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最新医学新闻 | Cell Reports 发表文章,科学家发现抑制脑癌细胞增殖的新药

小白老师 医学博士英语 2020-02-24

小白老师说:恶性胶质瘤是一种治疗困难的侵袭性脑癌。最新研究发现了一种新药,通过抑制特定蛋白质的方式来控制肿瘤发展。为方便大家获取信息,为大家做了详细注释。文章不难,很流畅,值得一读。


文章关键词:

Glioblastomas  [,ɡlioblæ'stomə]   n. 恶性胶质瘤


Scientists inhibit brain tumor cell growth, paving way for new treatment


Glioblastomas(恶性胶质瘤) are tumors that form out of the "sticky," supportive tissue of the brain and spinal cord(脊髓).


Most of the time, glioblastomas are aggressive malignant(恶性的); they are made of many different types of cells that reproduce very quickly and receive a significant blood supply. The 5-year survival rate is estimated to be less than 10 percent.


Glioblastoma can be difficult to treat because of the heterogenous(异质的) nature of its cells. Some of the cells may respond to therapy while others may not.


Typically, treatment includes a combination of surgery, radiation, and chemotherapy(化疗). So far, this has resulted in a median survival of about 2 to 3 years for patients receiving standard treatment.


Researchers may have found a way to inhibit the growth of brain tumors, here shown in an MRI scan.


Patients with more severe forms of glioblastoma, who receive a combination of drugs and radiation therapy, usually survive for an average of 14.6 months, and the 2-year survival rate is approximately 30 percent. Little can be done to treat recurrent(复发的) glioblastoma.


In this context, more and more researchers are exploring genetic options for treatment. Recent studies have pointed to mutations(突变) in the receptor tyrosine kinase (RTK) (受体酪氨酸激酶) genes as the key driver of glioblastoma, but clinical trials(临床试验) aimed specifically at neutralizing(中和) these driver mutations were not successful in treating this form of cancer.


However, researchers from the Peter O'Donnell Jr. Brain Institute and Harold C. Simmons Comprehensive Cancer Center may have found a way to inhibit(抑制) glioblastoma cells.


Their findings were published in the journal Cell Reports.


The team - co-led by Dr. Robert Bachoo, of the Annette G. Strauss Center for Neuro-Oncology at University of Texas Southwestern Medical Center, and Dr. Ralf Kittler, an assistant professor of pharmacology(药理学) in the Eugene McDermott Center for Human Growth and Development - successfully used a drug to target different proteins that drive the growth of glioblastoma tumors.


Mithramycin(光神霉素) inhibits glioblastoma-driving transcription factors


The new study suggests that so far, researchers have mistakenly focused on RTK gene mutations, which are only responsible for starting tumor growth, not for the continued growth of glioblastoma.


"Our work shows that the gene mutations which the pharmaceutical(制药的) industry and clinicians(临床医生) have been focusing on are essential only for starting tumor growth. Once the tumor has advanced to the stage where patients seek treatment, these mutations are no longer required for continued tumor growth; they are in effect redundant(多余的)," explains co-senior author Dr. Bachoo.


Instead of the RTK genes, the new study found three transcription factors(转录因子) to be responsible for glioblastoma: Sox2, Olig2, and Zeb1.


As co-senior author Dr. Kittler explains, the study shows that these "neurodevelopmental(神经发育的) transcription factors (master proteins that regulate the activity of hundreds of genes during normal brain development) are reactivated(再活化) to drive the growth of glioblastoma."


In their study, Dr. Kittler, Dr. Bachoo, and team found the drug mithramycin to inhibit these transcription factors.


"We can inhibit these transcription factors and prevent further tumor growth with the chemotherapy drug mithramycin, a drug that has not been in clinical use for years due to its side effects. Our discovery has the potential for the development of a new therapy that may increase survival time for glioblastoma patients."

                                                  —— Dr. Ralf Kittler


"These findings change our fundamental understanding of the molecular(分子的) basis of glioblastoma, and how to treat it," adds Dr. Bachoo. "We may have identified a set of critical genes we can target with drugs that are shared across nearly all glioblastomas."


However, the scientists warn that mithramycin may cause liver toxicity(肝毒性) in a number of patients, and that repurposing the drug to treat glioblastoma could take several years.

Written by Ana Sandoiu


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