毒死蜱对果蝇生长发育的影响

目的：研究毒死蜱（CPF）对果蝇生长发育的影响。方法：设定0.5、1.0、1.5、2.0、2.5、3.0和4.0 mg/L共7个CPF浓度梯度对果蝇进行急性染毒,统计每组果蝇96 h死亡数,Probit法计算毒死蜱染毒96 h对果蝇的半数致死浓度（LC₅₀）,依据LC₅₀分别设置含毒死蜱0.04、0.08、0.16、0.32 mg/L的培养基,用其染毒果蝇后,检测雌、雄果蝇体质量变化,各浓度组随染毒时间延长雌雄果蝇体质量日增减量及各染毒时间段随浓度增加雌雄果蝇体质量变化。结果：CPF对雌果蝇的毒性（LC₅₀为0.447 mg/L）大于雄果蝇（LC₅₀为0.858 mg/L）。CPF各浓度在染毒不同时间对雌果蝇的体质量无显著影响（P>0.05）。0.04~0.32 mg/L CPF使雄果蝇体质量平均日减轻0.01 mg/d,与对照组比较差异有统计学意义（P<0.05或P<0.01）,存在明显时间-效应关系。雄果蝇对低浓度0.04 mg/L（LC₅₀的1/20）CPF极为敏感,体质量显著下降（0.04～0.08 mg）,雄果蝇在0.16 mg/L浓度染毒时体质量增加（0.02 mg）,染毒72或96 h时各浓度组体质量差异有统计学意义（P<0.05）,存在明显剂量-效应关系。结论：CPF使雄性果蝇体质量发生变化,反映CPF可对雄性果蝇生长发育生理生化指标产生相应的影响。     

MAPO对雄性小鼠生殖细胞诱变作用的研究

MAPO[三-(2-甲基-1-氮丙啶)膦化氧]分成1、10和100ppm3个浓度组,对AMS雄性小鼠经口染毒60天,与正常雌鼠交配后发现雄鼠染毒>10ppm时其生育率为0％,阴性对照及MAPO1ppm组雄鼠生育率为100％,对小鼠附睾精子数量检测发现,MAPO10ppm和100ppm组的精子数量分别为0.62和0.51百万/ml/10g附睾,明显低于对     

刺山柑果风湿止痛凝胶膏对SD大鼠的一般生殖毒性

目的：评价刺山柑果风湿止痛凝胶膏对SD大鼠的一般生殖毒性。方法：SD大鼠随机分为辅料对照组(辅料贴)、阳性对照组(环磷酰胺)和刺山柑果风湿止痛凝胶膏高(117.8 g/m2)、中(58.9 g/m2)、低(29.5 g/m2)剂量组,每组雌、雄鼠各25只。每天经皮外贴给药1次,雄鼠给药4周、雌鼠给药2周后按1∶1合笼交配,雄鼠给药至交配成功,雌鼠给药至妊娠第6天,阳性对照组在大鼠给药第1天单次腹腔注射(0.1 g/kg环磷酰胺)。实验期间观察动物的一般状况,体质量、摄食量和交配情况;雄鼠于交配成功当天解剖检查睾丸、附睾及精子情况;雌鼠于妊娠第14天解剖检查子宫、卵巢及胚胎情况。结果：与辅料对照组比较,刺山柑果风湿止痛凝胶膏各剂量组对雄鼠和孕鼠的体质量、饲料消耗量均无明显差异(P>0.05);对雄鼠交配率、睾丸横径、精子数量、精子活动度和畸形率、附睾和睾丸质量均无明显影响(P>0.05);对雌鼠妊娠率、子宫连胎质量、平均黄体数、平均着床数、平均活胎数、平均死胎数、平均吸收胎数、死胎率、卵巢质量亦均无明显影响(P>0.05);但刺山柑果风湿止痛凝胶膏117.8 g/m2剂...     

硒酵母对大鼠的致畸性研究

本文研究了硒酵母对大鼠的致畸性和胚胎毒性。Sprague-Dawley处女鼠与雄鼠交配后随机分为4组,每组13-15只孕鼠,于孕期6-15d分别灌胃给予硒酵母0、1000、2000和4000mg/kg(含硒0、521.3、1042.6和2085.2μg/kg)。结果显示中、高剂量组孕鼠体重增长缓慢、不增或下降;胎鼠存活率下降、死胎率增加、平均身长、尾长和体重减少、枕骨和胸骨发育不良增加,提示大剂量硒酵母对Sprague-Dawley鼠有明显的母体毒性和胚胎毒性。但各剂量组未见明显的畸形。     

生育力与早期胚胎发育毒性试验中雄性大鼠阳性模型的建立

目的： 探讨生育力与早期胚胎发育毒性试验中,SD雄鼠交配前的环磷酰胺给药方法,以建立阳性对照模型。方法：SD大鼠按体质量随机分为3组,分别为溶剂对照组、环磷酰胺I组 (100 mg/kg)、环磷酰胺II组 (20 mg/kg);环磷酰胺I组和II组分别腹腔注射给予环磷酰胺1次和5次,溶剂对照组给予等量的生理盐水;雄鼠于首次给药后63 d开始交配,交配成功后当天检测阴茎勃起功能,随后处死,进行精子活动度和数量检测,腹主动脉采血后检测双氢睾酮、雌二醇和睾酮激素水平,称量睾丸、附睾、包皮腺、前列腺、精囊腺、提肛肌等的质量并计算脏器系数。结果：2个环磷酰胺组雄鼠主要表现为可逆性脱毛。与溶剂对照组比较,体质量和摄食量均明显降低 (P<0.05或0.01);雄鼠附属生殖器官质量降低 (P<0.01),阴茎勃起潜伏期明显延长 (P<0.01),附睾尾精子计数、Ⅰ和Ⅱ级活动精子数及精子活率降低,精子畸形率明显增高 (P<0.05或0.01),但激素水平未见明显异常。结论：给予环磷酰胺对于雄性大鼠的生育力产生明显影响,两种给药方式均可建立生育力与早期胚胎发育毒性试验阳性模型。     

海狗油脂肪乳对大鼠的一般生殖毒性研究

背景与目的:观察海狗油脂肪乳对大鼠配子成熟、交配行为、生育力和早期胚胎发育方面的毒性作用. 材料与方法:160只Wistar大鼠随机分为海狗油脂肪乳不同剂量组(250、500和1 000 mg/kg)和溶剂对照组,共4组.雄性大鼠在交配前连续腹腔注射海狗油脂肪乳35 d,雌性大鼠在交配前连续腹腔注射给予海狗油脂肪乳18 d,相同剂量组内大鼠按雄:雌=1:1同笼交配,连续10 d.在确定雌鼠受精后处死同笼的雄鼠,解剖检查睾丸和附睾等生殖器官及精子的活力.雌鼠交配期间继续给药至妊娠第14 d处死,解剖检查卵巢、子宫和胚胎的情况. 结果:给药期间各剂量组大鼠除体重增长缓慢(体重增重平均最大差值达到50 g,与对照组比较,差异显著,P<0.05)外,精神、行为、活动及被毛正常;雄性大鼠生殖器官发育良好,性功能正常,精子数量多、成熟.畸形率低.妊娠大鼠500 mg/kg和1 000 mg/kg组的活胎数减少(窝平均最大差值2.0个),胎仔平均体重降低(每只平均最大差值0.03 g)以及1 000mg/kg剂量组的交配率为65%(13/20),与对照组比较差异有统计学意义(P<0.05).妊娠率、黄体数、着床数、吸收胎数、死胎数、受精卵着床前后丢失率和胎仔体表畸形数等与对照组比较无显著差异(P>0.05).结论:海狗油脂肪乳可影响成年大鼠体重增长,引起妊娠大鼠早期胚胎和胎仔的生长发育障碍,但对大鼠其他生殖功能无明显损害作用.     

紫外线照射对秀丽隐杆线虫形态、寿命和ROS含量的影响

目的探讨紫外线照射对秀丽隐杆线虫形态、寿命和ROS含量的影响。方法线虫同步化培养至L4期,随机分为0 J/m2(对照组)、20 J/m2、40 J/m2、60 J/m2、80 J/m2、100 J/m2、120 J/m2和200 J/m2照射组共8组,用紫外交联仪进行照射。于照后1h、6 h、12 h和24 h,观察各组线虫形态变化;观察记录线虫死亡数和存活数,用于分析死亡率和寿命;于照后8 h、12 h和24 h,检测各组线虫体内ROS含量。结果与对照组比较,照后6～24 h,40 J/m2组线虫形态未观察到明显改变,而80 J/m2和120J/m2组中持续出现体型较小的线虫,且120 J/m2组明显多于80J/m2组。照后7 d各照射组线虫死亡率均高于对照组,且剂量越大死亡率越高,呈一定量效关系。各照射组线虫平均寿命均低于对照组,且照射剂量越大平均寿命越短。照后24 h内,80 J/m2和120 J/m2组线虫的荧光强度明显高于对照组;于照后8～24 h,120 J/m2组荧光强度均强于80 J/m2组。结论紫外线照射能明显诱导线虫形态学改变,影响线虫正常生长发育;大剂量照射可致线虫寿命缩短,推测线虫体内活性氧(ROS)含量增加可能是导致其寿命缩短的原因之一。     

硒化亚油酸及硒化亚麻酸对肿瘤细胞DNA合成的影响

本文报道用氚一胸腺嘧啶核苷（＾３Ｈ－ＴｄＲ）掺入法研究了新型抗癌药－硒化亚油酸及硒化亚麻酸对小鼠Ｓ１８０细胞ＤＮＡ合成的影响。结果表明，这两种新型抗肿瘤药物能明显抑制＾３Ｈ－ＴｄＲ掺入肿瘤细胞，在１００μｇ／ｍｌ的浓度下，它们对Ｓ１８０瘤细胞ＤＮＡ合成的抑制率分别达到８９．０％和８８．３％，这些结果表明硒化亚油酸及硒化亚麻酸的抗癌机理之一是它们对＾３Ｈ－ＴｄＲ掺入肿瘤细胞的干扰。     

抑癌因子对小鼠实体瘤生长抑制作用的研究

目的　观察人抑癌因子直接瘤内注射对小鼠实体瘤生长的影响。方法　小鼠右腋皮下分别接种S180 和肝癌细胞 ,成瘤后 ,让小鼠带瘤生长半月 ,再于瘤内注射抑癌因子 ,并设注射生理盐水为对照组 ,观察小鼠的肿瘤生长、瘤体变化及生存情况。结果　抑癌因子能强烈地抑制小鼠肿瘤的生长 ,使肿瘤体积明显缩小 ,实验组与对照组比较 ,差异非常显著 (P <0 .0 1 )。实验组小鼠的寿命显著延长 ,S180 和肝癌小鼠的寿命延长率分别为 1 6 3%和 1 4 8%。结论　抑癌因子可能通过某种机制启动细胞凋亡信号传递系统 ,诱导并加速癌细胞的凋亡 。     

己二酸二(2-乙基己基)酯灌胃染毒对大鼠的一般生殖毒性研究

目的： 观察己二酸二（2-乙基己基）酯（DEHA）灌胃染毒对亲代大鼠的一般毒性、交配行为和对胎仔生长发育的影响。方法： 将120只成年SPF级SD大鼠按体质量随机分为4组,分别为对照组（玉米油）和低、中、高剂量[分别为28、170、1 080 mg/（kg·d）]DEHA染毒组,每组30只,雌：雄比例2：1,采用灌胃方式给予受试物,每天灌胃1次,雄鼠染毒10周、雌鼠染毒2周后同组动物合笼。各组雄鼠结束染毒后,雌鼠在交配期、妊娠期持续染毒至实验结束,测定亲代大鼠体质量、相关脏器质量及其脏器系数并进行组织病理检查,测定亲代大鼠血清生化指标。记录交配成功天数、怀孕动物数、每窝胎仔数和胎仔体质量。结果： 与对照组比较,在亲代大鼠中,高剂量DEHA染毒组亲代雄性大鼠终体质量减少（P < 0.01）、睾丸脏器系数增加（P < 0.05）,谷草转氨酶（AST）水平、肌酐（CREA）水平均升高（P < 0.05）;与对照组比较,高剂量组亲代雌性大鼠肝脏和肾脏质量及肝、肾脏器系数均增加（P < 0.01或P < 0.05）,低剂量组亲代雌性大鼠AST水平降低（P < 0.05）;高剂量组亲代雌性大鼠血清球蛋白（GLO）、总胆固醇（TC）水平均升高（P < 0.05）;高剂量组的胎仔体质量降低（P < 0.01）。组织病理学检查结果未见明显异常。结论： DEHA灌胃染毒可影响亲代大鼠体质量增长,对亲代大鼠肝、肾有毒性作用,引起胎仔生长发育障碍。     

富马酸二甲酯慢性毒性与致癌性研究

给４４０只Ｗｉｓｔａｒ大鼠喂饲含０、１２５、２５０、５００及１０００ｐｐｍ富马酸二甲酯（ＤＩＭＥＦＵ）的饲料２４个月。实验结果，各实验组与对照组相比，食物利用率、掺入量、生长、一般表现、列亡率及平均寿命均无显著性差异。血液学检查仅个别指标出现差别，但波动在正常范围。１０００ｐｐｍ组动物血清ＧＰＴ、ＧＯＴ及肝、肾脏器系数呈现持续性改变。病理组织学检查表明各组非肿瘤性及肿瘤性病变发生率与饲料中ＤＩＭＥ     

Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster

In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies.     

Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin

Target of Rapamycin (TOR) is involved in cellular and organismal aging. Rapamycin extends lifespan and delays cancer in mice. It is important to determine the minimum effective dose and frequency of its administration that still extends lifespan and prevents cancer. Previously we tested 1.5 mg/kg of rapamycin given subcutaneously 6 times per two weeks followed by a two-week break (1.5 × 6/bi-weekly schedule: total of 6 injections during a 4-week period). This intermittent treatment prolonged lifespan and delayed cancer in cancer-prone female FVB/N HER-2/neu mice. Here, the dose was decreased from 1.5 mg/kg to 0.45 mg/kg per injection. This treatment was started at the age of 2 months (group Rap-2), 4 months (Rap-4), and 5 months (Rap-5). Three control groups received the solvent from the same ages. Rapamycin significantly delayed cancer and decreased tumor burden in Rap-2 and Rap-5 groups, increased mean lifespan in Rap-4 and Rap-5 groups, and increased maximal lifespan in Rap-2 and Rap-5 groups. In Rap-4 group, mean lifespan extension was achieved without significant cancer prevention. The complex relationship between life-extension and cancer-prevention depends on both the direct effect of rapamycin on cancer cells and its anti-aging effect on the organism, which in turn prevents cancer indirectly. We conclude that total doses of rapamycin that are an order of magnitude lower than standard total doses can detectably extend life span in cancer-prone mice.     

The effect of SSH&H on the lifespan and spontaneous cancer development in transgenic mice with HER-2/neu mutation

10 months old mice receiving SSH&H with daily food increased the lifespan in comparison to the control group. The maximal lifespan was increased by 1,6 months. For the long-living 10% group the mean lifespan increased by 8,7% compared to the control group (p<0,05). The mammary gland neoplasia rate was the same in both groups. The mean latent tumor development period duration, number and size of the tumors were also similar. There was a tendency to lower lung metastases rate in the experimental group. The cumulative neoplastic frequency curve for the experimental group was shifted to the right in comparison to the control group curve giving evidence to the inhibitory effect of SSH&H on the neoplastic rate in transgenic mice with HER-2/neu mutation.     

Mechanisms of human cell neoplastic transformation: relationship of specific abnormal clone formation to prolonged lifespan in X-irradiated human diploid fibroblasts

A total of 9 control and 46 X-irradiated human fibroblast cultures were followed throughout their lifespan in vitro; G-banded karyotypes were examined at regular intervals. The lifespan (mean population doublings) of irradiated cultures was slightly but significantly prolonged over that of controls. None of the cultures developed any changes in cell morphology characteristic of neoplastic transformation. A number of abnormal clones containing marker chromosomes emerged in the irradiated cultures. Most of these senesced early, but 2 clones were associated with a considerably increased lifespan. One of these had a deletion in the short arm of chromosome I (p22, p32), and the other had 2 specific translocations involving chromosome 22, t(1;22)(q25,q12) and t(6;22)(p22,q11). We hypothesize that the emergence of an abnormal clone with translocations in the vicinity of critical oncogenes may be associated with prolongation of lifespan and the induction of immortalization in human diploid cells, an event independent of the acquisition of other characteristics of the transformed phenotype.     

Dose-related enhancing effect of potassium bromate on renal tumorigenesis in rats initiated with N-ethyl-N-hydroxyethyl-nitrosamine

Dose-response studies were undertaken to investigate the enhancing activity of potassium bromate (KBrO3), a food additive, on renal tumorigenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN). A total of 180 male 6-week-old F344 rats were divided into 12 groups. EHEN was given in the drinking water for the first 2 weeks at a concentration of 500 ppm for initiation of carcinogenesis. Thereafter, the rats were treated orally either with KBrO3 at a concentration of 500, 250, 125, 60, 30 or 15 ppm, or with potassium bromide (KBr) at a concentration of 1750 or 350 ppm for 24 weeks. The mean numbers of kidney dysplastic foci were significantly increased in a dose-related manner in rats treated with more than 30 ppm KBrO3. The mean number of renal cell tumors was significantly higher after treatment with KBrO3 at the highest concentration of 500 ppm. On the other hand, KBr had no effect. It was concluded that KBrO3 at doses higher than 30 ppm in the drinking water has an enhancing effect on renal tumorigenesis.     

Variability of the depth of supraclavicular and axillary lymph nodes in patients with breast cancer: is a posterior axillary boost field necessary?

PURPOSE: To determine the variability of the depth of supraclavicular (SC) and axillary (AX) lymph nodes in patients undergoing radiation therapy for breast cancer and to relate this variability with the patient's anterior/posterior (A/P) diameter. The dosimetric consequences of the variability in depth are explored and related to the need for a posterior axillary boost field. METHOD AND MATERIALS: In 49 patients undergoing treatment-planning computed tomography (CT) scanning in the treatment position, the maximum depth of the SC and AX lymph nodes was measured on CT images. The A/P diameter was measured at the location of the SC and AX, respectively. The relationship between the SC/AX lymph node depth and patient diameter was determined using linear regression. For an anterior SC and AX field, the relative dose to the SC and AX lymph nodes were calculated for a 6 MV photon beam. RESULTS: The maximum depth of the SC lymph nodes ranged from 2.4 to 9.5 cm (median, 4.3 cm). The depth was less than 3 cm in 4 patients, 3-6 cm in 39 (80%), and greater than 6 cm in 6 patients. There was a linear relationship between the SC lymph node depth and the A/P diameter. The depth of the SC lymph nodes in cm equals approximately one-half of the A/P diameter minus 3.5 (r(2) = 0.69). In 94% (46 of 49) of patients, the SC lymph node depth was between one-fifth and one-half of the A/P diameter.The depth of the axillary lymph nodes ranged from 1.4 to 8 cm (median, 4.3 cm). The depth was less than 3 cm in 8 patients, 3-6 cm in 32 (65%), and greater than 6 cm in 9 patients. The AX lymph node depth in cm equals approximately one-half of the A/P diameter minus 3 (r(2) = 0.81). In all patients, the AX lymph nodes were shallower than mid-depth.The depth of the SC and AX lymph nodes was within +/- 1 cm in 53% (26 of 49) of patients. The AX lymph nodes were located at >/= 1 cm shallower or greater depth than the SC in 24.5% (12 of 49) and 22.5% (11 of 49) of patients, respectively. If an anterior 6-MV beam only is used to treat the SC and AX lymph nodes in these 49 patients, the dose to the AX is within +/- 5% of the SC dose in 53% (26 of 49) patients and is 90% or more of the dose delivered in the SC in 90% (44 of 49) of patients. CONCLUSION: The maximum depth of the SC and AX lymph nodes varies widely and is related to the patient's size represented by the A/P diameter. In most patients, the AX lymph nodes lie at approximately the same depth or shallower than the SC. Therefore, the rationale for a posterior axillary boost field needs to be further assessed. When the AX and SC lymph nodes are deep, opposed supraclavicular and axillary fields and/or the use of a higher energy beam might be reasonable.     

The dosimetric impact of supraclavicular nodal irradiation on the thyroid gland in patients with breast cancer

PurposeThe thyroid is not routinely considered an organ at risk in supraclavicular (SC) nodal radiation therapy (RT) for breast cancer. We compared the dosimetric impact of the following 2 RT planning techniques on the thyroid: (1) conventional single anterior field to encompass the SC nodal volume defined clinically; and (2) 3-dimensional conformal radiation therapy (3DCRT) planning to encompass the computed tomography (CT)-contoured SC nodal volume.Methods and MaterialsThe thyroid, SC nodal volumes, and organs at risk were contoured on the planning CT of 20 patients who received 50 Gy in 2-Gy daily fractions to the breast or chest wall, and SC nodes. Comparisons of dosimetric parameters between the techniques were performed: thyroid, mean and maximum dose, V5, V30, and V50 (percentage of thyroid receiving ≥ 5 Gy, ≥ 30 Gy, and ≥ 50 Gy, respectively); SC nodal volume, homogeneity index (HI, percentage volume receiving 95%-107% of prescribed dose); and maximum doses of spinal cord and brachial plexus. Anatomic characteristics that influenced the dose distributions were investigated.ResultsThe 3DCRT planning technique significantly increased all thyroid dosimetric measures (mean dose 17.2 Gy vs 26.7 Gy; maximum dose 48.5 Gy vs 51.9 Gy; V5 45.7% vs 64.9%; V30 33.7% vs 48%; and V50 0.6% vs 26.7%; P < .001). It improved HI for the SC nodal volumes (P < .001) but resulted in higher maximum doses to the spinal cord (6.1 Gy vs 30 Gy) and brachial plexus (43.2 Gy vs 51.4 Gy). The thyroid volume and depth of SC nodes did not influence the thyroid dose distribution. The depth of SC nodes impacted on the HI of SC nodal volumes in the conventional technique (P = .004).ConclusionsThe 3DCRT planning improved dosimetric coverage of the SC nodal volume but increased thyroid radiation doses. The potential adverse effects of incidental thyroid irradiation should be considered while improving dosimetric coverage in SC nodal irradiation for breast cancer.     

The cyclooxygenase-2 inhibitor, celecoxib, prevents the development of mammary tumors in Her-2/neu mice.

Evidence is now available showing that cyclooxygenase (COX)-2, which is involved in prostaglandin production, is overexpressed in many types of tumors including breast. Several reports have indicated that HER-2/neu-positive breast tumors are associated with an increased amount of COX-2 protein. In this study, we evaluated the effectiveness of the select COX-1 and COX-2 inhibitors in preventing mammary tumor development in HER-2/neu transgenic mice. At 4 weeks of age, female HER-2/neu mice were fed a #5020 rodent diet supplemented with 900 ppm celecoxib, a COX-2 inhibitor, 64 ppm of SC560, a COX-1 inhibitor, or the unsupplemented #5001 diet (control). The incidence of mammary tumors was significantly lower in the celecoxib-fed mice (71%; P = 0.001 versus control) than in the control mice (95%) or in the SC560-fed mice (91%). Celecoxib-treated mice also developed fewer tumors (1.3 +/- 1.1 SD; P = 0.039 versus control) than the control mice (2.2 +/- 1.2) or the SC560 treated mice (2.3 +/- 1.3). The median time to tumor development was 266 days in the control group versus 291 days in the celecoxib-treated group (P = 0.003 versus control). Lung metastasis was also reduced by treatment with celecoxib. The COX-1 inhibitor SC560 had no protective effect. The protection offered by celecoxib was associated with significantly lower concentrations of prostacyclin and prostaglandin E(2) in mammary tumors and their adjacent mammary glands. Our findings provide additional preclinical evidence to support the clinical studies to investigate the potential effectiveness of COX-2 inhibitors in protecting woman who are at high risk for breast cancer.     

Clinical Characteristics,Treatment and Survival Outcomes in Malignant Mesothelioma: Eighteen Years’ Experience in Turkey

Background: Malignant mesothelioma (MM) is an insidious tumor with poor prognosis, arising frommesothelial surfaces such as pleura, peritoneum and pericardium. We here aimed to evaluate the demographic,clinical, and radiological features of patients with MM followed in our center as well as their survival. Methods:The study included 228 patients (131 male, 97 female) who were followed up in our institution between 1993and 2010 with the diagnosis of MM. Results: The mean age was 59.1 years in men and 58.7 years in women andthe sex ratio was 1.4:1 in favor of males. Environmental asbestos exposure was present in 86% of the patientsfor a mean duration of 40±20 years (range: 3-70). Pleural effusion and thoracic/abdominal pain were the mostcommon presenting signs and symptoms (70.2% and 57.8%, respectively). One hundred-thirteen (66%) patientswere treated with platinum-based combination chemotherapy (PBCT) plus supportive care (SC) and 67 (34%)patients received SC alone. The median follow-up time was 10.0 months. The median overall survival wassignificantly improved with PBCT plus SC compared to SC alone (11.4 vs. 5.1 months; p=0.005). The 6, 12, 18,and 24-month survival rates were significantly improved with PBCT plus SC compared to SC alone (72%, 43%,19%, and 2% vs. 49%, 31%, 11%, and 1%). Conclusion: The survival of patients with MM improved in patientstreated with PBCT. The survival advantage continued 12- and 24-month after the initial time of combinationchemotherapy.