Impact of RB1 gene mutation type in retinoblastoma patients on clinical presentation and management outcome

Publication date: Available online 23 March 2020Source: Hematology/Oncology and Stem Cell TherapyAuthor(s): Mustafa Mehyar, Mohammad Mosallam, Abdelghani Tbakhi, Ala Saab, Iyad Sultan, Rasha Deebajah, Imad Jaradat, Reem AlJabari, Mona Mohammad, Ibrahim AlNawaiseh, Maysa Al-Hussaini, Yacoub A. Yousef
Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research

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CONCLUSION: We have demonstrated neural stem cell/CSC markers that facilitate the maintenance of cancer stem cells. Developing therapies targeting these factors will help in overcoming resistance and improving retinoblastoma treatment. PMID: 32364077 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
Abstract Three-dimensional (3D) organoid models derived from human pluripotent stem cells provide a platform for studying human development and understanding disease mechanisms. Most studies that examine biallelic inactivation of the cell cycle regulator Retinoblastoma 1 (RB1) and the link to retinoblastoma is in mice, however, less is known regarding the pathophysiological role of RB1 during human retinal development. To study the role of RB1 in early human retinal development and tumor formation, we generated retinal organoids from CRISPR/Cas9-derived RB1-null human embryonic stem cells (hESCs). We showed that R...
Source: Developmental Biology - Category: Biology Authors: Tags: Dev Biol Source Type: research
Publication date: Available online 30 January 2020Source: Stem Cell ReportsAuthor(s): Menno ter Huurne, Tianran Peng, Guoqiang Yi, Guido van Mierlo, Hendrik Marks, Hendrik G. StunnenbergSummaryMouse embryonic stem cells (ESCs) grown in serum-supplemented conditions are characterized by an extremely short G1 phase due to the lack of G1-phase control. Concordantly, the G1-phase-specific P53-P21 pathway is compromised in serum ESCs. Here, we provide evidence that P53 is activated upon transition of serum ESCs to their pluripotent ground state using serum-free 2i conditions and that is required for the elongated G1 phase chara...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
Authors: Coller HA Abstract The transition between proliferating and quiescent states must be carefully regulated to ensure that cells divide to create the cells an organism needs only at the appropriate time and place. Cyclin-dependent kinases (CDKs) are critical for both transitioning cells from one cell cycle state to the next, and for regulating whether cells are proliferating or quiescent. CDKs are regulated by association with cognate cyclins, activating and inhibitory phosphorylation events, and proteins that bind to them and inhibit their activity. The substrates of these kinases, including the retinoblasto...
Source: Comprehensive Physiology - Category: Physiology Tags: Compr Physiol Source Type: research
Contributors : Menno ter Huurne ; Tianran Peng ; Hendrik G StunnenbergSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusMouse Embryonic Stem Cells (ESCs) grown in serum-supplemented conditions are characterized by an extremely short G1-phase due to the lack of G1-phase control. Concordantly, the G1-phase-specific P53-P21 pathway is compromised in serum ESCs. Here we provide evidence that P53 is activated upon transition of serum ESCs to their pluripotent ground state using serum-free 2i conditions and modulates G1-phase progression. Our data shows that the elongated G1-phase characteris...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Menno ter Huurne ; Tianran Peng ; Hendrik G StunnenbergSeries Type : Genome binding/occupancy profiling by high throughput sequencingOrganism : Mus musculusMouse Embryonic Stem Cells (ESCs) grown in serum-supplemented conditions are characterized by an extremely short G1-phase due to the lack of G1-phase control. Concordantly, the G1-phase-specific P53-P21 pathway is compromised in serum ESCs. Here we provide evidence that P53 is activated upon transition of serum ESCs to their pluripotent ground state using serum-free 2i conditions and modulates G1-phase progression. Our data shows that the elongated G1-pha...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Mus musculus Source Type: research
The mesoderm is one of the three germ layers produced during gastrulation from which muscle, bones, kidneys, and the cardiovascular system originate. Understanding the mechanisms that control mesoderm specification could inform many applications, including the development of regenerative medicine therapies to manage diseases affecting these tissues. Here, we used human pluripotent stem cells to investigate the role of cell cycle in mesoderm formation. To this end, using small molecules or conditional gene knockdown, we inhibited proteins controlling G1 and G2/M cell cycle phases during the differentiation of human pluripot...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Cell Biology Source Type: research
In conclusion, these results suggest that Brd4 has great potential as a therapeutic target, and JQ1 has notable anti‑tumor effects against GBM which may be mediated via the VEGF/PI3K/AKT signaling pathway. PMID: 31485609 [PubMed - as supplied by publisher]
Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
Abstract Several clinical and experimental studies have demonstrated that regular use of aspirin (acetylsalicylic acid, ASA) correlates with a reduced risk of cancer and that the drug exerts direct anti-tumour effects. We have previously reported that ASA inhibits proliferation of human glioblastoma multiforme-derived cancer stem cells. In the present study, we analysed the effects of ASA on nervous system-derived cancer cells, using the SK-N-SH (N) human neuroblastoma cell line as an experimental model. ASA treatment of SK-N-SH (N) dramatically reduced cell proliferation and motility, and induced neuronal-like di...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
Publication date: Available online 29 July 2019Source: Stem Cell ResearchAuthor(s): Julia Menges, Martina Cremanns, Laura SteenpassAbstractBiallelic inactivation of the retinoblastoma tumor suppressor gene (RB1) causes formation of retinoblastoma, a retinal eye tumor occurring in early childhood. Using the CRISPR/Cas9 nickase system, exon 1 of RB1 was deleted, including the RB1 promoter. As a result, sublines were generated carrying deletions of RB1 exon 1/promoter on one or both alleles.
Source: Stem Cell Research - Category: Stem Cells Source Type: research
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