东北铁线莲对小鼠肿瘤的抑制作用

[目的]探讨东北铁线莲乙酸乙酯提取物的抗肿瘤作用.[方法]给小鼠接种S180肉瘤细胞制作S180肉瘤小鼠动物模型,随机分为空白对照组、东北铁线莲乙酸乙酯提取物大、中、小剂量组及环磷酰胺组,实验大、中、小剂量组分别给予0.8,0.4,0.2 g/kg东北铁线莲乙酸乙酯提取物,10 d后观察小鼠体重变化,计算肿瘤抑制率.[结果]东北铁线莲乙酸乙酯提取物大、中、小剂量组肿瘤抑制率分别为66.4%,55.3%,40.6%,与空白对照组比较有显著性差异.[结论]东北铁线莲乙酸乙酯提取物对小鼠S180肉瘤的生长具有抑制作用.     

香菇多糖抗肿瘤的基础研究及临床应用进展

香菇多糖是一种多糖类生物反应调节剂.大量动物实验和临床报告显示其具有调节免疫功能的作用,包括增强T、B淋巴细胞、巨噬细胞、NK细胞(natural killer cell)、淋巴因子激活杀伤细胞(lymphokine activated killer cells,LAK)、白细胞介素-2(interleukin 2,IL-2)等免疫相关因子的作用.目前在临床抗肿瘤方面的应用较为广泛.主要用于辅助药物治疗、联合放化疗和改善预后等方面.本文就香菇多糖在抗肿瘤方面的基础研究和临床应用进行综述.     

Human tumor cloning assays: Applications in clinical oncology and new antineoplastic agent development

The human tumor cloning assay (HTCA) has been available for preclinical and clinical applications for the last 11 years. This article examines the usefulness of that assay both in the practice of clinical oncology and in the development of new antineoplastic agents. In the area of prediction of response of an individual patient's tumor to a particular antineoplastic agent, in a total of 2274 correlations in a variety of clinical trials, the assay has shown a remarkably good ability to predict whether a patient's tumor would respond to a particular agent (percent true positives 69%; percent true negatives 91%). However, despite this ability to predict these responses, the assay has not yet been accepted for general clinical use, because there have not been rigorous trials to prove the assay will improve patient survival. These rigorous clinical trials are now underway. In the area of drug development, the HTCA has been used to screen for new antineoplastic agents as well as to pinpoint tumor types against which the new agent will be active in phase II clinical trials. As will be seen in this review, the HTCA has been most successful in this area.     

Use of chiral liquid chromatography for the evaluation of stereospecificity in the carbonyl reduction of potential benzo[c]fluorene antineoplastics benfluron and dimefluron in various species

Benfluron (B) [5-(2-dimethylaminoethoxy)-7H-benzo[c]fluorene-7-one hydrochloride] is a potential antineoplastic agent. In the organism, B undergoes a rapid phase I biotransformation through oxidative and reductive metabolic pathways. The carbonyl reduction of B leads to reduced benfluron, red-B, this is one of the principal pathways for the deactivation of this compound.

The structure of B was modified to suppress its rapid deactivation via the carbonyl reduction on C₇. Dimefluron, D (3,9-dimethoxy-benfluron) is one of the derivatives of B, in which an alternative metabolic pathway (O-desmethylation) prevails over the carbonyl reduction.

The goal of this study was to develop HPLC methods enabling chiral separations of the red-B and -D enantiomers. The separation of red-B enantiomers was successful done on a Chiralcel OD-R column (250 mm × 4.6 mm ID, 5 μm) using a mobile phase acetonitrile–1 M NaClO₄ (40:60, v/v). Another mobile phase, methanol–1 M NaClO₄ (75:25, v/v), had to be employed for the sufficient resolution of red-D enantiomers. Flow rate was 0.5 ml min⁻¹ in both cases. Red-B was detected at 340 nm, red-D at 370 nm.

The above chiral HPLC methods were used for the study of the biotransformation of B and D in the microsomal fractions of liver homogenates prepared from various species (rat, rabbit, pig, guinea pig, goat and human). The enantiospecificity of the respective carbonyl reductases was evaluated and discussed for both prochiral compounds, B and D.     

区域化疗对结肠癌术后复发及肝转移的影响

目的　探讨不同化疗方法对结肠癌术后局部复发和肝转移的影响．方法　Ｄｕｋｅｓ＇ Ｃ１ ～Ｃ３ 期结肠癌患者４９ 例,术后随机分成３ 组,以区域化疗（ ｎ ＝ ２６） 、全身化疗（ ｎ ＝ １２） 及口服化疗药（ ｎ ＝ １１）３ 种方法进行治疗．结果　区域化疗组术后复发和肝转移明显低（５０ ％ ｖｓ ９２ ％ 及９１ ％ ） 于全身化疗及口服化疗药组．结论　结肠癌术中、术后以ＦＭＣ 方案定期化疗,对减少复发和肝转移将起到积极作用．     

Efficacy and safety of dabrafenib–trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF‐V600 mutation: A systematic review and network meta‐analysis

The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib – trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF‐V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta‐analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF‐V600 mutation (NMA‐pBRAFV600) and another with mixed population (with or without the mutation: NMA‐pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA‐pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA‐pBRAFV600. Dabrafenib–trametinib was found to have a favorable effect on overall survival (OS) and progression‐free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA‐pMixed, dabrafenib–trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib–trametinib and vemurafenib–cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib–trametinib has a favorable effect on Grades 3 and 4 adverse events.     

Current perspectives on childhood brain tumours: a review

Tumours of the brain and spinal cord are the commonest solid tumour in children and the leading cause of cancer related morbidity and mortality. The increasing availability of modern imaging techniques has resulted in peak of incidences in the 1990s. Current challenges for the general public, paediatricians and general practitioners lie in increasing awareness of the presenting features so that an earlier diagnosis can be made. Specific issues and peculiarities relating to congenital/infantile brain tumours have been explored. Improved histological classification supported by biological markers and subgroup allocation has enabled better treatment planning and increased survival. The emphasis is now focussing on formulating treatment strategies associated with reduced risks of toxicities for favourable risk groups and intensification of treatment for those with worst prognosis. The interface between brain tumours and epilepsy, effects of anti-epileptic medications, antineoplastic medications and tumour surgery on epilepsy were touched upon. Advances in radiotherapy through the increasing availability of proton beam radiotherapy and its advantage over photon radiation therapy in brain tumours has also been discussed.     

瑞戈非尼的合成工艺优化

本研究对抗肿瘤药瑞戈非尼(1)的合成工艺进行优化。4-氯吡啶-2-甲酸甲酯(3)与甲胺反应得4-氯-N-甲基吡啶-2-甲酰胺(4)。以四丁基溴化铵为催化剂,4与4-氨基-3-氟苯酚(5)在二(口恶)烷中反应得4-(4-氨基-3-氟苯氧基)-N-甲基吡啶-2-甲酰胺(6)。三光气与4-氯-3-三氟甲基苯胺(7)在甲苯和吡啶中反应得4-氯-3-(三氟甲基)苯异氰酸酯(8)。6与8在乙酸乙酯中缩合得瑞戈非尼无水物(2),2在氯化氢的乙酸乙酯溶液作用下成盐酸盐,再在丙酮/水中加入碳酸氢钠转化为1,纯度99.8%。优化后的工艺反应条件温和,操作简单,总收率65%(以3计),较适合工业生产。