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| 1 | Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer显示文摘AIM: To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS: Endoscopic ultrasound (EUS)-guided fine needle aspiration cytology (FNA) was performed on 101 consecutive patients (63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis) with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis (CGCE) and single-strand conformation polymorphism (SSCP) techniques. In addition, allelic losses of tumor suppressor genes p16 (INK4, CDKN2A) and DPC4 (MADH4, SMAD4) were detected by monitoring the loss of heterozygosity (LOH) at 9p and 18q, respectively. RESULTS: Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictivevalue reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations (P < 0.001), 24% and 90% for p53 mutations (NS), 13% and 100% for p16 mutations (NS), 85% and 64% for allelic losses at 9p (P < 0.001) and 78% and 57% for allelic losses at 18q (P < 0.05). When tests for different molecular markers were combined, the best results were obtained with K-ras + LOH at 9p (92% and 64%, P < 0.001), K-ras + LOH at 18q (92% and 57%, P < 0.001), and K-ras + LOH 9q + LOH 18q (96% and 43%, P < 0.001). When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION: EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive. | C Salek L Benesova M Zavoral V Nosek L Kasperova M Ryska R Strnad E Traboulsi M Minarik | 2007 | World Journal of Gastroenterology2007，13，27： | 18 |
| 2 | Molecular biology of pancreatic cancer显示文摘In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remainsdismal. With most cases still being diagnosed at ad- vanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple mole melanoma, and Peutz-Jeghers and Lynch syn- dromes. Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancre- atic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect onco- genes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current ap- proaches for pancreatic cancer treatment. | Miroslav Zavoral Petra Minarikova Filip Zavada Cyril Salek Marek Minarik | 2011 | World Journal of Gastroenterology2011，17，24： | 6 |
| 3 | Temporal lobe interictal epileptic discharges affect cerebral activity in 'default mode' brain regions显示文摘 | Laufs H Hamandi K Salek Haddadi A | 2007 | Human Brain Mapping2007，28，10： | 1 |
| 4 | The TNFRfamily members ox40 and CD27 link viral virulence toprotective T cell vaccines in mice显示文摘 | Salek Aardakani S Flynn R Arens R | 2011 | J Clin Invest2011，121，1： | 1 |
| 5 | Even>re- lated fMRI with simultaneous and continuous EEG: de- scription of the method and initial case report显示文摘 | Lemieux L Salek Haddadi A Josephs O | 2001 | Neuro- image2001，14，3： | 1 |
| 6 | A review of the health?related quality of life and economic impact of Parkinson's disease显示文摘 | Dowding CH Shenton CL Salek SS | 2006 | Drugs Aging2006，23，9： | 1 |
| 7 | J Am Chem Soc显示文摘 | Petter R C Salek J S Sikorski C T | 1990 | 112 :38601990，112，： | 1 |
| 8 | The MetaboLights repository: curation challenges in metabolomics 显示文摘 | Salek RM Haug K Conesa P | 2013 | Database2013，2013，： | 1 |
| 9 | Development of external methods to evaluate the quality of pharmacy services offered by community pharmacists显示文摘 | AZZOPARDI L M SERRACINO-INGLOTT A SALEK S | 2003 | Qual Assur J2003，7，4： | 1 |
| 10 | Structural and electronic properties of polyacetylene and polyyne from hybrid and coulomb-attenuated density functionals 显示文摘 | PEACH M J G TELLGREN E I SALEK P | 2007 | J Phys Chem A2007，111，11： | 1 |
| 11 | NMR-based metabolomics in human disease diagnosis: applications, limitations, and recommendations 显示文摘 | Emwas A H M Salek R M Griffin J L | 2013 | Metabolomics2013，9，5： | 1 |
| 12 | Operational application of combinedradar and raingangesprecipitation estimation at the CHMI 显示文摘 | Salek M Novak P Seo D J | 2004 | Pro- ceedings of ERAD2004，，： | 1 |
| 13 | Diagnosis of intracranial serm cell tumors显示文摘 | Gupta A Shimao Y Salek T | 1999 | Radiology1999，210，2： | 1 |
| 14 | Constitutively active Lck kinase in T cells drives antigen receptor signal transduction 显示文摘 | Nika K Soldani C Salek M | 2010 | Immunity2010，32，6： | 1 |
| 15 | Immunotherapy of Chenopodium album induced asthma by intranasal administration of CpG oligodeoxynucleotides in BALB/c mice 显示文摘 | Mousavi T Salek Moghadam A Falak R | 2008 | Iran J Immunol2008，5，1： | 1 |
| 16 | The costimulation regulated duration of PKB activation controls T cell longevity显示文摘 | Song J Salek Ardakani S Rogers PR | 2004 | Nat Immunol2004，5，2： | 1 |
| 17 | Influence of metal ions on bioremediation activity of protoeateehuate 3, 4-dioxygenase from Stenotrophomonas maltophilia KB2 显示文摘 | Guzik U Hupert-Kocurek K Salek K | 2013 | World Journal of Microbiology & Biotechnology2013，29，2： | 1 |
| 18 | DHEA and DHEA-S: a review显示文摘 | Salek FS Pittenger AL | 1999 | J Clin Pharmacol1999，39，4： | 1 |
| 19 | Commentary: A quantitative approach to benefit-risk assessment of medicines-part 1: the development of a new model using multi-criteria decision analysis; part 2: the practical application of a new model 显示文摘 | Mussen F Salek S Walker S | 2007 | Pharmacoepidemiology and Drug Safety Supplement: A Quantitative Approach to Benefit- Risk Assessment of Medicines2007，16，1： | 1 |
| 20 | A metabolomic comparison of urinary changes in type 2 diabetes in mouse, rat, and human 显示文摘 | Salek RM Maguire ML Bentley E | 2007 | Phys- iol Genomics2007，29，2： | 1 |
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