32 research outputs found
Effects of Dietary Restriction on Cancer Development and Progression
The effects of caloric restriction on tumor growth and progression are known for
over a century. Indeed, fasting has been practiced for millennia, but just recently
has emerged the protective role that it may exert toward cells. Fasting cycles are
able to reprogram the cellular metabolism, by inducing protection against oxidative
stress and prolonging cellular longevity. The reduction of calorie intake as
well as short- or long-term fasting has been shown to protect against chronic and
degenerative diseases, such as diabetes, cardiovascular pathologies, and cancer.
In vitro and in vivo preclinical models showed that different restriction dietary
regimens may be effective against cancer onset and progression, by enhancing
therapy response and reducing its toxic side effects. Fasting-mediated beneficial
effects seem to be due to the reduction of inflammatory response and downregulation
of nutrient-related signaling pathways able to modulate cell proliferation
and apoptosis. In this chapter, we will discuss the most significant studies
present in literature regarding the molecular mechanisms by which dietary
restriction may contribute to prevent cancer onset, reduce its progression, and
positively affect the response to the treatments
Chemotherapy-Induced Late Transgenerational Effects in Mice
To our knowledge, there is no report on long-term reproductive and developmental side effects in the offspring of mothers treated with a widely used chemotherapeutic drug such as doxorubicin (DXR), and neither is there information on transmission of any detrimental effects to several filial generations. Therefore, the purpose of the present paper was to examine the long-term effects of a single intraperitoneal injection of DXR on the reproductive and behavioral performance of adult female mice and their progeny. C57BL/6 female mice (generation zero; G0) were treated with either a single intraperitoneal injection of DXR (G0-DXR) or saline (G0-CON). Data were collected on multiple reproductive parameters and behavioral analysis for anxiety, despair and depression. In addition, the reproductive capacity and health of the subsequent six generations were evaluated. G0-DXR females developed despair-like behaviors; delivery complications; decreased primordial follicle pool; and early lost of reproductive capacity. Surprisingly, the DXR-induced effects in oocytes were transmitted transgenerationally; the most striking effects being observed in G4 and G6, constituting: increased rates of neonatal death; physical malformations; chromosomal abnormalities (particularly deletions on chromosome 10); and death of mothers due to delivery complications. None of these effects were seen in control females of the same generations. Long-term effects of DXR in female mice and their offspring can be attributed to genetic alterations or cell-killing events in oocytes or, presumably, to toxicosis in non-ovarian tissues. Results from the rodent model emphasize the need for retrospective and long-term prospective studies of survivors of cancer treatment and their offspring