黏液样/圆细胞型脂肪肉瘤中FUS-CHOP mRNA和MDM_2、p53蛋白的表达

 目的探讨FUS-CHOP mRNA及MDM2、p53蛋白在黏液样/圆细胞型脂肪肉瘤(MRCLs)组织中的表达。方法收集经甲醛固定、石蜡包埋的MRCLs组织标本25例。以非MRCLs的脂肪肉瘤及其他软组织肉瘤共18例作对照组。用嵌套式RT-PCR的方法检测FUS-CHOP融合基因mRNA并做DNA测序证实,以β-actin基因作为内对照。用免疫组化SP法检测25例MRCLs中MDM2、p53蛋白表达情况。结果MRCLs组和阴性对照组β-actin阳性率分别为72%(18/25)和66.7%(12/18)。25例MRCLs中15例检出Ⅱ型FUS-CHOP融合基因表达,去除β-actin阴性病例后阳性率为83.3%(14/18)。对照组18例标本均未检出FUS-CHOP融合基因。MRCLs中MDM2、p53蛋白阳性表达率分别为56%(14/25)和44%(11/25),以圆细胞为主的病例组阳性表达率最高,差异有统计学意义。FUS-CHOP融合基因与MDM2及p53蛋白表达无相关性;而MDM2与p53蛋白表达呈正相关,有统计学意义。结论(1)FUS-CHOP融合基因是MRCLs的特异性分子遗传标志物,可用于该肿瘤的诊断与鉴别诊断。(2) MRCLs 中MDM2 、p53 蛋白表达与其预后相关。(3) MRCLs 中FUS2CHOP 融合基因与MDM2 、p53 蛋白的表达无相关性。     

粘液样/圆细胞型脂肪肉瘤石蜡包埋组织中FUS-CHOP融合基因的检测

目的:探讨逆转录-聚合酶链反应(RT-PCR)方法用于检测甲醛固定、石蜡包埋组织中FUS-CHOP融合基因的可行性及其对粘液样/圆细胞型脂肪肉瘤诊断的价值.方法:收集粘液样/圆细胞型脂肪肉瘤石蜡包埋组织标本25例,以其它类型脂肪肉瘤(包括分化良好型、去分化型、多形型),滑膜肉瘤,低度恶性纤维肉瘤,恶性纤维组织细胞瘤,粘液脂肪瘤,脂肪母细胞瘤,神经鞘瘤伴粘液变性和粘液软骨肉瘤作为阴性对照,共18例.所有标本均经过甲醛固定、石蜡包埋.用嵌套式RT-PCR的方法检测FUS-CHOP融合基因mRNA并经测序证实,以β-actin基因作为内对照检测mRNA质量.结果:43例标本中,30例可检出β-actin,阳性率为69.8%,其中粘液样/圆细胞型脂肪肉瘤标本β-actin阳性18例(72%),对照组β-actin阳性12例(66.7%).25例粘液/圆细胞型脂肪肉瘤中15例检出Ⅱ型FUS-CHOP融合基因表达,阳性率60%(15/25),去除β-actin阴性病例的阳性率为77.8%(14/18).其中1例β-actin阴性表达而检出FUS-CHOP融合基因.对照组18例标本均未检出FUS-CHOP融合基因.结论:FUS-CHOP融合基因在粘液样/圆细胞型脂肪肉中呈特异性表达,可作为该肿瘤的特异性标志物用于诊断.嵌套式RT-PCR的方法可用于甲醛固定、石蜡包埋组织中FUS-CHOPmRNA的检测.     

粘液样脂肪肉瘤TLS/FUS-CHOP融合基因的检测

目的:探讨在粘液样脂肪肉瘤石蜡包埋组织中检测TLS/FUS-CHOP特异性融合基因的可行性及TLS/FUS-CHOP融合基因表达在粘液样脂肪肉瘤诊断中的价值.方法:收集粘液样脂肪肉瘤石蜡包埋组织标本6例,以粘液样脂肪瘤、脂肪母细胞瘤、粘液瘤、骨外粘液样软骨肉瘤、粘液纤维肉瘤作为阴性对照,β-肌动蛋白和β2-微球蛋白作为内对照,用逆转录聚合酶链反应(RT-PCR)和巢式PCR检测TLS/FUS-CHOP融合基因的表达.结果:6例粘液样脂肪肉瘤中4例检出β-肌动蛋白mRNA表达,5例检出β2-微球蛋白mRNA表达,其中3例检出Ⅱ型TLS/FUS-CHOP融合基因mRNA表达.对照组均未检出TLS/FUS-CHOP融合基因的表达.结论:运用RT-PCR方法检测石蜡包埋组织中TLS/FUS-CHOP融合基因mRNA的表达可行,有助于粘液样脂肪肉瘤的诊断和鉴别诊断.     

MDM2基因在骨生肉瘤及脂肪肉瘤中的表达及临床意义

目的 研究MDM2基因与国人骨肉瘤和脂肪肉瘤的关系从而了解MDM2基因在肉瘤发生中的作用及其临床意义。方法 用免疫组化方法研究了31例骨肉瘤,2例骨旁骨肉瘤,6例软骨肉瘤,14例脂肪肉瘤MDM2的表达。结果 31例骨肉瘤中MDM2阳性表达者18例,为58.6％,骨旁骨肉瘤2例皆为阳性表达,6例软骨肉瘤中2例阳性表达;14例脂肪肉瘤中8例阳性表达,为57.1％。结论 MDM2癌基因异常与肉瘤的发生关系密切,但对肉瘤的恶性级别和预后的影响仍不明确,有待讲一步研究。     

EWS-ATF1融合基因在透明细胞肉瘤中的表达及其诊断意义

目的：探讨在透明细胞肉瘤（CCS）石蜡包埋组织中检测EWS-ATF1融合基因的可行性及EWS-ATF1融合基因表达在透明细胞肉瘤诊断中的意义。方法：收集1992年～2006年期间确诊的26例CCS石蜡包埋组织标本,20例非CCS石蜡包埋组织标本为对照组,β-肌动蛋白和β2微球蛋白作为内参照,用逆转录聚合酶链反应（RT-PCR）和巢式PCR检测EWS-ATF1融合基因的表达;过氧化物酶染色（SP）方法对26例CCS石蜡组织标本进行免疫组化染色,检测S-100、HMB-45蛋白的表达。结果：26例标本中,有22例β-肌动蛋白阳性;24例β2微球蛋白阳性,其中20例EWS-ATF1融合基因阳性（16例EWS-ATF1Ⅰ型,4为EWS-ATF1Ⅲ型）,余4例EWS-ATF1融合基因阴性。对照组均未检测到EWS-ATF1融合基因的表达。26例CCS石蜡组织标本中S-100及HMB-45的总阳性率分别为79.2%和70.8%。结论：在CCS石蜡包埋组织中运用RT-PCR检测EWS-ATF1融合基因是可行的,可作为辅助诊断和鉴别诊断的有力工具。     

脂肪肉瘤的临床病理和基因改变的研究进展

脂肪肉瘤是一种起源于原始间叶细胞的恶性肿瘤,具有显著的组织多样性,由分化和异型程度不同的细胞组成。脂肪肉瘤主要分为四个亚型:以MDM2-HMGA2为关键基因的非典型脂肪源性肿瘤(Atypical lipogenic tumors,ALT)/高分化脂肪肉瘤(Well-differentiated liposarcoma,WDLPS)和去分化脂肪肉瘤(Dedifferentiated liposarcoma,DDLPS),以FUS-CHOP基因融合为主要发生机制的黏液性脂肪肉瘤(Myxoid liposarcoma,MLPS)/圆形细胞脂肪肉瘤(Round cell liposarcoma,RCLPS),以及发病机制复杂且多变的多形性脂肪肉瘤(Pleomorphic liposarcoma,PLPS)。ALT/WDLPS的主要病理变化为多形性成熟脂肪细胞增殖,DDLPS为高级别肉瘤,MLPS/RCLPS主要由非脂质间质细胞组成,而PLPS以异型多空泡脂肪母细胞为特点。这四个亚型所包含的肿瘤基因及临床病理学改变,导致了这四种亚型具有不同的临床行为、治疗敏感性和生物学特性。本文将对这四个亚型的病理及基因改变进行总结和探讨。     

PLIN1在原发性腹膜后脂肪肉瘤组织中的表达及与阿帕替尼疗效的相关性

目的:探讨原发性腹膜后脂肪肉瘤中脂滴包被蛋白基因(perilipin-1,PLIN1)的蛋白表达及其与甲磺酸阿帕替尼疗效的相关性。方法:采用免疫组化SABC法检测36例原发性腹膜后脂肪肉瘤及20例脂肪瘤组织中PLIN1蛋白的表达,分析PLIN1蛋白与甲磺酸阿帕替尼疗效的关系。结果:PLIN1蛋白在原发性腹膜后脂肪肉瘤和脂肪瘤组织中表达阳性率分别为19.44%（7/36）、70.00%（14/20）,二者阳性率比较有显著性差异（P＜0.05）。不同类型脂肪肉瘤中,分化较差者阳性率明显低于分化较好者（P＜0.05）。PLIN1蛋白表达在原发者与复发者之间的差异无统计学意义（P＞0.05）。PLIN1蛋白与患者年龄、性别及肿瘤大小无相关性。PLIN1蛋白低表达组患者口服甲磺酸阿帕替尼的疗效优于高表达组, 原发性腹膜后脂肪肉瘤中PLIN1蛋白表达与疗效呈负相关（P＜0.05）。结论:PLIN1蛋白与原发性腹膜后脂肪肉瘤的发生发展、分化程度有关,可作为判断原发性腹膜后脂肪肉瘤分化程度及恶性程度的参考指标之一,但与肿瘤复发无关。PLIN1蛋白表达情况可作为口服甲磺酸阿帕替尼靶向治疗的生物学参考靶标。     

外阴鳞癌组织MDM2 mRNA和p53蛋白表达及其意义

目的探讨外阴鳞癌组织中MDM2 mRNA和p53蛋白的表达及在外阴鳞癌发生、发展中的作用.方法采用RT-PCR法检测31例外阴鳞癌组织中MDM2 mRNA表达情况,利用免疫组化S-P法检测p53蛋白的表达,并与31例癌旁正常外阴组织进行对照.结果在外阴鳞癌组织中MDM2 mRNA表达率为22.6%,明显高于对照组,P<0.05.MDM2表达与组织分化程度无关,P>0.05.外阴鳞癌组织中p53蛋白表达阳性率为58.1%,明显高于对照组.突变型p53在低、中、高分化外阴鳞癌组中的表达率分别为87.5%、64.3%及22.2%,其表达率随着分化程度的降低而升高,低分化组中的表达率明显高于高分化组,P<0.05.MDM2基因扩增与p53蛋白表达呈正相关,P<0.05.结论MDM2基因过表达是外阴鳞癌发生、发展过程中较常见的分子事件;p53基因突变在外阴鳞癌发生、发展中起重要作用.检测p53蛋白可能对估计外阴鳞癌的预后有所帮助.     

MDM2在去分化脂肪肉瘤中的表达及临床意义

[目的]探讨鼠双微粒体2(MDM2)在去分化脂肪肉瘤(DDLPS)中的表达及其临床意义。[方法]选取2013年4月至2021年12月陆军军医大学陆军特色医学中心收治的27例DDLPS患者的组织标本,分别利用免疫组化和荧光原位杂交(FISH)法检测肿瘤组织中MDM2的表达,并收集患者影像学、治疗方式、随访信息等相关临床病理资料。采用χ2检验或Fisher确切概率法分析不同MDM2表达组间临床特征构成比差异。采用Kaplan-Meier和Log-rank法分析不同MDM2表达组间无复发生存期和总生存期的差异。[结果] 27例DDLPS患者中免疫组化检测MDM2的阳性表达率为55.6%,而FISH检测MDM2基因扩增阳性表达率为100%。MDM2表达与性别、年龄、吸烟史、饮酒史、肿瘤家族史、肿瘤部位、肿瘤大小、是否手术、临床分期均无显著性相关(P均>0.05)。免疫组化MDM2阴性患者中位无复发生存期为26个月,而MDM2阳性患者中位无复发生存期为10个月,差异有统计学意义(χ²=4.013,P=0.045)。[结论]免疫组化检测组织MDM2的表达可能作为DDLP...     

脂肪肉瘤中HSP70和mdm2与p53及Rb表达的关系

p53蛋白的异常表达存在于多种肿瘤中[1～3].我们过去的实验也表明,脂肪肉瘤中p53蛋白表达异常,且随肿瘤恶性程度增加而增加;脂肪肉瘤中存在着p53基因的突变,但脂肪肉瘤中p53基因突变与p53蛋白异常表达率并不平行[4].HSP热休克蛋白70 (Heat shock protein 70,HSP70)、mdm2可影响p53蛋白的表达在上皮源性肿瘤中报道较多[5～7],但脂肪肉瘤中HSP70、mdm2与p53蛋白异常表达的关系尚未见报道.本实验用免疫组织化学方法,对43例脂肪肉瘤HSP70、mdm2蛋白表达进行检测,并对它们在脂肪肉瘤中与p53、Rb蛋白表达的关系进行了初步探讨.     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

Religiosity and physical and emotional functioning among African American and White colorectal and lung cancer patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum

We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.