Bioscience hypotheses最新文献

We propose a hypothesis for breast cancer (BC) development and its implications for BC prevention. We describe a model in which some breast cells function as both stem cells and steroid sensors (steroid sensitive stem cells). Estrogen receptors on those cells could be upregulated in women who had increased cumulative exposure to estrogen, leading to their progressive sensitization. At menopause, such women experience considerable decline of estrogen concentration in their blood. Consequently, the sensitized stem cells activate mechanisms of local estrogen synthesis including the activation of aromatase. The intracrine build-up of estrogen and its metabolites induces proliferation and genetic dysfunction. Eventually, a normal stem cell transforms into an estrogen-sensitive cancer stem cell that is capable of tumor initiation and delineation into other phenotypes of cancer cells. This hypothesis is supported by significant in-vitro and clinical research evidence. According to this model, we suggest that estrogen therapy could be protective against BC. Alternatively, aromatase inhibitors are expected to be effective in BC prevention. A combination of AIs and estrogen might augment the preventative merits of both drugs and maintain a good tolerability profile for long-term prevention protocols.

According to a classic paradigm, surgery only plays a palliative role in patients with metastatic cancer in whom the possibility of a radical resection is non-viable. However, some convincing data proceeding from two randomized trials carried out in patients with metastatic kidney cancer have challenged this assumption. The hypothesis proposes that the resection of the primary tumour in metastatic cancer is the first generation of forthcoming therapies aiming at stem cell niches. It will independently improve the prognosis of metastatic cancer in patients that are fit enough to tolerate major surgery. The phenomenon of late relapses could also be explained on this basis.

This is the last issue of Bioscience Hypotheses. In a short time we have demonstrated the demand for, and the value of, publishing hypotheses in the life sciences using an editorial choice model. I hope that others can build on our lessons of scientific and commercial success.

I propose a mechanism by which viruses successfully infect new individuals, despite being immotile particles with no ability for directed movement. Within cells, viral particle movements are directed by motors and elements of the cytoskeleton, but how viruses cross extracellular barriers, like mucus, remains a mystery. I propose that viruses cross these barriers by hitch-hiking on bacteria or sperm cells which can transport themselves across mucosal layers designed to protect the underlying cells from pathogen attack. An important implication of this hypothesis is that agents that block interactions between viruses and bacteria or sperm may be new tools for disease prevention.

Bisphosphonates (BPs) have became the treatment of choice for the prevention of skeletal complications in cancer patients with bone metastases as well as in patients suffering from osteoporosis, Paget's disease and rheumatoid arthritis. Osteonecrosis of the jaw (ONJ) is a recently described complication associated with the use of BPs in which the key finding is exposed necrotic bone in the oral cavity. Often, the precipitating event appears to be a dental invasive procedure. We recently provided evidence that ONJ is associated with dental extractions and use of dentures. It has been reported that the primary lesion lies in the bone and it is related to over-suppression of bone turnover, but it is unclear why such a lesion should present with loss of the soft tissue covering the jawbone. We propose that BP could be impairing molecular signalling not only of osteoblasts and osteoclasts but also of fibroblasts and keratinocytes, via cell to cell endocrine and paracrine interactions in a double manner. Such an impairment would result to fibroblast and keratinocyte impaired multiplication, proliferation and migration thereby leading to defective mucosal wound healing. This provides an open entry point for the oral flora to reach the underlying jawbone which is considered to have poor metabolic and immune properties when under BP treatment. We demonstrate that ONJ is associated with mucosal damage, which could be mediated via BP induced soft tissue toxicity. BPs have been reported to promote keratinocyte and fibroblast apoptosis and to impair various cellular activities like apoptosis, RANK, RANK-L and OPG signalling, bone morphogenetic protein signalling, growth factor signalling, immune homeostasis and wound healing. We discuss potential consequences of the above hypothesis for practitioners and investigators.

Papers submitted to Bioscience Hypotheses should be innovative, clear, compatible with at least most of the facts, and testable. Not all good, new, challenging ideas manage these exacting standards. Editorial policy has been altered to include both an increased role for peer advice and an occasional role for editorial advice to authors to bring out the ideas in a form that I think most likely to attract interest from our readership.