ObjectiveTo summarize the clinical application and future application prospects of organoid model in pancreatic cancer. MethodThe domestic and foreign literature related on the application of organoid model in pancreatic cancer was reviewed. ResultsIn recent years, the organoid model of pancreatic cancer was constructed mainly using patient-derived tissues, fine-needle aspiration samples, and human pluripotent stem cells. The biomarkers of pancreatic cancer were screened according to the histological and structural heterogeneities of the primary tumor retained in organoid model, such as microRNA, glypican-1, annexin A6 and protein biomarkers cytokeratin 7 and 20, cell tumor antigen p53, Claudin-4, carbohydrate antigen 19-9, etc.in the extracellular vesicles. The results of organoid model could maintain the original tumor characteristics and the higher correlation between the organoid model drug sensitivity data and the clinical results of pancreatic cancer patients suggested that, the drug sensitivity data of organoid model could be used to avoid ineffective chemotherapy, so as to improve the treatment response rate and reduce the toxicity of chemical drug treatment, and reasonably select individualized treatment plans for pancreatic cancer patients in future. ConclusionsOrganoid model has many research in screening biomarkers of pancreatic cancer, individualized drug screening, and drug sensitivity test. It can simulate the complex pathophysiological characteristics of pancreatic cancer in vitro, and retain the physiological characteristics and gene phenotype of original tumor cells. It is expected to become a new platform for selecting biomarkers of pancreatic cancer, testing drug sensitivity, and formulating individualized treatment methods for pancreatic cancer, which might further accelerate the research progress of pancreatic cancer.
OBJECTIVE To detect the immunoreaction after osteoblast xenotransplantation and to investigate the possibility of heterogenic osteocyte transplantation and tissue engineered bone reconstruction. METHODS: Rat osteoblasts were isolated by two-part bony digestion/elements in culturing, and incubated in vitro at 37 degrees C, 5% carbon dioxide for 5 days until they multiplied and formed a monolayer on the bottom of dish. Twenty-eight rabbits were divided into 3 groups. Autograft of osteoblasts(group A), xenograft of osteoblasts(group B) and normal saline(group C) were implanted into the rectus abdominus muscle. The immunological and histological observations were performed after 1, 2, 4 and 8 weeks of transplantation. RESULTS: Cultured cells reached confluence within 5 days and was identified as osteoblasts by ALP staining and Bon kossa staining. The result of host versus graft reaction was negative. In group B, specific antibody reaction was detected 2 weeks and 4 weeks after transplantation. Cell mediated cytotoxicity was detected after 2 weeks, reached the peak value 4 weeks later, and then began to decline 8 weeks later. HE staining showed mass inflammatory cells and no ectopic ossification after 8 weeks. CONCLUSION: Heterogenic osteoblast transplantation will lead to an obvious change in host humoral and cellular immunity and lost the ability of bone formation. So, it can not be used for the reliable cell sources for osteocyte transplantation or tissue-engineering bone reconstruction.
Objective To provide an overview of the main anti-tumor mechanisms of attenuated Salmonella typhimurium（ST） and explore potential reasons for the limited clinical application of attenuated ST. Methods The literatures related to clinical and basic research on attenuated ST tumor treatment and virulence at home and abroad in recent years were reviewed and the relevant mechanisms of attenuated ST tumor treatment were summarized. And then, analyses were made regarding the failure of clinical application experiments of attenuated ST based on the characteristics of attenuated ST and the human immune microenvironment. Results Attenuated ST could inhibit the growth of primary tumors and reduce the metastasis of secondary tumor due to its effect of tumor-targeting, its property of facultative anaerobic and its characteristic of being able to carry plasmids. On the other hand, the toxicity of wild strains to hosts had been reduced through biotechnology. In terms of clinical application, the anti-tumor effect of attenuated ST was far lower than expected due to excessive detoxification of ST, the elimination effect of foreign substances by the human immune system, and the inactivation effect of various proteases in the body. Conclusion As an emerging bacterial mediated anti-tumor therapy, attenuated ST will provide a new treatment option for precise treatment of cancer patients once its clinical application problems are solved.
ObjectiveTo summarize the latest research of long non-coding RNA (lncRNA) as competitive endogenous RNA (ceRNA) and its targeting technology in pancreatic cancer, so as to provide new ideas for lncRNA targeted intervention or as an early diagnostic marker of pancreatic cancer. MethodThe domestic and foreign literature on researches of lncRNA as ceRNA and its targeting technology in the pancreatic cancer was searched and reviewed. ResultsAt present, the growing number of evidences showed that in pathological states such as tumors, the abundance of intracellular lncRNAs was sufficient to trigger ceRNA crosstalk. The lncRNA played a role like “sponge” through the complementary binding of incomplete base of miRNA with miRNA response elements, then adsorbed miRNA, and thus changed the activity and effectiveness of miRNA. It also regulated the expression of downstream target genes. Moreover, a large number of studies had identified that the lncRNA-mediated ceRNA regulatory network, namely lncRNA/miRNA/mRNA axis, played a role in promoting or inhibiting the occurrence and progression of pancreatic cancer through a variety of cellular functions. In addition, many technologies targeting lncRNA, such as small interfering RNA, antisense oligonucleotides, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9, and small molecule inhibitors, etc. had been widely studied and acquired important results in preclinical research. ConclusionsThe ceRNA hypothesis is a functional complex composed by non-coding RNAs and mRNAs with non-coding properties, forming a ceRNA network of multi-level and cross-regulatory on the transcriptome. Epigenetic modification and key post-transcriptional regulation of lncRNA have been achieved through ceRNA network mechanism, which has become a successful paradigm for exploring the function of lncRNA. The tumor suppressive and promoting effects and mechanisms of many lncRNAs in the occurrence and development of pancreatic cancer are explored in many studies. Moreover, the continuous progress of targeted lncRNA technology provides conditions for study of lncRNA. LncRNA has a potential to be used as a biomarker for precancerous diagnosis and prognosis of pancreatic cancer.
ObjectiveTo summarize the biological function and molecular regulation mechanism of serine threonine tyrosine kinase 1 (STYK1) in tumor occurrence and development. MethodThe relevant literature about STYK1 and tumor progression in recent years was searched and reviewed. ResultsThe expression of STYK1 was up-regulated in a variety of tumors and was related to the prognosis. STYK1 might regulate the proliferation, apoptosis, migration, metastasis, aerobic glycolysis, drug resistance and other biological functions of tumor cells through MEK/ ERK, PI3K/AKT, JAK/STAT and their targeting proteins, and promote the malignant progress of tumors. Conclusion STYK1is expected to become a new target for the treatment of malignant tumors, but the molecular mechanism of its regulation of tumor progression and its upstream regulators need to be further explored.
ObjectiveTo evaluate the safety and clinical efficacy of transurethral holmium laser enucleation of the prostate (HoLEP) versus transurethral plasma kinetic enucleation of the prostate (PKEP) in the treatment of benign prostate hyperplasia (BPH).MethodsRandomized controlled trials of HoLEP versus PKEP in the treatment of BPH published between January 2000 and March 2021 were searched in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chongqing VIP database, and Wanfang database. Operative duration, estimated intraoperative blood loss, average duration of urinary catheterization, average duration of bladder irrigation, average length of hospital stay, and postoperative complications were used as safety evaluation indicators. Postoperative International Prostatic Symptomatic Score (IPSS), postoperative maximum urinary flow rate (Qmax), postoperative quality of life (QoL), and postvoid residual (PVR) were used as effective evaluation indicators.ResultsA total of 14 randomized controlled trials were included in this study, with a total of 1 478 patients (744 in the HoLEP group and 734 in the PKEP group). The results of the meta-analysis showed that the intraoperative blood loss in the HoLEP group was less than that in the PKEP group [weighted mean difference (WMD)=−25.95 mL, 95% confidence interval (CI) (−31.65, 20.25) mL, P=0.025], the average duration of urinary catheterization [WMD=−10.35 h, 95%CI (−18.25, −2.45) h, P=0.042], average duration of bladder irrigation [WMD=−10.28 h, 95%CI (−17.52, −3.04) h, P=0.038], and average length of hospital stay [WMD=−1.24 d, 95%CI (−1.85, −0.62) d, P=0.033] in the HoLEP group were shorter than those in the PKEP group, and the incidence of postoperative complications [risk ratio=0.70, 95%CI (0.56, 0.87), P=0.047] and 6-month postoperative Qmax [WMD=−0.89 m/s, 95%CI (−1.74, −0.05) m/s, P=0.037] in the HoLEP group were lower than those in the PKEP group. However, there was no significant difference in the operative duration, 3-month postoperative IPSS, 3-month postoperative Qmax, 3-month postoperative QoL, 3-month postoperative PVR, 6-month postoperative IPSS, 6-month postoperative QoL, or 6-month postoperative PVR between the two groups (P>0.05).ConclusionsIn the treatment of BPH, the effectiveness of HoLEP does not differ from that of PKEP, but HoLEP is safer. The conclusions of this study need to be verified in more precisely designed and larger sample-sized multi-center randomized controlled trials.