Drug-carrying cyst therapy technology brings "life" to bile tube cancer patients

bile tube cancer is a clinically difficult to treat malignant tumor, usually found when it is late. And even after treatment, the patient's prognosis effect is not good, such as advanced liver gate obstruction bile tube cancer patients have a survival of only 3 to 6 months.
data show that in the United States, bile tube cancer each year about 10,000 new cases, the incidence of bile tube cancer in the Asian population is about three per 100,000, of which China is one of the world's highest incidence of bile tube cancer, the incidence rate is increasing year by year.
Many clinicians believe that although the degree of malignant bile tube cancer is slightly lower than pancreatic cancer, but because of its special anatomical position, located in the bile drainage and liver function of the key position, and the tumor "shell" hard, bile tube cancer, especially liver door bile tube cancer patients are basically insensitive to chemotherapy, once the opportunity to operate, that is, face "no medicine" situation.
However, recently, nature-biomedical engineering published a study by Huang Bo of the Institute of Basic Medicine of the Chinese Academy of Medical Sciences, in cooperation with a team of Wang Ximo of Nanca University-affiliated Nanbei Hospital in Tianjin, which opened a "door" for the treatment of bile duodenal cancer. The study not only demonstrated the effectiveness and safety of the drug-carrying vesicle therapy technique in treating patients with bile tube cancer, but also explained in detail the mechanism of its treatment.cell vesicles were discovered in the middle of the last century and have long been thought of as cell-generated waste, which has not been studied in depth.
More than a decade ago, huangbo team conducted ground-breaking research on cell vesicles in tumors and immunity, encasing chemotherapy drugs to study the effects of cancer treatment, and finally demonstrated that drug-carrying vesicles are effective in killing tumor cells as a treatment, and published their findings in Nature Communications.
, the team published their findings in Cell Research Biomass, further confirming that drug-carrying vesicles give priority to killing drug-resistant tumor seed cells.
" On the basis of the above-mentioned research, we launched a clinical trial of drug-carrying vesicles in 2011 for the treatment of cancerous chest water and cancerous ascerine, and the results show that the technology is safe and effective, especially for cancerous thoracic water, with ideal results. Huang Bo, one of the authors of the paper, told China Science Daily.
Based on the above clinical trials, Huang Bo team put forward the idea of using the drug cysts to treat obstructive bile duodenal cancer, and since 2014 in cooperation with Nan kai Hospital in Tianjin, to carry out clinical trials of the drug-carrying cysts to treat bile duodenal cancer.
" Due to the poor quality of life of patients with advanced liver valve bile tube cancer, the use of ultrasound-guided transderriphageal bile flow (PTCD) for such patients, the drug-carrying cysts wrapped in methotrexate are injected into the bile tube cavity above the cholectic cancer obstruction site, through closed drainage tubes, so that the carrier cysts fully kill bile tube cancer cells, thus promising therapeutic effect. Huang Bo said.
clinical results show that about 30% of patients imaging shows changes in bile duct obstruction, about 50% of patients with the first course of jaundice symptoms reduced, liver function improved, detox color can be changed from clay to yellow, most patients diet, quality of life can be improved. In terms of safety, the patient's blood routine, liver and kidney function were not significantly changed, no abdominal pain, nausea, vomiting and other discomfort symptoms, good safety performance.Huang Bo (second from right) discusses the experiment with the team." Although bile tube cancer cells are almost insensitive to almost all chemotherapy drugs and radiotherapy, in the above clinical trials, the chemotherapy drugs containing only a few hundredths of the clinical conventional dose of the drug-carrying vesicles, can achieve the above-mentioned clinical therapeutic effect. Huang Bo said.
, but what's the mechanism behind it?
To this end, the Yellow Wave team found that the drug-carrying vesicles can cause bile duct cancer cells to swell like balloons until the cells burst, a form of inflammatory cell death called cell coke death, which causes the release of all cell contents and triggers a strong inflammatory response.
" gallbladder cancer cells high expression of a cell perforation protein GSDME prelude, the drug-carrying vesicles can be GSDME from the preconsumable state into an active form of perforated protein molecules, and then punch in the surface of bile tube cancer cells, causing cell coke death. Liu Yuying, one of the authors of the paper and an associate researcher at the Institute of Basic Medicine of the Chinese Academy of Medical Sciences, told the China Science Journal.
, however, bile tube cancerous tissue is hard and dense, and bile tube cancer cells are encased in dense mesh structures (medically known as extracellular substrings). Even if drug-carrying vesicles can effectively kill bile tube cancer cells, how can they overcome the barriers of the mesh structure to reach cancer cells and kill them?
, the mechanism behind it is immunity.
Huang Bo told reporters that the drug-carrying vesicle is actually an immunotherapy, but with the current PD-1 antibody, CAR-T cells (both using T-cells to kill tumor cells) immunotherapy, drug-carrying vesicles use neutral granulocytes to achieve anti-tumor immunotherapy effect.
we all know that the largest number of immune cells in the body is neutral granulocytes, which circulate in our blood and live for only 7 to 9 hours. The normal body dies every day in the number of neutral granulocytes above 1 billion, but once a pathogen invades, thousands of neutral granulocytes gather at the site of infection, removing the pathogens and inevitably destroying the surrounding extracellular substitline components.
The team's study found that when the capsules reached the gallbladder cavity above the gallbladder tumor body, a large number of neutral granulocytes were collected, which in turn destroyed the substation around the gallbladder cancer cells, exposing one cancer cell at a time, allowing them to be exposed to the capsules and then killed. The coke death of bile tube cancer cells further stimulates neutral granulocytes, which also attack cancer cells, which are immune cells that kill tumor cells.。 MTX-MPs treats obstructive hepatic and extracholeal cancer. MTX-MPs through UDPG/C5, the neutral granulocytes, the latter destroy the bile tube cancer substitline barrier, MTX-MPs into tumor cells, induce their coke death, further activate macrophage secretion degeneration factors, strengthen the trending of neutral granulocytes;" Drug-carrying vesicle treatment of bile tube cancer technology has shown good safety and effectiveness, this original new technology, so that bile tube cancer bile gallbladder cavity treatment to achieve a '0' to '1' breakthrough, with the subsequent expansion of sample size and the gradual optimization and upgrading of the program, the future is expected to become a bile tube cancer treatment program, change the current clinical pattern of bile tube cancer lack of effective treatment methods, so as to make a breakthrough in the field of bile tube cancer treatment. Wang Ximo, one of the paper's lead researchers, made the comments.Wang Ximo (first from left) discusses clinical issues with team members.
And, as an independent innovation technology, the drug-carrying vesicle tumor treatment technology has been gradually carried out in the fields of malignant thoracic fluid, malignant abdominal water, obstruction esophageal cancer, and its treatment of malignant fluid, also involves neutral granulocytes.
According to Huang Bo, the drug-carrying cysts can quickly and effectively remove cancerous cells from the fluid after being injected into the cancerous thoracic abdominal water through the drainage tube, but how can the cancerous thoracic abdominal water recede quickly? The trick is to be neutral granulocytes. Drug-carrying vesicles cause neutral granulocytes to release a DNA-histoprotein viscous complex that adheres to a damaged wall of blood vessels, like an ointment, effectively suppressing fluid leakage from blood vessels. The results will be published recently in the Journal of Cancer Immunology.
mechanism of safe and efficient tumor killing by "drug-carrying" capsule technology has been clarified, and its scientific, cutting-edge and innovative technology has been recognized by the international academic circles. "Huang Bo hopes that the technology can make greater breakthroughs in the future, and can serve the clinic at an early time for the benefit of patients. (Source: Zhang Siwei, China Science Journal)
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