- MeSH
- dolní končetina * patologie MeSH
- dospělí MeSH
- kardiovaskulární látky farmakologie terapeutické užití MeSH
- lidé MeSH
- patologická angiogeneze chirurgie etiologie MeSH
- recidiva * MeSH
- senioři MeSH
- ultrasonografie metody MeSH
- varixy * chirurgie diagnóza MeSH
- vena saphena patologie MeSH
- vény abnormality anatomie a histologie chirurgie MeSH
- výkony cévní chirurgie metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.
- MeSH
- antitumorózní látky * aplikace a dávkování farmakologie chemie MeSH
- chinazolinony * chemie aplikace a dávkování farmakologie MeSH
- hydrogely * aplikace a dávkování chemie MeSH
- kovové nanočástice aplikace a dávkování chemie MeSH
- lidé MeSH
- myši inbrední BALB C MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- patologická angiogeneze farmakoterapie MeSH
- piperidiny * farmakologie aplikace a dávkování chemie MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk * účinky léků MeSH
- stříbro * chemie aplikace a dávkování MeSH
- triple-negativní karcinom prsu * farmakoterapie MeSH
- xenogenní modely - testy antitumorózní aktivity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Centrální serózní chorioretinopatie (CSC) je onemocnění charakterizované serózním odchlípením neuroretiny zejména v zadním pólu oka. Často je doprovázené serózním odloučením retinálního pigmentového epitelu (RPE) a sdružené s prosakováním tekutiny do subretinálního prostoru skrze defektní RPE. CSC nejčastěji postihuje muže v produktivním věku. Přesná patofyziologie onemocnění není zcela známa. Na základě angiografického vyšetření s indocyaninovou zelení (ICG), která odhalila zvýšenou permeabilitu choroidálních cév, a optické koherenční tomografie (OCT) ukazující zvýšenou tloušťku choroidey se předpokládá choroidální vaskulopatie jako primární příčina vzniku CSC. Ve většině případů má CSC dobrou prognózu se spontánní resorpcí subretinální tekutiny (SRT) a úpravou zrakových funkcí. U malého procenta pacientů však onemocnění přechází do chronického či rekurentního průběhu a může vést k nevratným funkčním i anatomickým změnám sítnice s konečným klinickým obrazem difuzní retinální pigmentové epitelopatie (DRPE). Optimální léčebný přístup k pacientům s CSC zůstává kontroverzní. V posledních dekádách se v léčbě chronických forem CSC (cCSC) používalo nespočet léčebných přístupů; tyto zahrnovaly například laserovou fotokoagulaci, medikamentózní léčbu, standardní fotodynamickou terapii (PDT) či anti-VEGF. V posledních letech se v léčbě cCSC preferuje méně destruktivní metoda, kterou je PDT v redukovaných dávkovacích schématech, ať už s redukovanou dávkou verteporfinu nebo použité energie laserového paprsku. Je prokázána srovnatelná účinnost a bezpečnost při použití redukovaných schémat PDT u pacientů s cCSC, u kterých došlo ke zlepšení nejlépe korigované zrakové ostrosti i redukci SRT.
Central serous chorioretinopathy (CSC) is a disease characterized by serous detachment of the neuroretina, especially in the posterior pole of the eye. It is often accompanied by serous detachment of the retinal pigment epithelium (RPE) and associated with the leakage of fluid into the subretinal space through the defective RPE. CSC most often affects men of working age. The exact pathophysiology of the disease is not completely known. Based on indocyanine green angiography (ICG), which revealed increased permeability of choroidal vessels, and optical coherence tomography (OCT) showing increased choroidal thickness, choroidal vasculopathy is assumed to be the primary cause of CSC. In most cases, CSC has a good prognosis with spontaneous resorption of the subretinal fluid (SRF) and improvement of visual functions. However, in a small percentage of patients the disease progresses to a chronic or recurrent course, and can lead to irreversible functional and anatomical changes of the retina with a final clinical picture of diffuse retinal pigment epitheliopathy (DRPE). The optimal treatment approach for patients with CSC remains controversial. In recent decades, myriad therapeutic approaches have been used in the treatment of chronic forms of CSC (cCSC); these included for example laser photocoagulation, pharmaceutical treatment, standard photodynamic therapy (PDT) or anti-VEGF. In recent years a less destructive method, specifically PDT in reduced dose regimens, either with a reduced dose of verteporfin or the laser beam energy used, has been preferred in the treatment of cCSC. Comparable efficacy and safety has been demonstrated using reduced-dose or reduced-fluence PDT regimens in patients with cCSC, with an improvement in best-corrected visual acuity and reduction of SRF.
- MeSH
- centrální serózní chorioretinopatie * diagnostické zobrazování diagnóza klasifikace patofyziologie terapie MeSH
- fluoresceinová angiografie metody MeSH
- fotochemoterapie metody MeSH
- lidé MeSH
- multimodální zobrazování klasifikace metody MeSH
- neovaskularizace choroidey patofyziologie MeSH
- poruchy zraku diagnostické zobrazování diagnóza etiologie MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
We aim to report the ocular phenotype and molecular genetic findings in two Czech families with Sorsby fundus dystrophy and to review all the reported TIMP3 pathogenic variants. Two probands with Sorsby fundus dystrophy and three first-degree relatives underwent ocular examination and retinal imaging, including optical coherence tomography angiography. The DNA of the first proband was screened using a targeted ocular gene panel, while, in the second proband, direct sequencing of the TIMP3 coding region was performed. Sanger sequencing was also used for segregation analysis within the families. All the previously reported TIMP3 variants were reviewed using the American College of Medical Genetics and the Association for Molecular Pathology interpretation framework. A novel heterozygous variant, c.455A>G p.(Tyr152Cys), in TIMP3 was identified in both families and potentially de novo in one. Optical coherence tomography angiography documented in one patient the development of a choroidal neovascular membrane at 54 years. Including this study, 23 heterozygous variants in TIMP3 have been reported as disease-causing. Application of gene-specific criteria denoted eleven variants as pathogenic, eleven as likely pathogenic, and one as a variant of unknown significance. Our study expands the spectrum of TIMP3 pathogenic variants and highlights the importance of optical coherence tomography angiography for early detection of choroidal neovascular membranes.
- MeSH
- lidé MeSH
- makulární degenerace * MeSH
- mutace MeSH
- neovaskularizace choroidey * MeSH
- oči MeSH
- tkáňový inhibitor metaloproteinasy 3 genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Epithelial-mesenchymal transition (EMT) is a crucial process with significance in the metastasis of malignant tumors. It is through the acquisition of plasticity that cancer cells become more mobile and gain the ability to metastasize to other tissues. The mesenchymal-epithelial transition (MET) is the return to an epithelial state, which allows for the formation of secondary tumors. Both processes, EMT and MET, are regulated by different pathways and different mediators, which affects the sophistication of the overall tumorigenesis process. Not insignificant are also cancer stem cells and their participation in the angiogenesis, which occur very intensively within tumors. Difficulties in effectively treating cancer are primarily dependent on the potential of cancer cells to rapidly expand and occupy secondarily vital organs. Due to the ability of these cells to spread, the concept of the circulating tumor cell (CTC) has emerged. Interestingly, CTCs exhibit molecular diversity and stem-like and mesenchymal features, even when derived from primary tumor tissue from a single patient. While EMT is necessary for metastasis, MET is required for CTCs to establish a secondary site. A thorough understanding of the processes that govern the balance between EMT and MET in malignancy is crucial.
- MeSH
- epitelo-mezenchymální tranzice * MeSH
- fenotyp MeSH
- kmenové buňky metabolismus cytologie patologie MeSH
- lidé MeSH
- nádorové cirkulující buňky * patologie metabolismus MeSH
- nádorové kmenové buňky * patologie metabolismus MeSH
- nádory patologie metabolismus MeSH
- patologická angiogeneze * patologie MeSH
- proliferace buněk genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The loss of control of cell proliferation, apoptosis regulation and contact inhibition leads to tumor development. While benign tumors are restricted to their primary space, i.e. where these tumors first originate, the metastatic tumors not only disseminate- facilitated by hypoxia-driven neovascularization- to distant secondary sites but also show substantial changes in metabolism, tissue architectures, gene expression profiles and immune phenotypes. All these alterations result in radio-, chemo- and immune-resistance rendering these metastatic tumor cells refractory to therapy. Since the beginning of the transformation, these factors- which influence each other- are incorporated to the developing and metastasizing tumor. As a result, the complexities in the heterogeneity of tumor progressively increase. This space-time function in the heterogeneity of tumors is generated by various conditions and factors at the genetic as well as microenvironmental levels, for example, endogenous retroviruses, methylation and epigenetic dysregulation that may be etiology-specific, cancer associated inflammation, remodeling of the extracellular matrix and mesenchymal cell shifted functions. On the one hand, these factors may cause de-differentiation of the tumor cells leading to cancer stem cells that contribute to radio-, chemo- and immune-resistance and recurrence of tumors. On the other hand, they may also enhance the heterogeneity under specific microenvironment-driven proliferation. In this editorial, we intend to underline the importance of heterogeneity in cancer progress, its evaluation and its use in correlation with the tumor evolution in a specific patient as a field of research for achieving precise patient-tailored treatments and amelioration of diagnostic (monitoring) tools and prognostic capacity.
- MeSH
- extracelulární matrix MeSH
- lidé MeSH
- nádorové kmenové buňky MeSH
- nádorové mikroprostředí genetika MeSH
- nádory * genetika MeSH
- patologická angiogeneze MeSH
- proliferace buněk genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Healing of dense regular connective tissue, due to a high fiber-to-cell ratio and low metabolic activity and regeneration potential, frequently requires surgical implantation or reconstruction with high risk of reinjury. An alternative to synthetic implants is using bioscaffolds obtained through decellularization, a process where the aim is to extract cells from the tissue while preserving the tissue-specific native molecular structure of the ECM. Proteins, lipids, nucleic acids and other various extracellular molecules are largely involved in differentiation, proliferation, vascularization and collagen fibers deposit, making them the crucial processes in tissue regeneration. Because of the multiple possible forms of cell extraction, there is no standardized protocol in dense regular connective tissue (DRCT). Many modifications of the structure, shape and composition of the bioscaffold have also been described to improve the therapeutic result following the implantation of decellularized connective tissue. The available data provide a valuable source of crucial information. However, the wide spectrum of decellularization makes it important to understand the key aspects of bioscaffolds relative to their potential use in tissue regeneration.
- MeSH
- dítě MeSH
- injekce intravitreální metody MeSH
- lidé MeSH
- mladiství MeSH
- myopie komplikace MeSH
- neovaskularizace sítnice * diagnóza etiologie farmakoterapie klasifikace MeSH
- optická koherentní tomografie metody MeSH
- poruchy zraku etiologie klasifikace prevence a kontrola MeSH
- vaskulární endoteliální růstové faktory * antagonisté a inhibitory aplikace a dávkování terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Angiogenesis in healthy tissue and within malignant tumors differs on many levels, which may partly be explained by vascular mimicry formation resulting in altered contrast material or different radiopharmaceuticals distributions. Failed remodulation results in changes in the molecular exchange through the capillary wall and those consequences affect the behavior of contrast agents and radiopharmaceuticals. One of the most indicative signs of malignant tissue is the increased permeability and the faster molecular exchange that occurs between the extracellular and intravascular spaces. Dynamic imaging can help to assess the changed microenvironment. The fast-distribution of molecules reflects newly developed conditions in blood-flow redistribution inside a tumor and within the affected organ during the early stages of tumor formation. Tumor development, as well as aggressiveness, can be assessed based on the change to the vascular bed development, the level of molecular exchange within the tissue, and/or indicative distribution within the organ. The study of the vascular network organization and its impact on the distribution of molecules is important to our understanding of the image pattern in several imaging methods, which in turn influences our interpretation of the findings. A hybrid imaging approach (including PET/MRI) allows the quantification of vascularization and/or its pathophysiological impressions in structural and metabolic images. It might optimize the evaluation of the pretreatment imaging, as well as help assess the effect of therapy targeting neovascularization; antiVEGF drugs and embolization-based therapies, for example.
- MeSH
- kontrastní látky MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- nádorové mikroprostředí MeSH
- nádory * diagnostické zobrazování MeSH
- patologická angiogeneze diagnostické zobrazování patologie MeSH
- perfuze MeSH
- radiofarmaka * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- Bruchova membrána zranění MeSH
- dítě MeSH
- lidé MeSH
- neovaskularizace sítnice * diagnóza patologie MeSH
- oftalmoskopie metody MeSH
- optická koherentní tomografie metody MeSH
- retina * patologie zranění MeSH
- tupá poranění klasifikace komplikace MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
