Phase II, randomized, multicenter, comparative study of peginterferon-alpha-2a (40 kD) (Pegasys) versus interferon alpha-2a (Roferon-A) in patients with treatment-naïve, chronic-phase chronic myelogenous leukemia

The efficacy and safety of peginterferon-alpha-2a (40 kD) (PEG-IFNalpha-2a), 450 microg once weekly, versus IFNalpha-2a, 9 MIU once daily, for 12 months, was evaluated in a Phase II study in IFN-na?ve patients with chronic-phase, Philadelphia-chromosome-positive CML. At the end of the treatment, complete hematological response was observed in 66.2% (47/71) and 45.2% (33/73) of the PEG-IFNalpha-2a group and IFNalpha-2a groups, respectively (p = 0.009), and major cytogenetic response occurred in 35.2% and 17.8%, respectively (p = 0.016). PEG-IFNalpha-2a was at least as effective as IFNalpha-2a overall, including progression-free survival at the end of treatment, and overall survival after 30 months of follow-up. Adverse events necessitated fewer withdrawals but more dose adjustments in the PEG-IFNalpha-2a group compared with the IFNalpha-2a group (11%versus 23%, and 84.5%versus 65.8%, respectively). In conclusion, PEG-IFNalpha-2a (40 kD), 450 microg once weekly, compared with IFNalpha-2a, 9 MIU once daily, resulted in higher rates of hematologic and cytogenetic response and greater overall survival.     

Solid phase synthesis, radiolabeling and biological evaluation of a (99m) Tc-labeled α(V)β(3) tripeptide (RGD) conjugated to DOTA as a tumor imaging agent

Solid phase synthesis of peptides-radiometal chelator can facilitate the creation of radioactive peptide libraries to be utilized in high throughput in in vivo screening of targeted molecular imaging agents. An α(V)β(3) tripeptide derivative DOTA-NH-Arg-Gly-Asp was synthesized by Fmoc solid phase peptide synthesis and analyzed by spectroscopic techniques. In order to radiolabel this RGD peptide with (99m)Tc-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was incorporated as a chelator. The DOTA-peptide conjugate binds to (99m)Tc with high efficiency at ambient temperature. The resulting conjugate is stable under physiological conditions for at least 24 h after radiocomplexation. The receptor binding studies of (99m)Tc-DOTA- α(V)β(3)-tripeptide in established human tumor cell lines U-87MG and BMG revealed K(d) values in the nM and μM range respectively. U-87MG tumors in athymic mice were accumulated in the γ-images and major accumulation of the radiotracer was observed in kidneys followed by liver and lungs. High tumor uptake was shown in the U-87MG tumor bearing athymic mice; tumor to muscle ratios reached 8.13 ± 2.18 and 35.09 ± 4.78 at 1 and 4 h after post injection respectively.     

苯丙(a)蒽的毒性研究进展

苯丙（a）蒽（BaA）是一种四环结构的多环芳烃（PAH）类物质,是化石燃料不完全燃烧的副产物,与其他的PAHs以混合物的形式存在。BaA可通过口腔、鼻腔及皮肤等多种途径暴露于人类,对人的主要危害是致癌性。国际癌症研究机构（IARC）根据其分类标准将BaA归为2B类（对人可能致癌）。目前尚无充足数据支持通过计算剂量外推斜率因子（slope factor）来完成动物致癌系数与人体致癌系数之间的推导。本文对BaA的致癌性等毒性研究进行系统文献检索与综述,以期为今后进行BaA的健康风险评估提供可靠的毒理学数据基础。     

Cohorts and consortia conference: a summary report (Banff, Canada, June 17�C19, 2009)

Epidemiologic studies have adapted to the genomics era by forming large international consortia to overcome issues of large data volume and small sample size. Whereas both cohort and well-conducted case-control studies can inform disease risk from genetic susceptibility, cohort studies offer the additional advantages of assessing lifestyle and environmental exposure-disease time sequences often over a life course. Consortium involvement poses several logistical and ethical issues to investigators, some of which are unique to cohort studies, including the challenge to harmonize prospectively collected lifestyle and environmental exposures validly across individual studies. An open forum to discuss the opportunities and challenges of large-scale cohorts and their consortia was held in June 2009 in Banff, Canada, and is summarized in this report.     

Cigarette Smoking Among Lesbians, Gays, and Bisexuals: How Serious a Problem? (United States)

INTRODUCTION: Population-based health surveys seldom assess sexual orientation, which results in the absence of a reliable measure of smoking among lesbians, gays, and bisexuals (LGB), a population perceived to have higher risks of tobacco-related diseases. This is the first study to compare the cigarette smoking rate of LGB with that of heterosexual individuals using a population-based sample with both male and female adults, and to identify which sub segments of LGB population are particularly burdened by tobacco use. METHODS: California Health Interview Survey (CHIS), a population-based telephone survey was used to assess smoking prevalence and its correlates among respondents. Of 44,606 respondents, 343 self-identified as lesbian; 593 self-identified as gay; and 793 identified themselves as bisexual (511 female and 282 male). Statistical analysis was performed using SAS and SUDAAN. RESULTS: Lesbians' smoking rate (25.3%), was about 70% higher than that of heterosexual women (14.9%) Gay men had a smoking prevalence of 33.2%, comparing to heterosexual men (21.3%). After controlling for demographic variables, logistic regression analysis showed that lesbians and bisexual women were significantly more likely to smoke compared with heterosexual women (OR = 1.95 and OR = 2.08, respectively). Gay men were also significantly more likely to smoke than heterosexual men (OR = 2.13; 95% CI = 1.66-2.73). Being 35-44-years-old, non-Hispanic White, and having low-education attainment and low-household income were common demographic predictors of cigarette smoking among LGB. CONCLUSION: Our study provides the strongest evidence to date that lesbians, bisexual females, and gay men had significantly higher cigarette smoking prevalence rates than their heterosexual counterparts.     

表阿霉素(EPirubicin, Pharmorubicin)

一、蒽环类抗癌药物的发展 六十年代末进入临床的蒽环类化合物在肿瘤化疗中的地位愈来愈重要,成为四十年代应用性激素治疗乳腺癌和氮芥治疗恶性淋巴瘤,及五十年代末合成了环磷酰胺和氟脲嘧啶以来新的里程碑。柔红霉素对急性白血病有效,阿霉素对许多实体肿瘤有效,使肿瘤化疗在综合治疗中的地位有了相当提高。     

癌肿病人血浆阿朴脂蛋白(a)水平升高

癌肿病人脂蛋白代谢的变化早已报道,并建议将特定脂蛋白作为恶性肿瘤的潜在标记。Skipski从癌肿病人血清中,分离出在脂质构成和漂浮特性上类似于高密度脂蛋白(HDL)的糖基脂蛋白,称之为新蛋白质w和s(neopr-oteolipids W和s)。Wieczorek等描述了类似脂蛋白的颗粒,称之为含mRNA的脂蛋白,其某些特性类似于HDL。Mountford和Wright检测到癌肿病人的血浆脂蛋白并称之为恶性相关脂蛋白(MAL)。在这些研究中,作者分析     

红景天,抵御癌症好帮手(下)

在《新编药物学》第十六版(陈新谦等主编,人民卫生出版社出版)的"红景天"条目中,比第十五版增添了以下一段文字:"动物实验研究表明,红景天植物或其提取物有抗癌作用,可明显抑制和直接杀伤肝癌、喉癌、胃癌、肺癌细胞,对S-180细胞具有一定的抑制作用,这种抑制作用在无毒剂量范围内随浓度增加,抑制作用增强。"     

Primary treatment of low-grade non-Hodgkin's lymphoma using an all oral anthracycline-containing regimen, chlorambucil, idarubicin, dexamethasone (CID) – a phase II study

Purpose: The alkylating cytostatic prodrug cyclophosphamide is bioactivated by the human cytochrome P450 enzyme system. Since these enzymes are not only expressed in human liver, but also in extrahepatic tissue, local bioactivation of this drug may play an important role in its antineoplastic effects, e.g., chemotherapy of lung tumors. This would require uptake of significant amounts of cyclophosphamide into tumor tissue, which has not yet been demonstrated. Methods: We used a recently developed, ex vivo isolated, ventilated and perfused human lung model to study cyclophosphamide uptake into bronchial carcinoma and healthy lung tissue. Following a standard lobectomy, lung samples containing the tumor were perfused with buffer containing 2 mM cyclophosphamide for 2 h. Cyclophosphamide concentrations in perfusate and healthy peripheral tissue were measured during the perfusion and in tumors at the end of perfusion. Results: In all tissue samples, cyclophosphamide uptake was relatively poor, indicated by a tissue to perfusate ratio of 0.021. Moreover, in tumor samples, cyclophosphamide concentrations were significantly lower (P < 0.05) than in healthy lung tissue and showed pronounced interindividual variability. Median concentrations were 36.8 μg/g (26.9–44.2 μg/g) in healthy tissue and 5.1 μg/g (0.0–26.8 μg/g) in tumor samples. Tumor cyclophosphamide concentrations varied between 0 and 75% of those reached in healthy tissue. Conclusions: Our results indicate that CP tumor concentrations are modulated by factors different from dose and that expression of bioactivating enzymes in human lung or transfection of genes encoding these enzymes into tumor cells does not necessarily lead to local bioactivation of cyclophosphamide. Received: 4 March 1999 / Accepted: 8 June 1999     

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer (NSCLC)--is there a role for a new chemotherapy programme?

Phase II with single-agent docetaxel, in second-line NSCLC, demonstrated an overall response rate of 20%, with a median response duration of 7 months and a median survival time of 9 months. These results suggested that docetaxel had promising activity in patients with platinum-resistant or refractory NSCLC. Phase III studies in this patient population subsequently confirmed this activity; docetaxel prolonged survival when compared to either vinorelbine/ifosfamide or the best supportive care. The phase II studies with docetaxel in first-line NSCLC produced an overall response rate of 30% in evaluable patients, with a median response duration of 6 months and a median survival time of 9 months. A phase III randomized study demonstrated a significant improvement in survival and time to progression with docetaxel, compared to the best supportive care. Based on the activity observed with single-agent docetaxel, combination and multimodality studies with docetaxel have also been conducted. Docetaxel is an active agent in first- and second-line NSCLC. Ongoing studies in the front-line treatment of NSCLC will further define the role of docetaxel in the neo-adjuvant setting.     

Poly(ADP-ribose): a co-regulator of DNA methylation?

The formation of multiprotein complexes is l'ordre du jour in regulatory pathways. In this issue of Oncogene, Reale et al. report the formation of a particularly sophisticated complex of two important regulatory enzymes, DNMT1 (DNA methyltransferase-1) and PARP-1 (poly(ADP-ribose)polymerase-1). The former evolved with a specific sequence motif binding the enzymatic product of the latter. The product, poly(ADP-ribose), bonds the two partners into a heterodimeric complex and, as a consequence, the catalytic function of DNMT1 is silenced. Thus, PARP-1 becomes a conditional negative regulator of DNMT1. In a larger perspective, Reale et al. highlight the potential role of PARP-1 as a co-regulator of DNA methylation leading to epigenetic reprogramming of cancer cells.     

Huriet law: application in a regional cancer centre (Centre Léon-Bérard, Lyon)

Clinical research is one of the main activities in cancer centres and is submitted in France to a specific law (named "loi Huriet") which includes good clinical practices. We are now conducting a general program of quality evaluation and improvement in the regional cancer centre of Lyon (centre Léon-Bérard). Part of this program is an audit of the application of the Huriet law. Since no instrument exist for measuring this application, we have created a specific one, that attribute notation according to the different aspects of the law. Results show a good level of conformity but sometime non sufficient. There is no difference between the two studied years. Quality changes according to promoters (private or academic) and monitoring. Written procedures and specific training for the different actors are required to improve quality of clinical research with focus on the patient interest.     

Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): Is a clinical benefit still achievable?

Background:There are few clinical data on the sequentialuse of aromatase inhibitors (AI). This paper focuses on therelevance of clinical benefit CB (CR + PR + SD 6 months) inpostmenopausal metastatic breast cancer (MBC) patients treated with thesteroidal aromatase inhibitor (SAI) formestane (FOR), who had alreadyreceived non-steroidal aromatase inhibitor (nSAI): letrozole (LTZ) oranastrozole (ANZ). Patients and methods:Twentypostmenopausal women with MBC were analysed in this retrospectivetwo-centre study with the sequence nSAI-FOR. When receiving ANZ, 1 of 11achieved a complete response and 9 of 11 a stable disease 6 months,and receiving LTZ 1 of 9 achieved a partial response and 4 of 9 astable disease 6 months. The analysis of the entire populationtreated with FOR showed an overall CB of 55% (11 of 20) with amedian duration of 15 months and median time to progression (TTP) of 6months. Conclusions:Formestane 250 mg once bi-weeklyseems to be an attractive alternative third-line hormonal therapy forthe treatment of patients with MBC, previously treated with nSAI.