过热食物对食管粘膜上皮细胞增殖周期影响的放射自显影观察

 给小鼠灌饲75℃热水后前胃粘膜发生三种变化：1.上皮细胞变性和粘膜炎症；2.底层细胞的3H-TdR标记指数下降(P<；0.01)，即底层细胞的G₁期时相延长，表明过热饮食对细胞的核酸代谢有影响；3.菌群增殖并与上皮细胞接触，这可能为粘膜上皮细胞在细菌有害代谢产物的作用下发生癌变创造了有利条件。     

地塞米松不同剂量对小鼠前胃鳞状上皮癌变的研究

本文通过不同剂量地塞米松对小鼠前胃鳞状上皮癌变影响的实验研究,观察了大小剂量的作用效果。灌喂大剂量地塞米松(12mg/kg)经两次重复动物实验,70天和120天的抑制癌变率均在77.78％和46.15％左右,同时也促使癌组织向成熟方向分化。灌喂小剂量地塞米松(1mg/kg),70天和120天时诱发癌变率分别在43.75％和33.33％左右。并讨论了地塞米松抑制小鼠前胃鳞状上皮增生、癌变的机理。     

胃癌高发区庄河市咸猪肉致突变及致胃粘膜损伤作用的研究

作者对胃癌高发区庄河市咸猪肉与胃癌发生的关系进行了系统研究，包括咸猪肉致突变性研究、咸猪肉致人体胃粘膜损伤作用及其暴露水平与粘膜病变的关系研究以及咸猪肉致犬胃粘膜损伤的实验研究。结果发现，胃癌高发区庄河咸猪肉对沙门菌ＴＡ９８有强致突变作用；咸猪肉上清除菌液在２０～８０μｌ／ｍｌ范围内有直接诱导Ｖ７９细胞微核率（ＭＮＲ）和微核细胞率（ＭＮＣＲ）上升作用，两者存在量效关系。在膳食结构基本相同条件下，常年食用自腌咸猪肉居民，胃粘膜病变与对照组相比有明显不同，食用１０年者胃粘膜上皮呈现明显损伤及炎症反应，表现为变性坏死及糜烂灶形成；食用１０＋～２０年者，胃粘膜除上述改变外，尚见上皮腺体增生乃至异型增生；食用２０＋～３０年者胃粘膜上皮呈现不同程度的异型增生乃至癌变。咸猪肉对实验犬的胃粘膜有一定的损伤作用，喂饲时间越长，损伤程度越重。上述研究结果提示：胃粘膜上皮在致突变咸猪肉长期作用下，反复损伤、修复，最终可以发生重度变异乃至癌变。     

林县食管癌户酸菜中白地霉(Geotrichum candidum Link)促癌作用的实验研究——Ⅱ、白地霉对亚硝胺诱发小鼠前胃癌促癌作用的初步观察

 利用甲基苯甲基亚硝胺诱发的小鼠前胃癌模型,在灌喂亚硝胺的同时,灌喂0.5毫升的白地霉液体培养混悬液,观察小鼠前胃癌瘤发生时间与发生率的变化。实验采用A系和昆明两种小鼠。动物分别于14天及1—8个月时处理。发现在实验的第2—7个月,白地霉加亚硝胺组的小鼠的癌瘤发生率均较单独亚硝胺组者为高,而且上皮的癌变灶例数亦较多。单独灌喂白地霉液体培养混悬液的小鼠经过了80-226天,其前胃上皮发生了基底细胞增生、单纯增生、基底细胞花蕾样增生、外突型与内翻型乳头样增生等多种增生性病变。实验结果说明含有白地霉菌体的培养液有促进甲基苯甲基亚硝胺诱发小鼠前胃癌的作用。文中还就促癌作用的物质基础进行了讨论。     

甲基苄基亚硝胺诱发小鼠前胃癌过程中机体免疫反应的动态观察 小鼠对羊红细胞的免疫反应以及胸腺和幽门淋巴结的形态变化

 在以2.5毫克/公斤体重/日剂量的甲基苄基亚硝胺灌喂615系小鼠诱发前胃癌的过程中,小鼠免疫力(胸腺和脾脏重量、胸腺皮质萎缩与否、脾脏白细胞总数、脾脏玫瑰花结形成细胞数(T细胞)和溶血斑形成细胞数(B细胞)、以及血清抗羊红细胞溶血素滴度等发生了波形的变化。在前胃粘膜上皮增生期,它们处于抑制状态,到癌前早期,免疫力几乎回复到正常水平,癌前中晚期后,免疫力再次被重度地抑制。本文讨论了发生波形变化的原因和它带给临床实践的启示,提出了免疫治疗措施应该在癌变早期应用才可能有效的假想。另外,还就癌变过程中前胃粘膜上皮的抗元性问题进行了讨论。由于从实验第7天开始幽门淋巴结(胃的引流淋巴结)即开始肿大,其付皮质区的免疫母细胞亦开始增多,而且增生上皮周围有淋巴细胞浸润,就提示了增生的上皮细胞已经产生了新抗元的可能性。至于它是否就是肿瘤抗元,它在整个癌变过程中是否发生变化,是个必须解决的有关肿瘤免疫的重要问题。     

237例老年人胃癌癌前病变随访分析

目的：分析老年人胃癌癌前病变的特点。方法：237例经胃镜检查有胃癌癌前病变的老年病例,每半年作1次胃镜检查,随访3年,结果：237例中17例（7．2％）发生癌变,胃粘膜不典型增生6例（35．2％）,胃溃疡5例（29．3％）,胃粘膜上皮生化3例（17．7％）,慢性萎缩性胃炎2例（11．8％）,手术后残胃1例6％,结论：老年人胃癌癌前病变容易发生癌变,其中胃粘膜不典型增生癌变率最高。     

杂色曲霉素和脱氧雪腐镰刀菌烯醇对小鼠致癌作用的研究

目的探讨杂色曲霉素(ST)对NIH小鼠的致癌作用,同时研究脱氧雪腐镰刀菌烯醇(DON)对ST致癌作用的影响。方法将180只NIH小鼠随机分为ST 3μg/kg组、ST30μg／kg组、STμg/kg DON1．5pμg／kg组、ST30μg／kg DON1．5μg／kg组、DON1．5μg/kg组和对照组等6组,每组30只。各实验组按要求分别灌喂不同剂量的真菌毒素,对照组灌喂同等容量的生理盐水,3次／周,共24周。实验第58周和第74周处死小鼠,观察各器官组织病变。结果对照组小鼠各器官组织均未见明显病理改变。ST和DON处理组均有部分小鼠发生肺腺癌和腺胃黏膜上皮异型增生。ST3μg／kg组、ST30μg/kg组、ST3μg／kg DON1．5μg／kg组、ST30μg/kg DON1．5μg/kg组和DON1．5μg／kg组肺癌的发生率分别为25．0％、41．7％、62．5％、69．2％和37．5％,腺胃黏膜上皮异型增生发生率分别为50．0％、58．3％、37．5％、53.8％和25．0％。结论经口灌喂ST和DON可诱发NIH小鼠肺癌和腺胃黏膜异型增生。ST加DON可明显提高肺癌的发生率。     

六种中草药阻断食管上皮癌变的实验研究

为研究中草药对食管上皮癌变的阻断作用，我们选用了冬凌草、冬虫夏草、山豆根、乌骨膝、白花蛇舌草、斑蠢等6种文献报道具有抗癌作用的中草药，对380只小鼠前胃鳞状上皮癌变进行了阻断实验研究。现报告如下材料与方法8周龄雌性昆明小鼠380只，体重18－22g。共分对照组80只，其余300只按中草药名称分组，每组50只。参照蔡海英方法（中华医学杂志，1980，60（2）：87）进行诱癌。即用亚硝酸钠0．3g／kg体重和肌氨酸乙酯盐酸盐（NSEE）2g/kg体重，两者分别用0．lIIx）lxL的HCI配成3％和20％的水溶液，灌喂前等量混合，每周灌OW给药2次，…     

林县食管癌户酸菜中白地霉致瘤作用的初步观察

以林县食管癌户酸菜中分离出的白地霉菌灌喂大鼠和小鼠,经过20个月,诱发出前胃上皮增生性变(小鼠64/75例,大鼠23/38例),乳头状瘤及癌前病变(小鼠4/75例,大鼠3/38例)。部分乳头状瘤基底部的增生活跃。在食管引起少数上皮增生与个别癌前病变。本实验结果,白地霉培养物的长期灌喂,能单独引起大、小鼠的乳头状瘤,上皮早期浸润和上皮不典型增生等癌前病变。     

羧乙基锗倍半氧化物对实验诱发小鼠前胃癌变率的影响

用羧乙基锗倍半氧化物（Ｇｅ—１３２）处理ＮＳＥＥ诱发的小鼠前胃鳞状上皮增生、癌变，结果发现实验组的癌变率显著低于对照组（Ｐ＜０．０５），抑癌率为４２．９％，实验组核仁组成区相关嗜银蛋白（Ａｇ—ＮＯＲ）数目及不规则型颗粒的比例显著低子对照组（Ｐ＜０．０５），而实验组之癌周淋巴细胞浸润反应程度较对照组显著增强（Ｐ＜０，０５）。以上结果表明Ｇｅ—１３２可显著降低ＮＳＥＥ诱发小鼠前胃癌的癌变率，并可影响Ａｇ—ＮＯＲ在小鼠前胃鳞状上皮细胞中的表达，Ｇｅ—１３２的以上作用可能与其提高小鼠局部细胞免疫力有关。     

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.