多肿瘤标志物蛋白芯片对泌尿系肿瘤和男性生殖系肿瘤诊断的临床价值

目的：探讨多肿瘤标志物蛋白质芯片在泌尿系肿瘤和男性生殖系肿瘤诊断中的临床应用价值,并建立12项肿瘤标志物联合诊断泌尿系和男性生殖系肿瘤的函数。方法：采用C-12多肿瘤标志物蛋白质芯片检测57例泌尿系肿瘤患者、38例男性生殖系肿瘤患者、11例泌尿系良性病变患者、25例男性生殖系良性病变患者,以及1203例正常体检者。所有患者均经病理学、影像学或临床确诊。结果：用C-12芯片检测泌尿系肿瘤的灵敏度是49.12%,特异度是81.81%,阳性预测值是93.33%,阴性预测值是23.68%;男性生殖系肿瘤的灵敏度是62.16%,特异度是48.00%,阳性预测值是64.86%,阴性预测值是46.15%。除前列腺癌外,C-12芯片联合检测的阳性率在泌尿系肿瘤和其他男性生殖系肿瘤中显著高于单项肿瘤标志物的检测（P〈0.05）。建立的诊断判别函数对肾癌、膀胱输尿管肿瘤、前列腺癌、睾丸癌的诊断准确率分别为81.3%、94.5%、94.0%、91.0%,显著高于单项标志物检测（P〈0.01）。结论：除前列腺癌外,用多肿瘤标志物蛋白质芯片检测泌尿系和男性生殖系肿瘤可提高诊断的灵敏度,优于单项肿瘤标志物;诊断判别函数可明显提高泌尿系及男性生殖系肿瘤诊断的准确率,具有一定的临床参考价值。     

平顶山市老年恶性肿瘤发病现状分析

目的:初步了解平顶山市老年恶性肿瘤发病现状及特点。方法:收集平顶山市4家三级医院和2家市级专科医院2012年-2013年恶性肿瘤住院病例资料,应用ICD－10规则统一编码、归类,3位数类目统计恶性肿瘤分类构成并排序,统计发病例数、病种分布情况。结果:平顶山市老年恶性肿瘤患病率高,约占平顶山市全部恶性肿瘤病人的三分之二,男性多于女性,占据前五位是肺恶性肿瘤、食管恶性肿瘤、结直肠恶性肿瘤、胃恶性肿瘤、肝原发恶性肿瘤,占老年恶性肿瘤病人三分之二以上。高龄老年恶性肿瘤农村与市区患病趋势与老年组整体一致,肺恶性肿瘤、食管恶性肿瘤依然位居农村与市区的患病前两位。结论:肺恶性肿瘤、食管恶性肿瘤等是威胁平顶山市老年人的主要肿瘤,普及健康教育的同时,还应加大肿瘤筛查工作力度,力争早发现早诊断早治疗。     

Neuropilin-1在消化道恶性肿瘤发生发展中的生物学作用

消化道肿瘤是最常见的恶性肿瘤,发病率高,死亡率亦高。神经纤毛蛋白-1（Neuropilin-1）在消化道恶性肿瘤发生发展中的作用成为近年来研究的热点,其调控恶性肿瘤血管生成过程,介导肿瘤细胞的增殖与侵袭,从而促进肿瘤进展与转移。本文就Neuropilin-1在肿瘤血管生成、肿瘤增殖与侵袭、转移及肿瘤治疗靶标中的作用作一综述。     

Characterization of growth properties and demonstration of the tumor-specific transplantation antigens of Morris hepatomas.

The growth properties of single-tumor-cell suspensions prepared by enzymatic digestion of solid tumors from Morris hepatomas 7777, 5123tc, and 3924a and the presence of tumor-specific transplantation antigen for tumor lines 7777 and 3924a were described. Two of the tumor cell lines (7777 and 3924a) showed consistent i.m. tumor growth following the inoculation of 1 x 10(5) tumor cells, and a similar dose of 5123tc tumor cells resulted in inconsistent tumor growth. Two of the tumor lines (5123tc and 7777) were associated with rapid appearance of lung metastases, whereas with line 3924a metastatic lung lesions rarely developed despite its rapid i.m. tumor growth rate. Tumor resistance to rechallenge with a threshold inoculum of tumor cells was present in approximately 15 to 50% of the animals following amputation of an existing tumor mass. Resistance to a challenge tumor cell inoculum could also be accomplished by immunization with irradiated tumor cells. Tumor-specific resistance was demonstrated to tumor line 3924a in that "immune" animals were able to resist a challenge with 3924a tumor cells but did not resist a challenge with tumor line 9098.     

Induction of pulmonary metastases in both immune and nonimmune mice. Effect of the removal of a transplanted primary tumor.

In mice bearing a benzypyrene-induced fibrosarcoma tumor, the survival was determined of intravenously injected tumor cells at various intervals after previous immunization of experimental animals by induction and subsequent excision of a transplanted primary tumor in the soft tissues of the leg. Seven days after induction of a transplanted primary tumor, I.V. tumor cells produced fewer pulmonary metastases in immunized mice than in nonimmunized mice. When tumor cells were inoculated I.V. immediately following amputation of the transplanted primary tumor, the number of pulmonary metastases in the immunized and nonimmunized animals were similar; however, 6 hours, 7 days and 14 days after primary tumor excision, I.V. inoculated tumor cells produced a higher incidence of lung metastases in the immunized than in the nonimmunized mice. This increased survival of I.V. tumor cells following excision of the transplanted primary tumor may have relevance to the development of metastases after eradication of certain primary tumors in humans.     

膝部肿瘤切除后关节功能重建的方法分析

目的 探讨膝部肿瘤切除后关节功能重建的方法选择和疗效。方法 54例膝关节周围肿瘤中，骨巨细胞瘤25例，非骨化性纤维瘤2例，成纤维性纤维瘤2例，动脉瘤样骨囊肿1例，软骨黏液性纤维瘤2例，骨肉瘤15例，软骨肉瘤2例，恶性纤维组织细胞瘤5例。23例采用瘤体切除，吻合血管的自体髂骨、腓骨联合移植术，12例瘤段切除灭活再植术，19例瘤段切除人工假体置换术。结果 54例平均随访5年6个月，成活病例术后功能评价优良率为76％。结论 膝部肿瘤切除后关节功能的重建，应根据肿瘤的大小、包壳的完整性、软组织的侵及情况，以及肿瘤的病理组织学性质，选择适当的手术方法。瘤体切除，吻合血管的自体髂骨、腓骨联合移植术，是治疗膝关节周围良性侵袭性肿瘤或低度恶性肿瘤较为理想的方法。     

肿瘤标记物蛋白芯片诊断系统在肠道肿瘤检测中的应用

目的研究多种肿瘤标记物蛋白芯片诊断系统用于肠道肿瘤的诊断价值。方法采用多种肿瘤标记物蛋白芯片诊断系统测定分析30例肠道恶性肿瘤患者,20例良性肠道肿瘤患者,30例对照人群和30例肠道肿瘤术后复发患者血清中的组织特异性抗原(TPS)、癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、糖原125(CA125)、糖原153(CA153)、糖原242(CA242)、糖原199(CA199)、前列腺特异性抗原(PSA)、铁蛋白(FER)。结果30例肠道肿瘤患者血清有27例肿瘤标记物为阳性(阳性率为90.0%);20例良性肠道肿瘤患者血清有3例肿瘤标记物为阳性(阳性率为15.0%);30例对照人群血清3例肿瘤标记物为阳性(阳性率为10.0%);30例肠道肿瘤术后复发患者血清30例肿瘤标记物为阳性(阳性率为100.0%)。在肿瘤组和复发组中以TPS的阳性率最高(分别为83.3%、90.0%),其次为CEA、CA199和CA242。结论TPS在肿瘤的诊断中是1种敏感性较高的肿瘤标记物。多种肿瘤标记物蛋白芯片诊断系统的应用对肠道肿瘤患者的良恶性判断有一定的临床应用价值,对术后复发转移的判断也有一定的应用价值。     

乳腺癌患者外周血清中APC基因启动子甲基化异常的检测及其意义

背景与目的:检测肿瘤患者外周血中肿瘤相关标志物是当前肿瘤研究的热点之一,恶性肿瘤患者外周血中存在游离的肿瘤相关DNA已引起肿瘤学界的极大关注,人们曾在多种肿瘤患者血清中发现与原发肿瘤相同的DNA变异.本研究以APC(adenomatous polyposis coli)基因启动子甲基化作为肿瘤标志物,探讨乳腺癌患者外周血清中游离的肿瘤相关DNA与肿瘤组织及临床病理参数的相关性.方法:采用甲基化特异性PCR(methylation specific-PCR,MSP)方法,分别检测84例乳腺癌组织、癌旁正常腺体组织及外周血清中游离DNA APC基因启动子甲基化状况.结果:84例乳腺癌组织APC基因启动子甲基化频率为45.2%(38/84),相应外周血清中同样DNA变异阳性检出率为31.0%(26/84).外周血清中DNA甲基化变异与肿瘤组织的甲基化状况显著相关(r=0.977,P=0.002).检测外周血清中APC基因甲基化的敏感性为68.4%,特异性为97.8%.肿瘤组织及外周血清中游离DNA甲基化异常与临床分期、病理类型、肿块大小及受体状况无相关性(P＞0.05).肿瘤组织未检测到甲基化患者的血清中及健康人血清中均未检测到该基因甲基化变异.结论:乳腺癌患者外周血清中肿瘤相关DNA甲基化与肿瘤组织中相同基因的变异显著相关.     

肿瘤血管异质性的研究进展

肿瘤的生长和转移离不开血管生成。受肿瘤微环境的影响,肿瘤血管在形态、功能、蛋白表达、对细胞因子的反应性,以及在遗传学水平上与正常血管存在差异。肿瘤血管内皮细胞能动态的适应肿瘤微环境的变化,因此,在不同肿瘤,不同发展阶段,不同生长部位,同一条脉管不同区域,肿瘤血管内皮细胞均表现出异质性。了解肿瘤血管的异质性,不仅可以提高抗肿瘤血管生成药物的疗效,防止耐药性的产生,减少药物副反应,也为了解肿瘤组织中不同细胞间的相互作用打下基础。     

Enhancement or inhibition of tumor growth by interferon: dependence on treatment protocol

MSC cells are tumor cells originally induced in BALB/c mice by Moloney sarcoma virus. In these studies we demonstrated that, although these tumor cells are sensitive in vitro both to lysis by NK or NK-like cells and to the growth-inhibitory effect of murine L-cell interferon (IFN), the growth of the tumor in vivo could be either inhibited or enhanced by IFN. The outcome of in vivo IFN treatment was dependent on the timing and route of IFN administration relative to tumor challenge. IFN given systematically at the same time as tumor challenge resulted in enhancement of primary tumor formation, rate of tumor growth and subsequent progressive tumor growth. In contrast, IFN administered at the site of tumor inoculation on days 1-3 after tumor challenge inhibited tumor formation and growth. Histopathology of tissue sections obtained from the site of tumor challenge confirmed these results. Similar studies performed in mice given 450 rads of X-irradiation showed that IFN could still inhibit tumor growth when administered at the site of tumor inoculation on days 1-3 after tumor challenge. IFN administered simultaneously with tumor challenge, however, did not enhance tumor growth in irradiated mice. These results are consistent with the interpretation that 1) inhibition of MSC-induced tumor growth by IFN has a radioresistant component and 2) the enhancement of MSC-induced tumor formation by IFN is dependent on interaction with a radiosensitive population of cells, possibly lymphoid cells.     

Clonality and heterogeneity of pulmonary blastoma from the viewpoint of genetic alterations: a case report

Biphasic pulmonary blastoma is a rare lung tumor with epithelial and mesenchymal components. Genetic alterations in this tumor are largely unknown, except for the presence of beta-catenin and p53 mutations and the absence of KRAS mutation. To understand the molecular process of histogenesis of this tumor, a whole genome allelic imbalance (AI) scanning using a high-resolution single nucleotide polymorphism array as well as mutational analysis of the p53, EGFR, KRAS and beta-catenin genes were performed against the epithelial and mesenchymal components in the primary tumor and a metastatic tumor in a case of pulmonary blastoma. AI at chromosome regions 14q24-q32 and 17p11-p13 and beta-catenin mutation were commonly detected in all tumors. On the other hand, AI at chromosome regions 3p11-p14 and 9p21-p24 and p53 mutation were detected only in the mesenchymal component in the primary tumor but not in the epithelial component in the primary tumor and the brain metastasis. Likewise, AI at chromosome regions 6p24-p25 and 6q14-q27 was detected in the epithelial component in the primary tumor and the brain metastasis but not in the mesenchymal component in the primary tumor. Furthermore, the genetic alterations detected in the metastatic tumor were completely the same as those in the epithelial component in the primary tumor, indicating that a tumor cell(s) in the epithelial component in the primary tumor selectively metastasized to the brain. These results indicate that this biphasic tumor is of monoclonal origin and the phenotypic heterogeneity of the tumor is due to the differences in the accumulated genetic alterations in each component of the tumor.     

术前血清肿瘤标志物水平在直肠癌术前分期中的应用评价

[目的]探讨直肠癌术前血清肿瘤标志物水平与肿瘤浸润深度及淋巴结转移之间的关系,评价其在直肠癌术前分期中的应用价值。[方法]回顾性分析北京大学肿瘤医院178例行手术治疗直肠癌患者的术前血清肿瘤标志物（CEA、CA199、CA724、CA242）水平和临床病理资料。[结果]单因素分析结果表明直肠癌肿瘤浸润深度与术前CEA、CA242水平、肿瘤部位、最大径、大体类型、分化程度、淋巴结转移相关（P〈0.05）。淋巴结转移与肿瘤大体类型、分化程度、最大径、脉管癌栓、浸润深度相关（P〈0.05）。多因素分析表明直肠癌患者术前的CEA水平和肿瘤最大径是肿瘤浸润深度的独立危险因素;肿瘤浸润深度和脉管癌栓是淋巴结转移的独立危险因素。[结论]术前血清CEA水平是影响直肠癌术前T分期的重要因素,术前血清肿瘤标志物水平对直肠癌术前分期的应用价值有限。     

钙网蛋白的抗肿瘤作用

钙网蛋白（CRT）与多种肿瘤的进展及肿瘤细胞的凋亡有着密切的关系。最新研究表明,肿瘤细胞表面CRT的表达,能引起吞噬细胞对肿瘤细胞的吞噬作用,从而介导肿瘤细胞的免疫原性死亡。外源性重组CRT的注入或内源性CRT向细胞表面的转移可以加强吞噬细胞对肿瘤细胞的吞噬作用。在动物模型中,CRT相关的抗肿瘤疫苗能起到治疗肿瘤的作用,为肿瘤的免疫原性治疗及肿瘤的分子靶向治疗提供了广阔的前景。     

Carcinosarcoma of the Ureter with Unusual Histologic Features

We report a rare case of carcinosarcoma of the ureter presentedas a retroperitoneal tumor. The tumor originated in the ureteras a polypoid protrusion and spread around peri-ureteral, retroperitonealtissues. The polypoid ureteral tumor was composed of an intra-epithelialcarcinoma and a submucosal mesenchymal tumor; the histologyof the retroperitoneal tumor in the original site was that ofa carcinosarcoma. The bulk of the tumor in the retroperitoneumwas composed of blastematous, epithelial and sarcomatous neoplasticcells with foci resembling an incomplete glomeruloid formation,thus mimicking a Wilms' tumor. The lesion appeared to originatefrom multipotential cells in the mucosal layer of the ureter.Whether or not this tumor has a true nephrogenic property iscurrently unknown. When a retroperitoneal tumor of the adultresembling a Wilms' tumor is found, one should suspect a possiblecarcinosarcomatous origin in the ureter.     

Reduction of metastatic rate by immunotherapy: a comparison of the immunogenic properties of metastasizing tumor cells versus tumor cells in the primary mass.

The vasculature of a poorly immunogenic, highly metastatic transplantable fibrosarcoma (T-241) maintained in the femoral muscle of C57BL/6J mice was perfused. This permitted collection of tumor cells which had invaded into the tumor vascular channels (ie, metastasizing tumor cells). Also collected as a separate population were tumor cells from the primary tumor mass. Immunization was carried out with these cell populations in conjunction with BCG and the effect on the growth of primary tumor and metastatic rate was evaluated following rechallenge with unfractionated tumor cells. The rate of tumor growth at the primary site was not affected by any of the immunization schedules. However, immunization with venous effluent cells (metastasizing tumor cells) and BCG was two times more effective in reducing the number of pulmonary metastases than immunization using tumor cells isolated from the primary tumor mass. Passively transferred spleen cells from donors immunized with the cell populations listed above had exactly the same effect, that is, no effect on the growth of the primary tumor, but a dramatic reduction in the metastatic rate when effluent tumor cells were used to immunize cell donors. The data point to an antigenic heterogeneity with this particular transplantable tumor.     

Recent data on the immunology of tumors. Mechanisms of escape of immunological control. Role of suppressor cells]

Cells in spleens from tumor bearing animals were found to inhibit in vitro reactivity of lymphocytes to a variety of stimulants. These suppressor cells inhibited the stimulation of normal lymphocytes by mitogens : P.H.A.-Con A-L.P.S. They were adherent cells, bore immunoglobulins at their surface and did not bear the 0 marker. They were also demonstrated in T deprived tumor bearing animals. They might be B cells, or, more probably, macrophages. Other activities that are inhibited by the suppressor cells are: -reactivity to allogenic cells in the mixed lymphocyte culture, -in vitro generation of secondary anti tumor cytotoxic effector cells, -macrophage migration inhibition in the presence of immune lymphocytes and tumor extracts, -reactivity against syngeneic tumor cells or tumor extracts. Suppressor cells may play a role in the general immunodepression of tumor bearing hosts, and in the inability of tumor bearing hosts to reject the tumor. However, the biological role of these non T suppressor cells is not clear, as they also inhibit tumor cell growth, and in vivo experiments favour suppressor cells of thymic origin.     

Role of immunologic activity of host in radiotherapy

The results of our studies on immunologic activity of host following irradiation to tumor in mice were summarized in this paper. The spleen cells from tumor irradiated mice inhibited growth of tumor in mice inoculated tumor cells with these spleen cells. These spleen cells also inhibited the colony formation and tumor growth in vitro system. The cytostatic activity of these spleen cells were enhanced after tumor irradiation. These results suggest that the specific anti-tumor cell-mediated immunity in host is enhanced by local irradiation to tumor, and that these immunologic effects depend on the presence of both T cells and macrophages.     

钙网蛋白的抗肿瘤作用

钙网蛋白(CRT)与多种肿瘤的进展及肿瘤细胞的凋亡有着密切的关系.最新研究表明,肿瘤细胞表面CRT的表达,能引起吞噬细胞对肿瘤细胞的吞噬作用,从而介导肿瘤细胞的免疫原性死亡.外源性重组CRT的注入或内源性CRT向细胞表面的转移可以加强吞噬细胞对肿瘤细胞的吞噬作用.在动物模型中,CRT相关的抗肿瘤疫苗能起到治疗肿瘤的作用,为肿瘤的免疫原性治疗及肿瘤的分子靶向治疗提供了广阔的前景.     

磁场抗肿瘤生物效应机制

磁场抑制肿瘤机制较为复杂,并且有众多的影响因素制约着磁场作用效果。磁场可以抑制肿瘤细胞分裂,并可作用于肿瘤细胞的细胞器、细胞膜,以及非肿瘤组织,从而间接起到抑制肿瘤的作用。其可能机制为磁场能选择性破坏肿瘤细胞的DNA,抑制肿瘤细胞的恶性增殖;激活自由基间接损伤DNA;调控肿瘤细胞的增殖分裂周期;作用于肿瘤细胞质内线粒体、蛋白酶等生命物质以及肿瘤细胞的细胞膜,从而破坏肿瘤细胞功能,减少肿瘤细胞的养分而抑制或杀死肿瘤细胞等。