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 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.
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 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.
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.
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 summarize the role of exosomal proteins in the occurrence, development, and diagnosis and treatment of pancreatic cancer, providing a reference for the exploration of biomarkers and therapeutic targets in this field. MethodA systematic review of recent domestic and international literature on the mechanisms of exosomes and their proteins in pancreatic cancer was conducted. ResultsProteins carried by tumor-derived exosomes, such as galectin-3 binding protein, V-set andimmunoglobulin domain containing 2, Zrt- and Irt-like protein 4, aspartate aminotransferase 1, could effectively regulate the tumor microenvironment and influence the cell behavior, playing an important role in the occurrence, progression, and metastasis of pancreatic cancer. Additionally, exosomal proteins could serve as potential biomarkers for the early diagnosis of pancreatic cancer. For example, exosomal membrane proteins DNAJ heat shock protein family (HSP40) member B11, and glypican 1 were highly expressed in pancreatic cancer tissues, indicating their potential. ConclusionExosomal proteins are expected to become novel biomarkers and intervention targets for the early diagnosis and targeted therapy of pancreatic cancer, providing new ideas for improving the diagnosis and treatment of pancreatic cancer.
ObjectiveTo investigate the clinical effect and prognosis of laparoscopic complete mesocolic resection (CME) in the treatment of elderly patients with stage Ⅲ right colon cancer.MethodsClinical data of 280 elderly patients (aged 60 years or older) who underwent stage Ⅲ right hemicolectomy in the First Hospital of Lanzhou University from 2010 to 2015 were collected. Among them, 160 patients underwent laparoscopic CME treatment were set as the observation group, and 120 patients underwent conventional laparotomy were set as the control group. The mean operative time, intraoperative blood loss, postoperative first anal exhaust time, number of lymph nodes dissection, number of positive lymph nodes, length of hospital stay and postoperative complications were compared between the two groups. The postoperative local recurrence rate, distant metastasis rate, 3-year cumulative survival rate and postoperative recurrence risk factors were analyzed.ResultsThere were no statistically significant differences between the observation group and the control group in operative time, number of lymph node dissection, number of positive lymph nodes and postoperative distant metastasis rate (P>0.05). The amount of intraoperative blood loss, postoperative anal first exhaust time, days of hospitalization, and postoperative recurrence rate in the observation group were less or shorter or lower than those in the control group, with statistically significant differences (P<0.05). The 3-year survival rate in the observation group was higher than that in the control group (log-rank χ2 =11.865, P=0.001), and the disease free survival in the observation group was also higher than that in the control group (log-rank χ2=7.567, P=0.006). Logistic regression was used to analyze the cases of postoperative recurrence in the two groups, and it was found that the degree of tumor differentiation, vascular invasion and lymph node metastasis were independent risk factors for postoperative tumor recurrence.ConclusionLaparoscopic CME in the treatment of elderly patients with stage Ⅲ right colon cancer is effective, it is safe and feasible, which can effectively prolong the survival time of patients.
ObjectiveTo investigate the safety and clinical efficacy of dendritic cell (DC)-cytokine induced killer (CIK) cell adoptive immunotherapy combined with chemotherapy in patients with gastric cancer after radical gastrectomy.MethodsForty-eight patients with gastric cancer after the radical gastrectomy receiving the DC-CIK cell adoptive immunotherapy combined with XELOX or FOLFOX chemotherapy were enrolled as a study group in the First Hospital of Lanzhou University from January 2014 to January 2016. In addition, 48 patients with gastric cancer after the radical gastrectomy in the same period and only receiving XELOX or FOLFOX chemotherapy were collected as a control group. The CD3+, CD3+CD4+, CD3+CD8+, CD3–CD56+ (NK cell), and CD3+CD56+ (NKT cell), toxic reaction, quality of life were evaluated in both groups before and after the treatment, and the long term effect were compared in both groups.Results① There were no significant differences in the gender, age, clinical stage, etc. between the two groups (P>0.05). ② The CD3+, CD3+CD4+, CD3+CD8+, CD3–CD56+, and CD3+CD56+ cells in the peripheral blood had no significant changes between before and after treatment in the study group (P>0.05), which were decreased after the treatment in the control group as compared with before the treatment and were significantly lower than those in the study group (P<0.05). ③ The levels of CEA, CA19-9, and CA724 in the peripheral blood after the treatment in the study group and the control group were significantly lower than those before the treatment (P<0.05), which in the study group were significantly lower than those in the control group after the treatment (P<0.05). ④ The incidences of leukopenia, thrombocytopenia, and diarrhea in the study group were significantly lower than those in the control group (P<0.05). ⑤ Compared with before the treatment, the body function and emotional function after the treatment were significantly improved in the study group (P<0.05). And in the body function, emotion function, role function, cognitive function, and social function were significantly improved than those in the control group (P<0.05) after the treatment. ⑥ The progression-free survival in the study group was significantly better than that in the control group (P<0.05). There was no significant difference in the overall survival between the study group and the control group (P>0.05).ConclusionDC-CIK cell adoptive immunotherapy combined with chemotherapy could significantly improve immune status and quality of life of patients with gastric cancer after radical gastrectomy, reduce adverse effects of chemotherapy, improve long term effect, and prolong progression-free survival.