International Agency for Research on Cancer

About: International Agency for Research on Cancer is a government organization based out in Lyon, France. It is known for research contribution in the topics: Population & Cancer. The organization has 2989 authors who have published 9010 publications receiving 929752 citations. The organization is also known as: IARC.

The 2019 World Health Organization classification of tumours of the breast.

Abstract: The newly published World Health Organization (WHO) Classification of Tumours of the breast features significant changes compared to earlier editions. In this review, we outline the major changes in this important reference source for those diagnosing tumours, or engaged in cancer research, and describe the significant changes. For breast cancer, the overview acknowledges the treatment-relevant subtypes of invasive carcinoma (based on ER and HER2 status) and new data is added to support the differences in pathogenesis, treatment response and prognosis of these clinically relevant groupings. The WHO Classification of Tumours is increasingly evidence-based, with a clear update cycle, improved quality of illustrations, as well as content, led by an editorial board comprising pathologists, but increasingly incorporating input from other disciplines. The advent of the new website allows the use of whole slide images, and hyperlinks to evidence or external bodies that produce guidance on staging or reporting.

Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E-cadherin.

Abstract: Gap junctional intercellular communication (GJIC) of cultured mouse epidermal cells is mediated by a gap junction protein, connexin 43, and is dependent on the calcium concentration in the medium, with higher GJIC in a high-calcium (1.2 mM) medium. In several mouse epidermal cell lines, we found a good correlation between the level of GJIC and that of immunohistochemical staining of E-cadherin, a calcium-dependent cell adhesion molecule, at cell-cell contact areas. The variant cell line P3/22 showed both low GJIC and E-cadherin protein expression in low- and high-Ca2+ media. P3/22 cells showed very low E-cadherin mRNA expression. To test directly whether E-cadherin is involved in the Ca(2+)-dependent regulation of GJIC, we transfected the E-cadherin expression vector into P3/22 cells and obtained several stable clones which expressed high levels of E-cadherin mRNA. All transfectants expressed E-cadherin molecules at cell-cell contact areas in a calcium-dependent manner. GJIC was also observed in these transfectants and was calcium dependent. These results suggest that Ca(2+)-dependent regulation of GJIC in mouse epidermal cells is directly controlled by a calcium-dependent cell adhesion molecule, E-cadherin. Furthermore, several lines of evidence suggest that GJIC control by E-cadherin involves posttranslational regulation (assembly and/or function) of the gap junction protein connexin 43.

Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism

Abstract: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes parkinsonism in humans and nonhuman animals, and its use has led to greater understanding of the pathogenesis of Parkinson’s disease. However, its molecular targets have not been defined. We show that mice lacking the gene for poly(ADP-ribose) polymerase (PARP), which catalyzes the attachment of ADP ribose units from NAD to nuclear proteins after DNA damage, are dramatically spared from MPTP neurotoxicity. MPTP potently activates PARP exclusively in vulnerable dopamine containing neurons of the substantia nigra. MPTP elicits a novel pattern of poly(ADP-ribosyl)ation of nuclear proteins that completely depends on neuronally derived nitric oxide. Thus, NO, DNA damage, and PARP activation play a critical role in MPTP-induced parkinsonism and suggest that inhibitors of PARP may have protective benefit in the treatment of Parkinson’s disease.

European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics

Abstract: The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects' characteristics known possibly to influence dietary intakes was compared in both population groups This was the first time that calibration sub-studies had been set up in a large multi-centre European study These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice The average response in the calibration study was 783% and ranged from 465% to 925% The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres

Lead and cancer in humans: Where are we now?†

Abstract: Background Lead is only weakly mutagenic, but in vitro it inhibits DNA repair and acts synergistically with other mutagens. Lead acetate administered orally, cutaneously, or intraperitoneally causes kidney cancer, brain cancer (gliomas), and lung cancer in rodents, and acts synergistically with other carcinogens. Most cytogenetic studies of exposed workers have shown increases in chromosome aberrations or sister chromatid exchange, including some studies with positive-exposure response trends. There are eight studies of cancer mortality or incidence among highly exposed workers; most are cohort studies of lead smelter or battery workers exposed decades ago. Methods We reviewed the epidemologic studies with regard to cancer. Results These studies provide some evidence of increased risk of lung cancer (RR = 1.30, 1.15-1.46, 675 observed deaths) and stomach cancer (combined RR = 1.34, 1.14-1.57, 181 observed). However, the lung cancer findings are not consistent across studies, and confounding by arsenic may affect the study with the highest lung cancer RR. Exclusion of that study yields a combined lung cancer RR of 1.14 (1.04-1.73). There is little evidence of increased risk of kidney cancer (combined RR=1.01, 0.72-1.42, 40 observed) or brain cancer (combined RR=1.06, 0.81-1.40, 69 observed). However, two studies show a two-fold increase in kidney cancer, and one study shows a significant excess of gliomas. IARC classified lead as a possible human carcinogen based on sufficient animal data and insufficient human data in 1987. Six of the eight studies cited above have been published since 1987. Conclusion Overall, there is only weak evidence associating lead with cancer; the most likely candidates are lung cancer, stomach cancer, and gliomas.