INTRODUCTION: Pancreatic cancer (PDAC) is one of the most aggressive malignancies. Its incidence increases worldwide and, despite the developments in cancer research, mortality rates have not decreased. Poor prognosis of the disease is due to many factors, mainly late diagnosis. Distant metastases and peritoneal carcinomatosis are caused by hematogenous and lymphogenous spreading of the tumorous cells. One of the factors that may influence patient survival are so-called circulating tumor cells (CTCs). The aim of our work was to evaluate the possible influence of CTCs on the survival of patients with PDAC. METHOD: We included patients who underwent a radical or palliative surgical intervention at the First Department of Surgery of Medical Faculty and University Hospital in Olomouc between 1 January 2008 and 31 December 2012. The required samples for CTCs detection were taken from each patient. The detection of the CTCs was performed using real-time RT-PCR. The results were statistically processed and evaluated. RESULTS: We included 126 patients in total, of which 88 were treated radically and 38 received palliative treatment. Mean age was 63 years in patients with radical and 64 years in patients with palliative surgery. Mean survival time in radically treated patients was 29.6 months, in patients with palliative treatment the mean survival time was 8.5 months. The survival time of radically treated patients with CTCs was 27.2 months, without CTCs it was 33.8 months. CONCLUSION: We did not prove a statistically significant difference in survival between radically treated PDAC patients with and without detected CTCs in our work.Key words: pancreatic cancer - circulating tumor cells survival.
OBJECTIVE: Literature review of endometrial receptivity in embryo implantation and its diagnostic possibilities. DESIGN: Literature review. SETTING: Department of Obstetrics and Gynecology, University Hospital, Faculty of Medicine, Palacky University, Olomouc; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc. RESULTS: Endometrial tissue is very dynamic, undergoing cyclic proliferation, differentiation and cell transportation, especially of immune system cells under the influence of circulating estradiol and progesterone. Endometrial remodelling during embryo implantation is controlled by decidual cells senescence and effectivity of their immunologic destruction. Endometrial receptivity can be assessed by transcriptomic profiling of endometrial biopsy using ERA system or proteomic analysis of either endometrial secretome or cervical mucus by gel electrophoresis (DIGE) or mass spectrometry (MS). CONCLUSION: With respect to recent discoveries in endometrial physiology and molecular biology, clinical application of proteomic approaches in research of potential biomarkers of endometrial receptivity could be of interest.
- Klíčová slova
- endometrial receptivity, implantation, proteomic analysis, secretome cervical mucus.,
- MeSH
- endometrium fyziologie MeSH
- implantace embrya MeSH
- lidé MeSH
- proteomika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Multiple myeloma is a plasma cell dyscrasia. It is the second most common hematological malignancy which is characterized by proliferation of clonal plasma cells producing harmful monoclonal immunoglobulin. Despite treatment modalities greatly evolved during the last decade, small amount of aberrant residual cells reside in patients after therapy and can cause relapse of the disease. Characterization of the residual, resistant clones can help to reveal important therapeutic targets for application of effective and precious treatment. We use CD38, CD45, CD56 and CD19 sorted aberrant plasma cells to perform next generation sequencing of their exome. Among the 213 genes in which at least one variant was present, the most interesting was found gene NRAS, one of the most often mutated gene in multiple myeloma, and homologs of 88 gene panel previously used for multiple myeloma sequencing among which was a gene previously identified as gene meaningful in bortezomib resistance. Nevertheless, the results of next generation exome sequencing need to be interpreted with caution, since they rely on bioinformatical analysis, which is still being optimized. The results of next generation sequencing will also have to be confirmed by Sanger sequencing. Final results supported by larger cohort of patients will be published soon.Key words: multiple myeloma - minimal residual disease - exome - next generation sequencing.
- MeSH
- bortezomib farmakologie MeSH
- CD antigeny metabolismus MeSH
- chemorezistence účinky léků genetika MeSH
- GTP-fosfohydrolasy genetika MeSH
- lidé MeSH
- membránové proteiny genetika MeSH
- mnohočetný myelom farmakoterapie genetika patologie MeSH
- plazmatické buňky metabolismus patologie MeSH
- reziduální nádor MeSH
- sekvenování exomu * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- multicentrická studie MeSH
- Názvy látek
- bortezomib MeSH
- CD antigeny MeSH
- GTP-fosfohydrolasy MeSH
- membránové proteiny MeSH
- NRAS protein, human MeSH Prohlížeč
BACKGROUND: Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are a promising prognostic biomarker of gliomas. The purpose of our study was to examine the clinical prognostic properties of IDH1/2 mutations in a glioma patient cohort from the Czech Republic using an improved platform for simple and reliable IDH genotyping. MATERIAL AND METHODS: We retrospectively analyzed a group of 145 glioma patients by testing for the three most frequent IDH mutations, IDH1 R132H, IDH1 R132C, and IDH2 R172K, through the competitive amplification of differentially melting amplicons (CADMA) polymerase chain reaction (PCR). O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, copy number of EGFR, p53, RB1, MDM2, CDKN2A genes, and deletions in 1p, 19q and 10p chromosomal regions were also analyzed and correlated with clinical characteristics. RESULTS: Of 145 gliomas, 36 harbored IDH1 R132H mutation and 1 IDH1 R132C mutation. We did not detect any IDH2 R172K mutation. IDH1 mutations were positively associated with MGMT methylation (OR 3.08, 95% CI 1.387-7.282; p = 0.007), 1p/19q co-loss (OR 8.85, 95% CI 2.367-42.786; p = 0.002) and negatively associated with epidermal growth factor receptor amplification (OR 0.12, 95% CI 0.019-0.437; p = 0.006) and 10p loss (OR 0.09, 95% CI 0.005-0.436; p = 0.019). The overall survival of IDH-mutant was 25 months, but only 9 months in IDH-wild type gliomas (p = 0.035); at the same time, survival associated with methylated vs. unmethylated MGMT promoter did not significantly differ (p = 0.166). CONCLUSION: Despite IDH1 mutations being closely associated with MGMT methylation in glioma patients, IDH1 mutations in glioblastoma patients are stronger marker of overall survival than MGMT methylation and should be the marker of choice, especially when using genotyping by CADMA PCR.Key words: isocitrate dehydrogenase - polymerase chain reaction - glioma - glioblastoma.
- MeSH
- dospělí MeSH
- gliom genetika mortalita patologie MeSH
- isocitrátdehydrogenasa genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA MeSH
- mladý dospělý MeSH
- mutace MeSH
- nádorové biomarkery genetika MeSH
- nádory mozku genetika mortalita patologie MeSH
- O(6)-methylguanin-DNA-methyltransferasa genetika MeSH
- prognóza MeSH
- promotorové oblasti (genetika) MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- isocitrátdehydrogenasa MeSH
- nádorové biomarkery MeSH
- O(6)-methylguanin-DNA-methyltransferasa MeSH
Immunoglobulin light chain amyloidosis (AL amyloidosis - ALA) is a monoclonal gammopathy characterized by presence of aberrant plasma cells producing amyloidogenic immunoglobulin light chains. This leads to formation of amyloid fibrils in various organs and tissues, mainly in heart and kidney, and causes their dysfunction. As amyloid depositing in target organs is irreversible, there is a big effort to identify biomarker that could help to distinguish ALA from other monoclonal gammopathies in the early stages of disease, when amyloid deposits are not fatal yet. High throughput technologies bring new opportunities to modern cancer research as they enable to study disease within its complexity. Sophisticated methods such as next generation sequencing, gene expression profiling and circulating microRNA profiling are new approaches to study aberrant plasma cells from patients with light chain amyloidosis and related diseases. While generally known mutation in multiple myeloma patients (KRAS, NRAS, MYC, TP53) were not found in ALA, number of mutated genes is comparable. Transcriptome of ALA patients proves to be more similar to monoclonal gammopathy of undetermined significance patients, moreover level of circulating microRNA, that are known to correlate with heart damage, is increased in ALA patients, where heart damage in ALA typical symptom.Key words: amyloidosis - plasma cell - genome - transcriptome - microRNA.
- MeSH
- biologické markery analýza MeSH
- lidé MeSH
- plazmatické buňky patologie MeSH
- primární amyloidóza krev genetika MeSH
- stanovení celkové genové exprese MeSH
- transkriptom MeSH
- volné cirkulující nukleové kyseliny MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- biologické markery MeSH
- volné cirkulující nukleové kyseliny MeSH
INTRODUCTION: The investigation of prognostic and predictive factors for early diagnosis of tumors, their surveillance and monitoring of the impact of therapeutic modalities using hybrid laboratory models in vitro/in vivo is an experimental approach with a significant potential. It is preconditioned by the preparation of in vivo tumor models, which may face a number of potential technical difficulties. The assessment of technical success of grafting and xenotransplantation based on the type of the tumor or cell line is important for the preparation of these models and their further use for proteomic and genomic analyses. METHODS: Surgically harvested gastrointestinal tract tumor tissue was processed or stable cancer cell lines were cultivated; the viability was assessed, and subsequently the cells were inoculated subcutaneously to SCID mice with an individual duration of tumor growth, followed by its extraction. RESULTS: We analysed 140 specimens of tumor tissue including 17 specimens of esophageal cancer (viability 13/successful inoculations 0), 13 tumors of the cardia (11/0), 39 gastric tumors (24/4), 47 pancreatic tumors (34/1) and 24 specimens of colorectal cancer (22/9). 3 specimens were excluded due to histological absence of the tumor (complete remission after neoadjuvant therapy in 2 cases of esophageal carcinoma, 1 case of chronic pancreatitis). We observed successful inoculation in 17 of 28 tumor cell lines. CONCLUSION: The probability of successful grafting to the mice model in tumors of the esophagus, stomach and pancreas is significantly lower in comparison with colorectal carcinoma and cell lines generated tumors. The success rate is enhanced upon preservation of viability of the harvested tumor tissue, which depends on the sequence of clinical and laboratory algorithms with a high level of cooperation.Key words: proteomic analysis - xenotransplantation - prognostic and predictive factors - gastrointestinal tract tumors.
- MeSH
- biologické markery MeSH
- gastrointestinální nádory chirurgie MeSH
- karcinom chirurgie MeSH
- kardie MeSH
- kolorektální nádory chirurgie MeSH
- lidé MeSH
- myši SCID * MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory jícnu chirurgie MeSH
- nádory slinivky břišní chirurgie MeSH
- nádory žaludku chirurgie MeSH
- prognóza MeSH
- proteomika MeSH
- transplantace heterologní metody MeSH
- transplantace nádorů metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
Matrix metalloproteinases (MMPs) are potential biomarkers for disease activity in inflammatory bowel disease (IBD). However, clinical trials targeting MMPs have not succeeded, likely due to poor understanding of the biological functions of individual MMPs. Here, we explore the role of MMP-19 in IBD pathology. Using a DSS-induced model of colitis, we show evidence for increased susceptibility of Mmp-19-deficient (Mmp-19(-/-)) mice to colitis. Absence of MMP-19 leads to significant disease progression, with reduced survival rates, severe tissue destruction, and elevated levels of pro-inflammatory modulators in the colon and plasma, and failure to resolve inflammation. There was a striking delay in neutrophil infiltration into the colon of Mmp-19(-/-) mice during the acute colitis, leading to persistent inflammation and poor recovery; this was rescued by reconstitution of irradiated Mmp-19(-/-) mice with wild-type bone marrow. Additionally, Mmp-19-deficient macrophages exhibited decreased migration in vivo and in vitro and the mucosal barrier appeared compromised. Finally, chemokine fractalkine (CX3CL1) was identified as a novel substrate of MMP-19, suggesting a link between insufficient processing of CX3CL1 and cell recruitment in the Mmp-19(-/-) mice. MMP-19 proves to be a critical factor in balanced host response to colonic pathogens, and for orchestrating appropriate innate immune response in colitis.
- MeSH
- chemokin CX3CL1 metabolismus MeSH
- cytokiny metabolismus MeSH
- idiopatické střevní záněty imunologie MeSH
- infiltrace neutrofily genetika MeSH
- kolitida chemicky indukované imunologie MeSH
- kolon imunologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- makrofágy imunologie MeSH
- mediátory zánětu metabolismus MeSH
- metaloproteinasy secernované do matrix genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- pohyb buněk MeSH
- přirozená imunita MeSH
- progrese nemoci MeSH
- síran dextranu MeSH
- střevní sliznice imunologie patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chemokin CX3CL1 MeSH
- Cx3cl1 protein, mouse MeSH Prohlížeč
- cytokiny MeSH
- matrix metalloproteinase 19 MeSH Prohlížeč
- mediátory zánětu MeSH
- metaloproteinasy secernované do matrix MeSH
- síran dextranu MeSH
OBJECTIVES: Significant progress in treatment strategies improves the expectations of patients with extracranial cancers. Metastases are the primary consideration in patients with cancer history. In the case of neurologic disorders, the patient should undergo brain MRI. A rationale is presented for surgery, whole-brain or stereotactic radiotherapy, or chemotherapy. Recently, we have encountered misdiagnosed primary malignant brain tumours in patients with oncologic history who had been admitted for surgery for brain metastases. The aim of our study is to evaluate the incidence of concurrent cancers, to assess the relationship between previous cancer staging and primary brain tumour evaluation as well as to determine treatment efficiency. METHODS: From January 2007 to December 2011, we prospectively followed up patients with concurrent history of both extracranial cancer and subsequent glioblastoma multiforme. Information was collected on the clinical condition, imaging, history of extracranial cancer, previous and present surgical and oncologic procedures, and GBM histologic, cytogenetic, and molecular genetic investigations. RESULTS: Five patients were recruited: three females and two males. The average patient age at the time of GBM diagnosis was 65.6 years. Three patients had a history of breast carcinoma, one of renal carcinoma and one of colorectal carcinoma. Following the diagnosis of carcinoma, three patients received chemotherapy and radiotherapy, one patient had radiotherapy alone, and one had no adjuvant therapy. In all the cases, surgery revealed primary GBM, with a standard occurrence of genetic abnormalities (Table 1). The average time from the diagnosis of extracranial cancer to that of GBM was 4 years. Four patients underwent chemoradiotherapy and one had palliative radiotherapy. Two patients completed oncotherapy and their OS was 27 months and 19 months, respectively. One patient had post-surgical progression of hemiparesis. One patient had pulmonary embolism during oncotherapy and one had paraplegia caused by a pathological fracture of vertebras T5 due to breast carcinoma metastases. The OS was 11.8 months (range 3-27 months). All the patients succumbed to GBM progression.
- Klíčová slova
- Extracranial cancer, Glioblastoma Multiforme, Oncotherapy, Treatment strategy,
- MeSH
- glioblastom diagnostické zobrazování radioterapie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- nádory mozku diagnostické zobrazování radioterapie chirurgie MeSH
- následné studie MeSH
- počítačová rentgenová tomografie MeSH
- prospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
Great progress has been made in the diagnostics and treatment of childhood acute lymphoblastic leukemia (ALL) over the past decades. The vast majority of children are cured, however, there is need for further improvement, especially in specific patient subgroups. Our aim was to retrospectively evaluate disease characteristics and treatment outcomes of children with ALL enrolled in a single center into consecutive treatment protocols (ALL-BFM 90, ALL-BFM 95 and ALL IC-BFM 2002) between years 1990 and 2007 and comprehensively summarize diagnostic and therapeutic advances between protocols. In total, 97 patients aged 0 to 18 years were treated for ALL at University Hospital Olomouc in the Czech Republic and steadily high relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS) were observed during the evaluated time period without significant difference between the protocols (RFS 80-86%, EFS 75-83% and OS 84-92%). In conclusion, our center has demonstrated survival rates comparable to leading international study groups for childhood ALL over a substantial period of time. This has been achieved namely due to advances in diagnostics, excellent collaboration on regional, national and international level, quality assurance and high overall standard of care. The acquired experience has been crucial for current participation in the best performing Berlin-Frankfurt-Münster (BFM)-based international trials for childhood ALL.
- Klíčová slova
- BFM, Olomouc, acute lymphoblastic leukemia, childhood, prognosis.,
- MeSH
- akutní lymfatická leukemie genetika mortalita terapie MeSH
- dítě MeSH
- doba přežití bez progrese choroby MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- prognóza MeSH
- randomizované kontrolované studie jako téma MeSH
- retrospektivní studie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
OBJECTIVE: To get initial experience with alternative sampling (self-sampling) for HPV testing as the means of cervical cancer screening program. DESIGN: Original work. SETTING: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University in Olomouc. METHODS: Based on expression of interest, 215 self-sampling kits were posted to women. Evalyn(®) Brush Vaginal swabs obtained by self-sampling were analyzed for the presence of HPV infection by Cobas 4800 HPV (Roche) followed by genotyping using PapilloCheck(®) HPV-Screening (Greiner Bio-One). Sixty women randomly chosen from our sample were sent a questionnaire focused on their experience with self-sampling. RESULTS: One hundred seventy-four of 215 (81%) distributed self-sampling devices have been delivered to analysis. All cervicovaginal swabs were sampled correctly and it was possible to analyze them by Cobas 4800 HPV test. Similarly, 98% (171/174) samples were analyzable by PapilloCheck(®) HPV-Screening.One hundred twenty-five (72%) of 174 tested samples were HPV negative. Low risk HPV infection was detected only in 7 samples (4%), and high risk HPV (hrHPV) infection was present in 42 samples (24%). The most frequently detected hrHPV genotypes were HPV16 (11/42; 26%) and HPV53 (6/42; 14%). HrHPV co-infection was detected in 10 cases, in 5 of them lrHPV infection was find also.Of the 60 questionnaires, 48 (80%) were returned. From this group, 47 (98%) women rated their experience with self-sampling device as good to excellent. User manual of self-sampling device was considered good to excellent by all women (100%). All women also rated the convenience of self-sampling device using as good to excellent. As expected, most of the women (n = 42 [88%]) preferred self-sampling to physician sampling. CONCLUSION: Cervicovaginal self-sampling leads to valid results of HPV screening using two molecular genetics methods and was accepted by Czech women very well. The self-sampling as an opportunity to participate in cervical cancer screening could increase the attendance of the screening program and would help to reduce the incidence and mortality for this disease in the Czech population.
- Klíčová slova
- HPV, PCR., cervical cancer, cervical cancer screening, cytology, human papillomavirus, self-sampling,
- MeSH
- časná detekce nádoru metody MeSH
- dospělí MeSH
- genotyp MeSH
- infekce papilomavirem diagnóza virologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidský papilomavirus 16 MeSH
- nádory děložního čípku prevence a kontrola MeSH
- odběr biologického vzorku MeSH
- pacientův souhlas se zdravotní péčí MeSH
- péče o sebe metody MeSH
- pilotní projekty MeSH
- průzkumy a dotazníky MeSH
- spokojenost pacientů MeSH
- vaginální stěr metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
