脂质体多柔比星治疗淋巴瘤患者的疗效及安全性分析

背景与目的:蒽环类药物在淋巴瘤化疗中有很重要的地位,但相关不良反应限制了其在临床中的应用,尤其是心脏毒性。本文旨在分析脂质体多柔比星联合治疗淋巴瘤患者的有效率及安全性。方法:回顾性分析2006年1月—2011年10月在北京大学肿瘤医院淋巴肿瘤科住院并接受脂质体多柔比星联合化疗的68例患者的临床资料。其中初治患者47例,复治患者21例。应用SPSS 17.0统计软件统计分析治疗有效率和治疗相关不良反应,评价脂质体多柔比星的疗效及安全性。结果:68例患者中弥漫大B细胞淋巴瘤(diffuselarge B-cell lymphoma,DLBCL)42例。总有效率(ORR)为73.5%,其中完全缓解(CR)率57.4%,部分缓解(PR)率19.1%。初治DLBCL的ORR率为74.3%,CR率为60%,其中应用R-CCOP方案治疗患者的ORR率为81.5%,CR率为66.7%。骨髓抑制是最常见不良反应,3～4级粒细胞减少症的发生率55.9%;心电图异常发生率54.4%,3例患者出现心功能异常。仅1例伴有严重内科疾病的患者出现肺部感染并死亡。结论:使用脂质体多柔比星治疗淋巴瘤的有效率和安全性均较好。     

脂质体多柔比星治疗淋巴瘤临床观察

目的 研究脂质体多柔比星治疗淋巴瘤患者的临床疗效和毒副反应.方法 40例淋巴瘤患者均行脂质体多柔比星联合化疗,并观察其近期疗效和毒副反应.结果 40例淋巴瘤患者总有效率为80.0％,主要毒副反应为骨髓抑制和心脏毒性.结论 脂质体多柔比星治疗淋巴瘤安全有效.     

聚乙二醇脂质体多柔比星二线治疗晚期铂类敏感型复发性卵巢癌的临床疗效观察

目的观察聚乙二醇脂质体多柔比星治疗晚期铂类敏感型复发性卵巢癌的临床疗效。方法将100例晚期铂类敏感型复发性卵巢癌患者分为观察组50例(采用聚乙二醇脂质体多柔比星+卡铂治疗)和对照组50例(采用吉西他滨+卡铂治疗)。比较两组患者的治疗效果和不良反应发生情况。结果两组患者的治疗有效率(RR)和疾病控制率(DCR)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、血小板减少和恶心呕吐的发生率均低于对照组患者,手足综合征的发生率高于对照组患者,差异均有统计学意义(P﹤0.05)。结论聚乙二醇脂质体多柔比星可用于二线治疗晚期铂敏感型复发性卵巢癌,具有不良反应轻、患者依从性好的优点,值得临床推广应用。     

异环磷酰胺联合顺铂、聚乙二醇脂质体多柔比星方案治疗骨肉瘤的疗效及不良反应

目的:探讨异环磷酰胺联合顺铂、聚乙二醇脂质体多柔比星方案治疗骨肉瘤的疗效及不良反应。方法:选取骨肉瘤患者36例，接受聚乙二醇脂质体多柔比星剂量20 mg/m2，静脉滴注，第1天；异环磷酰胺剂量2.0 g/m2，静脉滴注，第1～5天；顺铂剂量80 mg/m2，静脉滴注，第8天；每21天一个周期。化疗期间行手术治疗。结果:32例患者完成8个周期化疗。25例患者存活，22例患者无瘤生存，中位无瘤生存时间为40.2个月(22.5～57.3个月)。化疗后3/4级不良反应包括白细胞下降6例(16.7%)、粒细胞下降8例(22.2%)、贫血1例(2.8%)和呕吐2例(5.6%)。25例长期生存患者的MSTS 93评分为16~30分，平均22.2分，优良率为80.0%；SF-36量表显示患者活力得分较低。结论:临床应用异环磷酰胺、顺铂、聚乙二醇脂质体多柔比星方案联合手术治疗骨肉瘤疗效确切，且不良反应较轻，值得进一步深入研究和推广。     

膀胱癌电切术后膀胱灌注多柔比星脂质体治疗浅表性膀胱癌的疗效观察

目的:探讨经尿道电切术后膀胱灌注多柔比星脂质体治疗浅表性膀胱癌的临床疗效。方法:78例患者随机分为2组:表柔比星灌注组（EOX）和多柔比星脂质体组（DOL）,随访比较2组患者术后复发情况和不良反应。结果:术后12个月和24个月,DOL复发率分别为5.0%和10.0%,明显低于EOX复发率18.4%和26.3%（P<0.05)。DOL组不良反应发生率低于EOX组（P<0.05）。结论:经尿道膀胱肿瘤电切术后膀胱灌注多柔比星脂质体疗效优于表柔比星而不良反应发生率低于表柔比星。     

聚乙二醇化脂质体多柔比星联合异环磷酰胺治疗晚期转移性软组织肉瘤

背景与目的：软组织肉瘤一旦出现远处转移,预后极差,中位生存时间不到1年。多柔比星联合异环磷酰胺(ifosfamide,IFO)(AI方案)是晚期软组织肉瘤常用的一线联合治疗方案。聚乙二醇脂质体多柔比星(pegylated liposomal doxorubicin,PLD)活性成分为盐酸多柔比星,药物包裹在脂质体中,可减少多柔比星的临床毒性反应。该研究探讨PLD联合IFO治疗晚期转移性软组织肉瘤的临床疗效和安全性。方法：选取晚期转移性软组织肉瘤患者25例,使用PLD联合IFO方案,PLD剂量30 mg/m²,静脉滴注,第1天;IFO剂量1.8 g/m²,静脉滴注,第1~5天;美司钠360 mg/m²,用IFO时0、4和8 h,21 d为1个周期。结果：所有患者化疗1~8个周期,中位周期数4。25例患者中部分缓解9例(36%),疾病稳定12例(48%),疾病进展4例(16%),疾病控制率(完全缓解+部分缓解+疾病稳定)为84%(21/25)。中位无进展生存时间为7.3个月(95%CI：4.6~10.0个月)。由于失访病例较多,中位总生存时间未随访到。化疗后3/4级不良反应包括白细胞下降(20%)、粒细胞下降(28%)、贫血(4%)和呕吐(4%)。只有1例患者治疗过程中予以减量。结论：临床应用PLD联合IFO方案治疗晚期转移性软组织肉瘤疗效确切,且毒性反应较轻,值得进一步深入研究。     

盐酸多柔比星脂质体所致手足综合征的临床管理进展

<正>盐酸多柔比星脂质体(pegylated liposomal doxorubicin,PLD)是一种蒽环类细胞毒性抗生素,其活性成分为盐酸多柔比星。与传统剂型相比,其具有许多独特的优点,包括增加药物在血液循环中的时间,增加药物的靶向性,增加对深层肿瘤细胞的杀伤作用,减少心脏毒性等不良反应~([1])。近年来被应用在实体瘤或血液系统肿瘤,包括淋巴瘤、乳腺癌、卵巢癌和骨髓瘤等,均取得了良好的疗效~([2])。该药发生率较高的剂量限制性不良反应为手足综合征,缓解手足综合征的方法为延长给药间隔,减少剂量,严重者需停药。手足综合征虽没有生命危险,但严重时会影响患者肢体功能,导致痛性残疾,降低生活质量,一旦发生会使有效的抗肿瘤治疗被迫中断或更改方案,间接影响治疗效果~([3])。因此,在PLD应用中,手足综合征的管理非常重要,目前尚缺乏有效的预防措施及对症处理药物,在临床干预中缺乏统一的认识,本文就PLD所致的手足综合征的临床干预方法进行综述,旨在为临床正确评估和早期识别管理提供借鉴。     

贝伐珠单抗联合多柔比星脂质体治疗铂类耐药复发性卵巢上皮性癌患 者的近期疗效和安全性评价

目的：探讨贝伐珠单抗联合多柔比星脂质体治疗铂类耐药复发性卵巢上皮性癌患者的近期疗效和不良反应,并随访生存情况。方法：选取中国人民解放军联勤保障部队第九〇一医院2018年1月至2019年12月收治的76例铂类耐药复发性卵巢上皮性癌患者,采用数字随机分组法分为对照组38例、观察组38例,对照组给予多柔比星脂质体单药化疗4个周期,观察组给予贝伐珠单抗联合多柔比星脂质体化疗4个周期,观察两组患者治疗后近期疗效和不良反应,以及血清肿瘤标志物人附睾蛋白4（human epididymis protein 4,HE4）、糖类抗原125（carbohydrate antigen 125,CA125）变化,并随访总生存期（OS）和无疾病进展生存期（PFS）。结果：对照组患者客观有效率（ORR）为40.54%、疾病控制率（DCR）为67.57%,观察组患者ORR为69.44%、DCR为88.89%,观察组ORR和DCR显著高于对照组（均P<0.05）。治疗后观察组患者血清HE4和CA125分别为（142.67±46.81）pmol/L、（31.79±11.65）U/L,显著低于对照组患者的（219.33±75.67）pmol/L、（57.05±17.85）U/L（均P<0.05）。两组患者的胃肠反应、骨髓抑制、肝肾功能损伤、心脏毒性、过敏反应、血栓栓塞和出血等不良反应相比较差异无统计学意义（均P>0.05）;观察组患者高血压发生率显著高于对照组（P<0.05）,但可控、可耐受。观察组患者中位OS 和中位PFS分别分别为17.2个月和10.9个月,显著长于对照组患者的14.1个月和7.8个月（均P<0.05）。结论：对于铂类耐药复发性卵巢上皮性癌患者,贝伐珠单抗联合多柔比星脂质体近期疗效可靠、安全性好、不良反应可耐受,值得临床推广。     

脂质体多柔比星治疗淋巴瘤的疗效

目的：探讨脂质体多柔比星用于临床治疗淋巴瘤的疗效以及安全性。方法：选取90例淋巴瘤患者作为研究对象,均采用脂质体多柔比星治疗,对患者临床资料、治疗结果、随访情况等进行回顾性分析。结果：90例淋巴瘤患者治疗总有效率为74.44%,初治者总有效率（79.25%）与复治者（67.57%）相近,组间无明显差异（P >0.05）。常见不良反应为骨髓抑制、心电图异常、心功能异常等;患者随访3年生存率为62.22%,初治者（71.70%）略高于复治者（48.65%）,但组间比较差异无显著性（P >0.05）。结论：采用脂质体多柔比星临床治疗淋巴癌,效果显著,不良反应较小,安全性高,建议在临床可作为治疗淋巴瘤的首选药物进行推广应用。     

表柔比星、脂质体多柔比星单药对乳腺癌细胞和树突状细胞生长的抑制作用

背景与目的:表柔比星(epirubicin)是临床上治疗乳腺癌的一线化疗药物,脂质体多柔比星(liposome doxorubicin)是一种新型脂质体类药物,相比传统蒽环类药物可以降低心脏毒性和骨髓抑制.树突状细胞(dentric cell,DC)在肿瘤免疫中起到重要作用.本实验旨在探讨这2种药物对人乳腺癌细胞株Bcap37和MDA-MB-231,以及人树突状细胞生长的抑制作用,以评估2种制剂在乳腺癌治疗中的价值.方法:用不同浓度(0、0.25、0.5、1.0、2.0、4.0 μg/ml)表柔比星和脂质体多柔比星分别作用于Bcap37、MDA-MB-231和树突状细胞,MTT法检测24、48和72 h时对细胞生长的抑制率.结果:2种药物对肿瘤细胞和正常细胞均有抑制作用.与对Bcap37、MDA-MB-231的作用相比,脂质体多柔比星对树突状细胞的抑制作用较小(F=22.208,P<0.01;F=20.534,P<0.01).脂质体药物对Bcap37的抑制作用强于MDA-MB-231(F=12.873,P<0.01).结论:恶性程度低的乳腺癌细胞对脂质体多柔比星的敏感性高,恶性程度高的细胞则化疗敏感性低.脂质体制剂较普通制剂对于正常树突状细胞的毒性小.     

The medically important dematiaceous fungi and their identification

Dematiaceous fungi include a large group of organisms that are darkly pigmented (dark brown, olivaceous, or black). In most cases the pigment is melanin, and specifically, dihydroxynaphthalene melanin. The diseases produced include chromoblastomycosis, eumycotic mycetoma, and phaeohyphomycosis. Phaeohyphomycosis is a new classification for a diverse group of previously known entities grouped together on the basis of finding dematiaceous hyphal and/or yeast-like forms in tissue; tissue involvement may be superficial, cutaneous and corneal, subcutaneous, or systemic. Identification of these fungi is based mostly upon morphology. Important structures include annellides (Phaeoannellomyces, Exophiala), phialides (Phialophora, Wangiella), adelophialides (Phialemonium without collarettes, Lecythophora with collarettes), differentiation of conidiophores (Xylohypha versus Cladosporium) and conidial hilum, septation and germination (Bipolaris, Drechslera, Exserohilum). Useful laboratory tests include the 12% gelatin test (controversial), nitrate assimilation (W. dermatitidis is negative, most other species are positive), and determination of temperature maxima (especially 37 degrees C for E. jeanselmei, 40 degrees C for W. dermatitidis and B. spicifera, 42 degrees C for X. bantiana, and 45 degrees C for Dactylaria constricta var. gallopava and Scedosporium inflatum).     

Laboratory Techniques Alternative to In Vivo Experiments for Studying the Liberation, Penetration and Fungicidal Action of Topical Antimycotic Agents in the Skin, Including Ciclopiroxolamine

Summary: Short-term experiments on excised skin (human, pig) gave the following results: 1. In the tissue activity test with direct inoculation (D-TAT) commercial preparations of the non-azole antimycotics ciclopiroxolamine, tolnaftate and naftifine, produced higher inhibitory activity against Trichophyton mentagrophytes (standard strain) in various levels of the horny layer than were produced by the azole antimycotics econazole, miconazole, clotrimazole, oxiconazole and bifonazole. Fast drying solutions of antimycotics invariably gave higher inhibitory activities than creams. In the ultrafiltration tissue activity test (UFT- TAT) against Candida albicans (2 strains), antimycotic agents ranked in order of effectiveness as follows: ciclopiroxolamine – most of the azole antimycotics – bifonazole and naftifine. 2. In tests of fungicidal activity against T. mentagrophytes (2 strains) and Microsporum gypseum (1 strain) the first step was to inoculate the skin surface. After the horny layer had been penetrated by fungal mycelia, antimycotic agents of documented fungicidal potency, chiefly in the form of creams, were applied to the skin surface and left to act for up to 18 hours. The horny layer and epidermis were then scraped off and the concentration of viable fungi was determined. Ciclopiroxolamine cream and lotion produced by far the greatest diminution in viable fungi; creams containing oxiconazole and naftifine were moderately effective and those containing tioconazole and bifonazole produced a relatively small decrease in viable fungi. To avoid erroneous results it is important to homogenize and dilute the skin scrapings; if this is not done certain antimycotics will give misleadingly high fungal killing rates. At this early stage the scatter of results is still wide and minor differences in efficacy cannot as yet be detected with certainty. 3. From the results of various comparative tests it is evident that pig skin can be used as a substitute for human skin in the tests listed under 1. and 2. above. This discovery may make a valuable contribution towards limiting the need for experiments on living animals and trials on human beings. Zusammenfassung: In Kurzzeitversuchen an exzidierter Haut (Mensch, Schwein) wurde gefunden: 1. Im Gewebeaktivitätstest mit direkter Inokulation (D-GAT) wurde mit Handelspräparaten der Nichtazol-Antimykotika Ciclopiroxolamin, Tolnaftat und Naftifin in verschiedenen Hornschichtniveaus eine höhere Hemmaktivität gegenüber Trichophyton mentagrophytes (Standard-Stamm) erzielt als mit solchen der Azol-Antimykotika Econazol, Miconazol, Clotrimazol, Oxiconazol und Bifonazol. Rasch trocknende Lösungen von Antimykotika ergaben durchweg höhere Hemmaktivitäten als Cremes. Im Ultrafiltrations-Gewebeaktivitätstest (UFT-GAT) gegenüber Candida albicans (2 Stämme) ergab sich nach erzielter Wirksamkeit die Rangfolge Ciclopiroxolamine – Mehrzahl der Azolantimykotika – Bifonazol und Naftifin. 2. In Fungizidie-Testen gegenüber T. mentagrophytes (2 Stämme) und Microsporum gypseum (1 Stamm) wurde zunächst die Hautoberfläche inokuliert. Nach Durchdringung der Hornschicht mit Pilzmyzelien wirkten auf die Hautoberfläche bis zu 18 Stunden lang überwiegend Cremes von als fungizid publizierten Antimykotika ein. Während sich in abgeschabter Hornschicht und Epidermis der so bearbeiteten Hautoberflächen mit Ciclopiroxolamin-Creme und -Lotion die weitaus höchste Verminderung lebensfähiger Keime ergab, bewirkten Cremes mit Oxiconazol und Naftifin eine mittlere und solche mit Tioconazol und Bifonazol eine relativ niedrige Keimeliminierung. Zur Vermeidung von fehlerhaften Ergebuissen mußten Homogenisierung und Verdünnung der Hautschabsel erfolgen, anderenfalls bei mehreren Antimykotika eine zu hohe Keimabtötung vorgetäuscht worden wäre. Wegen der vorerst noch hohen Streuung der Ergebnisse können kleinere Wirksamkeitsunterschiede noch nicht sicher erfaßt werden. 3. Nach dem Ergebnis verschiedener Vergleichstests kann in den Testen zu 1. und 2. Schweinehaut als Ersatz für Haut vom Menschen dienen und dürfte damit wesentlich zur Einschränkung von Versuchen am lebenden Tier und von Prüfungen am Menschen beitragen.     

Efficiency of crude and purified fungal antigens in serodiagnosis to discriminate mycotic from other respiratory diseases

Mycotic immunodiagnosis was performed in 186 hospitalized patients with different respiratory diseases, mostly considered as tuberculosis and others with a doubtful diagnosis. Crude histoplasmin, coccidioidin, paracoccidioidin, blastomycin, candidin, aspergillin, and sporotrichin, as well as purified polysaccharide-protein complexes (PPC) of Histoplasma capsulatum, Coccidioides immitis, and Paracoccidioides brasiliensis were used as antigens. Immune tests used included skin test (ST), gel immunodiffusion (ID), counterimmunoelectrophoresis (CIE), complement fixation (CF), and ELISA. A possible association with candidosis was observed in 17% of patients with tuberculosis and diabetes; one presumptive paracoccidioidomycosis, one confirmed aspergillosis, and six cases of active histoplasmosis were determined. Candidin ST showed 29% of positive reactions with an increased frequency in patients between 31 and 55 years of age. CF test showed the highest positivity percentages with crude antigens, specially for Candida antigen (26.3%) and histoplasmin (18.2%). Cross reactions were evident with crude antigens but decreased when PPC's were used in ELISA.     

Isoconazole nitrate in the treatment of tropical dermatomycoses

Summary. A total of 54 patients with culturally proven tropical dermatomycoses, comprising 23 with various types of dermatophytoses, one with foot infection due to Trichosporon beigelii and one with foot infection due to Geotrichum candidum , two with candidoses of the groin and 27 with pityriasis versicolor, were included in a clinical trial of efficacy of 1% isoconazole cream (Travogen^R, Schering, Berlin, Germany). Five patients were not evaluable. A clinical and mycological cure was achieved in 29 cases in 3–4 weeks. In 15 (31%) of the remaining patients treatment was required for 5–6 weeks, while another three patients required treatment for 8 weeks. In two patients the disease proved to be resistant to treatment with the drug.
Zusammenfassung. Insgesamt 54 Patienten mit kulturell gesicherter Dermatomykose, (23 unterschiedliche Dermatophytosen, eine Trichosporon beigelii - und eine Geotrichum candidum -Fußinfektion, 2 Candidosen der Leistengegend und 27 Pityriasis versicolor) wurden in einer klinischen Wirksamkeits-studie mit 1% iger Isoconazol-Creme (Travogen^R, Schering, Berlin, Deutschland) behandelt. Fünf Patienten waren nicht auswertbar. Eine klinische und mykologische Heilung wurde bei 47 von 49 Patienten (96%) erreicht. Bei 29 patienten (59%) wurde die Heilung bereits nach 3–4 Wochen Behandlung erreicht. Weitere 15 Patienten (31%) benötigten 5–6 Wochen und drei Patienten 8 Wochen Behandlungsdauer. Zwei Mykosesituationen erwiesen sich als therapieresistent.     

Orale Langzeitbehandlung von Onychomykosen mit Ketoconazol

Zusammenfassung: An der Studie zur Wirksamkeit und Anwendungssicherheit von Ketoconazol nahmen 27 Männer im Alter von 20 bis 80 (Median: 57) Jahre, davon 18 mit Onychomykosen und 9 als KontroUen bei den Laborwertbestimmungen, teil. Während des ersten Behandlungsmonats erhielten je 9 Patienten 200 mg und 400 mg Ketoconazol täglich. Danach wurden beide Gruppen 6 Monate mit 200 mg/d weiterbehandelt. Die klinische Beurteilung sowie hämatologische, biochemische und Plasmaspiegeluntersu-chungen erfolgten mindestens monafich, mykologische Untersuchungen wurden vor Aufnahme und bei Beendigung der Therapie vorgenommen. Erne letzte klinische Unter-suchung erfolgte 1 Jahr nach Beginn der Studie. Nach 7 Monaten Behandlung wurden 23 von 30 Nägeln mit “gebessert” bis “stark gebessert” beurteilt, nach dem behandlungsfreien Intervall galt dies für 28 von 30 Nägeln. Die Plasmaspiegel waren mit 200 mg/d ausreichend und uber den Behandlungszeit-raum konstant. Dies spricht für gute orale Resorption und Abwesenheit von Enzyminduktion. Die Laborwerte zeigten im Vergleich zu den Kontrollen und den Werten vor Behandlung keine signifikanten Abweichungen, so daß myelo-, nephro- und hepatotoxische Wirkungen von 400 bzw. 200 mg/d ausgeschlossen werden können. Der Lipidhaushalt wurde nicht beeinfluat und es trat unter Therapie als Folge der Ketoconazolwirkung lediglich Lanosterin im Serum auf. Nach Beendigung der Therapie ging der Lanosteringehalt schnell zurück. Damit erweist sich Ketoconazol in den angewandten Dosen als ein gut verträgliches und zur Langzeitbehandlung von Onychomykosen geeignetes Antimykotikum. Summary: Twenty-seven males with a median age of 57 (range: 20 to 80) years took part in this study on the efficacy and safety of ketoconazole. Eighteen men suffered from onychomycosis; nine served as controls in the safety evaluation. During the first month of treatment, nine patients received 200 mg and the nine other 400 mg ketoconazole daily. Then the treatment was uniformly continued with 200 mg/d for 6 months. Clinical evaluation and haematological, biochemical and plasma level investigations were carried out at least at monthly intervals; mycological controls were performed at the start and end of therapy. A final clinical evaluation was carried out one year after the start of the study. After 7 months of treatment, moderate or definite clinical improvement was obtained in 23 out of 30 nails. After 5 more months without antimycotic treatment this was the case in 28 of 30 nails. Plasma levels obtained with 200 mg ketoconazole daily were adequate and constant during the entire treatment period. This indicates a good oral resorption as well as the absence of induction of hepatic enzymes. The laboratory values did not show significant deviations as compared with the controls or with the pretreatment values. This excludes myelo-, nephro- and hepatotoxic effects of 400 and 200 mg ketoconazole daily. The lipid metabolism was not influenced, the only difference was the occurrence of lanosterol in the serum, which is a result of the mechanism of action of ketoconazole. After the medication period the lanosterol levels subsided rapidly. In the applied doses ketoconazole is a well-tolerated and effective drug for the systemic long-term treatment of onychomycosis.     

Large-scale molecular characterization and analysis of gastric cancer

The recent effort by The Cancer Genome Atlas （TCGA） Network has revealed that gastric cancer, which is a leading cause of cancerrelated deaths worldwide with a 5-year survival rate less than 25%, is a much more heterogeneous disease than previously thought. And yet, conventional treatment approaches and clinical trials have assumed it is a single disease. Although it is well known that under the microscope, gastric cancer cells appear quite different, the current classification scheme recognizes two main categories of gastric cancer： diffuse and intestinal.     

A conceptually new treatment approach for relapsed glioblastoma: Coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care

To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma''s compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.     

Endometrial cancers and predisposition

As nearly 5% of all endometrial cancers occur because of a predisposition, this possibility has systematically to be explored. The hallmarks of predisposition, a young age at diagnosis, a personal or a familial history of cancer, have to be searched systematically. The identification of a predisposition in a family has a major impact on the management of the proband or his relatives. The endometrial cancer main predisposition is Lynch's syndrome. In this review, we will focus on this condition and describe its clinical manifestations, the underlying molecular mechanisms, the cancer risks and the management guidelines. We will also get onto some far less frequent other predispositions.