- Klíčová slova
- Breast, Dynamics, Heterogeneity, Imaging, Mammary gland, Single cell RNA sequencing,
- MeSH
- analýza jednotlivých buněk metody trendy MeSH
- lidé MeSH
- mikroskopie metody trendy MeSH
- mléčné žlázy lidské * cytologie patologie fyziologie MeSH
- mléčné žlázy zvířat * cytologie patologie fyziologie MeSH
- myši MeSH
- nádory mléčné žlázy u zvířat patologie MeSH
- nádory prsu patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- úvodní články MeSH
- úvodníky MeSH
The field of mammary gland biology and breast cancer research encompasses a wide range of topics and scientific questions, which span domains of molecular, cell and developmental biology, cancer research, and veterinary and human medicine, with interdisciplinary overlaps to non-biological domains. Accordingly, mammary gland and breast cancer researchers employ a wide range of molecular biology methods, in vitro techniques, in vivo approaches as well as in silico analyses. The list of techniques is ever-expanding; together with the refinement of established, staple techniques in the field, new technologies keep emerging thanks to technological advances and scientific creativity. This issue of the Journal of Mammary Gland Biology and Neoplasia represents a compilation of original articles and reviews focused on methods used in mammary gland biology and breast cancer research.
- Klíčová slova
- Breast, Database, Exosomes, Heterogeneity, Mammary gland, Milk cells, Multiplexing, Organoid,
- MeSH
- biomedicínský výzkum metody MeSH
- laktace fyziologie MeSH
- lidé MeSH
- mléčné žlázy lidské patologie fyziologie MeSH
- mléčné žlázy zvířat patologie fyziologie MeSH
- nádory mléčné žlázy u zvířat patologie MeSH
- nádory prsu patologie MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- úvodní články MeSH
- úvodníky MeSH
Induction of selective thrombosis and infarction in tumor-feeding vessels represents an attractive strategy to combat cancer. Here we took advantage of the unique coagulation properties of staphylocoagulase and genetically engineered it to generate a new fusion protein with novel anti-cancer properties. This novel bi-functional protein consists of truncated coagulase (tCoa) and an NGR (GNGRAHA) motif that recognizes CD13 and αvβ3 integrin receptors, targeting it to tumor endothelial cells. Herein, we report that tCoa coupled by its C-terminus to an NGR sequence retained its normal binding activity with prothrombin and avβ3 integrins, as confirmed in silico and in vitro. Moreover, in vivo biodistribution studies demonstrated selective accumulation of FITC-labeled tCoa-NGR fusion proteins at the site of subcutaneously implanted PC3 tumor xenografts in nude mice. Notably, systemic administration of tCoa-NGR to mice bearing 4T1 mouse mammary xenografts or PC3 human prostate tumors resulted in a significant reduction in tumor growth. These anti-tumor effects were accompanied by massive thrombotic occlusion of small and large tumor vessels, tumor infarction and tumor cell death. From these findings, we propose tCoa-NGR mediated tumor infarction as a novel and promising anti-cancer strategy targeting both CD13 and integrin αvβ3 positive tumor neovasculature.
- MeSH
- antigeny CD13 metabolismus MeSH
- buněčná smrt fyziologie MeSH
- endoteliální buňky pupečníkové žíly (lidské) MeSH
- integrin alfaVbeta3 metabolismus MeSH
- koagulasa metabolismus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory mléčné žlázy u zvířat metabolismus patologie MeSH
- nádory prostaty metabolismus patologie MeSH
- oligopeptidy metabolismus MeSH
- patologická angiogeneze metabolismus patologie MeSH
- xenogenní modely - testy protinádorové aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- antigeny CD13 MeSH
- integrin alfaVbeta3 MeSH
- koagulasa MeSH
- NGR peptide MeSH Prohlížeč
- oligopeptidy MeSH
BACKGROUND: One approach to improve effect of chemotherapy is combination of classical cytostatic drugs with natural compounds, e. g. sesquiterpenes. In our previous study, sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) improved the anti-proliferative effect of doxorubicin (DOX) in intestinal cancer cell lines. PURPOSE: The present study was designed to evaluate the effect of CAO and NER on DOX efficacy, focusing on cell proliferation, migration, apoptosis and DOX accumulation in breast cancer cells MDA-MB-231 and MCF7 in vitro and in mice bearing solid Ehrlich tumors (EST) in vivo. METHODS: The impact of cytotoxic effect was assessed by the neutral red uptake test. The ability to migrate was tested using real-time measurement in x-CELLigence system. Expressions of molecules were examined using western blot analysis. The accumulation of DOX inside the cells using time lapse microscopy was observed. The mice with inoculated EST cells were treated repeatedly with DOX and DOX+CAO or DOX+NER and the growth of tumors were monitored. DOX concentrations in plasma and tumor were assayed using HPLC. RESULTS: In MDA-MB-231, combination of DOX with CAO enhanced anti-proliferative effect and acted strongly synergistic. NER increased accumulation of DOX inside the cells; moreover combination DOX with NER suppressed migration ability in vitro. In vivo, apoptosis was activated especially in group treated with DOX and CAO. However, none of tested sesquiterpenes was able to improve DOX accumulation in tumors and DOX-mediated inhibition of tumor growth. CONCLUSION: In conclusion, sesquiterpenes CAO and NER increased the efficacy of DOX in breast cancer cells in vitro, but did not improve its effect in vivo, in Ehrlich solid tumor bearing mice.
- Klíčová slova
- Anti-apoptotic effect, Breast cancer cells, Doxorubicin, Trans-nerolidol, Tumor bearing mice, β-Caryophyllene oxide,
- MeSH
- doxorubicin krev terapeutické užití MeSH
- inhibiční koncentrace 50 MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory mléčné žlázy u zvířat farmakoterapie patologie MeSH
- nádory prsu krev farmakoterapie patologie MeSH
- pohyb buněk účinky léků MeSH
- polycyklické seskviterpeny MeSH
- proliferace buněk účinky léků MeSH
- seskviterpeny chemie farmakologie terapeutické užití MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- caryophyllene oxide MeSH Prohlížeč
- doxorubicin MeSH
- nerolidol MeSH Prohlížeč
- polycyklické seskviterpeny MeSH
- seskviterpeny MeSH
The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design.
- MeSH
- chemorezistence genetika MeSH
- ethylenglykoly aplikace a dávkování chemie MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky aplikace a dávkování chemie MeSH
- genový knockdown MeSH
- glykoly chemie MeSH
- lidé MeSH
- mesoporfyriny aplikace a dávkování chemie MeSH
- MFC-7 buňky MeSH
- myši MeSH
- nádory mléčné žlázy u zvířat farmakoterapie genetika patologie MeSH
- P-glykoprotein genetika MeSH
- paclitaxel škodlivé účinky MeSH
- porfyriny aplikace a dávkování chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ethylenglykoly MeSH
- fotosenzibilizující látky MeSH
- glykoly MeSH
- mesoporfyriny MeSH
- P-glykoprotein MeSH
- paclitaxel MeSH
- porfyriny MeSH
- temoporfin MeSH Prohlížeč
149 biopsies and excisions of tumorous tissues of the mammary gland it bitches were examined histologically at a workplace of the State Veterinary Institute at Ceské Budĕjovice in the years 1970 to 1987. The tumours were classified according to the criteria recommended by the WHO classification system. The tumours were divided into three groups with respect to their histogenesis: epithelial (58.4%), mesenchymatous (2%) and mixed (39.6%). The ratio of malignant to benign tumours made 65.1% to 34.9%.
- MeSH
- nádory mléčné žlázy u zvířat patologie MeSH
- nemoci psů patologie MeSH
- psi MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
