Colorectal cancer (CRC) is the fourth most commonly diagnosed malignant condition in the world. Micro RNAs (miRNAs) as well as epithelial to mesenchymal transition (EMT) play an important role in the pathogenesis of CRC. We performed a comparative analysis of the expression of selected miRNA genes and EMT markers in bioptic samples from patients (n = 45) with primary CRC or metastatic (m)CRC to the regional lymph node using reverse transcription-quantitative PCR and IHC staining. Results: Out of all miRNA analyzed, the miR-17 expression was most significantly different and associated with lower risk of CRC spread to the lymph node. In addition, significant relationships were found between the tumor side localization and several miRNAs expressions (miR-9, miR-29b, miR-19a, miR-19b, miR-21, miR-106a, miR-20a and miR-17). In addition, of the examined EMT markers, only VEGFA expression correlated with tumor progression (tumor grade G2). In the examined set of patient samples and their matched healthy tissue, several specific molecular markers (miRNAs associated with EMT and tumor progression) were identified with a promising prognostic potential. Their further examination in larger patient cohorts is planned to validate the present data.
Ovarian cancer is the deadliest gynecologic cancer. The large-scale microRNA (miRNA) expression profiling and individual miRNA validation was performed to find potential novel biomarkers for ovarian cancer. The most consistent overexpression of miRs-200b-3p, 135 b-5p and 182-5p was found in both ascitic fluid and tumors and suggests their potential as oncogenes. miR-451a was consistently underexpressed so may be a tumor suppressor. Results were inconsistent for miR-204-5p, which was overexpressed in ascitic fluid but underexpressed in tumor tissue. miR-203a-3p was generally overexpressed but this failed to be proved in independent sample set in tissue validation.
- MeSH
- ascitická tekutina chemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA genetika MeSH
- nádorové biomarkery genetika MeSH
- nádory vaječníků genetika patologie MeSH
- ovarium chemie MeSH
- prognóza MeSH
- regulace genové exprese u nádorů MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů metody MeSH
- senioři MeSH
- staging nádorů MeSH
- stanovení celkové genové exprese metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Tamoxifen treatment in breast cancer patients is associated with increased risk of endometrial malignancies. Significantly, higher AGR2 expression was found in endometrial cancers that developed in women previously treated with tamoxifen compared to those who had not been exposed to tamoxifen. An association of elevated AGR2 level with myometrial invasion occurrence and invasion depth was also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular proliferation. Although adverse tamoxifen effects on endometrial cells remain elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent mechanism of action responsible for increased incidence of endometrial cancer.
- MeSH
- adenokarcinom chemicky indukované genetika metabolismus patologie MeSH
- antitumorózní látky hormonální toxicita MeSH
- buňky A549 MeSH
- endometrium účinky léků metabolismus patologie MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- MFC-7 buňky MeSH
- nádorová transformace buněk chemicky indukované genetika metabolismus patologie MeSH
- nádory endometria chemicky indukované genetika metabolismus patologie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk účinky léků MeSH
- proteiny genetika metabolismus MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- RNA interference MeSH
- signální transdukce účinky léků MeSH
- tamoxifen toxicita MeSH
- transfekce MeSH
- upregulace MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Univariate and multivariate analyses were carried out to identify factors associated with the failure of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to correctly predict relapse-free survival in patients with nonseminomatous germ cell tumours. Ninety-three patients with negative postchemotherapy FDG-PET scan were analyzed in the retrospective study. The FDG-PET result was validated by long-term follow-up and, in some patients, by resection of the residual tumour mass. The negative predictive value of FDG-PET was 81.7%. Higher tumour marker levels and nodal stage at diagnosis, presence of residual mass, and teratoma or teratocarcinoma in the primary histology were associated with FDG-PET failure.
- MeSH
- dospělí MeSH
- falešně negativní reakce MeSH
- fluorodeoxyglukosa F18 diagnostické užití MeSH
- germinální a embryonální nádory farmakoterapie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pozitronová emisní tomografie MeSH
- prediktivní hodnota testů MeSH
- přežití po terapii bez příznaků nemoci MeSH
- reziduální nádor MeSH
- teratom diagnóza MeSH
- testikulární nádory farmakoterapie mortalita MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Neoadjuvant chemotherapy (NCT) of breast cancer enabled improved outcomes especially in patients with advanced and inflammatory diseases. Biological heterogeneity of these tumors, however, requires better molecular characterization of the malignant tissue with consequent individualization in the selection of appropriate agents. To date, numerous molecular markers have been identified, and some of them (e.g., measurement of hormonal or growth factors receptors) are already routinely used for breast cancer classification before NCT. In the present article, we summarize current knowledge about established as well as promising biomarkers which have demonstrated prognostic or predictive value in NCT of breast cancer.
- MeSH
- adjuvantní chemoterapie MeSH
- antigen Ki-67 analýza MeSH
- cyklofosfamid terapeutické užití MeSH
- doxorubicin terapeutické užití MeSH
- fluorouracil terapeutické užití MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory prsu farmakoterapie imunologie metabolismus MeSH
- neoadjuvantní terapie * MeSH
- prognóza MeSH
- receptor erbB-2 analýza MeSH
- receptory pro estrogeny analýza MeSH
- receptory progesteronu analýza MeSH
- taxoidy terapeutické užití MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Many studies have demonstrated the importance of spontaneous metastases in cancer research. Until now, we still had only a few spontaneous metastatic models with high occurrence rate of metastasis in distant lymph and visceral tissues. We report a syngeneic heterotopic metastatic model using the Lewis lung cancer cell line with high metastatic ratio in C57BL/6 mice after transplantation by injection of cancer cells and without surgical intervention. Metastatic process was declared for each mouse in two groups ?sacrificed 3 or 5 weeks after subcutaneous (s.c.) injection of the tumor cells into the dorsal side of the tail. The total number of metastases was counted as the sum of observed macrometastases. Our model produced produced a 100% rate of spontaneous lymphatic and visceral metastases after a simple injection transplantation into the heterotopic site. In mice with large primary tumors which are non-lethal, visceral and lymph macrometastases were observed. Tumor volume correlated linearly not only with the tumor growth time, but also with the number of metastases in lymph nodes and organs. This new metastatic model could be useful for studying the metastasis mechanism and for developing therapy for lymph and visceral metastases.
Cytotoxicity and apoptosis induced by etoposide were studied during 72 hr in human melanoma cells. Etoposide initiated DNA-damage signaling via ATM kinase and activated p53 pathway and caspase-2. In response to treatment with etoposide, mitochondria of melanoma cells first increased their abundance and activity, and at later treatment intervals their dynamic behavior and functions became suppressed. Observed mitochondrial perturbation was not preceded by membrane potential loss but cytochrome c release was observed together with a rise in caspase-9 and caspase-3 activities. The pharmacological inhibition of relevant induced targets proved the importance of ATM and caspase-2 in etoposide-mediated cytotoxicity and apoptosis.
- MeSH
- adenosintrifosfát metabolismus MeSH
- antitumorózní látky fytogenní farmakologie MeSH
- apoptóza účinky léků MeSH
- benzothiazoly farmakologie MeSH
- cyklosporin farmakologie MeSH
- cysteinové endopeptidasy metabolismus MeSH
- DNA vazebné proteiny antagonisté a inhibitory metabolismus MeSH
- etoposid farmakologie MeSH
- inhibitory cysteinových proteinas farmakologie MeSH
- inhibitory proteinkinas farmakologie MeSH
- kaspasa 2 metabolismus MeSH
- kaspasa 3 antagonisté a inhibitory metabolismus MeSH
- kaspasa 9 antagonisté a inhibitory metabolismus MeSH
- lidé MeSH
- melanom patologie MeSH
- mitochondrie účinky léků MeSH
- nádorové buňky kultivované účinky léků MeSH
- nádorové proteiny antagonisté a inhibitory metabolismus MeSH
- nádorové supresorové proteiny antagonisté a inhibitory metabolismus metabolismus MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- poškození DNA MeSH
- protein X asociovaný s bcl-2 metabolismus MeSH
- protein-serin-threoninkinasy antagonisté a inhibitory metabolismus MeSH
- proteiny buněčného cyklu metabolismus MeSH
- superoxidy metabolismus MeSH
- toluen analogy a deriváty farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Effect of advanced glycation end products (AGEs) in the pathogenesis of cancer could be diminished by interaction with soluble RAGE or by reducing AGE-precursors via glyoxalase I. Glu111Ala polymorphism of glyoxalase I gene, AGEs, and sRAGE serum levels were studied in 113 breast cancer patients and in 58 controls. Higher frequency of the mutated C allele was found in patients with negative estrogen receptors and in patients in clinical stage III compared to controls (P< 0.05). The presence of the C allele could represent a negative prognostic factor; however, further studies are needed to confirm this hypothesis.
- MeSH
- fenotyp MeSH
- frekvence genu MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- laktoylglutathionlyasa genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu enzymologie genetika patologie MeSH
- produkty pokročilé glykace krev MeSH
- prognóza MeSH
- receptory imunologické krev MeSH
- receptory pro estrogeny analýza MeSH
- regulace genové exprese enzymů MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Tumor-infiltrating leukocytes and other immunohistochemical parameters were evaluated in pretherapeutic biopsies and resection specimens in 73 patients undergoing neoadjuvant chemotherapy with doxorubicin and paclitaxel. Ten patients with pathological complete response had significantly higher p53 expression, CD3(+) lymphocyte and CD83(+) cell counts, and lower progesterone receptor expression. In the remaining 63 patients, a significant decrease in the percentage of Ki-67, vascular endothelial growth factor expression, CD68(+) monocytes, and increased CD31(+), CD34(+), and SMA(+) stromal vessels, maximal CD3(+) and CD56(+) lymphocyte, maximal and mean CD83(+) cell, maximal CD1a(+), and maximal and mean S100(+) cell counts were observed after neoadjuvant chemotherapy.
- MeSH
- antigen Ki-67 analýza MeSH
- CD antigeny analýza MeSH
- dospělí MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádorové biomarkery analýza MeSH
- nádory prsu farmakoterapie patologie MeSH
- neoadjuvantní terapie metody MeSH
- počet lymfocytů MeSH
- prediktivní hodnota testů MeSH
- senioři MeSH
- staging nádorů MeSH
- tumor infiltrující lymfocyty patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Receptor for advanced glycation end products (RAGE) may be involved in the pathogenesis of the cancer progression and metastasis. Pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE), so the higher sRAGE levels may confer the patients with cancer with better outcome. The aim was to study sRAGE and RAGE gene polymorphisms in patients with breast cancer. The authors studied sRAGE and RAGE polymorphisms in 120 patients with breast cancer (subdivided based on the clinical stage, histologic grading, expression of hormonal and Her2/neu receptors) and in 92 healthy controls. Despite higher serum concentrations of AGEs, serum concentrations of sRAGE were lower in patients with breast cancer compared to healthy controls (1581 +/- 777 versus 1803 +/- 632 ng/mL, p < 0.05). Serum levels of sRAGE were higher in patients with advanced breast cancer (stage III), lower grade and positive estrogen receptors, and intermediate positivity of Her2/neu receptors and were also influenced genetically (Gly82Ser and 2184 AG polymorphisms of the RAGE gene). Decreased sRAGE levels in patients with breast cancer may contribute to the progression of the disease. Patients with better outcome (low grade and positive estrogen receptors) have higher sRAGE levels. Progression of the disease, may, however, increase sRAGE levels, possibly as a compensatory mechanism to counteract further progression.
- MeSH
- dospělí MeSH
- financování organizované MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu genetika krev MeSH
- polymorfismus genetický MeSH
- produkty pokročilé glykace krev MeSH
- receptor erbB-2 analýza MeSH
- receptory imunologické genetika krev MeSH
- receptory pro estrogeny analýza MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH