The Experts below are selected from a list of 147 Experts worldwide ranked by ideXlab platform
Santosh Shenoy - One of the best experts on this subject based on the ideXlab platform.
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cell plasticity in cancer a complex interplay of genetic epigenetic mechanisms and tumor micro environment
Surgical Oncology-oxford, 2020Co-Authors: Santosh ShenoyAbstract:Abstract Cell plasticity, also known as lineage plasticity is defined as the ability of a cell to reprogram and change its phenotype identity. Cell plasticity is context dependent and occurs during the development of an Embryo, Tissue regeneration, wound healing. However when deregulated and aberrant it also contributes to cancer initiation, progression, metastases and resistance to therapies. Tumors cells exhibit varying forms of cell plasticity in each stage of the disease to evade normal regulation as would have occurred in normal cell division and homeostasis. Current evidence demonstrates complex interplay between the genes, epigenes, tumor microenvironment and the EMT in cell reprogramming and cancer cell plasticity. Herein we present experimental evidence and evolving new developments in cell plasticity in cancer cells. Additionally “Deregulated/aberrant/hijacked cell plasticity” could be considered as an additional hallmark of a cancer. In the future, combining the advances in next generation sequencing and single cell RNA techniques with evolving AI (artificial intelligence) technologies such as deep learning techniques may predict the trajectories of cancer cells and assist in navigating through the complex intricacies of the cancers. A durable, precise, personalized oncologic treatment could be a reality.
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Cell plasticity in cancer: A complex interplay of genetic, epigenetic mechanisms and tumor micro-environment.
Surgical oncology, 2020Co-Authors: Santosh ShenoyAbstract:Cell plasticity, also known as lineage plasticity is defined as the ability of a cell to reprogram and change its phenotype identity. Cell plasticity is context dependent and occurs during the development of an Embryo, Tissue regeneration, wound healing. However when deregulated and aberrant it also contributes to cancer initiation, progression, metastases and resistance to therapies. Tumors cells exhibit varying forms of cell plasticity in each stage of the disease to evade normal regulation as would have occurred in normal cell division and homeostasis. Current evidence demonstrates complex interplay between the genes, epigenes, tumor microenvironment and the EMT in cell reprogramming and cancer cell plasticity. Herein we present experimental evidence and evolving new developments in cell plasticity in cancer cells. Additionally "Deregulated/aberrant/hijacked cell plasticity" could be considered as an additional hallmark of a cancer. In the future, combining the advances in next generation sequencing and single cell RNA techniques with evolving AI (artificial intelligence) technologies such as deep learning techniques may predict the trajectories of cancer cells and assist in navigating through the complex intricacies of the cancers. A durable, precise, personalized oncologic treatment could be a reality.
Kristin Schirmer - One of the best experts on this subject based on the ideXlab platform.
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abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish danio rerio Embryos
BMC Biology, 2013Co-Authors: Stephan Fischer, Nils Kluver, Kathleen Burkhardtmedicke, Mirko Pietsch, Annemarie Schmidt, Peggy Wellner, Kristin SchirmerAbstract:In mammals, ABCB1 constitutes a cellular “first line of defense” against a wide array of chemicals and drugs conferring cellular multidrug or multixenobiotic resistance (MDR/MXR). We tested the hypothesis that an ABCB1 ortholog serves as protection for the sensitive developmental processes in zebrafish Embryos against adverse compounds dissolved in the water. Indication for ABCB1-type efflux counteracting the accumulation of chemicals in zebrafish Embryos comes from experiments with fluorescent and toxic transporter substrates and inhibitors. With inhibitors present, levels of fluorescent dyes in Embryo Tissue and sensitivity of Embryos to toxic substrates were generally elevated. We verified two predicted sequences from zebrafish, previously annotated as abcb1, by cloning; our synteny analyses, however, identified them as abcb4 and abcb5, respectively. The abcb1 gene is absent in the zebrafish genome and we explored whether instead Abcb4 and/or Abcb5 show toxicant defense properties. Quantitative real-time polymerase chain reaction (qPCR) analyses showed the presence of transcripts of both genes throughout the first 48 hours of zebrafish development. Similar to transporter inhibitors, morpholino knock-down of Abcb4 increased accumulation of fluorescent substrates in Embryo Tissue and sensitivity of Embryos toward toxic compounds. In contrast, morpholino knock-down of Abcb5 did not exert this effect. ATPase assays with recombinant protein obtained with the baculovirus expression system confirmed that dye and toxic compounds act as substrates of zebrafish Abcb4 and inhibitors block its function. The compounds tested comprised model substrates of human ABCB1, namely the fluorescent dyes rhodamine B and calcein-am and the toxic compounds vinblastine, vincristine and doxorubicin; cyclosporin A, PSC833, MK571 and verapamil were applied as inhibitors. Additionally, tests were performed with ecotoxicologically relevant compounds: phenanthrene (a polycyclic aromatic hydrocarbon) and galaxolide and tonalide (two polycyclic musks). We show that zebrafish Abcb4 is a cellular toxicant transporter and provides protection of Embryos against toxic chemicals dissolved in the water. Zebrafish Abcb4 thus is functionally similar to mammalian ABCB1, but differs from mammalian ABCB4, which is not involved in cellular resistance to chemicals but specifically transports phospholipids in the liver. Our data have important implications: Abcb4 could affect bioavailability - and thus toxicologic and pharmacologic potency - of chemicals to zebrafish Embryos and inhibition of Abcb4 therefore causes chemosensitization, that is, enhanced sensitivity of Embryos to toxicants. These aspects should be considered in (eco)toxicologic and pharmacologic chemical screens with the zebrafish Embryo, a major vertebrate model.
Stephan Fischer - One of the best experts on this subject based on the ideXlab platform.
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abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish danio rerio Embryos
BMC Biology, 2013Co-Authors: Stephan Fischer, Nils Kluver, Kathleen Burkhardtmedicke, Mirko Pietsch, Annemarie Schmidt, Peggy Wellner, Kristin SchirmerAbstract:In mammals, ABCB1 constitutes a cellular “first line of defense” against a wide array of chemicals and drugs conferring cellular multidrug or multixenobiotic resistance (MDR/MXR). We tested the hypothesis that an ABCB1 ortholog serves as protection for the sensitive developmental processes in zebrafish Embryos against adverse compounds dissolved in the water. Indication for ABCB1-type efflux counteracting the accumulation of chemicals in zebrafish Embryos comes from experiments with fluorescent and toxic transporter substrates and inhibitors. With inhibitors present, levels of fluorescent dyes in Embryo Tissue and sensitivity of Embryos to toxic substrates were generally elevated. We verified two predicted sequences from zebrafish, previously annotated as abcb1, by cloning; our synteny analyses, however, identified them as abcb4 and abcb5, respectively. The abcb1 gene is absent in the zebrafish genome and we explored whether instead Abcb4 and/or Abcb5 show toxicant defense properties. Quantitative real-time polymerase chain reaction (qPCR) analyses showed the presence of transcripts of both genes throughout the first 48 hours of zebrafish development. Similar to transporter inhibitors, morpholino knock-down of Abcb4 increased accumulation of fluorescent substrates in Embryo Tissue and sensitivity of Embryos toward toxic compounds. In contrast, morpholino knock-down of Abcb5 did not exert this effect. ATPase assays with recombinant protein obtained with the baculovirus expression system confirmed that dye and toxic compounds act as substrates of zebrafish Abcb4 and inhibitors block its function. The compounds tested comprised model substrates of human ABCB1, namely the fluorescent dyes rhodamine B and calcein-am and the toxic compounds vinblastine, vincristine and doxorubicin; cyclosporin A, PSC833, MK571 and verapamil were applied as inhibitors. Additionally, tests were performed with ecotoxicologically relevant compounds: phenanthrene (a polycyclic aromatic hydrocarbon) and galaxolide and tonalide (two polycyclic musks). We show that zebrafish Abcb4 is a cellular toxicant transporter and provides protection of Embryos against toxic chemicals dissolved in the water. Zebrafish Abcb4 thus is functionally similar to mammalian ABCB1, but differs from mammalian ABCB4, which is not involved in cellular resistance to chemicals but specifically transports phospholipids in the liver. Our data have important implications: Abcb4 could affect bioavailability - and thus toxicologic and pharmacologic potency - of chemicals to zebrafish Embryos and inhibition of Abcb4 therefore causes chemosensitization, that is, enhanced sensitivity of Embryos to toxicants. These aspects should be considered in (eco)toxicologic and pharmacologic chemical screens with the zebrafish Embryo, a major vertebrate model.
Kathleen Burkhardtmedicke - One of the best experts on this subject based on the ideXlab platform.
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abcb4 acts as multixenobiotic transporter and active barrier against chemical uptake in zebrafish danio rerio Embryos
BMC Biology, 2013Co-Authors: Stephan Fischer, Nils Kluver, Kathleen Burkhardtmedicke, Mirko Pietsch, Annemarie Schmidt, Peggy Wellner, Kristin SchirmerAbstract:In mammals, ABCB1 constitutes a cellular “first line of defense” against a wide array of chemicals and drugs conferring cellular multidrug or multixenobiotic resistance (MDR/MXR). We tested the hypothesis that an ABCB1 ortholog serves as protection for the sensitive developmental processes in zebrafish Embryos against adverse compounds dissolved in the water. Indication for ABCB1-type efflux counteracting the accumulation of chemicals in zebrafish Embryos comes from experiments with fluorescent and toxic transporter substrates and inhibitors. With inhibitors present, levels of fluorescent dyes in Embryo Tissue and sensitivity of Embryos to toxic substrates were generally elevated. We verified two predicted sequences from zebrafish, previously annotated as abcb1, by cloning; our synteny analyses, however, identified them as abcb4 and abcb5, respectively. The abcb1 gene is absent in the zebrafish genome and we explored whether instead Abcb4 and/or Abcb5 show toxicant defense properties. Quantitative real-time polymerase chain reaction (qPCR) analyses showed the presence of transcripts of both genes throughout the first 48 hours of zebrafish development. Similar to transporter inhibitors, morpholino knock-down of Abcb4 increased accumulation of fluorescent substrates in Embryo Tissue and sensitivity of Embryos toward toxic compounds. In contrast, morpholino knock-down of Abcb5 did not exert this effect. ATPase assays with recombinant protein obtained with the baculovirus expression system confirmed that dye and toxic compounds act as substrates of zebrafish Abcb4 and inhibitors block its function. The compounds tested comprised model substrates of human ABCB1, namely the fluorescent dyes rhodamine B and calcein-am and the toxic compounds vinblastine, vincristine and doxorubicin; cyclosporin A, PSC833, MK571 and verapamil were applied as inhibitors. Additionally, tests were performed with ecotoxicologically relevant compounds: phenanthrene (a polycyclic aromatic hydrocarbon) and galaxolide and tonalide (two polycyclic musks). We show that zebrafish Abcb4 is a cellular toxicant transporter and provides protection of Embryos against toxic chemicals dissolved in the water. Zebrafish Abcb4 thus is functionally similar to mammalian ABCB1, but differs from mammalian ABCB4, which is not involved in cellular resistance to chemicals but specifically transports phospholipids in the liver. Our data have important implications: Abcb4 could affect bioavailability - and thus toxicologic and pharmacologic potency - of chemicals to zebrafish Embryos and inhibition of Abcb4 therefore causes chemosensitization, that is, enhanced sensitivity of Embryos to toxicants. These aspects should be considered in (eco)toxicologic and pharmacologic chemical screens with the zebrafish Embryo, a major vertebrate model.
Wendy S. Barclay - One of the best experts on this subject based on the ideXlab platform.
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The Emergence of H7N7 Highly Pathogenic Avian Influenza Virus from Low Pathogenicity Avian Influenza Virus Using an in ovo Embryo Culture Model.
Viruses, 2020Co-Authors: Amanda H. Seekings, Wendy A. Howard, Alejandro Núñez, Marek J. Slomka, Ashley C. Banyard, D. Hicks, Richard J. Ellis, Javier Nunez-garcia, Lorian C. Hartgroves, Wendy S. BarclayAbstract:Outbreaks of highly pathogenic avian influenza virus (HPAIV) often result in the infection of millions of poultry, causing up to 100% mortality. HPAIV has been shown to emerge from low pathogenicity avian influenza virus (LPAIV) in field outbreaks. Direct evidence for the emergence of H7N7 HPAIV from a LPAIV precursor with a rare di-basic cleavage site (DBCS) was identified in the UK in 2008. The DBCS contained an additional basic amino acid compared to commonly circulating LPAIVs that harbor a single-basic amino acid at the cleavage site (SBCS). Using reverse genetics, outbreak HPAIVs were rescued with a DBCS (H7N7DB), as seen in the LPAIV precursor or an SBCS representative of common H7 LPAIVs (H7N7SB). Passage of H7N7DB in chicken Embryo Tissues showed spontaneous evolution to a HPAIV. In contrast, deep sequencing of extracts from Embryo Tissues in which H7N7SB was serially passaged showed retention of the LPAIV genotype. Thus, in chicken Embryos, an H7N7 virus containing a DBCS appears naturally unstable, enabling rapid evolution to HPAIV. Evaluation in Embryo Tissue presents a useful approach to study AIV evolution and allows a laboratory-based dissection of molecular mechanisms behind the emergence of HPAIV.