Search results for "BLAST"
showing 10 items of 2136 documents
Epigenetic siRNA and Chemical Screens Identify SETD8 Inhibition as a Therapeutic Strategy for p53 Activation in High-Risk Neuroblastoma
2017
Given the paucity of druggable mutations in high-risk neuroblastoma (NB), we undertook chromatin-focused small interfering RNA and chemical screens to uncover epigenetic regulators critical for the differentiation block in high-risk NB. High-content Opera imaging identified 53 genes whose loss of expression led to a decrease in NB cell proliferation and 16 also induced differentiation. From these, the secondary chemical screen identified SETD8, the H4K20me1 methyltransferase, as a druggable NB target. Functional studies revealed that SETD8 ablation rescued the pro-apoptotic and cell-cycle arrest functions of p53 by decreasing p53K382me1, leading to activation of the p53 canonical pathway. I…
High-SETD8 inactivates p53 in neuroblastoma
2017
Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille’s heel to be exploited for the therapy of MYCN amplified neurob…
2012
The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mecha- nisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14ARF, significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treat- ment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Prote…
Nitinola matricas ar bioaktīvo slāni izveide pielietojumam asinsvadu ķirurģijā
2022
Darba mērķis bija izpētīt Nitinola matricas ar bioaktīvo slāni biosaderību un izvērtēt tās priekšrocības salīdzinājumā ar Nitinolu. Lai sasniegtu mērķus, tika veikta izpēte un apkopoti aktuālie zinātniskie dati par Nitinola pielietošanu asinsvadu ķirurģijā, plazmas elektrolītiskās oksidācijas Nitinola izveidi un biosaderību, nanodimantu biosaderību. Tika veikta Nitinola plazmas elektrolītiskā oksidēšana un iegūto biomateriālu raksturošana ar skenējošo elektronu mikroskopa metodi. Tika apstrādāti nitinola ar bioaktīvo nanodimantu pārklājumi un veikta to raksturošana ar fizikālām metodēm. Eksperimentāli tika izpētīta Nitinola matricas ar bioaktīvo nanodimantu slāņu biosaderība ar cilvēka fibr…
Effetti biologici del polifenoli dell'olio extravergine di oliva di cultivar nazionali su cellule tumorali umane sensibili e resistenti ai farmaci an…
2012
Controversies in ameloblastoma management: Evaluation of decision making, based on a retrospective analysis
2020
Background The ameloblastoma management is still challenging to the high recurrence rates and significant morbidity associated with radical treatment. The purpose of this 10-year retrospective study was to analyze the influence of ameloblastoma type and treatment strategy on the long-term outcomes and recurrence rates. Material and Methods The retrospective analyses of 64 histologically-confirmed ameloblastoma cases was performed. The possible risk factors for recurrence and the development of complications were estimated statistically. Results The treatment strategy applied for this group of patients was the following: thirty-four patients (53.1%) were treated conservatively with enucleati…
Molecular Mechanisms of the Blockage of Glioblastoma Motility
2021
Glioblastoma (GBM) is the most common and lethal brain tumor. GBM has a remarkable degree of motility and is able to infiltrate the healthy brain. In order to perform a rationale-based drug-repositioning study, we have used known inhibitors of two small Rho GTPases, Rac1 and Cdc42, which are upregulated in GBM and are involved in the signaling processes underlying the orchestration of the cytoskeleton and cellular motility. The selected inhibitors (R-ketorolac and ML141 for Cdc42 and R-ketorolac and EHT 1864 for Rac1) have been successfully employed to reduce the infiltration propensity of GBM in live cell imaging studies. Complementarily, all-atom simulations have elucidated the molecular …
Antitumor Effect of Cabozantinib in Bone Metastatic Models of Renal Cell Carcinoma
2021
Background: The presence of bone metastases in renal cell carcinoma (RCC) negatively affects patients’ survival. Data from clinical trials has highlighted a significant benefit of cabozantinib in bone metastatic RCC patients. Here, we evaluated the antitumor effect of cabozantinib in coculture models of renal cell carcinoma (RCC) and osteoblasts (OBs) to investigate whether and how its antiproliferative activity is influenced by OBs. Methods: Bone/RCC models were generated, coculturing green fluorescent protein (GFP)-tagged Caki-1 and 786-O cells with human primary OBs in a “cell–cell contact” system. RCC proliferation and the OB molecular profile were evaluated after the cabozantinib treat…
Photoluminescent Detection of Human T-Lymphoblastic Cells by ZnO Nanorods.
2020
The precise detection of cancer cells currently remains a global challenge. One-dimensional (1D) semiconductor nanostructures (e.g., ZnO nanorods) have attracted attention due to their potential use in cancer biosensors. In the current study, it was demonstrated that the possibility of a photoluminescent detection of human leukemic T-cells by using a zinc oxide nanorods (ZnO NRs) platform. Monoclonal antibodies (MABs) anti-CD5 against a cluster of differentiation (CD) proteins on the pathologic cell surface have been used as a bioselective layer on the ZnO surface. The optimal concentration of the protein anti-CD5 to form an effective bioselective layer on the ZnO NRs surface was selected. …
C8161-melanoomasolulinjan erittämien tekijöiden vaikutus fibroblastien hyaluronaanituotantoon
2011
Hyaluronaani on suurikokoinen soluväliaineen sokerirakenne. Se koostuu toistuvista sokerimolekyyleistä N- asetyyliglukosaminista ja glukuronihaposta. Hyaluronaani syntetisoidaan solukalvolla hyaluronaani- syntaasien (HAS) toimesta, joita nisäkkäillä on kolme isomuotoa (HAS1-3). Hyaluronaanin hajotus tapahtuu hyaluronidaasientsyymien (Hyal) toimesta. Hyaluronaanin pääasiallinen solukalvoreseptori on CD44, jonka avulla hyaluronaaniketjut ovat sitoutuneet solukalvoon. Hyaluronaania esiintyy runsaasti etenkin sidekudoksessa ja kerrostuneessa epiteelissä kuten ihossa. Hyaluronaanin määrän on havaittu lisääntyneen syövissä ja tämä korreloi useasti potilaan huonon ennusteen kanssa. Hyaluronaanin l…