High-efficiency, noninvasure precision sieve platform for patients with bladder cancer Protein & Cell。

Title: Continuous culture ofurine-derivedbladder cancer cells for precision medicine
Journal:
Shuai Jiang, Jiaqi Wang, Chen Yang, Renke Tan, Jun Hou, Yuan Shi, Huihui Zhang, Shiyu Ma, Jianan Wang, Mengmeng Zhang, George Philips, Zengxia Li, Jian Ma, Wanjun Yu, Guohua Wang
Published: 2019/07/25
DOI:
WeChat Link:
, Department of Biochemistry and Molecular Biology, Department of Metabolic Molecular Medicine, Fudan University School of Basic Medicine,
Researcher Professor
of Sun Yat-sen Hospital, affiliated with Fudan University, and a team of
professors from Georgetown University in the United States published the latest research
on
. The study
the technology has been patented under the title "Original Tumor Cell Culture Base, Culture Method and Application". The resultsincidence of cancer in the urinary system in China is the first. Bladder cancer usually originates from the endothelial tissue that covers the inner surface of the bladder, so urethra cancer is the most common type of bladder cancer, with about 90-95% of bladder cancers being urinary tract cancer (Urothelial cell carcinoma, UCC). Depending on the extent to which the tumor soaks the bladder wall, bladder cancer can be broadly divided into two broad categories:
(NMIBC) and
(MIBC) 1-3.
with the increasing level of global aging, the incidence of bladder cancer is increasing year by year. However,
, even with less malignant non-muscle-immersive bladder cancer (NMIBC), the recurrence rate over five years is as high as 60-70%, and many of these patients are at higher risk of developing MIBC. For advanced muscle-soaked bladder cancer (MIBC), there is a lack of reasonable and effective treatment plan, this part of the patient's overall prognostication is poor, recurrence rate, progression rate and transfer rate are very high, the risk of death in 5 years of follow-up is about 65% .6,7. In addition,
and whether the condition progresses after surgery still depends on regular cystoscopy for the next 3-6 months. Frequent follow-up and invasitable cystoscopy have put a huge economic and social burden on patients, doctors and hospitals, as well as on the country.
for cancer patients, tumors can be classified by patient characteristics, histological characteristics, and pathological stages, with different treatments depending on the classification. But from the clinical response of patients to treatment, these classifications are far from sufficient. Because of the degree of progress of tumors in different patients, genetic background and biological characteristics are not the same, so its sensitivity to traditional chemotherapy drugs, targeted drugs and immunotherapy drugs used in the clinic is very different, patients apply clinical first- and second-line drugs response rate and efficiency is not ideal. Therefore, the clinical use of the same drug for different patients can lead to unnecessary treatment, resulting in patient pain and waste of medical resources. Precision Oncology is a cancer treatment designed to tailor an effective treatment strategy for each patient. Targeted genetic testing is essential for accurate treatment of patients with advanced cancer. However, it has been found that even with changes in targeted genes, patients do not necessarily respond to treatment. This shows that it is not enough to hope that clinical evaluation and prediction can be achieved through genetic testing alone.
tumor primary cell culture has always been an important method for clinical evaluation of drugs, but because of the difficulty and success rate of different tumor tissues, it has been difficult to form a stable method. After a long period of exploration and research, it has been found that
(conditional reprogramming culture, CRC) using nourishing layer cells is considered a stable way to establish the cell line of primary tumors. In recent years, there have been many studies using CRC methods for the cultivation of primary cells, successfully making epithells from different tissues (e.g. prostate, breast cells, lung cancer, etc.) permanent biogenic. However, cell culture from these tissue sources requires the acquisition of specimens through surgery, an invasing method that is difficult to benefit from this emerging translational medicine for patients who have advanced and have developed tumor metastasis and cannot be treated with surgery.
many related studies have shown that liquid living tissue examination can provide relatively accurate and dynamic clinical information to some extent, while capturing complex gene mutations in primary and metastasis tumors. Urine is one of the most convenient, non-invasive, and least costly sources of liquid biopsy. Due to the particularity of bladder cancer, there will be a large number of bladder cortoma cells in the patient's urine, and patients with advanced bladder cancer will have relatively many tumor cells falling out of their urine due to the heavy tumor load. In the latest study, the Party Yongjun team and other
. Testing and immunogasification analysis by WES (whole exome sequencing, whole exome sequencing) provedin addition, the study also found some low-frequency mutations in tumor cells from urine sources that were not found in the original tumor biopsy. It is further demonstrated that this urine progenitocyto culture platform can not only be used as a model for clinical drug testing, but may also be used to simulate the production and development of tumor resistance, to better help us understand the interaction between the various clone groups within the tumor that lead to tumor progression and metastasis.The team used cultured primary tumor cells for high-volume drug screening and found that cells from different patient sources were indeed sensitive to the same drug, while primary cells from the same patient's urine and tissue source were relatively consistent with drug sensitivity, suggesting that cells from urine sources could replace cells from tissue sources as models for drug screening, and that its invasive and convenient advantages made the model more feasible. Subsequently, through clinical retrospective analysis, the drug screening results of primary cells were compared with the response of patients to clinical drug use, and it was found that there was a strong consistency between the two, which provided an important guarantee for subsequent studies.because urine samples are easy, fast, safe and non-invasible, they can be obtained at any time before and after treatment, giving them dynamic information about the progression of a patient's tumor. In addition, the study has demonstrated that the cultured primary cells also have the ability to form 3D spheres, suggesting that the platform can combine the advantages of rapid 2D culture with drug screening, as well as 3D simulations of tumor microenvironments. In short,
it is known that The Party Yongjun Researcher of Fudan University's School of Basic Medicine, Professor Guo Jianming of Sun Yat-sen Hospital affiliated with Fudan University and Professor Liu Xuefeng of Georgetown University in the United States are co-authors of the paper. Dr. Jiang Shuai, Dr. Wang Jiaxuan, Dr. Yang Yu and Master Tan Renco are the co-first authors of the thesis.
the Shanghai Pharmaceutical Research Fellow, Professor Wu Yuanming of the Fourth Military Medical University, Professor Wang Guohua of Harbin University of Technology and Professor Yu Wanxuan of Ningbo University Hospital were also involved in the work.
(Source: Science.com)