环氧化酶与妇科肿瘤的研究进展

环氧化酶(COX)是前列腺素(PGs)合成的限速酶,COX-2在多种癌组织中高表达,在肿瘤的发生、发展中起着重要的作用.文章综述国内外COX-2在妇科肿瘤中的表达、调控及其致癌机制方面的研究新进展,为妇科肿瘤的防治提供新的靶目标.     

血中循环DNA启动子甲基化与妇科肿瘤的关系

妇科恶性肿瘤患者外周血中存在着循环DNA,其含量明显高于健康人水平且具有与肿瘤原发灶相一致的基因异常改变,DNA基因启动子甲基化是基因异常中一项重要的表观遗传学改变,是导致肿瘤抑癌基因、DNA错配修复基因、转移抑制基因等表达沉默的重要分子生物学基础.目前已检测到妇科恶性肿瘤患者外周血循环DNA中有多种基因存在异常甲基化,且与肿瘤患者的临床病理特征存在不同程度的相关性.这使得非创伤性早期诊断肿瘤、及时发现肿瘤的复发或转移、监测疗效、预测预后成为可能.     

脆性组氨酸三联基因与妇科肿瘤

随着分子生物学的发展，许多癌基因和抑癌基因被发现。在肿瘤的发生发展和转移中，癌基因的激活和抑癌基因的失活有十分重要的作用。目前认为肿瘤是1种基因性疾病，多种癌基因和抑癌基因协同作用而导致肿瘤的发生和发展。脆性组氨酸三联基因(fragile histidine triad，FHIT)是1996年被分离出来的1种新的肿瘤抑制基因，在多种肿瘤中发现它有异常改变。现就FHIT与妇科肿瘤的研究进展作一综述。     

IOTA超声诊断模型在卵巢肿瘤诊断方面的应用进展

卵巢肿瘤是临床常见的妇科肿瘤之一,其中恶性肿瘤的发病率居妇科肿瘤第三位,仅次于宫颈癌和宫体癌.目前,超声仍是卵巢肿瘤患者的首选检查方法,国际卵巢肿瘤分析(IOTA)研究制订了多种标准化的卵巢超声诊断模型.本文就此研究中心超声诊断模型的应用进展进行综述.     

mRNA差异显示方法筛选卵巢癌相关基因

人和动物肿瘤的发生发展就细胞而言,是由于原癌基因的激活和抑癌基因的失活而造成的,所以癌基因与抑癌基因的研究对探索肿瘤发病机理,寻找预防和治疗肿瘤的新措施都具有重要意义.卵巢癌在妇科恶性肿瘤中以难治著称,不易早期发现,且存活率低.目前人类对卵巢癌的遗传基础认识仍然不很清楚,许多研究表明卵巢癌的发生涉及一系列基因的变化,包括显性癌基因、错配修复基因和众多的肿瘤抑制基因.mRNA差异显示方法因其简单、敏感、高效、快速等     

多肿瘤标志物联合检测在妇科恶性肿瘤临床治疗中的应用研究

目的探讨多肿瘤标志物联合检测在妇科恶性肿瘤治疗过程中的应用价值。方法采用多肿瘤标志物蛋白质芯片系统（C-12），检测了35例卵巢癌、38例宫颈癌和26例绒癌患者治疗前及治疗1个月后的血清肿瘤标志物含量，以肿瘤标志物含量的变化来评估治疗措施。结果治疗1个月后多数患者体内肿瘤标志物含量降至正常范围，但仍有40．1％的卵巢癌、34．2％的宫颈癌、23．1％的绒癌患者治疗后呈阳性，说明部分患者临床疗效不明显，建议改善治疗措施。结论肿瘤标志物联合检测对妇科恶性肿瘤卵巢癌、宫颈癌、绒癌具有高度敏感性，监测治疗前后患者体内的肿瘤标志物含量，对指导临床治疗妇科恶性肿瘤有很大的应用价值。     

血清相关肿瘤标志物联合检测在乳腺癌复发转移中的作用

乳腺癌容易发生复发转移,诊断其复发转移的早期指标主要依靠血清肿瘤标志物检测,肿瘤标志物（Tumor Marker,TM）在人体内含量很低或者没有,而在疾病发生发展后含量升高迅速,并与疾病病程、不同部位相关,多种标志物同时检测可以准确反应疾病状态,并且与肿瘤大小及淋巴结受累程度相关.其价值在后期乳腺癌患者中要明显高于早期患者,而多种肿瘤标志物联合检测有助于提高乳腺癌复发转移检出率.     

腹腔热灌注化疗对妇科癌性腹水的疗效观察

目的：评价腹腔热灌注化疗对妇科癌性腹水治疗的临床价值.方法：对49例晚期妇科恶性肿瘤合并癌性腹水患者,使用深静脉软管经皮腹腔内置管,经体外循环热灌注治疗后,注入顺铂,观察恶性腹水量的变化.同时检测腹水中的相关肿瘤标志物的变化情况.观察患者一般生活体力状况变化及生活质量情况.结果：行腹腔热灌注化疗后,1 1例患者腹水减少程度＞90％,28例患者腹水减少程度＞50％,总有效率79.59％.18.36％的患者发生恶心及呕吐等症状.治疗后患者一般生活状况评分、腹水最大直径等指标较治疗前好转（P＜0.01）,肿瘤标志物水平均明显低于治疗前（P＜0.05）.结论：腹腔热灌注化疗治疗妇科癌性腹水近期疗效好且安全,副作用小,患者耐受性好,是恶性腹水患者较可靠的治疗措施.     

KL-6在肿瘤中的研究进展

KL-6是由MUCI基因编码,相对分子量接近200000的糖蛋白。很早就已作为间质性肺疾病的血清学指标。近年来研究发现,KL-6在乳腺癌、肺癌、结肠癌、壶腹部癌等多种肿瘤中表达均增高,而且同有无淋巴结转移、远处转移密切相关。检测血清KL-6有助于了解乳腺癌、结肠癌等肿瘤的疾病发展和检测,并可以对肺癌某些靶向药物的疗效评估有预测作用。对于放射性肺炎有一定的预测作用。     

KL-6在肿瘤中的研究进展

KL-6是由MUCl基因编码,相对分子量接近200000的糖蛋白。很早就已作为间质性肺疾病的血清学指标。近年来研究发现,KL-6在乳腺癌、肺癌、结肠癌、壶腹部癌等多种肿瘤中表达均增高,而且同有无淋巴结转移、远处转移密切相关。检测血清KL-6有助于了解乳腺癌、结肠癌等肿瘤的疾病发展和检测,并可以对肺癌某些靶向药物的疗效评估有预测作用。对于放射性肺炎有一定的预测作用。     

表皮生长因子受体家族特点及与肿瘤关系的研究进展

人类表皮生长因子受体(human epidermal growth factor receptor,HER)家族属于酪氨酸激酶Ⅰ亚族的跨膜蛋白受体家族，包括4个成员，分别是HER1(EGFR/ErbB1)、HER2(ErbB2)、HER3(ErbB3)和HER4(ErbB4)，由erb基因编码，在细胞生长、增殖及凋亡等活动中起到重要的调节作用。同时，作为原癌基因家族，HER家族在许多人类肿瘤中异常激活及过度表达，是这些肿瘤发生和发展的关键因素，与多种肿瘤的临床病理特征及肿瘤患者的不良预后密切相关。HER家族一直是肿瘤领域基础实验研究和临床诊治研究的热点之一，以其为靶点的综合抗肿瘤治疗方案获得了良好的临床疗效。本文通过查阅对有关HER家族及其与肿瘤关系的相关文献，总结人表皮生长因子受体家族特点及其在肿瘤发生发展、生物靶向诊治方面的最新研究进展。相信随着HER家族临床研究成果的不断丰富及分子生物学技术的快速发展可为肿瘤临床诊治提供新的思路和帮助。     

Clinical significance of MET in gastric cancer

Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.     

Expression of angiogenic growth factor genes in primary human astrocytomas may contribute to their growth and progression.

Astrocytomas are highly malignant brain tumors and are among the most neovascularized solid tumors. We have investigated the expression of the angiogenic growth factors acidic fibroblast growth factor and transforming growth factor-alpha, together with its receptor epidermal growth factor receptor, in 30 primary astrocytomas. Both acidic fibroblast growth factor and transforming growth factor-alpha, together with epidermal growth factor receptor, are found to be greatly overexpressed in these tumors when compared with normal brain. This overexpression of angiogenic growth factors may underlie the intense neovascularization characteristic of astrocytomas.     

Receptors for epidermal growth factor and sex steroid hormones in human colorectal carcinomas

Iodinated epidermal growth factor was used to identify its specific receptor in 32 human colorectal carcinomas. The receptor was found in 25% of the tumors with values between 6.9 - 104.0 fmoles/mg DNA. Receptors for estrogen and progesterone were detected in 45 and 25% of the tumors respectively. No correlation was observed between short term survival and content of receptors for sex steroid hormones. Four of the 8 patients with detectable levels of epidermal growth factor receptor had experienced relapse.     

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer

Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.     

Interleukin 4 receptor expression on human lung tumors and normal lung.

Interleukin 4 (IL-4) receptors were detected by a monoclonal antibody on tumor cells of 10 of 29 squamous cell carcinomas and 6 of 17 adenocarcinomas of the lung. None of the small cell carcinomas or carcinoid tumors stained. Parallel sections stained for epidermal growth factor receptors showed that all but 2 of the IL-4 receptor-positive tumors also expressed epidermal growth factor receptors. Positive labeling for IL-4 receptors was also obtained on nonneoplastic bronchial epithelium and on lymphocytes and macrophages infiltrating the tumor stroma. The role of IL-4 and its receptor in normal human lung is unknown, but the expression of IL-4 receptors on particular subtypes of lung tumors suggests that they may have a role in differentiation or proliferation of squamous and adenocarcinomas.     

Molecular targeting therapy with angiotensin II receptor blocker for prostatic cancer

Angiotensin II (Ang-II) plays a key role as a vasoconstrictor in controlling blood pressure and electrolyte/fluid homeostasis. Recently it has also been shown that this peptide is a cytokine, acting as a growth factor in cardiovascular and stromal cells. In addition, the physiological function of Ang-II seems to be similar in prostate cancer and stromal cells. It is widely assumed that Ang-II facilitates the growth of both cells, and its receptor blockers (ARBs) have the potential to inhibit the growth of various cancer cells and tumors through the Ang-II receptor type 1 (AT1 receptor). The mechanism of cell growth inhibition by ARBs has been considered to be that of suppression of the signal transduction systems activated by growth factors or cytokines in prostate cancer cells, and suppression of angiogenesis. This review highlights the possible use of ARBs as novel agents for prostatic diseases including prostate cancer and benign hypertrophy, and covers related literature.     

Biodistribution of radioactive epidermal growth factor in normal and tumor bearing mice

The biodistribution of iodinated epidermal growth factor in normal and tumor bearing mice was analyzed. The uptake of epidermal growth factor was high in the liver, skin and submaxillary gland, which all have detected receptors for the growth factor. Organs, such as lung, heart, spleen, intestine, bone and central nervous system, which lack the receptor, did not retain the growth factor. In tumor bearing mice, the growth factor accumulated in receptor positive tumors, but to a lesser extent than in the liver. This finding will probably prevent the use of epidermal growth factor as a carrier for radionuclides for a therapeutic purpose.     

c-Met靶向成像在肿瘤诊断中的应用

肝细胞生长因子受体(c-Met)是一种酪氨酸激酶型受体，对于肿瘤的发生发展至关重要，c-Met靶向治疗已初步应用于临床，其对于癌症患者的治疗具有显著的益处。目前，由于无法对c-Met表达阳性的肿瘤患者进行有效的早期筛选，使得c-Met靶向治疗在肿瘤治疗中总体有效率偏低。c-Met靶向分子成像借助靶向分子成像探针能够实现肿瘤c-Met表达水平及活化状态的定量检测和直观揭示，对于肿瘤的早期诊断、治疗和预后具有重要意义和巨大的潜在价值。结合近年来c-Met靶向分子成像的研究，本文将深入分析、探讨c-Met靶向分子成像探针的构建及其在肿瘤诊断中的应用。     

Amphiregulin: a new growth factor in hepatocarcinogenesis

Amphiregulin (AR) is a member of the epidermal growth factor family and a ligand of the epidermal growth factor receptor (EGFR). As other ligands of the EGFR, AR is synthesized as a precursor that is shed from the plasma membrane by metalloproteases. Hyperactive autocrine loops involving AR production have been described in a variety of tumors, and this growth factor is thought to play a non-redundant role in cancer development. AR expression is not detected in the normal liver, however it is readily induced during acute liver injury and behaves as a potent pro-regenerative and survival factor. Increased AR expression is also detected in human chronic liver injury (liver cirrhosis), which is considered a pre-neoplastic condition. Recent evidences suggest that AR can play a unique role in liver tumorigenesis and in the maintenance of the neoplastic phenotype of hepatocarcinoma cells. In this review, we summarize some aspects of AR patho-biology and the rationale behind its definition as a novel target in hepatocarcinoma therapy.