沙门氏菌,癌症耐药 z-bo 2020-09-23 462

　　The unexpected results of the Salmonella test led to research showing that conventional chemotherapy can more easily cure drug-resistant cancer cells. Scientists at the University of Massachusetts Medical School have discovered that the Salmonella protein SipA can naturally reduce the well-known drug-resistant molecules found in many different types of cancer cells. By providing gold nanoparticles attached to the protein, researchers can significantly increase the sensitivity of tumors to several chemotherapeutics and shrink colon and breast cancer tumors in mice. ..

　　BethA, Professor and Deputy Director of Microbiology and Physiological Systems, University of Massachusetts Medical School. Assistant professors of biochemistry and molecular pharmacology, nanomedicine experts Dr. McCormick and Dr. Gang Han are co-authors of this article.

　　McCormick said: "Given the amazing clinical potential of this study to treat certain drug-resistant cancers, this is very interesting. Based on these findings, we are in the preclinical development stage. For more than 150 years, scientists have been observing different types The bacteria can reduce cancer tumors. Recently, researchers have discovered that Salmonella and other bacteria can be used to fight cancer cells. He suggested that they can directly stimulate the immune response. Researchers have also found that certain bacteria can selectively grow in tumors, as are other treatments. Possibly. Despite these observations, the mechanisms controlling these different effects are still unclear, due to multiple reasons related to immune-related reactions and concerns about potential infections, salmonella or other infections.

　　M As an infectious disease expert, Dr. McCormick has studied the biological tools used to overcome the natural defenses of Salmonella-infected cells. Specifically, she tested the effects of SipA on certain transporters in human intestinal cells and said that SipA can upregulate a protein and cause inflammation. It is believed that McCormick used the common transporter P-gp as a control to complete a series of experiments. She did not expect to find any abnormalities, but she was surprised. We found that the bacterial product almost completely eliminates the P-gp transporter. P-gp, which is usually present on the cell surface, removes waste products and removes foreign bodies, debris and toxins from the cells. Therefore, McCormick believes that Salmonella needs to disable the P-gp protein and promote cell infection. In the case of cancer recurrence, excessive P-gp in tumor cells can lead to the development of drug resistance. In these cells, the role of P-gp is Chemotherapeutic and anticancer agents are excreted from the cells before they accumulate and kill them. Want to know the importance of P-gp against cancer, this new evidence shows that SipA alone can eliminate the P-gp protein that causes multidrug resistance cancer. Can be used as an anti-cancer treatment. However, this protein needs to be delivered to tumors in the body. McCormick has partnered with Ganghan to develop a Salmonella nanoparticle mimic with SipA. Except for bacteria, SipA protein is very unstable and cannot be simply injected into potential patients. It does not use the entire bacteria, but simulates and stabilizes the bacteria. And developed a nanoparticle scaffold to transport, one of which is called a "nanoworm".

　　Because of its inertness and unique three-dimensional scaffold, Han Gang chose gold and developed nanoparticles small enough to invade tumors, but they were too big. It is absorbed by most biological tissues. Regino Mercado-Lubo, a postdoctoral researcher in McCormick’s laboratory, the first author of this article, said: “This tumor is different from the normal group. We expect our nanobacteria to invade the tumor and not accumulate in other tissues because of the tumor. Easy to invade."

　　Er. A researcher used SipA-nanobug and the widely used chemotherapy drug doxorubicin in a mouse model of colon cancer and a mouse model of humanized breast cancer. Mercado-Lubo said: "The results are amazing. Within 30 days, almost no tumor was found. This is abnormal. In some cases, the tumor is smaller than the thin part of the tissue." According to Mercado-Lub, it must be said. It is also important that gold nanoparticles do not accumulate in lung, heart and brain tissue.

　　Next, McCormick, Gang Han and colleagues conducted further research on preclinical development. This helps to determine the safety, toxicity, and dose levels of this nanobacteria into patient trials.

　　McCormick said: "In the past two decades, scientists have been hoping to reverse the drug resistance of cancer cells by screening thousands of small P-gp inhibitor molecules. These attempts have not yet been clinically transformed. Well, we have proven that SipA can be used to achieve natural priority and 2 million years of co-evolution to effectively eliminate intracellular P-gp without causing an immune response. Han Bang is as follows. Mimics have the potential to stabilize certain therapeutic proteins It can be used in combination with a variety of clinical chemotherapies to overcome multidrug resistance in a variety of tumors.