ObjectiveTo investigate the synergistic antitumor effects of ionizing radiation and the cytosine deaminase (CD)/5-flurocytosine (5-FC) system therapy in human pancreatic cancer cell.MethodsThe expression vector containing CD was transfected into the human pancreatic cancer cell line PC3. The clones were picked out after G418 selection. The CD gene integration and expression were confirmed by the RT-PCR. The cytotoxicity to the cells with or without CD and (or) ionizing radiation under the treatment with 5-FC was measured by the MTT assay. The clonogenic assay was used to investigate the radiosensitizing effect of 5-FC on the PC3 cells transfected or untransfected with CD gene.ResultsThe CD gene was stably expressed in the PC3 cells transfected with CD gene. The cytotoxic effect of 5-FC was superior on the PC3 cells transfected than that of untransfected with CD gene (P<0.05) and which were enhanced in combination with the ionizing radiation (P<0.05). The CD/5-FC enhanced the radiosensitivity of PC3 cells transfected with CD gene (P<0.05). The change in the radiosensitivity was quantified by calculating the sensitization enhancement ratio (SER) at the clinically relevant dose of 2 Gy. The SER was 1.5 in the PC3 cells transfected with CD gene by giving ionizing radiation of 2 Gy.ConclusionsCD/5-FC system is a potenial radiosensitizer in PC3 cells transfected with CD gene. Ionizing radiation and CD/5-FC system is more effective for killing effect of PC3 cells than ionizing radiation or CD/5-FC system alone.
Objective To summarize the changes in the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) in the context of immunotherapy and their impact on treatment outcomes. MethodsA systematic review of recent studies on the TME of PDAC was carried out to analyze the immune properties, intercellular interactions, and biological functions of its cellular and non-cellular components, disclose the molecular mechanisms of immunotherapy affects on the TME, explore the advancements in targeted therapy and potential biomarkers, and analyze the challenges in clinical applications and their impacts on the quality of life of patients. ResultsThe TME of PDAC exhibits highly immunosuppressive and heterogeneous characteristics, rich in diverse cells (such as pancreatic cancer cells, stellate cells, cancer-associated fibroblasts, immune cells) and non-cellular components (such as extracellular matrix). Immunotherapy is capable of regulating the immune balance in the TME and enhancing the anti-tumor response. Despite the progress made in multiple immunotherapy strategies (such as immune checkpoint inhibitors, chimeric antigen receptor cell therapy), challenges such as difficulty in selecting targets, drug resistance, and side effects still persist. Meanwhile, potential biomarkers such as programmed cell death-ligand 1, tumor-infiltrating lymphocytes, and leukemia inhibitory factor offer new directions for individualized treatment. ConclusionsThe TME of PDAC undergoes continuous changes during immunotherapy. In the future, it is requisite to integrate new technologies to deeply explore targets and biomarkers, optimize multimodal precise treatment strategies, enhance the safety and efficacy of immunotherapy, and improve the prognosis of patients.
ObjectiveTo explore the efficacy and safety of endoscopic sphincterotomy (EST) in the treatment of sphincter of Oddi dysfunction (SOD).MethodsThe clinical data of 95 cases of SOD treated with EST in Affiliated Hospital of Guizhou Medical University and Tumor Hospital Affiliated to Guizhou Medical University from January 2014 to January 2019 were collected retrospectively, to evaluate and analyze the effect of clinical diagnosis and treatment of EST on SOD patients.ResultsAmong 95 SOD patients, 86 were biliary type SOD and 9 were pancreatic type SOD. All 95 patients underwent EST. The Verbal Rating Scales-5 (VRS-5) scores before EST were all 3 or 4 points, and the VRS-5 scores decreased after treatment in each type of SOD patients, the difference were all statistically significant (P<0.05). After treatment, levels of ALT, AST, ALP, TBiL, and DBiL in biliary type SOD Ⅰ and type Ⅱ were significantly lower than before (P<0.05); ALT, AST, ALP, GGT, and blood and urine amylase in patients with pancreatic type SOD after EST were significantly decreased than before (P<0.05), and the biochemical indicators of patients with SOD Ⅲ before and after treatment did not change significantly (P>0.05). After EST treatment, 70 (81.4%) of the 86 patients with bile type SOD showed significant effect, and 10 patients (11.6%) were effective, with an overall effective rate of 93.0% (80/86). Among the 16 patients with bile type SOD Ⅰ, 14 patients (87.5%) received significant effect, and 1 patient (6.3%) was effective, with an overall effective rate of 93.8% (15/16). That 51 patients with bile type SOD Ⅱ received EST, of which 43 patients (84.3%) were significantly effective and 6 patients (11.8%) were effective, with an overall response rate of 96.1% (49/51). Among the 19 patients with bile type SOD Ⅲ treated with EST, 13 patients (68.4%) were significantly effective and 3 patients (15.8%) were effective, with the overall effective rate was 84.2% (16/19). There was no statistically significant difference in the overall effective rate of patients with 3 types of biliary type SOD patients (P>0.05). Endoscopic treatment was effective in all 9 cases of pancreatic type SOD, with an overall effective rate of 100%. There were 5 patients (5.3%) of acute pancreatitis after EST, and no bleeding, perforation, cholangitis or other complications occurred. All patients were interviewed for 1 to 5 years postoperatively, the median follow-up duration was 2.33 year, during the follow-up period, nolong-term complications such as Oddi sphincter restenosis and cholangitis caused by intestinal bile reflux.ConclusionESTis a minimally invasive, safe, and effective treatment for SOD in patients with bile duct type and pancreatic duct type, and it is an important treatment for SOD.
Objective To discuss the value of biliary stent in treatment of malignant biliary obstruction with different pathways of bile duct stent insertion. Methods Fourty-two cases of malignant biliary obstruction whose biliary stent insertions were through operation (n=18), PTCD (n=17) and ERCP (n=7) respectively were reviewed retrospectively. Results The bile duct stents were successfully inserted in all patients through the malignant obstruction and achieved internal biliary drainage. Compared with the level of the bilirubin before operation, it decreased about 100 μmol/L one week after the stent insertion in all patients. Compared with the levels of glutamic oxalacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and glutamyltranspeptidase before operation, they decreased 1 week after the stent insertion （Plt;0.05). The median survival time was 22 weeks. The average survival time was (32.89±33.87) weeks. Two patients died in hospital after PTCD, and the mortality was 4.76%. Complications included 8 cases of cholangitis, 3 cases of bile duct hemorrhage and 2 cases of hepatic failure. Conclusion The bile duct stent insertions through operation, PTCD and ERCP are all effective in relieving the bile duct construction with malignant biliary obstruction. Each method should be chosed according to the systemic and local condition for every patient so as to improve the safety and efficiency, and to decrease the occurrence of complications.