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Pancreatic cancer (PC) is a malignant tumor of the digestive tract with poor patient prognosis. The PC incidence is still increasing with a 5-year survival rate of only 10%. At present, surgical resection is the most effective method to treat PC, however, 80% of the patients missed the best time for surgery after they have been diagnosed as PC. Chemotherapy is one of the main treating methods but PC is insensitive to chemotherapy, prone to drug resistance, and is accompanied by many side effects which are related to a lack of specific target. Exosomes are nanoscale vesicles secreted by almost all cell types and can carry various bioactive substances which mediate cell communication and material transport. They are characterized by a low immunogenicity, low cytotoxicity, high penetration potential and homing capacity, and possess the potential of being used as advanced drug carriers. Therefore, it is a hot research topic to use drug-loaded exosomes for tumor therapy. They may alleviate chemotherapy resistance, reduce side effects, and enhance the curative effect. In recent years, exosome drug carriers have achieved considerable results in PC chemotherapy studies.
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Humans , Exosomes/metabolism , Drug Carriers/metabolism , Pancreatic Neoplasms/diagnosis , Antineoplastic Agents/therapeutic useABSTRACT
Objective:To explore the expressions of long non-coding RNA LINC00673 and ISG15 protein in pancreatic cancer and their clinical significances.Methods:The clinical data of 57 patients diagnosed as pancreatic ductal carcinoma (PDAC) at the Affiliated Cancer Hospital of Xiangya Medical College of Central South University from January 2014 to December 2018 were retrospectively analyzed. The relative expressions of LINC00673 in pancreatic cancer tissues and paracancerous normal tissues (within 3 cm from the edge of cancer tissues) were examined by using quantificational reverse transcription-polymerase chain reaction (qRT-PCR). The ISG15 protein expressions in pancreatic cancer tissues and paracancerous normal tissues were examined by using immunohistochemistry. The difference in LINC00673 expression between ISG15 protein positive and negative patients was compared. The correlation between LINC00673 and ISG15 protein expressions in pancreatic cancer was analyzed by Spearman rank correlation analysis. Moreover, the correlations of LINC00673 and ISG15 protein expressions with clinical stage and pathological classification of pancreatic cancer patients were analyzed.Results:The positive expression of ISG15 protein in pancreatic cancer tissues was 40.4% (23/57), which was higher than that in paracancerous normal tissues [15.8% (9/57)] ( χ2 = 7.90, P = 0.004), and the relative expression of LINC00673 in pancreatic cancer tissues was 0.99±0.36, which was lower than that in paracancerous normal tissues (1.26±0.41) ( t = 4.80, P < 0.001). For 23 (40.4%) ISG15-positive patients and 34 (59.7%) ISG15-negative patients, the relative expression of LINC00673 was 0.77±0.46 and 0.45±0.27 ( P < 0.001). Spearman analysis showed that there was a correlation between LINC00673 and ISG15 protein expressions ( ρ = -0.429, P = 0.001). The relative expression of LINC00673 decreased in patients with low differentiated or undifferentiated tumor, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between LINC00673 expression and patients' age, tumor site, preoperative CA199 level, and TNM stage (all P > 0.05); ISG15 protein expression increased in patients with low differentiated or undifferentiated tumor, TNM stage Ⅲ-Ⅳ, vascular invasion and lymph node metastasis (all P < 0.05), but there was no correlation between ISG15 protein expression and patients' gender, age, tumor site, and preoperative CA199 level (all P > 0.05). Conclusions:The expression of LINC00673 in pancreatic cancer is related to vascular invasion, tumor differentiation degree and lymph node metastasis, and the expression of ISG15 in pancreatic cancer is related to vascular invasion, tumor differentiation degree, lymph node metastasis and TNM stage. The combined detection of LINC00673 and ISG15 protein could be a valuable prognostic indicator for pancreatic cancer. The therapies targeting LINC00673 and ISG15 protein signaling pathways are expected to be a potential option for immunotherapy of pancreatic cancer.
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Objective:To explore the diagnosis, surgical methods and therapeutic effect of primary duodenal malignant tumor.Methods:The clinical data of 116 patients with primary duodenal malignant tumor from January 2010 to December 2018 were retrospectively analyzed.Results:Among 116 patients, adenocarcinoma was in 74 cases, interstitial tumor was in 25 cases, carcinoid was in 9 cases, the others was in 8 cases. Before operation, duodenoscopy was performed in 107 cases, and CT examination was performed in 76 cases. There were 57 cases of pancreaticoduodenectomy, 15 cases of duodenal segmental resection, 13 cases of subtotal gastrectomy and duodenal bulbar resection, 13 cases of duodenal partial resection, and 18 cases of palliative short circuit operation. The total incidence of postoperative complication was 31.9% (37/116), including pancreatic fistula in 8 cases (grade B 5 cases, grade C 3 cases), biliary fistula in 6 cases, abdominal infection in 5 cases, pulmonary infection in 4 cases, intestinal fistula in 3 cases, delayed gastric emptying in 3 cases, and hemorrhage in 8 cases. Four cases (3.4%) died during the perioperative period. Single factor Cox regression analysis result showed that the postoperative survival time was related to the tumor differentiation degree, operation method, tumor infiltration degree and lymphatic metastasis ( P<0.05 or <0.01); multi-factor Cox regression analysis results showed that the operation method, tumor infiltration degree and lymphatic metastasis were the independent risk factors for the postoperative survival time of patients with primary duodenal malignant tumor ( P<0.05). The patients were followed up until June 2021, and 9 cases were lost to follow-up. Kaplan-Meier survival curve analysis result showed that the postoperative overall 1-,3- and 5-year survival rates were 82.11%, 57.56% and 33.11%, respectively. Conclusions:Adenocarcinoma is the main primary malignant tumor of duodenum. Duodenoscopy and CT are the main examination methods. Radical resection is the most effective treatment for primary duodenal malignant tumor, and pancreaticoduodenectomy is the first choice. Surgical method, tumor infiltration degree and lymphatic metastasis are the independent risk factors affecting the prognosis of patients.
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Objective@#To investigate the expression and clinical significance of exosomal miR-1231 in plasma of pancreatic cancer (PC) patients and pancreatic cancer cells.@*Methods@#A total of 16 patients who were diagnosed with pancreatic cancer in Hunan Cancer Hospital were collected from April 2016 to August 2017. Meanwhile, 16 healthy volunteers were recruited as the healthy control group at the same period. The plasma exosomes were extracted, and the levels of miR-1231 were detected by qRT-PCR in PC and healthy control groups. Moreover, the clinicopathological significance of exosomal miR-1231 expression was analyzed. Furthermore, the expression of exosomal miR-1231 was detected in several pancreatic cancer cells (MIA PaCa-2, PANC-1, SW1990, AsPC-1 and BxPc-3) and two normal pancreatic epithelial cells (HPDE and human primary pancreatic epithelial cell).@*Results@#qRT-PCR results showed that the expression level of miR-1231 in plasma exosomes of pancreatic cancer patients (1.06±0.46) was significantly lower than that in healthy controls (2.30±0.99; P<0.05). The levels of exosomal miR-1231 in patients with stage Ⅰ-Ⅱ (1.515±0.531), no distant metastasis (1.236±0.461) and no lymph node metastasis (1.337±0.522) were significantly higher than those with stage Ⅲ-Ⅳ (0.848±0.224), distant metastasis (0.757±0.278) and lymph node metastasis (0.838±0.261), respectively (P<0.05 for all). In addition, there were no correlation between exosomal miR-1231 expression and age, sex, smoking history, CA19-9 levels and tumor sites (P>0.05). Furthermore, the expression level of exosomal miR-1231 in pancreatic cancer cell lines (0.142±0.135) was significantly lower than that in normal epithelial cells (1.127±0.179; P<0.05).@*Conclusions@#The downregulation of exosomal miR-1231 in plasma of pancreatic cancer patients and pancreatic cancer cells suggests that it is related to the initiation and development of PC. It may be a new diagnostic and prognostic marker for PC.
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Objective To investigate α-interferon (α-IFN) and cyclooxygenase-2 (COX-2)inhibitor celecoxib synergistically inhibit the growth of human liver cancer SMMC-7721 cells xenografts and tumor angiogenesis in a nude mouse model.Methods The effects of celecoxib and α-interferon on tumor volumes and weight were observed.The expressions of VEGF and Cox-2 were determined by immunohistochemistry and RT-PCR,and the effect of α-interferon on MVD also was observed by immunohisto chemistry.Results During the period of observation tumor volume increased progressively in control group,while it was suppressed obviously in other drug treatment groups.The average tumor volume was significantly smaller in celecoxib + α-IFN group than that in IFN group,celecoxib group and control group (P ＜ 0.01,respectively),its inhibitory rate was 61.84％.Immunohistochemistry showes that the VEGF and MVD was significantly smaller in celecoxib + IFN group than that in α-IFN group,celecoxib group and control group (P ＜ 0.01,respectively).RT-PCR shows that the COX-2mRNA and VEGF mRNA pression was lower in the celecoxib + α-IFN group than in α-IFN group,celecoxib group and control group (P ＜ 0.01).Conclusions The COX-2 inhibitor celecoxib and α-interferon synergistically reduces xenografts growth of human liver cancer SMMC-7721 cells effectively via suppressing tumor growth and angiogenesis.
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ObjectiveTo investigate clinical application of intraoperative intraperitoneal hyperthermic chemotherapy using sustained-release fluorouracil in radical gastrectomy for advanced gastric cancer.MethodsThe clinical data of 280 advanced gastric cancer patients admitted from September,2002 to September,2010 were analyzed retrospectively.They were divided into three groups randomly and followed up.The postoperative morbidity,the mortality and the overall survival rates were evaluated.ResultsThere were no significant differences in these three groups with respect to postoperative morbidity ( P ＞ 0.05 ).The incidence of recurrence in intraperitoneal chemotherapy using sustained-release fluorouracil ( treatment group) was significantly lower than those of intraperitoneal chemotherapy and operative treatment( 16.18％,37.61％ and 41.28％,P ＜0.05).The 1,3- and 5-year overall survival rates of treatment group were 85.51％,61.28％ and 53.67％,respectively,and the 1-,3- and 5-year overall survival rates were 84.11％,39.98％ and 28.12％,and 81.28％,29.88％ and 25.21％ respectively in intrapeitoneal chemotherapy group and operative group.1-year overall survival rate had no significant differences among three groups with respect to ( P＞0.05).3-and 5-year overall survival rates in treatment group were higher signfficantly than those of intraperitoneal chemotherapy and operative treatment( P＜0.05).Conclusions Intraoperative intrapeitoneal hyperthermic chemotherapy using sustained-release fluorouracil is a kind of convenient,safe,and highly effective comprehensive treatment method,and it can kill isolated intraperitoneal cancer cells.It may reduce postoperative recurrence and improve survival rates.
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Objective To investigate the approaches for diagnosis and treatment of intrahepatic cholangiocarcinoma(ICC)and asgess its prognosis factors.Methods The clinical data of 86 patients with ICC in our hospital from January 1995 to December2005 were retrospeetively analyzed.All patients were divided into two groups according to the treatment method,including hepatectomy and lymphatic clearance group(Group A,n=42)and hepateetomy group(Group B,n=44),and their clinicopathological variables were analyzed.Resuits The 1-,3-and 5-year survival rates were 77.81%and 35.21%,20.93%and 19.82%,2.31%and 0%respectively between group A and group B.There was significantly difference between these two groups(P＜0.01).The analysis showed that resection and lymphatic clearance were correlated to prognosis.The 1-,3-and 5-year survival rates were 59.21%,26.21%,and 20.11% respectively in 47 patients who were found no lymph node metastasis,and the 1-,3-and 5-year survival rates were 19.82%,2.31%and 0% respectively in 39 patients who were found lymph node metastasis.There was significantly difference in survival rate between group A and group B(P＜0.01).Condusions Reseetability and lymphatic clearance are two significant factors correlated to survival of the patients with ICC.Aggresgive treatment of lymph node metastasis in hepatoduodenal ligament is an important strategy to improve survival rates and strengthen patient's life quality.
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Objective To evaluate clinical features and the clinical application of radical transabdominal operation for the senile cardiac cancer by using the EEA(end-to-end anastomosis) stapler.Methods 80 senile patients underwent curative intent due to cardic cancer from 1991 to 2001,and the clinical effects of transabdominal operation for cardiac carcinoma by using the EEA stapler were investigated retrospectively.Results The average age of the patients was 70-year old, and the ratio of men to women was 5∶1. The average course of the disease was 3 2 months. Only 2 5% of the patients got early diagnosis, and the rate of the preoperative complications was 60%. Patients were treated by radical transabdominal operation by using stapler, and the rates of radical dissection and palliative dissection were 71 3% and 18 8% respectively. The incidence of postoperative complication was 5%, and the in-patient mortality was 1 25%, and the above indexes were significantly lower than those in the trans-thoracicoabdominal approach. The 5-year survival rate was 20% after gastrectomy.Conclusions This study showed that the approach exerted little effect on the respiratory and circulatory systems, and it could decrease the surgical risk and the incidence of diverse complications.
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A literature review was written to introduce the choice of therapy for primary liver cancer (PLC).It was concluded that hepatic resection, liver transplantation, cryotherapy, microwave coagulation treatment, radiofrequency ablation, transarterial embolization or transarterious chemoembolization, percutaneous ethanol injection, radiotherapy and biotherapy could increase the survival rate, and surgical resection combined with other therapeutic methods is the main treatment for primary liver cancer.
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Purpose:To explore the therapeutic effects of h epatectomy and chemotherapy of primary liver cancer(PLC) Methods:The clinical data of 380 PLC patients admitted from Jan uary, 1996 to December, 2003 were divided into two groups: 130 cases underwent h epatectomy (group A), 250 cases underwent hepatectomy and chemotherapy (B group) . Results:The 1-,3-and 5-year recurrence rates in the hepatect omy and chemotherapy group were 21.2%,35.1% and 45.3%. The 1, 3 and 5-y ear overall survival rates in the hepatectomy and chemotherapy group were 68.2%, 50.1% and 21.8%, which were significantly higher than hepatectomy group. The number of chemotherapy courses affected the effect of hepatectomy. Conclusions:Hepatectomy and regional chemotherapy may decrease tumor recurrence rates and improve the disease-free survival rates in patients with PLC.
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Objective To study the diagnosis and treatment of primary liver cancer(PLC) with bile duct cancer thrombus (BDT). Methods The clinical data of 21 patients with PLC and BDT admitted in the past 8 years were analyzed retrospectively . Results The major clinical manifestations were the symptoms of primary liver cancer and obstructive jaundice. The correct diagnosis rate was 76.2% before operation. The diagnosis rate of B-us, CT, MRI, ERCP and PTC was 14.3%, 9.52%, 14.3%, 71.4% and 100% respectively. The operative procedures included hepatectomy with removal of BDT ( n =10), hepatectomy combined with extrahepatic bile duct resection ( n =5), thrombectomy through choledochotomy with TACE ( n =3), removal of BDT with HAI ( n =3). The 3,5-year survival rate were 43.20% and 24.60% respectively. Conclusions Multi-examinations should be applied in the diagnosis of PLC with BDT. The comprehensive therapy including surgery and other therapies must be adoptted for PLC with BDT.