Death is the new sex, last great taboo in Western society and Western medicine, as Richard Smith discusses in his editorial (p 129). In the trinity of births, marriages, and deaths, only death does not have glossy magazines devoted to stylish consumption at the attendant ceremonies. On the web, of course, …

Death and dying

Childhood obesity and adult morbidities

IGF-I receptor (IGF-IR) signaling and functions are mediated through the activities of a complex molecular network of positive (e.g., type I IGF) and negative (e.g., the type II IGF receptor, IGF-IIR) effectors. Under normal physiological conditions, the balance between the expression and activities of these molecules is tightly controlled. Changes in this delicate balance (e.g., overexpression of one effector) may trigger a cascade of molecular events that can ultimately lead to malignancy. In recent years, evidence has been mounting that the IGF axis may be involved in human cancer progression and can be targeted for therapeutic intervention. Here we review old and more recent evidence on the role the IGF system in malignancy and highlight experimental and clinical studies that provide novel insights into the complex mechanisms that contribute to its oncogenic potential. Controversies arising from conflicting evidence on the relevance of IGF-IR and its ligands to human cancer are discussed. Our review highlights the importance of viewing the IGF axis as a complex multifactorial system and shows that changes in the expression levels of any one component of the axis, in a given malignancy, should be interpreted with caution and viewed in a wider context that takes into account the expression levels, state of activation, accessibility, and functionality of other interacting components. Because IGF targeting for anticancer therapy is rapidly becoming a clinical reality, an understanding of this complexity is timely because it is likely to have an impact on the design, mode of action, and clinical outcomes of newly developed drugs.

/pdf/the-role-of-the-igf-system-in-cancer-growth-and-metastasis-33yxkoa6sh.pdf

The role of the IGF system in cancer growth and metastasis: overview and recent insights.

The number of cancer cases caused by being obese is estimated to be 20% with the increased risk of malignancies being influenced by diet, weight change, and body fat distribution together with physical activity. Reports from the International Agency for Research into Cancer and the World Cancer Research Fund (WCRF) have shown that the strongest evidence exists for an association of obesity with the following cancer types: endometrial, esophageal adenocarcinoma, colorectal, postmenopausal breast, prostate, and renal, whereas the less common malignancies are leukemia, non-Hodgkin’s lymphoma, multiple myeloma, malignant melanoma, and thyroid tumours. To be able to develop novel methods in prevention and treatment, we first must understand the underlying processes which link cancer to obesity. Four main systems have been identified as potential producers of cancer in obesity: insulin, insulin-like growth factor-I, sex steroids, and adipokines. Various novel candidate mechanisms have been proposed: chronic inflammation, oxidative stress, crosstalk between tumour cells and surrounding adipocytes, migrating adipose stromal cells, obesity-induced hypoxia, shared genetic susceptibility, and the functional defeat of immune function. Herein, we review the major pathogenic links between obesity and susceptibility to cancer.

/pdf/obesity-as-a-major-risk-factor-for-cancer-23ganvywbu.pdf

Obesity as a Major Risk Factor for Cancer

Overweight and obesity are health problems of epidemic proportions, increasing the risk not only of cardiovascular disease and type 2 diabetes mellitus but also of various types of cancer. Obesity is strongly associated with changes in the physiological function of adipose tissue, leading to insulin resistance, chronic inflammation, and altered secretion of adipokines. Several of these factors, such as insulin resistance, increased levels of leptin, plasminogen activator inhibitor-1, and endogenous sex steroids, decreased levels of adiponectin, and chronic inflammation, are involved in carcinogenesis and cancer progression. This article reviews these mechanisms, focusing on adipose tissue dysfunction as a unifying causal factor. Although understanding of the link between obesity and cancer might provide therapeutic targets, preventing overweight and obesity still remains number one priority.

https://cebp.aacrjournals.org/content/cebp/18/10/2569.full.pdf

Obesity and Cancer: The Role of Dysfunctional Adipose Tissue

Adiponectin, an adipocyte-secreted hormone, is closely and inversely associated with insulin resistance and was recently found to be inversely and independently associated with endometrial cancer. Because insulin resistance in the setting of obesity has also been associated with the development of breast cancer, we have hypothesized that decreased adiponectin levels might underlie the association between breast cancer and obesity/insulin resistance. We evaluated the association of adiponectin with the occurrence of breast cancer in a case-control study comprising 174 women with newly diagnosed, histologically confirmed breast cancer and 167 controls. We found an inverse, fairly strong, and statistically significant association of serum adiponectin with breast cancer (odds ratio, 0.84; 95% confidence interval, 0.71-0.99). Importantly, despite a fairly robust inverse association of adiponectin with breast cancer risk among postmenopausal women (odds ratio, 0.82; 95% confidence interval, 0.67-1.00), no such significant association between adiponectin and breast cancer was found among premenopausal women. The observed associations were independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known risk factors for breast cancer. Future studies are needed to prove causality and provide further insights into both the mechanisms underlying the actions of this hormone and its potential role in breast cancer.

/pdf/adiponectin-and-breast-cancer-risk-20yun1olco.pdf

Adiponectin and breast cancer risk.

Cancer screening: evidence and practice in Europe 2008.

The term “cancer” is commonly used to cover a wide range of diseases which all share
a common feature, namely that cells in affected organs or tissues of the body (eg breast,
lung, skin or bone marrow) continue to grow indefinitely, without reference to the needs
of the body Many cancers have the capacity to spread to other parts of the body and to
kill the patient With more than 3 million new cases and 17 million deaths each year, cancer
currently represents the second most important cause of death and morbidity in Europe
This volume, published under the Slovenian Presidency of the European Union, is a
review of the current status of cancer control in the European Union The aim was to
summarize the evidence that should underpin policy for the prevention, management
and palliation of cancer in Europe
The book has been produced as a collaborative effort between internationally recognized
public health institutes in the European Union, under the umbrella Fighting Against
Cancer Today (FACT) FACT is co-funded by the Government of Slovenia and the
European Commission’s Health and Consumer Protection Directorate, with additional
support from the European Observatory on Health Systems and Policies

Responding to the challenge of cancer in Europe

The early (intrauterine and neonatal) life environment plays an important role in programming the susceptibility in later life to chronic degenerative diseases, such as obesity, cardiovascular diseases, diabetes mellitus, cancer and osteoporosis. Among other hormones, leptin plays a major role in the regulation of the overall metabolism and has multiple neuroendocrine (adeno- and neuro-hypophysis axes and the hypothalamus-pituitary-adrenal axis) and immune functions. The hormone exerts its actions beginning in the early life time period, regulating the intrauterine and early extrauterine life growth and development, as well as the adaptation to extrauterine life, neonatal thermogenesis and response to stress. Recent findings also support a role of leptin in the process of fetal bone remodeling and brain development. Therefore, it is of interest to explore the physiology of leptin in early life, as well as those factors that may perturb the balance of the hormone with pathological consequences in terms of confining an increased risk for disease in later life. This review aims to summarize reported findings concerning the role of leptin in early life, as well as the association of fetal, maternal and placental factors with leptin levels, while attempting to speculate mechanisms through which these factors may influence the risk for developing chronic diseases in later life.

/pdf/determinants-of-early-life-leptin-levels-and-later-life-a51tknf25q.pdf

Determinants of early life leptin levels and later life degenerative outcomes.

Objective: To calculate the preventable fraction of unintentional childhood injury deaths in the United States. 

Design: Ecological study of cause specific unintentional childhood injury mortality rates across the 50 states (and the District of Columbia) of the United States (US) over the 10 year period 1989–98. 

Methods: The internet accessible database from the National Center for Injury Prevention and Control was used in order to estimate unintentional childhood (0–14 years) injury mortality rates by external cause and time trends over the study period for each of the US states and for the four major geographical regions of the country. In the principal analysis, a calculation was made of the fraction and absolute number of unintentional childhood injury deaths that could have been prevented annually if the mortality rate in the region with the lowest rate also existed in the remaining three. In another scenario, the lowest external cause specific unintentional childhood injury mortality rates from the 50 US states and the District of Columbia were summed to provide the "ideal" lowest conceivable unintentional childhood injury mortality rate from all causes. Ecological correlations between unintentional childhood injury mortality rates from specified external causes, median income, and percent of the population with a college degree were made. 

Main outcome measures: Unintentional childhood injury mortality rates by cause. 

Results: Unintentional childhood injury mortality rate declined by 3.5% per year in the country as a whole. If every region of the US had experienced the same injury rate as the Northeast, then one third of all unintentional childhood injuries would not have occurred. 

More optimistic scenarios indicate that up to two thirds of all unintentional childhood injury deaths could be prevented. Across states, unintentional childhood injury mortality is strongly inversely related to median income. 

Conclusions: About one third of all unintentional childhood injury deaths in the US are preventable with the means and resources available in the Northeastern states. Among the relevant characteristics in the Northeast region, in comparison with other US regions, are the higher education level of parents, the lower gun ownership, the higher population density that implies shorter distances traveled by cars, a better developed emergency medical system, and the existence of several injury prevention programs.

https://injuryprevention.bmj.com/content/injuryprev/10/2/79.full.pdf

Delia Marina Alexe

Papers

Adiponectin and breast cancer risk.

Cancer screening: evidence and practice in Europe 2008.

Responding to the challenge of cancer in Europe

Determinants of early life leptin levels and later life degenerative outcomes.

A quantification of preventable unintentional childhood injury mortality in the united states