载脂蛋白D与肿瘤

载脂蛋白D(apoD)是一种高密度脂蛋白，与其他载脂蛋白相比存在较多特异性，但对其具体生理作用尚不甚了解。近来研究表明，apoD可能因配基的多样性而具有多种功能。在某些肿瘤中apoD的表达与其预后有关。现综述apoD的生物学特性及其在某些肿瘤中表达的临床意义。     

NGAL在卵巢上皮性肿瘤中的表达及临床意义

目的探讨中性粒细胞明胶酶相关载脂蛋白（NGAL）在卵巢上皮性肿瘤中的表达及其临床意义。方法应用免疫组织化学方法检测NGAL在60例卵巢癌、30例卵巢交界性肿瘤、10例卵巢良性肿瘤和10例正常卵巢组织中的表达,分析其与病变类型的关系及其在卵巢癌组的表达率与临床病理特征的联系。结果 NGAL在卵巢癌和卵巢交界性肿瘤中的阳性表达率分别为81.7%、60.0%,明显高于卵巢良性肿瘤（20.0%）和正常卵巢组织（10.0%）（P〈0.05）。NGAL表达与卵巢癌的病理分级、病理分期和淋巴结转移有关（P〈0.05）。结论 NGAL蛋白促进肿瘤的形成、浸润与转移。NGAL可能是卵巢癌早期诊断和预后的潜在生物学参考指标。     

甲状旁腺肿瘤中细胞周期素D1的表达及其临床意义

目的: 探讨细胞周期素D1在甲状旁腺组织中的表达及其临床意义.方法: 应用免疫组织化学法对3例甲状旁腺腺癌、8例甲状旁腺腺瘤、13例甲状旁腺增生、1例甲状旁腺囊肿以及10例正常甲状旁腺组织中细胞周期素D1的表达进行了检测.结果: 甲状旁腺腺瘤组和腺癌组的细胞周期素D1过度表达比例高于正常甲状旁腺组(P<0.05);而甲状旁腺增生组与甲状旁腺腺癌组、腺瘤组和正常甲状旁腺组比较,差异无统计学意义(P>0.05).结论: 细胞周期素D1的过度表达在甲状旁腺腺瘤和腺癌的发生中起重要作用.     

组织蛋白酶D、c-erbB-2基因表达与乳腺癌预后的相关性

目的探讨组织蛋白酶D、c-erbB-2基因与乳腺癌预后的关系。方法选取乳腺癌术后、化疗后Ⅱ期病例153例，应用免疫组化法检测组织蛋白酶D、c-erbB-2基因的表达。结果组织蛋白酶D、c-erbB-2基因的阳性表达与乳腺癌局部复发和远处转移、腋淋巴结转移呈正相关，与无瘤生存率呈负相关。结论组织蛋白酶D、c-erbB-2基因阳性表达提示预后不良；组织蛋白酶D、c-erbB-2基因、可作为判定预后的指标应用，以弥补常规指标的不足，具有重要的临床应用价值。     

程序性细胞死亡因子4在消化系统肿瘤中表达及其与肿瘤分化的关系

目的：探讨 PDCD4在胃癌、大肠癌和胰腺癌等消化系统肿瘤中的表达及其与肿瘤分化的关系.方法：应用Western印迹杂交和免疫组织化学研究方法检测了 PDCD4在胃癌（61例）、大肠癌（65例）和胰腺癌（69例）3种消化系统肿瘤中的表达,观察其与相应的临床病理学参数之间的关系.结果： Western印迹分析和免疫组化染色结果显示,同癌旁正常组织相比,癌组织PDCD4蛋白表达明显下调.PDCD4蛋白表达与癌的分化程度密切相关,在高分化癌中呈高表达,随着癌分化程度下降,表达明显下调.而与性别、年龄和肿瘤的临床分期无关.结论：PDCD4蛋白在包括胃癌、大肠癌和胰腺癌在内的消化系统肿瘤中表达下降,并与癌的分化程度密切相关.提高PDCD4蛋白表达,可能会诱导肿瘤细胞分化和凋亡,从而抑制肿瘤的发生和发展.     

血清胸苷激酶1与肿瘤

胸苷激酶1(TK1)是一种嘧啶补救途径的激酶,能催化脱氧胸苷磷酸化为一腺胸苷酸,与细胞周期调控和细胞增殖密切相关.多项试验表明,TK1可用于健康体检、肿瘤筛查、常规检测、疗效监视和预后评估,是一种灵敏有效地评估人体肿瘤增长的标志物.     

神经纤维与肿瘤的发生发展

肿瘤内是否有支配功能的神经纤维，这一直是困扰病理学界的问题。其存在的难点不仅仅是技术方面的原因，也因为神经纤维并不象肿瘤中新生血管那么常见。1993年，刘少君等发现人脑膜瘤中有肽能神经纤维的存在。2001年，德国波恩大学Seifert等在世界上首次用电子显微镜观察证实肿瘤组织内有神经纤维，这为肿瘤的研究提出了一个新     

细胞周期素D1在卵巢上皮性肿瘤中表达及临床意义

目的探讨CyclinD1在卵巢上皮性肿瘤发生、发展中的作用及临床意义.方法采用Sp免疫组化方法对10例正常卵巢组织、10例良性卵巢瘤、41例卵巢上皮性癌进行CyclinD1蛋白表达的检测.结果CyclinD1在正常卵巢组织及良性卵巢瘤中均无表达.41例卵巢上皮性癌组织中,CyclinD1阳性表达13例,CyclinD1在卵巢上皮性癌的表达与良性卵巢及正常卵巢组织有显著差异(P＜0.05).CyclinD1在卵巢癌早、晚期表达无显著差异(P＞0.05).CyclinD1表达随病理分级增加而增加,高分化组和中、低分化组CyclinD1表达有显著差异(P＜0.05).CyclinD1的阳性表达与预后无关.结论CyclinD1在卵巢上皮性肿瘤的发生、发展中起作用,CyclinD1是一常见的分子异常并且可以用来判断肿瘤的恶性程度.     

软组织肿瘤的免疫组织化学的研究

凡起源于纤维、脂肪、平滑肌、横纹肌、间皮、滑膜、血管、淋巴管等间叶组织并且位于软组织部位(内脏器官除外)的肿瘤称为软组织肿瘤。软组织虽然分布广泛,包含组织之种类众多,但其肿瘤却远较其他组织之肿瘤少见。软组织肿瘤约占全部恶性肿瘤的0.73～0.81％。根据上海医科大学肿瘤医院7533例软组织肿瘤的分析,其中6213例为良性,占82.40％,1320例为恶性,占17.60％,良性与恶性之比为4.7:1。软组织肿瘤的类型繁多,组织学表现又往往互相重叠,尤其是一些分化差的肉瘤在诊断和鉴别诊断上常会遇到困难。随着免疫组织化学在病理学上的应用,借助于各种单克隆抗体的标记,对这些肿     

不同生存期食管鳞癌患者载脂蛋白D表达水平的研究

  目的  通过对不同生存期食管鳞状细胞癌患者术前血清及组织中载脂蛋白D(ApoD)表达水平差异的研究, 探讨其与该病预后的相关性, 推测其是否可能成为预测食管癌患者预后的生物标记物。  方法  收集河南省食管癌高发地区安阳市肿瘤医院2008年3月至2009年9月行根治性切除食管癌的患者731例, 选择一般资料、血清标本及组织标本建立资料库; 随机从资料库抽取生存期≤3年和生存期≥5年的两个极端生存期患者各34例作为研究对象, 以健康人群作为正常对照组, 使用同位素标记相对和绝对定量法(isobaric tags for relative and absolute quantification, iTRAQ)联合基质辅助激光解吸离子化串联飞行时间质谱(MALDITOF/TOF MS)蛋白质组学技术对食管癌患者术前血清蛋白进行分析比照, 锁定目的蛋白ApoD; 采用Western blot技术验证ApoD在不同生存期食管鳞癌患者术前血清及健康人群血清的表达水平; 使用免疫组织化学技术观察不同生存期食管癌组织及正常组织中ApoD的表达水平。  结果  iTRAQ联合MALDI-TOF/TOF MS结果显示, 有52种蛋白的表达随生存期延长而上调, 具有显著性差异, ApoD是其中之一。Western blot结果显示ApoD在生存期≥5年组血清中表达最高, 正常人血清中表达其次, 而在生存期≤3年组中表达最低, 差异均有统计学意义(P < 0.05)。免疫组织化学结果显示ApoD在正常食管鳞状上皮中表达最高, 在生存期≥5年组表达其次, 在生存期≤3年组中表达最低, 差异均有统计学意义(P < 0.05)。  结论  ApoD表达水平与食管癌患者的生存期呈正相关, 可能与食管癌患者的预后相关, 可能成为预测食管癌患者预后情况的一种生物标记物。      

Apolipoprotein D expression in cutaneous malignant melanoma

BACKGROUND AND OBJECTIVES: Apolipoprotein D (Apo D) is a protein component of the human plasma lipid transport system, and an androgen-regulated protein in both breast and prostate cancer cell lines. Our goal was to evaluate the expression of Apo D in malignant cutaneous melanomas, as well as to assess its possible relationship to clinical and pathological parameters. METHODS: Apo D expression was analyzed in 32 paraffin-embedded tissues from patients with invasive cutaneous malignant melanomas, in 8 samples from in situ melanoma, and in 10 samples from 10 benign lesions (4 dermal melanocytic nevi, 4 compound melanocytic nevi, and 2 dysplastic melanocytic nevi), using immunohistochemical techniques. RESULTS: The benign lesions were consistently negative for Apo D, whereas 3 of the 8 "in situ" melanomas (37.5%) and 12 of the 32 invasive melanomas (37.5%) showed positive immunostaining for Apo D. The percentage of Apo D-positive tumors was significantly higher in nodular than in superficial spreading melanomas (P = 0.011) and in melanomas with vertical growth phase than in melanomas with radial growth phase (P = 0.02). In addition, the percentage of Apo D-positive tumors was positively and significantly correlated with Clark's level of invasion (P = 0.046). CONCLUSIONS: Apo D may be a new prognostic factor of unfavorable evolution in cutaneous malignant melanoma.     

Apolipoprotein C1 promotes tumor progression in gastric cancer

Background: Gastric cancer (GC) is a malignancy with the worst prognosis that seriously threatens humanhealth, especially in East Asia. Apolipoprotein C1 (apoc1) belongs to the apolipoprotein family. In addition, apoc1 hasbeen associated with various tumors. However, its role in GC remains unclear. Methods: Firstly, we quantified itsexpression in GC and adjacent tumor tissues, using The Cancer Genome Atlas (TCGA). Next, we assessed cellinvasion and migration abilities. Finally, we revealed the role of apoc1 in the tumor microenvironment (TME),immune cell infiltration and drug sensitivity. Results: Firstly, in TCGA database, it has been shown that elevatedexpression of apoc1 was identified in various cancers, including GC, then we found that high expression of apoc1 wassignificantly correlated with poor prognosis in GC. Histologically, apoc1 expression is proportional to grade, cancerstage, and T stage. The experimental results showed that apoc1 promoted cell invasion and migration. Then GO,KEGG, and GSEA pathway analyses indicated that apoc1 may be involved in the WNT pathway and immuneregulation. Furthermore, we found out the tumor-infiltrating immune cells related to apoc1 in the tumormicroenvironment (TME) using TIMER. Finally, we investigated the correlation between apoc1 expression and drugsensitivity, PD-1 and CTLA-4 therapy. Conclusions: These results suggest that apoc1 participates in the evolution ofGC, and may represent a potential target for detection and immunotherapy in GC.     

维生素 D 3 与胃肠道肿瘤的研究进展

维生素D3结构上属于甾体激素,它的主要生理功能是调节钙磷代谢和维持正常血钙水平、调节骨代谢和多种细胞的生理反应。近年来很多研究表明维生素D3在多种肿瘤中扮演重要角色,影响肿瘤细胞的增殖、凋亡等活动。维生素D3作用于不同癌细胞类型的细胞机制,有力地表明维生素D3可以发挥保护和抗肿瘤作用,延缓细胞转化、增生和肿瘤进展。流行病学研究发现血清维生素D水平与胃肠道肿瘤发病风险呈负相关,血清维生素D水平与胃肠道肿瘤患者预后正相关。进一步研究表明维生素D3可以通过多种途径诱导细胞凋亡、阻滞细胞周期、抑制胃肠道肿瘤细胞增殖。维生素D3能够与化疗药物协同作用促进肿瘤细胞凋亡、抑制肿瘤细胞增殖。维生素D3类似物不产生高血钙的副作用,也能够发挥其抑制肿瘤细胞生长的作用。维生素D3可能通过维生素D3受体VDR发挥其抗肿瘤作用。结合这些研究表明维生素D3有希望做为治疗和预防胃肠道肿瘤的新思路,更多的维生素D3抗肿瘤机制研究及临床实验能够为胃肠道肿瘤患者带来福音。     

Neonatal vitamin D and childhood brain tumor risk

Vitamin D deficiency among pregnant women is common. Compelling animal evidence suggests carcinogenic effects of vitamin D deficiency on the brains of offspring; however, the impact of circulating vitamin D [25(OH)D] on childhood brain tumor (CBT) risk has not been previously evaluated. Using linked birth‐cancer registry data in Washington State, 247 CBT cases (<15 years at diagnosis; born 1991 or later) were identified. A total of 247 birth year‐, sex‐ and race‐matched controls were selected from the remaining birth certificates. Liquid chromatography–tandem mass spectrometry was used to measure circulating levels of vitamin D₃ [25(OH)D3] in neonatal dried blood spots. Overall, no significant associations were observed. However, when stratified by median birth weight (3,458 g), there was evidence of increasing risk of CBT with increasing 25(OH)D3 among children in the higher birth weight category. Compared to the lowest quartile (2.8–7.7 ng/mL), odds ratios (ORs) and 95% confidence intervals (CIs) for the second (7.7–<11.0 ng/mL), third (11.0–<14.7 ng/mL) and fourth (14.7–37.0) quartiles of 25(OH)D3 were 1.7 (1.0–3.3), 2.4 (1.2–4.8) and 2.6 (1.2–5.6), respectively. Among children in the lower birth weight category, there was suggestive evidence of a protective effect: ORs and 95% CIs for the second, third and fourth quartiles were 0.9 (0.4–1.9), 0.7 (0.3–1.4) and 0.6 (0.3–1.3), respectively. Any associations of neonatal vitamin D with CBT may be birth weight‐specific, suggesting the possible involvement of insulin‐like growth factor 1, circulating levels of which have been associated with vitamin D and accelerated fetal growth.     

NKG2D及其配体与肿瘤免疫治疗研究新进展

NKG2D为自然杀伤(NK)细胞表面的C型凝集素样活化性受体,NKG2D与肿瘤细胞表面配体结合,杀伤肿瘤细胞,但在肿瘤患者和患肿瘤小鼠体内存在着依赖NKG2D的免疫逃避机制.近年来利用各种分子生物技术调节受体和配体的表达来避免免疫逃避.     

细胞周期素D1与肿瘤研究进展

肿瘤是一类细胞周期性疾病,细胞生长周期的失调在肿瘤的发生发展中起关键作用.细胞周期素D1(cyclin D1)在细胞周期的正常调控中扮演重要角色,其基因结构、功能的异常与肿瘤发生发展密切相关.现综述cyclin D1与肿瘤研究的最新进展.     

NKG2D ligands in tumor immunity

The activating receptor NKG2D (natural-killer group 2, member D) and its ligands play an important role in the NK, gammadelta(+) and CD8(+) T-cell-mediated immune response to tumors. Ligands for NKG2D are rarely detectable on the surface of healthy cells and tissues, but are frequently expressed by tumor cell lines and in tumor tissues. It is evident that the expression levels of these ligands on target cells have to be tightly regulated to allow immune cell activation against tumors, but at the same time avoid destruction of healthy tissues. Importantly, it was recently discovered that another safeguard mechanism controlling activation via the receptor NKG2D exists. It was shown that NKG2D signaling is coupled to the IL-15 receptor pathway in a cell-specific manner suggesting that priming of NKG2D-mediated activation depends on the cellular microenvironment and the distinct cellular context. This review will provide a broad overview of our up-to-date knowledge of the NKG2D receptor and its ligands in the context of tumor immunology. Strategies to amplify NKG2D-mediated antitumor responses and counteract tumor immune escape mechanisms will be discussed.     

Plexin D1 is ubiquitously expressed on tumor vessels and tumor cells in solid malignancies

Background  

Plexin D1 is expressed on both tumor-associated endothelium and malignant cells in a number of clinical brain tumors. Recently we demonstrated that Plexin D1 expression is correlated with tumor invasion level and metastasis in a human melanoma progression series. The objective of this study was to examine whether Plexin D1 might be clinically useful as a pan-tumor vessel and pan-tumor cell target in solid tumors.     

轴突导向蛋白4D 在肿瘤进展中的作用*

轴突导向蛋白4D（SEMAPHORIN 4D,SEMA 4D）又称CD100,是轴突导向蛋白Ⅳ亚族（SEMAs Ⅳ）的重要成员之一,其最初作为影响神经发育的轴突导向分子被发现。近来越来越多的研究表明,SEMA 4D 在免疫调节、血管发生及肿瘤生长转移等方面也有重要的生物学功能,尤其作为新的促血管生成分子,SEMA 4D 的相关研究引起广泛关注。本文旨在对SEMA 4D 的结构、受体特点、促血管生成及肿瘤侵袭转移等方面的最新研究进展进行综述。