A5082957078- Neuroblastoma Research and Treatments
- Cancer, Hypoxia, and Metabolism
- Cancer therapeutics and mechanisms
- Sperm and Testicular Function
- Neuroendocrine Tumor Research Advances
- Ion channel regulation and function
- Lung Cancer Research Studies
- Reproductive Biology and Fertility
- Ubiquitin and proteasome pathways
- Lung Cancer Treatments and Mutations
- Heat shock proteins research
- Orthopaedic implants and arthroplasty
- Genetic and Kidney Cyst Diseases
- Neurofibromatosis and Schwannoma Cases
- Protist diversity and phylogeny
- Hip disorders and treatments
- Cancer-related gene regulation
- Thyroid Cancer Diagnosis and Treatment
- Glioma Diagnosis and Treatment
- DNA Repair Mechanisms
- thermodynamics and calorimetric analyses
- Pelvic and Acetabular Injuries
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Signaling Pathways in Disease
- Microtubule and mitosis dynamics
University of Gothenburg
2015-2024
Zhengzhou Children's Hospital
2018-2024
Zhengzhou University
2018-2024
Karolinska Institutet
2008-2009
Chinese Academy of Medical Sciences & Peking Union Medical College
2003-2004
Aberrant activation of anaplastic lymphoma kinase (ALK) has been described in a range human cancers, including non-small cell lung cancer and neuroblastoma (Hallberg Palmer, 2013). Vertebrate ALK considered to be an orphan receptor the identity ligand(s) is critical issue. Here we show that FAM150A FAM150B are potent ligands for bind extracellular domain addition wild-type able drive 'superactivation' activated mutants from neuroblastoma. In conclusion, our data robustly by FAM150A/B provide...
ABSTRACT The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment ALK-positive non-small cell lung cancer. However, neuroblastoma, activating mutations the ALK kinase domain are typically refractory to treatment, highlighting need for more potent inhibitors. next-generation PF-06463922 is predicted exhibit increased affinity mutants prevalent neuroblastoma. We examined activity ALK-driven neuroblastoma models vitro vivo....
Significance Neuroblastoma is a pediatric tumor arising from the neural crest. Dysregulation of receptor tyrosine kinase ALK has been linked to neuroblastoma, making it important understand its function in native conditions. In zebrafish, related receptor—Ltk—is also expressed crest and regulates development specific pigment cells—iridophores. Ligands activating human were recently identified as ALKAL proteins (FAM150, AUG) by biochemical means. Our data show that this ligand–receptor pair...
High-risk neuroblastoma (NB) is responsible for a disproportionate number of childhood deaths due to cancer.One indicator highrisk NB amplification the neural MYC (MYCN) oncogene, which currently therapeutically intractable.Identification anaplastic lymphoma kinase (ALK) as an oncogene raised possibility using ALK tyrosine inhibitors (TKIs) in treatment patients with activating mutations.8-10% primary are ALK-positive, figure that increases relapsed population.ALK activated by ALKAL2 ligand...
During spermatogenesis, diploid stem cells differentiate, undergo meiosis and spermiogenesis, transform into haploid spermatozoa. Various factors have been demonstrated to regulate this marvelous process of differentiation, but the expression only a few genes specifically involved in spermatogenesis has studied. In present study, different types spermatogenic were isolated from Balb/c mice testes ages using velocity sedimentation method, we determined profiles 1176 known mouse six (primitive...
Anaplastic lymphoma kinase (ALK) is a tyrosine receptor which has been implicated in numerous solid and hematologic cancers. ALK mutations are reported about 5-7% of neuroblastoma cases but the ALK-positive percentage increases significantly relapsed patient population. Crizotinib, first clinically approved inhibitor for treatment lung cancer had less dramatic responses neuroblastoma. Here we investigate efficacy second-generation inhibitor, brigatinib, setting. Employing cell lines, mouse...
Tumors with anaplastic lymphoma kinase (ALK) fusion rearrangements, including non-small-cell lung cancer and large cell lymphoma, are highly sensitive to ALK tyrosine inhibitors (TKIs), underscoring the notion that such cancers addicted activity. Although mutations in heavily implicated childhood neuroblastoma, response TKI crizotinib has been disappointing. Embryonal tumors patients DNA repair defects as Fanconi anemia (FA) often have a poor prognosis, because of lack therapeutic options....
High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such strategy two independent genetically modified mouse NB models. Here, we identify underlying molecular mechanism, ALK signaling leads...
MEK inhibitors induce feedback AKT-mTORC2–mediated survival signaling in ALK-addicted neuroblastoma cells.
A transcription factor family and a phosphatase are identified as targets of ALK signaling in neuroblastoma.
Abstract Spermatogenesis occurs in successive mitotic, meiotic, and post‐meiotic phase, involves a number of unique processes including meiosis dramatic morphological changes. The differentiation mechanisms spermatogenesis suggest the existence germ‐cell‐specific molecules. most straight forward strategy to elucidate is identify characterize differentiation‐specific molecules their associated genes germ cells. However, only few specifically involved have been studied. In present study, six...
Aberrant activation of anaplastic lymphoma kinase (ALK) by activating point mutation or amplification drives 5-12% neuroblastoma (NB). Previous work has identified the involvement insulin-like growth factor 1 receptor (IGF1R) tyrosine (RTK) in a wide range cancers. We show here that many NB cell lines exhibit IGF1R activity, and inhibition led to decreased proliferation varying degrees ALK-driven cells. Furthermore, combined ALK resulted synergistic anti-proliferation effects, particular...
Abstract Background The sperm annulus is a septin-based fibrous ring structure connecting the midpiece and principal piece of mammalian flagellum. Although ultrastructural abnormalities functional importance have been addressed in Sept4 -null mutant mice subset human patients with asthenospermia syndrome, little known about how assembled positioned to midpiece-principal junction during flagellum development. Results By performing immunofluorescence biochemical approaches antibodies against...
Introduction Cellular senescence (CS) plays a critical role in cancer development, including clear cell renal carcinoma (ccRCC). Traditional RNA sequencing cannot detect precise molecular composition changes within tumors. This study aimed to analyze cellular senescence’s biochemical characteristics ccRCC using single (ScRNA-seq) and traditional (Bulk RNA-seq). Methods Researchers analyzed the of ScRNA-seq Bulk RNA-seq. They combined these approaches identify differences between malignant...
Abstract DNAJB13 is a type II HSP40/DnaJ protein. Using specific antibody raised against the recombinant protein, we characterized in mouse testes and epididymal spermatozoa. The expression of protein testis was undetectable until postnatal Week 4 revealed by Western blot analysis, whereas Dnajb13 mRNA detectable as early 1 RT‐PCR. Immunohistochemistry analyses showed that localized cytoplasm spermatids from step 2 to 3 onward with strongest 9–10, spermatid flagella. In mature spermatozoa,...
Numerous mutations have been observed in the Anaplastic Lymphoma Kinase (ALK) receptor tyrosine kinase (RTK) both germline and sporadic neuroblastoma. Here, we investigated Y1278S mutation, four patient cases, its potential importance activation of full length ALK receptor. is located 1278-YRASYY-1283 motif loop, which has previously reported to be important domain. In this study, characterized loop within context employing cell culture Drosophila melanogaster model systems. Our results show...
// Jikui Guan 1 , Georg Wolfstetter Joachim Siaw Damini Chand Fredrik Hugosson Ruth H. Palmer Bengt Hallberg Department of Medical Biochemistry and Cell Biology, Institute Biomedicine, Sahlgrenska Academy, University Gothenburg, SE-405 30 Sweden Correspondence to: Hallberg, email: Bengt.Hallberg@gu.se Keywords: brigatinib, ATC, ceritinib, crizotinib, neuroblastom Received: July 26, 2016 Accepted: November 21, Published: December 24, ABSTRACT Activating mutations in full length anaplastic...
Although activating mutations of the anaplastic lymphoma kinase (ALK) membrane receptor occur in ∼10% neuroblastoma (NB) tumors, role wild-type (WT) receptor, which is aberrantly expressed most non-mutated cases, unclear. Both WT and mutant proteins undergo extracellular domain (ECD) cleavage. Here, we map cleavage site to Asn654-Leu655 demonstrate that inhibition ALK significantly impedes NB cell migration with subsequent prolongation survival mouse models. Cleavage results downregulation...
It has been shown that DNAJB13, a type II heat shock protein 40, is highly expressed in the testis and an axonemal component of mouse mature spermatozoa. By multi-tissue reverse transcription polymerase chain reaction, we found Dnajb13 gene was not only but also several other ciliated cell-containing tissues like brain, lung oviduct. Immunohistochemistry on trachea oviduct sections DNAJB13 present motile cilia those tissues. To define further its localization axoneme, immunoelectron...
Aberrant activation of anaplastic lymphoma kinase (ALK) drives neuroblastoma (NB). Previous work identified the RET receptor tyrosine (RTK) as a downstream target ALK activity in NB models. We show here that response to ALKAL2 ligand results rapid phosphorylation cells, providing additional insight into contribution ALK-driven gene signature NB. To further address role NB, knockout (KO) SK-N-AS cells were generated by CRISPR/Cas9 genome engineering. Gene expression analysis KO reprogramming...
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine (RTK) that mutated in approximately 10% of pediatric neuroblastoma (NB). To shed light on ALK-driven signaling processes, we employed BioID-based vivo proximity labeling to identify molecules interact intracellularly with ALK. NB-derived SK-N-AS and SK-N-BE(2) cells expressing inducible ALK-BirA* fusion proteins were generated stimulated ALKAL ligands the presence absence ALK inhibitor (TKI) lorlatinib. LC/MS-MS analysis identified...
Protein-protein interactions (PPIs) play essential roles in Anaplastic Lymphoma Kinase (ALK) signaling. Systematic characterization of ALK interactors helps elucidate novel signaling mechanisms and may aid the identification therapeutics targeting related diseases. In this study, we used Mammalian Membrane Two-Hybrid (MaMTH) system to map phospho-dependent interactome. By screening a library 86 SH2 domain-containing full length proteins, 30 were identified. Many their are correlated...