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Article ; Online: COVID-19 in a Patient with Liver Cirrhosis.

Kreivenaite, Edita / Gedgaudas, Rolandas / Valantiene, Irena / Mickiene, Aukse / Kupcinskas, Juozas

Journal of gastrointestinal and liver diseases : JGLD

2020 Volume 29, Issue 2, Page(s) 263–266

Abstract: The outbreak of coronavirus disease 2019 (COVID-19) has recently become a serious issue affecting thousands of people worldwide. It is known that a substantial proportion of patients infected with COVID-19 have abnormal liver function tests; however, the ...

Abstract	The outbreak of coronavirus disease 2019 (COVID-19) has recently become a serious issue affecting thousands of people worldwide. It is known that a substantial proportion of patients infected with COVID-19 have abnormal liver function tests; however, the consequences of this information is still not clear. Here we present the first case report of a patient with liver cirrhosis and COVID-19 in our centre. Resolution of COVID-19 symptoms was observed after six days of fever onset. We observed only slight fluctuations of liver enzymes, bilirubin levels and INR without clinical consequences in our case. We suggest testing for severe acute respiratory syndrome coronavirus on any cirrhotic patient on initial presentation, even without symptoms of COVID-19 in areas where the epidemic was prevalent.
MeSH term(s)	Betacoronavirus/isolation & purification ; COVID-19 ; COVID-19 Testing ; Clinical Laboratory Techniques ; Coronavirus Infections/complications ; Coronavirus Infections/diagnosis ; Female ; Humans ; Liver Cirrhosis/complications ; Middle Aged ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/diagnosis ; SARS-CoV-2
Keywords	covid19
Language	English
Publishing date	2020-06-04
Publishing country	Romania
Document type	Case Reports
ZDB-ID	2427021-0
ISSN	1842-1121 ; 1841-8724
ISSN (online)	1842-1121
ISSN	1841-8724
DOI	10.15403/jgld-2440
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Article ; Online: Hepatitis C Virus Epidemiology in Lithuania: Situation before Introduction of the National Screening Programme.

Ciupkeviciene, Egle / Petkeviciene, Janina / Sumskiene, Jolanta / Dragunas, Gediminas / Dabravalskis, Saulius / Kreivenaite, Edita / Telksnys, Tadas / Urbonas, Gediminas / Kupcinskas, Limas

Viruses

2022 Volume 14, Issue 6

Abstract: In 2022, the Lithuanian health authorities decided to pay general practitioners a fee for performing serological tests for hepatitis C virus (HCV) antibodies in the population born from 1945 to 1994 once per life and annual HCV testing for PWID and HIV ... ...

Abstract	In 2022, the Lithuanian health authorities decided to pay general practitioners a fee for performing serological tests for hepatitis C virus (HCV) antibodies in the population born from 1945 to 1994 once per life and annual HCV testing for PWID and HIV infected patients. This study aimed to assess trends in HCV-related mortality in the country and the prevalence of HCV infection among patients with liver diseases and evaluate possibilities of screening for HCV infection at a primary health care center. Age-standardized mortality rates in 2010-2020 were calculated for deaths caused by chronic hepatitis C and some liver diseases. Data on HCV infection among patients with liver cirrhosis, cancer and transplant patients were collected from the tertiary care hospital Kauno Klinikos. The prevalence of anti-HCV and risk factors of HCV infection was assessed among patients registered with the health care center in Klaipeda, where a pilot study of screening was performed. No steady trend in mortality was observed. Analysis of medical documentation showed that 40.5% of patients with liver cirrhosis, 49.7% with cancers and 36.9% of transplant patients were HCV infected. Over the year, 4867 patients were screened in the primary health care center. Positive anti-HCV prevalence was 1.7% (2.1% in men and 1.3% in women). Blood transfusion and being a blood donor before 1993 also having tattoos were associated with higher odds of HCV infection. The study revealed the active participation of individuals in HCV screening.
MeSH term(s)	Female ; Hepacivirus ; Hepatitis C/complications ; Hepatitis C/diagnosis ; Hepatitis C/epidemiology ; Hepatitis C Antibodies ; Humans ; Lithuania/epidemiology ; Liver Cirrhosis ; Male ; Pilot Projects ; Prevalence
Chemical Substances	Hepatitis C Antibodies
Language	English
Publishing date	2022-05-30
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061192
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Article: Hepatitis C Virus Epidemiology in Lithuania: Situation before Introduction of the National Screening Programme

Ciupkeviciene, Egle / Petkeviciene, Janina / Sumskiene, Jolanta / Dragunas, Gediminas / Dabravalskis, Saulius / Kreivenaite, Edita / Telksnys, Tadas / Urbonas, Gediminas / Kupcinskas, Limas

Viruses. 2022 May 30, v. 14, no. 6

2022

Abstract	In 2022, the Lithuanian health authorities decided to pay general practitioners a fee for performing serological tests for hepatitis C virus (HCV) antibodies in the population born from 1945 to 1994 once per life and annual HCV testing for PWID and HIV infected patients. This study aimed to assess trends in HCV-related mortality in the country and the prevalence of HCV infection among patients with liver diseases and evaluate possibilities of screening for HCV infection at a primary health care center. Age-standardized mortality rates in 2010–2020 were calculated for deaths caused by chronic hepatitis C and some liver diseases. Data on HCV infection among patients with liver cirrhosis, cancer and transplant patients were collected from the tertiary care hospital Kauno Klinikos. The prevalence of anti-HCV and risk factors of HCV infection was assessed among patients registered with the health care center in Klaipeda, where a pilot study of screening was performed. No steady trend in mortality was observed. Analysis of medical documentation showed that 40.5% of patients with liver cirrhosis, 49.7% with cancers and 36.9% of transplant patients were HCV infected. Over the year, 4867 patients were screened in the primary health care center. Positive anti-HCV prevalence was 1.7% (2.1% in men and 1.3% in women). Blood transfusion and being a blood donor before 1993 also having tattoos were associated with higher odds of HCV infection. The study revealed the active participation of individuals in HCV screening.
Keywords	Hepatitis C virus ; blood donors ; blood transfusion ; chronic hepatitis C ; epidemiology ; health services ; hospitals ; liver ; liver cirrhosis ; mortality ; Lithuania
Language	English
Dates of publication	2022-0530
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14061192
Database	NAL-Catalogue (AGRICOLA)

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Article: COVID-19 in a Patient with Liver Cirrhosis

Kreivenaite, Edita / Gedgaudas, Rolandas / Valantiene, Irena / Mickiene, Aukse / Kupcinskas, Juozas

J Gastrointestin Liver Dis

Abstract	The outbreak of coronavirus disease 2019 (COVID-19) has recently become a serious issue affecting thousands of people worldwide. It is known that a substantial proportion of patients infected with COVID-19 have abnormal liver function tests; however, the consequences of this information is still not clear. Here we present the first case report of a patient with liver cirrhosis and COVID-19 in our centre. Resolution of COVID-19 symptoms was observed after six days of fever onset. We observed only slight fluctuations of liver enzymes, bilirubin levels and INR without clinical consequences in our case. We suggest testing for severe acute respiratory syndrome coronavirus on any cirrhotic patient on initial presentation, even without symptoms of COVID-19 in areas where the epidemic was prevalent.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #32530994
Database	COVID19

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Article ; Online: Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Ünal, Pelin / Lu, Ye / Bueno-de-Mesquita, Bas / van Eijck, Casper H J / Talar-Wojnarowska, Renata / Szentesi, Andrea / Gazouli, Maria / Kreivenaite, Edita / Tavano, Francesca / Małecka-Wojciesko, Ewa / Erőss, Bálint / Oliverius, Martin / Bunduc, Stefania / Nóbrega Aoki, Mateus / Vodickova, Ludmila / Boggi, Ugo / Giaccherini, Matteo / Kondrackiene, Jurate / Chammas, Roger /

Palmieri, Orazio / Theodoropoulos, George E / Bijlsma, Maarten F / Basso, Daniela / Mohelnikova-Duchonova, Beatrice / Soucek, Pavel / Izbicki, Jakob R / Kiudelis, Vytautas / Vanella, Giuseppe / Arcidiacono, Paolo Giorgio / Włodarczyk, Barbara / Hackert, Thilo / Schöttker, Ben / Uzunoglu, Faik G / Bambi, Franco / Goetz, Mara / Hlavac, Viktor / Brenner, Hermann / Perri, Francesco / Carrara, Silvia / Landi, Stefano / Hegyi, Péter / Dijk, Frederike / Maiello, Evaristo / Capretti, Giovanni / Testoni, Sabrina Gloria Giulia / Petrone, Maria Chiara / Stocker, Hannah / Ermini, Stefano / Archibugi, Livia / Gentiluomo, Manuel / Cavestro, Giulia Martina / Pezzilli, Raffaele / Di Franco, Gregorio / Milanetto, Anna Caterina / Sperti, Cosimo / Neoptolemos, John P / Morelli, Luca / Vokacova, Klara / Pasquali, Claudio / Lawlor, Rita T / Bazzocchi, Francesca / Kupcinskas, Juozas / Capurso, Gabriele / Campa, Daniele / Canzian, Federico

Human genomics

2024 Volume 18, Issue 1, Page(s) 12

Abstract: Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance ... ...

Abstract	Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10
MeSH term(s)	Humans ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/epidemiology ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Regulatory Sequences, Nucleic Acid ; Polymorphism, Single Nucleotide/genetics ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Binding Sites/genetics
Chemical Substances	Transcription Factors
Language	English
Publishing date	2024-02-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2147618-4
ISSN	1479-7364 ; 1479-7364
ISSN (online)	1479-7364
ISSN	1479-7364
DOI	10.1186/s40246-024-00576-x
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Article ; Online: Polymorphic variants involved in methylation regulation: a strategy to discover risk loci for pancreatic ductal adenocarcinoma.

Corradi, Chiara / Lencioni, Giulia / Gentiluomo, Manuel / Felici, Alessio / Latiano, Anna / Kiudelis, Gediminas / van Eijck, Casper H J / Marta, Katalin / Lawlor, Rita T / Tavano, Francesca / Boggi, Ugo / Dijk, Frederike / Cavestro, Giulia Martina / Vermeulen, Roel C H / Hackert, Thilo / Petrone, Maria Chiara / Uzunoğlu, Faik Güntac / Archibugi, Livia / Izbicki, Jakob R /

Morelli, Luca / Zerbi, Alessandro / Landi, Stefano / Stocker, Hannah / Talar-Wojnarowska, Renata / Di Franco, Gregorio / Hegyi, Péter / Sperti, Cosimo / Carrara, Silvia / Capurso, Gabriele / Gazouli, Maria / Brenner, Hermann / Bunduc, Stefania / Busch, Olivier / Perri, Francesco / Oliverius, Martin / Hegyi, Péter Jeno / Goetz, Mara / Scognamiglio, Pasquale / Mambrini, Andrea / Arcidiacono, Paolo Giorgio / Kreivenaite, Edita / Kupcinskas, Juozas / Hussein, Tamas / Ermini, Stefano / Milanetto, Anna Caterina / Vodicka, Pavel / Kiudelis, Vytautas / Hlaváč, Viktor / Soucek, Pavel / Theodoropoulos, George E / Basso, Daniela / Neoptolemos, John P / Nóbrega Aoki, Mateus / Pezzilli, Raffaele / Pasquali, Claudio / Chammas, Roger / Testoni, Sabrina Gloria Giulia / Mohelnikova-Duchonova, Beatrice / Lucchesi, Maurizio / Rizzato, Cosmeri / Canzian, Federico / Campa, Daniele

Journal of medical genetics

2023 Volume 60, Issue 10, Page(s) 980–986

Abstract: Introduction: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime ... ...

Abstract	Introduction: Only a small number of risk factors for pancreatic ductal adenocarcinoma (PDAC) has been established. Several studies identified a role of epigenetics and of deregulation of DNA methylation. DNA methylation is variable across a lifetime and in different tissues; nevertheless, its levels can be regulated by genetic variants like methylation quantitative trait loci (mQTLs), which can be used as a surrogate. Materials and methods: We scanned the whole genome for mQTLs and performed an association study in 14 705 PDAC cases and 246 921 controls. The methylation data were obtained from whole blood and pancreatic cancer tissue through online databases. We used the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium genome-wide association study (GWAS) data as discovery phase and the Pancreatic Disease Research consortium, the FinnGen project and the Japan Pancreatic Cancer Research consortium GWAS as replication phase. Results: The C allele of 15q26.1-rs12905855 showed an association with a decreased risk of PDAC (OR=0.90, 95% CI 0.87 to 0.94, p=4.93×10 Conclusion: We identified a novel PDAC risk locus which modulates cancer risk by controlling gene expression through DNA methylation.
MeSH term(s)	Humans ; Genome-Wide Association Study ; Pancreatic Neoplasms/genetics ; Carcinoma, Pancreatic Ductal/genetics ; DNA Methylation/genetics ; Pancreatic Neoplasms
Language	English
Publishing date	2023-05-02
Publishing country	England
Document type	Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	220881-7
ISSN	1468-6244 ; 0022-2593
ISSN (online)	1468-6244
ISSN	0022-2593
DOI	10.1136/jmg-2022-108910
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Article ; Online: Genetic and non-genetic risk factors for early-onset pancreatic cancer.

Nodari, Ylenia / Gentiluomo, Manuel / Mohelnikova-Duchonova, Beatrice / Kreivenaite, Edita / Milanetto, Anna Caterina / Skieceviciene, Jurgita / Landi, Stefano / Lawlor, Rita T / Petrone, Maria Chiara / Arcidiacono, Paolo Giorgio / Lovecek, Martin / Gazouli, Maria / Bijlsma, Maarten F / Morelli, Luca / Kiudelis, Vytautas / Tacelli, Matteo / Zanette, Dalila Lucíola / Soucek, Pavel / Uzunoglu, Faik /

Kaaks, Rudolf / Izbicki, Jakob / Boggi, Ugo / Pezzilli, Raffaele / Mambrini, Andrea / Pasquali, Claudio / van Laarhoven, Hanneke W / Katzke, Verena / Cavestro, Giulia Martina / Sperti, Cosimo / Loos, Martin / Latiano, Anna / Erőss, Bálint / Oliverius, Martin / Johnson, Theron / Basso, Daniela / Neoptolemos, John P / Aoki, Mateus Nóbrega / Greenhalf, William / Vodicka, Pavel / Archibugi, Livia / Vanella, Giuseppe / Lucchesi, Maurizio / Talar-Wojnarowska, Renata / Jamroziak, Krzysztof / Saeedi, Mohammed Al / van Eijck, Casper H J / Kupcinskas, Juozas / Hussein, Tamás / Puzzono, Marta / Bunduc, Stefania / Götz, Mara / Carrara, Silvia / Szentesi, Andrea / Tavano, Francesca / Moz, Stefania / Hegyi, Péter / Luchini, Claudio / Capurso, Gabriele / Perri, Francesco / Ermini, Stefano / Theodoropoulos, George / Capretti, Giovanni / Palmieri, Orazio / Ginocchi, Laura / Furbetta, Niccolò / Canzian, Federico / Campa, Daniele

Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver

2023 Volume 55, Issue 10, Page(s) 1417–1425

Abstract: Background: Early-onset pancreatic cancer (EOPC) represents 5-10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for ... ...

Abstract	Background: Early-onset pancreatic cancer (EOPC) represents 5-10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC. Methods: A genome-wide association study was performed, analysing 912 EOPC cases and 10 222 controls, divided into discovery and replication phases. Furthermore, the associations between a polygenic risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were also assessed. Results: Six novel SNPs were associated with EOPC risk in the discovery phase, but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk. The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69-5.04, P = 1.44 × 10 Conclusion: In conclusion, we did not identify novel genetic variants associated specifically with EOPC, and we found that established PDAC risk variants do not have a strong age-dependent effect. Furthermore, we add to the evidence pointing to the role of smoking and diabetes in EOPC.
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/complications ; Genome-Wide Association Study ; Pancreatic Neoplasms/pathology ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Risk Factors ; Pancreatic Neoplasms
Language	English
Publishing date	2023-03-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1459373-7
ISSN	1878-3562 ; 1125-8055
ISSN (online)	1878-3562
ISSN	1125-8055
DOI	10.1016/j.dld.2023.02.023
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Article ; Online: Genome-wide scan of long noncoding RNA single nucleotide polymorphisms and pancreatic cancer susceptibility.

Corradi, Chiara / Gentiluomo, Manuel / Gajdán, László / Cavestro, Giulia Martina / Kreivenaite, Edita / Di Franco, Gregorio / Sperti, Cosimo / Giaccherini, Matteo / Petrone, Maria Chiara / Tavano, Francesca / Gioffreda, Domenica / Morelli, Luca / Soucek, Pavel / Andriulli, Angelo / Izbicki, Jakob R / Napoli, Niccolò / Małecka-Panas, Ewa / Hegyi, Péter / Neoptolemos, John P /

Landi, Stefano / Vashist, Yogesh / Pasquali, Claudio / Lu, Ye / Cervena, Klara / Theodoropoulos, George E / Moz, Stefania / Capurso, Gabriele / Strobel, Oliver / Carrara, Silvia / Hackert, Thilo / Hlavac, Viktor / Archibugi, Livia / Oliverius, Martin / Vanella, Giuseppe / Vodicka, Pavel / Arcidiacono, Paolo Giorgio / Pezzilli, Raffaele / Milanetto, Anna Caterina / Lawlor, Rita T / Ivanauskas, Audrius / Szentesi, Andrea / Kupcinskas, Juozas / Testoni, Sabrina G G / Lovecek, Martin / Nentwich, Michael / Gazouli, Maria / Luchini, Claudio / Zuppardo, Raffaella Alessia / Darvasi, Erika / Brenner, Hermann / Gheorghe, Cristian / Jamroziak, Krzysztof / Canzian, Federico / Campa, Daniele

International journal of cancer

2021 Volume 148, Issue 11, Page(s) 2779–2788

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is projected to become the second cancer-related cause of death by 2030. Identifying novel risk factors, including genetic risk loci, could be instrumental in risk stratification and implementation of prevention strategies. Long noncoding RNAs (lncRNAs) are involved in regulation of key biological processes, and the possible role of their genetic variability has been unexplored so far. Combining genome wide association studies and functional data, we investigated the genetic variability in all lncRNAs. We analyzed 9893 PDAC cases and 9969 controls and identified a genome-wide significant association between the rs7046076 SNP and risk of developing PDAC (P = 9.73 × 10
MeSH term(s)	Aged ; Carcinoma, Pancreatic Ductal/genetics ; Case-Control Studies ; Computational Biology/methods ; Cyclin-Dependent Kinase Inhibitor p15/genetics ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; MicroRNAs/genetics ; Middle Aged ; Pancreatic Neoplasms/genetics ; Polymorphism, Single Nucleotide ; RNA, Long Noncoding/genetics
Chemical Substances	CDKN2B protein, human ; Cyclin-Dependent Kinase Inhibitor p15 ; MIRN1256 microRNA, human ; MicroRNAs ; RNA, Long Noncoding
Language	English
Publishing date	2021-02-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218257-9
ISSN	1097-0215 ; 0020-7136
ISSN (online)	1097-0215
ISSN	0020-7136
DOI	10.1002/ijc.33475
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Article ; Online: Associations between pancreatic expression quantitative traits and risk of pancreatic ductal adenocarcinoma.

Pistoni, Laura / Gentiluomo, Manuel / Lu, Ye / López de Maturana, Evangelina / Hlavac, Viktor / Vanella, Giuseppe / Darvasi, Erika / Milanetto, Anna Caterina / Oliverius, Martin / Vashist, Yogesh / Di Leo, Milena / Mohelnikova-Duchonova, Beatrice / Talar-Wojnarowska, Renata / Gheorghe, Cristian / Petrone, Maria Chiara / Strobel, Oliver / Arcidiacono, Paolo Giorgio / Vodickova, Ludmila / Szentesi, Andrea /

Capurso, Gabriele / Gajdán, László / Malleo, Giuseppe / Theodoropoulos, George E / Basso, Daniela / Soucek, Pavel / Brenner, Hermann / Lawlor, Rita T / Morelli, Luca / Ivanauskas, Audrius / Kauffmann, Emanuele Federico / Macauda, Angelica / Gazouli, Maria / Archibugi, Livia / Nentwich, Michael / Loveček, Martin / Cavestro, Giulia Martina / Vodicka, Pavel / Landi, Stefano / Tavano, Francesca / Sperti, Cosimo / Hackert, Thilo / Kupcinskas, Juozas / Pezzilli, Raffaele / Andriulli, Angelo / Pollina, Luca / Kreivenaite, Edita / Gioffreda, Domenica / Jamroziak, Krzysztof / Hegyi, Péter / Izbicki, Jakob R / Testoni, Sabrina Gloria Giulia / Zuppardo, Raffaella Alessia / Bozzato, Dania / Neoptolemos, John P / Malats, Núria / Canzian, Federico / Campa, Daniele

Carcinogenesis

2021 Volume 42, Issue 8, Page(s) 1037–1045

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and ... ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers. Its poor prognosis is predominantly due to the fact that most patients remain asymptomatic until the disease reaches an advanced stage, alongside the lack of early markers and screening strategies. A better understanding of PDAC risk factors is essential for the identification of groups at high risk in the population. Genome-wide association studies (GWAS) have been a powerful tool for detecting genetic variants associated with complex traits, including pancreatic cancer. By exploiting functional and GWAS data, we investigated the associations between polymorphisms affecting gene function in the pancreas (expression quantitative trait loci, eQTLs) and PDAC risk. In a two-phase approach, we analysed 13 713 PDAC cases and 43 784 controls and identified a genome-wide significant association between the A allele of the rs2035875 polymorphism and increased PDAC risk (P = 7.14 × 10-10). This allele is known to be associated with increased expression in the pancreas of the keratin genes KRT8 and KRT18, whose increased levels have been reported to correlate with various tumour cell characteristics. Additionally, the A allele of the rs789744 variant was associated with decreased risk of developing PDAC (P = 3.56 × 10-6). This single nucleotide polymorphism is situated in the SRGAP1 gene and the A allele is associated with higher expression of the gene, which in turn inactivates the cyclin-dependent protein 42 (CDC42) gene expression, thus decreasing the risk of PDAC. In conclusion, we present here a functional-based novel PDAC risk locus and an additional strong candidate supported by significant associations and plausible biological mechanisms.
MeSH term(s)	Aged ; Alleles ; Carcinoma, Pancreatic Ductal/genetics ; Case-Control Studies ; Female ; GTPase-Activating Proteins/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci
Chemical Substances	GTPase-Activating Proteins ; SRGAP1 protein, human
Language	English
Publishing date	2021-07-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603134-1
ISSN	1460-2180 ; 0143-3334
ISSN (online)	1460-2180
ISSN	0143-3334
DOI	10.1093/carcin/bgab057
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Article ; Online: Genetic Polymorphisms Involved in Mitochondrial Metabolism and Pancreatic Cancer Risk.

Peduzzi, Giulia / Gentiluomo, Manuel / Tavano, Francesca / Arcidiacono, Paolo Giorgio / Ermini, Stefano / Vodicka, Pavel / Boggi, Ugo / Cavestro, Giulia Martina / Capurso, Gabriele / Morelli, Luca / Milanetto, Anna Caterina / Pezzilli, Raffaele / Lawlor, Rita T / Carrara, Silvia / Lovecek, Martin / Souček, Pavel / Guo, Feng / Hackert, Thilo / Uzunoğlu, Faik G /

Gazouli, Maria / Párniczky, Andrea / Kupcinskas, Juozas / Bijlsma, Maarten F / Bueno-de-Mesquita, Bas / Vermeulen, Roel / van Eijck, Casper H J / Jamroziak, Krzysztof / Talar-Wojnarowska, Renata / Greenhalf, William / Gioffreda, Domenica / Petrone, Maria C / Landi, Stefano / Archibugi, Livia / Puzzono, Marta / Funel, Niccola / Sperti, Cosimo / Piredda, Maria L / Mohelnikova-Duchonova, Beatrice / Lu, Ye / Hlaváč, Viktor / Gao, Xin / Schneider, Martin / Izbicki, Jakob R / Theodoropoulos, George / Bunduc, Stefania / Kreivenaite, Edita / Busch, Olivier R / Małecka-Panas, Ewa / Costello, Eithne / Perri, Francesco / Testoni, Sabrina Gloria Giulia / Vanella, Giuseppe / Pasquali, Claudio / Oliverius, Martin / Brenner, Hermann / Loos, Martin / Götz, Mara / Georgiou, Konstantinos / Erőss, Bálint / Maiello, Evaristo / Szentesi, Andrea / Bazzocchi, Francesca / Basso, Daniela / Neoptolemos, John P / Hegyi, Péter / Kiudelis, Vytautas / Canzian, Federico / Campa, Daniele

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2021 Volume 30, Issue 12, Page(s) 2342–2345

Abstract: Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC ... ...

Abstract	Background: The mitochondrial metabolism has been associated with pancreatic ductal adenocarcinoma (PDAC) risk. Recent evidence also suggests the involvement of the genetic variability of the mitochondrial function in several traits involved in PDAC etiology. However, a systematic investigation of the genetic variability of mitochondrial genome (mtSNP) and of all the nuclear genes involved in its functioning (n-mtSNPs) has never been reported. Methods: We conducted a two-phase association study of mtSNPs and n-mtSNPs to assess their effect on PDAC risk. We analyzed 35,297 n-mtSNPs and 101 mtSNPs in up to 55,870 individuals (12,884 PDAC cases and 42,986 controls). In addition, we also conducted a gene-based analysis on 1,588 genes involved in mitochondrial metabolism using Multi-marker Analysis of GenoMic Annotation (MAGMA) software. Results: In the discovery phase, we identified 49 n-mtSNPs and no mtSNPs associated with PDAC risk ( Conclusions: Even though the mitochondrial metabolism might be involved in PDAC etiology, our results, obtained in a study with one of the largest sample sizes to date, show that neither n-mtSNPs nor mtSNPs are associated with PDAC risk. Impact: This large case-control study does not support a role of the genetic variability of the mitochondrial function in PDAC risk.
MeSH term(s)	Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/metabolism ; Case-Control Studies ; Genetic Variation ; Genome, Mitochondrial ; Humans ; Mitochondria/metabolism ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2021-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-21-0353
Database	MEDical Literature Analysis and Retrieval System OnLINE

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