Roberto Jun Arai, Elaine Santana Longo, Maria Helena Sponton and Maria Del Pilar Estevez Diz
http://ift.tt/2pWFimC
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Πέμπτη 18 Μαΐου 2017
Bringing a humanistic approach to cancer clinical trials
CRISPR/Cas9-based Pten Knock-out and Sleeping Beauty Transposon-mediated Nras Knock-in Induces Hepatocellular Carcinoma and Hepatic Lipid Accumulation in Mice.
CRISPR/Cas9-based Pten Knock-out and Sleeping Beauty Transposon-mediated Nras Knock-in Induces Hepatocellular Carcinoma and Hepatic Lipid Accumulation in Mice.
Cancer Biol Ther. 2017 May 17;:0
Authors: Gao M, Liu D
Abstract
Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten and overexpression of Nras were achieved in out-bred immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated Pten knock-out system. Concurrent Pten knock-out and Nras knock-in induced hepatocellular carcinoma, while individual gene manipulation failed. Tumor development was associated with liver fibrosis, hyperlipidemia, hepatic deposition of lipid droplets and glycogen, and hepatomegaly. At the molecular level, lipid droplet formation was primarily contributed by up-regulated expression of genes responsible for lipogenesis and fatty acid sequestration, such as Srebpf1, Acc, Pparg and its downstream targets. Our findings demonstrated that Pten disruption was synergized by Nras overexpression in driving hepatocyte malignant transformation, which correlated with extensive formation of lipid droplets.
PMID: 28513320 [PubMed - as supplied by publisher]
from Cancer via ola Kala on Inoreader http://ift.tt/2qw8pjv
via IFTTT
Immune Surveillance in Melanoma: From immune attack to melanoma escape and even counterattack.
Immune Surveillance in Melanoma: From immune attack to melanoma escape and even counterattack.
Cancer Biol Ther. 2017 May 17;:0
Authors: Mahmoud F, Shields B, Makhoul I, Avaritt N, Wong HK, Hutchins LF, Shalin S, Tackett AJ
Abstract
Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the programmed death receptor-1 (PD1) has resulted in unprecedented durable responses in metastatic melanoma. However, resistance to immunotherapy remains a major challenge. Effective immune surveillance against melanoma requires four essential steps: activation of the T lymphocytes, homing of the activated T lymphocytes to the melanoma microenvironment, identification and attack of melanoma cells by activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis. At each of these steps, there are multiple factors that may interfere with the immune surveillance machinery, thus allowing melanoma cells to escape immune attack and develop resistance to immunotherapy. We provide a comprehensive review of the complex immune surveillance mechanisms at play in melanoma, and a detailed discussion of how these mechanisms may allow for the development of intrinsic or acquired resistance to immunotherapeutic modalities, and potential avenues for overcoming this resistance.
PMID: 28513269 [PubMed - as supplied by publisher]
from Cancer via ola Kala on Inoreader http://ift.tt/2pO21W1
via IFTTT
CRISPR/Cas9-based Pten Knock-out and Sleeping Beauty Transposon-mediated Nras Knock-in Induces Hepatocellular Carcinoma and Hepatic Lipid Accumulation in Mice.
CRISPR/Cas9-based Pten Knock-out and Sleeping Beauty Transposon-mediated Nras Knock-in Induces Hepatocellular Carcinoma and Hepatic Lipid Accumulation in Mice.
Cancer Biol Ther. 2017 May 17;:0
Authors: Gao M, Liu D
Abstract
Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten and overexpression of Nras were achieved in out-bred immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated Pten knock-out system. Concurrent Pten knock-out and Nras knock-in induced hepatocellular carcinoma, while individual gene manipulation failed. Tumor development was associated with liver fibrosis, hyperlipidemia, hepatic deposition of lipid droplets and glycogen, and hepatomegaly. At the molecular level, lipid droplet formation was primarily contributed by up-regulated expression of genes responsible for lipogenesis and fatty acid sequestration, such as Srebpf1, Acc, Pparg and its downstream targets. Our findings demonstrated that Pten disruption was synergized by Nras overexpression in driving hepatocyte malignant transformation, which correlated with extensive formation of lipid droplets.
PMID: 28513320 [PubMed - as supplied by publisher]
http://ift.tt/2qw8pjv
Immune Surveillance in Melanoma: From immune attack to melanoma escape and even counterattack.
Immune Surveillance in Melanoma: From immune attack to melanoma escape and even counterattack.
Cancer Biol Ther. 2017 May 17;:0
Authors: Mahmoud F, Shields B, Makhoul I, Avaritt N, Wong HK, Hutchins LF, Shalin S, Tackett AJ
Abstract
Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the programmed death receptor-1 (PD1) has resulted in unprecedented durable responses in metastatic melanoma. However, resistance to immunotherapy remains a major challenge. Effective immune surveillance against melanoma requires four essential steps: activation of the T lymphocytes, homing of the activated T lymphocytes to the melanoma microenvironment, identification and attack of melanoma cells by activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis. At each of these steps, there are multiple factors that may interfere with the immune surveillance machinery, thus allowing melanoma cells to escape immune attack and develop resistance to immunotherapy. We provide a comprehensive review of the complex immune surveillance mechanisms at play in melanoma, and a detailed discussion of how these mechanisms may allow for the development of intrinsic or acquired resistance to immunotherapeutic modalities, and potential avenues for overcoming this resistance.
PMID: 28513269 [PubMed - as supplied by publisher]
http://ift.tt/2pO21W1
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