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Pancreatic Neoplasms: HELP
Articles by Zdenek Kala
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, Zdenek Kala wrote the following 8 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review The Use of Biomarkers in Early Diagnostics of Pancreatic Cancer. 2018

Kunovsky, Lumir / Tesarikova, Pavla / Kala, Zdenek / Kroupa, Radek / Kysela, Petr / Dolina, Jiri / Trna, Jan. ·Department of Gastroenterology, University Hospital Brno Bohunice, Faculty of Medicine, Masaryk University, Czech Republic. · Department of Surgery, University Hospital Brno Bohunice, Faculty of Medicine, Masaryk University, Czech Republic. · Department of Internal Medicine, Hospital Boskovice, Czech Republic. ·Can J Gastroenterol Hepatol · Pubmed #30186820.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal solid malignancies with increasing incidence. The poor prognosis is due to the aggressive nature of the tumor, late detection, and the resistance to chemotherapy and radiotherapy. A radical surgery procedure is the only treatment that has been shown to improve the 5-year survival rate to 20-25%. However, the majority of patients (80-85%) are diagnosed with locally advanced or metastatic disease and just 15-20% patients are diagnosed in an early stage allowing them to undergo the potentially curative surgical resection. The early detection of PDAC without the use of invasive methods is challenging and discovery of a cost-effective biomarker with high specificity and sensitivity could significantly improve the treatment and survival in these patients. In this review, we summarize current and newly examined biomarkers in early PDAC detection.

2 Article Pre-operative Plasma miR-21-5p Is a Sensitive Biomarker and Independent Prognostic Factor in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgical Resection. 2018

Karasek, Petr / Gablo, Natalia / Hlavsa, Jan / Kiss, Igor / Vychytilova-Faltejskova, Petra / Hermanova, Marketa / Kala, Zdenek / Slaby, Ondrej / Prochazka, Vladimir. ·Masaryk Memorial Cancer Institute, Department of Comprehensive Cancer Care, Brno, Czech Republic. · Central European Institute of Technology, Masaryk University, Brno, Czech Republic. · Department of Surgery, Faculty Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic. · Department of Pathological Anatomy, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic. · Department of Surgery, Faculty Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic Prochazka.Vladimir@fnbrno.cz. ·Cancer Genomics Proteomics · Pubmed #29976637.

ABSTRACT: Blood plasma microRNAs (miRNAs) are emerging as a clinically useful tool for non-invasive detection and prognosis estimation in various cancer types including pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to provide an independent validation of circulating miRNAs identified in previous studies as diagnostic and/or prognostic biomarkers in PDAC. Based on the literature search, 6 miRNAs were chosen as candidates for independent validation; miR-21-5p, miR-375, miR-155, miR-17-5p, miR-126-5p and miR-1290. Validation of these miRNAs was performed in a cohort of 25 patients with PDAC undergoing surgical resection and 24 healthy donors. Plasma levels of miRNAs were determined using quantitative real-time PCR. We confirmed significantly higher levels of all tested miRNA in blood plasma of PDAC patients in comparison to healthy controls with miR-21-5p showing the highest analytical performance (p<0.001; AUC>0.99). Increased levels of miR-21-5p (p=0.045) and miR-375 (p=0.013) were significantly associated with overall survival. Multivariate analysis demonstrated that miR-21-5p is a significant unfavorable prognostic factor independent on other clinical variables including adjuvant chemotherapy (hazard ratio 2.95; 95% CI 1.06-8.18; p=0.038). Our preliminary data indicate promising diagnostic and prognostic utility of plasma miR-21-5p in PDAC patients.

3 Article SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival. 2017

Mohelnikova-Duchonova, Beatrice / Strouhal, Ondrej / Hughes, David J / Holcatova, Ivana / Oliverius, Martin / Kala, Zdenek / Campa, Daniele / Rizzato, Cosmeri / Canzian, Federico / Pezzilli, Raffaele / Talar-Wojnarowska, Renata / Malecka-Panas, Ewa / Sperti, Cosimo / Federico Zambon, Carlo / Pedrazzoli, Sergio / Fogar, Paola / Milanetto, Anna Caterina / Capurso, Gabriele / Delle Fave, Gianfranco / Valente, Roberto / Gazouli, Maria / Malleo, Giuseppe / Teresa Lawlor, Rita / Strobel, Oliver / Hackert, Thilo / Giese, Nathalia / Vodicka, Pavel / Vodickova, Ludmila / Landi, Stefano / Tavano, Francesca / Gioffreda, Domenica / Piepoli, Ada / Pazienza, Valerio / Mambrini, Andrea / Pedata, Mariangela / Cantore, Maurizio / Bambi, Franco / Ermini, Stefano / Funel, Niccola / Lemstrova, Radmila / Soucek, Pavel. ·Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. · Department of Oncology, Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic. · Department of Physiology &Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland. · Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic. · Department of Transplantation Surgery, Institute of Clinical and Experimental Medicine, Prague, Czech Republic. · Department of Surgery, The University Hospital and Faculty of Medicine, Brno Bohunice, Czech Republic. · Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. · Department of Biology, University of Pisa, Pisa, Italy. · Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy. · Department of Digestive Diseases, Sant'Orsola-Malpighi Hospital, Bologna, Italy. · Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland. · Department of Surgery, Oncology and Gastroenterology -DiSCOG, University of Padova, Italy. · Department of Medicine - DIMED, University of Padova, Italy. · Clinica Chirurgica 4, University of Padova, Italy. · Department of Laboratory Medicine, University-Hospital of Padova, Italy. · Digestive and Liver Disease Unit, S. Andrea Hospital, 'Sapienza' University of Rome, Rome, Italy. · Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece. · Department of Surgery and Oncology, University and Hospital Trust of Verona, Verona, Italy. · ARC-NET Applied research on Cancer Centre, University and Hospital Trust of Verona, Verona, Italy. · Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany. · Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Science of Czech Republic, Prague, Czech Republic and First Faculty of Medicine, Charles University in Prague, Czech Republic. · Biomedical Centre, Faculty of Medicine in Pilsen, Charles University in Prague, Pilsen, Czech Republic. · Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital "Casa Sollievo della Sofferenza", San Giovanni Rotondo, Italy. · Department of Oncology, Azienda USL 1 Massa Carrara, Massa Carrara, Italy. · Blood Transfusion Service, Children's Hospital Meyer, Azienda Ospedaliero Universitaria, Florence, Italy. ·Sci Rep · Pubmed #28272475.

ABSTRACT: Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted.

4 Article MiR-21, miR-34a, miR-198 and miR-217 as diagnostic and prognostic biomarkers for chronic pancreatitis and pancreatic ductal adenocarcinoma. 2015

Vychytilova-Faltejskova, Petra / Kiss, Igor / Klusova, Sona / Hlavsa, Jan / Prochazka, Vladimir / Kala, Zdenek / Mazanec, Jan / Hausnerova, Jitka / Kren, Leos / Hermanova, Marketa / Lenz, Jiri / Karasek, Petr / Vyzula, Rostislav / Slaby, Ondrej. ·Molecular Oncology II - Solid Cancers, Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic. vychytilova.petra@seznam.cz. · Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic. vychytilova.petra@seznam.cz. · Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic. kiss@mou.cz. · Molecular Oncology II - Solid Cancers, Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic. sona.klusova@gmail.com. · Department of Surgery, Institutions shared with the Faculty Hospital Brno, Brno, Czech Republic. jhlavsa@fnbrno.cz. · Department of Surgery, Institutions shared with the Faculty Hospital Brno, Brno, Czech Republic. vprochazka@fnbrno.cz. · Department of Surgery, Institutions shared with the Faculty Hospital Brno, Brno, Czech Republic. zkala@fnbrno.cz. · Department of Pathology, Institutions shared with the Faculty Hospital Brno, Brno, Czech Republic. jmazanec@fnbrno.cz. · Department of Pathology, Institutions shared with the Faculty Hospital Brno, Brno, Czech Republic. jitka.hausnerova@fnbrno.cz. · Department of Pathology, Institutions shared with the Faculty Hospital Brno, Brno, Czech Republic. lkren@fnbrno.cz. · First Department of Pathological Anatomy, Institutions shared with St. Anne's Faculty Hospital, Brno, Czech Republic. marketa.hermanova@fnusa.cz. · First Department of Pathological Anatomy, Institutions shared with St. Anne's Faculty Hospital, Brno, Czech Republic. jiri.lenz@fnusa.cz. · Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic. karasek@mou.cz. · Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic. vyzula@mou.cz. · Molecular Oncology II - Solid Cancers, Molecular Medicine, Central European Institute of Technology, Masaryk University, Brno, Czech Republic. on.slaby@gmail.com. · Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Zluty kopec 7, Brno, Czech Republic. on.slaby@gmail.com. ·Diagn Pathol · Pubmed #25908274.

ABSTRACT: BACKGROUND: Pancreatic ductal adenocarcinoma is an aggressive malignancy with late presentation, metastatic potential and very poor prognosis. Therefore, there is an urgent need for novel diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. Altered expression of microRNAs has been reported in wide range of malignancies, including pancreatic ductal adenocarcinoma. The aim of this study was to analyze the expression of selected microRNAs in normal pancreas, chronic pancreatitis and pancreatic ductal adenocarcinoma tissues and evaluate their diagnostic and prognostic potential. FINDINGS: Using quantitative real-time PCR, expression levels of 4 microRNAs were examined in 74 tumor tissues, 18 tissues of chronic pancreatitis and 9 adjacent normal tissues and correlated with clinicopathological features of patients. Expression levels of miR-21, miR-34a and miR-198 were significantly higher, whereas levels of miR-217 were significantly lower in pancreatic ductal adenocarcinomas compared to healthy tissues and tissues of chronic pancreatitis. Moreover, increased expression of miR-21 and miR-198 was significantly associated with shorter disease free survival and overall survival. CONCLUSIONS: Our data suggest that altered expression of examined microRNAs is related to neoplastic transformation and progression of the disease and these microRNAs could serve as diagnostic and prognostic biomarkers for pancreatic ductal adenocarcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1373952531543898.

5 Article Anterior gradient 2 and mucin 4 expression mirrors tumor cell differentiation in pancreatic adenocarcinomas, but aberrant anterior gradient 2 expression predicts worse patient outcome in poorly differentiated tumors. 2014

Brychtova, Veronika / Hermanova, Marketa / Karasek, Petr / Lenz, Jiri / Selingerova, Iveta / Vojtesek, Borivoj / Kala, Zdenek / Hrstka, Roman. ·From the *Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute; †First Department of Pathological Anatomy, St Anne's University Hospital, Medical Faculty of Masaryk University; ‡Department of Complex Oncology Care, Masaryk Memorial Cancer Institute; §Department of Mathematics and Statistics, Faculty of Science, Masaryk University; and ∥Department of Surgery, University Hospital Brno, Medical Faculty of Masaryk University, Brno, Czech Republic. ·Pancreas · Pubmed #24177142.

ABSTRACT: OBJECTIVES: This study aimed to determine anterior gradient 2 (AGR2) expression in biopsies from pancreatic ductal adenocarcinomas (PDACs) and to evaluate AGR2 as a potential independent prognostic factor. METHODS: Tissue sample sections from a cohort of 135 consecutive surgically resectable PDACs were subjected to semiquantitative immunohistochemical analysis of AGR2 and mucin 4 (MUC4) expression. RESULTS: Anterior gradient 2 was over-expressed in PDAC compared with normal ductal cells. Since tumor lesions of PDAC are heterogeneous and constitute structures with various differentiation states, expression of both AGR2 and MUC4 was evaluated in each separate component. Expression levels of both proteins reflected the degree of tumor differentiation. Generally, well differentiated regions of tumor lesions expressed high levels of both proteins, moderately differentiated regions showed less AGR2 and MUC4, and poorly differentiated structures showed only weak positivity or were entirely negative. Of particular interest were occasional cases of strong AGR2 expression in high-grade tumors, where elevated protein levels were associated with shorter patient survival. CONCLUSIONS: Anterior gradient 2 and MUC4 reflect the level of differentiation of PDACs. However, in less differentiated tumors, aberrantly elevated AGR2 expression predicts poor patient outcome.

6 Article The association between the expression of solute carrier transporters and the prognosis of pancreatic cancer. 2013

Mohelnikova-Duchonova, Beatrice / Brynychova, Veronika / Hlavac, Viktor / Kocik, Matej / Oliverius, Martin / Hlavsa, Jan / Honsova, Eva / Mazanec, Jan / Kala, Zdenek / Melichar, Bohuslav / Soucek, Pavel. ·Toxicogenomics Unit, National Institute of Public Health, Srobarova 48, Prague 10, Czech Republic. D.Beatrice@seznam.cz ·Cancer Chemother Pharmacol · Pubmed #23934321.

ABSTRACT: OBJECTIVES: The aim of this study was to investigate the prognostic significance of fourteen anticancer drug-relevant solute carrier transporters (SLCs) in pancreatic cancer in the context of clinical-pathological characteristics and the KRAS mutation status of tumors. METHODS: Tumors and non-neoplastic pancreatic tissues were obtained from 32 histologically verified patients with pancreatic ductal adenocarcinoma. The transcript profile of SLCs was assessed using quantitative real-time PCR. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and confirmed by sequencing. RESULTS: SLC22A3 and SLC22A18 were upregulated and SLC22A1, SLC22A2, SLC22A11, SLC28A1, SLC28A3 and SLC29A1 were downregulated when compared with non-neoplastic pancreatic tissues. Moreover, significantly lower levels of SLC22A1, SLC22A11 and SLC29A1 were found in tumors with angioinvasion. There was also a significantly higher transcript level of SLC28A1 in tumors with regional lymph nodes affected by metastasis. The study found that a high expression of SLC28A1 was significantly associated with poor overall survival in unselected patients. In contrast, a high expression of SLC22A3 or SLC29A3 was significantly associated with longer overall survival in patients treated with nucleoside analogs. Protein expression of SLC22A1, SLC22A3 and SLC29A3 in tumor tissues of patients with pancreatic carcinoma was observed by immunoblotting for the first time. Finally, SLC levels were not found to be associated with KRAS mutation status in exon 2. CONCLUSIONS: This study identified a number of associations of transcript levels of SLCs with prognosis of pancreatic cancer patients.

7 Article Differences in transcript levels of ABC transporters between pancreatic adenocarcinoma and nonneoplastic tissues. 2013

Mohelnikova-Duchonova, Beatrice / Brynychova, Veronika / Oliverius, Martin / Honsova, Eva / Kala, Zdenek / Muckova, Katarina / Soucek, Pavel. ·Department of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic. mohelnikova@szu.cz ·Pancreas · Pubmed #23462326.

ABSTRACT: OBJECTIVES: The aim of this study was to evaluate transcript levels of all 49 human ATP-binding cassette transporters (ABCs) in one of the most drug-resistant cancers, namely, the pancreatic ductal adenocarcinoma (PDAC). Association of ABCs levels with clinical-pathologic characteristics and KRAS mutation status was followed as well. METHODS: Tumors and adjacent nonneoplastic tissues were obtained from 32 histologically verified PDAC patients. The transcript profile of ABCs was assessed using quantitative real-time polymerase chain reaction with a relative standard curve. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and sequencing. RESULTS: Most ABCs were deregulated in PDAC and 10 ABCs were associated with clinical-pathologic characteristics. KRAS mutations did not change the global expression profile of ABCs. CONCLUSIONS: The expression of ABC transporters was significantly deregulated in PDAC tumors when compared to nonmalignant tissues. The observed up-regulation of ABCB4, ABCB11, ABCC1, ABCC3, ABCC5, ABCC10, and ABCG2 in tumors may contribute to the generally poor treatment response of PDAC. The up-regulation of ABCA1, ABCA7, and ABCG1 implicates a serious impairment of cellular cholesterol homeostasis in PDAC. On the other hand, the observed down-regulation of ABCA3, ABCC6, ABCC7, and ABCC8 suggests a possible role of stem cells in the development and progression of PDAC.

8 Article Clinicopathological correlations of nestin expression in surgically resectable pancreatic cancer including an analysis of perineural invasion. 2011

Lenz, Jiri / Karasek, Petr / Jarkovsky, Jiri / Muckova, Katarina / Dite, Petr / Kala, Zdenek / Veselska, Renata / Hermanova, Marketa. ·First Department of Pathological Anatomy, Medical Faculty of Masaryk University and St. Anne´s University Hospital, Brno, Czech Republic. ·J Gastrointestin Liver Dis · Pubmed #22187705.

ABSTRACT: BACKGROUND AND AIMS: Nestin is considered to be a marker of stem/progenitor cells in different tissues. Nestin expression was also described in various tumors. In pancreatic ductal adenocarcinoma (PDAC), its role in cancer cell migration, invasion, and metastases has been suggested. The study aimed at examining the expression of nestin in PDAC, and to evaluate its clinicopathological correlations. METHODS: The expression of nestin was immunohistochemically examined in 117 PDAC resection specimens, analyzed, and correlated with clinico-pathological parameters including perineural invasion (PNI). Analysis of nestin expression in nerve fibers in tissues of chronic pancreatitis (CP) was added. RESULTS: Immunohistochemical analysis of nestin expression showed 79 nestin negative (67.5 %) and 38 nestin positive (32.5 %) PDACs. No significant correlations of nestin expression in tumor cells with the analyzed clinicopathological parameters were demonstrated. Tumor grade (p<0.001) and nodal status (p=0.009) proved to represent independent prognostic factors. PNI was identified in 94 PDAC (80.3 %), and did not correlate with nestin expression. Nestin immunostaining was displayed in nerve fibers of both CP and PDAC tissues. CONCLUSION: An intimate link of nestin to a biological process of pancreatic cancer was confirmed. The expression of nestin did not prove to be a valuable prognostic factor and an immunohistochemical assessment of nestin expression is not superior to conventional prognostic factors in PDAC. A correlation between nestin expression in tumor cells and PNI was not confirmed and expression of nestin in nerve fibers of both PDAC and CP tissues seems to reflect the process of neural remodeling responsible for pancreatic neuropathy.