A protein involved in transporting proteins and RNAs out of the cell nucleus offers an attractive target for treating cancer. In a review article, a team led by Qingxiang Sun and Da Jia from Sichuan University, China, discuss the role of the nuclear export factor CRM1 in cancer development. CRM1—which mediates the exit of molecular cargo out of the nucleus and into the cytoplasm—is overexpressed in tumors of the lungs, brain, liver and other organs, and its activity is associated with poor patient outcomes. Drugs that block CRM1 have been tested in clinical trials, with middling success. The authors outline a strategy for a new kind of CRM1 inhibitor that should produce fewer side effects and be less prone to drug resistance than existing agents.
Research elucidating how a protein suppresses the progression of liver cancer could provide new therapeutic targets, say researchers in China. A team led by Rong Xiang and Na Luo at Nankai University examined liver biopsies of patients with hepatocellular carcinoma (HCC), the third most common cause of cancer-related death worldwide. They also grafted HCC cells under the skin of mice. They found that a protein, called TIFA, suppresses the progression of HCC via one of three pathways. One involves competition with another protein, MALT1, to bind with the protein TRAF6, signaling pathways that induce cancer cell death. TIFA-induced cell death also results from suppressing MALT1. Finally, TIFA expression can also activate two genes, JNK and p38, which signal cell death and cell cycle arrest, respectively. The research may provide insights into drug targets that could affect HCC progression.
Treatment with aniron-transporting protein called transferrin could help reverse iron elevationin the Parkinsonian brain. David Finkelstein and colleagues from Australia'sUniversity of Melbourne compared post-mortem samples from 10 people withParkinson's disease and 10 individuals with no history of neurologicalproblems. They found that the substantia nigra region of the brain ofParkinson's patients had a 42% average elevation in iron deposits and a 35%average decrease in transferrin levels compared to the controls. In culturedneurons, adding transferrin helped traffic iron out of the cells. And in amouse model of Parkinson's, transferrin injections under the skin helped loweriron levels in the brain and improve motor symptoms of the disease. However,transferrin also caused iron depletion in the blood, leading to anemia, whichcould limit its therapeutic application in patients.
A new model for assessing disease progression of age-related macular degeneration (AMD) may improve the therapeutic responses of patients. The onset and progression of AMD — a leading cause of vision loss in seniors in developed countries — are linked to multiple genetic and environmental risk factors, including smoking and body mass index (BMI). Kang Zhang of University of California, San Diego with colleagues in the USA and China, has developed a prediction model by collecting data from three groups: patients with advanced AMD, those with intermediate AMD and a normal group. The researchers combined data for genetic variations within 15 genes previously linked to AMD risk with smoking status and BMI of individuals in the three groups. This resulted in a highly predictive model for AMD progression that is promising for improving personalized therapy of patients.
張康教授等在自然出版社與川大華西醫院生物治療國家重點實驗室聯合主辦的 《Signal Transduction and Targeted Therapy》（STTT）上發表了關于年齡相關性黃斑變性(AMD)疾病預測模型的文章(http://www.nature.com/articles/sigtrans 201616)，閱讀全文鏈接見最后。 這篇文章建立的預測模型可以給臨床上的黃斑變性(AMD)疾病診斷、治療和預后判斷等提供依據。
來自美國新澤西的 BioInvenu Corporation的Haifeng Eishingdrelo博士在自然出版社與川大華西醫院生物治療國家重點實驗室聯合主辦的 《Signal Transduction and Targeted Therapy》（STTT）上發表了GPCR/14-3-3蛋白相互作用機制的文章(http://www.nature.com/articles/sigtrans 201618，閱讀全文鏈接見最后）。 這篇文章發現了GPCR蛋白與14-3-3蛋白的相互作用機制。這項工作可能會對疾病的靶向治療帶來更多的機遇。
美國國家科學院院士Marvin Caruthers教授在自然出版社與川大華西醫院生物治療國家重點實驗室聯合主辦的 《Signal Transduction and Targeted Therapy》（STTT）上發表了有關合成寡脫氧核苷酸（ODN）的文章 （http://www.nature.com/articles/sigtrans 201619，可直接點擊本文最下方“閱讀原文”）。 這篇文章發現了具有更有更高穩定性和更高細胞攝取效率的合成寡脫氧核苷酸（ODNs）。這項工作可能會為基于DNA的藥物的研發提供新的思路。