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From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer?
Škrha, Pavel ; Anděl, Michal (advisor) ; Bendlová, Běla (referee) ; Krechler, Tomáš (referee)
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer? Pavel Škrha Abstract Introduction: Pancreatic cancer ranks among the cancers with the worst prognosis. High lethality of the disease is caused by late diagnose and a lack of powerful and early markers. The goal of this study was to observe the presence of early unspecific signs of the disease (new-onset diabetes mellitus and weight loss) and to test selected miRNAs as markers of pancreatic cancer, with subanalysis according to specific criteria (diabetes mellitus/prediabetes, its type, weight loss, cancer stage and size of the primary tumor, presence of chronic pancreatitis in cancer patients). Patients and methods: We have included 77 patients with ductal pancreatic adenocarcinoma, 26 with chronic pancreatitis, 39 patients with type 2 diabetes mellitus without any tumor disease and 25 control subjects. In the cancer group, there were 60 patients who also had diabetes/prediabetes and 18 with chronic pancreatitis in their personal history. Significant weight loss (> 5 % of body weight in 3 months or > 10 % of body weight in 6 months) was observed in 52 patients with the cancer. Relative expressions of miRNAs (miR-21, miR-30, miR-192, miR-196, miR-200, miR-423) were measured in the serum by real-time PCR...
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From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer?
Škrha, Pavel ; Anděl, Michal (advisor) ; Bendlová, Běla (referee) ; Krechler, Tomáš (referee)
From diabetes, chronic pancreatitis to pancreatic cancer: miRNA - a new marker of pancreatic cancer? Pavel Škrha Abstract Introduction: Pancreatic cancer ranks among the cancers with the worst prognosis. High lethality of the disease is caused by late diagnose and a lack of powerful and early markers. The goal of this study was to observe the presence of early unspecific signs of the disease (new-onset diabetes mellitus and weight loss) and to test selected miRNAs as markers of pancreatic cancer, with subanalysis according to specific criteria (diabetes mellitus/prediabetes, its type, weight loss, cancer stage and size of the primary tumor, presence of chronic pancreatitis in cancer patients). Patients and methods: We have included 77 patients with ductal pancreatic adenocarcinoma, 26 with chronic pancreatitis, 39 patients with type 2 diabetes mellitus without any tumor disease and 25 control subjects. In the cancer group, there were 60 patients who also had diabetes/prediabetes and 18 with chronic pancreatitis in their personal history. Significant weight loss (> 5 % of body weight in 3 months or > 10 % of body weight in 6 months) was observed in 52 patients with the cancer. Relative expressions of miRNAs (miR-21, miR-30, miR-192, miR-196, miR-200, miR-423) were measured in the serum by real-time PCR...
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Pathophysiology of chronic pancreatitis and pancreatic cancer.
Mačinga, Peter ; Hucl, Tomáš (advisor) ; Krechler, Tomáš (referee) ; Trna, Jan (referee)
Chronic pancreatitis is considered a risk factor for pancreatic cancer. An exact mechanism how chronic inflammation of the pancreas leads to pancreatic cancer is not yet understood; the possibility of a shared genetic predisposition for both diseases is also assumed. A similar association in patients with AIP has not yet been demonstrated. The aim of our work was to expand the knowledge about relationship between chronic pancreatitis and pancreatic cancer. We studied the association of the diseases in two synchronous projects. In the first one, we examined the occurrence of pancreatic cancer in patients with autoimmune pancreatitis. In the second project, we investigated the presence of genetics variants associated with chronic pancreatitis in patients with pancreatic cancer. In the retrospective study of our cohort of patients, we were one of the very first in the world to show occurrence of pancreatic cancer in patients with autoimmune pancreatitis, and as the only one, we have defined the characteristics of such patients. To assess the association of the diseases, we performed a systematic review where we identified all reported cases of coincidence of pancreatic cancer and autoimmune pancreatitis; the incidence of cancer in patients with autoimmune pancreatitis was similar to that of patients...
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Th Role of Experimental Treatment with Statins on the Expression of Genes Involved in the Pathogenesiis of Pancreatic Cancer
Marková, Lucie ; Vítek, Libor (advisor) ; Krechler, Tomáš (referee)
Úvod: Karcinom pankreatu patří mezi nádorová onemocnění s nejhorší prognózou. Vzhledem к lokalizaci pankreatu v retroperitoneu i dalším anatomickým a patofyziologickým souvislostem se příznaky karcinomu slinivky objevují velmi pozdě a u většiny nemocných již není možné zahájit radikální léčbu. Z těchto důvodů jen 5% nemocných přežívá 5 let od stanovení diagnózy. Většinou postihuje nemocné mezi 30-70 lety, přičemž průměrný věk v době stanovení diagnózy je přibližně 56 let. V posledním desetiletí se dostává do popředí zájmu tzv. DNA microarray technologie umožňující monitorování exprese genů. Exprese genů představuje komplexní proces, kterým je genetická informace uložená ve formě deoxyribonukleové kyseliny (DNA) přeměněna v konkrétní buněčné struktury a metabolické nástroje. Produkty exprese genů jsou molekuly bílkovin, jsou jimi však i ribonukleové kyseliny (RNA). Statiny (inhibitory HMG-CoA reduktázy) patří mezi klíčové léky v léčbě hypercholesterolémie. Z výzkumných studií vyplývá, že tato skupina léků má velmi významné protinádorové vlastnosti. Inhibicí HMGCoA reduktázy, klíčového enzymu v syntéze cholesterolu, totiž dochází také к depleci jednotlivých meziproduktů v syntéze cholesterolu, z nichž nejvýznamnější je farnesyl pyrofosfát hrající důležitou roli v buněčné signalizaci ovlivňující apoptózu....
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