scholarly journals Molecular drivers and cells of origin in pancreatic ductal adenocarcinoma and pancreatic neuroendocrine carcinoma

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
He-Li Gao ◽  
Wen-Quan Wang ◽  
Xian-Jun Yu ◽  
Liang Liu
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neuroendocrine Carcinoma ◽  
Pancreatic Neuroendocrine Tumor ◽  
Ductal Adenocarcinoma ◽  
Neuroendocrine Neoplasm ◽  
Cell Of Origin ◽  
Cells Of Origin ◽  
Pancreatic Neuroendocrine Neoplasm ◽  
Pancreatic Neuroendocrine Carcinoma

Abstract Pancreatic cancer is one of the most common causes of cancer-related deaths worldwide. The two major histological subtypes of pancreatic cancer are pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of all cases, and pancreatic neuroendocrine neoplasm (PanNEN), which makes up 3–5% of all cases. PanNEN is classified into well-differentiated pancreatic neuroendocrine tumor and poorly-differentiated pancreatic neuroendocrine carcinoma (PanNEC). Although PDAC and PanNEN are commonly thought to be different diseases with distinct biology, cell of origin, and genomic abnormalities, the idea that PDAC and PanNEC share common cells of origin has been gaining support. This is substantiated by evidence that the molecular profiling of PanNEC is genetically and phenotypically related to PDAC. In the current review, we summarize published studies pointing to common potential cells of origin and speculate about how the distinct paths of differentiation are determined by the genomic patterns of each disease. We also discuss the overlap between PDAC and PanNEC, which has been noted in clinical observations.

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

scholarly journals Roles of autophagy and metabolism in pancreatic cancer cell adaptation to environmental challenges

2017 ◽  
Vol 313 (5) ◽  
pp. G524-G536 ◽  
Author(s):  
Sandrina Maertin ◽  
Jason M. Elperin ◽  
Ethan Lotshaw ◽  
Matthias Sendler ◽  
Steven D. Speakman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Oxidative Phosphorylation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Environmental Stresses ◽  
Ductal Adenocarcinoma ◽  
Cell Adaptation ◽  
Autophagy Inhibition ◽  
Dependent Mechanism

Pancreatic ductal adenocarcinoma (PDAC) displays extensive and poorly vascularized desmoplastic stromal reaction, and therefore, pancreatic cancer (PaCa) cells are confronted with nutrient deprivation and hypoxia. Here, we investigate the roles of autophagy and metabolism in PaCa cell adaptation to environmental stresses, amino acid (AA) depletion, and hypoxia. It is known that in healthy cells, basal autophagy is at a low level, but it is greatly activated by environmental stresses. By contrast, we find that in PaCa cells, basal autophagic activity is relatively high, but AA depletion and hypoxia activate autophagy only weakly or not at all, due to their failure to inhibit mechanistic target of rapamycin. Basal, but not stress-induced, autophagy is necessary for PaCa cell proliferation, and AA supply is even more critical to maintain PaCa cell growth. To gain insight into the underlying mechanisms, we analyzed the effects of autophagy inhibition and AA depletion on PaCa cell metabolism. PaCa cells display mixed oxidative/glycolytic metabolism, with oxidative phosphorylation (OXPHOS) predominant. Both autophagy inhibition and AA depletion dramatically decreased OXPHOS; furthermore, pharmacologic inhibitors of OXPHOS suppressed PaCa cell proliferation. The data indicate that the maintenance of OXPHOS is a key mechanism through which autophagy and AA supply support PaCa cell growth. We find that the expression of oncogenic activation mutation in GTPase Kras markedly promotes basal autophagy and stimulates OXPHOS through an autophagy-dependent mechanism. The results suggest that approaches aimed to suppress OXPHOS, particularly through limiting AA supply, could be beneficial in treating PDAC. NEW & NOTEWORTHY Cancer cells in the highly desmoplastic pancreatic ductal adenocarcinoma confront nutrient [i.e., amino acids (AA)] deprivation and hypoxia, but how pancreatic cancer (PaCa) cells adapt to these conditions is poorly understood. This study provides evidence that the maintenance of mitochondrial function, in particular, oxidative phosphorylation (OXPHOS), is a key mechanism that supports PaCa cell growth, both in normal conditions and under the environmental stresses. OXPHOS in PaCa cells critically depends on autophagy and AA supply. Furthermore, the oncogenic activation mutation in GTPase Kras upregulates OXPHOS through an autophagy-dependent mechanism.

41 Cathepsin D Expression in Pancreatic Ductal Adenocarcinoma (PDAC) Cells Increases Proliferation and Reduces Survival of Pancreatic Cancer Patients

2015 ◽  
Vol 148 (4) ◽  
pp. S-13
Author(s):  
Ujjwal M. Mahajan ◽  
Enno Langhoff ◽  
Eithne Costello ◽  
William Greenhalf ◽  
Christopher Halloran ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Patients ◽  
Cathepsin D ◽  
Ductal Adenocarcinoma

Precursors of pancreatic cancer in background of chronic opisthorchiasis

2021 ◽  
Vol 22 (1) ◽  
pp. 118-121
Author(s):  
V. U. Rayn ◽  
◽  
M. A. Persidskiy ◽  
E. V. Malakhova ◽  
I. V. Anuchina ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Disease Free Survival ◽  
Morphological Data ◽  
Small Samples ◽  
Ductal Adenocarcinoma ◽  
Preneoplastic Lesions ◽  
Opisthorchis Felineus ◽  
Disease Free

Aim. To establish the association between pancreatic cancer precursor lesions and chronic opisthorchiasis. Materials and methods. A single center case-control study was conducted at a low-volume pancreatic surgery center in Khanty-Mansiysk. We retrospectively collected morphological data from 47 pancreatoduodenectomies performed for pancreatic ductal adenocarcinoma. The study group included 23 cases of pancreatic ductal adenocarcinoma with concomitant chronic Opisthorchis felineus invasion which were compared to 24 controls consisting of “pure” cancer. Qualitative analysis was performed using χ2 Pearson criterion. Exact Fisher test was used for small samples. Time to progression and overall survival rates were calculated using Kaplan-Meier survival analysis. Data were collected and analyzed in Statistica 7.0. Results. PanINs were seen in 41,7% pancreata resected for ductal adenocarcinoma of the head and in 95,7% cases of pancreatic cancer in background of chronic opisthorchiasis (р = 0,000; 95% CI 3,5-268). PanIN high grade were observed only in opisthorchiasis group. In mixed pathology invasive cancer component tended to be more dedifferentiated and advanced when compared to pure cancer group (p = 0,029). Median disease free survival was 9 mo. in both groups and overall survival was 13 mo. in non-opisthorchiasis group and 15,3 mo. in opisthorchiasis group (р = 0,437). Conclusion. Chronic opisthorchiasis is associated with pancreatic intraepithelial neoplasia. Pancreatic ductal adenocarcinoma in background of opisthorchiasis with preneoplastic lesions tend to be more advanced in stage and poorly differentiated. Disease free and overall survival have no statistically significant differences in patients with and without Opisthorchis felineus invasion.

scholarly journals Role of Oxidative and Nitro-Oxidative Damage in Silver Nanoparticles Cytotoxic Effect against Human Pancreatic Ductal Adenocarcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ewelina Barcińska ◽  
Justyna Wierzbicka ◽  
Agata Zauszkiewicz-Pawlak ◽  
Dagmara Jacewicz ◽  
Aleksandra Dabrowska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Pancreatic Cancer ◽  
Silver Nanoparticles ◽  
Oxidative Damage ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cytotoxic Effect ◽  
Mrna Level ◽  
Ductal Adenocarcinoma ◽  
Adenocarcinoma Cells

Pancreatic ductal adenocarcinoma is one of the most aggressive human malignancies, where the 5-year survival rate is less than 4% worldwide. Successful treatment of pancreatic cancer is a challenge for today’s oncology. Several studies showed that increased levels of oxidative stress may cause cancer cells damage and death. Therefore, we hypothesized that oxidative as well as nitro-oxidative stress is one of the mechanisms inducing pancreatic cancer programmed cell death. We decided to use silver nanoparticles (AgNPs) (2.6 and 18 nm) as a key factor triggering the reactive oxygen species (ROS) and reactive nitrogen species (RNS) in pancreatic ductal adenocarcinoma cells (PANC-1). Previously, we have found that AgNPs induced PANC-1 cells death. Furthermore, it is known that AgNPs may induce an accumulation of ROS and alteration of antioxidant systems in different type of tumors, and they are indicated as promising agents for cancer therapy. Then, the aim of our study was to evaluate the implication of oxidative and nitro-oxidative stress in this cytotoxic effect of AgNPs against PANC-1 cells. We determined AgNP-induced increase of ROS level in PANC-1 cells and pancreatic noncancer cell (hTERT-HPNE) for comparison purposes. We found that the increase was lower in noncancer cells. Reduction of mitochondrial membrane potential and changes in the cell cycle were also observed. Additionally, we determined the increase in RNS level: nitric oxide (NO) and nitric dioxide (NO2) in PANC-1 cells, together with increase in family of nitric oxide synthases (iNOS, eNOS, and nNOS) at protein and mRNA level. Disturbance of antioxidant enzymes: superoxide dismutase (SOD1, SOD2, and SOD3), glutathione peroxidase (GPX-4) and catalase (CAT) were proved at protein and mRNA level. Moreover, we showed cells ultrastructural changes, characteristic for oxidative damage. Summarizing, oxidative and nitro-oxidative stress and mitochondrial disruption are implicated in AgNPs-mediated death in human pancreatic ductal adenocarcinoma cells.

scholarly journals Anticancer Effect of Heparin–Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5775
Author(s):  
Hae Hyun Hwang ◽  
Hee Jeong Jeong ◽  
Sangwu Yun ◽  
Youngro Byun ◽  
Teruo Okano ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Endothelial Cells ◽  
Cancer Cells ◽  
Tumor Model ◽  
Pancreatic Neuroendocrine Tumor ◽  
Tube Formation ◽  
Ductal Adenocarcinoma ◽  
Orthotopic Model ◽  
Anticancer Efficacy

Pancreatic cancers are classified based on where they occur, and are grouped into those derived from exocrine and those derived from neuroendocrine tumors, thereby experiencing different anticancer effects under medication. Therefore, it is necessary to develop anticancer drugs that can inhibit both types. To this end, we developed a heparin–taurocholate conjugate, i.e., LHT, to suppress tumor growth via its antiangiogenic activity. Here, we conducted a study to determine the anticancer efficacy of LHT on pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET), in an orthotopic animal model. LHT reduced not only proliferation of cancer cells, but also attenuated the production of VEGF through ERK dephosphorylation. LHT effectively reduced the migration, invasion and tube formation of endothelial cells via dephosphorylation of VEGFR, ERK1/2, and FAK protein. Especially, these effects of LHT were much stronger on PNET (RINm cells) than PDAC (PANC1 and MIA PaCa-2 cells). Eventually, LHT reduced ~50% of the tumor weights and tumor volumes of all three cancer cells in the orthotopic model, via antiproliferation of cancer cells and antiangiogenesis of endothelial cells. Interestingly, LHT had a more dominant effect in the PNET-induced tumor model than in PDAC in vivo. Collectively, these findings demonstrated that LHT could be a potential antipancreatic cancer medication, regardless of pancreatic cancer types.

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