抑癌基因研究进展

本文通过分析近几年发表的癌基因与抑癌基因文献，发现细胞癌变机制研究的热点已由癌基因过渡到了抑癌基因，这对今后的肿瘤防治研究具有一定指导意义。本文还对克隆发现的多种抑癌基因的性质、功能、染色体定位、相关性肿瘤以及与癌基因区别的研究进展作了综述。     

抑癌基因,癌基因与肺癌

分子生物学研究表明，小细胞肺癌癌细胞的３号染色体短臂缺失频率为１００％，非小细胞肺癌为７４％，并发现抑癌基因Ｒｂ，ｐ５３和癌基因ｍｙｃ，ｒａｓ，ｅｒｂ，ｍｙｂ，ｎｅｕ等在肺癌中也起着重要作用，从而证实抑癌基因和癌基因与肺癌的发生发展有着非常密切的关系。     

卵巢肿瘤中癌基因和抑癌基因研究进展

卵巢肿瘤中癌基因和抑癌基因研究进展杨文涛沈铭昌上海医科大学附属肿瘤医院（上海２０００３２）在女性生殖系统肿瘤中，卵巢肿瘤的死亡率位居第一。近年来，对癌基因、抑癌基因在卵巢肿瘤的发生、发展中所起的作用及其与预后的关系进行了大量的研究。一、癌基因１．ＨＥ...     

化学致癌剂与癌基因和抑癌基因

化学致癌剂与癌基因和抑癌基因王冰，柯杨北京医科大学临床肿瘤医院北京市肿瘤防治研究所细胞遗传室（北京１０００３４）目前认为，人类肿瘤的形成与多种因素有关，其中化学致癌因素最为重要。对于化学致癌机理的探讨，经历了从动物肿瘤模型的建立、离体细胞的恶性转化，...     

鼻咽癌发生发展相关的癌基因和抑癌基因

鼻咽癌是一种常见的恶性肿瘤,癌基因的激活与抑癌基因的失活及其相互作用所致的平衡失调是肿瘤发生发展的分子基础。近年来,随着分子生物学技术的发展,与鼻咽癌相关的癌基因和抑癌基因的研究日益深入。本文拟对这些癌基因和抑癌基因以及相关候选癌基因和候选抑癌基因的研究近况作一综述。     

鼻咽癌发生发展相关的癌基因和抑癌基因

鼻咽癌是一种常见的恶性肿瘤,癌基因的激活与抑癌基因的失活及其相互作用所致的平衡失调是肿瘤发生发展的分子基础。近年来,随着分子生物学技术的发展,与鼻咽癌相关的癌基因和抑癌基因的研究日益深入。本文拟对这些癌基因和抑癌基因以及相关候选癌基因和候选抑癌基因的研究近况作一综述。     

癌症分子基础与临床：第二讲 癌基因与抑癌基因

癌的生成涉及多种基因的变化，现c发现与癌有关的主要的基因变化既响促进细胞生长的癌基因活化，也有抑制细胞增殖的抑癌基因的失活。分别简介如下。一、癌基因（Oncosene）癌基因是指其产物与细胞的肿瘤性转化有关的的基因，其发现可追溯自动物致瘤病毒的研究。R000于1门1年首先发现鸡肉瘤病毒，以后研究证明它是一种RNj＼逆转录病毒，它含有一种特殊的基因，能引起培养的细胞转化和恶性表型，也能在动物中引起恶性肿瘤，这种基因被称为病前的癌基因（v－one）。以后陆续分离和克隆出许多种动物的v－one，并且发现在脊椎动物的基因组中存…     

喉癌的癌基因及抑癌基因

喉癌的发生发展是多步骤进行的,喉癌的转移也是一个多基因参与调控的过程,本文从癌基因及抑癌基因两大方面综述其在喉癌发生发展中的作用。１　喉癌的发生发展与癌基因癌基因是由存在于正常细胞中的原癌基因在某些致癌因素作用下激活而成。肿瘤的发生与癌基因的激活密切相关［１］。１．１　ｒａｓ基因　ｒａｓ基因包括Ｈａｒａｓ、Ｋｉｒａｓ、Ｎｒａｓ,在人类的许多肿瘤中都发现了ｒａｓ基因,ｒａｓ基因编码一种２１ｋＤ的蛋白质与Ｇ蛋白有关,具有与鸟氨酸结合的能力及ＧＴＰ酶活性。ｒａｓ基因的扩增或突变可使其功能蛋白ｐ２…     

抑癌基因及人原发性肝癌中抑癌基因研究进展（Ⅱ）

抑癌基因及人原发性肝癌中抑癌基因研究进展（Ⅱ）顾健人上海市肿瘤研究所癌基因与相关基因国家重点实验室（上海２０００３２）五、研究新的抑癌基因／癌基因的战略目前各国有关的科学家都在为寻找新的抑癌基因／癌基因而努力，为此必须有新的战略，其中之一是与人基因组...     

癌基因及癌基因蛋白在肿瘤诊断中的临床意义

癌基因是指可在体外转化特殊的二倍体细胞成为癌细胞的一些病毒基因片段。癌基因蛋白则指癌基因编码的一些与病毒致病性有关的蛋白。不仅致癌病毒体内存在癌基因,在原核及真核动物细胞内也广泛存在这些癌基因片段。这已经过同位素标记的分子杂交技术证实。一般将存在于脊椎动物体内的癌基因称为原癌基因。从它们在进化过程中高度的保守性不难看出这些基因所编码的蛋白一定是与生物体最基本的特征——生长与繁殖功能相关的。近年来,肿瘤分子生物学家研究指出:当这些蛋白表达的时间或数量不受控制或出现紊乱时,正常细胞失去了精细的生物调节机制,显示出肿瘤细胞的特征。     

2016年上海市恶性肿瘤发病和死亡情况与2002—2016年的变化趋势分析

背景与目的：上海市疾病预防控制中心每年更新上海市恶性肿瘤发病和死亡及其趋势的统计资料。分析2016年上海市恶性肿瘤发病和死亡的基本情况及其2002—2016年的变化趋势。方法：采用上海市疾病预防控制中心建立的人群基础肿瘤登记管理系统和死因登记系统收集的2002—2016年恶性肿瘤发病和死亡资料,按诊断或死亡年份、性别和年龄组分层分析,计算数量、构成比、粗率、年龄别率、年龄标准化率（标化率）等指标,同时计算不同分组的主要癌症类型的数量、构成比和率值。按性别划分的所有恶性肿瘤和各主要癌症类型的发病和死亡标化率采用Joinpoint回归模型计算年度变化百分比（annual percent change,APC）分析变化趋势。应用Segi’s 1960年世界标准人口计算发病和死亡的标化率。结果：2016年上海市恶性肿瘤新发病例和死亡人数分别为74 422例和37 010人,粗发病率为513.94/10万,标化发病率为231.58/10万,女性的标化发病率高于男性。粗死亡率为255.58/10万,标化死亡率为90.01/10万,男性的标化死亡率高于女性。年龄别发病和死亡的数量和率值随着年龄的增长而增加,年龄别发病的数量和率值分别在60~64岁组和80~84岁组达到高峰,年龄别死亡的数量和率值分别在80~84岁组和85岁及以上组达到高峰。按发病例数排序,前10位常见癌症类型的部位依次为肺、结直肠、甲状腺、胃、乳腺、肝脏、前列腺、胰腺、脑和中枢神经系统、膀胱。按死亡人数排序,前10位依次为肺、结直肠、胃、肝、胰腺、乳腺、胆囊、食管、前列腺和淋巴系统。按性别划分的发病和死亡的前10位常见癌症类型与按常见组合年龄段划分的前5位常见癌症类型差异较大。总体上,男性的标化发病率在2002—2009年维持稳定状态,在2009—2016年以年均1.16%的增速上升,女性的标化发病率在2002—2009年维持稳定状态,在2009—2016年以年均4.48%的增速上升。2002—2016年,男性的标化死亡率以年均1.35%的减速下降,女性的标化死亡率以年均1.31%的减速下降。不同性别和癌症类型的变化趋势各不相同。结论：尽管男性和女性的标化发病率略有上升,但是对应的标化死亡率正在下降。按性别或年龄分层的总体和常见癌症类型的现况和趋势反映了上海户籍人口在癌症危险因素、筛查技术应用和诊疗水平等方面的变化。以人群为基础的癌症发病和死亡资料可用于减少癌症负担。     

An Atypical Rare Case of Extracranial Craniopharyngioma

We present a case of a purely extracranial, infrasellar craniopharyngioma that initially presented as a mass in nose and nasopharynx. Craniopharyngiomas are usually located within the sella. Purely infrasellar craniopharyngiomas have only rarely been reported in the literature. A 55-year-old man presented with 8-month history of progressive headache and epistaxis. Rhinoscopy revealed polypoidal mass in both the nasal cavities and nasopharynx. Pre-operative biopsy suggested Craniopharyngioma. A battery of tests necessary for the diagnosis of Craniopharyngioma was done which excluded other possibilities. Surgical resection was done and histopathology thereafter was confirmatory of Craniopharyngioma. Adjuvant radiotherapy was given to the patient. The patient is doing well. The Rathke’s pouch arises from the roof of the primitive mouth and grows toward the brain at the fourth week of gestation. Normally, it loses its attachment with the stomadeum completely by the eighth week of gestation. The craniopharyngeal canal (CPC) extends from the floor of the sella to the vomer and may rarely give rise to ectopic craniopharyngiomas. This case shows that such ectopic tumors may arise anywhere along the CPC. We are documenting this case as an atypical rare case of craniopharyngioma probably originating from tooth primordia.     

Gamma-irradiation enhances apoptosis induced by cannabidiol, a non-psychotropic cannabinoid, in cultured HL-60 myeloblastic leukemia cells

Two non-psychotropic cannabinoids, cannabidiol (CBD) and cannabidiol-dimethylheptyl (CBD-DMH), induced apoptosis in a human acute myeloid leukemia (AML) HL-60 cell line. Apoptosis was determined by staining with bisBenzimide and propidium iodide. A dose dependent increase of apoptosis was noted, reaching 61 and 43% with 8 μg/ml CBD and 15 μg/ml CBD-DMH, respectively, after a 24 h treatment. Prior exposure of the cells to γ-irradiation (800 cGy) markedly enhanced apoptosis, reaching values of 93 and 95%, respectively. Human monocytes from normal individuals were resistant to either cannabinoids or γ-irradiation. Caspase-3 activation was observed after the cannabinoid treatment, and may represent a mechanism for the apoptosis. Our data suggest a possible new approach to treatment of AML.     

细胞因子在肿瘤相关性贫血中的作用机制研究进展

肿瘤相关性贫血是肿瘤发生发展过程中最常见的并发症,肿瘤患者的贫血类型呈多样性,因影响红细胞生成或消耗的因素众多,如：慢性失血、溶血、铁代谢紊乱、肾功能不全、造血功能障碍（骨髓抑制）、炎性反应因子数量的增加、肿瘤患者恶性消耗、促红细胞生成素相对不足等均可导致贫血。目前肿瘤相关性贫血的具体发生机制尚未完全清楚,但炎性反应因子在肿瘤相关性贫血发生发展过程中起着决定性作用,其中hePcidin、IL-6、TNF-α及EPO等细胞因子扮演着重要角色。改善肿瘤患者的贫血状态,可以改善患者症状,提高患者生活质量,改善患者认知能力,增强患者社会能力,成为临床医师越来越关注的焦点。     

中国人群HBV基因型及亚型与肝细胞癌相关性的Meta分析

目的 探讨中国人群HBV基因型及亚型与肝细胞癌（以下简称“肝癌”）的相关性。方法 计算机检索文献,收集2007年1月至2017年2月公开发表的有关中国人群HBV基因型、亚型与肝癌相关性的病例对照研究,按纳入与排除标准筛选文献、评价质量并提取有效数据,采用RevMan 5.3进行Meta分析。结果 最终纳入中国人群HBV基因型与肝癌相关性研究37篇,其中病例组4 109例,对照组15 319例;HBV基因亚型（C1、C2、 B2）与肝癌相关性研究8篇,其中病例组931例,对照组5 793例;纳入文献质量评分均≥7分。Meta分析结果显示,携带HBV C基因型者罹患肝癌的风险较携带HBV B基因型高（OR=2.35,95%CI：1.93~2.87,P<0.001）;携带HBV C基因型与A/D基因型者罹患肝癌风险差异无统计学意义（OR=1.25,95%CI：0.20~7.82,P=0.81）;携带HBV C1亚型、HBV C2亚型者罹患肝癌的风险差异无统计学意义（OR=1.05,95%CI：0.66~1.68,P=0.82）,携带HBV C2亚型者罹患肝癌风险较HBV B2亚型者高（OR=1.77,95%CI：1.38~2.27,P<0.001）。结论 中国人群携带HBV C基因型者罹患肝癌风险较其他主要基因型高,携带HBV C1亚型和HBV C2亚型者罹患肝癌风险相当,但HBV C2亚型者罹患肝癌风险均较携带HBV B2亚型者高。     

“凤凰涅槃”通路与肿瘤的复发和转移

肿瘤放化疗导致肿瘤凋亡或死亡的同时,启动了凋亡或死亡通路中某些执行蛋白,使得濒死的肿瘤细胞释放大量的炎症介质至肿瘤微环境,从而促进临近的、残余的或静止期的肿瘤细胞再增殖,这种“凤凰涅槃”现象提示现行以诱导肿瘤细胞凋亡或死亡为主要目的治疗方案存在不足。因此,探索“凤凰涅槃”现象的根源,阐明肿瘤复发和转移的新机制将为肿瘤的防治提供新策略和新思路。     

基于三种CT图像勾画的非小细胞肺癌靶体积比较研究

目的 比较基于三维CT (3DCT)、四维CT (4DCT)和锥形束CT (CBCT)图像勾画所得非小细胞肺癌(NSCLC)靶区位置和体积差异。方法 31例周围型NSCLC患者,序贯完成胸部3DCT和4DCT扫描,基于3DCT制定放疗计划,放疗首次拍摄CBCT,并基于骨性标志配准校正。在3DCT、4DCT的50%时相、最大密度投影(MIP)、CBCT图像上勾画得到GTV_3D、GTV_4D50%、IGTV_MIP和IGTV_CBCT。对组间位移比较行Wilcoxon秩和检验,靶区位置及包含度比较行配对t检验,肿瘤三维运动相关性行Pearson法分析。结果 肺上叶组GTV_3D、GTV_4D50%、IGTV_MIP 与IGTV_CBCT比值分别为0.77、0.84和1.10(P=0.004、0.005、0.07);中下叶组比值分别为0.67、0.65和1.17(P=0.001、0.001、0.020)。全组患者GTV_4D50%与IGTV_CBCT比值与肿瘤三维运动呈负相关(P=0.012)。全组患者IGTV_CBCT对GTV_3D、GTV_4D50%、IGTV_MIP包含度分别为0.65、0.65和0.62,IGTV_CBCT对GTV_MIP包含度与IGTV_CBCT对GTV_3D或GTV_4D50%包含度差异无统计学意义(P=0.375、0.167),而GTV_3D、GTV_4D50%、IGTV_MIP对IGTV_CBCT包含度分别为0.47、0.49和0.67,IGTV_MIP对IGTV_CBCT包含度大于GTV_3D或GTV_4D50%对IGTV_CBCT包含度(P=0.000、0.000)。结论 CBCT图像包含的肿瘤运动信息量明显大于3DCT图像,但略小于4DCT的MIP图像。即使3DCT、4DCT与CBCT配准校正后也有可能导致较严重的脱靶,这是基于CBCT进行循证靶区和计划修正所需注意的。     

Potential usage of proteasome inhibitor bortezomib (Velcade, PS-341) in the treatment of metastatic melanoma: basic and clinical aspects

Protein degradation by proteasome is essential to the regulation of important cellular functions including cell cycle progression, proliferation, differentiation and apoptosis. Abnormal proteasomal degradation of key regulatory proteins perturbs the normal dynamics of these cellular processes culminating in uncontrolled cell cycle progression and decreased apoptosis leading to the characteristic cancer cell phenotype. Proteasome inhibitors are a novel group of therapeutic agents designed to oppose the increased proteasomal degradation observed in various cancers while restoring key cellular functions such as apoptosis, cell cycle progression, and the inhibition of angiogenesis. Several proteasome inhibitors have been evaluated in pre- and clinical studies for their potential usage in clinical oncology. Bortezomib (Velcade, PS-341) is the first Food and Drug Administration-approved proteasome inhibitor for the treatment of multiple myeloma and mantle cell lymphoma. Bortezomib's ability to preferentially induce toxicity and cell death in tumor cells while rendering healthy cells unaffected makes it a powerful therapeutic agent and has extended its use in other types of malignancies. The ability of bortezomib and other proteasome inhibitors to synergize with conventional therapies in killing tumors in various in vitro and in vivo models makes this class of drugs a powerful tool in overcoming acquired and inherent resistance observed in many cancers. This is achieved through modulation of aberrant cellular survival signal transduction pathways and their downstream anti-apoptotic gene products. This review will discuss the anti-neoplastic effects of various proteasome inhibitors in a variety of cancers with a special emphasis on bortezomib, its mechanism of action and role in cancer therapy. We further discuss the potential use of bortezomib in the treatment of metastatic melanoma.     

A novel immunomodulatory and molecularly targeted strategy for refractory Hodgkin's lymphoma

Although Hodgkin''s lymphoma (HL) was one of the first human cancers to be cured by chemotherapy, no new agents other than brentuximab vedotin (Adcetris®, CD 30 directed antibody drug conjugate) have received US Food and Drug Administration (FDA) approval for HL since 1977. Subsets of young adult patients with HL continue to relapse, even after stem cell transplantation, warranting new approaches. Against this background, we report a dramatic response in a young patient with advanced HL refractory to the standard treatment who responded to the combination of a pan-histone deacetylase inhibitor (vorinostat, suberoylanilide hydroxamic acid, SAHA) and mammalian target of rapamycin (mTOR) inhibitor therapy (sirolimus,rapamume). In-depth immunohistochemical and morphoproteomic analyses of this exceptional responder to targeted therapy have yielded potential insights into the biology of advanced HL. The PI3K/AKT/mTOR pathway is a commonly activated pathway in multiple tumor types including HL. The patient was treated using therapy based on mechanistic in vitro data demonstrating that combined histone deacetylase (HDAC) and mTOR inhibition act together on this pathway, resulting in inhibition of reciprocal feedback networks, leading to better anti-proliferative activity. The in vivo response signature from this patient''s tissue sample sheds light on immune dysregulation in HL. We describe the response signature achieved from targeting immune dysregulation in addition to targeting the key oncogenic PI3K/AKT/mTOR pathway. We also expand on the role of rapamycin analogs in oncology. This study supports a role for an immune-type pathogenesis that is amenable to immune modulating targeted therapy in refractory HL.Significance: We report an exceptional responder to molecularly targeted and immune modulator therapy in advanced Hodgkin''s lymphoma. The morphoproteomic/morphometric findings in this “unusual responder” patient''s relapsed HL that correlate best, as a response signature with the subsequent clinical remission following rapamycin (sirolimus) and vorinostat (SAHA) therapies, center on an immune dysregulation involving an imbalance between effector and functional T regulatory cells in addition to targeting the mTOR pathway. This underscores the need for an approach illustrated in our study – namely of focusing on pathogenetic mechanisms and combinatorial therapies that target both the pathogenesis and adaptive responses to contemplated therapies.