益气散结法联合化疗治疗转移去势抵抗性前列腺癌的疗效观察

目的探讨益气散结法联合化疗治疗转移去势抵抗性前列腺癌(metastatic castration-resistantprostate cancer,mCRPC)的有效性及安全性。方法将32例mCRPC患者,1∶1随机分为益气散结法联合多西他赛化疗研究组和单纯多西他赛化疗组。根据前列腺癌工作组PCWG-2标准进行疗效评价,比较2组无疾病进展生存期(progress free survival,PFS)、PSA反应率,并进行安全性评价。采用FACT-P问卷调查患者生活质量情况。结果研究组的中位PFS略长于对照组(7.4 m vs 6.6 m),但无统计学差异(P>0.05)。4周期治疗后,2组PSA水平均较治疗前有显著下降(P<0.05)。益气散结法研究组PSA反应率64.29%,对照组38.46%。安全性方面,研究组中性粒细胞减少症、疲劳发生率显著低于对照组(P<0.05)。生活质量评分2组患者均有明显下降(P<0.05)。结论益气散结法联合多西他赛方案化疗能较好提高mCRPC患者的生活质量,降低化疗毒性,改善生存,但仍需大样本随机对照临床研究加以证实。     

不同方案化疗联合同期放疗治疗不可手术食管癌的临床观察

目的探讨不同方案化疗联合同期放疗对不可手术的食管癌的治疗疗效及安全性。方法选取62例不可手术的食管癌患者,利用随机数字表法进行分组,分别设为研究组和对照组,每组各31例。对照组采取5-氟尿嘧啶(5-Fu)+顺铂(DDP)联合同期放疗,研究组采取奈达铂+多西他赛联合同期放疗。记录2组近期有效率、1年内局控率、1年内生存率及放化疗不良反应发生率,并进行对比分析。结果 1年内局控率2组差异无统计学意义(P>0.05);1年内有效率研究组高于对照组(P<0.05)。恶心、呕吐及放射性食管炎发生率研究组均低于对照组(P<0.05),骨髓抑制发生率研究组高于对照组(P<0.05)。研究组1年生存率为61.3%(19/31),对照组为45.2%(14/31),差异无统计学意义(c2=1.265,P>0.05)。结论奈达铂联合多西他赛同期放疗比顺铂联合5-Fu同期放疗,在治疗不可手术的食管癌方面疗效更佳,不良反应更轻且可控,患者治疗耐受性更好。     

乳腺癌术后化疗对骨质密度的影响

目的分析乳腺癌术后化疗对患者骨质密度的影响。方法选取2007年7月至2012年12月间收治的乳腺癌患者150例,分为3组,研究A组术后采用ET方案(表阿霉素+多西他赛)化疗,研究B组术后采用ECT方案(表阿霉素+环磷酰胺+多西他赛)化疗,对照组术后采用药物(吉西他滨+顺铂)继续治疗,对比3组患者治疗前后骨密度变化情况、血钙素(BGP)、碱性磷酸酶(ALP)和尿钙情况,以及研究组在化疗3个和6个疗程后的骨质疏松发生率。结果治疗后,研究A组和研究B组股骨和腰椎骨密度均出现比较明显减小(P<0.05),对照组未见明显变化(P>0.05);研究A组和研究B组的BGP、ALP及24h尿钙均出现明显升高(P<0.05),对照组无明显变化(P>0.05)。化疗3个和6个疗程后,研究A组和研究B组均出现较高比率的骨质疏松,且随治疗疗程的增加,骨质疏松发生率增加(P<0.05)。结论乳腺癌术后进行化疗,可对患者的骨质密度产生一定影响;对如何选用相对更合理的化疗方案,临床需作进一步探究。     

局部晚期非鳞非小细胞肺癌同步放化疗两种方案比较研究

目的 比较两种方案治疗局部晚期非鳞非小细胞肺癌副反应及近期疗效。方法 回顾2009年3月—2013年1月42例局部晚期非鳞非小细胞肺癌患者,所有患者均接受同步放化疗,A组放疗同步培美曲塞+顺铂化疗,B组放疗同步多西他赛+顺铂化疗,比较A、B两组患者副反应及近期疗效。结果 A组28例患者,B组14例患者,两组副反应比较,血液毒性:白细胞减少、中性粒细胞减少、血色素降低、血小板减少无统计学差异(P＞0.05)。非血液毒性:放射性肺损伤发生率、咳嗽发生率B组明显高于A组,有统计学差异(P＜0.05)。而其他非血液毒性:肝功能损伤、肾功能损伤、发热、呼吸困难、放射性食管炎、乏力、体重下降、消化道反应、皮肤反应均无统计学差异(P＞0.05)。近期疗效:A、B两组有效率分别为75%及71.43%,无统计学差异(P＞0.05)。结论 放疗同步培美曲塞+顺铂化疗与同步多西他塞+顺铂化疗的两组疗效无显著差异,但培美曲塞在治疗局部晚期非鳞非小细胞肺癌副反应方面存在一定优势。     

多西他赛为主的三药方案治疗高龄低分化胃癌的效果观察

目的分析以多西他赛为主的三药方案治疗高龄低分化胃癌患者的临床效果。方法随机数表法将91例高龄低分化胃癌患者随机分组对照组(n=45)和观察组(n=46),对照组患者接受多西他赛^+奥沙利铂方案化疗,观察组患者接受多西他赛^+奥沙利铂^+替吉奥方案化疗,比较两组患者的外周血T淋巴细胞(包括CD8^+、CD4^+、CD3^+)水平、临床疗效、生存情况及不良反应发生情况。结果治疗前后,两组患者CD3^+、CD4^+和CD8^+水平比较,差异均无统计学意义(P﹥0.05);治疗后,两组患者CD3^+、CD4^+和CD8^+水平均高于本组治疗前,差异均有统计学意义(P﹤0.05)。观察组患者疾病控制率(DCR)为56.5%(26/46),与对照组患者的51.1%(23/45)比较,差异无统计学意义(χ^2=0.268,P﹥0.05)。两组患者肿瘤进展时间和生存时间比较,差异均无统计学意义(P﹥0.05)。观察组患者中性粒细胞减少、白细胞减少、血小板减少、疲劳、脱发的发生率均高于对照组患者,差异均有统计学意义(P﹤0.05)。结论多西他赛为主的二药、三药方案治疗高龄低分化胃癌的临床效果相当,但三药方案的不良反应较重,考虑到高龄患者的身体条件,采用以多西他赛为主的二药方案治疗更为合适。     

两种新辅助化疗方案治疗进展期乳腺癌的疗效对比研究

目的探讨表柔吡星联合多西他赛(ED方案)与环磷酰胺+表柔吡星+5-氟尿嘧啶(CEF方案)两种新辅助化疗方案对进展期乳腺癌的临床疗效。方法选取2010年5月至2013年2月间收治的90例Ⅱ^Ⅲ期择期手术乳腺癌患者为研究对象,随机分为A(n=47例)和B(n=43例)两组,A组患者采用ED方案治疗,B组患者采用CEF方案治疗,对比两组患者的临床疗效和不良反应。结果化疗结束后,A组患者KPS得分(84.7±6.4)高于B组(81.4±5.5),差异有统计学意义(P=0.010)。A组患者临床完全缓解率、总有效率分别为10.6%和87.2%,B组患者分别为7.0%和83.7%,差异均无统计学意义(P=0.471,P=0.436)。两组患者不良反应类型、发生率和不良反应级别构成比较,差异均无统计学意义(P>0.05)。结论 ED方案与CEF方案的临床疗效与不良反应发生率相近,患者经前者治疗后表现出更高的生活质量,值得临床推广。     

多西他赛与奥沙利铂联合氟尿嘧啶类药物治疗晚期胃癌的临床对比研究

目的对比分析多西他赛与奥沙利铂分别联合氟尿嘧啶类药物在晚期胃癌一线化疗中的疗效及毒副反应,评价2种不同化疗方案在晚期胃癌化疗中的应用价值。方法 57例晚期胃癌患者分为多西他赛联合氟尿嘧啶类化疗组(A组,26例)和奥沙利铂联合氟尿嘧啶类化疗组(B组,31例),所有患者均化疗至少4周期,按RECIST标准评价并比较2组的客观疗效,按NCI-CTC 3.0标准评价并比较毒副反应发生情况。结果A组有效率为38.4%,疾病控制率为76.9%,中位疾病进展时间5.8个月,中位总生存时间12.5个月;B组分别为38.7%、80.6%、5.3个月、14.0个月,比较差异均无统计学意义(P>0.05)。毒副反应方面,A组白细胞减少总发生率为88.5%,高于B组的61.3%(P<0.05);A组外周神经毒性发生率为30.8%,显著低于B组的67.7%(P<0.05)。结论多西他赛联合氟尿嘧啶类化疗方案与奥沙利铂联合氟尿嘧啶类化疗方案治疗晚期胃癌疗效相当,毒副反应有差异,但均属可耐受范围,2种方案均可作为晚期胃癌化疗方案,临床制定化疗方案需个体化选择。     

不同二线化疗药物治疗晚期非小细胞肺癌的疗效和安全性比较

目的探讨单用培美曲塞或多西他赛二线化疗药物治疗化疗失败的晚期非小细胞肺癌(NSCLC)的临床疗效及安全性。方法共纳入60例一线治疗失败的局部晚期NSCLC患者,采用随机数字法平均分为A组、B组。A组单用培美曲塞化疗,B组单用多西他赛治疗。观察2组患者的近远期临床疗效及不良反应的发生情况。结果 A组、B组总有效率分别为66.67%、63.33%,2组比较,差异无统计学意义(P>0.05)。A组患者白细胞降低、脱发发生率明显低于B组患者,2组比较差异有统计学意义(P<0.05);血小板降低、贫血、恶性呕吐、皮疹等比较差异不明显(P>0.05)。A组患者6个月、1年生存率分别为46.67%、30.00%,B组6个月、1年生存率分别为40.00%、23.33%,2组比较差异无统计学意义(P>0.05)。结论单用培美曲塞或多西他赛治疗化疗失败的晚期NSCLC均有较好的临床疗效,可作为二线化疗药物,但培美曲塞白细胞降低不良反应较多西他赛发生率低。     

二联与多西他赛三联疗法对低分化胃癌的治疗观察

目的 对比二联与多西他赛三联疗法对低分化胃癌的治疗效果与安全性.方法 择取80例低分化胃癌患者作为研究对象,根据患者对治疗的意愿分为2组,即二联组(30例)与三联组(50例).二联组采用二联方案(奥沙利铂+替吉奥胶囊)治疗,三联组采用三联方案(多西他赛+顺铂+氟尿嘧啶)治疗.观察2组近期临床疗效、治疗前后外周血T淋巴细胞水平及治疗期间药物的毒副作用.结果 三联组总有效率(32/50,64.00%)高于二联组(12/30,40.00%)(P<0.05).治疗后三联组CD4+水平高于二联组(P<0.05).三联组神经毒性(20/50,40.00%)、粒细胞减少(23/50,46.00%)、手足综合征(10/50,20.00%)的发生率高于二联组(5/30,16.67%)、(7/30,23.33%)、(2/30,6.67%)(P<0.05).结论 多西他赛+顺铂+氟尿嘧啶三联疗法对低分化胃癌的治疗效果优于奥沙利铂+替吉奥胶囊二联疗法,但三联疗法的不良反应发生率高于二联疗法,临床工作中应结合患者的病情进行灵活选择.     

国产多西紫杉醇治疗非小细胞肺癌的Ⅱ期临床研究

目的 :评价国产多西紫杉醇 (艾素 ,江苏恒瑞医药股份有限公司产品 )单用以及艾素 +顺铂联合化疗方案对非小细胞肺的临床疗效和安全性 ,并以进口多西紫杉醇 (泰索帝 ,安万特公司产品 ) +顺铂联合化疗方案作对照。方法 :患者随机分入艾素单用组 (A组 ) :艾素 75mg/m2 ;艾素 +顺铂组 (B组 ) :艾素 75mg/m2 +顺铂 75mg/m2 ;泰索帝 +顺铂组 (C组 ) :泰索帝 75mg/m2 +顺铂 75mg/m2 ;3组均为每 3周重复。结果 :入组的 115例中 10 4例可评价疗效 ,A、B和C组有效率分别为 8 10 %、2 3 5 3%、2 7 2 7%。B和C组有效率相似。不良反应主要有中性粒细胞减少、贫血、粒细胞减少性发热、其他发热、脱发、恶心呕吐和乏力。C组中性粒细胞减少的发生率高于B组 ,两组间差异有显著性 (P <0 0 5 )。其余不良反应两组相似。结论 :国产多西紫杉醇 (艾素 ) +顺铂与进口多西紫杉醇 (泰索帝 ) +顺铂两联合化疗方案相似 ,对非小细胞肺癌有一定疗效 ,且毒性可耐受。     

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.