Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment

The tumor microenvironment consists of tumor, immune, stromal, and inflammatory cells which produce cytokines, growth factors, and adhesion molecules that promote tumor progression and metastasis. Of particular interest in this setting is interleukin-1 (IL-1), a pleiotropic cytokine with numerous roles in both physiological and pathological states. It is known to be up regulated in many tumor types and has been implicated as a factor in tumor progression via the expression of metastatic and angiogenic genes and growth factors. A number of studies have reported that high IL-1 concentrations within the tumor microenvironment are associated with a more virulent tumor phenotype. Solid tumors in which IL-1 has been shown to be up regulated include breast, colon, lung, head and neck cancers, and melanomas, and patients with IL-1 producing tumors have generally bad prognoses. The exact mechanisms by which IL-1 promotes tumor growth remain unclear, though the protein is believed to act via induction of pro-metastatic genes such as matrix metalloproteinases and through the stimulation of adjacent cells to produce angiogenic proteins and growth factors such as VEGF, IL-8, IL-6, TNFα, and TGFβ. The IL-1 receptor antagonist (IL-1ra) is a naturally occurring inhibitor to IL-1 and acts by binding to the IL-1 receptor without activating it. The protein has been shown to decrease tumor growth, angiogenesis, and metastases in murine xenograft models. Our focus in this review is to summarize the known data on the role of IL-1 in tumor progression and metastasis and the use of IL-1 inhibition as a novel therapeutic approach in the treatment of solid organ malignancies.     

Adenosine''s role in the genesis of bradyarrhythmias induced by acute myocardial hypoxia.

A close or even causal relation between myocardial adenosine and bradyarrhythmias during acute myocardial hypoxia was testified in guinea pig, rabbit and dog mainly by using specific competitive antagonist and synchronous quantitative analysis of 3 variables: intensity of myocardial hypoxia, degree of endogenous adenosine increment and severity of bradyarrhythmias. Results disclosed: A) striking resemblance of the bradyarrhythmias with hypoxic origin to those caused by exogenous adenosine, B) same locality of A-V conduction block induced by both myocardial hypoxia and exogenous adenosine, C) precise parallelism among the above-listed 3 variables with very high correlativity (r = 0.99, P < 0.01), D) frequent accompaniment of reversal of hypoxic bradyarrhythmias through resupply of 21% O2 with normalization of preexisted increase in myocardial adenosine, E) satisfactory blockade of hypoxic bradyarrhythmias by adenosine's specific antagonist--aminophylline and their augmentation by adenosine's uptake inhibitor--dipyridamole, F) close similarity of the characteristic curve representing relation among the above 3 variables to that among intensity of myocardial hypoxia, degree of endogenous adenosine increment and amount of coronary blood flow in which adenosine's role as a mediator has been well documented and G) reproducible persistence of bradyarrhythmias during myocardial hypoxia irrespective of preliminary vagotomy and atropinization, denoting independence of the occurrence of such dysarrhythmias upon vagal drive, suggestive of a mechanism other than vagotonia. We advocated that hypoxia-induced bradyarrhythmias was caused by increment in endogenous adenosine.

     

A cloned antigen for serological diagnosis of Wuchereria bancrofti microfilaremia with daytime blood samples.

By differentially screening an adult Brugia malayi cDNA library with sera from microfilaremic and amicrofilaremic donors infected with Wuchereria bancrofti, we have identified a novel parasite antigen denoted SXP-1. Recombinant SXP-1 filarial antigen is preferentially recognized by sera from microfilaremic persons with bancroftian filariasis and from skin snip-positive patients with onchocerciasis. Antibodies to SXP-1 are restricted to the IgG4 subclass and gradually decline after treatment with diethylcarbamazine. These findings indicate that it may be possible to replace microscopic examination of night blood films with a serological test designed to detect antibodies to a mix of SXP-1 and other suitable antigens for the diagnosis of microfilaremia due to bancroftian filariasis.     

Toluene vapor exposure and urinary excretion of hippuric acid among workers in China.

A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported.     

男性慢性胃炎患者人格特征初探

本文采用卡氏十六种人格因素量表，对纤维胃十二肠镜和活体组织病理检查确诊，剔除可能影响调查的疾患之后的５６例慢性胃炎患者做了测查，结果与中国男性成人常模对照，提示男性慢性胃炎患者的主要人格特征有：严谨、保守、忧郁、紧张、顺从、依赖、有焦虑倾向，非内向个性，不属于心理不健康人群，而与消化性溃疡个性特征有所不同，但是，矫治其人格缺损及属必要。     

甲状腺肿瘤X线造影与超声检查对比分析

本文报告了经手术病理证实的53例甲状腺肿瘤,均作了甲状腺造影和B超检查.通过比较分析,我们认为造影对确定肿瘤的良、恶性以及延伸到胸骨后的异位甲状腺肿瘤有其优越性,是一项有效的检查方法;超声则能准确地判断肿瘤的囊、实性,适合碘过敏患者的检查.两种检查各有特点,配合使用有利于对甲状腺肿瘤的诊断和治疗.     

沈阳口岸入出境人员传染病监测工作报告

本文阐述了1990年-1993年间沈阳口岸入境人员传染病监测工作的基本情况，在对6503名归国人员和2146名外籍人员进行传染病监测体检中，发现HIV感染者41人、隐性梅毒患者1人、开放性肺结核患者1人。     

胰岛素样生长因子-Ⅰ对软骨细胞凋亡的抑制

目的:探讨胰岛素样生长因子-Ⅰ(IGF-Ⅰ)对软骨细胞增殖及白细胞介素-1(IL-1)诱导软骨细胞凋亡的影响,揭示其抗损伤作用机制,为关节软骨损伤治疗提供理论依据。方法:分离培养人胚胎关节软骨细胞,采用四氮甲基唑蓝(MTT)法测定不同含量软骨细胞增殖活性的变化,利用光镜、电镜、DNA电泳及流式细胞仪测定作为凋亡检测指标。结果:IGF-Ⅰ呈剂量依赖式促软骨细胞增殖,当IGF-Ⅰ含量达50μg/L时,促软骨细胞增殖作用达最大值。IL-1组光镜、电镜下可见典型的细胞凋亡形态学改变,琼脂糖凝胶电泳示特征性的DNA梯状条带,IGF-Ⅰ处理组未见明显凋亡征象。流式细胞仪检测发现,IGF-Ⅰ处理后软骨细胞凋亡率显著降低。结论:IGF-Ⅰ能促进软骨细胞增殖,对IL-1诱导的软骨细胞凋亡具有保护作用。     

李振华教授调理脾胃用药规律探讨

李振华教授，生于1924年，河南省洛宁县人。著名中医脾胃学专家，全国片批名老中医。国务院特殊津贴专家，原中华中医药学会常务理事、第七届全国人大代表，曾任河南中医学院院长，从事中医临床与教学六十余载，长于内科杂病，晚年潜心于脾胃学说研究，著有《中国传统脾胃病学》等，并负责研究河南省重点科研项目“脾胃气虚本质的研究”及“七五”国家重点科技攻关项目“慢性萎缩性胃炎脾虚证临床及实验研究”，且均荣获河南省科技进步成果奖。经过多年临床实践，李老整理总结出调理脾胃的用药规律。提出通过药物件味归经，以及药效应用与脾胃的生理、病理特点相结合的川药大法。