A5025784233- Protein Degradation and Inhibitors
- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Virus-based gene therapy research
- Click Chemistry and Applications
- Ubiquitin and proteasome pathways
- Cancer-related gene regulation
- Metal complexes synthesis and properties
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- HER2/EGFR in Cancer Research
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- PARP inhibition in cancer therapy
- Peroxisome Proliferator-Activated Receptors
- Genetics, Aging, and Longevity in Model Organisms
- interferon and immune responses
- Phagocytosis and Immune Regulation
- MicroRNA in disease regulation
- PI3K/AKT/mTOR signaling in cancer
University of Gothenburg
2014-2023
Sahlgrenska University Hospital
2016-2017
Umeå University
2011-2015
Abbott (Sweden)
2011
Technical University of Munich
2011
Abbott Fund
2011
Significance Bromodomain and extraterminal (BET) proteins bind acetylated proteins, including histones, regulate transcription. Interestingly, inhibitors of BET (BETi) can block cancer cell proliferation induce apoptosis in a wide range tumor types. To date many the effects BETi have been attributed to transcriptional suppression genes like MYC oncogene. We show that genetically-engineered Myc-induced lymphoma mouse models are highly sensitive without transcription being suppressed. Our data...
The transcription factor c-Myc (or "Myc") is a master regulator of pathways driving cell growth and proliferation. MYC deregulated in many human cancers, making its downstream target genes attractive candidates for drug development. We report the unexpected finding that B-cell lymphomas from mice patients exhibit striking correlation between high levels Myc checkpoint kinase 1 (Chk1).By vitro biology studies as well preclinical using genetically engineered mouse model, we evaluated role Chk1...
The BRAF inhibitors vemurafenib and dabrafenib can be used to treat patients with metastatic melanomas harboring BRAFV600 mutations. Initial antitumoral responses are often seen, but drug-resistant clones reactivation of the MEK-ERK pathway soon appear. Recently, secretome tumor-derived extracellular vesicles (EVs) has been ascribed important functions in cancers. To elucidate possible EVs BRAF-mutant melanoma, we determined RNA content EVs, including apoptotic bodies, microvesicles,...
Abstract Neuroblastoma has a low mutation rate for the p53 gene. Alternative ways of inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation wild-type p53. However, mechanisms leading to via are not well investigated. Here we show that neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor NBAT1 is p53-responsive lncRNA regulates subcellular levels. Low expression provided resistance genotoxic drugs by promoting cytoplasm and loss from...
The molecular mechanisms by which dietary fatty acids are absorbed the intestine, and way in process is regulated poorly understood. In a genetic screen for mutations affecting fat accumulation intestine of Caenorhabditis elegans, nematode worms, we have isolated aex-5 gene, encodes Kex2/subtilisin-family, Ca2+-sensitive proprotein convertase known to be required maturation certain neuropeptides, discrete step an ultradian rhythmic phenomenon called defecation motor program. We demonstrate...
Abstract Metastatic malignant melanoma continues to be a challenging disease despite clinical translation of the comprehensive understanding driver mutations and how cells evade immune attack. In Myc-driven lymphoma, efficacy epigenetic inhibitors bromodomain extra-terminal domain (BET) family proteins can enhanced by combination therapy with DNA damage response kinase ATR. Whether this is active in solid malignancies like melanoma, it relates therapy, has not previously investigated. To...
Abstract Agents that trigger cell differentiation are highly efficacious in treating certain cancers, but such approaches not generally effective most malignancies. Compounds as DMSO and hexamethylene bisacetamide (HMBA) have been used to induce experimental systems, their mechanisms of action potential range uses on basis developed. Here, we show HMBA, a compound first tested the oncology clinic over 25 years ago, acts selective bromodomain inhibitor. Biochemical structural studies revealed...
Cancer development occurs in response to the successive accumulation of mutations that eventually targets key regulators cell proliferation. As most likely occur randomly, cancer driver can only be found if they are recurrent. Here we use exome sequencing mouse lines Panc02, L1210 and Colon 26 identify genetic alterations (single-nucleotide polymorphisms small insertion deletions) occurred three different strains mice resulted tumorigenesis. We known genes like Kras, Cdkn2a/b, Smad4 Trp53 a...
Chk1 kinase is downstream of the ATR in sensing improper replication. Previous cell culture studies have demonstrated that essential for Indeed, inhibitors are efficacious against tumors with high-level replication stress such as Myc-induced lymphoma cells. Treatment also combines well certain chemotherapeutic drugs, and effects associate induction DNA damage reduction protein levels. Most function relied on use inhibitors. Whether or not a mouse cancer cells could survive if kinase-dead...
Abstract Overexpression of one the three MYC genes is a hallmark many human cancers. They encode transcription factors that regulate expression number critical for tumor development. Conditional transgenic mouse models have shown Myc inhibition causes regression; therefore an attractive target therapy, and effective pharmacological has been long-standing goal in cancer research. Recent publication selective BET bromodomain extra-terminal (BET) domain family proteins, bind to acetylated...
Abstract Myc family of transcription factors contribute to pathogenesis in most cancers and their expression projects a poor prognosis. Genetic pharmacological inhibition several targets leads apoptosis tumor regression. Recently, inhibitors BET Bromodomain proteins (BETi) were shown have anti-tumor properties this has been attributed down-regulation. In study, we show that two structurally distinct BETi affects replication cell cycle progression at low concentrations where the transcriptome...
Abstract Myc family of transcription factors are deregulated in most cancers and their expression projects a poor prognosis. Genetic pharmacological inhibition several targets leads to tumor regression apoptosis. Recently, inhibitors BET Bromodomain proteins (BETi) were shown have anti-tumor properties this has been attributed down-regulation. Here we show that two structurally distinct BETi affects replication cell cycle progression at low concentrations where the transcriptome remains...
<p>Differentially expressed genes in SH-SY5Y neuroblastoma cells after treatment with nutlin-3a, as detected by RNA-seq.</p>
<div>Abstract<p>Agents that trigger cell differentiation are highly efficacious in treating certain cancers, but such approaches not generally effective most malignancies. Compounds as DMSO and hexamethylene bisacetamide (HMBA) have been used to induce experimental systems, their mechanisms of action potential range uses on basis developed. Here, we show HMBA, a compound first tested the oncology clinic over 25 years ago, acts selective bromodomain inhibitor. Biochemical...
<div>Abstract<p>Agents that trigger cell differentiation are highly efficacious in treating certain cancers, but such approaches not generally effective most malignancies. Compounds as DMSO and hexamethylene bisacetamide (HMBA) have been used to induce experimental systems, their mechanisms of action potential range uses on basis developed. Here, we show HMBA, a compound first tested the oncology clinic over 25 years ago, acts selective bromodomain inhibitor. Biochemical...
<div>Abstract<p>Neuroblastoma has a low mutation rate for the <i>p53</i> gene. Alternative ways of p53 inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation wild-type p53. However, mechanisms leading to via are not well investigated. Here we show that neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor <i>NBAT1</i> is p53-responsive lncRNA regulates subcellular levels. Low expression provided resistance...
<p>Differentially expressed genes in SH-SY5Y neuroblastoma cells after treatment with nutlin-3a, as detected by RNA-seq.</p>
<div>Abstract<p>Neuroblastoma has a low mutation rate for the <i>p53</i> gene. Alternative ways of p53 inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation wild-type p53. However, mechanisms leading to via are not well investigated. Here we show that neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor <i>NBAT1</i> is p53-responsive lncRNA regulates subcellular levels. Low expression provided resistance...
<p>Details of NB tumors with NBAT1 expression, p53 localization.</p>
<p>Supplementary Text, Supplementary Table Legends</p>
<p>Supplementary Figures S1-S6</p>
<p>Primers used in the current investigation.</p>