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Chawki S, Hamet G, Brun A, Lourenco N, Bouchaud O, Bottero J, Sellier P, Molina JM. Brief Report: Pancreatic Cancer in People With HIV: A Case-Control Study. J Acquir Immune Defic Syndr 2025; 98:321-325. [PMID: 39702512 DOI: 10.1097/qai.0000000000003585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 10/17/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND We aimed to estimate the incidence and to assess the risk factors associated with pancreatic cancer (PC) in people with HIV (PWH). SETTING We used electronic medical record data from 2009 to 2020 available in the COREVIH Ile-de-France-Est database of PWH treated in Paris public hospitals. METHODS We analyzed data on patient demographics, treatment history, and immunovirologic status. A case-control study was designed; each case (PWH and PC) was matched on age, gender, and duration of HIV infection to 4 controls (PWH without PC). RESULTS Twenty-four cases were identified from the database, with an incidence of PC estimated at 28 cases (95% confidence interval: 19 to 43) per 100,000 person-years. The median age was 57 years [interquartile range (IQR) 51-68] at cancer diagnosis. Twenty-one cases (88%) were male. The median CD4 + T-cell count at PC diagnosis was 587/mm 3 (IQR 317-748), and the nadir CD4 + T-cell count was 194 (IQR 98-380). Twenty cases (91%) had a suppressed HIV replication at PC diagnosis. Twelve patients (50%) had metastasis on diagnosis. The median time to death after cancer diagnosis was 11 months (IQR 1-19). Twenty-two cases were matched with 88 controls. There were no statistically significant risk factors of PC identified in our analysis. CONCLUSION PC remains rare in PWH and is associated with a severe prognosis at a relatively young age. Further studies are needed to identify risk factors associated with PC development in PWH.
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Affiliation(s)
- Sylvain Chawki
- UFR de Médecine, Université Paris Cité, Paris, France
- Département de Maladies Infectieuses, Hôpital Saint Louis et Hôpital Lariboisière, Assistance Publique Hôpitaux de Paris, Paris, France
- Unité U-944, INSERM, Paris, France
| | - Gwenn Hamet
- COREVIH Ile de France Est, Hôpital Saint Louis, Paris, France
| | - Alexandre Brun
- COREVIH Ile de France Est, Hôpital Saint Louis, Paris, France
| | - Nelson Lourenco
- UFR de Médecine, Université Paris Cité, Paris, France
- Service de Gastro-Entérologie, Hôpital Saint Louis, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Olivier Bouchaud
- Service de Maladies Infectieuses, Hôpital Avicenne, Assistance Publique Hôpitaux de Paris, Paris, France ; and
| | - Julie Bottero
- Service de Maladies Infectieuses, Hôpital Jean Verdier, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Pierre Sellier
- UFR de Médecine, Université Paris Cité, Paris, France
- Département de Maladies Infectieuses, Hôpital Saint Louis et Hôpital Lariboisière, Assistance Publique Hôpitaux de Paris, Paris, France
| | - Jean-Michel Molina
- UFR de Médecine, Université Paris Cité, Paris, France
- Département de Maladies Infectieuses, Hôpital Saint Louis et Hôpital Lariboisière, Assistance Publique Hôpitaux de Paris, Paris, France
- Unité U-944, INSERM, Paris, France
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Wik SL, Tian W, Zhong CC, Sawhney A, Gao M, Yu Q, Xue F, Chan SC, Chow SH, Adebisi YA, Yuan J, Lucero‐Prisno DE, Wong MCS, Huang J. Distribution, Risk Factors and Epidemiological Trends of Pancreatic Cancer Across Countries' Income Levels: A Comprehensive Analysis. Cancer Rep (Hoboken) 2025; 8:e70154. [PMID: 39957387 PMCID: PMC11830997 DOI: 10.1002/cnr2.70154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 01/03/2025] [Accepted: 01/31/2025] [Indexed: 02/18/2025] Open
Abstract
BACKGROUND Globally, pancreatic cancer poses a significant concern for public health. AIMS The objective of this study was to assess the burden of pancreatic cancer on varying income levels. METHODS AND RESULTS Data from the Global Burden of Disease Study (GBD) 2021 and Gross Domestic Product Per Capita data were utilised in this study. All countries were categorised into four groups based on their income levels. Age-standardised incidence, mortality and disability-adjusted life years (DALYs) rates were the primary parameters to analyse the burden of pancreatic cancer. The associations between pancreatic cancer burden and countries' economic levels were analysed with linear regression models. High-income-level countries generally had a higher burden compared to other income levels in 2021. Greenland had the highest rate of age-standardised DALYs at 374.93 per 100 000, followed by Uruguay (297.06) and Monaco (290.87). A higher gross domestic product (GDP) per capita was linked to a higher age-standardised incidence (β = 0.77, 95% CI = 0.63, 0.90, p < 0.001), mortality (β = 0.72, 95% CI = 0.59, 0.86, p < 0.001) and DALYs (β = 14.59, 95% CI = 11.38, 17.80, p < 0.001). From 1990 to 2021, the pancreatic cancer burden increased across all income levels, with the most pronounced rise seen in lower-middle-income countries. Smoking-related age-standardised DALYs have decreased since 1990. However, there was a notable increase in males in upper-middle-income countries during the same period. CONCLUSION In conclusion, the pancreatic cancer burden has been increasing globally. The burden of pancreatic cancer varies significantly among countries with different income levels. Effective preventions are needed to control the burden of pancreatic cancer.
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Affiliation(s)
- Sofia Laila Wik
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
- Karolinska InstituteSolnaSweden
| | - Wenxin Tian
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
| | - Claire Chenwen Zhong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
- Centre for Health Education and Health Promotion, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
| | - Apurva Sawhney
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
| | - Mingjun Gao
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
- Adam Smith Business School, College of Social Science, University of GlasgowGlasgowUK
| | - Qinyao Yu
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
- Jinan University‐University of Birmingham Joint Institute, Jinan UniversityGuangzhouChina
- School of Mathematics, College of Engineering and Physical Sciences, University of BirminghamBirminghamUK
| | - Fanyu Xue
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
- Faculty of Health Sciences, University of OttawaOttawaCanada
| | - Sze Chai Chan
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
| | - Shui Hang Chow
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
| | | | - Jinqiu Yuan
- Clinical Research Center, Big Data Center, the Seventh Affiliated Hospital, Sun Yat‐Sen UniversityShenzhenGuangdongChina
| | - Don Eliseo Lucero‐Prisno
- Department of Global Health and DevelopmentLondon School of Hygiene and Tropical MedicineLondonUK
| | - Martin C. S. Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
- Centre for Health Education and Health Promotion, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
| | - Junjie Huang
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
- Centre for Health Education and Health Promotion, Faculty of Medicine, the Chinese University of Hong KongHong Kong SARChina
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Baloyan E, Zohrabyan D, Safaryan L, Avagyan A, Harutyunyan L, Bardakhchyan V, Arakelyan J, Sargsyan A, Harutyunyan M, Mailyan M, Tamamyan G, Bardakhchyan S. Treatment and Outcomes of Pancreatic Cancer in Armenia: A Retrospective Study From Resource-Limited Settings. JCO Glob Oncol 2025; 11:e2400217. [PMID: 39883892 DOI: 10.1200/go.24.00217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 10/27/2024] [Accepted: 12/02/2024] [Indexed: 02/01/2025] Open
Abstract
PURPOSE Pancreatic cancer is one of the deadliest cancers in the world. In Armenia, it is 12th by incidence. The aim of this study is to evaluate treatment and outcomes of pancreatic cancer in Armenia during the past 12 years. METHODS This is a retrospective study with data from three oncology centers in Armenia: "Muratsan" Hospital of Yerevan State Medical University, Mikaelyan institute of surgery, and Yeolyan Hematology and Oncology Center. The information was obtained from the medical records of the patients with pancreatic cancer treated at these centers during January 1, 2010-January 1, 2022. Log-rank test and Kaplan-Meier curves were used for survival analysis. Cox regression analysis was performed for identification of main prognostic factors. RESULTS Of 70 patients involved in the final analysis, 45.7% was female. The median age at diagnosis was 63 years. The median follow-up time was 11 months (range, 2-146). A total of 11.4% of patients had stage I-II, 27.1% had stage III, and 60% had stage IV disease. The main independent prognostic factor for overall survival (OS) was the TNM stage, whereas grade of the tumor was not significant. The median OS was 11 months (range, 2-169 months): In stages I-III, patients who had surgery (44.4%) lived significantly longer than those who did not (20 v 11 months; P = .008). Main chemotherapy regimens were 5-fluorouracil, oxaliplatin, folinic acid and irinotecan (41.4%) and gemcitabine plus capecitabine (38.6%). No significant survival difference was found between these groups (13 v 11 months; P = .162). CONCLUSION Survival of patients with pancreatic cancer in Armenia is dismal, not exceeding 1 year. Hopefully, further research in the field and new treatment modalities will improve the situation.
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Affiliation(s)
- Elen Baloyan
- Department of Oncology, Yerevan State Medical University, Yerevan, Armenia
- Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
- Immune Oncology Research Institute, Yerevan, Armenia
| | - Davit Zohrabyan
- Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
| | - Liana Safaryan
- Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
| | - Armen Avagyan
- Department of Oncology, Yerevan State Medical University, Yerevan, Armenia
- Department of Chemotherapy, Mikaelyan Institute of Surgery, Yerevan, Armenia
| | - Lilit Harutyunyan
- Department of Oncology, Yerevan State Medical University, Yerevan, Armenia
- Department of Chemotherapy, Mikaelyan Institute of Surgery, Yerevan, Armenia
| | | | - Jemma Arakelyan
- Department of Oncology, Yerevan State Medical University, Yerevan, Armenia
- Immune Oncology Research Institute, Yerevan, Armenia
- City University of Hong Kong, Kowloon, Hong Kong
| | - Amalya Sargsyan
- Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
- Immune Oncology Research Institute, Yerevan, Armenia
| | - Martin Harutyunyan
- Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
| | - Mariam Mailyan
- Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
| | - Gevorg Tamamyan
- Department of Oncology, Yerevan State Medical University, Yerevan, Armenia
- Immune Oncology Research Institute, Yerevan, Armenia
- Pediatric Cancer and Blood Disorders Center of Armenia, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
| | - Samvel Bardakhchyan
- Adults Solid Tumors Chemotherapy Department, Yeolyan Hematology and Oncology Center, Yerevan, Armenia
- Immune Oncology Research Institute, Yerevan, Armenia
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Harne PS, Harne V, Wray C, Thosani N. Endoscopic innovations in diagnosis and management of pancreatic cancer: a narrative review and future directions. Therap Adv Gastroenterol 2024; 17:17562848241297434. [PMID: 39664230 PMCID: PMC11632891 DOI: 10.1177/17562848241297434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Accepted: 10/15/2024] [Indexed: 12/13/2024] Open
Abstract
Pancreatic cancer serves as the third leading cause of cancer-associated morbidity and mortality in the United States, with a 5-year survival rate of only 12% with an expected increase in incidence and mortality in the coming years. Pancreatic ductal adenocarcinomas constitute most pancreatic malignancies. Certain genetic syndromes, including Lynch syndrome, hereditary breast and ovarian cancer syndrome, hereditary pancreatitis, familial adenomatous polyposis, Peutz-Jeghers syndrome, familial pancreatic cancer mutation, and ataxia telangiectasia, confer a significantly higher risk. Screening for pancreatic malignancies currently targets patients with germline mutations or those with significant family history. Screening the general population is not currently viable owing to overall low incidence and lack of specific tests. Endoscopic ultrasound (EUS) and its applied advances are increasingly being used for surveillance, diagnosis, and management of pancreatic malignancies and have now become an indispensable tool in their management. For patients with risk factors, EUS in combination with magnetic resonance imaging/magnetic resonance cholangiopancreatography is used for screening. The role of endoscopic modalities has been expanding with the increased utilization of endoscopic retrograde cholangiopancreatography, EUS-directed therapies include EUS-guided fine-needle aspiration and EUS-fine-needle biopsy (FNB). EUS combined with FNB has the highest specificity and sensitivity for detecting pancreatic cancer amongst available modalities. Studies also recognize that artificial intelligence assisted EUS in the early detection of pancreatic cancer. At the same time, surgical resection has been historically considered the only curative treatment for pancreatic cancer, over 80% of patients present with unresectable disease. We also discuss EUS-guided therapies of physicochemicals (radiofrequency ablation, brachytherapy, and intratumor chemotherapy), biological agents (gene therapies and oncolytic viruses), and immunotherapy. We aim to perform a detailed review of the current burden, risk factors, role of screening, diagnosis, and endoscopic advances in the treatment modalities available for pancreatic cancer.
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Affiliation(s)
- Prateek Suresh Harne
- Division of Gastroenterology, Allegheny Health Network, Pittsburgh, PA 15212, USA
| | - Vaishali Harne
- Division of Pediatric Gastroenterology, The University of Texas
- Health Science Center and McGovern School of Medicine, Houston, TX, USA
| | - Curtis Wray
- Department of Surgery, The University of Texas Health Science Center and McGovern School of Medicine, Houston, TX, USA
| | - Nirav Thosani
- Department of Surgery and Interventional Gastroenterology, The University of Texas
- Health Science Center and McGovern School of Medicine, Houston, TX, USA
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Akbar Z, Ahmad MS. In vitro, in silico and crystallographic-based identification of serine protease inhibitors. Nat Prod Res 2024:1-7. [PMID: 39520718 DOI: 10.1080/14786419.2024.2425793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 10/08/2024] [Accepted: 10/27/2024] [Indexed: 11/16/2024]
Abstract
Serine proteases are involved in various ailments, including pancreatitis, and colon cancer. Based on substrate recognition serine proteases are classified into different groups. Trypsin and trypsin-like serine proteases are among most studied group of serine proteases. Trypsin is among the chief hydrolysing enzyme involved in the pathogenesis of pancreatitis. Its inhibition can help to manage the disease. Herein, we investigated the trypsin inhibitory effect of some arginine-based small molecules, through in vitro, in silico, and crystallographic methods. Compounds 1-3 were evaluated against bovine pancreatic trypsin (BPT). Compound 1 was found to be active against trypsin with IC50 value of 247.98 ± 2.44 μM. Molecular docking studies were used to investigate the binding energy and binding conformation of inhibitor. All three compounds were subjected to crystallisation with trypsin. Compounds 1-2 were successfully crystallised with BPT The crystal structures of trypsin in complexed with compounds 1, and 2 were determined at 2.30 and 2.50 Å resolution, respectively. Both molecules showed their binding affinity with the active site residues of trypsin. This study will provide insight into the binding mechanism of E-64 and arginine and might be useful in designing effective inhibitors of serine proteases.
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Affiliation(s)
- Zeeshan Akbar
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
| | - Malik Shoaib Ahmad
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan
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Fazli HR, Mohamadkhani A, Godarzi HR, Pourshams A, Jafarinia M. Protective Effect of Dehydroepiandrosterone (DHEA) On Pancreatic Cancer Through C-Reactive Protein (CRP) Production Inhibition. Rep Biochem Mol Biol 2024; 13:174-183. [PMID: 39995642 PMCID: PMC11847585 DOI: 10.61186/rbmb.13.2.174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2024] [Accepted: 11/18/2024] [Indexed: 02/26/2025]
Abstract
Background The relationship between inflammation and pancreatic cancer (PC) has been previously explored, but the precise role of inflammatory markers in disease risk and progression remains unclear. This case-control study aimed to investigate the association between C-reactive protein (CRP), systemic inflammation marker, and dehydroepiandrosterone (DHEA), systemic cytokines regulator, in relation to pancreatic cancer risk. Methods Serum levels of DHEA and CRP were measured in 50 pancreatic cancer patients and 50 age and sex-matched healthy controls using enzyme-linked immunosorbent assay (ELISA) and latex particle-enhanced immunoturbidimetric assay, respectively. Data analysis was performed using STATA software. Results The results showed that while DHEA levels were lower in pancreatic cancer patients compared to healthy subjects, the difference did not reach statistical significance (p=0.74). Conversely, CRP levels were significantly elevated in pancreatic cancer patients (p=0.001). Subgroup analysis based on sex revealed significant differences in DHEA and CRP concentrations between male patients and controls. Furthermore, a marginally significant inverse relationship was observed between log CRP and DHEA levels in pancreatic cancer patients (p=0.054). Risk assessment analysis, adjusted for age and sex, demonstrated an increased risk of pancreatic cancer associated with elevated log CRP levels (p=0.001; OR=1.671), and a decreased risk associated with higher DHEA levels (p=0.024, OR=0.479). Conclusions our findings highlight the direct association of pancreatic cancer with CRP and the inverse relationship with DHEA, suggesting the involvement of inflammation in pancreatic cancer development. Moreover, the observed inverse correlation between CRP and DHEA among pancreatic cancer patients suggests a potential inhibitory effect of DHEA on CRP levels.
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Affiliation(s)
- Hamid Reza Fazli
- Department of Genetics, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran.
| | - Ashraf Mohamadkhani
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hamed Reza Godarzi
- Department of Genetics, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran.
| | - Akram Pourshams
- Digestive Oncology Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mojtaba Jafarinia
- Department of Biology, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran.
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Kouchaki H, Kamyab P, Darbeheshti F, Gharezade A, Fouladseresht H, Tabrizi R. miR-939, as an important regulator in various cancers pathogenesis, has diagnostic, prognostic, and therapeutic values: a review. J Egypt Natl Canc Inst 2024; 36:16. [PMID: 38679648 DOI: 10.1186/s43046-024-00220-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 04/06/2024] [Indexed: 05/01/2024] Open
Abstract
BACKGROUND MicroRNAs (miRNAs or miRs) are highly conserved non-coding RNAs with a short length (18-24 nucleotides) that directly bind to a complementary sequence within 3'-untranslated regions of their target mRNAs and regulate gene expression, post-transcriptionally. They play crucial roles in diverse biological processes, including cell proliferation, apoptosis, and differentiation. In the context of cancer, miRNAs are key regulators of growth, angiogenesis, metastasis, and drug resistance. MAIN BODY This review primarily focuses on miR-939 and its expanding roles and target genes in cancer pathogenesis. It compiles findings from various investigations. MiRNAs, due to their dysregulated expression in tumor environments, hold potential as cancer biomarkers. Several studies have highlighted the dysregulation of miR-939 expression in human cancers. CONCLUSION Our study highlights the potential of miR-939 as a valuable target in cancer diagnosis, prognosis, and treatment. The aberrant expression of miR-939, along with other miRNAs, underscores their significance in advancing our understanding of cancer biology and their promise in personalized cancer care.
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Affiliation(s)
- Hosein Kouchaki
- Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Parnia Kamyab
- USERN Office, Fasa University of Medical Sciences, Fasa, Iran
| | - Farzaneh Darbeheshti
- Department of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - Arezou Gharezade
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hamed Fouladseresht
- Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Reza Tabrizi
- Clinical Research Development Unit, Valiasr Hospital, Fasa University of Medical Sciences, Fasa, Iran.
- Noncommunicable Diseases Research Center, Fasa University of Medical Science, Fasa, Iran.
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Reshkin SJ, Cardone RA, Koltai T. Genetic Signature of Human Pancreatic Cancer and Personalized Targeting. Cells 2024; 13:602. [PMID: 38607041 PMCID: PMC11011857 DOI: 10.3390/cells13070602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/27/2024] [Accepted: 03/27/2024] [Indexed: 04/13/2024] Open
Abstract
Pancreatic cancer is a highly lethal disease with a 5-year survival rate of around 11-12%. Surgery, being the treatment of choice, is only possible in 20% of symptomatic patients. The main reason is that when it becomes symptomatic, IT IS the tumor is usually locally advanced and/or has metastasized to distant organs; thus, early diagnosis is infrequent. The lack of specific early symptoms is an important cause of late diagnosis. Unfortunately, diagnostic tumor markers become positive at a late stage, and there is a lack of early-stage markers. Surgical and non-surgical cases are treated with neoadjuvant and/or adjuvant chemotherapy, and the results are usually poor. However, personalized targeted therapy directed against tumor drivers may improve this situation. Until recently, many pancreatic tumor driver genes/proteins were considered untargetable. Chemical and physical characteristics of mutated KRAS are a formidable challenge to overcome. This situation is slowly changing. For the first time, there are candidate drugs that can target the main driver gene of pancreatic cancer: KRAS. Indeed, KRAS inhibition has been clinically achieved in lung cancer and, at the pre-clinical level, in pancreatic cancer as well. This will probably change the very poor outlook for this disease. This paper reviews the genetic characteristics of sporadic and hereditary predisposition to pancreatic cancer and the possibilities of a personalized treatment according to the genetic signature.
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Affiliation(s)
- Stephan J. Reshkin
- Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy;
| | - Rosa Angela Cardone
- Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, 70125 Bari, Italy;
| | - Tomas Koltai
- Oncomed, Via Pier Capponi 6, 50132 Florence, Italy
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Adrees S, Imtiaz A, Yaseen A, Irfan Fareed M, Anwar W, Ashraf A, Shabbir RMK, Andlib S, Hussain M, Tariq A, Mateen RM, Saqib MAN, Parveen R. In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma. J Biomol Struct Dyn 2024:1-17. [PMID: 38469816 DOI: 10.1080/07391102.2024.2318484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2023] [Accepted: 02/07/2024] [Indexed: 03/13/2024]
Abstract
NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was -6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with -9.2 kcal/mol of NEK7 and -7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA).
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Affiliation(s)
- Safa Adrees
- Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Anam Imtiaz
- Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Aiman Yaseen
- Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Muhammad Irfan Fareed
- Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Waqar Anwar
- Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan
| | - Asma Ashraf
- Department of Zoology, Division of science and Technology, University of Education, Lahore, Pakistan
| | | | - Shaista Andlib
- Department of Microbiology, Faculty of Biological Sciences, Quaid-e-Azam University, Islamabad, Pakistan
| | - Mureed Hussain
- Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan
- Center for Regenerative Medicine and Stem Cell Research, Agha Khan University, Karachi, Pakistan
| | - Asma Tariq
- School of Biochemistry and Biotechnology, University of the Punjab, Lahore, Pakistan
| | - Rana Muhammad Mateen
- Department of Life sciences, School of Science, University of Management and Technology, Lahore, Pakistan
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | | | - Rukhsana Parveen
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
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Li S, Jiang F, Chen F, Deng Y, Huang H. Silencing long noncoding RNA LINC01133 suppresses pancreatic cancer through regulation of microRNA-1299-dependent IGF2BP3. J Biochem Mol Toxicol 2024; 38:e23534. [PMID: 37718503 DOI: 10.1002/jbt.23534] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 05/26/2023] [Accepted: 09/01/2023] [Indexed: 09/19/2023]
Abstract
The deregulation of long noncoding RNAs (lncRNAs) holds great potential in the treatment of multiple cancers, including pancreatic cancer (PC). However, the specific molecular mechanisms by which LINC01133 contributes to pancreatic cancer remain unknown. Subsequent to bioinformatics analysis, we predicted and analyzed differentially expressed lncRNAs, microRNAs, and genes in pancreatic cancer. We determined the expression patterns of LINC01133, miR-1299, and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in pancreatic cancer cells, and validated their interactions through luciferase reporter and RNA immunoprecipitation assays. We implemented loss-of-function and gain-of-function experiments for LINC01133, miR-1299, and IGF2BP3 to assay their potential effects on pancreatic cancer cell functions. We observed high expression of LINC01133 and IGF2BP3, but low expression of miR-1299, in pancreatic cancer cells. Furthermore, we found that LINC01133 enhances IGF2BP3 through binding with miR-1299. Silencing LINC01133 or IGF2BP3 and/or overexpressing miR-1299 limited pancreatic cancer cell proliferation, invasion, epithelial-mesenchymal transition, and suppressed tumorigenic abilities in mice lacking T cells (nude mice). Overall, our findings identified that silencing LINC01133 downregulates IGF2BP3 by upregulating miR-1299 expression, ultimately leading to the prevention of pancreatic cancer.
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Affiliation(s)
- Sumei Li
- Clinical Laboratory, Huadu District People's Hospital of Guangzhou, Guangzhou, People's Republic of China
| | - Fengru Jiang
- Clinical Laboratory, Huadu District People's Hospital of Guangzhou, Guangzhou, People's Republic of China
| | - Feiyu Chen
- Clinical Laboratory, Huadu District People's Hospital of Guangzhou, Guangzhou, People's Republic of China
| | - Yinzhao Deng
- Clinical Laboratory, Huadu District People's Hospital of Guangzhou, Guangzhou, People's Republic of China
| | - Haiying Huang
- Clinical Laboratory, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People's Republic of China
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11
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Xiang X, Chen X, He Y, Wang Y, Xia W, Ye S, Wang S, Xiao Y, Li Q, Wang X, Luo W, Li J. Pancreatic cancer challenge in 52 Asian countries: age-centric insights and the role of modifiable risk factors (1990-2019). Front Oncol 2023; 13:1271370. [PMID: 37849795 PMCID: PMC10577443 DOI: 10.3389/fonc.2023.1271370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Accepted: 09/19/2023] [Indexed: 10/19/2023] Open
Abstract
Background Pancreatic cancer is renowned for its elevated incidence and mortality rates on a global scale. The disease burden of pancreatic cancer is anticipated to increase, particularly in Asia, due to its vast and rapidly aging population. Methods Data from the Global Burden of Disease 2019 were analyzed for pancreatic cancer burden across 52 countries in Asia, including the incidence, mortality, and disability-adjusted life years (DALY) for pancreatic cancer, with a focus on risk factors such as high body mass index (BMI), elevated fasting plasma glucose, and smoking. We applied the Estimated Annual Percentage Change, the Age-Period-Cohort model, and decomposition analysis to evaluate incidence trends and effects. Results From 1990 to 2019, both incidence and mortality rates of pancreatic cancer in Asia significantly increased, with an average annual standardized incidence rate change of 1.73%. Males consistently exhibited higher rates than females, with smoking as a key risk factor. Central Asia reported the highest rates, and South Asia the lowest. The incidence rose with age, peaking in those aged 70~74. The disease burden increased in all age groups, particularly in populations aged 55 and above, representing 84.41% of total cases in 2019, up from 79.01% in 1990. Pancreatic cancer ranked the fifth in incidence among six major gastrointestinal tumors but presented a significant growth rate of mortality and DALY. Conclusion With the growing, aging population in Asia, the pancreatic cancer burden is projected to escalate, bringing a significant public health challenge. Hence, comprehensive public health strategies emphasizing early detection, risk modification, and optimized treatment of pancreatic cancer are imperative.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Weiwei Luo
- *Correspondence: Weiwei Luo, ; Jingbo Li,
| | - Jingbo Li
- *Correspondence: Weiwei Luo, ; Jingbo Li,
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12
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Tanaka T, Lynch CF, Yu KJ, Morawski BM, Hsieh MC, Alverson G, Austin AA, Zeng Y, Engels EA. Pancreatic cancer among solid organ transplant recipients in the United States. J Cancer Res Clin Oncol 2023; 149:3325-3333. [PMID: 35932302 DOI: 10.1007/s00432-022-04227-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/18/2022] [Indexed: 12/01/2022]
Abstract
INTRODUCTION Pancreatic cancer (PC) in solid organ transplant (SOT) recipients is not well studied. Some PC cases may be incidentally detected during hepatobiliary imaging. METHODS We evaluated PC among 374,106 SOT recipients during 1995-2017 in the United States using linked data from the national transplant registry and multiple state/regional cancer registries. Standardized incidence ratios (SIRs) were used to compare PC risk in recipients to the general population. We used multivariate Poisson regression to identify independent risk factors for PC. We assessed survival after PC diagnosis using Kaplan-Meier curves and log-rank tests. RESULTS SOT recipients had elevated incidence for PC compared with the general population (SIR 1.40, 95% CI 1.29-1.52), and this increase was strongest in liver recipients (1.65, 1.41-1.92). Among all recipients, PC incidence was especially increased for cases arising in the head of the pancreas (SIR 1.50, 95% CI 1.34-1.68) and for cases diagnosed at localized stage (1.85, 1.37-2.44). Among SOT recipients, factors independently associated with increased incidence were consistent with those in general population including male sex, older age, non-O blood type, and history of diabetes. Additionally, compared to other organ recipients, liver transplant recipients had higher PC incidence (adjusted incidence rate ratio 1.28; 95% CI 1.06-1.54). Overall survival after PC diagnosis was poor (median 4 months) and similar between liver and other organ transplant recipients (p = 0.08). CONCLUSIONS PC incidence is elevated among SOT recipients, and more commonly diagnosed in liver transplant recipients perhaps related to incidental detection. However, survival is poor even in liver recipients, arguing against routine PC screening.
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Affiliation(s)
- Tomohiro Tanaka
- Division of Gastroenterology and Hepatology, The University of Iowa, Iowa City, IA, USA.
| | - Charles F Lynch
- Department of Epidemiology, The University of Iowa, Iowa City, IA, USA
| | - Kelly J Yu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Bozena M Morawski
- Cancer Data Registry of Idaho, Idaho Hospital Association, Boise, ID, USA
| | - Mei-Chin Hsieh
- Louisiana Tumor Registry and Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Georgetta Alverson
- Michigan Cancer Surveillance Program, Michigan Department of Health and Human Services, Lansing, MI, USA
| | - April A Austin
- New York State Cancer Registry, New York State Department of Health, Albany, NY, USA
| | - Yun Zeng
- North Dakota Statewide Cancer Registry, Grand Forks, ND, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
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13
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Dahiya DS, Chandan S, Ali H, Pinnam BSM, Gangwani MK, Al Bunni H, Canakis A, Gopakumar H, Vohra I, Bapaye J, Al-Haddad M, Sharma NR. Role of Therapeutic Endoscopic Ultrasound in Management of Pancreatic Cancer: An Endoscopic Oncologist Perspective. Cancers (Basel) 2023; 15:3235. [PMID: 37370843 DOI: 10.3390/cancers15123235] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 06/08/2023] [Accepted: 06/17/2023] [Indexed: 06/29/2023] Open
Abstract
Pancreatic cancer is a highly lethal disease with an aggressive clinical course. Patients with pancreatic cancer are usually asymptomatic until significant progression of their disease. Additionally, there are no effective screening guidelines for pancreatic cancer in the general population. This leads to a delay in diagnosis and treatment, resulting in poor clinical outcomes and low survival rates. Endoscopic Ultrasound (EUS) is an indispensable tool for the diagnosis and staging of pancreatic cancer. In the modern era, with exponential advancements in technology and device innovation, EUS is also being increasingly used in a variety of therapeutic interventions. In the context of pancreatic cancer where therapies are limited due to the advanced stage of the disease at diagnosis, EUS-guided interventions offer new and innovative options. Moreover, due to their minimally invasive nature and ability to provide real-time images for tumor localization and therapy, they are associated with fewer complication rates compared to conventional open and laparoscopic approaches. In this article, we detail the most current and important therapeutic applications of EUS for pancreatic cancer, namely EUS-guided Fine Needle Injections, EUS-guided Radiotherapy, and EUS-guided Ablations. Furthermore, we also discuss the feasibility and safety profile of each intervention in patients with pancreatic cancer to provide gastrointestinal medical oncologists, radiation and surgical oncologists, and therapeutic endoscopists with valuable information to facilitate patient discussions and aid in the complex decision-making process.
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Affiliation(s)
- Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, USA
| | - Saurabh Chandan
- Division of Gastroenterology and Hepatology, CHI Creighton University Medical Center, Omaha, NE 68131, USA
| | - Hassam Ali
- Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA
| | - Bhanu Siva Mohan Pinnam
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL 60612, USA
| | | | - Hashem Al Bunni
- Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Andrew Canakis
- Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | - Harishankar Gopakumar
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
| | - Ishaan Vohra
- Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, USA
| | - Jay Bapaye
- Department of Internal Medicine, Rochester General Hospital, Rochester, NY 14621, USA
| | - Mohammad Al-Haddad
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
| | - Neil R Sharma
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
- Interventional Oncology & Surgical Endoscopy Programs (IOSE), GI Oncology Tumor Site Team, Parkview Cancer Institute, Parkview Health, Fort Wayne, IN 46845, USA
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14
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Clinical Features and Outcomes of Patients with Pancreaticobiliary Malignancies in Los Angeles County and Their Association with CA 19-9 Levels. Cancers (Basel) 2023; 15:cancers15061723. [PMID: 36980609 PMCID: PMC10046349 DOI: 10.3390/cancers15061723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/23/2023] [Accepted: 03/08/2023] [Indexed: 03/14/2023] Open
Abstract
Although CA 19-9 is a commonly used tumor marker in the management of PBMs, the literature describing outcomes in patients with PBMs who have undetectable or low (hereinafter “low”) CA 19-9 levels remains scarce. In this study, we sought to compare clinical features and outcomes in patients with PBMs and low CA 19-9 levels to those with normal and elevated CA 19-9 levels. Methods: We retrospectively collected data on patients with biopsy-confirmed PBMs and stratified patients into categories based on their CA 19-9 level at diagnosis. Survival curves were estimated for patients in each of the three aforementioned CA 19-9 groups using the Kaplan–Meier method and compared using a Cox proportional hazards regression model. Results: Of the 283 patients identified, 23 (8.1%) had low, 70 (24.7%) had normal, and 190 (67.1%) had elevated CA 19-9 levels. After controlling for sex, age, BMI, the presence of metastases at the time of diagnosis, and treatment with curative intent, the hazard ratio for death in the elevated CA 19-9 group compared to the low CA 19-9 group was 1.993 (95% CI 1.089–3.648; p = 0.025). Conclusion: The elevated CA 19-9 level compared to the low CA 19-9 level and the presence of metastases were associated with an increased hazard of death, while treatment with curative intent was associated with a decreased hazard of death.
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15
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Sharifi M, Khalilzadeh B, Bayat F, Isildak I, Tajali H. Application of thermal annealing-assisted gold nanoparticles for ultrasensitive diagnosis of pancreatic cancer using localized surface plasmon resonance. Microchem J 2023. [DOI: 10.1016/j.microc.2023.108698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2023]
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16
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Chen C, Lin X, Lin R, Huang H, Lu F. A high serum creatine kinase (CK)-MB-to-total-CK ratio in patients with pancreatic cancer: a novel application of a traditional marker in predicting malignancy of pancreatic masses? World J Surg Oncol 2023; 21:13. [PMID: 36653771 PMCID: PMC9847085 DOI: 10.1186/s12957-023-02903-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 01/11/2023] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The finding that some benign pancreatic masses mimic the imaging appearance of carcinomas poses a challenge for pancreatic surgeons. Preoperative markers that assist in the diagnosis are critical under this circumstance. Abnormal serum creatine kinase (CK) isozyme levels were reported in cancer patients, and this study aimed to explore the potential value of the CK-MB-to-total-CK ratio (CK ratio) in differentiating pancreatic cancer (PC) from benign masses when combined with carbohydrate antigen 19-9 (CA19-9). METHODS A total of 190 patients primarily diagnosed with pancreatic masses were retrospectively reviewed and assigned to the PC group and the benign pancreatic mass (BPM) group. Sixty-eight controls were enrolled for comparison. Levels of preoperative parameters, including total serum CK, CK-MB, absolute neutrophil count, absolute lymphocyte count, albumin, and CA19-9, were recorded as well as pathological information. A logistic regression model was established to assess the application value of the combination of CA19-9 and the CK ratio in diagnosis. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of the markers. RESULTS The CK ratio was significantly elevated in the PC group compared with the BPM group (P < 0.001). In the multivariate analysis, a CK ratio greater than 0.220 was a statistically significant variable for predicting malignancy of pancreatic masses (P=0.001). Patients with stage III/IV PC had a higher CK ratio than those with stage I/II PC (P<0.01). Combined detection of CA19-9 and the CK ratio produced an increased Youden index (0.739 vs. 0.815) with improved sensitivity (82.2% vs. 89.8%). CONCLUSIONS The CK ratio is elevated in patients with pancreatic adenocarcinoma and is an independent factor predicting pancreatic adenocarcinoma. The CK ratio augments the diagnostic capacity of CA19-9 in detecting malignancy.
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Affiliation(s)
- Cong Chen
- grid.411176.40000 0004 1758 0478Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian China
| | - Xianchao Lin
- grid.411176.40000 0004 1758 0478Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian China
| | - Ronggui Lin
- grid.411176.40000 0004 1758 0478Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian China
| | - Heguang Huang
- grid.411176.40000 0004 1758 0478Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian China
| | - Fengchun Lu
- grid.411176.40000 0004 1758 0478Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001 Fujian China
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17
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Adverse Effects of Tobacco Products (Cigarettes, E-Cigarettes, Hookah, Smokeless Tobacco) Use on Health. Respir Med 2023. [DOI: 10.1007/978-3-031-24914-3_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
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18
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He Y, Liu Y, Wu D, Chen L, Luo Z, Shi X, Li K, Hu H, Qu G, Zhao Q, Lian C. Linc-UROD stabilizes ENO1 and PKM to strengthen glycolysis, proliferation and migration of pancreatic cancer cells. Transl Oncol 2022; 27:101583. [PMID: 36413861 PMCID: PMC9679386 DOI: 10.1016/j.tranon.2022.101583] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 09/19/2022] [Accepted: 10/31/2022] [Indexed: 11/21/2022] Open
Abstract
Pancreatic cancer (PC) is a fatal malignancy, threatening human health in worldwide. Long non-coding RNAs (lncRNAs) have been acknowledged to be essential regulators in various biological processes of human cancers. However, the role of some novel lncRNAs in PC remain to be explored. In this study, we focused on the function and molecular mechanism of a novel lncRNA linc-UROD (also named TCONS_00002016 or XLOC_000166) in PC. The expression of linc-UROD was found to be upregulated in PC cells. The results of loss-of-function assays demonstrated that linc-UROD knockdown suppressed cell proliferation and migration, induced cell cycle G0/G1 arrest, and accelerated apoptosis of PC cells. Through mechanistic experiments, we found that IGF2BP3 stabilized linc-UROD through METTL3-mediated m6A modification. In addition, linc-UROD enhances the stability of ENO1 and PKM through interacting with them to inhibit ubiquitination. Detection on glucose consumption, pyruvate kinase activity and lactate production indicated that linc-UROD accelerated glycolysis of PC cells through PKM/ENO1-mediated pathway. To summarize, linc-UROD stabilized by IGF2BP3/METTL3 contributes to glycolysis and malignant phenotype of PC cells by stabilizing ENO1 and PKM. The findings suggest that linc-UROD may be a novel therapeutic target for PC patients.
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Affiliation(s)
- Yuan He
- Changzhi Medical College, Changzhi, Shanxi 046000, China,Department of General Surgery, Heping Hospital, Changzhi Medical College, No.110 South Yan'an Road, Changzhi, Shanxi 046000, China
| | - Yaxing Liu
- Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Dongkai Wu
- Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Luyao Chen
- Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Zhonglin Luo
- Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Xingsong Shi
- Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Keyan Li
- Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Hao Hu
- Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214041, China
| | - Gexi Qu
- Changzhi Medical College, Changzhi, Shanxi 046000, China
| | - Qiang Zhao
- Department of General Surgery, Heping Hospital, Changzhi Medical College, No.110 South Yan'an Road, Changzhi, Shanxi 046000, China,Corresponding authors.
| | - Changhong Lian
- Department of General Surgery, Heping Hospital, Changzhi Medical College, No.110 South Yan'an Road, Changzhi, Shanxi 046000, China,Corresponding authors.
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19
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Hameed BS, Krishnan UM. Artificial Intelligence-Driven Diagnosis of Pancreatic Cancer. Cancers (Basel) 2022; 14:5382. [PMID: 36358800 PMCID: PMC9657087 DOI: 10.3390/cancers14215382] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Revised: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 08/01/2023] Open
Abstract
Pancreatic cancer is among the most challenging forms of cancer to treat, owing to its late diagnosis and aggressive nature that reduces the survival rate drastically. Pancreatic cancer diagnosis has been primarily based on imaging, but the current state-of-the-art imaging provides a poor prognosis, thus limiting clinicians' treatment options. The advancement of a cancer diagnosis has been enhanced through the integration of artificial intelligence and imaging modalities to make better clinical decisions. In this review, we examine how AI models can improve the diagnosis of pancreatic cancer using different imaging modalities along with a discussion on the emerging trends in an AI-driven diagnosis, based on cytopathology and serological markers. Ethical concerns regarding the use of these tools have also been discussed.
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Affiliation(s)
- Bahrudeen Shahul Hameed
- Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), Shanmugha Arts, Science, Technology and Research Academy, Deemed University, Thanjavur 613401, India
- School of Chemical & Biotechnology (SCBT), Shanmugha Arts, Science, Technology and Research Academy, Deemed University, Thanjavur 613401, India
| | - Uma Maheswari Krishnan
- Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), Shanmugha Arts, Science, Technology and Research Academy, Deemed University, Thanjavur 613401, India
- School of Chemical & Biotechnology (SCBT), Shanmugha Arts, Science, Technology and Research Academy, Deemed University, Thanjavur 613401, India
- School of Arts, Sciences, Humanities & Education (SASHE), Shanmugha Arts, Science, Technology and Research Academy, Deemed University, Thanjavur 613401, India
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20
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CircDUSP22 Overexpression Restrains Pancreatic Cancer Development via Modulating miR-1178-3p and Downstream BNIP3. Biochem Genet 2022; 61:651-668. [PMID: 36063260 DOI: 10.1007/s10528-022-10275-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 08/07/2022] [Indexed: 11/02/2022]
Abstract
Aberrant expression of circular RNAs (circRNAs) is important in carcinogenesis, however, many differentially expressed circRNAs have not been functionally characterized. This study aimed to unveil the role of circRNA-dual specificity phosphatase 22 (circDUSP22) in pancreatic cancer (PaCa). Expression analyses of circDUSP22, miR-1178-3p and BCL2 interacting protein 3 (BNIP3) were carried out using quantitative real-time PCR (qRT-PCR) or western blotting. Cell growth was assessed by MTT, EdU and colony formation assays. Cell cycle distribution and cell apoptosis were investigated using flow cytometry assay. The assumed binding relationship between miR-1178-3p and circDUSP22 or BNIP3 was testified by dual-luciferase reporter and pull-down assays. The effect of circDUSP22 in vivo was identified by animal studies. The decreased expression of circDUSP22 was observed in PaCa samples and cells. CircDUSP22 ectopic expression in vitro blocked PaCa cell proliferation, arrested cell cycle and provoked cell apoptosis. CircDUSP22 targeted miR-1178-3p, whose expression was reinforced in PaCa. The inhibitory cell growth caused by circDUSP22 ectopic expression was reversed by miR-1178-3p enrichment. In addition, miR-1178-3p targeted BNIP3, whose expression was declined in PaCa. The inhibitory cell growth caused by circDUSP22 ectopic expression was reversed by BNIP3 knockdown. CircDUSP22 overexpression in vivo decelerated tumor growth. CircDUSP22 upregulation blocked PaCa development partly by targeting miR-1178-3p and increasing BNIP3, implying the potential implication of circDUSP22 in targeted therapy of PaCa.
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Phaseolus vulgaris Erythroagglutinin (PHA-E)-Positive Ceruloplasmin Acts as a Potential Biomarker in Pancreatic Cancer Diagnosis. Cells 2022; 11:cells11152453. [PMID: 35954297 PMCID: PMC9367852 DOI: 10.3390/cells11152453] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/31/2022] [Accepted: 08/02/2022] [Indexed: 11/17/2022] Open
Abstract
Pancreatic cancer (PC) remains one of the top 10 causes of cancer-related death in recent years. Approximately 80% of PC patients are diagnosed at the middle or advanced stage and miss the opportunity for surgery. The demand for early diagnostic methods and reliable biomarkers is increasing, although a number of tumor markers such as CA19-9 and CEA have already been utilized in clinics. In this study, we analyzed the alteration of N-glycan of serum glycoproteins by mass spectrometry and lectin blotting. The results showed that bisecting GlcNAc structures of glycoproteins are significantly increased in PC patients' sera. With Phaseolus vulgaris Erythroagglutinin (PHA-E) lectin that specifically recognizes bisecting GlcNAc N-glycans, the serum glycoproteins bearing bisecting GlcNAc in PC patients' sera were pulled down and identified by nano-LC-MS/MS. Among them, ceruloplasmin (Cp) was screened out with a satisfied sensitivity and specificity in identifying PC from acute pancreatitis patients (AUC: 0.757) and normal healthy persons (AUC: 0.972), suggesting a close association between Cp and PC development and diagnosis. To prove that, the Cp expression in tumor tissues of PC patients was examined. The results showed that Cp was significantly upregulated in PC tissues compared to that in adjacent normal tissues. All these results suggested that PHA-E-positive Cp could be a potential PC-specific glycoprotein marker to distinguish PC patients from acute pancreatitis patients and normal persons.
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22
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Marra-López Valenciano C. Factors associated with pancreatic cancer in Spain. What can we learn from epidemiological studies? REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2022; 114:445-447. [PMID: 35704373 DOI: 10.17235/reed.2022.8927/2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
The incidence of pancreatic cancer (PC) in Spain has progressively increased over the past 6 decades. Pancreatic ductal adenocarcinoma represents over 80 % of all pancreatic neoplasms. The study by Enrique Gili-Ortiz on pancreatic cancer-related mortality trends in Spain revealed a significant increase in death rates in our country, which may be partly attributed to population ageing and increased smoking, obesity, and diabetes rates. Other known factors, including chronic pancreatitis, seem to play a less significant role from a quantitative perspective.
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23
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Deng CF, Zhu N, Zhao TJ, Li HF, Gu J, Liao DF, Qin L. Involvement of LDL and ox-LDL in Cancer Development and Its Therapeutical Potential. Front Oncol 2022; 12:803473. [PMID: 35251975 PMCID: PMC8889620 DOI: 10.3389/fonc.2022.803473] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Accepted: 01/12/2022] [Indexed: 01/17/2023] Open
Abstract
Lipid metabolism disorder is related to an increased risk of tumorigenesis and is involved in the rapid growth of cancer cells as well as the formation of metastatic lesions. Epidemiological studies have demonstrated that low-density lipoprotein (LDL) and oxidized low-density lipoprotein (ox-LDL) are closely associated with breast cancer, colorectal cancer, pancreatic cancer, and other malignancies, suggesting that LDL and ox-LDL play important roles during the occurrence and development of cancers. LDL can deliver cholesterol into cancer cells after binding to LDL receptor (LDLR). Activation of PI3K/Akt/mTOR signaling pathway induces transcription of the sterol regulatory element-binding proteins (SREBPs), which subsequently promotes cholesterol uptake and synthesis to meet the demand of cancer cells. Ox-LDL binds to the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and cluster of differentiation 36 (CD36) to induce mutations, resulting in inflammation, cell proliferation, and metastasis of cancer. Classic lipid-lowering drugs, statins, have been shown to reduce LDL levels in certain types of cancer. As LDL and ox-LDL play complicated roles in cancers, the potential therapeutic effect of targeting lipid metabolism in cancer therapy warrants more investigation.
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Affiliation(s)
- Chang-Feng Deng
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Neng Zhu
- Department of Urology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Tan-Jun Zhao
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Hong-Fang Li
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Jia Gu
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Duan-Fang Liao
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
| | - Li Qin
- Division of Stem Cell Regulation and Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China
- Institutional Key Laboratory of Vascular Biology and Translational Medicine in Hunan Province, Hunan University of Chinese Medicine, Changsha, China
- *Correspondence: Li Qin,
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24
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Hu SC, Min S, Kang HK, Yang DJ, Basavarajappa M, Lewis SM, Davis KJ, Patton RE, Bryant MS, Sepehr E, Trbojevich R, Pearce MG, Bishop ME, Ding W, Heflich RH, Maisha MP, Felton R, Chemerynski S, Yee SB, Coraggio M, Rosenfeldt H, Yeager RP, Howard PC, Tang Y. 90-day nose-only inhalation toxicity study of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in Sprague-Dawley rats. Food Chem Toxicol 2022; 160:112780. [PMID: 34965465 DOI: 10.1016/j.fct.2021.112780] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 12/17/2021] [Accepted: 12/22/2021] [Indexed: 11/29/2022]
Abstract
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. Repeated dose inhalation toxicity data on NNK, particularly relevant to cigarette smoking, however, is surprisingly limited. Hence, there is a lack of direct information available on the carcinogenic and potential non-carcinogenic effects of NNK via inhalational route exposure. In the present study, the subchronic inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 23 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.2, 0.8, 3.2, or 7.8 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.0066, 0.026, 0.11, or 0.26 mg/L air) for 1 h/day for 90 consecutive days. Toxicity was evaluated by assessing body weights; food consumption; clinical pathology; histopathology; organ weights; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); tissue levels of the DNA adduct O6-methylguanine; blood and bone marrow micronucleus (MN) frequency; and bone marrow DNA strand breaks (comet assay). The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic lesions in the nose. Although the genotoxic biomarker O6-methylguanine was detected, genotoxicity from NNK exposure was negative in the MN and comet assays. The Lowest-Observed-Adverse-Effect-Level (LOAEL) was 0.8 mg/kg BW/day or 0.026 mg/L air of NNK for 1 h/day for both sexes. The No-Observed-Adverse-Effect-Level (NOAEL) was 0.2 mg/kg BW/day or 0.0066 mg/L air of NNK for 1 h/day for both sexes. The results of this study provide new information relevant to assessing the human exposure hazard of NNK.
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Affiliation(s)
- Shu-Chieh Hu
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Seonggi Min
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Hyun-Ki Kang
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Dong-Jin Yang
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Mallikarjuna Basavarajappa
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Sherry M Lewis
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Kelly J Davis
- Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR, 72079, USA
| | - Ralph E Patton
- Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR, 72079, USA
| | - Matthew S Bryant
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Estatira Sepehr
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Raul Trbojevich
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Mason G Pearce
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Michelle E Bishop
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Wei Ding
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Robert H Heflich
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - MacKean P Maisha
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Robert Felton
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Susan Chemerynski
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA
| | - Steven B Yee
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA
| | - Melis Coraggio
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA
| | - Hans Rosenfeldt
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA
| | - R Philip Yeager
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA
| | - Paul C Howard
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA
| | - Yunan Tang
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR, 72079, USA.
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Yang J, Chheda C, Lim A, Hauptschein D, Zayou L, Tang J, Pandol SJ, Edderkaoui M. HDAC4 Mediates Smoking-Induced Pancreatic Cancer Metastasis. Pancreas 2022; 51:190-195. [PMID: 35404896 PMCID: PMC9004243 DOI: 10.1097/mpa.0000000000001998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Cigarette smoking is an established risk factor for pancreatic ductal adenocarcinoma (PDAC). In this project, we investigated the effect of smoking and the role of histone deacetylase 4 (HDAC4) in PDAC invasion and metastasis. METHODS Cells were treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and cigarette smoke extract and the mRNA levels of HDACs were measured by real-time polymerase chain reaction. Invasion was measured using the Matrigel Invasion Assay. Syngeneic PDAC mice were treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and metastasis measured. Human PDAC primary and metastatic tissues were analyzed by immunohistochemistry. RESULTS Levels of HDAC4 mRNA were increased by smoking. Smoking compounds significantly promoted invasion of cancer cells and promoted metastasis of PDAC cells to different organs, including the liver and the lung, whereas inhibition of HDAC4 prevented this effect. The effect of HDAC4 inhibition on preventing smoking-induced metastasis was greater in the liver compared with the lung. We found that HDAC4 is highly expressed in primary and metastatic PDAC tumors. CONCLUSIONS We found that HDAC4 is the only HDAC induced by smoking among all HDACs analyzed. We found that smoking promotes invasion and metastasis of PDAC cells through a mechanism that involves HDAC4 and that HDAC4 is a promising target for preventing PDAC metastasis.
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Affiliation(s)
- Jiyong Yang
- Department of General Surgery Longhua Hospital, Shanghai University of TCM, Shanghai, China
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Chintan Chheda
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Adrian Lim
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Dina Hauptschein
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Latifa Zayou
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Josiah Tang
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Stephen J. Pandol
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Mouad Edderkaoui
- Departments of Medicine and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA
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26
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Aryannejad A, Tabary M, Ebrahimi N, Mohammadi E, Fattahi N, Roshani S, Masinaei M, Naderimagham S, Azadnajafabad S, Jamshidi K, Fateh SM, Moghimi M, Kompani F, Rezaei N, Farzadfar F. Global, regional, and national survey on the burden and quality of care of pancreatic cancer: a systematic analysis for the Global Burden of Disease study 1990-2017. Pancreatology 2021; 21:1443-1450. [PMID: 34561167 DOI: 10.1016/j.pan.2021.09.002] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 08/24/2021] [Accepted: 09/03/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic cancer (PC) is among the most lethal cancers worldwide, and the quality of care provided to PC patients is a vital public health concern. We aimed to investigate the quality of care of PC globally and to report its current burden. METHODS The Quality of Care Index (QCI) was achieved by performing a Principal Component Analysis utilizing the results of the GBD study 2017. The QCI was defined as a range between 0 and 100, in which higher QCIs show higher quality of care. Possible gender- and age-related inequalities in terms of QCI were explored based on WHO world regions and the sociodemographic index (SDI). RESULTS In 2017, Japan had the highest QCI among all countries (QCI = 99/100), followed by Australia (QCI = 83/100) and the United States (QCI = 76/100). In Japan and Australia, males and females had almost the same QCIs in 2017, while in the United States, females had lower QCIs than males. In contrast to these high-QCI nations, African countries had the lowest QCIs in 2017. Besides, QCI increased by SDI, and high-SDI regions had the highest QCIs. Regarding patients' age, elderly cases had higher QCIs than younger patients globally and in high-SDI regions. CONCLUSION This study provides clinicians and health authorities with a wider vision around the quality of care of PC worldwide and highlights the existing disparities. This could help them investigate possible effective strategies to improve the quality of care in regions with lower QCIs and higher gender- and age-related inequities.
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Affiliation(s)
- Armin Aryannejad
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammadreza Tabary
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Narges Ebrahimi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Esmaeil Mohammadi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Nima Fattahi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shahin Roshani
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoud Masinaei
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shohreh Naderimagham
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sina Azadnajafabad
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Kosar Jamshidi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Mohammadi Fateh
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mana Moghimi
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farzad Kompani
- Division of Hematology and Oncology, Children's Medical Center, Pediatrics Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
| | - Negar Rezaei
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Farshad Farzadfar
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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27
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Rosato V, Gómez-Rubio P, Molina-Montes E, Márquez M, Löhr M, O'Rorke M, Michalski CW, Molero X, Farré A, Perea J, Kleeff J, Crnogorac-Jurcevic T, Greenhalf W, Ilzarbe L, Tardón A, Gress T, Barberá VM, Domínguez-Muñoz E, Muñoz-Bellvís L, Balsells J, Costello E, Iglesias M, Kong B, Mora J, O'Driscoll D, Poves I, Scarpa A, Ye W, Hidalgo M, Sharp L, Carrato A, Real FX, La Vecchia C, Malats N. Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study. Eur J Cancer Prev 2021; 30:423-430. [PMID: 34545020 DOI: 10.1097/cej.0000000000000588] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND AND AIMS The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.
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Affiliation(s)
- V Rosato
- Unit of Medical Statistics and Biometry, National Cancer Institute, IRCCS Foundation, Milan, Italy
| | - P Gómez-Rubio
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- CIBERONC, Spain
| | - E Molina-Montes
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- CIBERONC, Spain
| | - M Márquez
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- CIBERONC, Spain
| | - M Löhr
- Gastrocentrum, Karolinska Institutet and University Hospital, Stockholm, Sweden
| | - M O'Rorke
- Centre for Public Health, Belfast, Queen's University Belfast, Belfast, UK
| | - C W Michalski
- Department of Surgery, Technical University of Munich, Munich
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - X Molero
- Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Universitat Autònoma de Barcelona, Barcelona
- CIBEREHD
| | - A Farré
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona
| | - J Perea
- Department of Surgery, University Hospital 12 de Octubre
- Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - J Kleeff
- Department of Surgery, Technical University of Munich, Munich
- Department of Visceral, Vascular and Endocrine Surgery, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany
| | - T Crnogorac-Jurcevic
- Barts Cancer Institute, Centre for Molecular Oncology, Queen Mary University of London, John Vane Science Centre, London
| | - W Greenhalf
- Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, UK
| | - L Ilzarbe
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- Hospital del Mar-Parc de Salut Mar, Barcelona
| | - A Tardón
- Department of Medicine, Instituto Universitario de Oncología del Principado de Asturias, Oviedo
- CIBERESP, Spain
| | - T Gress
- Department of Gastroenterology, University Hospital of Giessen and Marburg, Marburg, Germany
| | - V M Barberá
- Molecular Genetics Laboratory, General University Hospital of Elche
| | - E Domínguez-Muñoz
- Department of Gastroenterology, University Clinical Hospital of Santiago de Compostela
| | - L Muñoz-Bellvís
- General and Digestive Surgery Department, Salamanca University Hospital, Elche, Santiago de Compostela, and Salamanca, Spain
| | - J Balsells
- Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Barcelona, Universitat Autònoma de Barcelona, Barcelona
- CIBEREHD
| | - E Costello
- Department of Molecular and Clinical Cancer Medicine, The Royal Liverpool University Hospital, Liverpool, UK
| | - M Iglesias
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- Hospital del Mar-Parc de Salut Mar, Barcelona
| | - Bo Kong
- Department of Surgery, Technical University of Munich, Munich
| | - J Mora
- Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona
| | - D O'Driscoll
- National Cancer Registry Ireland and HRB Clinical Research Facility, University College Cork, Cork, Ireland
| | - I Poves
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- Hospital del Mar-Parc de Salut Mar, Barcelona
| | - A Scarpa
- ARC-Net centre for Applied Research on Cancer and Department of Pathology and Diagnostics, University and Hospital trust of Verona, Verona, Italy
| | - W Ye
- Gastrocentrum, Karolinska Institutet and University Hospital, Stockholm, Sweden
| | - M Hidalgo
- Madrid-Norte-Sanchinarro Hospital, Madrid, Spain
| | - L Sharp
- National Cancer Registry Ireland and HRB Clinical Research Facility, University College Cork, Cork, Ireland
- Newcastle University, Institute of Health & Society, Newcastle, UK
| | - A Carrato
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- Department of Oncology, Ramón y Cajal University Hospital, IRYCIS, Alcala University
| | - F X Real
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- Epithelial Carcinogenesis Group
- Spanish National Cancer Research Centre (CNIO), Madrid
- Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
| | - C La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - N Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid
- CIBERONC, Spain
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28
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Hu SC, Min S, Kang HK, Yang DJ, Lewis SM, Davis KJ, Patton RE, Bryant MS, Sepehr E, Trbojevich R, Pearce MG, Bishop ME, Heflich RH, Maisha MP, Felton R, Chemerynski S, Yee SB, Coraggio M, Rosenfeldt H, Yeager RP, Howard PC, Tang Y. 14-Day Nose-Only Inhalation Toxicity and Haber's Rule Study of NNK in Sprague-Dawley Rats. Toxicol Sci 2021; 183:319-337. [PMID: 34329464 DOI: 10.1093/toxsci/kfab094] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the key tobacco-specific nitrosamines that plays an important role in human lung carcinogenesis. However, repeated inhalation toxicity data on NNK, which is more directly relevant to cigarette smoking, are currently limited. In the present study, the subacute inhalation toxicity of NNK was evaluated in Sprague Dawley rats. Both sexes (9-10 weeks age; 16 rats/sex/group) were exposed by nose-only inhalation to air, vehicle control (75% propylene glycol), or 0.8, 3.2, 12.5, or 50 mg/kg body weight (BW)/day of NNK (NNK aerosol concentrations: 0, 0, 0.03, 0.11, 0.41, or 1.65 mg/L air) for 1 hour/day for 14 consecutive days. Toxicity was evaluated by assessing body and organ weights; food consumption; clinical pathology; histopathology observations; blood, urine, and tissue levels of NNK, its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), and their glucuronides (reported as total NNK, tNNK, and total NNAL, tNNAL, respectively); O6-methylguanine DNA adduct formation; and blood and bone marrow micronucleus frequency. Whether the subacute inhalation toxicity of NNK followed Haber's Rule was also determined using additional animals exposed 4 hours/day. The results showed that NNK exposure caused multiple significant adverse effects, with the most sensitive endpoint being non-neoplastic histopathological lesions in the nose. The lowest-observed-adverse-effect level (LOAEL) was 0.8 mg/kg BW/day or 0.03 mg/L air for 1 hour/day for both sexes. An assessment of Haber's Rule indicated that 14-day inhalation exposure to the same dose at a lower concentration of NNK aerosol for a longer time (4 hours daily) resulted in greater adverse effects than exposure to a higher concentration of NNK aerosol for a shorter time (1 hour daily).
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Affiliation(s)
- Shu-Chieh Hu
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Seonggi Min
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Hyun-Ki Kang
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Dong-Jin Yang
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Sherry M Lewis
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Kelly J Davis
- Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR
| | - Ralph E Patton
- Toxicologic Pathology Associates, National Center for Toxicological Research, Jefferson, AR
| | - Matthew S Bryant
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Estatira Sepehr
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Raul Trbojevich
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Mason G Pearce
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Michelle E Bishop
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Robert H Heflich
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - MacKean P Maisha
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Robert Felton
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Susan Chemerynski
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD
| | - Steven B Yee
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD
| | - Melis Coraggio
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD
| | - Hans Rosenfeldt
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD
| | - R Philip Yeager
- The Center for Tobacco Products (CTP), U.S. Food and Drug Administration, Silver Spring, MD
| | - Paul C Howard
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
| | - Yunan Tang
- National Center for Toxicological Research (NCTR), U.S. Food and Drug Administration (FDA), Jefferson, AR
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29
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Draus T, Ansari D, Wikström F, Persson U, Andersson R. Projected economic burden of pancreatic cancer in Sweden in 2030. Acta Oncol 2021; 60:866-871. [PMID: 33729903 DOI: 10.1080/0284186x.2021.1892821] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Pancreatic cancer is predicted to become the second most common cause of cancer-related death by 2030. The objective of this study was to estimate the economic burden of pancreatic cancer for the years 2018 and 2030 based on changing demographics and incidence rates in Sweden. METHOD The incidence of pancreatic cancer in Sweden and additional relevant data were obtained from official statistics. A linear regression model and the mean incidence rates 2008-2018 were applied to calculate the incidence in 2030. An economic model based on the human capital method was created to calculate the indirect cost of pancreatic cancer in 2018 and 2030. Costs associated with surgery, radiology, oncology, and palliative care constituted the direct costs. A sensitivity analysis was performed. RESULTS The incidence of pancreatic cancer in Sweden in the year 2018 was 1352 patients and projected to between 1554 (+15%) and 1736 (+28%) in 2030. The total cost was calculated to €125 million in 2018 and between €210 million (+68%) and €225 million (+80%) in 2030. The indirect cost in the ≤65-year-old group was €328,344 in 2018 and between €380,738 and €382,109 per individual in 2030. CONCLUSIONS The economic burden of pancreatic cancer is expected to increase in Sweden by 2030 due to the increasing incidence of the disease and changing demographics. Pancreatic cancer is a growing health care problem in urgent need of advancements in prevention, early detection, treatment, and control of the disease.
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Affiliation(s)
- Tomasz Draus
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
| | - Daniel Ansari
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
| | - Filip Wikström
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
| | - Ulf Persson
- School of Economics, The Swedish Institute for Health Economics Lund, Lund, Sweden
| | - Roland Andersson
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
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30
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Aoki MN, Stein A, de Oliveira JC, Chammas R, Uno M, Munhoz FBDA, Marin AM, Canzian F. Susceptibility loci for pancreatic cancer in the Brazilian population. BMC Med Genomics 2021; 14:111. [PMID: 33879152 PMCID: PMC8056496 DOI: 10.1186/s12920-021-00956-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 04/08/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Pancreatic adenocarcinoma (PA) is a very aggressive cancer and has one of the poorest prognoses. Usually, the diagnosis is late and resistant to conventional treatment. Environmental and genetic factors contribute to the etiology, such as tobacco and alcohol consumption, chronic pancreatitis, diabetes and obesity. Somatic mutation in pancreatic cancer cells are known and SNP profile by GWAS could access novel genetic risk factors for this disease in different population context. Here we describe a SNP panel for Brazilian pancreatic cancer, together with clinical and epidemiological data. METHODS 78 pancreatic adenocarcinoma and 256 non-pancreatic cancer subjects had 25 SNPs genotyped by real-time PCR. Unconditional logistic regression methods were used to assess the main effects on PA risk, using allelic, co-dominant and dominant inheritance models. RESULTS 9 SNPs were nominally associated with pancreatic adenocarcinoma risk, with 5 of the minor alleles conferring protective effect while 4 related as risk factor. In epidemiological and clinical data, tobacco smoking, diabetes and pancreatitis history were significantly related to pancreatic adenocarcinoma risk. Polygenic risk scores computed using the SNPs in the study showed strong associations with PA risk. CONCLUSION We could assess for the first time some SNPs related with PA in Brazilian populations, a result that could be used for genetic screening in risk population such as familial pancreatic cancer, smokers, alcohol users and diabetes patients.
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Affiliation(s)
- Mateus Nóbrega Aoki
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, PR, Brazil.
| | - Angelika Stein
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | | | - Roger Chammas
- Departamento de Radiologia E Oncologia, Centro de Investigação Translacional Em Oncologia, Instituto Do Câncer Do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brasil
| | - Miyuki Uno
- Departamento de Radiologia E Oncologia, Centro de Investigação Translacional Em Oncologia, Instituto Do Câncer Do Estado de São Paulo (ICESP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brasil
| | - Francielle Boçon de Araújo Munhoz
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, PR, Brazil
| | - Anelis Maria Marin
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, PR, Brazil
| | - Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
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31
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Jin Y, Zhang Z, Zou S, Li F, Chen H, Peng C, Deng X, Wen C, Shen B, Zhan Q. A Novel c-MET-Targeting Antibody-Drug Conjugate for Pancreatic Cancer. Front Oncol 2021; 11:634881. [PMID: 33816276 PMCID: PMC8010262 DOI: 10.3389/fonc.2021.634881] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 02/22/2021] [Indexed: 12/20/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated death in the United States and has a 5-year survival rate of <4%. Although much effort has been invested in the research and development of pancreatic cancer drugs over the past 30 years, due to the lack of effective targetable carcinogenic drivers, no new targeted therapies that can improve patient prognosis have been approved for clinical use. SHR-A1403 is a new c-mesenchymal-epithelial transition factor (c-MET) antibody-drug conjugate that can be used for the targeted treatment of PDAC with high c-MET expression. This study reports for the first time the application prospects of SHR-A1403 in preclinical models of PDAC. SHR-A1403 significantly inhibited the proliferation, migration, and invasion of pancreatic cancer cells and induced cell cycle arrest and apoptosis. These changes were caused by inhibition of intracellular cholesterol biosynthesis by SHR-A1403. Therefore, targeting c-MET through SHR-A1403 showed strong preclinical anti-tumour efficacy in pancreatic cancer. Our work suggests the potential application of c-MET-targeted antibody-drug conjugate treatment for PDAC in clinical practise.
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Affiliation(s)
- Yangbing Jin
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zehui Zhang
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Siyi Zou
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Fanlu Li
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hao Chen
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chenghong Peng
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xiaxing Deng
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chenlei Wen
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Baiyong Shen
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qian Zhan
- Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogenes and Related Genes, Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
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Role of targeted immunotherapy for pancreatic ductal adenocarcinoma (PDAC) treatment: An overview. Int Immunopharmacol 2021; 95:107508. [PMID: 33725635 DOI: 10.1016/j.intimp.2021.107508] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/18/2021] [Accepted: 02/12/2021] [Indexed: 12/15/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid tumors with a high mortality rate and poor survival rate. Depending on the tumor stage, PDAC is either treated by resection surgery, chemotherapies, or radiotherapies. Various chemotherapeutic agents have been used to treat PDAC, alone or in combination. Despite the combinations, chemotherapy exhibits many side-effects leading to an increase in the toxicity profile amongst the PDAC patients. Additionally, these standard chemotherapeutic agents have only a modest impact on patient survival due to their limited efficacy. PDAC was previously considered as an immunologically silent malignancy, but recent findings have demonstrated that effective immune-mediated tumor cell death can be used for its treatment. PDAC is characterized by an immunosuppressive tumor microenvironment accompanied by the major expression of myeloid-derived suppressor cells (MDSC) and M2 tumor-associated macrophages. In contrast, the expression of CD8+ T cells is significantly low. Additionally, infiltration of mast cells in PDAC correlates with the poor prognosis. Immunotherapeutic agents target the immunity mediators and empower them to suppress the tumor and effectively treat PDAC. Different targets are studied and exploited to induce an antitumor immune response in PDAC patients. In recent times, site-specific delivery of immunotherapeutics also gained attention among researchers to effectively treat PDAC. In the present review, existing immunotherapies for PDAC treatment along with their limitations are addressed in detail. The review also includes the pathophysiology, traditional strategies and significance of targeted immunotherapies to combat PDAC effectively. Separately, the identification of ideal targets for the targeted therapy of PDAC is also reviewed exhaustively. Additionally, the review also addresses the applications of targeted immunotherapeutics like checkpoint inhibitors, adoptive T-cell therapy etc.
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Huang J, Lok V, Ngai CH, Zhang L, Yuan J, Lao XQ, Ng K, Chong C, Zheng ZJ, Wong MCS. Worldwide Burden of, Risk Factors for, and Trends in Pancreatic Cancer. Gastroenterology 2021; 160:744-754. [PMID: 33058868 DOI: 10.1053/j.gastro.2020.10.007] [Citation(s) in RCA: 262] [Impact Index Per Article: 65.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 08/02/2020] [Accepted: 10/03/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We evaluated global and regional burdens of, risk factors for, and epidemiologic trends in pancreatic cancer among groups of different sexes and ages. METHODS We used data from the GLOBOCAN database to estimate pancreatic cancer incidence and mortality in 184 countries. We examined the association between lifestyle and metabolic risk factors, extracted from the World Health Organization Global Health Observatory database, and pancreatic cancer incidence and mortality by univariable and multivariable linear regression. We retrieved country-specific age-standardized rates (ASRs) of incidence and mortalities from cancer registries from 48 countries through 2017 for trend analysis by joinpoint regression analysis. RESULTS The highest incidence and mortality of pancreatic cancer were in regions with very high (ASRs, 7.7 and 4.9) and high human development indexes (ASRs, 6.9 and 4.6) in 2018. Countries with higher incidence and mortality were more likely to have higher prevalence of smoking, alcohol drinking, physical inactivity, obesity, hypertension, and high cholesterol. From 2008 to 2017, 2007 to 2016, or 2003 to 2012, depending on the availability of the data, there were increases in incidence among men and women in 14 (average annual percent changes [AAPCs], 8.85 to 0.41) and 17 (AAPCs, 6.04 to 0.87) countries, respectively. For mortality, the increase was observed in 8 (AAPCs, 4.20 to 0.55) countries among men and 14 (AAPCs, 5.83 to 0.78) countries among women. Although the incidence increased in 18 countries (AAPCs, 7.83 to 0.91) among individuals 50 years or older, an increasing trend in pancreatic cancer was also identified among individuals younger than 50 years and 40 years in 8 (AAPCs, 8.75 to 2.82) and 4 (AAPCs, 11.07 to 8.31) countries, respectively. CONCLUSIONS In an analysis of data from 48 countries, we found increasing incidence and mortality trends in pancreatic cancer, especially among women and populations 50 years or older, but also among younger individuals. More preventive efforts are recommended for these populations.
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Affiliation(s)
- Junjie Huang
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Veeleah Lok
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Chun Ho Ngai
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lin Zhang
- School of Public Health, The Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Melbourne School of Population and Global Health, The University of Melbourne, Victoria, Australia
| | - Jinqiu Yuan
- Clinical Research Centre, Scientific Research Centre, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Xiang Qian Lao
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Kelvin Ng
- Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Charing Chong
- Department of Surgery, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China
| | - Zhi-Jie Zheng
- Department of Global Health, School of Public Health, Peking University, Beijing, China.
| | - Martin C S Wong
- The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong SAR, China; School of Public Health, The Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Global Health, School of Public Health, Peking University, Beijing, China.
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Sun H, Zhang B, Li H. The Roles of Frequently Mutated Genes of Pancreatic Cancer in Regulation of Tumor Microenvironment. Technol Cancer Res Treat 2020; 19:1533033820920969. [PMID: 32372692 PMCID: PMC7225789 DOI: 10.1177/1533033820920969] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
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.
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Affiliation(s)
- Hongzhi Sun
- Department of General Surgery, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Bo Zhang
- Department of General Surgery, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Haijun Li
- Department of General Surgery, Shenzhen Luohu People's Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China
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Guler GD, Ning Y, Ku CJ, Phillips T, McCarthy E, Ellison CK, Bergamaschi A, Collin F, Lloyd P, Scott A, Antoine M, Wang W, Chau K, Ashworth A, Quake SR, Levy S. Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA. Nat Commun 2020; 11:5270. [PMID: 33077732 PMCID: PMC7572413 DOI: 10.1038/s41467-020-18965-w] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2018] [Accepted: 09/18/2020] [Indexed: 12/15/2022] Open
Abstract
Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92-0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.
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Affiliation(s)
- Gulfem D Guler
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA
| | - Yuhong Ning
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA
| | - Chin-Jen Ku
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA
| | - Tierney Phillips
- Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA
| | - Erin McCarthy
- Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA
| | | | - Anna Bergamaschi
- Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA
| | - Francois Collin
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA
| | - Paul Lloyd
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA
| | - Aaron Scott
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA
| | - Michael Antoine
- Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA
| | - Wendy Wang
- Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA
| | - Kim Chau
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA
| | - Alan Ashworth
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, 94158, USA
| | - Stephen R Quake
- Departments of Bioengineering and Applied Physics, Stanford University, Stanford, CA, 94304, USA
- Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA
| | - Samuel Levy
- Bluestar Genomics, 185 Berry Street, Lobby 4, Suite 210, San Francisco, CA, 94107, USA.
- Bluestar Genomics, 10578 Science Center Drive Suite 210, San Diego, CA, 92121, USA.
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Rosato V, Negri E, Bosetti C, Malats N, Gomez-Rubio P, Consortium P, Maisonneuve P, Miller AB, Bueno-de-Mesquita HB, Baghurst PA, Zatonski W, Petersen GM, Scelo G, Holcatova I, Fabianova E, Serraino D, Olson SH, Vioque J, Lagiou P, Duell EJ, Boffetta P, La Vecchia C. Gallbladder disease, cholecystectomy, and pancreatic cancer risk in the International Pancreatic Cancer Case-Control Consortium (PanC4). Eur J Cancer Prev 2020; 29:408-415. [PMID: 32740166 DOI: 10.1097/cej.0000000000000572] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND The association among gallbladder disease, cholecystectomy, and pancreatic cancer is unclear. Moreover, time interval between gallbladder disease or cholecystectomy and pancreatic cancer diagnosis is not considered in most previous studies. AIM To quantify the association among gallbladder disease, cholecystectomy, and pancreatic cancer, considering time since first diagnosis of gallbladder disease or cholecystectomy. METHODS We used data from nine case-control studies within the Pancreatic Cancer Case-Control Consortium, including 5760 cases of adenocarcinoma of the exocrine pancreas and 8437 controls. We estimated pooled odds ratios and the corresponding 95% confidence intervals by estimating study-specific odds ratios through multivariable unconditional logistic regression models, and then pooling the obtained estimates using fixed-effects models. RESULTS Compared with patients with no history of gallbladder disease, the pooled odds ratio of pancreatic cancer was 1.69 (95% confidence interval, 1.51-1.88) for patients reporting a history of gallbladder disease. The odds ratio was 4.90 (95% confidence interval, 3.45-6.97) for gallbladder disease diagnosed <2 years before pancreatic cancer diagnosis and 1.11 (95% confidence interval, 0.96-1.29) when ≥2 years elapsed. The pooled odds ratio was 1.64 (95% confidence interval, 1.43-1.89) for patients who underwent cholecystectomy, as compared to those without cholecystectomy. The odds ratio was 7.00 (95% confidence interval, 4.13-11.86) for a surgery <2 years before pancreatic cancer diagnosis and 1.28 (95% confidence interval, 1.08-1.53) for a surgery ≥2 years before. CONCLUSIONS There appears to be no long-term effect of gallbladder disease on pancreatic cancer risk, and at most a modest one for cholecystectomy. The strong short-term association can be explained by diagnostic bias and reverse causation.
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Affiliation(s)
- Valentina Rosato
- Unit of Medical Statistics and Biometry, National Cancer Institute, IRCCS Foundation
| | - Eva Negri
- Department of Biomedical and Clinical Sciences, University of Milan
| | - Cristina Bosetti
- Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy
| | - Núria Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain
| | - Paulina Gomez-Rubio
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain
| | - PanGenEU Consortium
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) and CIBERONC, Madrid, Spain
| | - Patrick Maisonneuve
- Division of Epidemiology and Biostatistics, IEO European Institute of Oncology IRCCS, Milan, Italy
| | - Anthony B Miller
- Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
| | - H Bas Bueno-de-Mesquita
- National Institute for Public Health and the Environment (RIVM), Bilthoven
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Peter A Baghurst
- Public Health, Women's and Children's Hospital, Adelaide, South Australia, Australia
| | - Witold Zatonski
- Health Promotion Foundation, Nadarzyn
- Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Gloria M Petersen
- Department of Health Sciences Research, Medicine and Medical Genetics, Mayo Clinic, Rochester, New York, USA
| | - Ghislaine Scelo
- International Agency for Research on Cancer (IARC), Lyon, France
| | - Ivana Holcatova
- Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
| | - Eleonora Fabianova
- Regional Authority of Public Health, Banská Bystrica, Slovak Republic
- Faculty of Health, Catholic University, Ružomberok, Slovak Republic
| | - Diego Serraino
- Cancer Epidemiology Unit, National Cancer Institute Centro di Riferimento Oncologico, IRCCS, Aviano, Italy
| | - Sara H Olson
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Jesús Vioque
- Institute for Health and Biomedical Research ISABIAL-UMH, Alicante
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Pagona Lagiou
- Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, University of Athens, Athens, Greece
- Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
| | - Eric J Duell
- Unit of Biomarkers and Susceptibility, Oncology Data Analytics Program, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
| | - Paolo Boffetta
- The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, New York, USA
| | - Carlo La Vecchia
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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Baum C, Soliman AS, Brown HE, Seifeldin IA, Ramadan M, Lott B, Nguyen A, El-Ghawalby A, Hablas A. Regional Variation of Pancreatic Cancer Incidence in the Nile Delta Region of Egypt over a Twelve-Year Period. J Cancer Epidemiol 2020; 2020:6031708. [PMID: 32733561 PMCID: PMC7376424 DOI: 10.1155/2020/6031708] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2020] [Revised: 06/03/2020] [Accepted: 06/19/2020] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Pancreatic cancer is one of the deadliest forms of cancer, with incidence rates rising in many countries around the world. Geographic variation in pancreatic cancer incidence has not been studied extensively, especially in low- and middle-income countries. The aim of this study was to characterize the distribution of pancreatic cancer incidence in the central Nile Delta region of Egypt and to examine differences by urban and rural patient residence using the nation's only population-based cancer registry. METHODS Utilizing the Gharbiah province population-based cancer registry, data were abstracted for 1,089 pancreatic cancer cases diagnosed over twelve years from 1999 to 2010. Age- and sex-specific incidence rates were calculated and compared for urban and rural areas of the eight districts of Gharbiah. RESULTS Age-adjusted incidence of pancreatic cancer within Gharbiah varied considerably by urban/rural patient residence and by district. Incidence rates were 1.3 times higher in urban compared to rural areas (4.45 per 100,000 in urban areas and 3.43 per 100,000 in rural areas). The highest incidence rates were observed in urban centers of Kotour, El Santa, and Kafr El-Zayat districts (12.94, 8.32, and 7.89, respectively). CONCLUSION Incidence rates varied greatly by urban and rural areas and by district of residence in the Nile Delta region of Egypt. Future studies should examine potential environmental risk factors that may contribute to the geographic distribution of pancreatic cancer in this region.
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Affiliation(s)
- Christina Baum
- Department of Epidemiology & Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA
| | - Amr S. Soliman
- Department of Community Health and Social Medicine, City University of New York Medical School, New York City, NY 10031, USA
| | - Heidi E. Brown
- Department of Epidemiology & Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA
| | | | | | - Breanne Lott
- Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA
| | - An Nguyen
- Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington, DC 20052, USA
| | - Ahmed El-Ghawalby
- Department of Surgery, Liver Transplantation Unit, Gastrointestinal Surgery Center, College of Medicine, Mansoura University, Mansoura, Egypt
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Hocevar SE, Kamendulis LM, Hocevar BA. Perfluorooctanoic acid activates the unfolded protein response in pancreatic acinar cells. J Biochem Mol Toxicol 2020; 34:e22561. [PMID: 32578922 DOI: 10.1002/jbt.22561] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/21/2020] [Accepted: 06/11/2020] [Indexed: 01/09/2023]
Abstract
Perfluoroalkyl substances, such as perfluorooctanoic acid (PFOA), are widely used in consumer and industrial applications. Human epidemiologic and animal studies suggest that PFOA exposure elicits adverse effects on the pancreas; however, little is known about the biological effects of PFOA in this organ. In this study, we show that PFOA treatment of mouse pancreatic acinar cells results in endoplasmic reticulum (ER) stress and activation of the protein kinase-like endoplasmic reticulum kinase (PERK), inositol-requiring kinase/endonuclease 1α (IRE1α), and activating transcription factor 6 arms of the unfolded protein response (UPR) pathway. PFOA-stimulated activation of the UPR was blocked by pretreatment with specific PERK and IRE1α inhibitors and the chemical chaperone 4-phenyl butyrate, but not the antioxidants N-acetyl- l-cysteine and Tiron. PFOA treatment led to increased cytosolic Ca+2 levels and induction of the UPR was blocked by an inhibitor of the inositol 1,4,5-trisphosphate receptor. These findings indicate that PFOA-induced ER stress may be the mechanistic trigger leading to oxidative stress in the pancreas.
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Affiliation(s)
- Sarah E Hocevar
- Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, Indiana
| | - Lisa M Kamendulis
- Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, Indiana
| | - Barbara A Hocevar
- Department of Environmental and Occupational Health, School of Public Health, Indiana University, Bloomington, Indiana
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39
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Ozcan-Sınır G, Inan S, Suna S, Tamer CE, Akgül MB, Bagdas D, Sonmez G, Evrensel T, Kaya E, Sarandol E, Dündar HZ, Tarım OF, Ercan I, Sıgırlı D, Incedayı B, Copur OU. Effect of High Fructose Corn Sirup on Pancreatic Ductal Adenocarcinoma Induced by Dimethyl Benzantracene (DMBA) in Rats. Nutr Cancer 2020; 73:339-349. [PMID: 32475178 DOI: 10.1080/01635581.2020.1770811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Increased risk of pancreatic cancer may be associated with consumption of sugar containing foods. The aim of this study was to evaluate the effect of peach nectar containing high fructose corn sirup (HFCS) consumption in a pancreatic carcinogenesis rat model induced by 7,12-Dimethyl benzanthracene (DMBA). Fifty-day-old male Sprague Dawley rats were fed with peach nectar containing HFCS + chow, peach nectar containing sucrose + chow and only chow. After 8 mo, feeding period, each group was divided into two subgroups, in which the rats were implanted with DMBA and no DMBA (sham). Histologic specimens were evaluated according to the routine tissue processing protocol. The animals with ad libitum access to pn-HFCS, pn-sucrose and chow (only) showed significant differences in chow consumption and glucose level. Necropsy and histopathologic findings showed tumor formation in the entire group treated with DMBA. Excluding one rat in chow group, which was classified as poorly differentiated type, the others were classified as moderately differentiated pancreatic ductal adenocarcinoma (PDAC). This study demonstrated that daily intake of HFCS did not increase body weight and there was no effect of peach nectar consumption on the development of PDAC induced by DMBA in rats.
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Affiliation(s)
- Gulsah Ozcan-Sınır
- Department of Food Engineering, Faculty of Agriculture, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Sevda Inan
- Department of Pathology, Faculty of Veterinary Medicine, Tekirdag Namik Kemal University, Tekirdag, Turkey
| | - Senem Suna
- Department of Food Engineering, Faculty of Agriculture, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Canan Ece Tamer
- Department of Food Engineering, Faculty of Agriculture, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Mustafa Barış Akgül
- Department of Surgery, Faculty of Veterinary Medicine, Siirt University, Siirt, Turkey
| | - Deniz Bagdas
- Department of Psychiatry, Yale University School of Medicine, New Heaven, CT, USA
| | - Gursel Sonmez
- Department of Pathology, Faculty of Veterinary Medicine, Bursa Uludag University, Bursa, Turkey
| | - Turkkan Evrensel
- Department of Medical Oncology, Faculty of Medicine, Bursa Uludag University, Bursa, Turkey Görükle
| | - Ekrem Kaya
- Department of Surgery, Faculty of Medicine, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Emre Sarandol
- Department of Biochemistry, Faculty of Medicine, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Halit Ziya Dündar
- Department of Surgery, Faculty of Medicine, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Omer Faruk Tarım
- Department of Paediatric Endocrinology, Faculty of Medicine, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Ilker Ercan
- Department of Biostatistic, Faculty of Medicine, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Deniz Sıgırlı
- Department of Biostatistic, Faculty of Medicine, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Bige Incedayı
- Department of Food Engineering, Faculty of Agriculture, Bursa Uludag University, Görükle, Bursa, Turkey
| | - Omer Utku Copur
- Department of Food Engineering, Faculty of Agriculture, Bursa Uludag University, Görükle, Bursa, Turkey
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40
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Principe DR, Rana A. Updated risk factors to inform early pancreatic cancer screening and identify high risk patients. Cancer Lett 2020; 485:56-65. [PMID: 32389710 DOI: 10.1016/j.canlet.2020.04.022] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 04/06/2020] [Accepted: 04/23/2020] [Indexed: 02/07/2023]
Abstract
Pancreatic adenocarcinoma (PDAC) is associated with poor clinical outcomes and incomplete responses to conventional therapy. Therefore, there is an unmet clinical need to better understand the predisposing factors for pancreatic cancer in hopes of providing early screening to high-risk patients. While select risk factors such as age, race, and family history, or predisposing syndromes are unavoidable, there are several new and established risk factors that allow for intervention, namely by counseling patients to make the appropriate lifestyle modifications. Here, we discuss the best-studied risk factors for PDAC such as tobacco use and chronic pancreatitis, as well as newly emerging risk factors including select nutritional deficits, bacterial infections, and psychosocial factors. As several of these risk factors appear to be additive or synergistic, by understanding their relationships and offering coordinated, multidisciplinary care to high-risk patients, it may be possible to reduce pancreatic cancer incidence and improve clinical outcomes through early detection.
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Affiliation(s)
- Daniel R Principe
- Medical Scientist Training Program, University of Illinois College of Medicine, Chicago, IL, USA; Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA.
| | - Ajay Rana
- Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago, Chicago, IL, USA; Jesse Brown VA Medical Center, Chicago, IL, USA.
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41
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Tao H, Chen X, Du Z, Ding K. Corn silk crude polysaccharide exerts anti-pancreatic cancer activity by blocking the EGFR/PI3K/AKT/CREB signaling pathway. Food Funct 2020; 11:6961-6970. [DOI: 10.1039/d0fo00403k] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
S1, a crude polysaccharide from corn silk, may significantly inhibit pancreatic cancer cell proliferation in vitro and in vivo. It can induce apoptosis, arrest the cell cycle in S phase and impede pancreatic cancer cell migration and invasion.
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Affiliation(s)
- Hong Tao
- Glycochemistry & Glycobiology Lab
- Key Laboratory of Receptor Research
- Shanghai Institute of Materia Medica
- Chinese Academy of Sciences
- Shanghai
| | - Xia Chen
- Glycochemistry & Glycobiology Lab
- Key Laboratory of Receptor Research
- Shanghai Institute of Materia Medica
- Chinese Academy of Sciences
- Shanghai
| | - Zhenyun Du
- Glycochemistry & Glycobiology Lab
- Key Laboratory of Receptor Research
- Shanghai Institute of Materia Medica
- Chinese Academy of Sciences
- Shanghai
| | - Kan Ding
- Glycochemistry & Glycobiology Lab
- Key Laboratory of Receptor Research
- Shanghai Institute of Materia Medica
- Chinese Academy of Sciences
- Shanghai
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42
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Zhang S, He F, Chen X, Ding K. Isolation and structural characterization of a pectin from Lycium ruthenicum Murr and its anti-pancreatic ductal adenocarcinoma cell activity. Carbohydr Polym 2019; 223:115104. [DOI: 10.1016/j.carbpol.2019.115104] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 07/14/2019] [Accepted: 07/16/2019] [Indexed: 12/14/2022]
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43
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Affiliation(s)
- Paulo Andrade Lotufo
- MD, DrPH. Full Professor, Department of Internal Medicine, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo (SP), Brazil
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44
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Stevens CL, Watters DAK. Short-term outcomes of pancreaticoduodenectomy in the state of Victoria: hospital resources are more important than volume. ANZ J Surg 2019; 89:1577-1581. [PMID: 31222880 DOI: 10.1111/ans.15298] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 04/22/2019] [Accepted: 04/23/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Pancreaticoduodenectomy (PD) is a high-risk procedure. Australian hospitals perform a relatively low volume of PD. This study sought to gain an understanding of hospital volume and short-term outcomes of the procedure in the Australian state of Victoria. METHODS The Dr Foster Quality Investigator tool was used to interrogate the Victorian Admitted Episodes Database for the Australian Classification of Health Intervention code for PD (30584) from July 2010 to June 2016. The data set included patients from a peer group of 14 hospitals that included all the public hospitals performing PD during this period. Patient characteristics, inpatient mortality, 30-day readmission rates and median length of stay were reported for each de-identified hospital. RESULTS There were 547 PD conducted over 6 years in 10 public hospitals. The median patient age was 65 years. Inpatient mortality was 2.7%. There was a significant risk adjusted difference in mortality between principal referral and other public hospitals. Annual hospital volume ranged from 3 to 20 PD, and there was no significant relationship between mortality, readmission rates or length of stay and hospital volume. CONCLUSION The inpatient mortality associated with PD in Victorian public hospitals is comparable to that seen in overseas studies. While hospital volume is relatively low, there does not seem to be a relationship between volume and short-term outcomes. Variability between hospital peer groups suggests that resource availability is more important than volume. The development of a procedure specific registry would be useful to test the outcomes of this study and determine long-term PD outcomes.
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Affiliation(s)
- Claire L Stevens
- Discipline of Surgery, The University of Adelaide, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia
| | - David A K Watters
- Department of Surgery, University Hospital Geelong, Geelong, Melbourne, Australia
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45
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Cirera L, Huerta JM, Chirlaque MD, Overvad K, Lindström M, Regnér S, Tjønneland A, Boutron-Ruault MC, Rebours V, Fagherazzi G, Katzke VA, Boeing H, Peppa E, Trichopoulou A, Valanou E, Palli D, Grioni S, Panico S, Tumino R, Ricceri F, van Gils C, Vermeulen RCH, Skeie G, Braaten T, Weiderpass E, Merino S, Sánchez MJ, Larrañaga N, Ardanaz E, Sund M, Khaw KT, Key TJ, Jenab M, Naudin S, Murphy N, Aune D, Ward H, Riboli E, Bueno-de-Mesquita B, Navarro C, Duell EJ. Socioeconomic Effect of Education on Pancreatic Cancer Risk in Western Europe: An Update on the EPIC Cohorts Study. Cancer Epidemiol Biomarkers Prev 2019; 28:1089-1092. [PMID: 31160392 DOI: 10.1158/1055-9965.epi-18-1153] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 03/05/2019] [Accepted: 03/07/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND To analyze the potential effect of social inequality on pancreatic cancer risk in Western Europe, by reassessing the association within the European Prospective Investigation into Cancer and Nutrition (EPIC) Study, including a larger number of cases and an extended follow-up. METHODS Data on highest education attained were gathered for 459,170 participants (70% women) from 10 European countries. A relative index of inequality (RII) based on adult education was calculated for comparability across countries and generations. Cox regression models were applied to estimate relative inequality in pancreatic cancer risk, stratifying by age, gender, and center, and adjusting for known pancreatic cancer risk factors. RESULTS A total of 1,223 incident pancreatic cancer cases were included after a mean follow-up of 13.9 (±4.0) years. An inverse social trend was found in models adjusted for age, sex, and center for both sexes [HR of RII, 1.27; 95% confidence interval (CI), 1.02-1.59], which was also significant among women (HR, 1.42; 95% CI, 1.05-1.92). Further adjusting by smoking intensity, alcohol consumption, body mass index, prevalent diabetes, and physical activity led to an attenuation of the RII risk and loss of statistical significance. CONCLUSIONS The present reanalysis does not sustain the existence of an independent social inequality influence on pancreatic cancer risk in Western European women and men, using an index based on adult education, the most relevant social indicator linked to individual lifestyles, in a context of very low pancreatic cancer survival from (quasi) universal public health systems. IMPACT The results do not support an association between education and risk of pancreatic cancer.
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Affiliation(s)
- Lluís Cirera
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. .,CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.,Department of Health and Social Sciences, University of Murcia, Murcia, Spain
| | - José María Huerta
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.,CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - María Dolores Chirlaque
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.,CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.,Department of Health and Social Sciences, University of Murcia, Murcia, Spain
| | - Kim Overvad
- Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Martin Lindström
- Department of Clinical Sciences, Social Medicine and Health Policy, Lund University, Malmö, Sweden
| | - Sara Regnér
- Department of Clinical Sciences, Social Medicine and Health Policy, Lund University, Malmö, Sweden
| | - Anne Tjønneland
- Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark.,Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Marie-Christine Boutron-Ruault
- CESP, Faculté de Médecine - Université Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.,Gustave Roussy Institute, Villejuif, France
| | - Vinciane Rebours
- Pancreatology Unit, Beaujon Hospital, Clichy, France.,INSERM - UMR 1149, University Paris 7, France
| | - Guy Fagherazzi
- CESP, Faculté de Médecine - Université Paris-Sud, Faculté de Médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France.,Gustave Roussy Institute, Villejuif, France
| | | | - Heiner Boeing
- Department of Epidemiology German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany
| | | | | | | | - Domenico Palli
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
| | - Sara Grioni
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy
| | - Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico ii University, Naples, Italy
| | - Rosario Tumino
- Department of Cancer Registry and Histopathology, "Civic - M.P. Arezzo" Hospital, ASP Ragusa, Italy
| | - Fulvio Ricceri
- Department of Clinical and Biological Sciences, University of Turin, Italy.,Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy
| | - Carla van Gils
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Roel C H Vermeulen
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.,Environmental Epidemiology Division, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
| | - Guri Skeie
- Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Tonje Braaten
- Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway
| | - Elisabete Weiderpass
- Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.,Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Genetic Epidemiology Group, Folkhälsan Research Center, and Faculty of Medicine, Helsinki University, Helsinki, Finland
| | - Susana Merino
- Public Health Directorate, Regional Government of Asturias, Oviedo, Spain
| | - María José Sánchez
- Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain
| | - Nerea Larrañaga
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.,Public Health Division of Gipuzkoa, Regional Government of the Basque Country, Donostia, Spain
| | - Eva Ardanaz
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.,Navarra Public Health Institute, Pamplona, Spain.,IdiSNA, Navarra Institute for Health Research, Pamplona, Spain
| | - Malin Sund
- Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Kay-Tee Khaw
- University of Cambridge, School of Clinical Medicine Addenbrooke's Hospital, Cambridge, United Kingdom
| | - Timothy J Key
- Nuffield Department of Population Health, Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom
| | - Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Sabine Naudin
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, United Kingdom
| | - Heather Ward
- Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, United Kingdom
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, United Kingdom
| | - Bas Bueno-de-Mesquita
- Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.,Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands.,Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, United Kingdom.,Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Carmen Navarro
- Department of Health and Social Sciences, University of Murcia, Murcia, Spain
| | - Eric J Duell
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L'Hospitalet de Llobregat, Spain
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Huang BZ, Stram DO, Le Marchand L, Haiman CA, Wilkens LR, Pandol SJ, Zhang Z, Monroe KR, Setiawan VW. Interethnic differences in pancreatic cancer incidence and risk factors: The Multiethnic Cohort. Cancer Med 2019; 8:3592-3603. [PMID: 31066497 PMCID: PMC6601579 DOI: 10.1002/cam4.2209] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 04/11/2019] [Accepted: 04/12/2019] [Indexed: 12/14/2022] Open
Abstract
While disparity in pancreatic cancer incidence between blacks and whites has been observed, few studies have examined disparity in other ethnic minorities. We evaluated variations in pancreatic cancer incidence and assessed the extent to which known risk factors account for differences in pancreatic cancer risk among African Americans, Native Hawaiians, Japanese Americans, Latino Americans, and European Americans in the Multiethnic Cohort Study. Risk factor data were obtained from the baseline questionnaire. Cox regression was used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer associated with risk factors and ethnicity. During an average 16.9-year follow-up, 1,532 incident pancreatic cancer cases were identified among 184,559 at-risk participants. Family history of pancreatic cancer (RR 1.97, 95% CI 1.50-2.58), diabetes (RR 1.32, 95% CI 1.14-1.54), body mass index ≥30 kg/m2 (RR 1.25, 95% CI 1.08-1.46), current smoking (<20 pack-years RR 1.43, 95% CI 1.19-1.73; ≥20 pack-years RR 1.76, 95% CI 1.46-2.12), and red meat intake (RR 1.17, 95% CI 1.00-1.36) were associated with pancreatic cancer. After adjustment for these risk factors, Native Hawaiians (RR 1.60, 95% CI 1.30-1.98), Japanese Americans (RR 1.33, 95% CI 1.15-1.54), and African Americans (RR 1.20, 95% CI 1.01-1.42), but not Latino Americans (RR 0.90, 95% CI 0.76-1.07), had a higher risk of pancreatic cancer compared to European Americans. Interethnic differences in pancreatic cancer risk are not fully explained by differences in the distribution of known risk factors. The greater risks in Native Hawaiians and Japanese Americans are new findings and elucidating the causes of these high rates may improve our understanding and prevention of pancreatic cancer.
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Affiliation(s)
- Brian Z. Huang
- Department of EpidemiologyUCLA Fielding School of Public HealthLos AngelesCalifornia,Department of Research & EvaluationKaiser Permanente Southern CaliforniaPasadenaCalifornia
| | - Daniel O. Stram
- Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCalifornia
| | - Loic Le Marchand
- Epidemiology ProgramUniversity of Hawaii Cancer CenterHonoluluHawaii
| | - Christopher A. Haiman
- Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCalifornia,Norris Comprehensive Cancer CenterLos AngelesCalifornia
| | - Lynne R. Wilkens
- Epidemiology ProgramUniversity of Hawaii Cancer CenterHonoluluHawaii
| | - Stephen J. Pandol
- Division of Gastroenterology, Department of MedicineCedars‐Sinai Medical Center and Department of Veterans AffairsLos AngelesCalifornia
| | - Zuo‐Feng Zhang
- Department of EpidemiologyUCLA Fielding School of Public HealthLos AngelesCalifornia
| | - Kristine R. Monroe
- Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCalifornia
| | - Veronica Wendy Setiawan
- Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCalifornia,Norris Comprehensive Cancer CenterLos AngelesCalifornia
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Gao Z, Peng M, Chen L, Yang X, Li H, Shi R, Wu G, Cai L, Song Q, Li C. Prion Protein Protects Cancer Cells against Endoplasmic Reticulum Stress Induced Apoptosis. Virol Sin 2019; 34:222-234. [PMID: 31020572 PMCID: PMC6513834 DOI: 10.1007/s12250-019-00107-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 02/28/2019] [Indexed: 12/20/2022] Open
Abstract
Unfolded protein response (UPR) is an adaptive reaction for cells to reduce endoplasmic reticulum (ER) stress. In many types of cancers, such as lung cancer and pancreatic cancer, cancer cells may harness ER stress to facilitate their survival and growth. Prion protein (PrP) is a glycosylated cell surface protein that has been shown to be up-regulated in many cancer cells. Since PrP is a protein prone to misfolding, ER stress can result in under-glycosylated PrP, which in turn may activate ER stress. To assess whether ER stress leads to the production of under-glycosylated PrP and whether under-glycosylated PrP may contribute to ER stress thus leading to cancer cell apoptosis, we treated different cancer cells with brefeldin A (BFA), thapsigargin (Thps), and tunicamycin (TM). We found that although BFA, Thps, and TM treatment activated UPR, only ATF4 was consistently activated by these reagents, but not other branches of ER stress. However, the canonical PERK-eIF2α-ATF4 did not account for the observed activation of ATF4 in lung cancer cells. In addition, BFA, but neither Thps nor TM, significantly stimulated the expression of cytosolic PrP. Finally, we found that the levels of PrP contributed to anti-apoptosis activity of BFA-induced cancer cell death. Thus, the pathway of BFA-induced persistent ER stress may be targeted for lung and pancreatic cancer treatment.
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Affiliation(s)
- Zhenxing Gao
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
| | - Min Peng
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Liang Chen
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Xiaowen Yang
- Department of the First Abdominal Surgery, Jiangxi Tumor Hospital, Nanchang, 330029, China
| | - Huan Li
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
| | - Run Shi
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
| | - Guiru Wu
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
| | - Lili Cai
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China
| | - Qibin Song
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, China
| | - Chaoyang Li
- State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China.
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48
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Helicobacter pylori infection, atrophic gastritis, and risk of pancreatic cancer: A population-based cohort study in a large Japanese population: the JPHC Study. Sci Rep 2019; 9:6099. [PMID: 30988344 PMCID: PMC6465350 DOI: 10.1038/s41598-019-42365-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 03/29/2019] [Indexed: 12/24/2022] Open
Abstract
Helicobacter pylori (H. pylori), an established risk factor for gastric cancer, is suggested to also play a role in the development of pancreatic cancer; however, the association remains inconclusive. We examined this association among Japanese men and women. H. pylori and atrophic gastritis (AG) status were determined serologically, using blood sample collected during health checkups. A total of 20,116 subjects enrolled in the Japan Public Health Center-based Prospective Study Cohort II with available data on H. pylori seropositivity (anti-H. pylori) and AG were followed until the end of 2010. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI), using the information from the baseline survey. During 320,470 person-years of follow-up, 119 cases of pancreatic cancer were identified. No statically significant increase or decrease in pancreatic cancer risk was observed for H. pylori and AG status, independently or in combination. In a multivariable-adjusted model, we observed a non-significant decrease in the risk among those who had AG but were anti-H. pylori seronegative (HR 0.57, 95% CI 0.31–1.03). In a stratified analysis, we observed a statistically significant increased risk of pancreatic cancer for AG+ (HR 3.64, 95% CI 1.37–9.66), and AG+/anti-H. pylori− or AG+/anti-H. pylori+ (HR 5.21, 95% CI 1.14–23.87) among current smokers. Non-smokers in all categories of AG and anti-H. pylori showed a non-statistical decrease in the risk. There was no statistically significant interaction between H. pylori infection, AG status, and smoking status. Our findings suggest H. pylori seropositivity and AG, individually or in combination, are not associated with the risk of pancreatic cancer in a general Japanese population. Among current smokers, pancreatic cancer risk increased with AG, regardless of H. pylori infection status.
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Serum selenium and pancreatic cancer: a prospective study in the Prostate, Lung, Colorectal and Ovarian Cancer Trial cohort. Cancer Causes Control 2019; 30:457-464. [PMID: 30915619 DOI: 10.1007/s10552-019-01147-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 02/14/2019] [Indexed: 12/20/2022]
Abstract
PURPOSE Pancreatic cancer(PCa) is one of the most lethal cancers with few known consistent nutrition-related risk factors. Epidemiologic associations between the trace element selenium and PCa are inconsistent. This study examined the association of pre-diagnostic serum selenium with incident PCa. METHODS We conducted a nested case-control study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Study (PLCO) cohort of men and women 55-70 years old at baseline (1993-2001). In total, 303 PCa cases developed during the 17-year follow-up period (1993-2009). We selected two controls (n = 606) for each case who were alive at the time the case was diagnosed who were matched on age, sex, race, and date of blood draw. We used conditional logistic regression analysis to calculate the odds ratio (OR) and 95% confidence intervals (CI) adjusting for smoking status and diabetes mellitus. RESULTS Mean serum selenium concentrations were slightly lower in cases (mean, 95% CI: 139.0 ng/ml, 135.6-138.9) compared to controls (142.5 ng/ml, 140.4-142.4, p = 0.08). Overall, serum selenium was not associated with PCa risk (continuous OR: 0.66; 0.32-1.37). There was no significant interaction by sex, smoking, diabetes, or follow-up time (p > 0.05). CONCLUSION Our results do not support the hypothesis that serum selenium is associated with PCa risk.
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Maisonneuve P. Epidemiology and burden of pancreatic cancer. Presse Med 2019; 48:e113-e123. [PMID: 30878335 DOI: 10.1016/j.lpm.2019.02.030] [Citation(s) in RCA: 85] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 02/13/2019] [Indexed: 02/07/2023] Open
Abstract
Pancreatic cancer, although infrequent, has a very poor prognosis, making it currently the fourth common causes of cancer mortality in most developed countries including the European Union (EU). Its incidence varies across regions, which suggests that lifestyle factors play an important role in its etiology, although part of the variation could be ascribed to difference in diagnostic and coding practices. Because pancreatic cancer is strongly age-dependent, increasing population longevity and ageing will lead to an increase of the global burden of pancreatic cancer. It was estimated that, by 2040, the total number of cases in the EU will increase by more than 30%. Pancreatic cancer is a multifactorial disease and many risk factors have been identified. Hereditary factors are responsible for less than 10% of the cases while tobacco smoking and excess body weight, the two most important potentially modifiable risk factors, are responsible for 10 to 30% of the cases, affording a unique opportunity for preventing one of our deadliest cancers.
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Affiliation(s)
- Patrick Maisonneuve
- Unit of Clinical Epidemiology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
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