C—erbB2、PCNA、ER、PR在126例乳腺癌中的表达及临床意义

目的：研究C—erbB2、PCNA、ER、PR在乳腺癌中的表达及其与乳腺癌临床、病理因素之间的关系。方法：采用免疫组化SP法检测126例乳腺癌组织CerbB2、PCNA、ER、PR蛋白的表达。结果：C—erbB2、pCNA、ER、PR在乳腺癌阳性表达率分别为：36．5％,95．2％,65．1％,54％。C—erbB2、pCNA、ER、PR蛋白阳性表达率和表达强度与乳腺癌患者的年龄、淋巴结转移、肿瘤大小、pTNM分期差异性无统计学意义（P〉0．05）。C—erbB2、PCNA与组织学分级差异具有统计学意义（P〈0．05）。C—erbB2与ER、PR均呈负相关（r=-0．344,P=0．000;r=-0．226,P=0．011）。结论：C—erbB2,PCNA过表达者预后差,可以作为判断乳腺癌患者预后的有效指标。     

399例蒙古族患者乳腺癌ER、PR、C-erbB2、p53、PCNA的表达及其临床意义

目的探讨雌孕激素受体(ER、PR)、原癌基因(C-erbB2)、抑癌基因(p53)、增殖细胞核抗原(PCNA)与蒙古族患者乳腺癌组织学分级、肿瘤大小、淋巴结转移及术后生存期的关系.方法收集399例乳腺癌标本,均为本院病理科外检存档资料.利用免疫组化技术对ER、PR、C-erbB2、p53和PCNA进行检测,使用S-P法,DAB显色.结果 ER、PR阳性表达率随乳腺癌分级升高而降低.C-erbB2、p53、PCNA阳性表达率随着乳腺癌分级的升高而升高.C-erbB2、p53、PCNA SⅡ值在术后生存期＜5年组表达率高,而在术后生存期≥5年组表达率低.C-erbB2、p53、PCNA与淋巴结转移个数呈正相关,与ER、PR呈负相关.结论 ER、PR是用于判断预后、指导内分泌治疗的一项重要指标.C-erbB2、p53及 PCNA可为判断预后提供依据.     

乳腺癌组织中HPA蛋白的表达及其与ER、PR、HER-2、P53表达的相关性

目的 探讨乙酰肝素酶(heparanase,HPA)蛋白在乳腺癌组织中表达的临床意义及其与雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体2(HER2)、P53表达的关系.方法 采用免疫组化S-P法检测78例乳腺癌组织中HPA蛋白的表达.结果HPA蛋白在乳腺癌组织中的阳性表达率为69.2％.HPA蛋白在乳腺癌组织中的表达与乳腺癌患者年龄、肿瘤大小无关(P＞0.05),与淋巴结转移、临床分期有关(P＜0.05).HPA蛋白在乳腺癌组织中的表达与ER、PR蛋白的表达无明显相关性(r=0.178、0.056,P＞0.05),与HER-2、P53蛋白表达呈正相关关系(r=0.436、0.310,P＜0.05).结论 HPA蛋白可能与乳腺癌疾病进展有关,且与HER-2、P53蛋白表达呈正相关关系.     

乳腺癌nm23基因和雌、孕激素受体表达及其临床意义

[目的]研究nm23基因,雌激素受体(ER)、孕激素受体(PR)在乳腺癌中的表达及临床意义.[方法]应用免疫组化SP法检测60例临床及随访资料完整的乳腺癌患者标本nm23、ER、PR的表达,结合临床表现及随访结果作统计学分析.[结果]nm23、ER、PR阳性表达率分别为60.0%、73.3%、66.7%.nm23阳性表达与临床分期相关(P＜0.05).nm23基因的表达与乳腺癌远处转移及腋淋巴结转移呈显著负相关(P＜0.05),与生存率呈正相关(P＜0.05).ER、PR阳性表达率与年龄、临床分期和淋巴结转移无关(P＞0.05).ER、PR的阳性表达与乳腺癌远处转移呈显著负相关(P＜0.05),与生存率呈正相关(P＜0.05).在判断转移和预后方面,ER( )PR( )与nm23基因阳性表达之间存在着正相关性.[结论]检测乳腺癌组织nm23、ER、PR对评价乳腺癌患者的预后和指导临床治疗有重要价值.     

乳腺癌超声征象与雌激素受体、孕激素受体及C-erbB-2表达的相关性分析

目的 探讨乳腺癌超声征象与雌激素受体(ER)、孕激素受体(PR)及C-erbB-2表达的相关性.方法 选取的82例乳腺癌患者均接受超声检查,观察肿瘤大小、分级、类型、淋巴结转移及脉管侵犯情况等;免疫组化法检测乳腺癌患者乳腺癌组织中ER、PR及C-erbB-2的阳性表达率,并分析不同超声征象与ER、PR及C-erbB-2阳性表达的相关性.结果 82例乳腺癌患者乳腺癌组织中ER、PR及C-erbB-2的阳性表达率分别为60.98％、58.54％和48.78％.不同边缘情况、恶性晕环情况、淋巴结转移情况和后方回声衰减情况乳腺癌患者乳腺癌组织中ER阳性表达率比较,差异均有统计学意义(P﹤0.05).不同边缘情况、淋巴结转移情况乳腺癌患者乳腺癌组织中PR阳性表达率比较,差异均有统计学意义(P﹤0.05).不同微钙化情况、血流情况、淋巴结转移情况乳腺癌患者乳腺癌组织中C-erbB-2阳性表达率比较,差异均有统计学意义(P﹤0.05).肿瘤边缘毛刺征与ER、PR的阳性表达均呈正相关(P﹤0.05),恶性晕环、后方回声衰减与ER的阳性表达均呈正相关(P﹤0.05),肿瘤微钙化、血流丰富与C-erbB-2的阳性表达均呈正相关(P﹤0.05),腋窝淋巴结转移与ER、PR的阳性表达呈负相关(P﹤0.05),与C-erbB-2的阳性表达呈正相关(P﹤0.05).结论 乳腺癌患者超声征象与ER、PR及C-erbB-2阳性表达存在一定的相关性,在预测乳腺癌生物学特性中具有一定指导价值.     

乳腺癌雌孕激素受体与C-erbB-2、p53、nm23基因表达及相关分析

目的观察乳腺癌组织中雌、孕激素受体(ER、PR)与C-erbB-2、p53、nm23基因表达及其相互关系,及乳腺癌淋巴结转移与基因表达关系.方法应用免疫组织化学方法对85例乳腺癌进行了ER、PR、CerbB-2、p53、nm23检测,结果作统计学分析.结果(1)ER、PR阳性表达率分别为63.52%和72.94%;(2)C-erbB-2、p53、nm23的表达率各为68.23%、32.94%、63.52%;(3)ER、PR阳性患者的C-erbB-2或p53的阳性表达明显低于ER、PR阴性患者(P＜0.05);(4)淋巴结有转移的乳腺癌患者nm23阳性表达明显低于无淋巴结转移的患者(P＜0.05),p53表达则在有淋巴结转移者的乳癌中表达高(P＜0.01).结论ER、PR与C-erbB-2、p53、nm23这两种不同特性产物在乳腺癌组织中有一定的内在联系,p53、nm23的阳性表达对判断乳癌的肿瘤转移及预后有重要意义.     

乳腺癌雌、孕激素受体与腋淋巴结转移的关系

目的探讨乳腺癌雌、孕激素受体(ER、PR)与淋巴结转移之间的关系.方法应用免疫组织化学方法对257例乳腺癌组织石蜡切片进行ER、PR检测,将ER、PR结果与病理检出淋巴结的结果进行统计学分析.结果 ER、PR的阳性表达率分别为63.27%和59.27%.在ER、PR的4种组合中淋巴结转移率基本相同,经统计学处理均无显著差异(P＞0.05).结论乳腺癌组织中的ER、PR阳性表达与淋巴结转移无关.ER、PR测定对指导内分泌治疗和估计预后有重要意义.     

乳腺癌ER、PR、p53及C—erbB-2癌基因的多因素分析

目的:探讨乳腺癌组织ER、PR、 p53及c-erbB-2 癌基因蛋白表达与淋巴结转移、患者年龄及组织学类型的相关性.方法: 采用乳腺组织免疫组化SP法检测124例乳腺癌患者中ER、PR、 p53及c-erbB-2的表达,并分析其临床意义.结果:ER、 PR 的阳性表达率与淋巴结转移、患者年龄及组织学类型的无关.(P>0.05),ER、 PR 与 p53及c-erbB-2、表达之间存在负相关性,p53、 c-erbB-2 阳性表达率与有无淋巴结转移、年龄有关(P<0.05),与组织学类型无关(P> 0.05).结论:ER、PR、 p53及c-erbB-2 的检测对乳腺癌治疗方案的制定和预后估计有重要临床意义.     

多种基因突变、蛋白表达异常与乳腺癌发生、发展及预后

目的: 探讨乳腺癌p53基因突变及突变类型与预后的关系,p53、Bcl-2、C-erbB-2、PCNA和Ki67表达与乳腺癌变、发展的关系,并比较乳腺癌p53基因突变与蛋白表达检测结果.方法:应用PCR-SSCP方法检测45例乳腺癌的基因突变,应用免疫组化SP方法检测96例正常乳腺组织、异型增生和乳腺癌的蛋白表达.结果:乳腺癌p53基因突变及突变类型杂合性缺失(LOH)与不良预后因素(PCNA高表达,ER、PR阴性)显著相关(P<0.05或P<0.01).乳腺癌变、发展过程(正常乳腺组织→异型增生→淋巴结阴性→淋巴结阳性)的p53、C-erbB-2、PCNA和Ki67表达率渐增(P<0.05或P<0.01),而Bcl-2表达率渐减(但P>0.05).乳腺癌p53基因突变与蛋白表达检测结果基本吻合.结论:p53基因突变(尤其是杂合性缺失)是乳腺癌预后不良的因素和指标.p53、C-erbB-2、PCNA和Ki67高表达是乳腺癌变、发展的因素和指标,其中C-erbB-2、PCNA和Ki67表达的检测对癌前病变的鉴别诊断及恶变可能性估计有指导意义.免疫组化法结果有临床参考价值.     

DNA复基因XRCC1基因多态性与乳腺癌临床病理参数的相关性

目的:研究XRCC1基因Arg194Trp和Arg399Gln多态性与中国女性乳腺癌临床病理参数的关系,探讨其在乳腺癌预后中的潜在意义.方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法.对250例原发性乳腺癌患者进行XRCC1基因Arg194Trp、Arg399Gln多态性分析,用Pearson χ2检验分析基因型与临床病理特征的关系.结果:XRCC1基因Arg194Trp和Arg399Gln多态性与乳腺癌患者的月经状态、肿瘤大小、腋窝淋巴结转移、TNM分期、雌激素受体均无显著相关性(P＜0.05).但该多态位点与乳腺癌患者的孕激素受体(PR)状态和C-erbB2蛋白表达显著相关.携带194纯合突变型的患者PR阴性率(81.0%)显著高于携带194野生型和杂合型患者(55.4%),(P=0.034);携带399纯含突变型的患者C-erbB2蛋白表达阳性率(61.1%)显著高于携带399野生型和杂合型的患者(29.3%),(P=0.006).结论:PR阴性和(或)C-erbB2高表达的乳腺癌患者常提示预后不良.XRCC1基因多态性与PR阴性或C-erbB2高表达显著相关,提示携带XRCC1纯合突变(194或399)乳腺癌患者可能预后不良.     

Fat, fiber, fruits, vegetables, and risk of colorectal adenomas

A case-control study was conducted at the National Naval Medical Center (Maryland, USA) from 1994 to 1996 to investigate the possible association between dietary factors and colorectal adenomas. Cases (n = 239) were subjects diagnosed with adenomas (146 new and 93 recurrent) by sigmoidoscopy or colonoscopy. Those with no evidence of adenomas found by sigmoidoscopy were recruited as controls (n = 228). Dietary variables, assessed by a 100-item food frequency questionnaire, were analyzed by the logistic regression model, which was adjusted for age, gender and total energy intake. Variables of fat intake were further adjusted for red meat intake. An increased risk of 7% [odds ratio (OR): 1.07; 95% confidence interval (95% CI): 0.94-1.22] per 5% energy/day from total fat was observed. Every additional 5% unit of oleic acid intake/day significantly increased the adenoma risk by 115% (OR: 2.15; 95% CI: 1.05-4.39). Red meat fat increased the risk by 20% (OR: 1.20; 95% CI: 0.71-2.04), and white meat fat decreased the risk by 67% (OR: 0.33; 95% CI: 0.19-0.95) for every additional 5% unit of respective intake/day. Risk decreased by 41% (OR: 0.59; 95% CI: 0.41-0.86) for every additional 5% unit of fiber intake/day. Vegetable [OR per 100 g of vegetable intake/day: 0.83, 95% CI: 0.67-1.04] and fruit (OR per 100 g of fruit intake/day: 0.92, 95% CI: 0.82-1.03) intake showed an inverse association, and the results are suggestive of an association with the risk for adenomas. In conclusion, a strong positive association between oleic acid intake and colorectal adenoma risk was observed. This is likely to be an indicator of "unhealthy" food (meat, dairy, margarine, mayonnaise, sweet baked food) consumption in this population. Increased intake of dietary fiber was associated with a moderately decreased risk of adenomas.     

Susceptibility of Ureaplasma urealyticum to Tetracycline,Doxycycline, Erythromycin,Roxithromycin, Clarithromycin,Azithromycin, Levofloxacin and Moxifloxacin

Abstract

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The miC50 and miC90 of the tested agents after 24 h of incubation were as follows: Tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC₉₀). Overall, moxifloxacin was the most active agent in vitro against U. Urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.     

Occurrence,Efficacy, Metabolism,and Toxicity of Triclosan

Triclosan has broad-spectrum anti-microbial activity against most gram-negative and gram-positive bacteria. It is widely used in personal care products, household items, medical devices, and clinical settings. Due to its extensive use, there is potential for humans in all age groups to receive life-time exposures to triclosan, and, indeed, triclosan has been detected in human tissues and the environment. Data gaps exist regarding the chronic dermal toxicity and carcinogenicity of triclosan, which is needed for the risk assessment of triclosan. The US Food and Drug Administration (FDA) nominated triclosan to the National Toxicology Program (NTP) for toxicological evaluations. Currently, the NTP is conducting several dermal toxicological studies to determine the carcinogenic potential of triclosan, evaluate its endocrine and developmental-reproductive effects, and investigate the potential UV-induced dermal formation of chlorinated phenols and dioxins of triclosan. This paper reviews data on the human exposure, environmental fate, efficacy of anti-microbial activity, absorption, distribution, metabolism and elimination, endocrine disrupting effects, and toxicity of triclosan.     

Age,Race, Sex,Stage, and Incidence of Cutaneous Lymphoma

BackgroundThe incidence of the T- and B-cell CLs has been well documented, but information pertaining to racial incidence by age, and by burden of disease (stage) have not been extensively documented.Materials and MethodsThe SEER 2004-2008 public use database was investigated. The relative incidence of CL in different races and age groups was examined. Univariate and multivariate stepwise logistic regression was performed for the likelihood of presenting at a higher stage.ResultsOf 4496 patients diagnosed with CL between 2004 and 2008; 1713 patients were diagnosed with MF, 1518 with non-MF cutaneous T-cell lymphoma, and 1265 patients with cutaneous B-cell lymphoma. For MF, there was a trend for females to be less likely to present with a higher T-stage (T3-T4) than males (odds ratio [OR], 0.73) on multivariate analysis (P = .06). For race, AA had a significantly increased risk of presenting with higher T-stage (T3-T4) MF (OR, 1.72) on multivariate analysis (P = .02), compared with white patients. For white, AA, Asian/Pacific Islander, and Native American/other/unknown, the mean age at diagnosis was 59.2, 51.5, 51.3, and 53.8. These groups presented at a significantly different age than white (P = .0001, 0.0001, and 0.0006).ConclusionNonwhite racial groups present with MF at an earlier age compared with white, and AA have increased risk of presenting with higher T-stage compared with white. These findings have significant implications regarding need for earlier diagnosis and understanding the reasons for racial disparity in age and stage of presentation.     

Tobacco, alcohol, diet, occupation, and carcinoma of the esophagus

Information on occupation, smoking, food and beverage consumption, and medical history were compared between 275 incident cases of carcinoma of the esophagus and 275 neighborhood controls who were matched to the cases on age (within 5 years), race, and sex. Tobacco use, mainly cigarette smoking, was a significant risk factor for carcinoma of the esophagus. Ex-smokers of cigarettes showed a reduced risk relative to those who continued to smoke, and current smokers of two or more packs per day displayed a higher risk than those who smoked less. Alcohol consumption was another significant risk factor for carcinoma of the esophagus; there was a highly significant trend with average daily dose of ethanol. Relative to controls, cases also consumed significantly more fried bacon or ham, less fresh fruits and raw vegetables, and were more likely to prefer white than whole grain bread. Finally, there was a significant association between carcinoma of the esophagus and long-term occupational exposure to metal dust; this association was largely confined to the lower one-third section of the esophagus.     

Susceptibility of Ureaplasma urealyticum to tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin

The in vitro activity of tetracycline, doxycycline, erythromycin, roxithromycin, clarithromycin, azithromycin, levofloxacin and moxifloxacin was tested against 63 clinical isolates of Ureaplasma urealyticum. The minimal inhibitory concentrations (MICs) and the minimal bactericidal concentrations (MBCs) were determined by the broth microdilution method in A7 medium. The MIC(50) and MIC(90) of the tested agents after 24 h of incubation were as follows: tetracycline, 0.5 and 2.0 μg/ml; doxycycline, 0.125 and 0.25 μg/ml; erythromycin, 2.0 and 8.0 μg/ml; roxithromycin, 2.0 and 4.0 μg/ml; clarithromycin, 0.25 and 1.0 μg/ml; azithromycin, 2.0 and 4.0 μg/ml; levofloxacin, 1.0 and 2.0 μg/ml; and moxifloxacin, 0.5 and 0.5 μg/ml, respectively. The MIC values after 24 h and 48 h incubation differed by no more than one dilution for all the agents with the exception of doxycycline (two dilution difference for MIC(90)). Overall, moxifloxacin was the most active agent in vitro against U. urealyticum, with the narrowest difference between MIC and MBC values, followed closely by levofloxacin. Clarithromycin was the most active macrolide.     

Cutaneous,gastrointestinal, hepatic,endocrine, and renal side-effects of anti-PD-1 therapy

BackgroundAnti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.Methods and findingsIn total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis.ConclusionAnti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.     

Antitumor activity of halogen analogs of phosphoramide,isophosphoramide, and triphosphoramide mustards,the cytotoxic metabolites of cyclophosphamide,ifosfamide, and trofosfamide

A series of halogen analogs of phosphoramide mustard, isophosphoramide mustard, and triphosphoramide mustard, the cytotoxic metabolites of the antitumor drugs cyclophosphamide, ifosfamide, and trofosfamide, respectively, was evaluated in vitro against human tumor cell lines and in vivo against experimental tumors to investigate the effect of replacement of chlorine with bromine or fluorine on the antitumor activity of the parent phosphoramide mustards. In the experimental tumors L1210 leukemia, B16 melanoma, mammary adenocarcinoma 16/C, and ovarian sarcoma M5076, the antitumor activity of the analogs was observed to be generally comparable with that of the parent mustards when chlorine was replaced by bromine but uniformly lower when chlorine was replaced by fluorine. Furthermore, the monobromo analog of isophosphoramide mustard displayed equal or somewhat greater activity in comparison with cyclophosphamide when evaluated against subcutaneously implanted L1210 leukemia with intraperitoneal drug treatment and against mammary adenocarcinoma 16/C.This work was financially supported by NIH, NCI grant PO1 CA34200