NBE . . . Independent innovation: Huang Bo/Wang Ximo developed a new technology for the treatment of vesicle bile duct cancer.

Cholangiocarcinoma with high malignancy and poor prognosis, especially extrahepatic cholangiocarcinoma, is the difficulty in clinical treatment of digestive system tumors. The survival time of patients with advanced hilar obstructive cholangiocarcinoma is only 3-6 months.on July 6, 2020, Huang Bo team of Institute of basic medicine, Chinese Academy of Medical Sciences and Wang Ximo's team from Tianjin Nankai Hospital Affiliated to Nankai University published in the journal Nature biomedical engineering the title "methotrexate loaded tumor cell derived microorganisms can relieve biliary obstruction in patients with external choledochocarcinoma This study not only demonstrated the efficacy and safety of drug loaded vesicle therapy for patients with cholangiocarcinoma, but also clarified its therapeutic mechanism.the new breakthrough of drug-loaded vesicle technology, death is not destruction.when a cell dies, the cell membrane can wrap and form vesicles within the cell and release it to the outside of the cell for the uptake and reuse of the surrounding cells. Just as the poem goes, "the falling red is not a heartless thing, but turned into spring mud to protect flowers more.".although cell vesicles were discovered in the middle of last century, they have been regarded as the waste of cells and have not been studied.Professor Huang Bo's team carried out a pioneering research on the role of cell vesicles in tumor and immunity more than 10 years ago (bbrc, 2010), and creatively wrapped chemotherapy drugs in it to carry out cancer treatment research. It has proved that drug loaded vesicles, as a therapeutic method, can kill tumor cells effectively. This work was published in nature communications in 2012.the team further confirmed that drug-loaded vesicles preferentially kill drug-resistant tumor seed cells, and the relevant results were published in mainstream journals such as cell research and biomaterials.on the basis of these studies, the team launched a clinical trial of drug loaded vesicles in 2011 for the treatment of Cancerous Pleural Effusion and cancerous ascites, which showed that the technology was safe and effective, especially for Cancerous Pleural effusion.based on the above clinical trials, Huang Bo team creatively proposed the use of drug loaded vesicles in the treatment of obstructive cholangiocarcinoma, and has cooperated with Tianjin Nankai hospital since 2014 to carry out a clinical trial of drug loaded vesicles in the treatment of cholangiocarcinoma.because the survival time of patients with advanced hilar cholangiocarcinoma is generally 3-6 months, and the quality of life is very poor. For these patients, percutaneous transhepatic biliary drainage (PTCD) guided by ultrasound is used to inject methotrexate loaded vesicles into the bile duct cavity above the obstruction site of cholangiocarcinoma through the drainage tube, so that the drug loaded vesicles can play a full role in killing cholangiocarcinoma Therefore, it is expected to produce good therapeutic effect.clinical research results show that about 30% of patients with biliary obstruction change, about 50% of patients with the first course of treatment jaundice symptoms reduced, liver function improved, defecation color can change from clay color to yellow, most of the patients' diet and quality of life can be improved.in terms of safety, there were no significant changes in blood routine, liver and kidney function, no abdominal pain, nausea, vomiting and other discomfort symptoms. The safety performance was good, showing potential clinical application value.although cholangiocarcinoma cells are not sensitive to all chemotherapeutic drugs and radiotherapy, in the above clinical trials, the chemotherapeutic drugs contained in the above-mentioned clinical trials are only a few hundred times of the clinical conventional drug dosage, which can achieve the above-mentioned clinical therapeutic effect, and the underlying mechanism remains to be clarified.previous studies by Huang Bo team have found that drug loaded vesicles can kill tumor seed cells. The team further found that drug loaded vesicles can make cholangiocarcinoma cells inflate and burst like balloons, which is a form of inflammatory cell death, called pyrotosis, which causes the release of all cell contents and then causes strong inflammation Reaction.the team found that cholangiocarcinoma cells highly express a precursor of the cell punching protein gsdme. Drug loaded vesicles can transform the precursor state of gsdme into the active form of perforin molecules, and then punch holes on the surface of cholangiocarcinoma cells, leading to cell death.however, the cholangiocarcinoma tissue is hard and dense, and the cells are surrounded by a dense reticular structure (called extracellular matrix in medicine).even though drug loaded vesicles can kill cholangiocarcinoma cells efficiently, how can the vesicles overcome the obstruction of reticular structure and contact cancer cells to kill them? Unexpectedly, the mechanism behind it is immunity.Huang Bo team confirmed that drug loaded vesicles are actually an immunotherapy, but different from the current immunotherapy of PD-1 antibody and car-t cells (which use T cells to kill tumor cells), drug loaded vesicles use neutrophils to achieve the effect of anti-tumor immunotherapy.the largest number of immune cells in the human body is neutrophils, which circulate in our blood, and their life span is only 7-9 hours.the number of neutrophils dead in normal body is more than 1 billion orders of magnitude every day. However, once a pathogen invades, thousands of neutrophils gather at the infected site to remove the pathogen, and at the same time, it inevitably destroys the extracellular matrix components around.the team found that when drug loaded vesicles reached the bile duct cavity above the cholangiocarcinoma, a large number of neutrophils were collected, and then destroyed the matrix around the cholangiocarcinoma cells, exposing one cancer cell after another, so that they could be contacted by the drug loaded vesicles, and then killed, that is, the charring death found.the scorching death of cholangiocarcinoma cells further stimulates neutrophils, making the latter also attack cancer cells, which is called immune cells killing tumor cells.then, how does drug loaded vesicles recruit neutrophils? Huang Bo's team confirmed two pathways: first, drug loaded vesicles contain udpg (uridine diphosphate glucose), and second, drug loaded vesicles contain complement C5 (a serum protein), both of which can directly chemotactic neutrophils.in addition, inflammatory factors released by cholangiocarcinoma cells can also effectively attract neutrophils.in this way, neutrophils recruited through a variety of ways carry out the secondary killing of cholangiocarcinoma cells.it is precisely because of the unique action mechanism of drug-carrying vesicles, that is, it has part of the role of chemotherapy drugs, and has the characteristics of biological carrier. It also mobilizes the immune army of neutrophils, and skillfully uses the extremely narrow space of cholangiocarcinoma, and finally produces an unusual curative effect on obstructive cholangiocarcinoma. Incidence rate of incidence rate of cholangiocarcinoma is about 3/100000 in China. The incidence rate of cholangiocarcinoma in China is increasing. The incidence of cholangiocarcinoma in the United States is about 10 thousand. The incidence of cholangiocarcinoma in Asia is more than 3/100000, and the incidence of cholangiocarcinoma is one of the highest in the world. The incidence rate ofis higher in the world. The incidence ofis increasing.the malignant degree of cholangiocarcinoma is slightly lower than that of pancreatic cancer, but its anatomical location is special. It is located in the key position of bile drainage and normal operation of liver function, and the tumor "shell" is hard. Patients with cholangiocarcinoma, especially hilar cholangiocarcinoma, are not sensitive to chemotherapy and radiotherapy. Once they lose the opportunity of radical surgery, they will face the situation of "no medicine to cure" and become the most difficult tumor at present One of the types.in this regard, Professor Wang Ximo, one of the main researchers in this paper, said that "drug loaded vesicles for the treatment of cholangiocarcinoma" has shown good safety and effectiveness. This original new technology has made the "0" to "1" breakthrough in the Endobiliary treatment of cholangiocarcinoma. With the expansion of the follow-up sample size and the gradual optimization and upgrading of the scheme, it is expected to become the treatment of cholangiocarcinoma in the future To change the current clinical pattern of lack of effective treatment for cholangiocarcinoma, so as to make a breakthrough in the current treatment of cholangiocarcinoma.as an independent and innovative technology, drug-carrying vesicular tumor treatment technology has been gradually carried out in the fields of malignant pleural effusion, malignant ascites, obstructive esophageal cancer and so on.among them, the treatment mechanism of malignant effusion also involves neutrophils.after the drug carrying vesicles are injected into the malignant pleural effusion and ascites through the drainage tube, the cancerous cells in the effusion can be quickly and effectively removed, but how can the cancerous pleural effusion and ascites disappear quickly? The trick is that drug loaded vesicles induce neutrophils to release a DNA histone viscous complex, which can adhere to the damaged vessel wall like a plaster, thus effectively inhibiting fluid leakage from the blood vessel. This work will be published in the journal Cancer Immunology Research in the near future. after more than ten years of research by Huang Bo team, its safe and efficient tumor killing mechanism has been clarified, and its scientific, cutting-edge and innovative nature has been recognized by the international academic community. Huang Bo's team expressed the hope that the technology will have a greater breakthrough in the future and be able to serve the clinic as soon as possible. original link: plate maker: 11