M2型丙酮酸激酶在肿瘤代谢中的作用

M2型丙酮酸激酶（PKM2）是糖酵解途径的一个关键限速酶,在多种恶性肿瘤细胞中高表达.在肿瘤糖代谢通路中,PKM2可以通过在高活性的四聚体和低活性的二聚体之间相互转化,促进肿瘤的糖酵解和细胞增殖.肿瘤细胞通过多种方式调节PKM2的表达和酶活性如转录调节、变构调节和翻译后修饰调节.PKM2在肿瘤发生和肿瘤代谢中的重要作用使它有望成为肿瘤治疗的新靶点.     

M2型丙酮酸激酶的抗肿瘤作用研究进展

摘 要：糖酵解（Warburg效应）是肿瘤细胞的重要特征，其相比于线粒体氧化磷酸化来说更高效地产生能量及大量的中间产物用于生物合成，还可抑制活性氧的生成。M2型丙酮酸激酶（pyruvate kinase M2，PKM2）多以低活性的二聚体形式存在于肿瘤细胞等快速增殖细胞中，作为催化糖酵解最后一个步骤的限速酶，是肿瘤细胞Warburg效应的一个关键调节因子。PKM2在肿瘤细胞中也发挥着重要的非代谢作用。PKM2被诱导转移入细胞核后，通过磷酸化特定的核蛋白后激活诸多基因的转录，促进肿瘤的生长。基于这些研究成果，该文综述了PKM2在肿瘤生长中的作用，并对PKM2的抑制剂和激活剂的抗肿瘤疗效分别进行讨论，并预测PKM2可能成为癌症治疗的潜在靶点。     

M2型丙酮酸激酶及其在肿瘤生长中的作用

肿瘤细胞的快速增殖导致它和正常细胞比较需要更多的代谢原料。为维持其自身的高度增殖,肿瘤细胞往往过表达M2型丙酮酸激酶（pyruvate kinase subtypeM2,PKM2）。在肿瘤的糖代谢通路中,二聚体形式的PKM2（抑制型）促进葡萄糖中间产物进行生物大分子合成代谢,而四聚体结构的PKM2（激活型）则促进葡萄糖的氧化磷酸化为细胞提供能量,二聚体PKM2在肿瘤细胞中占主要地位。PKM2的过表达以及PKM2二聚体、四聚体之间的转化使肿瘤细胞能在各种氧含量和营养环境下生存并增殖,与肿瘤的发生和扩散有密切的关系。     

恶性肿瘤患者血清中PKM2水平的诊断和预后预测价值

PKM2作为有氧糖酵解关键酶,与肿瘤发生发展密切相关,在其诊断、预后及治疗方面均有很好的临床应用价值。恶性肿瘤患者血清中PKM2的浓度显著高于非恶性肿瘤患者及正常人,但在不同亚型的泌尿系统肿瘤中PKM2的诊断价值不同;PKM2与传统肿瘤标志物联合时,能显著提高诊断的灵敏度和特异性;PKM2浓度的上升与OS和PFS降低相关;治疗有效时PKM2浓度随之下降。另外,基础研究提示PKM2是重要的治疗靶点。     

肿瘤标志物GW112在胃癌及结直肠癌等消化道肿瘤中的研究进展

GW112是近年来发现的嗅觉介导素相关蛋白家族的新成员,在神经发育、细胞间黏附、细胞周期调控及肿瘤发生等多种细胞功能中起重要作用。GW112调节肿瘤细胞增殖、凋亡、黏附,并对关键信号转导通路起调控作用。GW112在消化道肿瘤中异常表达,且在早期胃癌及结直肠癌中呈高度特异性表达,提示其可能成为新的早期诊断胃癌及结直肠癌的靶点基因。     

α-烯醇酶与消化系统肿瘤的研究进展

α-烯醇酶(α-enolase,ENO1)是糖酵解过程中的关键酶之一,在能量代谢过程中发挥重要作用,可催化磷酸甘油向磷酸烯醇式丙酮酸的转化.最近研究发现,ENO1作为潜在的肿瘤分子标志物,可参与肿瘤细胞的增殖、凋亡、侵袭和迁移等过程,有望成为肿瘤早期诊断、治疗及预后评估的重要分子靶标.本文对ENO1与消化系统肿瘤的研究进展做一综述.     

PKM2蛋白在胃癌组织中的表达及其预后价值

目的 探讨M2型丙酮酸激酶（PKM2）在人胃癌组织中的表达,并分析其与胃癌临床病理特征的关系及预后价值。方法 构建含202例胃癌组织及其对应癌旁组织的组织芯片,采用免疫组化法检测胃癌组织中PKM2蛋白的表达,分析其阳性表达与临床病理参数和预后间的关系。结果PKM2在胃癌组织中的阳性表达率为62.4％（126／202）,高于癌旁组织的14.4％（29／202）,差异有统计学意义（P＜0.05）;胃癌组织中PKM2的阳性表达率与年龄、性别、肿瘤最大直径及分化程度均无关（P＞0.05）,与T分期、N分期及TNM分期有关,差异有统计学意义（P＜0.05）。PKM2表达阳性者的中位总生存期为42.9个月,短于阴性表达者的78.4个月（χ2=23.119, P＜0.001）,且PKM2阳性表达情况是影响胃癌预后的独立因素之一。结论PKM2蛋白在胃癌的发生和发展过程中起了重要作用,是评估胃癌患者预后的重要因素。     

Survivin基因在胃癌中的研究进展

Survivin是细胞凋亡抑制蛋白（IAP）家族的一个新成员，是分子量最小的IAP，具有抑制细胞凋亡的作用。研究表明，Survivin在胃癌以及许多恶性肿瘤中广泛特异表达，与肿瘤的早期发生、淋巴结转移及预后有很高的相关性，并可能参与肿瘤细胞耐药性的产生。同时，Survivin基因也为胃癌的早期诊断、靶向基因治疗应用提供了新的前景。     

M2型丙酮酸激酶与Warburg效应在肺癌中的研究进展

靶向肿瘤代谢途径是肺癌治疗的新兴策略之一。Warburg效应是肿瘤代谢的主要特征,表现为肿瘤细胞在有氧条件下通过糖酵解获得能量。最近研究表明,M2型丙酮酸激酶作为糖酵解途径关键酶的异常表达与肺癌的增殖、转移、诊断、治疗及预后密切相关,是肺癌治疗的潜在靶点。     

胃癌分子病理学及其相关标志物的研究进展

 胃癌是发病率及死亡率较高的常见肿瘤,胃癌的进展过程涉及多种癌基因及抑癌基因参与,是多阶段、多途径协同作用的产物,因此早期发现这些基因及标志物与胃癌发生、发展及预后的关系,对胃癌的早期诊断、治疗及判断预后起着极其重要的作用。     

Ringworm in animals in a farm in Assiut

Bericht über das Auftreten von Hautmykosen bei Tieren auf der Farm der Landwirtschaftlichen Fakultät der Universität Assiut. Von 70 Kälbern waren 42 pilzkrank, davon 22 durch T. mentagrophytes, 20 durch T. verrucosum. Von 180 Kühen waren 8 pilzbefalien, sämtlich durch T. mentagrophytes. Von 2 kranken Bullen wurde T. verrucosum isoliert. Auch die 3 Pferde und 2 Maultiere der Farm waren pilzinfiziert; Erreger war in diesen Fällen T. equinum. Auch ein Kalb war von T. equinum befallen. Die gleiche Pilzart wurde ferner von 3 Tierpflegern isoliert, die Pilzherde am Hals und an den Armen aufwiesen.     

Statistical challenges in preprocessing in microarray experiments in cancer

Many clinical studies incorporate genomic experiments to investigate the potential associations between high-dimensional molecular data and clinical outcome. A critical first step in the statistical analyses of these experiments is that the molecular data are preprocessed. This article provides an overview of preprocessing methods, including summary algorithms and quality control metrics for microarrays. Some of the ramifications and effects that preprocessing methods have on the statistical results are illustrated. The discussions are centered around a microarray experiment based on lung cancer tumor samples with survival as the clinical outcome of interest. The procedures that are presented focus on the array platform used in this study. However, many of these issues are more general and are applicable to other instruments for genome-wide investigation. The discussions here will provide insight into the statistical challenges in preprocessing microarrays used in clinical studies of cancer. These challenges should not be viewed as inconsequential nuisances but rather as important issues that need to be addressed so that informed conclusions can be drawn.     

Trends in zygomycosis in children

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.     

Hemoglobin in lymphogranulomatosis in children

The peculiarities of hemoglobin content and properties in lymphogranulomatosis were studied in children by different methods. In most patients the content of fetal hemoglobin and methhemoglobin was found to increase and the rate of ferricyanide oxidation of hemoglobin also increases. Simultaneously, the rate of non-homogenicity of basic hemoglobin fractions was observed to increase on account of immunologically different components.     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Sex hormones in women in rural China and in Britain

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.     

Temozolomide treatment in glioma--experiences in two university hospitals in Finland

Thirty-two patients with relapsing glioma were treated with temozolomide in two university hospitals in Finland. One patient (3%) had complete response and 9 (28%) partial response, with 8 patients (25%) showing stable disease. Median progression-free survival for these 18 patients (56%) was 7 months (range 2-11+). The remaining either had progressive disease (25%) or only clinical evaluation (19%). Karnofsky score improved in 34% of patients and decreased in 3%. Symptoms were alleviated in 44% and deteriorated in 9%. Grade 3-4 toxicity was detected in 9% of the patients. Only 4% of the days in treatment were spent in hospital. An average 1.8 neuroradiological investigations, 6.9 laboratory visits, and 5.3 visits to the oncologist were made. This study confirms that temozolomide has positive effects on the outcome of often heavily pretreated glioma patients. High drug costs are compensated by prolonged home care and even the possibility to maintain working capacity.