Circulating tumor cells (CTC) represent a very small subpopulation of the cancer cells found in the bloodstream of patients in the metastatic phase of neoplastic disease. Due to the timeline of the disease, they are regarded as a negative prognostic marker. This study focused on determining CTC percentages; these values vary be-tween different types of cancer. In addition to their diagnostic use, CTCs may also be used to treat the disease. Calculating CTC population size and analyzing their biology in patients in advanced stages of cancer may prove valuable in creating a molecular profile for the disease. This would strongly encourage diagnostics and enable personalized treatment. We here present an analysis of recent data on CTCs in urological cancers and their potential uses.
- Klíčová slova
- CTCs, bladder cancer, circulating tumor cells, cultivation, gene expression, in vitro, kidney cancer, prostate cancer,
- MeSH
- lidé MeSH
- nádorové cirkulující buňky * MeSH
- urologické nádory diagnóza patologie MeSH
- výpočetní biologie trendy MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Liquid biopsies are noninvasive tests using blood or body fluids to detect circulating tumor cells (CTCs) or the products of tumor cells, such as fragments of nucleic acids or proteins that are shed into biological fluids from primary tumor or its metastates. The analysis of published clinical studies provides coherent evidence that the presence of CTCs detected in peripheral blood is a strong prognostic factor in patients with colorectal carcinoma (CRC). The aim of the study was to implement size-based separation protocol of CTCs in CRC patients. MATERIAL AND METHODS: Patients diagnosed with different stages of CRC (n = 98) were included in the study. All patients have been diagnosed for colorectal adenocarcinoma by pathology examination, 45 patients with colon carcinoma and 53 with rectosigmoid cancer. A size-based separation method (MetaCell®) for viable CTC enrichment from peripheral blood was used to assess the presence of CTCs by cytomorphological evaluation using vital fluorescence microscopy. RESULTS: Cytomorphological analysis revealed that 81 (83%) tested samples were CTC-positive and 17 (17%) were CTC-negative. We report a successful isolation of CTCs with proliferation potential in patients with CRC. The CTCs were cultured in vitro for further downstream applications. Some of the isolated CTCs were able to grow in vitro for 6 months as a standard cell culture. CONCLUSIONS: We established a reliable, inexpensive and relatively fast protocol for CTCs enrichment in CRC patients by means of vital fluorescence staining which enables their further analysis in vitro.
- Klíčová slova
- MetaCell®, cell culture, circulating tumor cells, colon cancer, rectosigmoid cancer, staging,
- MeSH
- adenokarcinom diagnóza patologie MeSH
- fluorescenční mikroskopie MeSH
- kolorektální nádory diagnóza patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové buňky kultivované MeSH
- nádorové cirkulující buňky patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The presence of circulating tumor cells (CTCs) in patients with metastatic carcinoma is generally associated with poor clinical outcome. There have been many investigations showing a possible use of CTCs as minimally invasive predictive and prognostic biomarker in cancer medicine. In this report a size-based method (MetaCell®) for quick and easy enrichment and cultivation of CTCs is presented to enable possible CTCs use in esophageal cancer (EC) management. In total, 43 patients with diagnosed EC, 20 with adenocarcinoma (AdenoCa) and 23 with squamous cell carcinoma (SCC), were enrolled into the adaptive prospective-like study .All the patients were candidates for surgery. The CTCs were detected in 27 patients (62.8%), with a higher rate in adenocarcinoma (75%) than SCC (52%). Finally, there were 26 patients with resectable tumors exhibiting CTCs-positivity in 69.2% and 17 patients with non-resectable tumors with 41.7% CTCs-positivity. Interestingly, in the patients undergoing neoadjuvant therapy, the CTCs were detected at time of surgery in 55.5% (10/18). The overall size-based filtration approach enabled to isolate viable CTCs and evaluate to their cytomorphological features by means of vital fluorescent staining. The CTCs were cultured in vitro for further downstream applications including immunohistochemical analysis. This is the first report of the successful culturing of esophageal cancer CTCs. The detection of CTCs presence could help in the future to guide timing of surgical treatment in EC patients.
- MeSH
- adenokarcinom diagnóza patologie MeSH
- barvení a značení MeSH
- filtrace MeSH
- lidé MeSH
- nádorové cirkulující buňky * MeSH
- nádory jícnu krev diagnóza MeSH
- počet buněk MeSH
- prospektivní studie MeSH
- spinocelulární karcinom diagnóza patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of the study was to assess the immunohistochemical (IHC) profiles of SRC3, Pax2, ER, PgR, Her2, EGFR, CK5/6, and Ki67 proteins in breast-cancer brain metastasis. The study utilized tumor samples from 30 metastatic patients and calculated correlations between all IHC variables. In fourteen cases, primary breast cancers paired with secondary deposits were analyzed. We evaluated the association between IHC status in the primary and secondary deposits, grade, and histotype of the tumors. The examination of the metastatic deposits in all 30 patients resulted in positive detection in the following cases: SRC3 in 20 cases (66.6%), Pax2 in 22 (73.3%), ER in 22 (73.3%), PgR in 25 (83.3%), Her2 in 10 (33.3%), EGFR in 12 (40%), CK5/6 in 7 (23.3%), and Ki67 in 23 (76.6%). Grade 2 was found in 13.3% of all patients, and grade 3 in 86.7%. SRC3 and Pax2 were positive in both G2 and G3. Invasive lobular carcinoma and invasive ductal carcinoma were diagnosed in 23.3% and 76.7% of cases, respectively. There were no differences between the IHC expression of the studied proteins in either grading or histotype of the tumors. In the IHC profiles, which included SRC3, Pax2, ER, PgR, Her2, CK5/6, Ki67, and EGFR, we found no statistically significant differences between the primary cancer and the brain metastasis. In our study of metastatic breast carcinoma deposits, there was no correlation between SRC3, Pax2 status and histotype, and tumor grade. The IHC status of the paired primary and metastatic deposits did not differ in a statistically significant manner.
- MeSH
- alfa receptor estrogenů genetika metabolismus MeSH
- antigen Ki-67 genetika metabolismus MeSH
- dospělí MeSH
- erbB receptory genetika metabolismus MeSH
- karcinom diagnóza metabolismus MeSH
- koaktivátor 3 jaderných receptorů genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory mozku diagnóza metabolismus sekundární MeSH
- nádory prsu diagnóza metabolismus MeSH
- receptor erbB-2 genetika metabolismus MeSH
- receptory progesteronu genetika metabolismus MeSH
- regulace genové exprese u nádorů * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- transkripční faktor PAX2 genetika metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alfa receptor estrogenů MeSH
- antigen Ki-67 MeSH
- erbB receptory MeSH
- ERBB2 protein, human MeSH Prohlížeč
- koaktivátor 3 jaderných receptorů MeSH
- NCOA3 protein, human MeSH Prohlížeč
- PAX2 protein, human MeSH Prohlížeč
- receptor erbB-2 MeSH
- receptory progesteronu MeSH
- transkripční faktor PAX2 MeSH
Circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) are responsible for the development of metastatic disease, and may also hold the key to determining tailored therapies of advanced cancer disease. Our review summarizes the prognostic significance of the detection of CTCs and DTCs in various gastrointestinal cancers with an overview of their possible use as prognostic biomarkers. This could be used inthe future as a starting point for new clinical trials focusing on the predictive potential of circulating and disseminated tumor cells.
- MeSH
- gastrointestinální nádory krev diagnóza patologie MeSH
- klinické zkoušky jako téma * MeSH
- lidé MeSH
- nádorové biomarkery krev metabolismus MeSH
- nádorové cirkulující buňky metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- nádorové biomarkery MeSH
The present study was undertaken to provide information on the nucleolar and cytoplasmic density in specimens stained for RNA during "cell dedifferentiation" represented by blastic transformation of mature T lymphocytes. Nucleolar and cytoplasmic RNA's were visualized using a simple cytochemical method followed by computer assisted densitometry and size measurements of digitised images. An increased nucleolar and cytoplasmic RNA density accompanying the blastic transformation was significant after 48 hours of cultivation with phytohemaglutinin (PHA) when stimulated cells were characterized the largest nucleolar size reflecting S or G2 phase of the cell cycle. On the other hand, significantly larger ratio of the nucleolar to cytoplasmic density was noted only after a shorter cultivation when stimulated cells were presumably in the G1 phase. Thus the increased nucleolar and cytoplasmic RNA density together represented an accompanying phenomenon of the cell proliferation and cycling state. From the methodical point of view, the nucleolar and cytoplasmic RNA densitometry appeared as a simple as well as useful additional method to study "dedifferentiation" or various cell states at the single cell level. In addition, it was also interesting that the increase of the nucleolar diameter in stimulated cells was much larger than that of the nucleolar density. Such difference suggested that the RNA content in nucleoli was related mainly to their size.
- MeSH
- aktivace lymfocytů imunologie MeSH
- buněčné jadérko metabolismus MeSH
- cytoplazma metabolismus MeSH
- dediferenciace buněk * MeSH
- imunohistochemie MeSH
- lidé MeSH
- RNA metabolismus MeSH
- T-lymfocyty cytologie imunologie MeSH
- velikost organel MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- RNA MeSH
Class III beta-tubulin has been discovered as a marker of early phases of neuronal differentiation in developmental conditions, as well as in different tumours of neuronal origin. More recently, the expression of class III beta-tubulin molecule has been described as a marker of different types of malignant epithelial tumours. This study attempts to compare the immunostaining features of two different mouse monoclonal antibodies TU-20 and TuJ-1, both detecting class III beta-tubulin, in a group of twenty bioptically evaluated carcinomas of various sites. The proposal that class III beta-tubulin expression can correlate with the degree of tumour differentiation and thus could be potentially used as predictive marker of prognosis has been previously done; one of aims of our study was to confirm this hypothesis. Our results showed that both TuJ- 1 and TU-20 antibodies displayed similar immunostaining profile and pattern within individual tumours. Surprisingly, we discovered that only 50% of tumours included in our group showed expression of class III beta-tubulin, however, positive immunoreaction did not correspond with the degree of differentiation of individual tumours. In our group of carcinomas, the class III beta-tubulin positivity was not related to the tumour site, histologic type of tumour or its grade.
- MeSH
- dospělí MeSH
- imunohistochemie MeSH
- karcinom diagnóza patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- monoklonální protilátky imunologie MeSH
- myši MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tubulin imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- monoklonální protilátky MeSH
- TUBB3 protein, human MeSH Prohlížeč
- tubulin MeSH
The aim of the study was to determine the expression of proliferating cell nuclear antigen protein (PCNA) in the pig ovary. The localization of PCNA was demonstrated in paraffin sections of pig ovarian tissue using primary mouse monoclonal anti-PCNA antibody. In primordial follicles, no remarkable staining for PCNA either in granulosa cells or in the oocytes was observed. In primary to secondary follicles, positive staining in oocytes and in some granulosa cells was detected. The advanced preantral and particularly actively growing small to large antral follicles showed extensive PCNA labeling in the layers of granulosa and theca cells and in the cumulus cells encircling the oocyte. PCNA labeling was expressed in nuclei of oocytes in preantral and small antral follicles. In atretic follicles, the level of PCNA protein expression was dependent on the stage of atresia. Follicles demonstrating advanced atresia showed only limited or no PCNA labeled granulosa and theca cells. The results of the study demonstrate that follicular growth and development in pig ovary may be effectively monitored by determining the granulosa cell expression of PCNA.
- MeSH
- buněčné jádro metabolismus MeSH
- folikulární buňky cytologie metabolismus MeSH
- imunohistochemie MeSH
- oocyty cytologie metabolismus MeSH
- prasata MeSH
- proliferace buněk * MeSH
- proliferační antigen buněčného jádra biosyntéza MeSH
- regulace genové exprese fyziologie MeSH
- thekální buňky cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- proliferační antigen buněčného jádra MeSH
Human embryonic stem cells (hESCs) are pluripotent stem cells with long-lasting capacity to self-renew and differentiate into various cell types of endodermal, ectodermal or mesodermal origin. Unlike mouse ESCs (mESCs), which can be maintained in an undifferentiated state simply by adding leukemia inhibitory factor (LIF) into the culture medium, hESCs are notorious for the sustained willingness to differentiate and not yet clearly defined signaling pathways that are crucial for their "stemness". Presently, our knowledge involves only limited number of growth factor signaling pathways that appear to be biologically relevant for stem cell functions in vitro. These include BMP, TGFbeta, Wnt, and FGF signaling pathway. The purpose of this review is to summarize recent data on the expression of FGFs and their receptors in hESCs, and critically evaluate the potential effects of FGF signals for their undifferentiated growth and/or differentiation in context with our current understanding of FGF/FGFR biology.
- MeSH
- biologické modely MeSH
- buněčná diferenciace fyziologie MeSH
- embryo savčí cytologie fyziologie MeSH
- fibroblastový růstový faktor 2 * genetika metabolismus fyziologie MeSH
- kmenové buňky cytologie fyziologie MeSH
- lidé MeSH
- receptory fibroblastových růstových faktorů * genetika metabolismus fyziologie MeSH
- signální transdukce fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- fibroblastový růstový faktor 2 * MeSH
- receptory fibroblastových růstových faktorů * MeSH
Human exposure to endocrine disrupters (EDs) is widespread and is considered to pose a growing threat to human health. Recent advances in molecular and genetic research and better understanding of mechanisms of blastic cell transformation have led to efforts to improve cancer risk assessment for populations exposed to this family of xenobiotics. In risk assessment, low dose extrapolation of cancer incidence data from both experimental animals and epidemiology studies has been largely based on models assuming linear correlation at low doses, despite existence of evidence showing otherwise. Another weakness of ED risk assessment is poor exposure data in ecological studies. Those are frequently rough estimates derived from contaminated items of local food basket surveys. Polyhalogenated hydrocarbons are treated as examples. There is growing sense of urgency to develop a biologically based dose response model of cancer risk, integrating emerging data from molecular biology and epidemiology to provide more realistic data for risk assessors, public, public health managers and environmental issues administrators.
- MeSH
- endokrinní systém účinky léků MeSH
- hodnocení rizik trendy MeSH
- karcinogeny životního prostředí škodlivé účinky MeSH
- lidé MeSH
- nádory chemicky indukované epidemiologie MeSH
- vystavení vlivu životního prostředí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- karcinogeny životního prostředí MeSH