Anthrax,MEK and Cancer

The MEK family of protein kinases plays key roles in regulating cellular responses to mitogens as well as environmental stress. Inappropriate activation of these kinases contributes to tumorigenesis. In contrast, anthrax lethal factor, the principal virulence factor of anthrax toxin, has been demonstrated to selectively inactivate MEKs. In this article we will discuss recent advances in our understanding of molecular aspects of the pathogenesis of anthrax, emphasizing the potential role of MEK signalling in this disease, and outline novel strategies to use anthrax lethal toxin in the treatment of cancer.

Key Words

Anthrax, MEK, MAPK, Cancer     

Viruses, Genes and Cancer

Cancer takes many forms and has many causes. But it is possibleto unite these many forms and causes with a single hypothesis:that cancer may be a malady of genes, that abnormalities ofgenes usually lie at the heart of the disease. Recent researchhas uncovered evidence that this hypothesis may be correct.Many human tumors contain genetic damage that can account forcancerous growth. The damage affects genes that are normallyvital to normal growth and development, but that have run amokin cancer cells. The prevention and treatment of cancer hasuntil now been based on trial and error. The identificationand characterization of damaged genes in human tumors pointsthe way to new and more rational strategies for the diagnosis,prognosis and therapy of cancer.     

环境、基因组与肿瘤

肿瘤是当前危害人类健康最严重的疾病之一。从某种程度上说,它是一种遗传性疾病,然而在肿瘤发生、发展的多个阶段里,环境因素及其它非遗传性因素也起到了明显的作用。现在认为单纯遗传因素仅能解释大约5%的肿瘤的发病机制,而大部分肿瘤的发病机制归因于外界环境因素与遗传性、获得性肿瘤易感性之间的协同作用。值得注意的是,部分肿瘤易感性来自人类基因组的多样性。因此,环境、人类基因组及肿瘤三者之间有密不可分的关系。综合所有来自流行病学和实验室研究的信息,净化环境、给予高危人群特殊的保护,将会逐渐降低肿瘤的发病率。 Abstract：Cancer is one of the most serious diseases that thre aten human being today.To some degree,it is a genetic disease but environmental and other nongenetic factors clearly play a role in many stages of neoplastic pr ocess.Genetic factors by themselves are thought to explain only about 5% of all cancer.The remainder can be attributed to external,“environment” factors that act in conjunction with both genetic and acquired susceptibility.Of note,part of the susceptibility is owing to the variety of human genome.So,environment,human genome and cancer have much to do with each other.Combining all of the informat ion from epidemiology and from research works in laboratory with policy-making and clinical works,purifying the environment,giving special protection to the po pulation at high risk,the mobility of cancer may decrease gradually in the future.     

Cancer therapy, vomiting, and antiemetics

Both radiotherapy and chemotherapy for cancer are capable of causing nausea and vomiting. With both treatment modalities, the nausea and vomiting is thought to be a second-order process rather than being due to direct stimulation of neuromechanisms that control vomiting. Both a peripheral (gastrointestinal tract) and central (chemoreceptor trigger zone) effect may be operating with both radiotherapy- and chemotherapy-induced vomiting. With radiotherapy, gastrointestinal toxicity is affected by the type of radiation, radiation dose and field size, fractionation schedule, individual patient factors, and the part of the patient that is radiated. Many different factors also influence the frequency and severity of nausea and vomiting following chemotherapy. With both radiotherapy and chemotherapy, the frequency and severity of nausea and vomiting is probably mediated by a reduction in breakdown of various neurotransmitters. It is presumed that as the levels of neurotransmitters increase, nausea and vomiting develop. Antagonists of these neurotransmitters may afford some antiemetic protection. Nausea and vomiting may be so severe in patients with cancer that they may refuse potentially curative therapy because of it. Anticipatory nausea and vomiting may develop in patients who have become quite sick after receiving treatment. Exposure to stimuli associated with the emetogenic agent is then sufficient to trigger nausea and vomiting. Standard antiemetics do not help anticipatory nausea and vomiting, although behavioural training may. A variety of different drugs have proven useful as antiemetics, including dopamine antagonists such as phenothiazines, metoclopramide, corticosteroids (dexamethasone and methylprednisolone), cannabinoids, and benzodiazapines. Antihistamines and anticholinergics are of value in some situations. New serotonin antagonists appear to be very promising and are currently undergoing clinical studies. Multiagent antiemetic regimens appear to be more effective than single agent regimens in some situations.