多西紫杉醇联合顺铂治疗蒽环类耐药性晚期乳腺癌的疗效分析

目的:观察多西紫杉醇(DXL)联合顺铂(DDP)方案治疗蒽环类耐药性晚期乳腺癌的临床疗效与毒副作用.方法:2002年1月-2006年6月采用DXL联合DDP方案治疗蒽环类耐药性晚期乳腺癌患者40例.多西紫杉醇75ms/m2,静滴,第1天;顺铂30mg/m2,静滴,第1-3天加水化、利尿、止吐等治疗;21d为1周期.本组中位化疗周期数为4(2-8)周期.结果:40例均可评价疗效.完全缓解(CR)3例(7.5%),部分缓解(PR)19例(47.5%),稳定(SD)9例(22.5%),进展(PD)9例(22.5%),总有效率(CR PR)55%,中位肿瘤进展时间(TTP)6个月.1年生存率66.7%.主要毒性为胃肠道副反应和骨髓抑制.结论:DXL联合DDP方案治疗蒽环类耐药的晚期乳腺癌疗效好,不良反应轻,是蒽环类耐药性乳腺癌的有效解救治疗方案.     

两组解救方案治疗蒽环类耐药的晚期乳腺癌疗效观察

目的:比较两组化疗方案作为晚期乳腺癌蒽环类耐药患者的解救治疗疗效及不良反应.方法:采用多西紫杉醇(DXL) 顺铂(DDP)、长春瑞滨(NVB) 顺铂方案治疗蒽环类耐药的晚期乳腺癌64例,比较患者的近期有效率、不良反应、疾病进展时间及1年生存率.DXL DDP方案:DXL 60mg/m2,持续1小时静脉滴注,d1;DDP 30mg/m2d2～4.NVB DDP方案:NVB 25mg/m2d1,8;DDP 30mg/m2,d2～4,上述两个方案每3周为一个周期.结果:DXL DDP方案的总有效率为52.9%(18/34),其中CR 5.9%(2/34),PR 47.1%(16/34);中位疾病进展时间(TTP)8个月;中位生存时间18个月,1年生存率62.9%.NVB DDP方案的总有效率为43.3%(13/30),其中CR 3.3%(1/30),PR 40.0%(12/30);中位TTP 7个月;中位生存时间15个月,1年生存率54.8%.两组方案的主要不良反应为骨髓抑制及胃肠道反应.结论:两组方案对于蒽环类耐药的晚期乳腺癌患者均有较好疗效,不良反应可耐受,其近期疗效无明显差异.     

吉西他滨联合顺铂治疗蒽环类和(或)紫杉类耐药晚期乳腺癌的近期疗效观察

背景与目的:蒽环类和(或)紫杉类药物在新辅助和(或)辅助治疗中的广泛应用增加了乳腺癌复发转移后选择解救治疗药物的难度,有研究证明吉西他滨(gemcitabine,GEM)、顺铂(cisplatin,DDP)对乳腺癌明确有效。据此,本文旨在评估GEM联合DDP治疗蒽环类和(或)紫杉类耐药晚期乳腺癌的近期疗效。方法:收集2005年5月8日—2007年1月31日,采用GEM1000mg/m2(d1,d8)及DDP30mg/m2(d1～d3)3周方案治疗蒽环类和(或)紫杉类耐药的晚期乳腺癌患者34例。中位化疗5个周期(2～6个周期),所有患者随访超过6个月。结果:完全缓解(CR)3例(8.8%),部分缓解(PR)13例(38.2%),稳定(SD)12例(35.3%),进展(PD)6例(17.7%);总有效率(CR PR)47.0%,中位疾病进展时间(TTP)6.5个月。不良反应Ⅲ/Ⅳ血小板减少或腹泻常见。结论:GEM联合DDP方案可用于蒽环类和(或)紫杉类耐药晚期乳腺癌的解救治疗。     

吉西他滨联合顺铂治疗耐药转移性乳腺癌的临床观察

观察吉西他滨联合顺铂(DDP)方案治疗蒽环类和(或)紫杉类耐药转移性乳腺癌的疗效和不良反应.采用吉西他滨联合DDP方案治疗蒽环类和(或)紫杉类均耐药转移性乳腺癌患者52例.吉西他滨1 000 mg/m2,静脉滴入,d1,d8;DDP 25 mg/m2,静脉滴入,d1～d3.21 d为1个周期,至少用2个周期.本组患者治疗有效率为44.2%(23/52),中位生存时间11.0个月,中位疾病进展时间为5.3个月,1年生存率为42.3%.主要不良反应为胃肠道反应和骨髓抑制.Ⅲ～Ⅳ度呕吐发生率为28.9%(15/52).Ⅲ～Ⅳ度中性粒细胞减少发生率为15.4%(8/52),Ⅲ～Ⅳ度血小板减少发生率为17.3%(9/52).初步研究结果显示,吉西他滨联合DDP方案治疗蒽环类和(或)紫杉类均耐药的转移性乳腺癌疗效较好,毒副反应可耐受,是蒽环类及紫杉类耐药的转移性乳腺癌的有效选择.     

多西紫杉醇联合卡培他滨治疗蒽环类耐药的晚期乳腺癌

目的:观察多西紫杉醇联合卡培他滨(DC)治疗蒽环类耐药晚期乳腺癌的疗效和安全性.方法:31例经病理证实的蒽环类耐药的转移性乳腺癌患者,采用多西紫杉醇联合卡培他滨化疗.剂量为多西紫杉醇75mg/m2,静滴,d1;希罗达2 500mg/m2,口服,d1～d14,21天为1个周期,化疗至疾病进展或不良反应无法耐受.根据WHO制定的实体瘤客观疗效评价标准和抗癌药物毒性分级标准评价疗效和不良反应.结果:31例患者共完成118个周期化疗,每例患者化疗2个～8个周期,中位周期数4个.31例患者中,完全缓解1例(3.2%),部分缓解16例(51.6%),稳定10例(32.3%),进展4例(12.9%),总有效率为54.8%.中位肿瘤进展时间6.3个月,中位生存期13个月,1年生存率为58.8 %.主要不良反应为骨髓抑制、胃肠道反应和手足综合征,患者均可耐受.结论:多西紫杉醇联合卡培他滨治疗蒽环类耐药晚期乳腺癌的疗效较好,不良反应可以耐受,是治疗蒽环类耐药晚期乳腺癌的有效方案.     

NP和TP方案治疗蒽环类耐药晚期乳腺癌的前瞻性研究

目的比较两组化疗方案对蒽环类耐药晚期乳腺癌患者的治疗疗效及不良反应.方法采用长春瑞滨(NVB)+顺铂(DDP)和紫杉醇+DDP方案治疗蒽环类耐药的晚期乳腺癌70例.TP方案紫杉醇75 mg/m2,持续静脉滴入3 h,d1、d8和d15;DDP 80 mg/m2,静脉滴入,d1～d3.NP方案NVB 30 mg/m2,静脉推注,d1、d8;DDP 80 mg/m2,静脉滴入,d1～d3.上述2个方案,每4周为1个疗程.结果NP方案的总有效率为45.16%(14/31),其中CR 3.22%(1/31),PR 41.93%(13/31),中位缓解期9个月,中位生存期20个月,1、2和3年生存率分别为51.51%、33.33%和20.00%.TP方案的总有效率为54.54%(18/33),其中CR 6.06%(2/33),PR 48.48%(16/33),中位缓解期13个月,中位生存期26个月,1、2和3年生存率分别为59.46%、40.54%和23.33%.两组方案的主要不良反应为骨髓抑制及胃肠道反应.结论两组方案对蒽环类耐药的晚期乳腺癌患者均有较好疗效,不良反应可耐受,近期疗效差异无明显差异.     

多西紫杉醇联合卡培他滨治疗蒽环类耐药性晚期乳腺癌的疗效观察

目的 观察多西紫杉醇联合卡培他滨治疗蒽环类耐药性晚期乳腺癌的疗效和不良反应.方法 43例经病理证实的蒽环类耐药性晚期乳腺癌患者,采用多西紫杉醇联合卡培他滨方案化疗.多西紫杉醇75 mg/m<'2>、静脉滴注、dl,卡培他滨1600 mg/d、分2次口服、dl～14,21 d为1个周期,化疗周期数为3～6个周期,中位周期数4个,直至病情进展或不良反应无法耐受.结果 43例患者中,完全缓解9例(20.9%),部分缓解19例(44.2%),稳定9例(20.9%),疾病进展6例(14.0%),有效率为65.1%.中位肿瘤进展时间为7.5个月,中位生存期为15个月,1年生存率为62.8%,2年生存率为41.9%.不良反应主要为胃肠道反应、骨髓抑制和手足综合征,患者均可耐受.结论 多西紫杉醇联合卡培他滨治疗蒽环类耐药性晚期乳腺癌的疗效显著,不良反应可以耐受,可作为蒽环类耐药的晚期乳腺癌的有效解救治疗方案.     

长春瑞滨联合顺铂治疗蒽环类耐药晚期乳腺癌的临床观察

目的 观察长春瑞滨(vinorelbine,NVB)联合顺铂(cisplatin,DDP)组成的NP方案治疗蒽环类耐药晚期乳腺癌患者的疗效和毒副反应.方法 我院2002年10月-2006年10月,采用NP方案治疗蒽环类耐药的晚期乳腺癌48例.长春瑞滨25 mg/m2加入生理盐水100 mL,快速静脉滴人,d1,8,顺铂50 mg静脉滴注,d3-5,21 d为1周期.本组中位化疗周期为3个.结果 完全缓解(CR)2例(4.2%),部分缓解(PR)20例(41.7%),稳定(SD)17例(35.4%),进展(PD)9例(18.8%).客观有效率(RR)(CR PR)为45.8%,肿瘤控制率DCR(CR PR SD)为81.3%.有内脏转移患者的疗效低于无内脏转移的患者(68.4% vs 31.0%,P<0.05).主要毒副反应为骨髓抑制及胃肠道反应.结论 长春瑞滨联合顺铂治疗蒽环类耐药性晚期乳腺癌疗效较好,使用方便,毒副反应可以耐受.是蒽环类耐药晚期乳腺癌的有效解救方案.     

以紫杉醇为主的联合化疗方案治疗转移性乳腺癌的临床研究

目的观察以紫杉醇为主的联合化疗方案治疗转移性乳腺癌的近期疗效和不良反应。方法既往未用过蒽环类化疗者选用TE方案:表阿霉素70~80mg/m2,静滴,第1天,紫杉醇135~175mg/m2,静滴,第2天。既往用过蒽环类化疗者选用TP方案:紫杉醇135~175mg/m2,静滴,第1天,DDP80mg/m2,静滴,分三天用(第2、3、4天)。21~28天为一周期,至少治疗2周期。中位化疗周期数3个(2~6周期)。结果全组70例,CR7例(10.0%),PR36例(51.4%),SD24例(34.3%),PD3例(4.3%),总有效率61.4%。TE方案有效率61.2%,TP方案有效率62.8%。中位肿瘤进展时间TTP9.8个月,中位生存期17.5个月。主要不良反应为骨髓抑制和消化道反应。结论以紫杉醇为主的联合化疗方案对转移性乳腺癌有较好的疗效,毒副反应能忍受,对蒽环类耐药及对铂类抗药的晚期乳腺癌也有很好的疗效。     

多西他赛联合洛铂治疗蒽环类耐药的晚期乳腺癌疗效分析

目的:观察多西他赛联合洛铂方案对蒽环类耐药的晚期乳腺癌患者的临床疗效及毒副作用。方法:采用多西他赛联合洛铂方案治疗晚期乳腺癌患者42例。多西他赛75mg/m2静脉滴注第1天,洛铂30mg/m2静脉滴注第1天。每21天重复,至少应用2个周期。结果:42例患者中,CR、PR分别为4、19例,总有效率为54.8%(23/42),1年生存率为64.3%(27/42),主要不良反应为骨髓抑制。结论:多西他赛联合洛铂方案治疗蒽环类耐药的晚期乳腺癌疗效好,不良反应轻,是治疗蒽环类耐药的晚期乳腺癌较好的方案。     

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.