肾细胞癌组织中HIF-1α和HIF-2α的表达及与血管生成的关系

目的探讨缺氧诱导因子（HIF）-1α、HIF-2α、CD34在肾细胞癌组织中的表达及其与血管生成癌转移的关系。方法应用免疫组化技术检测60例肾细胞癌组织中HIF-1α，HIF-2α的表达。用抗CD34单克隆抗体显示血管内皮细胞，对CD34阳性血管进行微血管密度（MVD）计数。结果肾细胞癌组织中HIF-2α的阳性染色率（78．3％）高于HIF-1α的阳性染色率（61．7％），差异具有统计学意义（P〈0．05），HIF-2α阳性组MVD值高于其阴性组（t=4．336，P〈0．05），HIF-2α的表达与MVD存在正相关（r=0．545，P〈0．01），但肿瘤的分级、分期与HIF-1α、HIF-2α的表达无关（P〉0．05）。结论HIF-2α在肾细胞癌组织中的表达比HIF-1α更广泛，HIF-2α的表达可能对肾细胞癌的发生、发展及血管生成具有更为重要的作用。     

N—myc下游调节基因1蛋白在肾细胞癌中的表达及其意义

目的探讨N—myc下游调节基因1（NDRG1）蛋白在肾细胞癌组织中的表达及其与微血管密度（MVD）和临床病理因素之间的关系。方法应用免疫组织化学sP法检测49例肾细胞癌及相应癌旁正常肾组织NDRG1和CD34表达,采用CD34染色进行MVD计数。结果NDRG1为细胞质和（或）膜表达蛋白,在正常肾近曲小管、远曲小管表达率为100％（49／49）,显著高于在。肾细胞癌组织中的阳性率[51％（25／49）]（P〈0．05）。NDRG1表达随组织学分级增高而降低（x^2=9．968,P=0．007）;有淋巴结转移组和无淋巴结转移组NDRG1表达率分别为0（0／5）和56．8％（25／44）,差异有统计学意义（X^2=5．800,P=0．016）;NDRG1表达越低,临床分期越晚（X^2=6．437,P=0．011）,MVD值越高（t=2．235,P=0．030）。结论NDRGI在肾细胞癌中可能为一种抑癌基因,其表达降低与肾细胞癌侵袭、转移有关,且可能通过参与调节肾细胞癌血管形成而发挥抑制肿瘤生长和转移的作用。     

4-1BB/4-1BBL在胃癌组织及其外周血中的表达及临床意义

目的探讨胃癌局部免疫与全身免疫状态。方法应用流式细胞术,测定胃癌患者癌组织及外周血中T淋巴细胞亚群、NK细胞水平,同时测定癌组织、癌周正常胃黏膜、淋巴结及外周血单个核细胞中4-1BB、4-1BBL含量。结果胃癌患者外周血中CD3^＋、CD4^＋、CD4^＋/CD8^＋比值和NK细胞表达水平均显著高于胃癌组织（P〈0.05）,CD8^＋细胞计数反之（P〈0.05）。4-1BB表达量由低到高的顺序为外周血单个核细胞、正常胃黏膜、淋巴结、癌组织、癌组织中单个核细胞;其中癌组织明显高于正常黏膜（P〈0.05）,有统计学意义;外周血单个核细胞中4-1BB表达量明显低于其他组织,有统计学意义（P〈0.01）。癌组织中4-1BBL表达量低于正常黏膜,有统计学意义（P〈0.05）。癌组织中4-1BB表达量与CD4^＋/CD8^＋比值、NK细胞表达水平呈负相关关系,4-1BBL与CD4^＋/CD8^＋比值、NK细胞表达水平呈正相关关系,有统计学意义（P〈0.05）。结论胃癌组织内免疫力低下,处于免疫抑制状态,胃癌组织的低免疫状态与4-1BBL缺乏有关;4-1BB与胃癌患者局部和全身的免疫状态亦有密切关系。总之,胃癌组织中4-1BB/4-1BBL的表达失衡与胃癌的免疫逃逸、低免疫状态有关。     

左肾黏液样小管状和梭形细胞癌1例并文献复习

目的:探讨肾黏液样小管状和梭形细胞癌患者的临床病理特征、治疗方法、疗效评价及预后。方法:回顾性分析我们收治的1例左肾黏液样小管状和梭形细胞癌患者的临床病理资料,并复习相关文献。患者女,54岁。因左侧腰部疼痛就诊,CT检查提示左肾下极见大小约44 mm×37 mm×31 mm团块样影。结果:行左肾部分切除术,术后病理诊断:左肾黏液样小管状和梭形细胞癌。免疫组化:肿瘤细胞P-CK（+）,EMA（+）,CD68（PGM1）（-）,CK7（+）,CAM5.2（-）,PAX-8（+）,CK20（-）,Inhibin-a（-）,RCC（-）,Vimentin（+）,CD10（-）。术后患者恢复良好,康复出院,随访至今未见复发及转移。结论:肾黏液样小管状和梭形细胞癌是一类罕见的肾细胞癌,恶性程度相对较低,预后相对较好,治疗方法目前主张手术治疗,但术后仍需注意规律随访。     

胆管癌合并多房囊性肾细胞癌临床病理观察

目的：探讨胆管癌合并多房囊性肾细胞癌的临床病理特点。方法：对1例胆管癌合并多房囊性肾细胞癌进行临床资料分析和光镜、免疫组化（SP法）观察。结果：胆管为中分化腺癌;右肾上极肿物呈多房、囊性,内衬透明细胞,细胞异型性不明显,囊壁间可见透明细胞巢。免疫组化示：胆管肿物：CK19（＋＋＋）、CK35（＋＋＋）;右肾上极肿物：肾细胞癌（＋）、Vimentin（＋＋）、CD10（＋）。结论：胆管癌合并多房囊性肾细胞癌极少见,病理学检查是诊断的主要依据。     

CD4+CD25+调节性T 细胞对乳腺癌细胞上皮间质转化和ALDH1+干样细胞的影响*

目的:研究CD4+CD25+调节性T 细胞（regulatory T cells ,Tregs）对乳腺癌细胞上皮间质转化（epithelial-mesenchymal transition ,EMT ）、细胞迁移侵袭能力,及ALDH1+干样细胞比例的影响。方法:采用免疫磁珠法分离乳腺癌患者外周血中CD4+CD25+Tregs,CD4+CD25+Tregs与乳腺癌BT474、MCF-7 细胞系共培养（共培养组）,BT474、MCF-7 单独培养（对照组）。 检测共培养组和对照组乳腺癌细胞EMT 相关标志物表达的变化,及细胞迁移和侵袭能力的变化。此外,检测BT474 细胞中ALDH1+干样细胞、微球形成能力和自我更新能力的变化。结果:CD4+CD25+Tregs诱导BT474 和MCF-7 细胞间质性标志物表达增高,诱导MCF-7 细胞上皮性标志物E-cadherin 表达降低。CD4+CD25+Tregs诱导BT474 和MCF-7 细胞迁移和侵袭能力上调。共培养组BT474 细胞中ALDH1+干样细胞比例、微球体形成能力、自我更新能力较对照组增强。结论:CD4+CD25+Tregs可诱导乳腺癌细胞发生EMT ,增强细胞体外迁移和侵袭能力,同时促进ALDH1+干样细胞增加。      

Wnt通路拮抗基因SFRP1 SFRP2 SFRP4 SFRP5甲基化状态与肾透明细胞癌关系的研究

研究SFRPs家族中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状况,探讨基因的甲基化与肾透明细胞癌发生发展的关系。方法:采用甲基化特异性PCR（methylation specific PCR,MSP）方法检测66例肾透明细胞癌及30例癌旁组织中SFRP1、SFRP2、SFRP4、SFRP5基因启动子区甲基化状态及其与临床病理学资料之间的关系。结果:肾透明细胞癌组织中SFRP1、SFRP2、SFRP4、SFRP5基因甲基化率分别为77.3%（51/66）、72.7%（48/66）、59.1%（39/66）、69.7%（46/66）,均显著高于相应的癌旁组织,结果有统计学意义（P<0.05）。与临床病理学资料相联系,肾透明细胞癌组织中SFRP1、SFRP5基因甲基化与肿瘤TNM分期相关;SFRP4基因甲基化与肿瘤的病理学分级相关（P<0.05）。结论:SFRP1、SFRP2、SFRP4、SFRP5基因的甲基化均可能参与肾透明细胞癌的发生。SFRP1、SFRP5基因甲基化可能与肾透明细胞癌的发展,浸润和转移有关。SFRP4基因甲基化可能与肾透明细胞癌的恶性行为有关。      

肝细胞性肝癌组织浸润淋巴细胞表型与分布研究

目的:肝细胞性肝癌组织浸润淋巴细胞与外周血T 细胞表型可能与肿瘤进展及预后相关,本研究检测肝癌患者组织及外周血T 细胞表型与分布,分析淋巴细胞表型变化与预后的关系。方法:分析2007年10月至12月中山医院147 例肝癌及癌旁组织浸润淋巴细胞表型（T 细胞或B 细胞表面标志物:CD3、CD8、CD4、CD20、CD19、Foxp 3）,表型与临床病理特征及预后的关系;检测26例肝癌外周血CD3、CD8、CD4 +T细胞数量并其比例变化。结果:癌巢内肿瘤浸润细胞明显少于癌周组织（P < 0.01）,癌周淋巴细胞主要分布于癌旁正常肝组织、汇管区,其与患者肝炎病史及肝硬化相关,表型以CD3 +T细胞为主,其中又以CD8 + 细胞毒性T 细胞为主;CD4 染色在多数病例为阴性,Foxp 3 仅在个别病例（15/ 109）呈阳性。肿瘤浸润淋巴细胞B 细胞标志CD20、CD19均为阴性。肿瘤组织内CD8 +T细胞浸润数量与预后正相关,而癌周浸润淋巴细胞数目与患者转移及复发无显著关系。结论:肝癌肿瘤浸润细胞在癌巢内明显少于癌周组织,肿瘤及癌周浸润细胞以CD8 + 细胞毒性T 细胞为主。肿瘤组织内CD8 +T细胞浸润数量与预后相关,而癌周浸润淋巴细胞数量与患者转移及复发无显著关系。      

基于TCGA泛癌症分析线粒体裂变调节因子1的表达和预后意义

目的:基于TCGA泛癌症分析线粒体裂变调节因子1(mitochondrial fission regulator 1,MTFR1)的表达、预后意义及作用机制。方法:应用TCGA门户网站UALCAN泛癌症分析MTFR1的表达变化及预后关系；通过蛋白质相互作用平台STRING下载与MTFR1相互作用的蛋白质谱，经DAVID 6.8进行基因本体（GO）和KEGG信号通路分析。结果:UALCAN分析表明MTFR1在乳腺癌、肺鳞状细胞癌、头颈部鳞状细胞癌和食管癌中高表达（P＜0.001），而在肾透明细胞癌和甲状腺癌中低表达（P＜0.001）。MTFR1表达不利于乳腺癌、肺鳞状细胞癌和甲状腺癌的预后（P=0.014、P=0.022、P=0.001 3），而利于肾透明细胞癌的预后（P=0.005 3）。DAVID 6.8分析表明MTFR1相互作用蛋白主要定位于细胞膜；参与蛋白水解、线粒体靶向蛋白、蛋白质靶向内质网、信号肽处理过程；主要结合金属离子，具有金属肽酶、丝氨酸型肽酶和丝氨酸型内切酶活性等功能；参与的信号通路主要包括肾素-血管紧张素系统和谷胱甘肽代谢等。结论:MTFR1在乳腺癌、肺鳞状细胞癌、头颈部鳞状细胞癌和食管癌中高表达，而在肾透明细胞癌和甲状腺癌中低表达。MTFR1表达不利于乳腺癌、肺鳞状细胞癌和甲状腺癌的预后，而利于肾透明细胞癌的预后，可作为上述肿瘤预后的潜在标志物。     

肾细胞癌CD44V6、nm23—H1、PCNA、bcl—2的表达及其意义

目的：研究肾细胞癌组织中CD44V6、nm23-H1、PCNA和bcl-2的表达及其与临床病理的关系。方法：应用免疫组化S－P法检测30例肾细胞癌细胞中上述4项蛋白达的变化。结果肾细胞癌组织中CD44V6、nm23-H1、PCNA和bcl-2的表达率分别为23．3％、50．0％、66．7％和36．75。CD44V6、PCNA的高表达与肾细胞癌的脉管浸润密切相关。CD44V6的高表达还与组织学类型密切相关。nm23-H1、bcl-2的表达与肾细胞癌的脉管浸细胞、组织学类型及组织分级无关,结论CD44V6、PCNA高表达是判断肾细胞癌生物学行的良好指标。     

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.