Fotodynamická terapia (PDT, photodynamic therapy) je jednou z najmodernejších a najperspektívějších terapeutických metód pri liečení nádorových ochorení. Princíp PDT je založený na deštrukcii nádoru, ktorá nastane po podaní fotosenzibilizátora (FTS) a následnom ožiarení nádoru, v ktorom sa nachádza FTS [1]-[4]. Selektívna akumulácia a retencia FTS v nádorových tkanivách, v porovnaní s okolitým zdravým tkanivom, vedie k selektívnej deštrukcii nádoru, pričom okolité zdravé tkanivo ostáva nepoškodené. Takáto selektivita je jednou z najväčších výhod tejto metódy, ktorá umožňuje v istých prípadoch nahradiť chemoterapiu, rádioterapiu, či chirurgický zákrok při liečbě nádorových ochorení. PDT má oproti ostatným "klasickým" prístupom k liečbě rakoviny (chirurgia, chemoterapia, rádioterapia) tieto následujúce výhody: I) zanedbateĺné vedĺajšie efekty, II) nízka úroveň komplikácii počas a po terapeutickom zákroku, III) vyššia kvalita života pacienta, IV) možnosť terapie mimo zdravotníckeho zariadenia, V) možnosť opakovanej liečby, VI) možnosť diagnostiky a terapie v jednom kroku, VII) nižšie finančné náklady liečby v porovnaní s chemoterapiou a rádioterapiou., Pavol Miškovský, Daniel Jancura, Jozef Uličný, Gabriela Fabríciová., and Obsahuje seznam literatury
Hypoxia-inducible factors (HIFs) are transcription factors controlling energy, iron metabolism, erythropoiesis, and development. Dysregulation of these proteins contributes to tumorigenesis and cancer progression. Recent findings revealed the important role of HIFs in the pathogenesis of neuroendocrine tumors, especially pheoch romocytoma (PHEO) and paraganglioma (PGL). PHEOs and PGLs are catecholamine- producing tumors arising from sympathetic- or parasympathetic- derived chromaffin tissue. To date, eighte en PHEO/PGL susceptibility genes have been identified. Based on the main signaling pathways, PHEOs/PGLs have been divided into two clusters, pseudohypoxic cluster 1 and cluster 2, rich in kinase receptor signaling and protein translation pathways. Recent data suggest that both clusters are interconnected via the HIF signaling and its role in tumorigenesis is supported by newly described somatic and germline mutations in HIF2A gene in patients with PHEOs/PGLs associated with polycythemia, and in some of them also with somatostatinoma. Moreover, HIF α signaling has also been sh own to be upregulated in neuroendocrine tumors other than PHEO/PGL. Some of these tumors are components of hereditary tumor syndromes which can be associated with PHEO/PGL, but also in ileal carcinoids or melanoma. HIF signaling appears to be one of the crucial players in tumorigenesis, which could suggest new therapeutic approaches for treatment of neuroendocrine tumors., I. Jochmanová, T. Zelinka, J. Widimský Jr., K. Pacak., and Obsahuje bibliografii
napsal Lad. Syllaba., KČSN (sg. S-L 403), Z I. kliniky nemocí vnitřních při Universitě Karlově, Předloženo II. třídě dne 4. dubna 1930, and Obsahuje bibliografii a rejstřík
The aim of the present study was to introduce methods for exome sequencing of two ATP-binding cassette (ABC) transporters ABCC8 and ABCD2 recently suggested to play a putative role in breast cancer progression and prognosis of patients. We performed next generation sequencing targeted at analysis of all exons in ABCC8 and ABCD2 genes and surrounding noncoding sequences in blood DNA samples from 24 patients with breast cancer. The revealed alterations were characterized by in silico tools. We then compared the most frequent functionally relevant polymorphism rs757110 in ABCC8 with clinical data of patients. In total, the study identified 113 genetic alterations (>70 % novel ones) in both genes. Of these alterations, 83 were noncoding, 13 synonymous, 10 frameshifts and 7 were missense alterations. Four in silico programs predicted pathogenicity of two polymorphisms and four newly identified alterations. Rs757110 polymorphism in ABCC8 did not significantly associate with clinical data of the patients. In conclusion, exome sequencing identified several functionally relevant alterations in ABCC8 and ABCD2 genes that may further be used for a larger follow-up study aiming to assess their clinical significance., P. Soucek, V. Hlavac, K. Elsnerova, R. Vaclavikova, R. Kozevnikovova, K. Raus., and Obsahuje bibliografii