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.
ObjectiveTo summarize the recent advances in the pathogenic mechanism of microorganisms and pancreatic cancer.MethodThrough the retrieval of relevant literatures, the recent progresses in the study of microorganism and pathogenesis of pancreatic cancer were reviewed.ResultsIn recent years, the potential role of intestinal microbiota in the pathogenic mechanism of pancreatic cancer had been studied. The studies found that the microbiome played an important role in the development of pancreatic cancer. Among them, the infections of Helicobacter pylori, oral pathogenic bacteria such as the Porphyromonas ginggivalis, Aggregatibacter actinomycetemcomitans and Phylum fusobacteria, and the changes of composition and diversity of intestinal microflora were closely related to the pancreatic cancer. The microorganisms induced the chronic inflammation and immune response through multiple pathways. The bacterial lipopolysaccharide stimulated the mutations in the KARS gene and mediated the inflammatory response by activating the nuclear factor-κB signaling pathway through Toll like receptor. The oral pathogenic microorganisms and Helicobacter pylori could also promote the cancer progression by secreting toxins that activated cancer-related signaling pathways.ConclusionsBacteria might be important carcinogens. These microorganisms promote development of cancer by causing chronic inflammation, activating cancer-related pathways, activating immune response, oxidative stress, and damaging DNA double strands.
ObjectiveTo summarize the research progress of relation between visceral fat and pancreatic cancer. MethodThe domestic and foreign literature on the accumulation of visceral fat, the potential mechanism of association between visceral fat and pancreatic cancer, the measurement of visceral fat, and the association of visceral fat with prognosis for pancreatic cancer in recent years was reviewed. ResultsThe accumulation of visceral fat was the result of multiple factors, including age, gender, sex hormones, endocannabinoid system, etc. A variety of adipokines secreted by visceral fat played a crucial role in the occurrence and development of pancreatic cancer, which played a pro-tumor and anti-tumor effects mainly through a variety of different signal pathways. ConclusionsIn clinical treatment, the quality of life and prognosis of patients with pancreatic cancer can be improved by reducing visceral fat mass by adjusting diet, physical training, and other methods, as well as intervening the action signal pathways of various adipokines without affecting the disease progression.
Objective To evaluate safety and long-term efficacy of fully covered self-expandable mental stent (FCSEMS) in treatment of biliary stricture after liver transplantation (LT). Methods From January 2010 to June 2018, the data of patients with the biliary stricture after the LT underwent the endoscopic retrograde cholangiagraphy (ERCP) at the First Hospital of Lanzhou University were collected retrospectively. The therapeutic effect of the FCSEMS was evaluated. Results A total of 21 patients with the biliary stricture after the LT were treated. The success rate of the stent placement was 100%. The FCSEMSs were used in 7 cases and the only multiple plastic stents (MPSs) were used in 14 cases. There were no significant differences in the gender, age, time of biliary stricture, frequency of ERCP, recurrence time of biliary stricture, cure time of biliary stricture, curative effect, recurrence of biliary stricture, and incidence of complications between the patients treated with the FCSEMS and the MPS (P>0.050), but the number of plastic stents in the patients treated with the FCSEMS was significantly less than that in the patients treated only with the plastic stents (P<0.050), while the duration of stent retention was longer than that in the patients treated only with the plastic stents (P<0.050). Six patients were cured, 1 was remitted, and 2 were relapsed by the FCSEMS. Eight were cured, 3 were remitted, 3 were ineffective, and 5 were relapsed by the MPS alone. Conclusions FCSEMS might be an safe effective alternative to plastic stent in treatment of biliary stricture after LT, resulting in a longer duration placement, less number of plastic stent use. It is necessary to further accumulate cases to validate cure rate and recurrence rate of biliary stricture.
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 investigate the relationship between the changes of nerve cells in sphincter of Oddi and acute pancreatitis. MethodsThe rabbit models of acute pancreatitis were prepared by using sodium taurocholate perfusion. Immunohistochemical method was used to detect the expressions of nitric oxide synthase (NOS) and vasoactive intestinal peptide (VIP) in neurons of the sphincter of Oddi. ResultsIn the control group, (45.83±2.17)% of myenteric neurons were NOS-positive, (52.46±2.47)% of myenteric neurons were VIP positive, and (22.73±1.95)% of myenteric neurons were NOS and VIP double positive. In contrast, (11.26±0.93)% of myenteric neurons were NOS-positive and (28.62±2.83)% of myenteric neurons were VIP positive in SAP group, which were significantly less than those of control group (P < 0.01). ConclusionsThe sphincter of Oddi of normal rabbits is rich in VIP and NOS positive neurons. The significant reduction of NOS-positive and VIP-positive neurons when SAP, which may be the reason of decreased the activities of the sphincter of Oddi.
ObjectiveTo explore the prognostic factors of pancreatic cancer. MethodsClinical data of 71 patients of pancreatic cancer who treated in The First Hospital of Lanzhou University from January 2010 to December 2014 were retrospectively collected to analyze the prognostic factors of pancreatic cancer. ResultsSixty patients of the 71 patients were followed up for 5-36 months, with the median time of 16 months, and the 1, 2, and 3-year cumulative survival rates were 60.6%, 23.9%, and 1.4% respectively. Univariate analysis results showed that, gender (P=0.043), lymph node metastasis (P=0.002), distant metastasis (P=0.000), TNM staging (P=0.000), and peripancreatic invasion (P=0.000) were correlated with the prognosis of pancreatic cancer, that female patients, patients with the presence of lymph node metastasis, distant metastasis, later TNM staging, and peripancreatic invasion had worse prognosis. Cox proportional hazard model results showed that, distant metastasis (P=0.047), TNM staging (P=0.002), and peripancreatic invasion (P=0.016) were prognostic factors of pancreatic cancer, patients with the presence of distant metastasis, later TNM staging, and peripancreatic invasion had poor prognosis. ConclusionDistant metastasis, TNM staging, and peripancreatic invasion were independent prognostic factors of pancreatic cancer.