The Experts below are selected from a list of 21072 Experts worldwide ranked by ideXlab platform
Richard Carr - One of the best experts on this subject based on the ideXlab platform.
-
anticancer drug Oxaliplatin induces acute cooling aggravated neuropathy via sodium channel subtype nav1 6 resurgent and persistent current
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Ruth Sittl, Angelika Lampert, Tobias Huth, Theresa E Schuy, Andrea S Link, Johannes Fleckenstein, Christian Alzheimer, Peter Grafe, Richard CarrAbstract:Infusion of the chemotherapeutic agent Oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute Oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute Oxaliplatin neuropathy, whereas a common symptom of chronic Oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform NaV1.6 in mediating the symptoms of acute Oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of Oxaliplatin (30–100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of Oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8amed/med mice, which lack functional NaV1.6, no effect of Oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNaV1.6r in ND7 cells, an effect consistent with prolonged NaV open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that NaV1.6 plays a central role in mediating acute cooling-exacerbated symptoms following Oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy.
-
anticancer drug Oxaliplatin induces acute cooling aggravated neuropathy via sodium channel subtype na v 1 6 resurgent and persistent current
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Ruth Sittl, Angelika Lampert, Tobias Huth, Theresa E Schuy, Andrea S Link, Johannes Fleckenstein, Christian Alzheimer, Peter Grafe, Richard CarrAbstract:Infusion of the chemotherapeutic agent Oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute Oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute Oxaliplatin neuropathy, whereas a common symptom of chronic Oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform NaV1.6 in mediating the symptoms of acute Oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of Oxaliplatin (30–100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of Oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8amed/med mice, which lack functional NaV1.6, no effect of Oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNaV1.6r in ND7 cells, an effect consistent with prolonged NaV open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that NaV1.6 plays a central role in mediating acute cooling-exacerbated symptoms following Oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy.
Ruth Sittl - One of the best experts on this subject based on the ideXlab platform.
-
anticancer drug Oxaliplatin induces acute cooling aggravated neuropathy via sodium channel subtype nav1 6 resurgent and persistent current
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Ruth Sittl, Angelika Lampert, Tobias Huth, Theresa E Schuy, Andrea S Link, Johannes Fleckenstein, Christian Alzheimer, Peter Grafe, Richard CarrAbstract:Infusion of the chemotherapeutic agent Oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute Oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute Oxaliplatin neuropathy, whereas a common symptom of chronic Oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform NaV1.6 in mediating the symptoms of acute Oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of Oxaliplatin (30–100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of Oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8amed/med mice, which lack functional NaV1.6, no effect of Oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNaV1.6r in ND7 cells, an effect consistent with prolonged NaV open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that NaV1.6 plays a central role in mediating acute cooling-exacerbated symptoms following Oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy.
-
anticancer drug Oxaliplatin induces acute cooling aggravated neuropathy via sodium channel subtype na v 1 6 resurgent and persistent current
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Ruth Sittl, Angelika Lampert, Tobias Huth, Theresa E Schuy, Andrea S Link, Johannes Fleckenstein, Christian Alzheimer, Peter Grafe, Richard CarrAbstract:Infusion of the chemotherapeutic agent Oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute Oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute Oxaliplatin neuropathy, whereas a common symptom of chronic Oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform NaV1.6 in mediating the symptoms of acute Oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of Oxaliplatin (30–100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of Oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8amed/med mice, which lack functional NaV1.6, no effect of Oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNaV1.6r in ND7 cells, an effect consistent with prolonged NaV open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that NaV1.6 plays a central role in mediating acute cooling-exacerbated symptoms following Oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy.
Fernando Rivera - One of the best experts on this subject based on the ideXlab platform.
-
bevacizumab in combination with Oxaliplatin based chemotherapy as first line therapy in metastatic colorectal cancer a randomized phase iii study
Journal of Clinical Oncology, 2008Co-Authors: Leonard Saltz, A Figer, Stephen Clarke, Eduardo Diazrubio, Sheryl Koski, Werner Scheithauer, Ralph Wong, Mikhail Lichinitser, Tsaishen Yang, Fernando RiveraAbstract:Purpose To evaluate the efficacy and safety of bevacizumab when added to first-line Oxaliplatin-based chemotherapy (either capecitabine plus Oxaliplatin [XELOX] or fluorouracil/folinic acid plus Oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).
-
bevacizumab in combination with Oxaliplatin based chemotherapy as first line therapy in metastatic colorectal cancer a randomized phase iii study
Journal of Clinical Oncology, 2008Co-Authors: Leonard Saltz, A Figer, Stephen Clarke, Eduardo Diazrubio, Sheryl Koski, Werner Scheithauer, Ralph Wong, Mikhail Lichinitser, Tsaishen Yang, Fernando RiveraAbstract:Purpose To evaluate the efficacy and safety of bevacizumab when added to first-line Oxaliplatin-based chemotherapy (either capecitabine plus Oxaliplatin [XELOX] or fluorouracil/folinic acid plus Oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).
Jui-i Chao - One of the best experts on this subject based on the ideXlab platform.
-
regulation of gamma h2ax and securin contribute to apoptosis by Oxaliplatin via a p38 mitogen activated protein kinase dependent pathway in human colorectal cancer cells
Toxicology Letters, 2008Co-Authors: Shujun Chiu, Jui-i ChaoAbstract:Abstract Oxaliplatin, a chemotherapeutic drug, induces DNA strand breaks leading to apoptosis in colorectal cancer cells. γ-H2AX is a phosphorylated histone H2AX that can act as a marker of DNA double-strand breaks (DSBs). It has been shown that securin proteins were over-expressed in a variety of cancer cells. However, the roles of γ-H2AX and securin on the Oxaliplatin-induced apoptosis in human colorectal cancer cells remain unclear. Treatment of Oxaliplatin (1–10 μM for 6–24 h) persistently induced γ-H2AX formation and inhibited securin protein expression via a time- and concentration-dependent manner in HCT116 securin-wild type colorectal cancer cells. Compared with HCT116 securin-wild type cells, the induction of apoptosis and persistent γ-H2AX formation by Oxaliplatin was reduced in the HCT116 securin-null colorectal cancer cells. Furthermore, the blockage of caspases by specific caspase inhibitors reduced the levels of γ-H2AX proteins and cytotoxicity but increased securin protein expression in the Oxaliplatin-exposed cells. The gene knockdown of H2AX by transfection with a short interfering RNA of H2AX enhanced the Oxaliplatin-induced cell death. Interestingly, the phosphorylation of p38 mitogen-activated protein kinase (MAPK) was markedly increased by Oxaliplatin. Pre-treatment of a specific p38 MAPK inhibitor SB202190 reduced γ-H2AX proteins and increased securin protein expression in the Oxaliplatin-treated cells. Our findings suggest that p38 MAPK may oppositely regulate securin protein expression and γ-H2AX formation in the Oxaliplatin-induced apoptosis of human colorectal cancer cells.
-
opposing securin and p53 protein expression in the Oxaliplatin induced cytotoxicity of human colorectal cancer cells
Toxicology Letters, 2006Co-Authors: Shujun Chiu, Jui-i ChaoAbstract:Abstract Oxaliplatin, a clinical anticancer drug, has been used to treat colorectal cancer. Securin and p53 have been shown to regulate the cell cycle arrest and apoptosis. However, roles of securin and p53 on the Oxaliplatin-induced cytotoxicity in human colorectal cancer cells remain unclear. Treatment with 1–10 μM Oxaliplatin for 24 h induced the cell death, growth inhibition, and cell cycle arrest in RKO colorectal carcinoma cells. The phospho-p53 (Ser-15), total p53, and p21 proteins were elevated by Oxaliplatin in RKO cells; conversely, Oxaliplatin decreased the securin protein expression. The p53-functional RKO cells were higher on the cytotoxicity and cell cycle arrest at the G 1 and G 2 /M phases than the p53-mutational SW480 cells after treatment with Oxaliplatin. Oxaliplatin inhibited the securin protein expression in the p53-functional cells but not in the p53-mutational cells. The securin-wild type cells were more sensitive than the securin-null cells on the increases of cytotoxicity and sub-G 1 fractions following treatment with Oxaliplatin. Nevertheless, Oxaliplatin elevated the activation of p53 in both securin-wild type and securin-null cells. As a whole, it is the first time to demonstrate that Oxaliplatin inhibits the securin protein expression via a p53-dependent pathway, and p53 and securin may modulate the Oxaliplatin-induced cytotoxicity in human colorectal cancer cells.
Tobias Huth - One of the best experts on this subject based on the ideXlab platform.
-
anticancer drug Oxaliplatin induces acute cooling aggravated neuropathy via sodium channel subtype nav1 6 resurgent and persistent current
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Ruth Sittl, Angelika Lampert, Tobias Huth, Theresa E Schuy, Andrea S Link, Johannes Fleckenstein, Christian Alzheimer, Peter Grafe, Richard CarrAbstract:Infusion of the chemotherapeutic agent Oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute Oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute Oxaliplatin neuropathy, whereas a common symptom of chronic Oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform NaV1.6 in mediating the symptoms of acute Oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of Oxaliplatin (30–100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of Oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8amed/med mice, which lack functional NaV1.6, no effect of Oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNaV1.6r in ND7 cells, an effect consistent with prolonged NaV open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that NaV1.6 plays a central role in mediating acute cooling-exacerbated symptoms following Oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy.
-
anticancer drug Oxaliplatin induces acute cooling aggravated neuropathy via sodium channel subtype na v 1 6 resurgent and persistent current
Proceedings of the National Academy of Sciences of the United States of America, 2012Co-Authors: Ruth Sittl, Angelika Lampert, Tobias Huth, Theresa E Schuy, Andrea S Link, Johannes Fleckenstein, Christian Alzheimer, Peter Grafe, Richard CarrAbstract:Infusion of the chemotherapeutic agent Oxaliplatin leads to an acute and a chronic form of peripheral neuropathy. Acute Oxaliplatin neuropathy is characterized by sensory paresthesias and muscle cramps that are notably exacerbated by cooling. Painful dysesthesias are rarely reported for acute Oxaliplatin neuropathy, whereas a common symptom of chronic Oxaliplatin neuropathy is pain. Here we examine the role of the sodium channel isoform NaV1.6 in mediating the symptoms of acute Oxaliplatin neuropathy. Compound and single-action potential recordings from human and mouse peripheral axons showed that cooling in the presence of Oxaliplatin (30–100 μM; 90 min) induced bursts of action potentials in myelinated A, but not unmyelinated C-fibers. Whole-cell patch-clamp recordings from dissociated dorsal root ganglion (DRG) neurons revealed enhanced tetrodotoxin-sensitive resurgent and persistent current amplitudes in large, but not small, diameter DRG neurons when cooled (22 °C) in the presence of Oxaliplatin. In DRG neurons and peripheral myelinated axons from Scn8amed/med mice, which lack functional NaV1.6, no effect of Oxaliplatin and cooling was observed. Oxaliplatin significantly slows the rate of fast inactivation at negative potentials in heterologously expressed mNaV1.6r in ND7 cells, an effect consistent with prolonged NaV open times and increased resurgent and persistent current in native DRG neurons. This finding suggests that NaV1.6 plays a central role in mediating acute cooling-exacerbated symptoms following Oxaliplatin, and that enhanced resurgent and persistent sodium currents may provide a general mechanistic basis for cold-aggravated symptoms of neuropathy.
