CA : A Cancer Journal for Clinicians

The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

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Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

Oxidative DNA damage is an inevitable consequence of cellular metabolism, with a propensity for increased levels following toxic insult. Although more than 20 base lesions have been identified, only a fraction of these have received appreciable study, most notably 8-oxo-2'deoxyguanosine. This lesion has been the focus of intense research interest and been ascribed much importance, largely to the detriment of other lesions. The present work reviews the basis for the biological significance of oxidative DNA damage, drawing attention to the multiplicity of proteins with repair activities along with a number of poorly considered effects of damage. Given the plethora of (often contradictory) reports describing pathological conditions in which levels of oxidative DNA damage have been measured, this review critically addresses the extent to which the in vitro significance of such damage has relevance for the pathogenesis of disease. It is suggested that some shortcomings associated with biomarkers, along with gaps in our knowledge, may be responsible for the failure to produce consistent and definitive results when applied to understanding the role of DNA damage in disease, highlighting the need for further studies.

Oxidative DNA damage: mechanisms, mutation, and disease

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Food, Nutrition, Physical Activity, and the Prevention of Cancer : a Global Perspective : 食物、栄養、身体活動とがんの予防 : 世界的展望(後篇)

Physiological changes in fish from stress in aquaculture with emphasis on the response and effects of corticosteroids

OBJECTIVE
To investigate whether leptin is linked to reproduction, circulating levels were measured longitudinally throughout spontaneous menstrual cycles and during pregnancy in normal women.

DESIGN
Longitudinal blood samples were collected from normal volunteers, either during regular menstrual cycles or during successful singleton pregnancies.

PATIENTS
Six healthy, regularly cycling, women volunteers (31.5 ± 3.0 years old, BMI = 21.6 + 0.5) were recruited for serial venous blood sampling throughout one complete menstrual cycle. In addition, five healthy, women (31.8 ± 1.2 years old, pre-pregnant BMI = 30.0 ± 3.1) provided serial venous blood samples throughout one complete singleton pregnancy.

MEASUREMENTS
Circulating venous oestradiol, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), leptin and (pregnant group only) human chorionic gonadotrophin (hCG).

RESULTS
In spontaneously cycling women, changes in circulating leptin levels were associated with menstrual phase (P < 0.001) and correlated with progesterone levels (P < 0.05). Peak leptin concentrations were recorded during the luteal phase (P < 0.01), coincident with maximal progesterone levels (P < 0.05). Leptin concentrations were elevated throughout gestation (P < 0.05), and especially during the second trimester (P < 0.05). Post-partum, circulating leptin levels fell sharply to below pre-pregnant values. Leptin correlated with oestradiol (P < 0.05) and human chorionic gonadotrophin (hCG, P < 0.01) levels during pregnancy. First trimester (P < 0.05) and postpartum (P < 0.05) oestradiol concentrations and post-partum hCG levels exhibited the greatest correlation with circulating leptin.

CONCLUSIONS
We conclude that the relationship between body mass index and circulating leptin varies during the course of spontaneous cycles in women, the best correlation occurring during the luteal phase when progesterone and leptin concentrations are highest. This, together with the correlation between circulating oestradiol, hCG and leptin levels during pregnancy, strongly suggests a dynamic relationship between leptin and reproductive events in women.

Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy

Circadian (∼24-hour) timing systems pervade all kingdoms of life and temporally optimize behavior and physiology in humans. Relatively recent changes to our environments, such as the introduction of artificial lighting, can disorganize the circadian system, from the level of the molecular clocks that regulate the timing of cellular activities to the level of synchronization between our daily cycles of behavior and the solar day. Sleep/wake cycles are intertwined with the circadian system, and global trends indicate that these, too, are increasingly subject to disruption. A large proportion of the world's population is at increased risk of environmentally driven circadian rhythm and sleep disruption, and a minority of individuals are also genetically predisposed to circadian misalignment and sleep disorders. The consequences of disruption to the circadian system and sleep are profound and include myriad metabolic ramifications, some of which may be compounded by adverse effects on dietary choices. If not addressed, the deleterious effects of such disruption will continue to cause widespread health problems; therefore, implementation of the numerous behavioral and pharmaceutical interventions that can help restore circadian system alignment and enhance sleep will be important.

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

Circulating Leptin Levels Are Modulated by Fasting, Cold Exposure and Insulin Administration in Lean but Not Zucker (fa/fa) Rats as Measured by ELISA

The effect of vitamin E on the immune response of the Atlantic salmon (Salmo salar L.).

The incidence of oesophageal adenocarcinoma is increasing rapidly in Western populations. Gastro-oesophageal reflux disease is a strong risk factor for both this tumour and the pre-cancerous lesion Barrett's oesophagus, but the underlying disease mechanisms remain unclear. Developing a better understanding of the aetiology and pathogenesis of Barrett's oesophagus, including the induction of DNA damage and genetic alterations, might provide opportunities for improved management of individuals with this disease. This could include a better rationale for screening and surveillance programmes, as well as targeted intervention strategies.

Laura J. Hardie

Papers

Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy

Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures

Circulating Leptin Levels Are Modulated by Fasting, Cold Exposure and Insulin Administration in Lean but Not Zucker (fa/fa) Rats as Measured by ELISA

The effect of vitamin E on the immune response of the Atlantic salmon (Salmo salar L.).

Reflux, Barrett's oesophagus and adenocarcinoma: burning questions