遏制癌症,胰腺癌,前列腺癌,肺癌,结肠癌,膀胱癌 z-bo 2020-09-16 348

　　When activated, Ral protein drives tumor growth and metastasis in several human cancers such as pancreatic cancer, prostate cancer, lung cancer, colon cancer and bladder cancer. Unfortunately, there is currently no drug that can block the activity of Ral. A research report published in the journal Nature on September 14 stated that a new method was used to block the activation of these Ral proteins. This is very important to inhibit the development and spread of various cancers.

　　"If you want to prevent the crocodile from biting you, you can tie the crocodile's mouth tightly. We took another approach-put a stick in the crocodile's mouth to keep it open." Senior author of the paper, Colorado Said Dr. Dan Theodorescu, director of the University Cancer Center and professor of urology and pharmacology.

　　Ral can drive cancer development

　　Previous studies have shown that when the proteins RalA and RalB are present, cells replicate in a form that promotes the aggressiveness of cancer.

　　RalA and RalB can cause cancer genetic changes. Theodorescu and his colleagues discovered markers of these changes. Up-regulation and down-regulation of genes can predict aggressive cancer.

　　Theodorescu said: These Ral proteins themselves do not promote the development of cancer, but Ral proteins can cause genetic changes to drive the development of cancer.

　　Theodorescu explained: Ral of the GTPase family is currently known as a member of the RAS oncogene family. These RAS family GTPases exist in leukemia, lung cancer, colon cancer and other cancer types. Researchers have been working hard to find targeted cancer therapy targets. The Ral family is a good cancer treatment target.

　　compounds reduce Ral activation

　　The new research uses some advanced computer models to detect when the Ral protein is in an inactive state (referring to the phenomenon that proteins, amino acids, genes, etc. are affected by physical or chemical factors, resulting in the loss of its biological activity. The structure of refolding) specifically investigates the changes in this structure when the protein is activated. The results show that the inactivated Ral has a cavity, which disappears when this protein is activated. This is the crocodile's mouth, and what Theodorescu and colleagues need now is a stick.

　　In order to find the required stick, the researchers used a computer to get 500,000 compounds into this cavity, and found that 88 small candidate molecules can bind to the inactivated Ral and prevent its activation. The researchers then tested these results in human cancer cells, and they used these compounds to treat cancer cells to see which compounds can minimize Ral activation. From this group of compounds, they found a few compounds that can reduce Ral activation especially in lung cancer cells.

　　Oral or injection is uncertain

　　Further tests evaluated the ability of these compounds to slow the growth of suspended human cancer cells (some cancer cells grow in suspension, some grow against the wall). One called RBC8 is the most successful in this regard. In order to further transform this functional molecule, the research team synthesized derivatives of RBC8, and compared these derivatives with the parent molecule, and found that a compound they labeled BQU57 was very effective.

　　Next, the test turned to a mouse human lung cancer cell model. Whether the cells in the animal model will absorb BQU57, making the compound a potential drug for cancer patients is an important question to be answered by this test. In other words, the researchers want to confirm whether the drugs that work in petri dishes also work in animals?

　　As expected, BQU57 entered the tumor tissue a few hours after the administration. And not only did it get into it, the drugs also slowed the growth of these tumors. The results of the analysis showed that BQU57 prevented Ral activation in the treatment of tumors.

　　Theodorescu said: "Before entering the clinic, we still need to optimize these compounds, determine the toxicity characteristics of these drugs in several animal species, and determine their best delivery route, such as oral or intravenous administration. We will This research work is regarded as a valuable first step in the development of a new type of Ral targeted therapy."

　　Skin cells lose memory and become white blood cells

　　Recently, for the first time, scientists have turned human skin cells into transplantable white blood cells, which are soldiers of the immune system that can fight infection and invasion. This research conducted at the Salk Biological Research Center allows researchers to create a new therapy that introduces new white blood cells into the body to attack cancer or diseased cells.

　　This research published in the journal Stem Cells shows that skin cells can be transformed into human white blood cells with a little creative manipulation. "This process is very fast and safe in mice," the researchers said.

　　The latest method only takes two weeks, does not form tumors, and can be injected into organs well. "We program the skin cells to forget what they are, but to develop into the type of cell we want it to form, that is, white blood cells." One of the article’s first authors and researcher Ignacio Sancho Martine Si said, "It takes only two biomolecules to induce such cell memory loss and create new cell types."

　　The technology demonstrated in this study uses a molecule called SOX2 to make skin cells plastic to a certain extent—that is, the state of losing the memory of becoming a specific cell type. Then, the researchers used a genetic factor called miR-NA125b to direct the cells to become white blood cells. Researchers are currently conducting toxicology research and proof-of-concept of cell transplantation, and then conduct potential preclinical and clinical research.

　　Use less medicine or better effect for cancer

　　New research shows that doctors can reduce the treatment of certain cancer patients because some drugs can reduce the frequency of taking.

　　Researchers at the MD Anderson Cancer Research Center in Houston found that women with breast cancer and metastases to the bones can safely reduce their dosage to once every three months after receiving bisphosphonates every month for the first year. This change can reduce the risk of kidney problems, while reducing a rare but serious side effect, that is, part of the jaw bone becomes weak and necrotic.

　　The lead author of this study, Gabriel Hortobagy, said: “Reducing the number of treatments can also reduce the inconvenience and cost of patients.”

　　Another study funded by the National Institutes of Health found that patients with specific head and neck cancers caused by human papillomavirus can reduce the dose of radiation therapy.

　　Another federally funded study shows that for cancer patients who survive less than a year, cholesterol-lowering statins can be stopped. This will save approximately US$603 million in the United States.

　　This study found that discontinuing statins does not shorten survival, but it can reduce the occurrence of cancer symptoms, including pain, depression, nausea and fatigue.

　　American Society of Clinical Oncology expert Patricia Ganz said: “We now have evidence that stopping certain drugs—especially the commonly prescribed statins—is safe and can improve the quality of life of patients.”