Suppressive Properties of Extracts from Japanese Edible Plants regarding Nitric Oxide Generation

Acetone extracts from a total of 30 species (197 samples) of plants commonly eaten in Japan were tested fortheir in vitro inhibitory properties against nitric oxide (NO) generation in a murine macrophage cell line, RAW264.7, that had been stimulated with lipopolysaccharide in combination with interferon-γ. Evaluation of theeffects of treatment with 100 mg/mL revealed that 6 extracts (3.1%) exerted a strong inhibitory effect (inhibitionrate (IR) ≥70%) with strong cell viability (CV≥70%). However, nine extracts that exhibited an IR of greaterthan 70% were not considered to exert a significant effect at 100 μg/mL due to their low CV (<70%). Of the 14plant families evaluated, Cucurbitaceae (extracts of watermelon 1 and melon 2), Liliaceae (extracts of garlic 1and 2) and Solanaceae (extracts of tomato 3 and eggplant 5) were shown to be promising candidates for theinhibition of NO generation at the tested concentration. When tested at 20 μg/mL, 6 extracts, one of garlandchrysamthemums(sample 5), one of lettuce (sample 2), one of tomatoes (sample 3), two of Japanese hornworts(Mitsuba 1 and 2), and one of carrots (sample 4) showed strong inhibition of NO generation (IR≥70%). Eventhough one of the test samples (sample 2) of Japanese hornwort had a CV of less than 70% (67.8%), Japanesehornwort was still considered to be a highly promising species for the inhibition of NO generation. Furthermore,the activity varied significantly among samples from the same species for several plants. This variation mayhave been due to differences between cultivars and/or growing districts, or to differences in post-harvestingtreatment. Taken together, the results of the present study may provide an experimental basis for new strategiesfor the production of highly functional dietary plants and food items.     

Inhibition of Heinz Body Induction in an inVitro Model and Total Antioxidant Activity of Medicinal Thai Plants

Herbs have been used for medicinal purposes for centuries and known to possess antioxidant properties that ‍may help to reduce the risk of chronic diseases, cardiovascular disease, and cancer. We screen aqueous extracts from ‍20 medicinal plants in Thailand that were believed to possess anti-tumor activity, help immune-stimulating property ‍and maintain blood stasis. The antioxidant activities were investigated in two bioassays. Firstly, we demonstrated ‍inhibition of Heinz bodies induction caused by oxidants under in vitro condition. The percentages of Heinz body ‍inhibition activity in plant extracts from Terminalia citrina, Cassia timoriensis, and Derris elliptica were the highest ‍followed by Anamirta cocculus, and Oroxylum indicum respectively. In addition, we investigated total antioxidant ‍activity in plant extracts by improved ABTS radical cation decolorization assay. The total antioxidant activity of the ‍extract from Terminalia citrina was also the highest activity followed by Ficus pubigera, Derris elliptica, Anamirta ‍cocculus, Caesalpinia sappan, and Oroxylum indicum respectively. Our results suggest medicinal Thai plants as ‍valuable sources of antioxidants, which may have a potential anti-carcinogenic activity.     

Anti-proliferative activity of essential oil extracted from Thai medicinal plants on KB and P388 cell lines

Anti-proliferative activity of essential oil from 17 Thai medicinal plants on human mouth epidermal carcinoma (KB) and murine leukemia (P388) cell lines using MTT assay were investigated. An amount of 1 x 10(4)cells/well of KB cell line and 1 x 10(5) cells/well of P388 cell line were treated with the oil samples at different concentrations ranging from 0.019 to 4.962 mg/ml. In KB cell line, Guava (Psidium guajava L.) leaf oil showed the highest anti-proliferative activity with the IC(50) value of 0.0379 mg/ml (4.37 times more potent than vincristine) whereas Sweet Basil (Ocimum basilicum L.) oil gave the highest anti-proliferative activity with the IC(50) value of 0.0362 mg/ml (12.7 times less potent than 5-FU) in P388 cell line. The results demonstrated the potential of essential oil from Thai medicinal plants for cancer treatment.     

熊果酸对体外血管形成的抑制作用

目的 :探讨熊果酸对体外血管形成的抑制作用。方法 :用MTT法、细胞迁移及小管实验观察熊果酸对培养血管内皮细胞 (VEC)增殖、迁移和小管形成的影响。结果 :熊果酸质量浓度为 62 5～ 50 0μg/mL时 ,对VEC增殖呈剂量依赖性抑制 ;质量浓量为 12 5μg/mL时 ,对VEC迁移及小管形成均有抑制作用 (P <0 0 5) ;质量浓度为 50 0 μg/mL时 ,对VEC迁移及小管形成均有较强的抑制作用 (P <0 0 1)。结论 :熊果酸对体外血管形成具有抑制作用。     

巨噬细胞中诱导型一氧化氮合酶来源的NO对共培养HL60 细胞凋亡的影响

 目的 研究巨噬细胞中诱导型一氧化氮合酶（iN—OS）来源的一氧化氮（NO）对共培养HL60细胞凋亡的影响。方法 以脂多糖（LPS）和γ素（INF-γ）诱导RAW264．7巨噬细胞iNOS基因的表达产生过量NO为实验模型，通过噻唑蓝（MTT）试验、蛋白质印迹分析、荧光分析、流式细胞术（FCM）、透射电镜和DNA琼脂糖凝胶电泳等分析技术，观察No对共培养的HL60细胞存活率、bcl-2和bax蛋白表达、Caspase-3活性和细胞凋亡的影响。结果 RAW264．7巨噬细胞中iNOS来源的No对共培养HL60细胞能造成氧化损伤，降低细胞的存活率；bcl-2表达明显下降，而bax表达增加；激活Caspase-3和促进DNA的降解。结论 巨噬细胞中iNoS来源的No在诱导细胞凋亡中发挥重要的作用。     

熊果酸抗小鼠H22肝癌移植瘤及对免疫功能的影响

[目的]研究熊果酸(UA)对小鼠H22肝癌移植瘤的抑制作用及免疫功能的影响。[方法]采用移植性H22肝癌小鼠模型,随机分为模型组(对照)、氟尿嘧啶(5-Fu)处理组、UA高、低剂量组,分别连续腹腔注射5-Fu(25mg/kg)、UA(50mg/kg、25mg/kg)14d后,处死小鼠,计算抑瘤率、外周血白细胞数、脾脏指数、胸腺指数、白细胞介素2(IL-2)、肿瘤坏死因子α(TNF-α)等指标,分析UA对小鼠H22肝癌移植瘤的生长抑制作用及免疫功能的影响。[结果]与模型组相比,UA高、低剂量组能显著减少移植瘤瘤重,其抑瘤率分别为51.03%、32.54%,差异有显著性(P<0.01,P<0.05)。UA高剂量组与5-Fu组抑瘤率(71.33%)比较,差异没有显著性(P>0.05)。UA各组可不同程度地升高荷瘤小鼠的外周血白细胞数和脾脏指数、胸腺指数,同时还能提高荷瘤小鼠血清中TNF-α的水平(P<0.05)。[结论]熊果酸能明显抑制H22荷瘤小鼠的肿瘤生长,其作用可能与增强机体的免疫功能有关。     

Nitric Oxide Generation from Hydroxyurea via Copper-catalyzed Peroxidation and Implications for Pharmacological Actions of Hydroxyurea

We investigated the generation of nitric oxide (NO) by H₂O₂dependent peroxidation of hydroxyurea in the presence of copper-containing proteins such as Cu, Zn-snperoxide dismutase (Cu, Zn-SOD) or ceruloplasmin as a catalyst. In the reaction mixture of hydroxyurea, Cu, Zn-SOD, and H₂O₂, "NO generation was identified by measuring the specific electron spin resonance (ESR) signal of 2-phenyl-4,4,5,5-tetramethylimidazoline-l-oxyl 3-oxide (PTIO). The ESR signal of the NO-hemoglobin adduct was also detected in human red blood cells during copper-catalyzed pcroxidation of hydroxyurea. The'NO production during peroxidation of hydroxyurea was quantified as NO₂ formation, measured by using the Griess assay, and the amount of NO₂ was dependent on the concentration of hydroxyurea of the reaction mixture. ESR spin trapping with 5,5-dimethyl-l-pyrroline JV-oxide (DMPO) showed hydroxy radical COH) generation in the reaction of H₂O₂ with either Cu, Zn-SOD or ceruloplasmin. Several "OH scavengers, such as ethanol, thiourea, DMPO, and dimethylsulfoxide, and the metalchelating agent diethylenetriaminepentaacetic acid significantly inhibited'NO generation from hydroxyurea. This indicates that'NO release from hydroxyurea may be mediated by'OH derived from the copper-catalyzed Fenton-like reaction. Incubation of hydroxyurea and Cu, Zn-SOD with xanthine oxidase and hypoxanthine in a system forming O₂→ H₂O₂ also resulted in appreciable'NO production. These results suggest that'NO production from hydroxyurea catalyzed by copper-containing proteins may be the molecular basis of the pharmacological and antitumor action of hydroxyurea.     

Chemopreventive Effects of Edible Canna (Canna edulis Kerr.) Against Colorectal Carcinogenesis: Effects on Expression of Adenomatous Polyposis Coli and Inducible Nitric Oxide Synthase in Rat Inflammatory Model

Objective: Dietary high fibre and calcium intake has been suggested to reduce colorectal cancer risk. However, thereis limited information available regarding the potential of edible canna (Ganyong), with high dietary fibre and calciumcontent, to act as a preventive agent for colorectal cancer. This experimental study was conducted to investigate thepreventive effect of Ganyong in reducing colorectal carcinogenesis with attention to effects on adenomatous polyposiscoli (APC) and inducible nitric oxide synthase (iNOS) expression. Methods: Thirty male Wistar rats were dividedinto 5 equal groups; a normal control group without azoxymethane/dextran sodium sulphate (AOM/DSS) inductionand Ganyong, a ‘cancer’ control group with AOM/DSS induction only, and three treatment groups with AOM/DSSinduction and different percentages (5%, 10% and 20%) of Ganyong. Paraffin-embedded sections of rat colon tissuewere analysed by haematoxylin-eosin and immunohistochemical staining against antibodies against APC and iNOS.Variation in rates of APC and iNOS expression were analyzed using the Kruskal-Wallis test followed by the Dunn’stest (SPSS statistic version 24). Pthe expression of APC (p=0.013) and iNOS (p=0.013) compared to the normal control group. APC expression in thetreated groups was lower than in the ‘cancer’ control group (p=0.049), especially in the 10% Ganyong group (p=0.02).In contrast, there was no significant variation among the treated groups regarding iNOS expression. Histopathologicalfeatures of the colon supported the data for APC and iNOS expression. Conclusion: This study indicated potentialchemopreventive effects of Ganyong reducing expression of factors contributing to colorectal carcinogenesis.     

杜香熊果酸提取物对小鼠遗传损伤的保护作用

背景与目的:研究杜香熊果酸提取物对小鼠遗传损伤是否具有保护作用.材料与方法:以环磷酰胺(cyclophosphamide,CP)所导致的遗传损伤小鼠作为损伤模型,采用小鼠骨髓嗜多染红细胞微核试验,检测杜香熊果酸提取物对遗传损伤的保护作用.结果:杜香熊果酸提取物1.16、2.30、4.60 g/kg的骨髓嗜多染红细胞微核发生率分别为2.00‰±0.37‰、2.00‰±0.4,‰、1.80‰±0.37‰,与正常组(2.00‰±0.45‰)比较差异均无统计学意义(P＞0.05),与阳性对照组(24.00‰±0.71‰)其差异均具有统计学意义(P＜0.01).杜香熊果酸提取物1.16、2.30、4.60 g/kg加环磷酰胺组骨髓嗜多染红细胞微核发生率分别为17.20‰±1.24‰、16.40‰±1.5‰、16.00‰±0.51‰,明显低于阳性对照组(24.00‰±0.71‰),其差异均具有统计学意义(P＜0.05).结论:杜香熊果酸提取物对遗传损伤有保护作用.     

熊果酸诱导人胃癌BGC823细胞凋亡及其作用机制初探

背景与目的：熊果酸（ursolic acid,UA）广泛存在于夏枯草、白花蛇舌草等清热解毒药中,可抑制多种肿瘤细胞增殖并诱导其凋亡,具有广泛生物学活性。本研究将UA作用于人胃癌BGC823细胞,观察其对细胞凋亡的影响,并探讨其可能的作用机制。方法：MTT法检测UA对BGC823细胞增殖的影响;流式细胞术检测细胞周期与凋亡的变化;Realtime-PCR检测细胞bax、bcl-2mRNA表达的变化。结果：UA呈时间-剂量依赖性抑制BGC823细胞增殖,分别作用24、48、72h后半数抑制浓度依次为36.88、34.72、32.18μmol/L;UA能诱导BGC823细胞凋亡,并阻滞细胞于G2/M期;此外,其还可上调BGC823细胞bax及下调bc1-2mRNA表达,且作用随剂量的增加而加强。结论：UA呈时间-剂量依赖性抑制BGC823细胞增殖,并诱导其凋亡,阻滞细胞于G2/M期;其凋亡机制可能与上调bax及下调bcl-2基因的表达有关。     

内源性一氧化氮在5—氟尿嘧啶诱导人肝癌细胞凋亡过程中的作用

目的:观察内源性NO在5-氟尿嘧啶(5-fluorouracil,5-FU)诱导人肝癌细胞凋亡中的作用,为进一步研究5-FU的作用机理和提高5-FU的临床疗效寻找辅剂。方法:人肝癌细胞Bel-7402按常规条件培养于含10%小牛血清且无L-精氨酸(L-Arg)的DMEM培养液中。在5-FU作用下,采用免疫组化法观察诱生型一氧化氮合酶的表达情况,并在其底物L-Arg存在的前提下,采用酶法测定硝酸盐/亚硝酸盐量,反映NO的生成,并证明它的作用。用电镜观察凋亡细胞的形态,流式细胞仪进行凋亡细胞的定量。用L-Arg的竞争性拮抗剂L-NAME(Nω-nitro-L-Argininemethylester)对研究结果进行验证。应用高清晰度病理彩色图文分析系统对免疫组化结果进行光密度定量分析。采用方差分析和t检验进行统计学分析。结果:在5-FU的作用下,诱生型一氧化氮合酶表达增强(5-FU组0.16870±0.01968,对照组0.10490±0.01266,P<0.05),在其底物L-Arg存在的前提下,内源性NO的浓度为(73.0±10.2)μmol/L,有显著性提高(P<0.05);人肝癌Bel-7402细胞株的凋亡率明显增高(17.85±0.78)%,细胞坏死率和残渣率减少犤分别为(32.99±0.83)%,(3.18±1.01)%犦,与5-FU组相比P<0.05,有统计学意义。L-NAME能够拮抗内源性NO的作用。结论:内源性NO参与5-FU诱导肝癌细胞凋亡。5-FU通过诱导诱生型一氧     

熊果酸诱导人肝癌BEL-7404细胞凋亡的作用及其机制

目的 探讨熊果酸(UA)对人肝癌BEL-7404细胞凋亡的诱导作用及其机制.方法 采用MTT法检测UA对BEL-7404细胞增殖的抑制作用,流式细胞术检测BEL-7404细胞凋亡率,Western blot法检测BEL-7404细胞proeaspase-3、caspase-9、survivin蛋白的表达.并用顺铂(DDP)作为阳性对照.结果 UA和DDP对BEL-7404细胞增殖具有明显抑制作用,并呈浓度、时间依赖性;作用48 h后,阴性对照组、uA 50μmoL/L组、DDP 10 mg/L组的BEL-7404细胞凋亡率分别为(0.83±0.25)%、(16.10±0.30)%、(31.87±0.65)%,差异有统计学意义(P<0.01);作用48 h后,与阴性对照组相比,UA 50μmol/L组、DDP 10 mg/L组的procaspase-3、survivin蛋白表达降低,caspase-9蛋白表达升高,差异有统计学意义(P<0.01).结论 UA能够诱导BEL-7404细胞凋亡,其作用机制与procaspase-3、survivin蛋白表达降低及caspase-9蛋白表达升高有关.     

自分泌一氧化氮在氟尿嘧啶诱导人肝癌细胞凋亡中的作用研究

目的 :观察肝细胞Bel74 0 2自分泌一氧化氮 (NO)在 5 -氟尿嘧啶 (5 FU)诱导人肝癌细胞凋亡过程中的作用 ,进一步揭示 5 FU的作用机理 ,同时寻找提高 5 FU的临床疗效的辅剂。方法 :人肝癌细胞Bel74 0 2按常规条件培养于含 10 %小牛血清的无L 精氨酸 (L Arg)的DMEM (dulbecco’smodifiedeagle’smedium)培养液中。在 5 FU作用下 ,采用免疫组化法观察诱生型一氧化氮合酶 (iNOS)的表达情况 ,并在其底物L Arg存在的前提下 ,采用酶法测定硝酸盐 /亚硝酸盐 ,反映NO的生成 ,并证明其作用。用电镜观察凋亡细胞的形态 ,流式细胞仪进行凋亡细胞的定量。用L Arg的竞争性拮抗剂L NAME(Nω nitro l argininemethylester)对研究结果进行验证。应用病理彩色图文分析系统对免疫组化结果进行光密度定量分析。采用方差分析和t检验进行统计学分析。结果 :在 5 FU的作用下 ,iNOS表达增强 ,5 FU组 (0 1687± 0 0 1968) ,对照组 (0 10 4 9± 0 0 12 66) ,P <0 0 5 ,在其底物L Arg存在的前提下 ,内源性NO的浓度为 (73 0± 10 2 ) μmol/L(P <0 0 5 ) ,有显著性提高 ;人肝癌Bel74 0 2细胞株的凋亡率显著性增高为 (17 85± 0 78) % ,细胞坏死率和残渣率显著减少分别为 (32 99± 0 83) %、(3 18± 1 0 1) %。L NAME     

Suppressive Effects of Dietary Genistin and Daidzin on Rat Prostate Carcinogenesis

High intake of phytoestrogens through soybeans and their products is thought to be associated with low incidences of prostate and/or breast cancer in Asian countries. Possible chemopreventive effects of genistin or daidzin on rat prostate carcinogenesis were therefore investigated. Male F344 rats were given 10 biweekly subcutaneous injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB) and then either genistin or daidzin in the diet at a concentration of 0.1% for 40 weeks. Other groups of rats given DMAB were treated with genistin or daidzin together with a high dose of testosterone propionate (TP). Both genistin and daidzin reduced the numbers of ventral prostate carcinomas (P<0.05), with a tendency for decrease in incidence. Invasive carcinomas which developed in the anterior prostate and seminal vesicles with TP were, however, not influenced by the two isoflavones. Thus, the present data suggest that genistin and daidzin possess anti-cancer effects at relatively early stages of prostate cancer development, providing experimental support for epide-miological findings.     

阿霉素对兔心功能及心肌一氧化氮合酶表达的影响

目的：探讨阿霉素对兔心功能及心肌一氧化氮合酶（NOS）表达的影响。方法：测定实验组和对照组兔心输出量（CO）、左心室收缩压（LVSP）、左心室舒张末压（LVEDP）。取心肌组织进行HE染色和NADPH组织化学染色并进行图像定量分析,所测得数据均进行统计学处理。结果：实验组CO、LVSP均明显低于对照组（P＜0．01）,LVEDP明显高于对照组（P＜0．01）,心肌组织NADPH组织化学染色及图像定量分析结果显示,实验组NOS表达明显增强（P＜0．01）,且与CO呈负相关（γ=-0．8304,P＜0．01）,与LVSP呈负相关（γ=0．7815,P＜0．05）,与LVEDP呈正相关（γ＝0．7356,P＜0．05）。结论NOS过度表达,导致NO生成过量,参与阿霉素慢性心功能损伤的过程。     

A pilot study on the safety of combining chrysin, a non-absorbable inducer of UGT1A1, and irinotecan (CPT-11) to treat metastatic colorectal cancer

Purpose: Recently, it was shown that chrysin causes upregulation of UGT1A1 in Caco-2 intestinal cells. Therefore, we proposed that oral chrysin may reduce irinotecan (CPT-11) induced diarrhoea by shifting the SN-38G/SN-38 equilibrium towards the inactive SN-38G in the gastrointestinal mucosa. The purpose of this study was to examine the safety of combining single agent CPT-11 with chrysin. Patients and methods: Twenty patients with previously treated advanced colorectal cancer were administered chrysin twice daily for 1 week preceding and succeeding treatment with single agent CPT-11 (350 mg/m² over 90 min every 3 weeks). Loperamide usage and bowel frequency/consistency were recorded by patients into a study diary and blood samples were collected for CPT-11 pharmacokinetic analysis. Results: There were no observable toxicities that could be attributed to chrysin use. The grades and frequency of delayed diarrhoea were mild, with only 10% of patients experiencing grade 3 toxicity. Loperamide usage was also modest with a median of 1–5 tablets per cycle (range: 0–22). Pharmacokinetic results revealed a mass ratio of plasma SN-38G/SN-38, which was very similar to historical controls (7.15±5.67, n=18). Conclusions: These findings, combined with the observation of clinical activity and grade 3/4 neutropenia in 25% of patients, suggest that combining chrysin with CPT-11 may be a safe and potentially useful means of preventing diarrhoea, although this needs to be further investigated in the setting of a randomised trial.     

乌苏酸联合吉西他滨对胰腺癌PANC-1细胞增殖和凋亡的影响

目的: 探讨乌苏酸联合吉西他滨对胰腺癌PANC-1细胞增殖和凋亡的影响。 方法: 以乌苏酸、吉西他滨单独用药作 用于体外培养的胰腺癌细胞PANC-1细胞,采用细MTT法检测细胞半抑制浓度（IC 50 ）,确定药物给药浓度;以乌苏酸(2 μ mol/L) 、 吉西他滨(0.2 μ mol/L)单独及联合作用于PANC-1细胞,采用锥虫蓝染色法检测PANC-1细胞存活率,PI染色后PANC-1细胞中检 测细胞凋亡,采用细胞划痕实验检测PANC-1细胞迁移和伤口愈合情况,采用Western blotting检测对照组、乌苏酸组与吉西他滨 组单独及联合用药组细胞中P-JNK、Bcl-2、IL-6、P-Stat 3、NF-κB和Cox-2蛋白的表达。 结果: 乌苏酸和吉西他滨对胰腺癌 PANC-1细胞均有较强的抑制作用,其IC 50 分别是13.67和2.78 μ mol/L,据此选择它们的实验浓度分别为2和0.2 μ mol/L。两者联 合用药比分别单独用药能更显著抑制癌细胞的增殖活性[(46.47±5.07)% vs (78.38±8.65)%、(76.12±3.23)%,均P<0.05],能更明显 诱导癌细胞凋亡[(39.78±7.01)% vs (20.35±8.51)%、(20.35±8.51)%,均P<0.01]和抑制细胞迁移能力（P<0.01）,同时更显著抑制凋亡 相关蛋白Bcl-2、IL-6的表达及促进P-JNK的表达。 结论: 乌苏酸和吉西他滨协同增强抑制胰腺癌PANC-1细胞的增殖和迁移以 及促凋亡作用,其机制可能与抑制Bcl-2、IL-6、P-Stat 3和促进P-JNK蛋白表达有关。     

Suppressive Effects of S-Methyl Methanethiosulfonate on Promotion Stage of Diethylnitrosamine-initiated and Phenobarbital-promoted Hepatocarcinogenesis Model

Modifying effects of S-methyl methanethiosulfonate (MMTS) on diethylnitrosamine (DEN)-initiated and phenobarbital (PB)-promoted hepatocarcinogenesis were examined in rats. Five-week-old male F344 rats were divided into 8 groups. After a week, groups 1–5 were given DEN (100 mg/kg body weight, i.p.) once a week for 3 weeks, whereas groups 6–8 received vehicle treatment. Group 2 was given 100 ppm MMTS containing diet in the initiation phase. From 4 weeks after the start of experiment, groups 3 and 5 were fed MMTS, and groups 1–3 and 7 received drinking water containing 500 ppm PB. Group 6 was given MMTS diet alone throughout the experiment (24 weeks). The incidences of hepatocellular adenoma and total liver tumors were significantly smaller in group 3 than those of group 1. The average numbers of hepatocellular adenoma, carcinoma and total tumors in group 3 were significantly smaller than in group 1. Glutathione, S-transferase placental form-positive foci were also significantly decreased by MMTS treatment in the promotion phase. MMTS treatment in the initiation or promotion phase reduced ornithine decarboxylase activity in the liver of rats given DEN. The antioxidant activity against lipid peroxidation of MMTS was confirmed in tests with rabbit erythrocyte membrane ghosts or rat hepatocytes. These results suggest that MMTS is a promising chemopreventive agent for liver neoplasia when concurrently administered with PB.     

Effects of Complementary and Alternative Medicine on Chemotherapy Delivery in Thai Patients

Background: Complementary and Alternative Medicine (CAM) is widely used among cancer patients worldwide. This prospective observational study aimed to show the effect of CAM use on chemotherapy delivery in Thai patients. Methods: During March 2014 to February 2015, the patients with breast, lung or colorectal cancer receiving first cycle chemotherapy at King Chulalongkorn Memorial Hospital were enrolled. The correlation between CAM using and chemotherapy schedule delay and dose reduction, dose intensity, quality of life and adverse event rates were analyzed. Results: There were 80 (44.20%) patients using CAM among 181 enrolled patients.  Seventy six CAM users and 97 non-CAM users receiving 2nd cycle of chemotherapy were included for primary analysis. The chemotherapy schedules were delayed and/or reduced in 40 (52.6%) and 48 (49.5%) in CAM users and non-CAM users, respectively, p =0.681. The mean relative dose intensity (RDI) were 92.4% and 94.1% in CAM and non-CAM users, respectively, p=0.244. However, there were significantly more CAM users receiving chemotherapy less than 90% RDI (34.8% vs 19.8%, p=0.033). As compared to first cycle, at third cycle, the mean QOL score changes were -4.63 (95% CI -2.49-9.27) and -8.02 (-2.36- 9.142) in CAM user and non-CAM user, respectively (p=0.255). There were significantly higher rates of grade 3 or 4 anemia (5.1% vs 0%, p=0.024), and grade 2 malaise (19.0% vs 5.1%, p=0.004) in CAM users. Conclusions: There were similar overall rates of chemotherapy schedule delay and dose reduction between CAM- and non-CAM users. However, there were less CAM-users achieving 90% chemotherapy RDI.     

Suppressive Effects of Okinawan Food Items on Free Radical Generation from Stimulated Leukocytes and Identification of Some Active Constituents: Implications for the Prevention of Inflammation-associated Carcinogenesis

Okinawa prefecture in Japan is a distinct area characterized by unique traditional food habits and longevity. ‍Prolonged exposure to activated leukocytes, playing pivotal roles in chronic inflammation-associated carcinogenesis, ‍is known to lead to oxidative and nitrosative damage to macromolecules in the body since they are primary sources ‍of free radicals, such as superoxide anion (O2 ‍-) and nitric oxide (NO). In this study, we estimated anti-oxidative and ‍anti-nitrosative activities of Okinawan food items by employing two cellular experimental systems: (1) phorbol ‍ester-induced O2 ‍- generation from differentiated HL-60 human promyelocytic leukemia cells; and (2) ‍lipopolysaccharide (LPS)-induced NO generation in RAW264.7 murine macrophages. A total of 138 food items, ‍consisting of 42 samples unique to Okinawa and 96 common in the Japanese main island, were purchased at local ‍markets in Okinawa and extracted with chloroform. When tested at a concentration of 100 ìg/ml, 38% (16/42) of ‍the former showed 70% or more inhibition of O2 ‍- generation while 21% (20/96) of the latter did so. In parallel, 64% ‍(27/42) of the former showed significant NO generation suppression in contrast to 48% (46/96) of the latter . Twentyone ‍active species were further tested at a concentration of 20 ìg/ml, and eleven species, including sugar cane, wild ‍turmeric, and zedoary, were indicated to be most promising items with anti-oxidative and anti-nitrosative properties. ‍In addition, some of the active constituents (chebulagic acid, a resveratrol derivative, and sesquiterpenoids) were ‍identified. Our results suggest that food items typical in the Okinawa area have higher cancer preventive potential ‍than those common in Japan.