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1.
目的探讨恶性肿瘤家族史(MN-FH)与乳腺癌患者临床病理特征之间的关系。方法回顾性分析东南大学附属中大医院2016年1月—2018年12月收治的417例乳腺癌患者的临床病理资料,根据有无MN-FH分成两组。采用χ2检验分析两组患者临床病理特征之间的关系。结果417例乳腺癌患者中,有MN-FH者67例(16.1%)。有MN-FH组的患者有更高比例的脉管癌栓(P=0.046)和淋巴结转移(P=0.023),肿瘤更易表现为ER阴性(P=0.025)、PR阴性(P=0.031)和HER2阳性(P=0.041)。进一步亚组分析发现,有乳腺癌家族史的患者较无MN-FH的患者有更晚的肿瘤分期(P=0.011),肿瘤更易表现为三阴性和HER2扩增型(P=0.010)。其他恶性肿瘤家族史的患者较无MN-FH的患者有更高比例的脉管癌栓(P=0.036)和淋巴结转移(P=0.034)。结论有MN-FH的乳腺癌患者肿瘤恶性程度更高,对于有MN-FH的人群体检非常重要。 相似文献
2.
目的系统评价中国人群肿瘤家族史及与鼻咽癌之间的关系及相关强度,为我国鼻咽癌的防治策略提供依据。方法系统检索CNKI、万方和维普3个中文数据库及PudMed、ScienceDirect和SpringerLink 3个英文数据库2013-03之前发表的鼻咽癌病例对照研究及队列研究。文献检索、选取、信息提取及质量评价(NOS评分)均由2人独立进行。采用基于方差倒数加权的随机效应模型合并研究结果。结果纳入合格研究文献16篇,鼻咽癌患者7 478例,对照8 456例。肿瘤家族史与鼻咽癌患病的合并OR=2.63,95%CI为1.56~4.01;I2=49.2%,P=0.023;N=13;鼻咽癌家族史与鼻咽癌患病的合并OR=3.12,95%CI为2.47~3.78;I2=0,P=0.700;N=8。结合漏斗图及发表偏倚检验的结果,尚不能排除潜在的发表偏倚对结果的影响。结论在中国,肿瘤家族史,尤其是鼻咽癌家族史,会显著增加鼻咽癌的患病风险。 相似文献
3.
目的探讨有、无胃癌家族史的胃癌患者之间临床病理特征及预后的差异。方法回顾性分析2011年至2015年456例胃癌患者的临床病例资料,其中有胃癌家族史者102例。采用双侧χ~2检验分析有、无胃癌家族史患者的临床病理特征;生存分析用Kaplan-Meier法,并行Log-rank检验;用Cox比例风险模型分析影响胃癌预后的因素。结果在有胃癌家族史的患者中,年龄≥50岁、肿瘤最大径<5 cm、组织学分级为Ⅰ~Ⅱ级以及M_0分期的比例均显著高于无胃癌家族史者(P<0.05)。有胃癌家族史患者的中位总生存时间(OS)为56.1个月,高于无胃癌家族史者的51.0个月(P=0.318);但在发病年龄<50岁的亚组中,有胃癌家族史患者的中位OS显著优于无胃癌家族史患者(未达vs.53.0个月,P=0.021)。Cox比例风险模型显示,影响有胃癌家族史患者OS的因素为N分期和M分期(P<0.05),影响无胃癌家族史患者OS的因素为肿瘤最大径、肿瘤部位和M分期(P<0.05)。结论有、无胃癌家族史的胃癌患者之间存在临床病理特征的差异,其OS亦可能存在差异。 相似文献
4.
目的探讨恶性肿瘤家族史与子宫内膜癌发病的关系。方法回顾性分析303例子宫内膜癌患者和同期收治的425例功能失调性子宫出血患者的临床资料,统计并比较分析2组直系亲属恶性肿瘤的发病情况。结果子宫内膜癌患者直系亲属恶性肿瘤发病率为22.1%(67/303),而功能失调性子宫出血患者直系亲属恶性肿瘤发病率为4.9%(21/425)。差异有统计学意义(P<0.05)。结论子宫内膜癌的发病与恶性肿瘤家族史关系密切。 相似文献
5.
吸烟与Ⅲ~ⅣA期鼻咽癌预后关系 总被引:1,自引:0,他引:1
目的 研究显示,吸烟示鼻咽癌致病因子之一,但吸烟对鼻咽癌预后的影响暂不明确.本研究探讨评价吸烟对Ⅲ~ⅣA期鼻咽癌(nasopharygeal carcinoma,NPC)患者预后的影响,探讨晚期NPC患者中吸烟者戒烟的必要性.方法 回顾性分析2008-05-01-2012-05-31广州医科大学附属肿瘤医院确诊为初治、无转移的Ⅲ~ⅣA期330例NPC患者.按有无吸烟分为吸烟组(158例)和非吸烟组(172例),统计分析吸烟与晚期NPC复发、转移与预后的关系.定性资料采用x2检验,采用Kaplan-Meier法进行生存分析,差异比较应用Log-rank法,采用Cox风险回归模型进行预后因素分析.结果 吸烟组和非吸烟组4年总生存率(overall survival,OS)分别为72.2%和84.9%,P=0.034;无局部复发生存率(locoregional recurrence-fee survival,LRFS)分别为78.4%和89.1%,P=0.01.吸烟组和非吸烟组4年无远处转移生存率(distant metastasis-freesurvival,DMFS)分别为71.1%和77.5%,P=0.290;无进展生存率(progression-free survival,PFS)分别为59.6%和69.6%,P=0.068.多因素分析发现,临床分析吸烟和N分期均是患者OS的独立预后因素,因临床分期对预后影响明显,故依据OS的吸烟和N分期2个独立预后因素,将患者分为低危组(无吸烟者与N0+N1期)、中危组(无吸烟者与N2 +N3期和有吸烟者和N0+N1期)和高危组(有吸烟者和N2+N3期).经生存分析示,低危组、中危组和高危组4年OS分别为88.2%、84.7%和68.3%,P=0.010;LRFS分别为94.1%、88.7%和74.6%,P=0.005;DMFS分别为88.2%、79.6%和63.3%,P=0.025;PFS分别为82.4%、71.4%和51.2%,P=0.002;差异均有统计学意义.结论 吸烟是Ⅲ~ⅣA期NPC的不良预后因素.吸烟且N分期越晚者,生存率越低,对该部分患者需严密随访,建议戒烟. 相似文献
6.
目的:探讨恶性肿瘤家族史(familial history of malignant neoplasm,MN-FH)对胃癌贡献比例及与临床病理特征之间的关系。方法:回顾我院2010年1月-2014年12月间收治的资料齐全的310例胃癌患者的临床病理资料,以有无肿瘤家族史分组,利用SPSS软件统计分析组间临床病理特征关系。结果:96例(31.0%)胃癌患者具有肿瘤家族史,其一级和二级亲属中共有64例(66.7%)具有消化道相关肿瘤,包括食管癌(19.8%)、胃癌(24.0%)、肝癌(6.3%)和结直肠癌(16.7%)。泌尿系肿瘤占12.5%,其他(包括甲状腺癌、乳腺癌、喉癌等)占20.8%。相关性分析显示有无肿瘤家族史在性别及肿瘤发生部位均没有差异(P>0.05)。病理分型显示有MN-FH的胃癌患者以低分化、未分化多见,占60.4%(58/96),无MN-FH占12.6%(27/214),两组相比,P<0.05。而在高、中分化腺癌类型上则相反,有MN-FH胃癌组占39.6%,无MN-FH胃癌组占87.3%,P<0.05。胃癌临床分期显示有MN-FH多以Ⅲ、Ⅳ期为主(73.0%),无MN-FH组以Ⅱ期为主(57.9%),两组相比,P<0.05,具有显著性差异。结论:我院超过1/3的胃癌患者具有阳性MN-FH。其中最常见的MN-FH是消化道肿瘤。MN-FH胃癌具有分化程度低,病理特征恶性程度高特点。对于有家族史人群定期体检非常重要,早诊和早治是提高生存率的关键。 相似文献
7.
肿瘤家族史与卵巢恶性肿瘤发病的关系 总被引:1,自引:0,他引:1
目的:探讨恶性肿瘤家族史与卵巢恶性肿瘤发病的关系。方法:对531例卵巢肿瘤患者的临床资料进行回顾性分析。结果:良性卵巢肿瘤435例,有恶性肿瘤家族史者19例,占4.37%;恶性卵巢肿瘤96例,有恶性肿瘤家族史者11例,占11.5%。结论:卵巢恶性肿瘤患者有恶性肿瘤家族史者发病率明显高于良性肿瘤患者。 相似文献
8.
恶性肿瘤家族史与子宫内膜癌关系的流行病学研究 总被引:1,自引:0,他引:1
目的 研究一级亲属恶性肿瘤家族史与子宫内膜癌的关系。方法 采用全人群病例对照研究的方法,收集1997年1月-2000年6月诊断的30-69岁,具有上海市区常住户口的子宫内膜癌病例及其对照一级亲属的恶性肿瘤家族史,分析恶性肿瘤史在病例与对照组一级亲属的恶性肿瘤家族史,分析恶性肿瘤史在病例与对照组一级亲属中的分布情况及其对子宫内膜癌发生的影响。结果 病例组中有较多的一级亲属患有恶性肿瘤(调整OR=1.3,95%CI1.0-1.7),尤其是结肠直肠癌(CRC)(调整OR6.1,95%CI1.8-21.1)和子宫内膜癌(调整OR4.8,95%CI1.0-22.1)。调整年龄、一级亲属人数、体质指数(BMI)、腰围 臀围比(WHR)、月经生育史和避孕药的使用、饮食等可能的混杂因素进行非条件Logistic回归分析发现,一级亲属中恶性肿瘤史、子宫内膜癌家施行史和CRC家族史的OR值仍有意义,且分别上升为1.4(95%CI1.1-1.9),5.2(95%CI1.1-25.3)和8.9(95%CI2.5-31.3),但家庭史和这些危险因素对子宫内膜癌的发生无交互作用。一级亲属中恶性肿瘤史、子宫内膜癌家庭史和CRC家族史的人群归因危险度分别为9.5%、1.6%和3.2%。结论 研究结果表明,子宫呐膜癌具有明显的家族聚集性。子宫内膜癌和结肠直肠癌家族史是子宫内膜癌发生的独立的危险因素。 相似文献
9.
为探讨鼻咽癌咽旁间隙侵犯与预后的关系,我们对1987年6月一1992年6月间收治的有病理证实且疗前咽旁间隙受侵的鼻咽癌患者104例进行了分析,现报告如下。1临床资料1.1一般资料男81例,女23例,男:女=1:0.3,年龄在20岁~80岁之间,所有病... 相似文献
10.
血管内皮生长因子与鼻咽癌预后的关系 总被引:3,自引:0,他引:3
鼻咽癌 (NPC)治疗后失败的主要原因是复发及远地转移 ,近年研究表明 ,肿瘤的生长及远地转移与肿瘤诱导血管生成密切相关。检测 75例NPC组织中血管内皮生长因子(VEGF)的表达 ,以探讨NPC中VEGF的表达与其复发、转移及生存期的关系。一、材料与方法1 .临床资料 :1991年 1月至 1995年 12月在本科接受治疗的 75例NPC ,男 49例 ,女 2 6例 ;年龄在 14~ 75岁之间 ,中位年龄 46岁 ;均为初次治疗 ,病检标本为治疗前经鼻咽活检取材。根据福州分期 ,T1期 2 6例 ,T2 期 2 5例 ,T3 期 18例 ,T4期 6例 ;N0 期 13例 ,N1期 31例 ,… 相似文献
11.
Background:
Family history of cancer is associated with developing nasopharyngeal carcinoma (NPC); however, the impact of it on survival among established NPC patients remains unknown.Methods:
We retrospectively analysed 1773 southern Chinese patients. Associations between a first-degree family history of NPC and overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated by Cox regression.Results:
Among 1773 patients, 207 (11.7%) reported a first-degree family history of NPC. Compared with patients without a family history, the adjusted hazard ratios among those with it were 0.60 (95% confidence interval (CI), 0.37–0.98; P=0.040) for OS, 0.52 (95% CI, 0.24–1.12; P=0.096) for LRFS and 0.51 (95% CI, 0.27–0.97; P=0.040) for DMFS. There were trends for improving OS, LRFS and DMFS with increasing number of affected relatives (Ptrend: 0.050, 0.114 and 0.044, respectively). But no significant benefits of family history in second- or third-degree relatives were observed. In subgroup analysis, we observed the effects of family history with restriction to male patients and those of advanced stage and treated with conventional radiotherapy and addition of chemotherapy.Conclusion:
A first-degree family history of NPC is associated with improved survival of patients. 相似文献12.
Katja K. Aben J. Alfred Witjes Sita H. Vermeulen 《International journal of cancer. Journal international du cancer》2015,136(5):1117-1124
A history of urinary bladder cancer (UBC) in first‐degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first‐degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non‐muscle‐invasive bladder cancer (NMIBC) and 250 muscle‐invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence‐free survival (RFS) and progression‐free survival (PFS) of NMIBC patients according to self‐reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan‐Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance‐index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first‐degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non‐significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53–1.07) and 0.45 (95% CI = 0.18–1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan‐Meier 10‐year risk: 41% and 25%) died within 10 years. Family history did not improve the c‐index of prediction models. This study shows that a first‐degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. 相似文献
13.
Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma
Xiao-Lin Luo Guang-Zheng Zhong Li-Yang Hu Jie Chen Ying Liang Qiu-Yan Chen Qing Liu Hui-Lan Rao Kai-Lin Chen Qing-Qing Cai 《Oncotarget》2015,6(41):44037-44048
Background
We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC).Patients and methods
We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I.Results
The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis.Conclusion
Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC. 相似文献14.
Spangler E Zeigler-Johnson CM Malkowicz SB Wein AJ Rebbeck TR 《International journal of cancer. Journal international du cancer》2005,113(3):471-474
Genetic factors may be used not only to assess risk of prostate cancer development but also to evaluate prostate cancer outcomes including clinical prognosis, treatment methods, and treatment response. To assess the role of family history on prostate cancer outcomes, we evaluated tumor characteristics, diagnostic precursors and biochemical (prostate specific antigen) relapse-free survival in men with and without a family history of prostate cancer. A total of 684 prostate cancer cases unselected for family history were identified from an ongoing hospital based prostate cancer case-control study between 1995 and 2002. Self-reported family history was grouped within the following categories: none, any, moderate (one affected first or second degree relative) and high (2 or more affected first or second degree relatives). We further considered groups defined by early (before age 60) and late (after age 60) age at diagnosis. Overall, tumor stage was not significantly associated with any (odds ratio [OR] = 1.43 95% confidence interval [CI] = 1.00-2.05) or moderate (OR = 1.48, 95% CI = 1.0-2.19) family histories. Men diagnosed before age 60, however, had higher tumor stages if they had any (OR = 2.19, 95% CI = 1.28-3.75) or moderate (OR = 2.15, 95% CI = 1.2-3.9) family histories. Men diagnosed after age 60 with any family history were significantly more likely to experience biochemical (PSA) failure (Hazard ratio [HR] = 2.60, 95%CI = 1.08-6.25). Men with any and moderate family histories were at significantly increased risk of biochemical failure (HR = 2.49, 95%CI = 1.25-4.95 and HR = 2.46, 95% CI = 1.17-5.16, respectively). Moderate family history increased probability of seminal vesicle invasion (OR = 2.14, 95%CI = 1.06-4.34). Our results suggest that a family history of prostate cancer may be associated with predictors of clinical outcome in prostate cancer cases unselected for a family history of prostate cancer. 相似文献
15.
Ng WT Yau TK Yung RW Sze WM Tsang AH Law AL Lee AW 《International journal of cancer. Journal international du cancer》2005,113(6):998-1001
Nasopharyngeal carcinoma (NPC) is well known for its peculiarly skewed distribution with highest incidence in Southern Chinese population. Familial aggregation is evident, hence screening for early detection is offered by oncology centers in Hong Kong to first-degree relatives of patients with NPC. During the period 1994-2001, 929 family members were screened in our center. The screenees were advised to attend an annual examination that includes serological test against Epstein Barr Virus (EBV), physical examination to exclude cervical lymphadenopathy and cranial nerve palsy, and endoscopic examination of the nasopharyngeal region. Two different methods were used for the serology test: indirect immuno-fluorescent (IF) test for IgA against viral capsid antigen; and starting in 1997 enzyme-linked immunosorbent assay (ELIZA) against nuclear antigen and viral capsid antigen. Twelve cases of nasopharyngeal carcinoma were diagnosed, giving a detection rate of 5/1,155 (433/100,000) person-year for male and 7/1,404 (499/100,000) person-year for female participants observed. The corresponding average annual incidence in Hong Kong during this period was 24.1 and 9.6 per 100,000, respectively. Forty-one percent of these detected cases had Stage I disease, whereas only 2% of patients referred to the department for primary treatment presented with such early disease. Six cases were detected at first visit, and all were EBV-positive. Another 78 screenees with positive serology at first visit were followed up for 204 person years, and thus far NPC was detected in 3 after an interval of 6-32 months. Of the 845 initially EBV-negative screenees followed up for 2,337 person-years, NPC was detected in 3 after an interval of 12-45 months. One showed sero-conversion at the time of diagnosis. We conclude that family members of known patients do show a substantially higher risk of developing NPC, and regular screening by current method improves the chance of early detection. 相似文献
16.
新辅助化疗联合放疗治疗中晚期鼻咽癌的疗效观察 总被引:3,自引:0,他引:3
目的研究新辅助化疗在治疗中晚期鼻咽癌(NPC)中的疗效。方法63例中晚期NPC病人随机分为单纯放疗组30例、新辅助化疗联合放疗组33例。化疗方案PFL方案(DDP80mg/m2~100mg/m2,d1;5-FU3.5/m248h;CF0.3,d1),共2~3疗程;化疗后2周常规放射治疗鼻咽癌原发灶DT68.0Gy/7周,颈转移灶DT65.0Gy/6周,颈预防剂量55.0Gy。结果新辅助化疗联合放疗组原发灶及颈转移灶完全缓解率优于单纯放疗组,毒性反应与单纯放疗组相比无明显差异。结论新辅助化疗联合放疗可提高中晚期NPC患者近期肿瘤缓解率,毒性反应可耐受,但远期生存率需进一步观察。 相似文献
17.
Uchino K Tateishi R Shiina S Kanda M Masuzaki R Kondo Y Goto T Omata M Yoshida H Koike K 《Cancer》2011,117(19):4475-4483
BACKGROUND:
Despite significant advances in the treatment of intrahepatic lesions, the prognosis for patients with hepatocellular carcinoma (HCC) who have extrahepatic metastasis remains poor. The objective of this study was to further elucidate the clinical course and prognostic determinants of patients with this disease.METHODS:
In total, 342 patients who had HCC with extrahepatic metastasis were enrolled. The metastases were diagnosed at initial presentation with HCC in 28 patients and during follow‐up in the remaining patients. The authors analyzed clinical features, prognoses, and treatments and established a scoring system to predict prognosis using a split‐sample method with a testing set and a training set.RESULTS:
The most frequent site of extrahepatic metastasis was the lung followed by lymph nodes, bone, and adrenal glands. These metastases were related directly to death in only 23 patients (7.6%). The median survival after diagnosis of extrahepatic metastasis was 8.1 months (range, 0.03‐108.7 months). In univariate analysis of the training set (n = 171), performance status, Child‐Pugh classification, the number and size of intrahepatic lesions, macroscopic vascular invasion, symptomatic extrahepatic metastases, α‐fetoprotein levels, and complete responses to treatment were associated significantly with prognosis. On the basis of multivariate analysis, a scoring system was developed to predict prognosis that assessed uncontrollable intrahepatic lesions, extent of vascular invasion, and performance status. This scoring system was validated in the testing set (n = 171) and produced a concordance index of 0.73.CONCLUSIONS:
The controllability of intrahepatic lesions and performance status were identified as important prognostic factors in patients with advanced HCC who had extrahepatic metastasis. Cancer 2011. © 2011 American Cancer Society. 相似文献18.
目的:探讨诱导加同期化放疗及同期化放疗对N晚期鼻咽癌患者的远期临床疗效。方法:选取160例N晚期鼻咽癌患者,分为诱导加同期化放疗组80例(A组)和同期化放疗组80例(B组),两组放疗方法相同。A组在放疗前给予2个周期诱导化疗,DDP 20mg/m2,d1-5,5-FU 500mg/m2,d1-5,21天为1周期。两组均于放疗第1周及放疗第4周给予DDP 20mg/m2,d1-3,5-FU 500mg/m2,d1-3,同期化疗。结果:A组和B组5年总生存率(OS)分别为67.5%和51.3%(P<0.05);5年无进展生存率(PFS)分别为65.0%和48.8%(P<0.05);局部复发率分别为17.5%和22.5%(P>0.05);远处转移率分别为13.8%和27.5%(P<0.05)。结论:诱导加同期化放疗可提高N晚期鼻咽癌患者的5年OS、PFS。 相似文献
19.
目的:回顾性分析局部晚期鼻咽癌患者外周血中淋巴细胞与单核细胞比例(lymphocyte-to-monocyte ratio,LMR)与预后的相关性。方法:收集既往接受同期放化疗的219例Ⅲ/Ⅳa,b期(AJCC第7版分期)鼻咽癌患者,采用外周血中LMR中位值4.31作为阈值来对所有患者进行分层。Log-rank检验对生存结果进行分析。主要生存终点为无进展生存率(PFS)。结果:低LMR值组(<4.31)与更差的T分期(P=0.038)、N分期(P=0.004)、临床分期(P=0.005)、EBV DNA(P=0.000)和死亡(P=0.050)相关。低LMR值组(<4.31)与高LMR值组(≥4.31)患者4年PFS分别为68.2%vs 77.8%(P=0.048)。Cox风险模型多因素分析显示影响PFS的预后因素为N分期(HR=3.27,95%CI=1.72~5.27;P=0.032)、临床分期(HR=1.72,95%CI=1.08~2.43;P=0.001)和EBV DNA(HR=3.55,95%CI=2.50~7.53;P<0.001),而LMR(HR=0.43,95%CI=0.37~1.05;P=0.057)不是独立的预后因素。结论:LMR值下降提示鼻咽癌患者更晚的分期和更差的预后,但对生存的总体预测作用低于传统的AJCC分期和EBV DNA。 相似文献
20.
Hu ZY Zhu XF Zhong ZD Sun J Wang J Yang D Zeng YX 《International journal of cancer. Journal international du cancer》2008,123(10):2418-2429
Nasopharyngeal carcinoma (NPC) is a common malignant tumor in South China. It has been reported that overexpression of antiapoptotic Bcl-2 family proteins in NPC has caused the lack of long-term efficacy of conventional therapies. Apogossypolone (ApoG2), a novel small-molecule inhibitor of antiapoptotic Bcl-2 family proteins, has been discovered as the optimized derivative of gossypol. In this study, we found that in NPC cells, ApoG2 totally blocked the antiapoptotic function of Bcl-2 family proteins without affecting the expression levels of these proteins. ApoG2 selectively inhibited proliferation of 3 NPC cell lines (C666-1, CNE-1 and CNE-2) that highly expressed the antiapoptotic Bcl-2 proteins. This inhibitory activity was associated with release of cytochrome c, activation of caspase-9 and caspase-3 and apoptosis of sensitive NPC cells. However, ApoG2 had no obvious inhibitory effect on NPC cell line HONE-1, which expressed antiapoptotic Bcl-2 and Bcl-xL at a low level. We further found that ApoG2 effectively suppressed tumor growth of NPC xenografts in nude mice and enhanced the antitumor effect of CDDP (cisplatin) on NPC cells in vitro and in vivo. Immunohistochemical results showed that the expression of CD31 decreased after ApoG2 treatment, which suggested inhibition of angiogenesis in NPC xenografts. Our findings strongly suggest that ApoG2 may serve as a novel inhibitor of Bcl-2 family proteins and, by targeting these proteins, may become a promising drug for the treatment of NPC. 相似文献