Mammary cancer and epithelial stem cells: a problem or a solution?

The existing paradigms for stem cells in adult tissues include the integument, the alimentary canal, the lung, the liver, skeletal muscle and bone marrow. The mammary gland, by contrast, is the 'new kid on the block'. What little is known about stem cells in the mammary gland indicates that they possess a prodigious capacity for self-renewal. More importantly, in rodents, they persist with undiminished reproductive vigor throughout the organism's lifetime without regard to age or reproductive history. Do these stem cells represent primary targets for mammary neoplasia? If so, what are the implications for prevention/therapy?     

Mitochondrial recoupling: a novel therapeutic strategy for cancer?

Recent findings link metabolic transformation of cancer cells to aberrant functions of mitochondrial uncoupling proteins (UCPs). By inducing proton leak, UCPs interfere with mitochondrial synthesis of adenosine 5'-triphosphate, which is also a key determinant of glycolytic pathways. In addition, UCP suppress the generation of superoxide, a byproduct of mitochondrial electron transport and a major source of oxidative stress. The near ubiquitous UCP2 becomes highly abundant in some cancers and may advance metabolic reprogramming, further disrupt tumour suppression, and promote chemoresistance. Here we review current evidence to suggest that inhibition of mitochondrial uncoupling may eliminate these responses and reveal novel anti-cancer strategies.     

Is D2 lymphadenectomy for gastric cancer a staging tool or a therapeutic intervention?

The extent of lymphadenectomy for gastric cancer is a controversial topic widely debated by those treating the disease. Regional differences in outcome have been noted between patients treated in Japan centers and those treated in Western centers. Technical differences have been investigated within the context of two large, prospective randomized trials, which found no benefit to more extensive lymphadenectomy procedures with increased morbidity. Subsets of patients being treated for cure may benefit from extended resections. The impact of tumor features, such as depth of invasion and number of metastatic lymph nodes, has been described and incorporated into current staging systems. The role of enhanced pathologic evaluation of surgical specimens and impact on staging and treatment strategies is evolving.     

Psychoneuroimmunology and cancer: fact or fiction?

There is substantial evidence from both healthy populations as well as individuals with cancer linking psychological stress with immune downregulation. This discussion highlights natural killer (NK) cells, because of the role that they may play in malignant disease. In addition, distress or depression is also associated with two important processes for carcinogenesis: poorer repair of damaged DNA, and alterations in apoptosis. Conversely, the possibility that psychological interventions may enhance immune function and survival among cancer patients clearly merits further exploration, as does the evidence suggesting that social support may be a key psychological mediator. These studies and others suggest that psychological or behavioural factors may influence the incidence or progression of cancer through psychosocial influences on immune function and other physiological pathways.     

Methionine dependency of cancer cells: a new therapeutic approach?

Metabolic abnormalities of tumor cells offer opportunities of therapeutic targeting. In contrast to normal cells, tumor cells have absolute requirement for methionine (Met), an essential amino acid. Many molecular mechanisms have been considered to explain Met dependency. Several approaches have been used To reduce Met in vivo. As the main Met source was food, synthetic Met free diet were widely used. Alternatively, Met restriction was archived by the use of Met analogs or enzymatic degradation by methioninase. In animal models, Met restriction permit to limit tumor growth and to reduce tumor volume. However, interruption of Met restriction induce the regrowth of tumor. Moreover Met restriction induce several cells modifications suggesting its use in association with conventional chemotherapy. Preclinical studies have shown synergistic effect of the association of Met restriction and different cytostatic agents. Currently, few clinical investigations have been realised to test this therapeutic strategy.     

Cognitive impairment and cancer mortality: a biological or health care explanation?

Purpose

To examine whether the documented association of suboptimal cognitive function with total and cardiovascular (CVD) mortality also applies to cancer mortality and probe whether the explanation for this association is biomedical or health care related.

Methods

In a subsample of 733 participants of the EPIC-Greece cohort from Athens and surrounding area, we assessed cognitive function at age 65 or older in the period 2004–2006, using the Mini-Mental State Examination (MMSE). Incidence of cancer, mortality from cancer and CVD, and overall mortality were ascertained through active follow-up for a median of 4 years after MMSE assessment using Cox proportional hazards models.

Results

A total of 86 participants died during follow-up. A 2-point decrease in MMSE score was associated with increase in overall (hazard ratio (HR) 1.26, 95 % confidence interval (CI) 1.11–1.43), CVD (HR 1.26, 95 % CI 1.02–1.56), and cancer (HR 1.32, 95 % CI 1.02–1.70) mortality. In contrast, there was no noticeable difference in cancer incidence associated with a 2-point decrease in MMSE score (HR 1.07, 95 % CI 0.79–1.45).

Conclusions

Cognitive function appears to be inversely associated not only with CVD and overall, but also with cancer mortality. Although for CVD mortality there is a biomedical explanation invoking vascular mechanisms, for cancer mortality we may need to focus on socially conditioned factors, such as compromised ability to identify early signs and suboptimal compliance to treatment. Our hypothesis-generating results need to be confirmed in larger studies, as the issue is of major importance, since cognitive decline is not uncommon among the elderly.     

HPV and cervical cancer: screening or vaccination?

Following the demonstration of the superior validity of human papillomavirus (HPV) tests in screening for cervical cancer and the arrival of highly efficacious HPV 16 and 18 vaccines, cervical cancer prevention enters a time of sustainable introduction in developing countries. Multidisciplinary efforts and novel protocols are being developed, and challenging situations are being faced to make cervical cancer, still the number two cancer in women worldwide, an eradicable condition.     

Telomerase and telomere stability: a new class of tumor suppressor?

Introduction of telomerase into normal cells provides telomere maintenance and an extended cellular life span, establishing the critical role of telomere attrition in cellular senescence. Additional data surrounding this observation suggest that expression of telomerase renders these "mortal" cells genomically stable with decreased frequencies of mutation, ultimately leading to continued proliferation without signs of changes typically associated with progression to a cancer-like phenotype. Interestingly, oncogenic insult after exogenous telomerase expression does not result in cellular transformation, yet addition of an oncogene first followed by telomerase does transform cells. Taken together, these results imply that order of addition is important for telomerase-mediated genomic protection and that telomerase expression is critical for the transformation process. The hypothesis proposed here is that telomerase, via its function in telomere stabilization, is capable of protecting cells from acquiring the required mutations and genomic instability necessary for malignant transformation, suggesting that telomerase is not an oncogene but may act as a novel class of tumor suppressor.