1.Clinicopathological significance of the expression of calreticulin in human pancreatic cancer.
Wei-wei SHENG ; Ming DONG ; Jian-ping ZHOU ; Xin LI ; Qi DONG
Chinese Journal of Surgery 2013;51(1):58-61
OBJECTIVETo study the clinicopathological significance of the expression of calreticulin (CRT) protein and mRNA in pancreatic ductal adenocarcinoma (PDAC).
METHODSThe expression of CRT protein in 33 paired paraffin embedded PDAC specimens and adjacent non-cancerous pancreatic tissues were detected by immunohistochemistry. Western blot and RT-PCR were used to examine the expression of CRT protein and mRNA in 12 paired fresh PDAC specimens and adjuvant non-cancerous pancreatic tissues. The relationship between the protein expression and clinicopathological features was analyzed.
RESULTSCRT expression was much higher in 33 PDAC tissues than that in paired adjacent non-cancerous pancreatic samples (t = 2.323, P = 0.027). CRT was over expressed in 16 PDAC tissues, but only in 8 adjuvant non-cancerous pancreatic tissues (48.5% vs. 24.2%). The expression of CRT protein had no correlation with tumor position (χ(2) = 1.588, P = 0.208), differentiation (χ(2) = 1.517, P = 0.218), TNM stage (χ(2) = 2.528, P = 0.112) and lymph node metastasis (χ(2) = 1.963, P = 0.161), but had statistic significancy with the prognosis of the patients (χ(2) = 4.080, P = 0.043). The median survival time in the patients with high expression of CRT protein was longer than that in the patients with low expression. The expression of CRT mRNA was higher in PDAC than that in non-cancerous tissues detected by RT-PCR (t = 2.539, P = 0.025), but no significant difference was found in protein level (t = 1.292, P = 0.223).
CONCLUSIONSCRT is up-regulated in PDAC and may be a prognosis factor for patients with PDAC.
Calreticulin ; metabolism ; Carcinoma, Pancreatic Ductal ; metabolism ; Humans ; Immunohistochemistry ; Pancreatic Neoplasms ; metabolism ; Prognosis
2.Research progress in the relationship between pancreatic carcinoma and glycolysis.
Jiapeng HUANG ; Chunlin GE ; Email: GECHUNLIN@139.COM.
Chinese Journal of Surgery 2015;53(10):798-800
Pancreatic carcinoma is currently one of the most intractable malignant tumors of the digestive tract. Studies have found that the occurrence, progression and metastasis of pancreatic carcinoma are closely associated with the tumor's glycolytic pathway, most pancreatic carcinomas show the elevated glycolytic phenotype. To some extent, affecting the glycolytic pathway can influence the energy metabolism of the tumor without affecting the normal cells theoretically. Therefore, glycolytic pathway may become a new target for the treatment of pancreatic carcinoma.
Energy Metabolism
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Glycolysis
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Humans
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Pancreatic Neoplasms
;
metabolism
;
physiopathology
3.The role of cholesterol metabolism reprogramming in pancreatic cancer and the application of cholesterol-targeted metabolism drugs.
Rui-Li ZHAO ; Qian-Qian LI ; Yue-Se LIU ; Juan ZHANG
Acta Physiologica Sinica 2023;75(3):413-428
Pancreatic cancer has an insidious onset and lacks effective treatment methods, which is one of the tumors with the worst prognosis, so it is urgent to explore new treatment directions. Metabolic reprogramming is one of the important hallmarks of tumors. Pancreatic cancer cells in the harsh tumor microenvironment have comprehensively increased cholesterol metabolism in order to maintain strong metabolic needs, and cancer associated fibroblasts also provide cancer cells with a large amount of lipids. Cholesterol metabolism reprogramming involves the changes in the synthesis, uptake, esterification and metabolites of cholesterol, which are closely related to the proliferation, invasion, metastasis, drug resistance, and immunosuppression of pancreatic cancer. Inhibition of cholesterol metabolism has obvious anti-tumor effect. In this paper, the important effects and complexity of cholesterol metabolism in pancreatic cancer were comprehensively reviewed from perspectives of risk factors for pancreatic cancer, energy interaction between tumor-related cells, key targets of cholesterol metabolism and its targeted drugs. Cholesterol metabolism has a strict regulation and feedback mechanism, and the effect of single-target drugs in clinical application is not clear. Therefore, multi-target therapy of cholesterol metabolism is a new direction for pancreatic cancer treatment.
Humans
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Pancreatic Neoplasms/pathology*
;
Cholesterol/metabolism*
;
Tumor Microenvironment
4.Crosstalk Between Peripheral Innervation and Pancreatic Ductal Adenocarcinoma.
Bo NI ; Yiqing YIN ; Zekun LI ; Junjin WANG ; Xiuchao WANG ; Kaiyuan WANG
Neuroscience Bulletin 2023;39(11):1717-1731
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive lethal malignancy, characterized by late diagnosis, aggressive growth, and therapy resistance, leading to a poor overall prognosis. Emerging evidence shows that the peripheral nerve is an important non-tumor component in the tumor microenvironment that regulates tumor growth and immune escape. The crosstalk between the neuronal system and PDAC has become a hot research topic that may provide novel mechanisms underlying tumor progression and further uncover promising therapeutic targets. In this review, we highlight the mechanisms of perineural invasion and the role of various types of tumor innervation in the progression of PDAC, summarize the potential signaling pathways modulating the neuronal-cancer interaction, and discuss the current and future therapeutic possibilities for this condition.
Humans
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Carcinoma, Pancreatic Ductal/pathology*
;
Pancreatic Neoplasms/therapy*
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Signal Transduction
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Peripheral Nerves/metabolism*
;
Tumor Microenvironment
5.Mucin gene family and its role in diagnosis of pancreas neoplasms.
Chinese Journal of Pathology 2006;35(2):113-116
Adenocarcinoma, Papillary
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diagnosis
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metabolism
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Carcinoma, Pancreatic Ductal
;
diagnosis
;
metabolism
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Cystadenoma, Mucinous
;
diagnosis
;
metabolism
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Gene Expression Regulation, Neoplastic
;
Humans
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Mucins
;
classification
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genetics
;
metabolism
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Pancreas
;
metabolism
;
Pancreatic Neoplasms
;
diagnosis
;
metabolism
7.Prognostic Significance of Maspin in Pancreatic Ductal Adenocarcinoma.
Yun Jeong LIM ; Jong Kyun LEE ; Woo Young JANG ; Sang Yong SONG ; Kyu Taek LEE ; Seung Woon PAIK ; Jong Chul RHEE
The Korean Journal of Internal Medicine 2004;19(1):15-18
BACKGROUND: Maspin is a serpin family of protease inhibitors. Althouth maspin has been considered a tumor suppressor that inhibits the motility, invasion, and metastasis of breast and prostatic cancer cells, there are many conflicting reports about maspin expression and cancer prognosis. METHODS: To investigate whether the expression of maspin could be used as a prognostic marker in pancreatic cancer, 72 paraffin-embedded pancreatic ductal adenocarcinomas were analyzed using immunohistochemistry. We examined the prognostic value of maspin as well as its relationship with clinicopathological features. RESULTS: Maspin expression was observed in all pancreatic ductal adenocarcinoma. Unlike cancer tissues, however, faint or no expression was observed in the corresponding normal pancreatic tissues. In the Cox proportional hazard model, high maspin expression predicted a high hazard rate. Maspin expression had a positive correlation with tumor stage, but there were also no statistically significant relationships between maspin expression and other clinicopathological features. CONCLUSION: These findings suggest maspin expression to have biological relevance in the progression of pancreatic cancers, with potential use as a prognostic marker for pancreatic neoplasm with epithelial origin.
Adolescent
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Adult
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Aged
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Biological Markers
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Carcinoma, Pancreatic Ductal/*metabolism/surgery
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Female
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Human
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Immunohistochemistry
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Male
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Middle Aged
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Pancreatic Neoplasms/*metabolism/surgery
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Prognosis
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Proteins/*metabolism
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Serpins/*metabolism
8.Clinicopathological significance of the expression of carbonic anhydrase II in human pancreatic invasive ductal cancer.
Wei-wei SHENG ; Jian-ping ZHOU ; Fan-min KONG ; Yu-ji LI ; Ming DONG
Chinese Journal of Surgery 2012;50(8):728-731
OBJECTIVETo study the clinicopathological significance of the expression of carbonic anhydrase (CA)II protein and mRNA in primary invasive ductal cancer (IDC) of human pancreas.
METHODSThe expression of CAII protein in 33 paired paraffin embedded IDC specimens of the pancreas and paired adjacent non-cancerous pancreatic tissues was detected by immunohistochemistry. Western blot and reverse transcription polymerase chain reaction (RT-PCR) were used to examine the expression of CAII protein and mRNA level in 12 paired fresh IDC specimens of the pancreas and adjuvant non-cancerous pancreatic tissues. The relationship between the protein expression and clinicopathological features was analyzed.
RESULTSOverexpression of CAII protein was shown in 11 cases of pancreatic IDC tissues (33.3%, 11/33), which was much lower than that in paired non-cancerous pancreatic tissues (72.7%, t = 6.275, P = 0.000). The expression of CAII protein had no correlation with tumor position (χ² = 0.992, P = 0.319), differentiation (χ² = 0.866, P = 0.352), TNM stage (χ² = 1.210, P = 0.271) and Lymph node metastasis (χ² = 0.798, P = 0.372), but had bordering statistic sig with the prognosis of the patients (χ² = 3.233, P = 0.072). The median survival time in the patients with high expression of CAII protein was 540 days, while that in the patients with low expression was 320 days. The expression of CAII protein and mRNA was lower in IDC than that in paired non-cancerous pancreatic tissues detected by Western blot and RT-PCR respectively (t = 3.399, P = 0.006; t = 2.281, P = 0.043).
CONCLUSIONCAII is down regulated in pancreatic IDC and might be relative with the prognosis.
Carbonic Anhydrase II ; genetics ; metabolism ; Carcinoma, Pancreatic Ductal ; metabolism ; pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Pancreas ; metabolism ; Pancreatic Neoplasms ; metabolism ; pathology ; RNA, Messenger ; genetics
9.Exosomes secreted from human umbilical cord mesenchymal stem cells promote pancreatic ductal adenocarcinoma growth by transferring miRNAs.
Yi Xuan DING ; Yu Ting WANG ; Wen Tong MEI ; Zhi ZHENG ; Yuan Xu QU ; Kuo LIANG ; Jia LI ; Feng CAO ; Fei LI
Chinese Journal of Oncology 2023;45(1):50-55
Objective: To observe the effects of exosomes derived from human umbilical cord mesenchymal stem cells on the proliferation and invasion of pancreatic cancer cells, and to analyze the contents of exosomes and explore the mechanisms affecting pancreatic cancer cells. Methods: Exosomes extracted from human umbilical cord mesenchymal stem cells were added to pancreatic cancer cells BxPC3, Panc-1 and mouse models of pancreatic cancer, respectively. The proliferative activity and invasion abilities of BxPC3 and Panc-1 cells were measured by cell counting kit-8 (CCK-8) and Transwell assays. The expressions of miRNAs in exosomes were detected by high-throughput sequencing. GO and KEGG were used to analyze the related functions and the main metabolic pathways of target genes with high expressions of miRNAs. Results: The results of CCK-8 cell proliferation assay showed that the absorbance of BxPC3 and Panc-1 cells in the hucMSCs-exo group was significantly higher than that in the control group [(4.68±0.09) vs. (3.68±0.01), P<0.05; (5.20±0.20) vs. (3.45±0.17), P<0.05]. Transwell test results showed that the number of invasion cells of BxPC3 and Panc-1 in hucMSCs-exo group was significantly higher than that in the control group (129.40±6.02) vs. (89.40±4.39), P<0.05; (134.40±7.02) vs. (97.00±6.08), P<0.05. In vivo experimental results showed that the tumor volume and weight in the exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs-exo) group were significantly greater than that in the control group [(884.57±59.70) mm(3) vs. (695.09±57.81) mm(3), P<0.05; (0.94±0.21) g vs. (0.60±0.13) g, P<0.05]. High-throughput sequencing results showed that miR-148a-3p, miR-100-5p, miR-143-3p, miR-21-5p and miR-92a-3p were highly expressed. GO and KEGG analysis showed that the target genes of these miRNAs were mainly involved in the regulation of glucosaldehylation, and the main metabolic pathways were ascorbic acid and aldehyde acid metabolism, which were closely related to the development of pancreatic cancer. Conclusion: Exosomes derived from human umbilical cord mesenchymal stem cells can promote the growth of pancreatic cancer cells and the mechanism is related to miRNAs that are highly expressed in exosomes.
Mice
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Animals
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Humans
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MicroRNAs/metabolism*
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Exosomes/genetics*
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Sincalide/metabolism*
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Pancreatic Neoplasms/metabolism*
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Carcinoma, Pancreatic Ductal/genetics*
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Mesenchymal Stem Cells/metabolism*
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Umbilical Cord
10.Obesity and Pancreatic Diseases.
The Korean Journal of Gastroenterology 2012;59(1):35-39
Obesity is defined as BMI (calculated as weight in kg divided by height in m2) more than 30, and overweight is defined as BMI of 25-29.9. Obesity has been considered as a risk factor for pancreatic diseases, including pancreatitis and pancreatic cancer. Severe acute pancreatitis is significantly more frequent in obese patients. Furthermore, obese patients develop systemic and local complications of acute pancreatitis more frequently. The underlying mechanisms are increased inflammation and necrosis from increased amount of intra- and peri-pancreatic fat. In addition, obesity is a poor prognostic factor in acute pancreatitis, and overweight before disease onset appears to be a risk factor for chronic pancreatitis. Overweight and/or obesity are associated with greater risk of pancreatic cancer and younger age of onset. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight. Long-standing diabetes increases the risk of pancreatic cancer. The pathogenic mechanism is that obesity and physical inactivity increase insulin resistance. In a state of hypersinulinemia, increased circulating level of insulin-like growth factor-1 induces cellular proliferation of pancreatic cancer. Obesity is associated with negative prognostic factor and increased mortality in pancreatic cancer. However, there are controversies regarding the effects of obesity on long-term post-operative results in the patient with pancreatic cancer.
Body Mass Index
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Humans
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Hypertriglyceridemia/complications
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Obesity/*complications
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Overweight
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Oxidative Stress
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Pancreatic Diseases/*etiology
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Pancreatic Neoplasms/etiology
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Somatomedins/metabolism/physiology