术前血清C-反应蛋白水平在卵巢癌患者预后判断中的价值

[目的]探讨术前卵巢癌血清中C-反应蛋白(C-reactive protein,CRP)与临床病理参数及预后的关系.[方法]回顾性分析2008年1月至2014年4月手术的187例初治卵巢癌患者的病例资料,分析术前CRP值与年龄、国际妇产科联盟(International Federation of Gynecologists and Obstetricians,FIGO)分期、组织分级、腹水量及术后残余病灶大小的关系.[结果] 82例(44.09％)卵巢癌患者术前血清CRP值为阳性,平均值为26.41 mg/L.CRP值与FIGO分期(P＜0.05),残余肿瘤大小(P＜0.01)和腹水量(P＜0.01)显著性相关.术前血清CRP阳性率与腹水量相关(P＜0.01),与年龄、组织分级和FIGO分期无关.CRP阳性的卵巢癌患者5年生存率(62.3％)低于CRP阴性的患者(79.6％)(P＜0.01).[结论]检测术前血清CRP值对卵巢癌病情严重程度及预后有重要临床意义.     

胸腹腔镜与传统Ivor-Lewis手术对早中期食管癌患者术后生活质量的影响

[目的]比较胸腹腔镜与传统Ivor-Lewis手术对Ⅰ、Ⅱ期食管癌患者术后近期生活质量的影响.[方法]收集2014年2月至2014年6月浙江省肿瘤医院胸外科手术的I、Ⅱ期食管癌患者112例,其中胸腹腔镜食管癌根治术53例,传统Ivor-Lewis术式59例.采用欧洲癌症研究与治疗组织开发的EORTC QLQ-C30 V3.0中文版及EORTC QLQ-OES18中文版评价患者术前、术后1月、6月及12月生活质量.[结果]术后1月两组总体健康状况和功能领域评分相比术前基线显著性下降(P＜0.05),两组相比,总体健康状况(37.25±15.03 vs 27.34±12.38,P=0.000),躯体功能(49.93±8.04 vs 36.73±13.34,P=0.000),角色功能(38.89±10.36 vs27.78±14.88,P=0.000),胸腹腔镜组评分优于Ivor-Lewis组.在症状领域,术后1个月两组症状(疲劳、疼痛、失眠、食欲下降、腹泻、恶心呕吐)评分比术前基线显著性升高,两组相比,疲劳症状(50.33±14.80 vs 58.87±18.30,P=0.009),疼痛症状(54.58±16.01vs71.64±14.42,P=0.009),返流症状(33.66±15.45 vs 46.78±15.8,P=0.000),胸腹腔镜组评分优于Ivor-Lewis组.术后6月及12月,患者总体健康状况、功能领域及症状领域较术前恢复趋势,其中疲劳、疼痛、返流症状在术后1月、6月、12月胸腹腔镜组均优于Ivor-Lewis组(P＜0.05).[结论]胸腹腔镜食管癌根治术患者总体术后近期生活质量优于Ivor-Lewis手术.     

血清C反应蛋白水平与非小细胞肺癌患者近期疗效及预后的关系

[目的]探讨非小细胞肺癌(NSCLC)患者治疗前后血清C反应蛋白(CRP)的水平及其与肿瘤近期疗效及预后的关系.[方法]用免疫比浊法分别检测215例NSCLC患者(其中105例患者行手术治疗,110例患者行化疗)和102名健康对照者血清中的CRP表达水平,并进行24个月的随访.[结果] NSCLC患者手术后血清CRP浓度(12.52±4.37)mg/L与术前(18.13±5.78)mg/L相比,差异有统计学意义(P＜0 05).经化疗后,30例缓解组患者血清CRP浓度(10.49±3.85)mg/L与治疗前(18.64±4.63)mg/L相比显著下降(P＜0.05);44例进展组患者血清CRP浓度(20.14±7.68)mg/L与治疗前(14.53±4.56)mg/L相比显著升高(P＜0.05); 36例稳定组患者血清CRP浓度治疗前后差异无统计学意义(P＞0.05).手术后CRP阳性率显著下降,而化疗后阳性率下降不明显.手术前CRP阳性患者肿瘤复发或转移率(26.7％)高于术前阴性患者(7.5％).[结论]检测NSCLC患者血清CRP水平对预测肿瘤转移有一定的临床意义,有助于疗效的评估以及预后的预测.     

大肠癌中DPC4蛋白表达及与临床病理特征的关系

[目的]探讨大肠癌组织中DPC4蛋白的表达及其与患者临床病理特征的关系.[方法]免疫组化Elivison二步法检测60例大肠癌手术切除标本中DPC4蛋白的表达,并探讨其与患者组织学类型、浸润深度、淋巴结转移和远处转移等临床病理特征的关系.并取40例癌旁正常大肠组织作对照.[结果] DPC4蛋白主要在大肠癌和癌旁正常大肠组织的胞浆表达,呈棕黄色细颗粒.60例大肠癌标本中DPC4的阳性表达为21例(35.0％),其中强阳性为4例(6.7％).40例癌旁正常大肠组织中DPC4蛋白表达均为阳性,其中强阳性34例(85.0％).大肠癌组织中DPC4蛋白阳性表达率明显低于癌旁正常大肠组织(x2=42.62,P＜0.01).大肠癌组织中DPC4蛋白表达水平随组织分化程度的增加而增加(P＜0.01),随原发病灶的浸润深度增加、淋巴结转移和远处转移的出现而下降(P＜0.01).[结论]且DPC4蛋白表达降低或缺失在大肠癌的发生发展过程起重要作用,有望成为大肠癌基因诊断和治疗的新靶点.     

lncRNARP11-259P1.1在食管鳞状细胞癌中的表达及其与临床预后的关系

目的:探讨lncRNA RP 11-259P 1.1在食管鳞状细胞癌(esophageal squamous cell cancer,ESCC)中的表达水平及其与患者临床病理特征和预后的关系.方法:收集2012年1月1日至2016年12月31日西南医科大学附属医院行手术切除的130例ESCC原发病灶及对应癌旁组织标本、人ESCC细胞株KYSE510、Eca109及食管上皮细胞株Het-1A,采用实时荧光定量PCR法检测lncRNA RP11-259P 1.1在ESCC组织及细胞中的表达水平,分析其在组织中表达水平与患者临床病理特征及预后的关系.结果:lncRNA RP11-259P1.1在ESCC细胞及组织中表达水平显著高于正常管上皮细胞及癌旁组织(均P＜0.01).lncRNA RP11-259P1.1高表达与肿瘤大小、肿瘤分期、淋巴结转移及术前放化疗(CRT)后肿瘤缓解明显相关(均P＜0.05),与患者年龄、性别、肿瘤部位、吸烟状况等无关(均P＞0.05).在63例术前接受新辅助CRT治疗患者中,低表达lncRNA RP11-259P1.1患者与高表达患者比较:(1)病理完全缓解率明显升高(60.00％ vs 21.21％,P＜0.01);(2)术前CRT的疗效更佳(P＜0.05);(3)中位无进展生存时间和生存时间均明显延长[(28.00±2.47) vs(17.00±1.90)个月,(41.57±2.45) vs (30.00±2.55)个月;均P＜0.01].lncRNA RP11-259P1.1为ESCC患者独立的预后因素(P＜0.05).结论:lncRNA RP11-259P1.1可能是ESCC潜在的预后和术前CRT疗效评价的分子标志物,低表达lncRNA RP 11-259P 1.1的患者术前给予CRT疗效更佳.     

Cables在子宫内膜癌中的表达缺失及意义

[目的]探讨Cables在子宫内膜癌组织中的表达及意义.[方法]免疫组化法检测79例子宫内膜癌患者组织中Cables的表达,并进行生存分析.[结果]Cables在子宫内膜癌中表达缺失与患者年龄、TNM分期、肿瘤分化、淋巴转移无显著相关性,但与复发有显著相关性(r=0.231,P=0.042),COX比例风险回归分析显示Cables是子宫内膜癌预后的独立影响因素(P=0.024),相比Cables阳性表达患者,Cables表达缺失的患者复发率高,中位生存期明显缩短(22个月vs45个月,P＜0.01).[结论]Cables参与了子宫内膜癌的发生发展过程,是子宫内膜癌患者独立的预后影响因素.     

中期因子蛋白在脑星形细胞瘤中的表达

[目的]探讨中期因子(MK)蛋白在脑星形细胞瘤中的表达及其与微血管密度(MVD)、组织分级和预后的关系.[方法]应用免疫组织化学方法检测52例星形细胞瘤组织中MK蛋白的表达和MVD计数.[结果]52例星形细胞瘤组织中MK蛋白阳性率为63.5%(33/52),MK阳性染色定位在瘤细胞胞质内.其中Ⅰ～Ⅱ级和Ⅲ～Ⅳ级阳性率分别为44.4%、73.5%,两者间有显著差异(P＜0.05);星形细胞瘤组织中MVD均值为71.8±27.8,其中,Ⅰ～Ⅱ级和Ⅲ～Ⅳ级MVD分别为52.8±18.4、81.7±26.9,两者间差异有显著性(P＜0.01);星形细胞瘤MK蛋白阳性组MVD高于阴性组(P＜0.01).术后生存期＜2年的患者MK蛋白阳性率及MVD均高于术后生存期≥2年者(P＜0.05,P＜0.01).[结论]MK的蛋白表达水平能反映星形细胞瘤的恶性程度,可作为星形细胞瘤预后分析的指标.     

特异性生长因子在胃癌、食管癌患者中表达及意义

[目的]探讨特异性生长因子(tumor specific growth factor,TSGF)在胃癌、食管癌中的表达及意义.[方法]检测108例胃癌、84例食管癌患者术前、术后及无肿瘤史的对照组血清TSGF值,并进行对比分析.[结果]胃癌、食管癌患者的术前TSGF均值为70.28U/ml,高于对照组55.62U/ml(P＜0.01);胃癌、食管癌患者术后TSGF均值为62.37U/ml,与术前组及对照组比较升高(P＜0.01);胃癌、食管癌患者术后2～3个月和9～10个月的TSGF值分别为59.72U/ml,64.49U/ml.[结论]TSGF可以作为胃癌、食管癌辅助诊断,治疗效果及预后的判断指标之一.     

胃癌患者手术前后外周血Th1 / Th2细胞因子表达

[目的]评价胃癌患者外周血Th1/Th2细胞因子表达水平.[方法]流式细胞仪检测82例胃癌患者手术前后和50例胃良性疾病患者(对照组)外周血Th1类细胞因子(IFN-γ、IL-2)和Yh2类细胞因子( IL-4、5、10)的表达水平.[结果]与对照组比较,胃癌患者Th1类细胞因子(IFN-γ、IL-2)低于对照组,但差异无统计学意义(P＞0.05);Th2类细胞因子(IL-4、5、10)高于对照组,且IL-4、IL-10表达水平差异有统计学意义(P均＜0.05).术后胃癌Th1类细胞因子IFN-γ较术前有所升高(18.65±6.74 vs23.07±4.15,P＜0.01);Th2类细胞因子(IL-10)较术前有所下降(6.56±3.46 vs 4.67±2.75,P＜0.01).[结论]胃癌患者Th1细胞向Th2细胞漂移,手术治疗能逆转其漂移状态. Th1/Th2细胞因子检测可为胃癌的免疫治疗提供参考依据.     

GRHL3和c-Myc在食管鳞状细胞癌组织中的表达及其临床意义

目的:研究食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)患者肿瘤组织及癌旁组织中GRHL3和c-Myc的表达情况及其临床意义.方法:收集2015年4月至2016年7月在河北医科大学第四医院胸外科行肿瘤切除并经病理证实的64例ESCC患者的肿瘤组织、癌旁组织,采用Real-time PCR法和免疫组化法检测GRHL3和c-Myc基因的mRNA和蛋白表达情况,分析其与患者临床特征的关系.结果:与癌旁组织相比,ESCC组织中GRHL3 mRNA表达水平和蛋白阳性表达水平均显著升高[(2.85±2.83) vs(2.06±2.02),P＜0.01;81.30％ vs 25.00％,P＜0.01],ESCC组织中c-Myc mRNA表达水平和蛋白阳性表达水平均显著升高[5.13±5.11)vs (2.03±2.00),P＜0.01;42.20％ vs.20.30％,P＜0.01].ESCC组织中GRHL3 mRNA的表达与c-Myc mRNA的表达呈显著正相关关系(P＜0.05),GRHL3蛋白表达和c-Myc蛋白表达也呈显著正相关(P＜0.01).GRHL3蛋白表达和c-Myc蛋白表达与患者肿瘤浸润程度、淋巴结转移、临床分期、分化程度相关.结论:ESCC患者肿瘤组织中GRHL3与c-Myc表达水平显著提高,两者表达呈正相关,且两者与患者临床病理特征密切相关,可能是影响ESCC病理进程的重要因素.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

Effect of tumor therapeutic irradiation on the mechanical properties of teeth tissue

Tumor irradiation of the head-neck area is accompanied by the development of a so-called radiation caries in the treated patients. In spite of conservative therapeutic measures, the process results in tooth destruction. The present study investigated the effects of irradiation on the demineralization and remineralization of the dental tissue. For this purpose, retained third molars were prepared and assigned either to a test group, which was exposed to fractional irradiation up to 60 Gy, or to a non-irradiated control group. Irradiated and non-irradiated teeth were then demineralized using acidic hydroxyl-cellulose gel; afterwards the teeth were remineralized using either Bifluorid12 or elmex gelee. The nanoindentation technique was used to measure the mechanical properties, hardness and elasticity, of the teeth in each of the conditions. The values were compared to the non-irradiated control group. Irradiation decreased dramatically the mechanical parameters of enamel and dentine. In nonirradiated teeth, demineralization had nearly the same effects of irradiation on the mechanical properties. In irradiated teeth, the effects of demineralization were negligible in comparison to non-irradiated teeth. Remineralization with Bifluorid12 or elmex gelee led to a partial improvement of the mechanical properties of the teeth. The enamel was more positively affected by remineralization than the dentine.     

Consultation multidisciplinaire pour les patients atteints d’une pathologie tumorale (carcinome infiltrant ou lésion précancéreuse) liée à HPV : la consultation multidisciplinaire papillomavirus

Given the recent increase in the number of human papillomavirus (HPV)-induced cancers in other locations than gynaecological, the number of patients with two cancers at distinct sites, and because of the lack of exhaustive data, we decided to create a multidisciplinary network around an HPV consultation at the Georges-Pompidou European Hospital (HEGP). This network aims to set up the best tools for detecting HPV-associated “multisite” precancerous lesions in order to determine the possible impact of dedicated care for this at-risk population. This monthly consultation was created at the HEGP in June 2014. It is currently organized around five consultations: gynaecological, ENT, urological, digestive and immunological. Every patient who has been diagnosed with HPV-related cancer and whose care is provided at the HEGP is offered this particular follow-up: systematically, once the initial lesion has been treated, the patient is convened annually for a day during which it benefits from the consultations mentioned above. A consultation with a psychologist is systematically proposed. Local samples are taken at each site: a cytological examination, the analysis of known predictive and prognostic virological markers are carried out. This study fits more broadly in a theme of clinical and fundamental research around cancers related to HPV.     

Differentiation state and invasiveness of human breast cancer cell lines

Summary Eighteen breast cancer cell lines were examined for expression of markers of epithelial and fibroblastic differentiation: E-cadherin, desmoplakins, ZO-1, vimentin, keratin and ₁ and ₄ integrins. The cell lines were distributed along a spectrum of differentiation from epithelial to fibroblastic phenotypes. The most well-differentiated, epithelioid cell lines contained proteins characteristic of desmosomal, adherens and tight junctions, were adherent to one another on plastic and in the basement membrane matrix Matrigel and were keratin-positive and vimentin-negative. These cell lines were all weakly invasive in anin vitro chemoinvasion assay. The most poorly-differentiated, fibroblastic cell lines were E-cadherin-, desmoplakin- and ZO-1-negative and formed branching structures in Matrigel. They were vimentin-positive, contained only low levels of keratins and were highly invasive in thein vitro chemoinvasion assay. Of all of the markers analyzed, vimentin expression correlated best within vitro invasive ability and fibroblastic differentiation. In a cell line with unstable expression of vimentin, T47D_CO, the cells that were invasive were of the fibroblastic type. The differentiation markers described here may be useful for analysis of clinical specimens and could potentially provide a more precise measure of differentiation grade yielding more power for predicting prognosis.