The Experts below are selected from a list of 18 Experts worldwide ranked by ideXlab platform
William T Purcell - One of the best experts on this subject based on the ideXlab platform.
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Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial.
Cancers, 2021Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Tudor Eliade Ciuleanu, Petar Petrov, Ioana Adriana Pusca, Muhammad Shaalan Beg, William T PurcellAbstract:Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child–Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated Namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) Namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for Namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49–1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 Namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45–1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 Namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, Namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.
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a phase ii randomized double blind placebo controlled trial evaluating efficacy and safety of Namodenoson cf102 an a3 adenosine receptor agonist a3ar as a second line treatment in patients with child pugh b cpb advanced hepatocellular carcinoma hcc
Journal of Clinical Oncology, 2019Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Ioana Adriana Puscas, Tudor Eliade Ciuleanu, William T Purcell, Petar Petrov, Adinaemilia CroitoruAbstract:2503Background: There is no established primary treatment for patients with advanced HCC and severe liver dysfunction (Child-Pugh B class; CPB), thus this representing a clear unmet need. Namodenos...
Salomon M Stemmer - One of the best experts on this subject based on the ideXlab platform.
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Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial.
Cancers, 2021Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Tudor Eliade Ciuleanu, Petar Petrov, Ioana Adriana Pusca, Muhammad Shaalan Beg, William T PurcellAbstract:Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child–Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated Namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) Namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for Namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49–1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 Namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45–1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 Namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, Namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.
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a phase ii randomized double blind placebo controlled trial evaluating efficacy and safety of Namodenoson cf102 an a3 adenosine receptor agonist a3ar as a second line treatment in patients with child pugh b cpb advanced hepatocellular carcinoma hcc
Journal of Clinical Oncology, 2019Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Ioana Adriana Puscas, Tudor Eliade Ciuleanu, William T Purcell, Petar Petrov, Adinaemilia CroitoruAbstract:2503Background: There is no established primary treatment for patients with advanced HCC and severe liver dysfunction (Child-Pugh B class; CPB), thus this representing a clear unmet need. Namodenos...
Pnina Fishman - One of the best experts on this subject based on the ideXlab platform.
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The A3 adenosine receptor agonist, Namodenoson, ameliorates non-alcoholic steatohepatitis in mice
International journal of molecular medicine, 2019Co-Authors: Pnina Fishman, Shira Cohen, Inbal Itzhak, Johnny Amer, A. Salhab, Faina Barer, Rifaat SafadiAbstract:The Wnt/β-catenin pathway confers a chain of molecular events in livers affected by non-alcoholic steato-hepatitis (NASH). Namodenoson, a selective agonist of the A3 adenosine receptor (A3AR), which is highly expressed in pathological liver cells, induces a robust anti-inflammatory effect in the liver, mediated via the de-regulation of the Wnt/β-catenin pathway. Namodenoson also acts as a liver protective agent by inhibiting ischemia/reperfusion injury. Based on these unique characteristics, we investigated the anti-NASH effect of Namodenoson in murine models of steato-hepatitis and in the LX2 human hepatic stellate cell line (HSC). In the STAM model, Namodenoson significantly decreased the non-alcoholic fatty liver disease (NAFLD) activity score, NAS, demonstrating anti-inflammatory and anti-steatotic effects. In the carbon tetrachloride (CCl4) model, Namodenoson reversed alanine aminotransferase (ALT) to normal values and signifi-cantly improved liver inflammation and fibrosis, as well as the adiponectin and leptin levels. Namodenoson de-regulated the Wnt/β-catenin pathway in the liver extracts of the CCl4 model mice and in the LX2 HSCs, manifested by a decrease in the expression of phosphoinositide 3-kinase (PI3K), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), β-catenin, lymphoid enhancer-binding factor 1 (Lef-1) and cyclin D1, and an increase in the expression level of glycogen synthase kinase 3β (GSK-3β). The fibrosis marker, α-smooth muscle actin (α-SMA) was also de-regulated, supporting the anti-fibrotic effect of Namodenoson. On the whole, the findings of this study demonstrate that Namodenoson exerts an anti-NASH effect mediated via the de-regulation of the PI3K/NF-κB/Wnt/β-catenin signaling pathway. Thus, targeting A3AR may prove to be a novel direction in the pharmacotherapy of NAFLD/NASH.
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Targeting the A 3 adenosine receptor to treat cytokine release syndrome in cancer immunotherapy
Drug design development and therapy, 2019Co-Authors: Shira Cohen, Pnina FishmanAbstract:Cancer patients undergoing immunotherapy may develop cytokine release syndrome (CRS), an inflammatory cytokine storm condition, followed by neurotoxic manifestations and may be life-threatening. The current treatments for CRS successfully reduce the inflammatory response but may limit the anticancer effect of the given immunotherapy and fail to overcome the neurotoxic adverse events. Adenosine, a ubiquitous purine nucleoside, induces a plethora of effects in the body via its binding to four adenosine receptors A1, A2a, A2b, and the A3. Highly selective agonists to the A3 adenosine receptor act as inhibitors of proinflammatory cytokines, possess robust anti-inflammatory and anticancer activity, and concomitantly, induce neuroprotective effects. Piclidenoson and Namodenoson belong to this group of compounds, are effective upon oral administration, show an excellent safety profile in human clinical studies, and therefore, may be considered as drug candidates to treat CRS. In this article, the detailed anti-inflammatory characteristics of these compounds and the rationale to use them as drugs to combat CRS are described.
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Adenosine Receptors and Current Opportunities to Treat Cancer
The Adenosine Receptors, 2018Co-Authors: Stefania Gessi, Shira Cohen, Stefania Merighi, Pier Andrea Borea, Pnina FishmanAbstract:Adenosine is an endogenous modulator exerting its physiological effects by activating four A1, A2A, A2B, and A3 adenosine receptors. This nucleoside increases in hypoxia that characterizes solid tumors, thus affecting vasculature, immunoescaping, and cancer growth. This chapter offers an updated overview on the current opportunities to treat tumors coming from the adenosinergic field. Several years of research has led to the conclusion that A2A and A3 subtypes are the most promising for drug development. As for A3 receptors, consequent to the efficacy of their agonists in numerous animal models of cancer, the lead compound, Namodenoson, has entered in clinical trials for hepatocellular carcinoma. Phase I results proved its optimal safety profile and efficacy, so that phase II studies are in progress. Specifically, A2A receptor is responsible for immunosuppressive effects, reducing antitumor immunity and promoting immunoescaping of cancer. Therefore, A2A receptor antagonists have been proposed to fight cancer by enhancing immunotherapy, supported also by their safety already demonstrated in clinical trials for Parkinson’s disease. Overall, from these positive results, it may be expected that A3 agonists and A2A antagonists may become future anticancer drugs with the ability to save and improve human health also for diseases with very limited treatment options.
Nelly Cherciu - One of the best experts on this subject based on the ideXlab platform.
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Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial.
Cancers, 2021Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Tudor Eliade Ciuleanu, Petar Petrov, Ioana Adriana Pusca, Muhammad Shaalan Beg, William T PurcellAbstract:Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child–Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated Namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) Namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for Namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49–1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 Namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45–1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 Namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, Namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.
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a phase ii randomized double blind placebo controlled trial evaluating efficacy and safety of Namodenoson cf102 an a3 adenosine receptor agonist a3ar as a second line treatment in patients with child pugh b cpb advanced hepatocellular carcinoma hcc
Journal of Clinical Oncology, 2019Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Ioana Adriana Puscas, Tudor Eliade Ciuleanu, William T Purcell, Petar Petrov, Adinaemilia CroitoruAbstract:2503Background: There is no established primary treatment for patients with advanced HCC and severe liver dysfunction (Child-Pugh B class; CPB), thus this representing a clear unmet need. Namodenos...
Petar Petrov - One of the best experts on this subject based on the ideXlab platform.
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Namodenoson in Advanced Hepatocellular Carcinoma and Child-Pugh B Cirrhosis: Randomized Placebo-Controlled Clinical Trial.
Cancers, 2021Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Tudor Eliade Ciuleanu, Petar Petrov, Ioana Adriana Pusca, Muhammad Shaalan Beg, William T PurcellAbstract:Namodenoson, an A3 adenosine-receptor agonist, showed promising results in advanced hepatocellular carcinoma (HCC) and moderate hepatic dysfunction (Child–Pugh B; CPB) in a phase I/II clinical study. This phase II study investigated Namodenoson as second-line therapy in such patients. Patients were randomized 2:1 to twice a day (BID) Namodenoson (25 mg; n = 50) or placebo (n = 28). The primary endpoint (overall survival [OS]) was not met. Median OS was 4.1/4.3 months for Namodenoson/placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI] 0.49–1.38; p = 0.46). Pre-planned subgroup analysis of CPB7 patients (34 Namodenoson-treated, 22 placebo-treated) showed a nonsignificant improvement in OS/progression-free survival (PFS). OS: 6.9 versus 4.3 months; HR, 0.81; 95% CI: 0.45–1.43, p = 0.46. PFS: 3.5 versus 1.9 months; HR, 0.89; 95% CI: 0.51–1.55, p = 0.67 (log-rank test). The difference in 12-month OS was significant (44% versus 18%, p = 0.028). Response rates were determined in patients for whom ≥ 1 assessment post-baseline was available (34 Namodenoson-treated, 21 placebo-treated). Partial response was achieved by 3/34 (8.8%) and 0/21 (0%) patients, respectively. Namodenoson was well-tolerated, with a safety profile comparable to that of the placebo group. No treatment-related deaths were reported; no patients withdrew due to toxicity. In conclusion, Namodenoson demonstrated a favorable safety profile and a preliminary efficacy signal in HCC CPB.
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a phase ii randomized double blind placebo controlled trial evaluating efficacy and safety of Namodenoson cf102 an a3 adenosine receptor agonist a3ar as a second line treatment in patients with child pugh b cpb advanced hepatocellular carcinoma hcc
Journal of Clinical Oncology, 2019Co-Authors: Salomon M Stemmer, Nebojsa Manojlovic, M Marinca, Nelly Cherciu, Doina Ganea, Ioana Adriana Puscas, Tudor Eliade Ciuleanu, William T Purcell, Petar Petrov, Adinaemilia CroitoruAbstract:2503Background: There is no established primary treatment for patients with advanced HCC and severe liver dysfunction (Child-Pugh B class; CPB), thus this representing a clear unmet need. Namodenos...
