analyzed clinical data of MDS patients at Samsung Medical Center between August 2008 and August 2011. The response assessment was conducted using the International Working Group (IWG) response criteria for MDS. We analyzed 101 MDS patients (total 613 cycles) who received decitabine for a median of four cycles. The overall response was 52.5% (n = 53/101). The median time to any response was two cycles with the median overall survival of 16.7 months. Patients who showed hematologic improvement had significantly longer survival than those who did not (9.8 vs. 22.9 months, p = 0.004). The difference in OS was evident in the Intermediate-2/High risk group (p = 0.002) but not in the Intermediate-1 risk group (p = 0.145). Multivariate analysis confirmed that platelet response (no platelet transfusions for at least 3 days) during the second cycle of treatment was an independent predictor for response, OS and Leukemia free survival. Based on the results of this study, for patients with hematological improvement, recovery of platelet count by the second cycle of therapy can be used as an early predictive marker of improved survival and an increased response rate.     

血小板：肿瘤诊断与治疗的新兴靶点

血小板是肿瘤发生发展过程中的重要参与者，能够通过构建炎性微环境、促进血管生成和介导肿瘤免疫逃逸，直接或间接地影响肿瘤生长和转移进程。随着肿瘤微环境的动态变化，血小板的数量、体积和分子组学也发生相应改变，提示血小板相关的生物标志物具有反映肿瘤负荷演变的巨大潜力。基于血小板对肿瘤发生发展的促进效应，血小板被视为肿瘤生物治疗的重要靶点。靶向抑制血小板功能可以显著控制肿瘤的发生发展并改善患者的预后。此外，血小板对肿瘤组织具有较强的亲和能力。应用靶向血小板或血小板功能模拟的思路研发抗肿瘤靶向制剂以有效地增加纳米药物的肿瘤靶向性和生物相容性，是提高肿瘤靶向治疗效率的新兴策略。本文聚焦于血小板与肿瘤之间的复杂相互作用，在总结作用机制的基础上，对血小板相关的肿瘤标志物和抗肿瘤靶向治疗进行了重点阐述。     

血小板计数与非小细胞肺癌分期及预后的关系

目的探讨血小板计数与非小细胞肺癌分期及预后之间的关系。方法对102例病理确诊肺癌病例首治前进行周围血小板计数检查。结果血小板减低占3.9%,正常占60.8%,增高占35.3%,肺癌II、III、IV期患者血小板计数平均值统计学上有显著性差异(P<0.01),血小板升高患者经治疗其值明显下降(P<0.05)。结论晚期肺癌常继发血小板增多,血小板计数可作为肺癌辅助诊断指标。     

老年癌症患者手术前后血小板活化状态检测的临床意义

应用流式细胞免疫学技术对58例肿瘤患者手术前后外周血小板活化分子P-选择素和凝血酶敏感蛋白进行了对比研究。结果术后外周血P-选择素及凝血酶敏感蛋白较术均明显增加，有统计学意义。其中P-选择素增加更为显著（P<0．01）。男性患者术前后血小板活化状态较女性患者更为明显。本研究提示手术对癌症患者血小板有明显的活化作用，在男性更为显著，应重视手术后的防凝措施，防止血栓病的发生。     

The inhibition of platelet aggregation of metastatic H-ras-transformed fibroblasts with castanospermine, an N-linked glycoprotein processing inhibitor

A series of T24-H-ras-transformed fibroblasts with varying metastatic potential was tested for the ability to aggregate platelets. Results indicate that although platelet activation was always detected in the highly metastatic cells, some non-metastatic cells also have the ability to cause platelet aggregation, suggesting that this is a necessary but not sufficient characteristic of the metastatic phenotype. Apyrase, an ADP scavenger, effectively inhibited platelet aggregation by metastatic cells, however, there was no significant increase in ADP secretion or relation to the ability of the tumor cells to activate platelets. Hirudin, a thrombin inhibitor, did not affect aggregation, suggesting that the pathway of activation is thrombin-independent. The glycoprotein processing inhibitor, castanospermine, which reduces glycosidase I activity and metastatic capability, inhibited the ability of metastatic cells to cause platelet aggregation. However, another inhibitor of oligosaccharide processing, swainsonine, which inhibits mannosidase II activity and does not reduce metastasis, had no effect on platelet aggregation. These results show that the integrity of N-linked oligosaccharide structure of glycoproteins is an important feature of the ability of ras-transformed fibroblasts to activate platelets.     

外周血血小板计数及纤维蛋白原含量在上皮性卵巢癌诊治中的意义

[目的]探讨外周血血小板（PLT）计数及血浆纤维蛋白原（FIB）与上皮性卵巢癌生物学行为的关系。[方法]回顾性分析上皮性卵巢癌初次手术病例82例,并与同期收治的52例卵巢良性肿瘤作对照,比较两组术前血小板计数和纤维蛋白原含量。同时分析血小板计数和纤维蛋白原含量与上皮性卵巢癌生物学行为的关系。[结果]术前上皮性卵巢癌患者血小板计数增高者占52.44%,良性肿瘤中占11.54%;在上皮性卵巢癌中血浆纤维蛋白原增高者占53.66%,而良性肿瘤中占7.69%,差异均有统计学意义（P=0.000）。血小板计数与上皮性卵巢癌的FIGO分期、腹水、分化程度、是否行理想的肿瘤细胞减灭术有关（P〈0.05）,与CA125及病理类型无关。血浆纤维蛋白原与上皮性卵巢癌的各项临床病理因素均无关（P〉0.05）。单因素及多因素分析结果显示血小板计数及纤维蛋白原均与卵巢癌复发无关。[结论]血小板计数增高可能是反映上皮性卵巢癌浸润程度的指标。纤维蛋白原增高可能是卵巢癌的结果,其与血小板的关系有待于进一步研究。