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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first option, liver transplantation and percutaneous ablation. Unfortunately, there is a high frequency of tumor recurrence after surgical resection and most HCC seem resistant to conventional chemotherapy and radiotherapy. Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic option for patients with advanced hepatocellular carcinoma. Patients treated with Sorafenib have a significant increase in overall survival of about three months. Therefore, there is an urgent need to develop alternative treatments. Due to its role in cell growth and development, the insulin-like growth factor system is commonly deregulated in many cancers. Indeed, the insulin-like growth factor (IGF) axis has recently emerged as a potential target for hepatocellular carcinoma treatment. To this aim, several inhibitors of the pathway have been developed such as monoclonal antibodies, small molecules, antisense oligonucleotides or small interfering RNAs. However recent studies suggest that, unlike most tumors, HCC development requires increased signaling through insulin growth factor II rather than insulin growth factor I. This may have great implications in the future treatment of HCC. This review summarizes the role of the IGF axis in liver carcinogenesis and the current status of the strategies designed to target the IGF-I signaling pathway for hepatocellular carcinoma treatment.

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CD133 has recently been used as a reliable marker for brain tumor stem cells isolation. Sonic hedgehog (SHH) is implicated in medulloblastoma and central primitive neuroectodermal tumor (cPNET) formation. It has recently been suggested a role for the EWS/FLI1 fusion protein--typical of pPNET--in the upregulation of GLI1 and PTCH1 genes. Cyclopamine inhibits the SHH pathway in medulloblastoma cell lines, but its effect on cPNET and pPNET cell lines has not been well established yet. Our purpose was to study the effect of cyclopamine on medulloblastoma and PNET cell lines and to analyze whether CD133 expression might be able to modify this effect. We analyzed gene expression, cell viability, apoptosis, and tumorigenic capability before and after cyclopamine treatment in CD133 high-expressing and CD133 low-expressing cell lines. All medulloblastoma and PNET cell lines displayed an inhibitory effect on the expression of SHH pathway genes, on viability, and on tumorigenic potential after treatment. Nevertheless, CD133 expression made the cells more resistant to cyclopamine inhibition. These results open new doors to the understanding of CD133+ cancer stem cells as residual cells that might be responsible for treatment resistance.

Since the beginning of the COVID-19 pandemic, the ABO blood group has been described as a possible biological marker of susceptibility for the disease. This study evaluates the role of ABO group on the risk of SARS-CoV-2 infection and related complications in a population-based cohort including 87,090 subjects from the Navarre population (Northern Spain) with no history of SARS-CoV-2 infection and with known ABO blood group, after one year of the pandemic (May 2020 – May 2021). The risk of infection, hospitalization, Intensive Care Unit (ICU) admission and death was analyzed using multivariate logistic regression, adjusting for possible confounding variables. A lower risk of infection was observed in group 0 vs non-0 groups [OR 0.94 (95%CI 0.90-0.99)], a higher risk of infection in group A vs non-A groups [OR 1.09 (95%CI 1.04-1.15)] and a higher risk of infection in group A vs group 0 [OR 1.08 (95CI 1.03-1.14)] (when the 4 groups are analyzed separately). No association was observed between blood groups and hospitalization, ICU admission, or death in SARS-CoV-2 infected subjects. Regarding the risk of SARS-CoV-2 infection, we observed a protective role of group O and a greater risk in the A group.

INTRODUCTION: Delayed bleeding (DB) is the most common major complication of endoscopic mucosal resection (EMR). Two randomized clinical trials recently demonstrated that clip closure after EMR of large nonpedunculated colorectal polyps (LNPCPs) reduces the risk of DB. We analyzed the cost-effectiveness of this prophylactic measure. METHODS: EMRs of LNCPCPs were consecutively registered in the ongoing prospective multicenter database of the Spanish EMR Group from May 2013 until July 2017. Patients were classified according to the Spanish Endoscopy Society EMR group (GSEED-RE2) DB risk score. Cost-effectiveness analysis was performed for both Spanish and US economic contexts. The average incremental cost-effectiveness ratio (ICER) thresholds were set at 54,000 € or $100,000 per quality-adjusted life year, respectively. RESULTS: We registered 2,263 EMRs in 2,130 patients. Applying their respective DB relative risk reductions after clip closure (51% and 59%), the DB rate decreased from 4.5% to 2.2% in the total cohort and from 13.7% to 5.7% in the high risk of the DB GSEED-RE2 subgroup. The ICERs for the universal clipping strategy in Spain and the United States, 469,706 € and $1,258,641, respectively, were not cost effective. By contrast, selective clipping in the high-risk of DB GSEED-RE2 subgroup was cost saving, with a negative ICER of −2,194 € in the Spanish context and cost effective with an ICER of $87,796 in the United States. DISCUSSION: Clip closure after EMR of large colorectal lesions is cost effective in patients with a high risk of bleeding. The GSEED-RE2 DB risk score may be a useful tool to identify that high-risk population. JOURNAL/ajgast/04.03/00000434-202102000-00022/inline-graphic1/v/2023-07-18T070738Z/r/image-tiff