Liver cancer mortality at national and provincial levels in Iran between 1990 and 2015: A meta regression analysis

Background: Liver cancer is a highly lethal cancer with 5 year survival rate of about 18. This cancer is a leading cause of death in many countries. As there is not a comprehensive population base study on liver cancer mortality rates by cause in national and provincial level in Iran. We aimed to estimate the liver cancer mortality rate, its patterns, and temporal trends during 26 years by sex, age, geographical distribution, and cause. Methods: We used the Iranian death registration system (DRS), in addition to demographic and statistical methods, to address the incompleteness and misclassification and uncertainty of death registration system to estimate annual liver cancer mortality rate. Direct age standardized approach was applied using Iran national population 2015 as a standard population to facilitate the comparison between the provinces. Results: Liver cancer age standardized mortality rate in Iran increased by more than four times from 1.18 (95 uncertainty interval; 0.86 to 1.61) deaths per 100,000 person in 1990 to 5.66 (95 uncertainty interval; 4.20 to 7.63) deaths per 100,000 person in 2015. Male to female age adjusted mortality ratio changed from 0.87 to 1.82 during the 26 years of the study. With increasing age, liver cancer mortality rate increased in both sex and all provinces. At provincial level, the province with highest mortality rate have 2.96 times greater rate compare to the lowest. Generally, about 71 of mortality at national level is due to hepatitis B and C infection. Conclusions: In order to reduce liver cancer mortality rate, it is recommended to control main risk factors including chronic hepatitis infections. Because of the growing rate of mortality from liver cancer, augmenting life expectancy, and increasing number of the elderly in Iran, policy makers are more expected to adopt measures including hepatitis B vaccination or hepatitis C treatment. © 2018, Hepatitis Monthly

Liver cancer mortality at national and provincial levels in Iran between 1990 and 2015: A meta regression analysis

Background: Liver cancer is a highly lethal cancer with 5 year survival rate of about 18. This cancer is a leading cause of death in many countries. As there is not a comprehensive population base study on liver cancer mortality rates by cause in national and provincial level in Iran. We aimed to estimate the liver cancer mortality rate, its patterns, and temporal trends during 26 years by sex, age, geographical distribution, and cause. Methods: We used the Iranian death registration system (DRS), in addition to demographic and statistical methods, to address the incompleteness and misclassification and uncertainty of death registration system to estimate annual liver cancer mortality rate. Direct age standardized approach was applied using Iran national population 2015 as a standard population to facilitate the comparison between the provinces. Results: Liver cancer age standardized mortality rate in Iran increased by more than four times from 1.18 (95 uncertainty interval; 0.86 to 1.61) deaths per 100,000 person in 1990 to 5.66 (95 uncertainty interval; 4.20 to 7.63) deaths per 100,000 person in 2015. Male to female age adjusted mortality ratio changed from 0.87 to 1.82 during the 26 years of the study. With increasing age, liver cancer mortality rate increased in both sex and all provinces. At provincial level, the province with highest mortality rate have 2.96 times greater rate compare to the lowest. Generally, about 71 of mortality at national level is due to hepatitis B and C infection. Conclusions: In order to reduce liver cancer mortality rate, it is recommended to control main risk factors including chronic hepatitis infections. Because of the growing rate of mortality from liver cancer, augmenting life expectancy, and increasing number of the elderly in Iran, policy makers are more expected to adopt measures including hepatitis B vaccination or hepatitis C treatment. © 2018, Hepatitis Monthly

Inceptor counteracts insulin signalling in β-cells to control glycaemia.

Resistance to insulin and insulin-like growth factor 1 (IGF1) in pancreatic β-cells causes overt diabetes in mice; thus, therapies that sensitize β-cells to insulin may protect patients with diabetes against β-cell failure1–3. Here we identify an inhibitor of insulin receptor (INSR) and IGF1 receptor (IGF1R) signalling in mouse β-cells, which we name the insulin inhibitory receptor (inceptor; encoded by the gene Iir). Inceptor contains an extracellular cysteine-rich domain with similarities to INSR and IGF1R4, and a mannose 6-phosphate receptor domain that is also found in the IGF2 receptor (IGF2R)5. Knockout mice that lack inceptor (Iir−/−) exhibit signs of hyperinsulinaemia and hypoglycaemia, and die within a few hours of birth. Molecular and cellular analyses of embryonic and postnatal pancreases from Iir−/− mice showed an increase in the activation of INSR–IGF1R in Iir−/− pancreatic tissue, resulting in an increase in the proliferation and mass of β-cells. Similarly, inducible β-cell-specific Iir−/− knockout in adult mice and in ex vivo islets led to an increase in the activation of INSR–IGF1R and increased proliferation of β-cells, resulting in improved glucose tolerance in vivo. Mechanistically, inceptor interacts with INSR–IGF1R to facilitate clathrin-mediated endocytosis for receptor desensitization. Blocking this physical interaction using monoclonal antibodies against the extracellular domain of inceptor resulted in the retention of inceptor and INSR at the plasma membrane to sustain the activation of INSR–IGF1R in β-cells. Together, our findings show that inceptor shields insulin-producing β-cells from constitutive pathway activation, and identify inceptor as a potential molecular target for INSR–IGF1R sensitization and diabetes therapy

Author Correction: Inceptor counteracts insulin signalling in β-cells to control glycaemia.

In this Article, the affiliations for author Ünal Coskun were incorrect. They should be ‘German Center for Diabetes Research (DZD), Neuherberg, Germany’, ‘Paul Langerhans Institute Dresden of Helmholtz Center Munich, Technical University Dresden, Dresden, Germany’ and ‘Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine and University Clinic Carl Gustav Carus, Technical University Dresden, Dresden, Germany’ (affiliations 2, 10 and 14, respectively), and not ‘Department of Microsystems Engineering (IMTEK), University of Freiburg, Freiburg, Germany’ (affiliation 5). The original Article has been corrected online