The melanin-concentrating hormone system in human, rodent and avian brain

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A melanoma és az agyi áttétképződés molekuláris háttere | Molecular background of the melanoma and the brain metastasis

Absztrakt: A melanoma malignum az egyik legagresszívebb daganat, amely gyakran képez áttétet távoli szervekbe. Az előrehaladott tumorok közel felében figyeltek meg agyi metasztázist. A korai diagnózis a betegség kimenetele szempontjából nagy jelentőségű. Az új, hatékony terápiák kialakításában fontos a bekövetkező genetikai és epigenetikai eltérések feltérképezése, ami ígéretes terápiás célpontokat jelölhet ki. Leggyakrabban a mitogénaktivált proteinkináz útvonal, a foszfatidil-inozitol-3-kináz jelátviteli útvonal és a sejtciklus-szabályozó molekulák génjeinek mutációi vezethetnek melanoma kialakulásához. A melanoma agyi áttétképzésének molekuláris folyamata nem teljesen feltárt. Közleményünkben összefoglaljuk a melanoma, illetve az agyi metasztázis kialakulásában szerepet játszó genetikai eltéréseket és molekuláris mechanizmusokat. Orv Hetil. 2017; 158(28): 1083–1091. | Abstract: Malignant melanoma is one of the most aggressive tumors which often gives metastasis to distant organs thereby limiting the chances of survival. Brain metastasis occurs in nearly half of the advanced tumors. In order to improve outcome early diagnosis is important. The discovery and better understanding of genetic and epigenetic changes is essential for developing new effective therapies, which can designate promising therapeutic targets. Melanoma most often is caused by gene mutations of the mitogen-activated protein kinase pathway, the phosphatidylinositol 3-kinase signaling pathway, and the cell cycle regulatory molecules, respectively. The molecular process of brain metastasis has not been fully elucidated. In our review we summarize the genetic alterations and molecular mechanisms playing a role in the development of melanoma and its brain metastasis. Orv Hetil. 2017; 158(28): 1083–1091

Epigenetics of Meningiomas.

Meningiomas account for one-third of all adult central nervous system tumours and are divided into three WHO grades. In contrast to the relatively well characterized genetic alterations, our current understanding of epigenetic modifications involved in the meningioma-genesis and progression is rather incomplete. Contrary to genetic alterations, epigenetic changes do not alter the primary DNA sequence and their reversible nature serves as an excellent basis for prevention and development of novel personalised tumour therapies. Indeed, growing body of evidence suggests that disturbed epigenetic regulation plays a key role in the pathogenesis of meningiomas. Altered DNA methylation, microRNA expression, histone, and chromatin modifications are frequently noted in meningiomas bearing prognostic and therapeutic relevance. In this review we provide an overview on recently identified epigenetic alterations in meningiomas and discuss their role in tumour initiation, progression, and recurrence

A melanoma és az agyi áttétképződés molekuláris háttere | Molecular background of the melanoma and the brain metastasis

Absztrakt: A melanoma malignum az egyik legagresszívebb daganat, amely gyakran képez áttétet távoli szervekbe. Az előrehaladott tumorok közel felében figyeltek meg agyi metasztázist. A korai diagnózis a betegség kimenetele szempontjából nagy jelentőségű. Az új, hatékony terápiák kialakításában fontos a bekövetkező genetikai és epigenetikai eltérések feltérképezése, ami ígéretes terápiás célpontokat jelölhet ki. Leggyakrabban a mitogénaktivált proteinkináz útvonal, a foszfatidil-inozitol-3-kináz jelátviteli útvonal és a sejtciklus-szabályozó molekulák génjeinek mutációi vezethetnek melanoma kialakulásához. A melanoma agyi áttétképzésének molekuláris folyamata nem teljesen feltárt. Közleményünkben összefoglaljuk a melanoma, illetve az agyi metasztázis kialakulásában szerepet játszó genetikai eltéréseket és molekuláris mechanizmusokat. Orv Hetil. 2017; 158(28): 1083–1091. | Abstract: Malignant melanoma is one of the most aggressive tumors which often gives metastasis to distant organs thereby limiting the chances of survival. Brain metastasis occurs in nearly half of the advanced tumors. In order to improve outcome early diagnosis is important. The discovery and better understanding of genetic and epigenetic changes is essential for developing new effective therapies, which can designate promising therapeutic targets. Melanoma most often is caused by gene mutations of the mitogen-activated protein kinase pathway, the phosphatidylinositol 3-kinase signaling pathway, and the cell cycle regulatory molecules, respectively. The molecular process of brain metastasis has not been fully elucidated. In our review we summarize the genetic alterations and molecular mechanisms playing a role in the development of melanoma and its brain metastasis. Orv Hetil. 2017; 158(28): 1083–1091

Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with tumour grade in meningiomas

Meningiomas are one of the most frequent intracranial tumours, with 13 histological types and three grades according to the 2007 WHO Classification of Tumours of the Central Nervous System. p53, as one of the most potent tumour suppressor proteins, plays a role in nearly 50% of human tumours. Poly(ADP-ribose) polymerase (PARP) is a DNA repair enzyme with high ATP demand. It plays a role in apoptosis by activating an apoptosis inducing factor, and in necrosis by consuming NAD+ and ATP. Only PARP1 has been investigated in detail in tumours out of the 17 members of the PARP superfamily; however, its role has not been studied in meningiomas yet. The aim of this study was to determine the role of p53 and PARP1 in meningiomas of different grade and to establish whether there is any correlation between the p53 and PARP1 expression. Both PARP1 and p53 have been expressed in all examined meningiomas. PARP1 labelled grade II tumours with a higher intensity as compared to grade I and III neoplasms, respectively. An increased p53 expression was noted in grade III meningiomas. There was no statistical correlation between p53 and PARP1 expression. Our data indicate that both PARP1 and p53 activation is a feature in meningiomas of higher grade, PARP1 overexpression being an early, whereas p53 overexpression, a late event in tumour progression