Journal articles on the topic 'Pancreatic ductal cancer'
To see the other types of publications on this topic, follow the link: Pancreatic ductal cancer.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Pancreatic ductal cancer.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Chen, Yan, Huiyun Zhu, Yuqiong Wang, Yingxiao Song, Pingping Zhang, Zhijie Wang, Jun Gao, Zhaoshen Li, and Yiqi Du. "MicroRNA-132 Plays an Independent Prognostic Role in Pancreatic Ductal Adenocarcinoma and Acts as a Tumor Suppressor." Technology in Cancer Research & Treatment 18 (January 1, 2019): 153303381882431. http://dx.doi.org/10.1177/1533033818824314.
Abstract:
The role of microRNA-132 in human pancreatic ductal adenocarcinomas is still ambiguous. We explored the association between microRNA-132 and pancreatic ductal adenocarcinoma prognosis. The expression of microRNA-132 in 50 pancreatic ductal adenocarcinoma tissue samples and pancreatic ductal adenocarcinoma cell lines was examined, and the association between its expression and pancreatic ductal adenocarcinoma prognosis was assessed. Functional analysis and factors downstream of microRNA-132 were investigated. Kaplan-Meier survival curves showed that high expression of microRNA-132 was a significant prognostic factor for 1-year survival of patients with pancreatic ductal adenocarcinoma ( P = .028). Multivariate analysis for overall survival indicated that high expression of microRNA-132 was an independent prognostic factor for patients with pancreatic ductal adenocarcinoma ( P = .044). Low expression of microRNA-132 was associated with poor prognosis in pancreatic ductal adenocarcinoma. Ectopic expression of microRNA-132 significantly inhibited proliferation and promoted apoptosis of 2 pancreatic ductal adenocarcinoma cell lines. Bioinformatic analysis revealed that microRNA-132 may exert its effects on pancreatic ductal adenocarcinoma through downregulating mitogen-activated protein kinase 3 and nuclear transcription factor Y subunit α. The results of this study further our understanding of the relationship between microRNA-132 and pancreatic ductal adenocarcinoma by showing that microRNA-132 might inhibit the progression of pancreatic ductal adenocarcinoma by regulating mitogen-activated protein kinase and nuclear transcription factor Y subunit alpha.
2
González-Boja, Iranzu, Antonio Viúdez, Saioa Goñi, Enrique Santamaria, Estefania Carrasco-García, Jairo Pérez-Sanz, Irene Hernández-García, et al. "Omics Approaches in Pancreatic Adenocarcinoma." Cancers 11, no. 8 (July 25, 2019): 1052. http://dx.doi.org/10.3390/cancers11081052.
Abstract:
Pancreatic ductal adenocarcinoma, which represents 80% of pancreatic cancers, is mainly diagnosed when treatment with curative intent is not possible. Consequently, the overall five-year survival rate is extremely dismal—around 5% to 7%. In addition, pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this area. Beyond the use of cytological or histological samples focusing in diagnosis, a plethora of new approaches are currently being used for a deeper characterization of pancreatic ductal adenocarcinoma, including genetic, epigenetic, and/or proteo-transcriptomic techniques. Accordingly, the development of new analytical technologies using body fluids (blood, bile, urine, etc.) to analyze tumor derived molecules has become a priority in pancreatic ductal adenocarcinoma due to the hard accessibility to tumor samples. These types of technologies will lead us to improve the outcome of pancreatic ductal adenocarcinoma patients.
3
Rayn, V. U., M. A. Persidskiy, E. V. Malakhova, I. V. Anuchina, A. A. Khalikova, Ya E. Timofeeva, and L. V. Bereshkeeva. "Precursors of pancreatic cancer in background of chronic opisthorchiasis." Medical Science And Education Of Ural 22, no. 1 (March 31, 2021): 118–21. http://dx.doi.org/10.36361/1814-8999-2021-22-1-118-121.
Abstract:
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.
4
Melzer, Michael Karl, Frank Arnold, Katja Stifter, Friedemann Zengerling, Ninel Azoitei, Thomas Seufferlein, Christian Bolenz, and Alexander Kleger. "An Immunological Glance on Pancreatic Ductal Adenocarcinoma." International Journal of Molecular Sciences 21, no. 9 (May 8, 2020): 3345. http://dx.doi.org/10.3390/ijms21093345.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Different factors such as mutational landscape, intra- and intertumoral heterogeneity, stroma, and immune cells impact carcinogenesis of PDAC associated with an immunosuppressive microenvironment. Different cell types with partly opposing roles contribute to this milieu. In recent years, immunotherapeutic approaches, including checkpoint inhibitors, were favored to treat cancers, albeit not every cancer entity exhibited benefits in a similar way. Indeed, immunotherapies rendered little success in pancreatic cancer. In this review, we describe the communication between the immune system and pancreatic cancer cells and propose some rationale why immunotherapies may fail in the context of pancreatic cancer. Moreover, we delineate putative strategies to sensitize PDAC towards immunological therapeutics and highlight the potential of targeting neoantigens.
5
Djanani, Angela, Andreas Schmiderer, Lukas Niederreiter, Markus Niederreiter, and Herbert Tilg. "Management of ductal pancreatic cancer." European Surgery 51, no. 3 (May 15, 2019): 135–38. http://dx.doi.org/10.1007/s10353-019-0583-z.
6
Sun, Hongzhi, Bo Zhang, and Haijun Li. "The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382092096. http://dx.doi.org/10.1177/1533033820920969.
Abstract:
Pancreatic ductal adenocarcinoma has extremely high malignancy and patients with pancreatic ductal adenocarcinoma have dismal prognosis. The failure of pancreatic ductal adenocarcinoma treatment is largely due to the tumor microenvironment, which is featured by ample stromal cells and complicated extracellular matrix. Recent genomic analysis revealed that pancreatic ductal adenocarcinoma harbors frequently mutated genes including KRAS, TP53, CDKN2A, and SMAD4, which can widely alter cellular processes and behaviors. As shown by accumulating studies, these mutant genes may also change tumor microenvironment, which in turn affects pancreatic ductal adenocarcinoma progression. In this review, we summarize the role of such genetic mutations in tumor microenvironment regulation and potential mechanisms.
7
Hartl, Leonie, JanWillem Duitman, Hella L. Aberson, Kan Chen, Frederike Dijk, Joris J. T. H. Roelofs, Mark P. G. Dings, et al. "CCAAT/Enhancer-Binding Protein Delta (C/EBPδ): A Previously Unrecognized Tumor Suppressor that Limits the Oncogenic Potential of Pancreatic Ductal Adenocarcinoma Cells." Cancers 12, no. 9 (September 7, 2020): 2546. http://dx.doi.org/10.3390/cancers12092546.
Abstract:
CCAAT/enhancer-binding protein δ (C/EBPδ) is a transcription factor involved in growth arrest and differentiation, which has consequently been suggested to harbor tumor suppressive activities. However, C/EBPδ over-expression correlates with poor prognosis in glioblastoma and promotes genomic instability in cervical cancer, hinting at an oncogenic role of C/EBPδ in these contexts. Here, we explore the role of C/EBPδ in pancreatic cancer. We determined C/EBPδ expression in biopsies from pancreatic cancer patients using public gene-expression datasets and in-house tissue microarrays. We found that C/EBPδ is highly expressed in healthy pancreatic ductal cells but lost in pancreatic ductal adenocarcinoma. Furthermore, loss of C/EBPδ correlated with increased lymph node involvement and shorter overall survival in pancreatic ductal adenocarcinoma patients. In accordance with this, in vitro experiments showed reduced clonogenic capacity and proliferation of pancreatic ductal adenocarcinoma cells following C/EBPδ re-expression, concurrent with decreased sphere formation capacity in soft agar assays. We thus report a previously unrecognized but important tumor suppressor role of C/EBPδ in pancreatic ductal adenocarcinoma. This is of particular interest since only few tumor suppressors have been identified in the context of pancreatic cancer. Moreover, our findings suggest that restoration of C/EBPδ activity could hold therapeutic value in pancreatic ductal adenocarcinoma, although the latter claim needs to be substantiated in future studies.
8
Perkins, Corey Melissa, Jinmai Jiang, Hesamedin Hakimjavadi, Julie K. Bray, Alyssa Gosling, Lais da Silva, Gamze Bulut, et al. "Abstract 780: Transcriptional profile of human pancreatic acinar ductal metaplasia." Cancer Research 82, no. 12_Supplement (June 15, 2022): 780. http://dx.doi.org/10.1158/1538-7445.am2022-780.
Abstract:
Abstract Aberrant acinar to ductal metaplasia (ADM), one of the earliest events involved in exocrine pancreatic cancer development, is typically studied using pancreata from transgenic mouse models. We used primary, human pancreatic acinar cells to evaluate the transcriptional profile during the course of ADM. Following six days of culture on Matrigel, acinar cells underwent morphological and molecular changes reminiscent of ADM. RNA was sequenced from 14 donor’s paired pancreata (day 0 and 6 of culture). Unsupervised hierarchical clustering demonstrated complete separation of the gene expression profile between culture day 0 (acinar phenotype) and day 6 (ductal phenotype). By and large, acinar-specific genes were downregulated in the samples from day 6 ADM while ductal-specific genes were upregulated. Using a gene set enrichment approach, we identified regulons that are involved in regulating ADM including downregulated, acinar-associated transcription factors (including PTF1A, RBPJL, and XBP1) and upregulated, ductal- and progenitor-associated transcription factors (SOX11, SOX4, and YAP1). The expression of pancreatic cancer associated genes significantly correlated with the gene expression/regulon activity observed in normal pancreas undergoing ADM. We reported a detail analysis of the transcriptional profile during human ADM. Our findings confirm that many ADM-related transcription factors and signaling pathways discovered in transgenic mouse models are applicable to human ADM and highlights the relevancy of in vitro models of pancreas plasticity using human tissue. Citation Format: Corey Melissa Perkins, Jinmai Jiang, Hesamedin Hakimjavadi, Julie K. Bray, Alyssa Gosling, Lais da Silva, Gamze Bulut, Jamel Ali, Wendy Setiawan, Martha Campbell-Thompson, Srikar Chamala, Thomas D. Schmittgen. Transcriptional profile of human pancreatic acinar ductal metaplasia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 780.
9
Shabunin, A. A., A. A. Karpov, E. V. Kizhaev, V. V. Bedin, M. M. Tavobilov, O. V. Paklina, and G. R. Setdikova. "Combined surgical treatment of pancreatic head cancer." Annaly khirurgicheskoy gepatologii = Annals of HPB surgery 23, no. 3 (October 21, 2018): 8–13. http://dx.doi.org/10.16931/1995-5464.201838-13.
Abstract:
Aim.To improve the outcomes in patients with pancreatic head cancer using intraoperative radiotherapy (IORT).Material and methods.Prospective trial included patients with ductal adenocarcinoma of the pancreatic head who underwent pancreatic surgery followed by IORT.Results.There were 63 patients with pancreatic ductal adenocarcinoma for the period from January 2013 till December 2016. IORT was applied in 31 cases. Annual, 3-year survival and disease-free survival were analyzed.Conclusion.Surgery followed by IORT is safe and current approach for pancreatic head cancer.
10
Jansen, Kristina, Franziska Büscheck, Katharina Moeller, Martina Kluth, Claudia Hube-Magg, Niclas Christian Blessin, Daniel Perez, et al. "DOG1 is commonly expressed in pancreatic adenocarcinoma but unrelated to cancer aggressiveness." PeerJ 9 (August 3, 2021): e11905. http://dx.doi.org/10.7717/peerj.11905.
Abstract:
Background DOG1 (ANO1; TMEM16A) is a voltage-gated calcium-activated chloride and bicarbonate channel. DOG1 is physiologically expressed in Cajal cells, where it plays an important role in regulating intestinal motility and its expression is a diagnostic hallmark of gastrointestinal stromal tumors (GIST). Data on a possible role of DOG1 in pancreatic cancer are rare and controversial. The aim of our study was to clarify the prevalence of DOG1 expression in pancreatic cancer and to study its association with parameters of cancer aggressiveness. Methods DOG1 expression was analyzed by immunohistochemistry in 599 pancreatic cancers in a tissue microarray format and in 12 cases of pancreatitis on large tissue sections. Results DOG1 expression was always absent in normal pancreas but a focal weak expression was seen in four of 12 cases of pancreatitis. DOG1 expression was, however, common in pancreatic cancer. Membranous and cytoplasmic DOG1 expression in tumor cells was highest in pancreatic ductal adenocarcinomas (61% of 444 interpretable cases), followed by cancers of the ampulla Vateri (43% of 51 interpretable cases), and absent in 6 acinus cell carcinomas. DOG1 expression in tumor associated stroma cells was seen in 76 of 444 (17%) pancreatic ductal adenocarcinomas and in seven of 51 (14%) cancers of the ampulla Vateri. Both tumoral and stromal DOG1 expression were unrelated to tumor stage, grade, lymph node and distant metastasis, mismatch repair protein deficiency and the density of CD8 positive cytotoxic T-lymphocytes in the subgroups of ductal adenocarcinomas and cancers of ampulla Vateri. Overall, the results of our study indicate that DOG1 may represent a potential biomarker for pancreatic cancer diagnosis and a putative therapeutic target in pancreatic cancer. However, DOG1 expression is unrelated to pancreatic cancer aggressiveness.
11
Wei, Honglong, Zongzhen Xu, Feng Liu, Fuhai Wang, Xin Wang, Xueying Sun, and Jie Li. "Hypoxia induces oncogene yes-associated protein 1 nuclear translocation to promote pancreatic ductal adenocarcinoma invasion via epithelial–mesenchymal transition." Tumor Biology 39, no. 5 (May 2017): 101042831769168. http://dx.doi.org/10.1177/1010428317691684.
Abstract:
Pancreatic ductal adenocarcinoma is one of the most lethal cancers. The Hippo pathway is involved in tumorigenesis and remodeling of tumor microenvironments. Hypoxia exists in the microenvironment of solid tumors, including pancreatic ductal adenocarcinoma and plays a vital role in tumor progression and metastasis. However, it remains unclear how hypoxia interacts with the Hippo pathway to regulate these events. In this study, expressions of yes-associated protein 1 and hypoxia-inducible factor-1α were found to be elevated in pancreatic ductal adenocarcinoma samples compared with those in matched adjacent non-tumor samples. Moreover, hypoxia-inducible factor-1α expression was positively correlated with yes-associated protein 1 level in pancreatic ductal adenocarcinoma tissues. The higher expression of nuclear yes-associated protein 1 was associated with poor histological grade and prognosis for pancreatic ductal adenocarcinoma patients. In vitro, yes-associated protein 1 was highly expressed in pancreatic ductal adenocarcinoma cells. Depletion of yes-associated protein 1 inhibited the invasion of pancreatic ductal adenocarcinoma cells via downregulation of Vimentin, matrix metalloproteinase-2, and matrix metalloproteinase-13, and upregulation of E-cadherin. In addition, hypoxia promoted the invasion of pancreatic ductal adenocarcinoma cells via regulating the targeted genes. Hypoxia also deactivated the Hippo pathway and induced yes-associated protein 1 nuclear translocation. Furthermore, depletion of yes-associated protein 1 or hypoxia-inducible factor-1α suppressed the invasion of pancreatic ductal adenocarcinoma cells under hypoxia. Mechanism studies showed that nuclear yes-associated protein 1 interacted with hypoxia-inducible factor-1α and activated Snail transcription to participate in epithelial–mesenchymal transition–mediated and matrix metalloproteinase–mediated remodeling of tumor microenvironments. Collectively, yes-associated protein 1 is an independent prognostic predictor that interacts with hypoxia-inducible factor-1α to enhance the invasion of pancreatic cancer cells and remodeling of tumor microenvironments. Therefore, yes-associated protein 1 may serve as a novel promising target to enhance therapeutic effects for treating pancreatic cancer.
12
Tamiolakis, Demetrio, Constantine Simopoulos, Athanasia Kotini, Ioannis Venizelos, Theodoros Jivannakis, and Nikolaos Papadopoulos. "Pancreatic-Polypeptide in the Human Pancreas: Expression and Quantitative Variation During Development and in Ductal Adenocarcinoma." Acta Medica (Hradec Kralove, Czech Republic) 46, no. 1 (2003): 9–14. http://dx.doi.org/10.14712/18059694.2019.2.
Abstract:
Aim: To determine the immunoreactivity of pancreatic-polypeptide (PP) during the development of the human fetal pancreas and ductal pancreatic adenocarcinoma, given that, PP positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. Methods: Tissue sections from 15 pancreatic fetal specimens, and equal number of ductal adenocarcinoma specimens, were assessed. Results: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly higher than the relevant density in the neoplastic pancreatic tissue of mixed (ductal – endocrine) and pure ductal type (p1=0.001, p2<0.0005, p3 =0.046 and p4<0.0005 respectively). The above values were estimated during the 10th to 12th week. There was no significant difference in the density of positive cells in the mantle zone of the islets from the 13th to the 24th week, and the neoplastic tissue of mixed (p5=0.11) and pure ductal type (p6=0.23). Conclusion: The immunostaining for PP identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component, initially considered as pure ductal tumors, and mixed ductal and neuroendocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, raising the question of therapeutic efficacy of PP and analogues as potential adjuvant treatment of pancreatic cancer.
13
Sharaiha, Reem Z., Jessica Widmer, and Michel Kahaleh. "Palliation of Pancreatic Ductal Obstruction in Pancreatic Cancer." Gastrointestinal Endoscopy Clinics of North America 23, no. 4 (October 2013): 917–23. http://dx.doi.org/10.1016/j.giec.2013.06.010.
14
Anderson, Eric M., Shant Thomassian, Jun Gong, Andrew Hendifar, and Arsen Osipov. "Advances in Pancreatic Ductal Adenocarcinoma Treatment." Cancers 13, no. 21 (November 3, 2021): 5510. http://dx.doi.org/10.3390/cancers13215510.
Abstract:
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the deadliest malignancies among all cancers. Despite curative intent, surgery and the use of standard cytotoxic chemotherapy and radiation therapy, PDAC remains treatment-resistant. In recent years, more contemporary treatment modalities such as immunotherapy via checkpoint inhibition have shown some promise in many other malignancies, yet PDAC still eludes an effective curative treatment. In investigating these phenomena, research has suggested that the significant desmoplastic and adaptive tumor microenvironment (TME) of PDAC promote the proliferation of immunosuppressive cells and act as major obstacles to treatment efficacy. In this review, we explore challenges associated with the treatment of PDAC, including its unique immunosuppressive TME. This review examines the role of surgery in PDAC, recent advances in surgical approaches and surgical optimization. We further focus on advances in immunotherapeutic approaches, including checkpoint inhibition, CD40 agonists, and discuss promising immune-based future strategies, such as therapeutic neoantigen cancer vaccines as means of overcoming the resistance mechanisms which underly the dense stroma and immune milieu of PDAC. We also explore unique signaling, TME and stromal targeting via novel small molecule inhibitors, which target KRAS, FAK, CCR2/CCR5, CXCR4, PARP and cancer-associated fibroblasts. This review also explores the most promising strategy for advancement in treatment of pancreatic cancer by reviewing contemporary combinatorial approaches in efforts to overcome the treatment refractory nature of PDAC.
15
Clark, Clancy J., Janani S. Arun, Rondell P. Graham, Lizhi Zhang, Michael Farnell, and Kaye M. Reid-Lombardo. "Clinical Characteristics and Overall Survival in Patients with Anaplastic Pancreatic Cancer." American Surgeon 80, no. 2 (February 2014): 117–23. http://dx.doi.org/10.1177/000313481408000218.
Abstract:
Anaplastic pancreatic cancer (APC) is a rare undifferentiated variant of pancreatic ductal adenocarcinoma with poor overall survival (OS). The aim of this study was to evaluate the clinical outcomes of APC compared with differentiated pancreatic ductal adenocarcinoma. We conducted a retrospective review of all patients treated at the Mayo Clinic with pathologically confirmed APC from 1987 to 2011. After matching with control subjects with pancreatic ductal adenocarcinoma, OS was evaluated using Kaplan-Meier estimates and log-rank test. Sixteen patients were identified with APC (56.3% male, median age 57 years). Ten patients underwent exploration of whom eight underwent pancreatectomy. Perioperative morbidity was 60 per cent with no mortality. The median OS was 12.8 months. However, patients with APC who underwent resection had longer OS compared with those who were not resected, 34.1 versus 3.3 months ( P = 0.001). After matching age, sex, tumor stage, and year of operation, the median OS was similar between patients with APC and those with ductal adenocarcinoma treated with pancreatic resection, 44.1 versus 39.9 months, ( P = 0.763). Overall survival for APC is poor; however, when resected, survival is similar to differentiated pancreatic ductal adenocarcinoma.
16
Li, Shentao, He Li, Weiwei Ge, Kai Song, Chunyu Yuan, and Ran Yin. "Effect of miR-184 on Proliferation and Apoptosis of Pancreatic Ductal Adenocarcinoma and Its Mechanism." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382094323. http://dx.doi.org/10.1177/1533033820943237.
Abstract:
Objective: Previous studies have shown that abnormal expression of microRNA-184 leads to a variety of cancers, including pancreatic ductal adenocarcinoma, suggesting microRNA-184 as a new treatment target for pancreatic ductal adenocarcinoma. However, the molecular mechanism of microRNA-184 in pancreatic ductal adenocarcinoma remains unclear. It is important to investigate the effect and role of microRNA-184 in pancreatic ductal adenocarcinoma. Methods: The clinical and laboratory inspection data of 120 patients with pancreatic cancer admitted to the First Affiliated Hospital of Anhui Medical University were compared. MicroRNA-184 expression in tumor tissues and cells was evaluated using reverse transcription polymerase chain reaction. Flow cytometry and Annexin V/propidium iodide staining were performed to examine cell cycle and apoptosis. Western blotting analysis was conducted to measure the protein expression of p-PI3K, p-AKT, JNK1, C-Myc, C-Jun, caspase-9, and caspase-3. Results: MicroRNA-184 expression was low in patients with pancreatic ductal adenocarcinoma. Survival curve showed that patients with lower expression of microRNA-184 in tumor tissues had a worse prognosis and shorter survival time ( P < .05), and the multivariate analysis identified that microRNA-184 was an independent prognostic indicator ( P < .05). In vitro studies showed that microRNA-184 overexpression induced apoptosis and suppressed cell cycle transition from G1 to S and G2 phases in pancreatic ductal adenocarcinoma cells. Furthermore, molecular studies revealed that inhibition of microRNA-184 promoted the gene expression of p-PI3K, p-AKT, JNK1, C-Myc, and C-Jun compared with the control group. Overexpression of microRNA-184 led to significantly increased expression of caspase-9 and caspase-3 and significantly decreased expression of Bcl-2. Conclusion: This study suggests that microRNA-184 inhibits the proliferation and promotes the apoptosis of pancreatic ductal adenocarcinoma cells by downregulating the expression of C-Myc, C-Jun, and Bcl-2. Our verification of the role of microRNA-184 may provide a novel biomarker for the diagnosis, therapy, and prognosis of pancreatic ductal adenocarcinoma.
17
Tuveson, DavidA. "Experimental approaches to ductal pancreatic cancer." Hamdan Medical Journal 9, no. 4 (2016): 277. http://dx.doi.org/10.7707/hmj.693.
18
Link, Karl-Heinrich, Frank Gansauge, Jürgen Pillasch, and Hans-Günther Beger. "Multimodal therapies in ductal pancreatic cancer." International Journal of Pancreatology 21, no. 1 (February 1997): 71–83. http://dx.doi.org/10.1007/bf02785923.
19
Klapdor, R., U. Klapdor, H. Greten, M. Dietel, H. van Ackeren, B. Kremer, and H. W. Schreiber. "Palliative therapy of ductal pancreatic cancer." Journal of Cancer Research and Clinical Oncology 111, S1 (February 1986): S87. http://dx.doi.org/10.1007/bf02580116.
20
Sirivatanauksorn, V., Y. Sirivatanauksorn, and N. R. Lemoine. "Molecular pattern of ductal pancreatic cancer." Langenbecks Archiv für Chirurgie 383, no. 2 (1998): 105. http://dx.doi.org/10.1007/s004230050101.
21
Yeo, C. J., and J. L. Cameron. "Prognostic factors in ductal pancreatic cancer." Langenbecks Archiv für Chirurgie 383, no. 2 (1998): 129. http://dx.doi.org/10.1007/s004230050104.
22
Ushio, Jun, Atsushi Kanno, Eriko Ikeda, Kozue Ando, Hiroki Nagai, Tetsurou Miwata, Yuki Kawasaki, et al. "Pancreatic Ductal Adenocarcinoma: Epidemiology and Risk Factors." Diagnostics 11, no. 3 (March 20, 2021): 562. http://dx.doi.org/10.3390/diagnostics11030562.
Abstract:
The number of new cases of pancreatic ductal adenocarcinoma is increasing with a cumulative total of 495,773 cases worldwide, making it the fourteenth most common malignancy. However, it accounts for 466,003 deaths per year and is the seventh leading cause of cancer deaths. Regional differences in the number of patients with pancreatic ductal adenocarcinoma appear to reflect differences in medical care, as well as racial differences. Compared to the prevalence of other organ cancers in Japan, pancreatic ductal adenocarcinoma ranks seventh based on the number of patients, eighth based on morbidity, and fourth based on the number of deaths, with a continuing increase in the mortality rate. Risk factors for developing pancreatic ductal adenocarcinoma include family history, genetic disorders, diabetes, chronic pancreatitis, and intraductal papillary mucinous neoplasms. An issue that hinders improvement in the prognosis of patients with pancreatic ductal adenocarcinoma is the development of a strategy to identify patients with these risk factors to facilitate detection of the disease at a stage when intervention will improve survival.
23
Coppola, Alessandro, Daniela Pozzi, and Damiano Caputo. "Novel Biomarkers in Pancreatic Cancer." Cancers 16, no. 3 (January 31, 2024): 628. http://dx.doi.org/10.3390/cancers16030628.
24
Coppola, Alessandro, Tommaso Farolfi, Vincenzo La Vaccara, Roberto Cammarata, and Damiano Caputo. "Role of Neoplastic Markers in Pancreatic Adenocarcinoma." Journal of Clinical Medicine 11, no. 21 (November 2, 2022): 6509. http://dx.doi.org/10.3390/jcm11216509.
25
Vernuccio, Federica, Carlo Messina, Valeria Merz, Roberto Cannella, and Massimo Midiri. "Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma: Role of the Radiologist and Oncologist in the Era of Precision Medicine." Diagnostics 11, no. 11 (November 22, 2021): 2166. http://dx.doi.org/10.3390/diagnostics11112166.
Abstract:
The incidence and mortality of pancreatic ductal adenocarcinoma are growing over time. The management of patients with pancreatic ductal adenocarcinoma involves a multidisciplinary team, ideally involving experts from surgery, diagnostic imaging, interventional endoscopy, medical oncology, radiation oncology, pathology, geriatric medicine, and palliative care. An adequate staging of pancreatic ductal adenocarcinoma and re-assessment of the tumor after neoadjuvant therapy allows the multidisciplinary team to choose the most appropriate treatment for the patient. This review article discusses advancement in the molecular basis of pancreatic ductal adenocarcinoma, diagnostic tools available for staging and tumor response assessment, and management of resectable or borderline resectable pancreatic cancer.
26
Shi, Chanjuan, Ralph H. Hruban, and Alison P. Klein. "Familial Pancreatic Cancer." Archives of Pathology & Laboratory Medicine 133, no. 3 (March 1, 2009): 365–74. http://dx.doi.org/10.5858/133.3.365.
Abstract:
Abstract Context.—Approximately 5% to 10% of individuals with pancreatic cancer report a history of pancreatic cancer in a close family member. In addition, several known genetic syndromes, such as familial breast cancer (BRCA2), the Peutz-Jeghers syndrome, and the familial atypical multiple mole melanoma syndrome, have been shown to be associated with an increased risk of pancreatic cancer. The known genes associated with these conditions can explain only a portion of the clustering of pancreatic cancer in families, and research to identify additional susceptibility genes is ongoing. Objective.—To provide an understanding of familial pancreatic cancer and the pathology of familial exocrine pancreatic cancers. Data Sources.—Published literature on familial aggregation of pancreatic cancer and familial exocrine pancreatic tumors. Conclusions.—Even in the absence of predictive genetic testing, the collection of a careful, detailed family history is an important step in the management of all patients with pancreatic cancer. While most pancreatic cancers that arise in patients with a family history are ductal adenocarcinomas, certain subtypes of pancreatic cancer have been associated with familial syndromes. Therefore, the histologic appearance of the pancreatic cancer itself, and/or the presence and appearance of precancerous changes in the pancreas, may increase the clinical index of suspicion for a genetic syndrome.
27
Gu, Meichen, Yanli Gao, and Pengyu Chang. "KRAS Mutation Dictates the Cancer Immune Environment in Pancreatic Ductal Adenocarcinoma and Other Adenocarcinomas." Cancers 13, no. 10 (May 18, 2021): 2429. http://dx.doi.org/10.3390/cancers13102429.
Abstract:
Generally, patients with pancreatic ductal adenocarcinoma, especially those with wide metastatic lesions, have a poor prognosis. Recently, a breakthrough in improving their survival has been achieved by using first-line chemotherapy, such as gemcitabine plus nab-paclitaxel or oxaliplatin plus irinotecan plus 5-fluorouracil plus calcium folinate. Unfortunately, regimens with high effectiveness are still absent in second- or later-line settings. In addition, although immunotherapy using checkpoint inhibitors definitively represents a novel method for metastatic cancers, monotherapy using checkpoint inhibitors is almost completely ineffective for pancreatic ductal adenocarcinomas largely due to the suppressive immune milieu in such tumors. Critically, the genomic alteration pattern is believed to impact cancer immune environment. Surprisingly, KRAS gene mutation is found in almost all pancreatic ductal adenocarcinomas. Moreover, KRAS mutation is indispensable for pancreatic carcinogenesis. On these bases, a relationship likely exists between this oncogene and immunosuppression in this cancer. During pancreatic carcinogenesis, KRAS mutation-driven events, such as metabolic reprogramming, cell autophagy, and persistent activation of the yes-associated protein pathway, converge to cause immune evasion. However, intriguingly, KRAS mutation can dictate a different immune environment in other types of adenocarcinoma, such as colorectal adenocarcinoma and lung adenocarcinoma. Overall, the KRAS mutation can drive an immunosuppression in pancreatic ductal adenocarcinomas or in colorectal carcinomas, but this mechanism is not true in KRAS-mutant lung adenocarcinomas, especially in the presence of TP53 inactivation. As a result, the response of these adenocarcinomas to checkpoint inhibitors will vary.
28
Satoi, Sohei. "Surgical Treatment of Pancreatic Ductal Adenocarcinoma." Cancers 13, no. 16 (August 10, 2021): 4015. http://dx.doi.org/10.3390/cancers13164015.
Abstract:
This special issue, “Surgical Treatment of Pancreatic Ductal Adenocarcinoma” contains 13 articles (five original articles, five reviews, and three systematic reviews/meta-analyses) authored by international leaders and surgeons who treat patients with pancreatic ductal adenocarcinoma (PDAC) [...]
29
Kriz, D., D. Ansari, and R. Andersson. "Potential biomarkers for early detection of pancreatic ductal adenocarcinoma." Clinical and Translational Oncology 22, no. 12 (May 23, 2020): 2170–74. http://dx.doi.org/10.1007/s12094-020-02372-0.
Abstract:
Abstract Pancreatic cancer has the highest mortality amongst all major organ cancers. Early detection is key to reduce deaths related to pancreatic cancer. However, early detection has been challenged by the lack of non-invasive biomarkers with enough sensitivity and specificity to allow for screening. The gold standard is still carbohydrate antigen (CA 19-9), against which all new biomarkers must be evaluated. In this paper, we describe recent progress in the development of new pancreatic cancer biomarkers, focusing on proteins, metabolites, and genetic and epigenetic biomarkers. Although several promising biomarkers have been identified, they are all derived from retrospective studies and additional prospective studies are needed to confirm their clinical validity.
30
Cao, Liwei, Chen Huang, Daniel Cui Zhou, Yingwei Hu, Mamie Lih, Sara R. Savage, Karsten Krug, et al. "Abstract IA-003: Proteogenomic characterizations of pancreatic ductal adenocarcinoma." Cancer Research 81, no. 22_Supplement (November 15, 2021): IA—003—IA—003. http://dx.doi.org/10.1158/1538-7445.panca21-ia-003.
Abstract:
Abstract Pancreatic cancer is one of the deadliest cancers and the five-year survival rate is less than 10%. Pancreatic ductal adenocarcinoma (PDAC) represents more than 90% of all pancreatic malignancies, and is responsible for the majority of pancreatic cancer-related deaths. Towards understanding the underlying molecular alterations that drive PDAC oncogenesis and identify therapeutic targets for personalized treatments, we comprehensively characterized 140 pancreatic cancers and 67 normal adjacent tissues. To ensure robust, downstream analyses, tumor neoplastic cellularity was assessed via multiple, orthogonal strategies using molecular features, and verified via pathological estimation of tumor cellularity based on histological review to select tumors with sufficient tumor cellularity. We also included the analysis of 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole genome sequencing, whole exome sequencing, methylation, RNA-seq, and miRNA-seq were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. These characterizations revealed functional impacts of genomic and epigenomic alterations on proteins and protein modifications, delineated PDAC cell microenvironment compositions and the immune signatures for immunotherapy, also uncovered putative kinase inhibitors that could be tested for therapy. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets. Citation Format: Liwei Cao, Chen Huang, Daniel Cui Zhou, Yingwei Hu, Mamie Lih, Sara R. Savage, Karsten Krug, David J. Clark, Michael Schnaubelt, Lijun Chen, Felipe da Veiga Leprevost, Rodrigo Vargas Eguez, Alexey I. Nesvizhskii, D.R. Mani, Gilbert S. Omenn, Emily S. Boja, Mehdi Mesri, Ana I. Robles, Henry Rodriguez, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang, Clinical Proteomic Tumor Analysis Consortium. Proteogenomic characterizations of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr IA-003.
31
Yousaf, Muhammad Nadeem, Fizah S. Chaudhary, Amrat Ehsan, Alejandro L. Suarez, Thiruvengadam Muniraj, Priya Jamidar, Harry R. Aslanian, and James J. Farrell. "Endoscopic ultrasound (EUS) and the management of pancreatic cancer." BMJ Open Gastroenterology 7, no. 1 (May 2020): e000408. http://dx.doi.org/10.1136/bmjgast-2020-000408.
Abstract:
Pancreatic cancer is one of the leading causes of cancer-related mortality in western countries. Early diagnosis of pancreatic cancers plays a key role in the management by identification of patients who are surgical candidates. The advancement in the radiological imaging and interventional endoscopy (including endoscopic ultrasound (EUS), endoscopic retrograde cholangiopancreatography and endoscopic enteral stenting techniques) has a significant impact in the diagnostic evaluation, staging and treatment of pancreatic cancer. The multidisciplinary involvement of radiology, gastroenterology, medical oncology and surgical oncology is central to the management of patients with pancreatic cancers. This review aims to highlight the diagnostic and therapeutic role of EUS in the management of patients with pancreatic malignancy, especially pancreatic ductal adenocarcinoma.
32
Ottenhof, Niki A., Roeland F. de Wilde, Anirban Maitra, Ralph H. Hruban, and G. Johan A. Offerhaus. "Molecular Characteristics of Pancreatic Ductal Adenocarcinoma." Pathology Research International 2011 (March 27, 2011): 1–16. http://dx.doi.org/10.4061/2011/620601.
Abstract:
Pancreatic cancer is an almost universally lethal disease and despite extensive research over the last decades, this has not changed significantly. Nevertheless, much progress has been made in understanding the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) suggesting that different therapeutic strategies based on these new insights are forthcoming. Increasing focus exists on designing the so-called targeted treatment strategies in which the genetic characteristics of a tumor guide therapy. In the past, the focus of research was on identifying the most frequently affected genes in PDAC, but with the complete sequencing of the pancreatic cancer genome the focus has shifted to defining the biological function that the altered genes play. In this paper we aimed to put the genetic alterations present in pancreatic cancer in the context of their role in signaling pathways. In addition, this paper provides an update of the recent advances made in the development of the targeted treatment approach in PDAC.
33
Matar, Somer M., Britton C. Goodale, Xiaoying Liu, Annie Katanga, Nicole F. Gallien, Sandra Blazquez, Direna Alonso-Curbelo, and Steven D. Leach. "Abstract B112: Single-cell profiling of neoplastic cell populations in a KRAS-initiated zebrafish pancreatic cancer model." Cancer Research 84, no. 2_Supplement (January 16, 2024): B112. http://dx.doi.org/10.1158/1538-7445.panca2023-b112.
Abstract:
Abstract While the majority of human pancreatic cancers are classified as ductal adenocarcinomas, the cell of origin of these tumors remains uncertain and many tumors are comprised of dedifferentiated cell types, making it imperative to understand the full spectrum of neoplastic differentiation and how it is regulated. We have developed a new zebrafish model of pancreatic cancer driven by tissue-specific expression of UAS:mK02-KRASG12D under the regulation of a Ptf1a:Gal4/VP16 transcriptional driver. Transgenic zebrafish generate mixed tumors comprised histologically of mixed acinar and ductal elements, providing the opportunity to interrogate specific transcriptional and epigenetic modifiers responsible for regulating neoplastic pancreatic cellular differentiation. Single-cell RNA sequencing of these tumors has confirmed neoplastic cell populations expressing exclusively acinar and ductal markers, as well as distinct clusters expressing markers of both cell lineages. Screening a panel of 21 unique chromatin modifiers and chromatin readers for differential expression in these distinct cell clusters reveals hdac9b to be upregulated in the progenitor-like ductal population. Gain- and loss-of-function genetic studies will be used to determine the functional role of hdac9b in generating distinct neoplastic cell differentiation states. We are also generating pseudo-time trajectory inferences to further determine the directionality of differentiation states in these cells. By generating new insights into regulation of distinct differentiation states in pancreatic cancer, we hope that new strategies for therapeutic manipulation of neoplastic cell differentiation will emerge. Citation Format: Somer M. Matar, Britton C. Goodale, Xiaoying Liu, Annie Katanga, Nicole F. Gallien, Sandra Blazquez, Direna Alonso-Curbelo, Steven D. Leach. Single-cell profiling of neoplastic cell populations in a KRAS-initiated zebrafish pancreatic cancer model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B112.
34
Sun, Hongli, Xianwei Dai, and Bing Han. "TRIM29 as a Novel Biomarker in Pancreatic Adenocarcinoma." Disease Markers 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/317817.
Abstract:
Background and Aim. Tripartite motif-containing 29 (TRIM29) is structurally a member of the tripartite motif family of proteins and is involved in diverse human cancers. However, its role in pancreatic cancer remains unclear.Methods. The expression pattern of TRIM29 in pancreatic ductal adenocarcinoma was assessed by immunocytochemistry. Multivariate logistic regression analysis was used to investigate the association between TRIM29 and clinical characteristics.In vitroanalyses by scratch wound healing assay and invasion assays were performed using the pancreatic cancer cell lines.Results. Immunohistochemical analysis showed TRIM29 expression in pancreatic cancer tissues was significantly higher (n=186)than that in matched adjacent nontumor tissues. TRIM29 protein expression was significantly correlated with lymph node metastasis(P=0.019). Patients with positive TRIM29 expression showed both shorter overall survival and shorter recurrence-free survival than those with negative TRIM29 expression. Multivariate analysis revealed that TRIM29 was an independent factor for pancreatic cancer over survival (HR=2.180, 95% CI: 1.324–4.198,P=0.011).In vitro,TRIM29 knockdown resulted in inhibition of pancreatic cancer cell proliferation, migration, and invasion.Conclusions. Our results indicate that TRIM29 promotes tumor progression and may be a novel prognostic marker for pancreatic ductal adenocarcinoma.
35
Yamasaki, Akio, Kosuke Yanai, and Hideya Onishi. "Hypoxia and pancreatic ductal adenocarcinoma." Cancer Letters 484 (August 2020): 9–15. http://dx.doi.org/10.1016/j.canlet.2020.04.018.
36
Wang, Ya-Dong, Jia-Ding Mao, Jun-Feng Wang, and Mao-Qi Xu. "MiR-590 Suppresses Proliferation and Induces Apoptosis in Pancreatic Cancer by Targeting High Mobility Group A2." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382092814. http://dx.doi.org/10.1177/1533033820928143.
Abstract:
Background: Pancreatic ductal adenocarcinoma is a common malignancy with high morbidity. MicroRNAs have been demonstrated to be critical posttranscriptional regulators in tumorigenesis. This study aimed to investigate the effect of microRNA-590 on the proliferation and apoptosis of pancreatic ductal adenocarcinoma. Material and Methods: The expression of microRNA-590 and high mobility group AT-hook 2 were examined in clinical pancreatic ductal adenocarcinoma tissues. Pancreatic ductal adenocarcinoma cell line Capan-2 was employed and transfected with microRNA-590 mimics or inhibitor. The correlation between microRNA-590 and high mobility group AT-hook 2 was verified by luciferase reporter assay. Cell viability and apoptosis were detected by MTT and flow cytometry assay. The protein level of high mobility group AT-hook 2, AKT, p-AKT, mTOR, and phosphorylated mTOR were analyzed by Western blotting. Results: MicroRNA-590 was found to be negatively correlated with the expression of high mobility group AT-hook 2 in pancreatic ductal adenocarcinoma tissues. Further studies identified high mobility group AT-hook 2 as a direct target of microRNA-590. Moreover, overexpression of microRNA-590 downregulated expression of high mobility group AT-hook 2, reduced cell viability, and promoted cell apoptosis, while knockdown of miR-590 led to an inverse result. MicroRNA-590 also suppressed the phosphorylation of AKT and mTOR without altering total AKT and mTOR levels. Conclusion: Our study indicated that microRNA-590 negatively regulates the expression of high mobility group AT-hook 2 in clinical specimens and in vitro. MicroRNA-590 can inhibit cell proliferation and induce cell apoptosis in pancreatic ductal adenocarcinoma cells. This regulatory effect of microRNA-590 may be associated with AKT signaling pathway. Therefore, microRNA-590 has the potential to be used as a biomarker for predicting the progression of pancreatic ductal adenocarcinoma.
37
Bubin, Roman, Romans Uljanovs, and Ilze Strumfa. "Cancer Stem Cells in Pancreatic Ductal Adenocarcinoma." International Journal of Molecular Sciences 24, no. 8 (April 10, 2023): 7030. http://dx.doi.org/10.3390/ijms24087030.
Abstract:
The first discovery of cancer stem cells (CSCs) in leukaemia triggered active research on stemness in neoplastic tissues. CSCs represent a subpopulation of malignant cells, defined by unique properties: a dedifferentiated state, self-renewal, pluripotency, an inherent resistance to chemo- and radiotherapy, the presence of certain epigenetic alterations, as well as a higher tumorigenicity in comparison with the general population of cancer cells. A combination of these features highlights CSCs as a high-priority target during cancer treatment. The presence of CSCs has been confirmed in multiple malignancies, including pancreatic ductal adenocarcinoma, an entity that is well known for its dismal prognosis. As the aggressive course of pancreatic carcinoma is partly attributable to treatment resistance, CSCs could contribute to adverse outcomes. The aim of this review is to summarize the current information regarding the markers and molecular features of CSCs in pancreatic ductal adenocarcinoma and the therapeutic options to remove them.
38
Messina-Pacheco, J., and A. Gregorieff. "A57 VANISHING PANCREAS: HIPPO-MEDIATED FOCAL REPLACEMENT OF THE EXOCRINE PANCREAS WITH ADIPOSE TISSUE." Journal of the Canadian Association of Gastroenterology 6, Supplement_1 (March 1, 2023): 31–32. http://dx.doi.org/10.1093/jcag/gwac036.057.
Abstract:
Abstract Background The pancreas exhibits remarkable inherent cellular plasticity in response to injury. To prevent inflammatory injury or death, acinar cells can undergo transient acinar-to-ductal metaplasia (ADM) by suspending normal cell functions and adopting characteristics of ductal cells. However, persistent ADM in the setting of chronic pancreatitis predisposes to pancreatic cancer. Less frequently, acinar cells have also been found to undergo acinar-to-adipocyte transdifferentiation, but the mechanisms and clinical significance of this process are largely unknown. Recent studies have identified that the Hippo signaling pathway and its effectors are vital for pancreatic development and function. Purpose YAP is highly expressed in normal pancreatic ducts and transiently in acinar cells undergoing ADM, suggesting a dual role for YAP in (1) the homeostatic maintenance of pancreatic ductal cells, and (2) the regenerative response to injury in acinar cells. However, little is known about the cell type-specific effects of YAP/TAZ on pancreas homeostasis and regeneration. Method We investigated the homeostatic functions of Yap and Taz in the pancreas by conditionally ablating Yap/Taz in both acinar cells and ductal cells using the previously described CluCreERT mouse line. We also established a pancreatic ductal cell-derived organoid system. The efficiency of in vitro Cre recombinase induction was confirmed in Yapfl/fl;Tazfl/fl;CluCre-ERT;LSL-tdTomato (YTKO) ductal organoids. Result(s) We observed severe atrophy and a pancreatitis-like phenotype in the pancreata of YTKO mice following tamoxifen induction. At later time-points, YTKO pancreata were progressively remodeled – the exocrine pancreas was almost entirely replaced by adipose tissue and large hyperplastic ductal structures. We will perform further lineage tracing experiments to determine whether infiltrating adipose cells derive directly from transdifferentiating acinar cells. YTKO pancreatic ductal organoids exhibited disrupted survival and proliferation, evidenced by increased expression of cleaved Caspase3 and decreased EdU incorporation compared to vehicle-treated controls. Conclusion(s) Although some flexibility in cell fate potential is beneficial for the regenerative capacity of the pancreas, dramatic changes in cellular identity can have disastrous consequences. Overall, this study revealed that disruptions in Hippo signaling in the adult murine pancreas led to failure of regeneration and the complete remodeling of the exocrine pancreas, and has shed light on the previously uncharacterized role of Hippo signaling in acinar-to-adipocyte transdifferentiation. The potential contribution of fatty infiltration of the pancreas to the pathogenesis of diabetes mellitus and pancreatic cancer merits further exploration. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; Fonds de recherche du Quebec - Sante (FRQS) Disclosure of Interest None Declared CELLULAR & MOLECULAR GASTROENTEROLOGY
39
Goggins, Michael. "Molecular Markers of Early Pancreatic Cancer." Journal of Clinical Oncology 23, no. 20 (July 10, 2005): 4524–31. http://dx.doi.org/10.1200/jco.2005.19.711.
Abstract:
Pancreatic cancer is a deadly disease and the fourth most common cause of cancer death in the United States. Since chemotherapy and radiotherapy have thus far largely failed to significantly improve the survival of patients with pancreatic ductal adenocarcinoma, there is considerable interest in identifying better diagnostic markers of pancreatic neoplasia. Not only could better markers improve the early diagnosis of pancreatic cancer and allow more patients to undergo curative surgical resection, but also could potentially be used for patients at high risk of developing pancreatic cancer to identify precancerous lesions while they are amenable to cure. A wealth of information has recently become available about gene expression, DNA methylation, and proteomics alterations that occur in pancreatic cancers creating hope that better diagnostic markers of pancreatic cancer will be soon forthcoming.
40
Yang, Hae-Jun, Bong-Seok Song, Bo-Woong Sim, Yena Jung, Unbin Chae, Dong Gil Lee, Jae-Jin Cha, et al. "Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-RasG12D." International Journal of Molecular Sciences 21, no. 22 (November 21, 2020): 8820. http://dx.doi.org/10.3390/ijms21228820.
Abstract:
In recent decades, many studies on the treatment and prevention of pancreatic cancer have been conducted. However, pancreatic cancer remains incurable, with a high mortality rate. Although mouse models have been widely used for preclinical pancreatic cancer research, these models have many differences from humans. Therefore, large animals may be more useful for the investigation of pancreatic cancer. Pigs have recently emerged as a new model of pancreatic cancer due to their similarities to humans, but no pig pancreatic cancer cell lines have been established for use in drug screening or analysis of tumor biology. Here, we established and characterized an immortalized miniature pig pancreatic cell line derived from primary pancreatic cells and pancreatic cancer-like cells expressing K-rasG12D regulated by the human PTF1A promoter. Using this immortalized cell line, we analyzed the gene expression and phenotypes associated with cancer cell characteristics. Notably, we found that acinar-to-ductal transition was caused by K-rasG12D in the cell line constructed from acinar cells. This may constitute a good research model for the analysis of acinar-to-ductal metaplasia in human pancreatic cancer.
41
Singh, Gurkaranjot, Drew Kutcher, Rajeshwar Lally, and Vikrant Rai. "Targeting Neoantigens in Pancreatic Ductal Adenocarcinoma." Cancers 16, no. 11 (May 31, 2024): 2101. http://dx.doi.org/10.3390/cancers16112101.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is currently the third leading cause of cancer-related death in the United States after lung and colon cancer. PDAC is estimated to be the second leading cause of cancer-related death by 2030. The diagnosis at a late stage is the underlying cause for higher mortality and poor prognosis after surgery. Treatment resistance to chemotherapy and immunotherapy results in recurrence after surgery and poor prognosis. Neoantigen burden and CD8+ T-cell infiltration are associated with clinical outcomes in PDAC and paucity of neoantigen-reactive tumor-infiltrating lymphocytes may be the underlying cause for treatment resistance for immunotherapy. This suggests a need to identify additional neoantigens and therapies targeting these neoantigens to improve clinical outcomes in PDAC. In this review, we focus on describing the pathophysiology, current treatment strategies, and treatment resistance in PDAC followed by the need to target neoantigens in PDAC.
42
Mendes, Inês, and Nuno Vale. "Overcoming Microbiome-Acquired Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma." Biomedicines 12, no. 1 (January 19, 2024): 227. http://dx.doi.org/10.3390/biomedicines12010227.
Abstract:
Gastrointestinal cancers (GICs) are one of the most recurrent diseases in the world. Among all GICs, pancreatic cancer (PC) is one of the deadliest and continues to disrupt people’s lives worldwide. The most frequent pancreatic cancer type is pancreatic ductal adenocarcinoma (PDAC), representing 90 to 95% of all pancreatic malignancies. PC is one of the cancers with the worst prognoses due to its non-specific symptoms that lead to a late diagnosis, but also due to the high resistance it develops to anticancer drugs. Gemcitabine is a standard treatment option for PDAC, however, resistance to this anticancer drug develops very fast. The microbiome was recently classified as a cancer hallmark and has emerged in several studies detailing how it promotes drug resistance. However, this area of study still has seen very little development, and more answers will help in developing personalized medicine. PC is one of the cancers with the highest mortality rates; therefore, it is crucial to explore how the microbiome may mold the response to reference drugs used in PDAC, such as gemcitabine. In this article, we provide a review of what has already been investigated regarding the impact that the microbiome has on the development of PDAC in terms of its effect on the gemcitabine pathway, which may influence the response to gemcitabine. Therapeutic advances in this type of GIC could bring innovative solutions and more effective therapeutic strategies for other types of GIC, such as colorectal cancer (CRC), due to its close relation with the microbiome.
43
Cheng, Xianliang, Gang Zhao, and Yunqi Zhao. "Combination Immunotherapy Approaches for Pancreatic Cancer Treatment." Canadian Journal of Gastroenterology and Hepatology 2018 (2018): 1–7. http://dx.doi.org/10.1155/2018/6240467.
Abstract:
Pancreatic ductal adenocarcinoma is a lethal malignant disease with a very low medium survival. Currently, metastatic pancreatic cancer poorly responds to conventional treatments and exhibits an acute resistance to most chemotherapy. Few approaches have been shown to be effective for metastatic pancreatic cancer treatment. Novel therapeutic approaches to treat patients with pancreatic adenocarcinoma are in great demand. Last decades, immunotherapies have been evaluated in clinical trials and received great success in many types of cancers. However, it has very limited success in treating pancreatic cancer. As pancreatic cancer poorly responds to many single immunotherapeutic agents, combination immunotherapy was introduced to improve efficacy. The combination therapies hold great promise for enhancing immune responses to achieve better therapeutic effects. This review summarizes the existing and potential combination immunotherapies for the treatment of pancreatic cancer.
44
Ghanaatgar-Kasbi, Sadaf, Shadi Khorrami, Amir Avan, Seyed A. Aledavoud, and Gordon A. Ferns. "Targeting the C-MET/HGF Signaling Pathway in Pancreatic Ductal Adenocarcinoma." Current Pharmaceutical Design 24, no. 39 (March 14, 2019): 4619–25. http://dx.doi.org/10.2174/1381612825666190110145855.
Abstract:
The c-mesenchymal-epithelial transition factor (c-MET) is involved in the tumorigenesis of various cancers. HGF/Met inhibitors are now attracting considerable interest due to their anti-tumor activity in multiple malignancies such as pancreatic cancer. It is likely that within the next few years, HGF/Met inhibitors will become a crucial component for cancer management. In this review, we summarize the role of HGF/Met pathway in the pathogenesis of pancreatic cancer, with particular emphasize on HGF/Met inhibitors in the clinical setting, including Cabozantinib (XL184, BMS-907351), Crizotinib (PF-02341066), MK-2461, Merestinib (LY2801653), Tivantinib (ARQ197), SU11274, Onartuzumab (MetMab), Emibetuzumab (LY2875358), Ficlatuzumab (AV- 299), Rilotumumab (AMG 102), and NK4 in pancreatic cancer.
45
Chouari, Tarak, Francesca La Costa, Nabeel Merali, Maria-Danae Jessel, Shivan Sivakumar, Nicola Annels, and Adam Frampton. "Advances in Immunotherapeutics in Pancreatic Ductal Adenocarcinoma." Cancers 15, no. 17 (August 25, 2023): 4265. http://dx.doi.org/10.3390/cancers15174265.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) accounts for up to 95% of all pancreatic cancer cases and is the seventh-leading cause of cancer death. Poor prognosis is a result of late presentation, a lack of screening tests and the fact some patients develop resistance to chemotherapy and radiotherapy. Novel therapies like immunotherapeutics have been of recent interest in pancreatic cancer. However, this field remains in its infancy with much to unravel. Immunotherapy and other targeted therapies have yet to yield significant progress in treating PDAC, primarily due to our limited understanding of the disease immune mechanisms and its intricate interactions with the tumour microenvironment (TME). In this review we provide an overview of current novel immunotherapies which have been studied in the field of pancreatic cancer. We discuss their mechanisms, evidence available in pancreatic cancer as well as the limitations of such therapies. We showcase the potential role of combining novel therapies in PDAC, postulate their potential clinical implications and the hurdles associated with their use in PDAC. Therapies discussed with include programmed death checkpoint inhibitors, Cytotoxic T-lymphocyte-associated protein 4, Chimeric Antigen Receptor-T cell therapy, oncolytic viral therapy and vaccine therapies including KRAS vaccines, Telomerase vaccines, Gastrin Vaccines, Survivin-targeting vaccines, Heat-shock protein (HSP) peptide complex-based vaccines, MUC-1 targeting vaccines, Listeria based vaccines and Dendritic cell-based vaccines.
46
Arshad, Tariq. "A novel RAS inhibitor for pancreatic ductal adenocarcinoma." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e16263-e16263. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16263.
Abstract:
e16263 Background: Pancreatic cancer has a dismal survival rate and no good therapeutic options. Of all types of cancer, it is Pancreatic cancer that is most closely associated with activating mutations in the RAS oncoprotein. Approximately 90% of pancreatic adenocarcinomas carry point mutations activating RAS. Ras directed targeted therapy is the obvious approach to enhancing treatment options for the disease. There is now an FDA approved targeted RAS therapeutic specific to the RAS12C mutant form. However, this particular mutation is uncommon in Pancreatic cancer. Therefore, drugs which act more broadly on RAS are required. There are currently no approved pan-RAS inhibitors. We have developed a small molecule pan-RAS inhibitor which binds directly to all forms of RAS. It acts to block the ability of RAS and to bind and signal through its effectors. It is active in vitro and in vivo against multiple models of pancreatic cancer. Methods: In silico screening of a virtual compound library was performed to identify an initial candidate inhibitor. Iterative rounds of Medicinal Chemistry informed by structural modeling and bioassay in 3D vs 2D growth assays were performed to identify an enhanced activity derivative. Target binding was confirmed by Microscale Thermophoresis and NMR. RAS/RAF complex status was measured by co-immunoprecipitation of the endogenous proteins. Ras signaling was assayed by Western analysis of Phospho-ERK and RAL-GTP pull down assays. In vitro activity was measured using 3D soft agar assays. In vivo activity was measured by ip or po administration against pancreatic tumor cell line xenografts and pdx systems. Results: The current lead, designated RAS-F binds all three main isoforms of RAS at low uM kd and modulates the RAS effector domain in NMR studies. It suppresses RAS signaling pathways in transient assays and suppresses pancreatic tumor cell growth in soft agar with IC50s below 500nM. It suppresses xenograft development of human and mouse RAS driven pancreatic tumor cell lines and reduces the growth of a pancreatic cancer pdx. Conclusions: We have developed a pre-clinical pan-RAS inhibitor that is active in vitro and in vivo against pancreatic cancer models. Funding: NIH 5U01HL127518-03, Kentucky Lung Cancer Research Program (GJC), Qualigen Therapeutics LLC.
47
Wei, Kongyuan, and Thilo Hackert. "Surgical Treatment of Pancreatic Ductal Adenocarcinoma." Cancers 13, no. 8 (April 20, 2021): 1971. http://dx.doi.org/10.3390/cancers13081971.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) represents an aggressive tumor of the digestive system with still low five-year survival of less than 10%. Although there are improvements for multimodal therapy of PDAC, surgery still remains the effective way to treat the disease. Combined with adjuvant and/or neoadjuvant treatment, pancreatic surgery is able to enhance the five-year survival up to around 20%. However, pancreatic resection is always associated with a high risk of complications and regarded as one of the most complex fields in abdominal surgery. This review gives a summary on the surgical treatment for PDAC based on the current literature with a special focus on resection techniques.
48
Karamitopoulou, Eva. "Molecular Pathology of Pancreatic Cancer." Cancers 14, no. 6 (March 16, 2022): 1523. http://dx.doi.org/10.3390/cancers14061523.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a biologically aggressive malignancy showing a remarkable resistance to existing therapies and is often diagnosed at an advanced stage, leaving only about 15–20% of patients with an option for surgical resection [...]
49
Kang, Chang Moo, and Woo Jung Lee. "Is Laparoscopic Pancreaticoduodenectomy Feasible for Pancreatic Ductal Adenocarcinoma?" Cancers 12, no. 11 (November 18, 2020): 3430. http://dx.doi.org/10.3390/cancers12113430.
Abstract:
Margin-negative radical pancreatectomy is the essential condition to obtain long-term survival of patients with pancreatic cancer. With the investigation for early diagnosis, introduction of potent chemotherapeutic agents, application of neoadjuvnat chemotherapy, advancement of open and laparoscopic surgical techniques, mature perioperative management, and patients’ improved general conditions, survival of the resected pancreatic cancer is expected to be further improved. According to the literatures, laparoscopic pancreaticoduodenectomy (LPD) is also thought to be good alternative strategy in managing well-selected resectable pancreatic cancer. LPD with combined vascular resection is also feasible, but only expert surgeons should handle these challenging cases. LPD for pancreatic cancer should be determined based on surgeons’ proficiency to fulfil the goals of the patient’s safety and oncologic principles.
50
McAllister, Josiah, Saber Amin, and Chi Lin. "Association of facility type with overall survival in patients with nonsurgically managed pancreatic cancer." Future Oncology 18, no. 10 (March 2022): 1273–84. http://dx.doi.org/10.2217/fon-2021-0986.
Abstract:
Aim: To investigate the association between receiving treatment at academic centers and overall survival in pancreatic ductal adenocarcinoma patients who do not receive definitive surgery of the pancreatic tumor. Methods: Using the National Cancer Database, patients who were diagnosed with pancreatic ductal adenocarcinoma between 2004 to 2016 were identified. Results: Of 262,209 patients, 101,003 (38.5%) received treatment at academic centers. In the multivariable Cox regression analysis, patients who received treatment at a nonacademic facility had significantly worse overall survival compared with patients who were treated at an academic center (hazard ratio: 1.279; 95% CI: 1.268–1.290; p = 0.001). Conclusion: Compared with treatment at academic centers, treatment at nonacademic centers was associated with significantly worse overall survival in patients with nonsurgically managed pancreatic ductal adenocarcinoma.