羧乙基锗倍半氧化物对亚硝基哌嗪诱导大鼠鼻咽癌早期增生病变的阻断作用

羧乙基锗倍半氧化物（Ｇｅ－１３２）在多种体外及动物试验系统中均已证实具有抗致癌作用。本研究在亚硝基哌嗪（ＤＮＰ）诱导大鼠鼻咽癌癌前增生病变（Ⅱ级）模型中，再次证实了Ｇｅ－１３２这类作用。所用ＤＮＰ剂量为３０ｍｇ／ｋｇ，皮下注入每ｗｋ２次，共６ｗｋ，分别在实验的第１２０、２２０、２７０及３００ｄ杀鼠作病理形态及组化检查，随着时间加长，ＤＮＰ引起鼻咽部非典型加重。由柱状上皮转化为圆形储备细胞出现多层增生及鳞状化生，部分细胞大核肥大，深染及空泡形成。核内染色质增加．基底膜嗜银纤维变细，以至成颗沥状。粘液减少或消失。饲料拌入Ｇｅ－１３２，按１５０ｍｇ／ｋｇ／ｄ及３０Ｏｍｇ／ｋｇ／ｄ饲养大鼠，直至实验结束。见不典型增生明显下降，表明Ｇｅ－１３２确有对抗ＤＮＰ诱导大鼠鼻咽癌癌前增生病变的作用。     

Antagonistic combinations of occupational carcinogens

Several epidemiological and experimental studies demonstrate that combinations of carcinogens may interact in a synergistic way. This has prompted speculations that modulating interactions of individual chemical carcinogens are synergistic as a rule. However, various combinations of chemical carcinogens have been described which interact not even additively but in an antagonistic way. The aim of this review is to collect information of antagonistic interactions of occupational carcinogens obtained by epidemiologic and animal studies. In addition, appropriate in vitro studies with the genotoxic endpoints DNA-adducts and micronuclei are included. The toxicological mechanisms of antagonistic interactions, although speculative in some cases, are discussed.     

South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides--a review

Rooibos (Aspalathus linearis (Brum.f) Dahlg.) and honeybush (Cyclopia Vent. species) are popular indigenous South African herbal teas enjoyed for their taste and aroma. Traditional medicinal uses of rooibos in South Africa include alleviation of infantile colic, allergies, asthma and dermatological problems, while a decoction of honeybush was used as a restorative and as an expectorant in chronic catarrh and pulmonary tuberculosis. Traditional medicinal uses of Athrixia phylicoides DC., or bush tea, another indigenous South African plant with very limited localised use as herbal tea, include treatment of boils, acne, infected wounds and infected throats. Currently rooibos and honeybush are produced for the herbal tea market, while bush tea has potential for commercialisation. A summary of the historical and modern uses, botany, distribution, industry and chemical composition of these herbal teas is presented. A comprehensive discussion of in vitro, ex vivo and in vivo biological properties, required to expand their applications as nutraceutical and cosmeceutical products, is included, with the main emphasis on rooibos. Future research needs include more comprehensive chemical characterisation of extracts, identification of marker compounds for extract standardisation and quality control, bioavailability and identification of bio-markers of dietary exposure, investigation of possible herb-drug interactions and plant improvement with regards to composition and bioactivity.     

Development of the Bowman-Birk inhibitor for oral cancer chemoprevention and analysis of Neu immunohistochemical staining intensity with Bowman-Birk inhibitor concentrate treatment

OBJECTIVES/HYPOTHESIS: Cancer chemoprevention is a rapidly evolving approach to reverse or inhibit carcinogenesis, and there is active interest in development of effective chemopreventive agents against head and neck cancers. The retinoids are archetypal chemopreventive agents for oral premalignant lesions. They have significant clinical effect, but widespread use is limited by significant clinical toxicity. The Bowman-Birk Inhibitor is one of several nontoxic compounds exhibiting both potent anticarcinogenic activity and minimal toxicity. The purposes of the study were to summarize the preclinical and clinical development of Bowman-Birk Inhibitor and a Bowman-Birk Inhibitor concentrate against oral premalignant lesions and to evaluate Neu immunohistochemical staining intensity for lesions and simultaneously obtained biopsy specimens of normal-appearing mucosa from the Phase IIa Bowman-Birk Inhibitor concentrate oral leukoplakia chemoprevention trial. STUDY DESIGN: Part I is a selected literature review. Part II is a retrospective analysis of pathological specimens prospectively obtained from the Phase IIa clinical trial of Bowman-Birk Inhibitor concentrate. METHODS: Thirty-two sets of biopsy specimens from lesions and uninvolved oral mucosa before and after treatment with Bowman-Birk Inhibitor concentrate in doses ranging from 200 to 1066 chymotrypsin inhibitory units were examined in blinded fashion for Neu immunohistochemical staining intensity using the 3B-5 monoclonal antibody. Staining intensity scores among the lesion and control biopsy specimens before and after Bowman-Birk Inhibitor concentrate treatment were analyzed and compared with previously obtained values for serum Neu, oral mucosal cell Neu, protease activity, and clinical response to treatment. RESULTS: Mean Neu staining score was significantly higher in lesions compared with uninvolved mucosa (P <.001). Pretreatment staining scores for biopsy specimens of lesions and control biopsy specimens of normal-appearing tissues were correlated (Spearman correlation coefficient [r] = 0.375, P =.045), but no correlation between lesion and control biopsy specimen scores was evident after treatment. The change in Neu staining score with Bowman-Birk Inhibitor concentrate treatment in control site biopsy specimens demonstrated an inverse relationship of change in lesion area with Bowman-Birk Inhibitor concentrate treatment (Spearman r = -0.493, P <.007). CONCLUSION: Bowman-Birk Inhibitor concentrate shows promise to become an effective nontoxic chemopreventive agent based on results of extensive preclinical studies, and Phase I and Phase IIa clinical trials. Bowman-Birk Inhibitor concentrate has dose-related clinical activity against oral leukoplakia and modulates levels of Neu and protease activity. The current investigation identified increased Neu staining intensity in hyperplastic lesions compared with simultaneously obtained biopsy specimens of normal-appearing mucosa both before and after Bowman-Birk Inhibitor concentrate treatment. This finding supports prior observations that increased Neu expression is present in a subset of oral premalignant lesions and head and neck cancers. The trend of increased Neu staining score in control biopsy tissues of subjects exhibiting decreased lesion area following Bowman-Birk Inhibitor concentrate treatment raises questions about the mechanisms of Bowman-Birk Inhibitor concentrate action. One possible explanation is that Bowman-Birk Inhibitor stabilizes the extracellular domain of Neu, thereby preventing receptor truncation and internalization. Further study of modulation of Neu and protease activity by Bowman-Birk Inhibitor concentrate treatment may provide insights into the role of proteases and protease inhibitors in oral premalignant lesions and the mechanisms underlying Bowman-Birk Inhibitor concentrate effects. A Phase IIb randomized, placebo-controlled clinical trial to determine the clinical effectiveness of Bowman-Birk Inhibitor concentrate and further evaluate these candidate biomarkers is under way.     

Anticarcinogenic compounds in the Uzbek medicinal plant, Helichrysum maracandicum

An ethanol extract of Helichrysum maracandicum showed antiproliferative activity against cultured cells of SENCAR mouse in an in vitro assay, and activity-guided fractionation of the extract resulted in the isolation of isosalipurposide as an active substance. Naringenin chalcone, the aglycone of isosalipurposide, also showed strong antiproliferative activity. An in vivo assay of two-stage carcinogenesis on mouse skin revealed that epidermal application of isosalipurposide resulted in delayed formation of papillomas. Western blot analysis showed that the expression of p38 mitogen-activated protein kinase was suppressed by the administration of naringenin chalcone or isosalipurposide, which might be related to the anticarcinogenic activity.     

Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization

Sanguinarine is a benzopheanthridine alkaloid present in the root of Sanguinaria canadensis L. and Chellidonium majus L. In this study, sanguinarine (2 and 3 microM) exhibited cytotoxicity to KB cancer cells by decreasing MTT reduction to 83% and 52% of control after 24-h of exposure. Sanguinarine also inhibited the colony forming capacity (>52-58%) and growth of KB cancer cells at concentrations higher than 0.5-1 microM. Short-term exposure to sanguinarine (>0.5 microM) effectively suppressed the adhesion of KB cells to collagen and fibronectin (FN). Sanguinarine (2 and 3 microM) induced evident apoptosis as indicated by an increase in sub-G0/G1 populations, which was detected after 6-h of exposure. Only a slight increase in cells arresting in S-phase and G2/M was noted. Induction of KB cell apoptosis and necrosis by sanguinarine (2 and 3 microM) was further confirmed by Annexin V-PI dual staining flow cytometry and the presence of DNA fragmentation. The cytotoxicity by sanguinarine was accompanied by an increase in production of reactive oxygen species (ROS) and depolarization of mitochondrial membrane potential as indicated by single cell flow cytometric analysis of DCF and rhodamine fluorescence. NAC (1 and 3 mM) and catalase (2000 U/ml) prevented the sanguinarine-induced ROS production and cytotoxicity, whereas dimethylthiourea (DMT) showed no marked preventive effect. These results suggest that sanguinarine has anticarcinogenic properties with induction of ROS production and mitochondrial membrane depolarization, which mediate cancer cell death.     

静脉注射抗癌药物渗漏致组织损伤的临床研究

目的 :研究静脉注射强刺激性抗癌药物渗漏对组织损伤的有效疗法。方法 :对强刺激性抗癌药物渗漏 96例采用穴位注射治疗 ,并与皮下注射法进行对照研究。结果 :穴注组 96例治愈 94例 ,显效 2例 ,有效率 10 0 % ,明显优于对照组 (P <0 0 0 5 )。穴注 30min后患者持续性剧痛逐渐缓解 ,12h后疼痛、组织红肿明显减轻。第 2次穴注后 ,多数患者症状完全消失。结论 :穴位注射治疗对止痛、消肿、消炎、防止组织坏死有独特之处。只要在抗癌药物渗漏后及时给予穴位注射 ,就能有效防止渗漏性组织损伤的发生。对处理不及时、措施不恰当引起严重静脉炎及组织坏死者 ,穴位注射的效果也很满意     

抗癌中药的新用法

选用无毒抗癌中药内服，选用有毒抗癌中药外用，并阐述了几种中药的抗癌防癌机理：一是药物直接抗癌，二是提高自身免疫力间接抗癌，这种免疫尚能预防癌症复发；外用药除抗癌外尚能有效地止痛。中药在防治癌症中的优势一是内服药因无毒性可长期服用，二是医生可根据每个病人的病症灵活组方，中药治疗确能改善病人的生活质量。     

Biomedical issues of dietary fiber beta-glucan

Beta-glucan is a polysaccharide in the form of fiber and the main element of fiber in grains such as barley, oats, yeast and mushrooms. Many studies have examined the efficacy of beta-glucan in terms of the lipid lowering effects, blood sugar reduction, weight reduction, immune modulator, and anticarcinogenic effect. However, there is no comprehensive review article on the biomedical issues regarding beta-glucan. The authors searched for systematic reviews and clinical experiments for each relevant topic and reviewed the biomedical effects of beta-glucan, for the purpose of developing research strategies for the future.