消炎痛抑制胶质瘤细胞合成前列腺素E2的实验研究

目的 探讨脑胶质瘤与ＰＧＥ２之间的内在联系，找出消炎痛类药物做为胶质瘤辅助治疗的可能性。方法 对２０例胶质瘤标本进行细胞培养１周，测其上清液中的ＰＥＧ２含量。对１０例胶质瘤细胞培养液中加入不同浓度消炎痛溶液，培养１周后测其上清液ＰＧＥ２的含量。同时对１５例胶质瘤患者血浆中ＰＧＥ２的水平进行测定。结果 胶质瘤合成ＰＧＥ２的量高于正常脑组织合成ＰＧＥ２的２倍以上（Ｐ＜０．００１）。不同浓度的消炎瘤对胶     

射波刀对复发脑胶质瘤患者Th1／Th2细胞因子的影响

[目的]观察射波刀治疗对复发脑胶质瘤患者Th1/Th2细胞因子含量的影响,探讨射波刀治疗复发脑胶质瘤的效果和可能机制。[方法]33例脑胶质瘤患者接受射波刀治疗,在治疗前、治疗后1周、2周、4周、8周、16周分别采用酶联免疫吸附试验(ELISA)测定患者外周血中的Th1细胞因子白细胞介素-2(IL-2)、干扰素-γ(IFN-γ)以及Th2细胞因子白细胞介素-4(IL-4)、白细胞介素-10(IL-10)含量,并与正常对照组比较。[结果]治疗前脑胶质瘤患者外周血IL-2、IFN-γ含量低于对照组,而IL-4、IL-10含量高于对照组,差异有统计学意义(P<0.05)。射波刀治疗后2周患者外周血中IL-2、IFN-γ含量开始升高,而IL-4、IL-10水平开始下降,于射波刀治疗后16周IL-2、IFN-γ、IL-4、IL-10含量达正常水平。射波刀治疗复发胶质瘤有效率33.33%,控制率69.69%。[结论]脑胶质瘤患者体内存在Th1/Th2细胞因子失平衡状态。射波刀治疗复发脑胶质瘤疗效可靠,其治疗作用可能与纠正患者体内Th1/Th2细胞因子的失平衡状态有关。     

环氧合酶-2、前列腺素E2在大肠腺瘤和腺癌组织中的表达

目的:研究COX-2、PGE2在大肠腺瘤和腺癌组织中的表达和意义。方法:选取组织标本118例,其中正常大肠黏膜30例,大肠腺瘤43例,大肠腺癌组织45例。Real Time PCR法检测组织中COX-2mRNA的表达,免疫组织化Elivision法检测组织中COX-2的蛋白表达,放射免疫法测定组织中PGE2含量。结果:COX-2在大肠腺癌组织中的mRNA的表达、阳性表达率及光密度值分别高于大肠腺瘤及正常黏膜组(P<0.05);且大肠腺瘤组高于正常黏膜组(P<0.05)。大肠腺癌组织PGE2含量高于大肠腺瘤及正常大肠黏膜(P<0.01);且大肠腺瘤高于正常大肠黏膜(P<0.01)。结论:大肠黏膜癌变过程中COX-2表达增高,PGE2合成增多。     

非小细胞肺癌患者肺组织环氧合酶-2表达的变化及其临床意义

目的探讨非小细胞肺癌(NSCLC)患者肺组织中环氧合酶-2(COX-2)的表达和血浆PGE 2含量的变化及其与临床病理参数之间的关系.方法采用逆转录聚合酶联反应(RT-PCR)和放射免疫法,分别检测38例NSCLC患者和正常健康者肺组织中COX-2 mRNA的表达以及血浆PGE 2含量的变化.结果 38例肺癌患者肺癌组织和正常肺组织中分别有34例和3例检测到COX-2 mRNA表达,阳性表达率分别为13.16%和89.47%;半定量分析肺癌组织中的COX-2 mRNA平均吸光度显著高于正常肺组织(P＜0.001).肺癌患者和正常健康者血浆中PGE 2浓度分别为(42.33±6.13)μg/L和(5.87±1.40)μg/L,二者比较,差异亦具有显著性(P＜0.01).直线相关分析肺癌组织中COX-2 mRNA的表达和PGE 2浓度的变化呈正相关(r=0.552,P＜0.05).COX-2 mRNA表达在不同性别、年龄、组织分型、TNM分期和分化程度之间差异分别均无显著性(P＞0.05).结论 NSCLC患者肺癌级织中COX-2 mRNA和PGE 2表达增强,可能在NSCLC的发生和发展中具有重要作用.     

脑胶质瘤组织中的circSORBS1水平及临床意义分析

目的 探讨脑胶质瘤组织的circSORBS1(hsa＿circ＿0094606)水平及临床意义。方法 收集本院2017年1月至2020年12月手术切除并经病理证实的脑胶质瘤组织97例，以颅内减压术中切除的正常脑组织31例为参照采用实时荧光定量PCR(qPCR)检测脑胶质瘤组织的circSORBS1水平，结合临床病理特征和随访数据分析circSORBS1的临床意义。结果 脑胶质瘤组织的circSORBS1水平为4.281±0.192,高于31例正常脑组织的1.453±0.138,差异有统计学意义(t=8.107,P<0.001);组织circSORBS1水平诊断脑胶质瘤的曲线下面积为0.889(95%CI:0.835～0.943,P<0.001)。分层分析显示circSORBS1水平与性别、年龄和瘤周水肿无关(P>0.05),而与病理类型、分化程度、病理分级和浸润深度有关(P<0.05)。全组随访8～36个月，中位随访22.0个月，中位OS为22.0个月，circSORBS1高水平组的中位OS为16.0个月，劣于高水平组的25.0个月(HR=3.487,95%CI...     

肺腺癌细胞对RAW264.7巨噬细胞分化的影响

摘 要：［目的］ 体外探究Lewis肺腺癌（Lewis lung carcinoma,LLC）细胞培养上清液对小鼠RAW264.7巨噬细胞极化的影响及其可能机制。［方法］ RAW264.7细胞按如下分组：空白对照组、IL-4处理组、LLC细胞培养上清液条件培养基（LLC-CM）培养组和TC-1细胞培养上清液条件培养基（TC-1-CM）培养组。各组培养48h后收集上清液和细胞,酶联免疫吸附测定（ELISA）检测空白对照组、IL-4组、LLC-CM组和TC-1-CM组巨噬细胞及LLC细胞和TC-1细胞培养上清液中补体C1q的含量,实时荧光定量PCR（qRT-PCR）检测巨噬细胞CD68、CD80、CD206、Arg-1、IL-10和IL-27 mRNA,Western blot检测CD68、CD80、CD206、Arg-1、JAK2、p-JAK2、STAT5和p-STAT5的表达。［结果］ 巨噬细胞经IL-4处理后,上清液中补体C1q含量较空白对照组升高（P<0.001）;与空白对照组及IL-4处理组相比,LLC-CM组巨噬细胞培养上清液中补体C1q含量明显升高（P均<0.001）。与空白对照组相比,LLC-CM组巨噬细胞CD80表达明显降低（P<0.001）,CD206、Arg-1、IL-10和IL-27表达明显升高（P均<0.001）,p-JAK2、p-STAT5（P均<0.001）含量降低。此外,LLC-CM组巨噬细胞p-JAK2、p-STAT5表达量低于IL-4处理组（P均<0.001）。［结论］ LLC细胞培养上清液可以通过抑制RAW264.7细胞JAK2/STAT5通路诱导其发生M2型极化并促进补体C1q高表达,高水平补体C1q可能参与促进RAW264.7细胞的M2型极化。     

胶质瘤组织中PTTG、MMP-2和Survivin的表达及意义

目的:检测脑胶质瘤组织中PTTG、MMP-2和Survivin的表达情况并探讨其意义。方法:采用免疫组织化学SP法检测50例脑胶质瘤、10例正常脑组织中三者的表达情况。结果:脑胶质瘤组织中PTTG、MMP-2和Survivin表达定位于细胞浆,其阳性表达率分别为80.00%(40/50)、74.00%(37/50)和60.00%(30/50)与正常脑组织0、0和10%存在差异(P<0.05)。与胶质瘤患者的年龄、性别无明显相关性(P>0.05),但Ⅲ-Ⅳ组与Ⅰ-Ⅱ组之间表达有差异,具有统计学意义(P<0.05)。在脑胶质瘤组织中PTTG、MMP-2和Survivin的阳性表达呈正相关(P<0.05)。结论:PTTG、MMP-2和Survivin在脑胶质瘤组织中的表达情况,提示PTTG、MMP-2和Survivin高表达可能与胶质瘤发生有关,且与胶质瘤的浸润、发展、转移有关。     

人脑胶质瘤中PI3K/AKT通路蛋白的表达及其与胶质瘤发生发展的相关性

目的探讨人脑胶质瘤中PI3K/AKT通路蛋白的表达及其与胶质瘤发生发展的相关性。方法选取脑胶质瘤患者84例,依据病理分级将这些患者分为低恶性组(Ⅰ~Ⅱ级,n=42)和高恶性组(Ⅲ~Ⅳ级,n=42)。将这些患者作为脑胶质瘤组,另选取同期采集的20例正常脑组织作为正常对照组。对胶质瘤不同病理分级与正常脑组织中PI3K、AKT、PTEN蛋白表达、人脑胶质瘤中PI3K、AKT、PTEN蛋白表达之间的相关性进行统计分析。结果脑胶质瘤组PI3K、AKT阳性率均显著高于正常对照组(P<0.05),PTEN阳性率显著低于正常对照组(P<0.05);脑胶质瘤组中高恶性组PI3K、AKT阳性率均显著高于低恶性组(P<0.05),PTEN阳性率显著低于低恶性组(P<0.05);高恶性组、低恶性组PI3K、AKT阳性率均显著高于正常对照组(P<0.05),PTEN阳性率显著低于正常对照组(P<0.05)。84例人脑胶质瘤组织中,66例PI3K、AKT蛋白共同阳性表达,2例共同阴性表达。人脑胶质瘤中PI3K、AKT与PTEN蛋白表达均呈负相关关系(P<0.05),而PI3K与AKT呈显著的正相关关系(P<0.05)。结论人脑胶质瘤中PI3K/AKT通路蛋白在脑胶质瘤中的表达提升,与胶质瘤病理分级呈显著的正相关关系。     

乳腺癌手术前后血浆前列腺素E2水平变化及意义

目的　研究血浆前列腺素E2 (ProstaglandinE2 ,PGE2 )水平与乳腺癌的诊断和预后的关系。方法　应用放射免疫分析法测定 80例乳腺癌患者、10例正常献血员的血浆PGE2 水平。结果　乳腺癌患者血浆PGE2 水平显著高于正常对照组 (P <0 .0 1) ,转移性乳腺癌患者的血浆PGE2 水平显著高于无转移者 (P <0 .0 1) ,术后血浆PGE2 水平较术前下降显著 (P <0 .0 1)。结论　乳腺癌组织产生PGE2 并释放入血 ,血浆PGE2 水平与乳腺癌的转移有密切的关系。     

不同强度有氧运动对脑胶质瘤术后化疗患者癌因性疲乏及HPA轴功能的影响

目的探讨不同强度有氧运动对脑胶质瘤术后化疗患者癌因性疲乏(CRF)及下丘脑-垂体-肾上腺皮质(HPA)轴功能的影响。方法选取脑胶质瘤术后化疗并发CRF患者76例,随机分为2组,各38例。A组予以25%VO2max的强度进行有氧运动,B组予以50%VO2max的强度进行有氧运动,2组均连用8周。统计分析2组治疗前后HPA轴功能[血清促肾上腺皮质激素(ACTH)和皮质醇(CORT)]和Piper疲乏量表评分的变化,并比较其临床疗效。结果治疗8周后,2组血清ACTH较前明显降低,CORT水平较前明显提升(P<0.05或P<0.01),且B组降低或提升幅度明显优于A组(P<0.05)。2组Piper疲乏评分较前明显减低(P<0.05或P<0.01),且B组降低明显优于A组(P<0.05)。B组患者临床总有效率(94.74%)高于A组(78.95%)(χ²=4.040,P<0.05)。结论50%VO2max的有氧运动对脑胶质瘤术后化疗患者患者CRF及HPA轴的影响明显优于25%VO2max的有氧运动。     

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).     

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.     

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.     

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.