Is mucin a determinant of peritoneal dissemination of gastrointestinal cancer? Analysis of mucin depletion in two preclinical models

Background. Mucinous gastrointestinal cancers may indicate a higher propensity for widespread peritoneal seeding than their non-mucinous counterparts. We hypothesized that mucin content of gastrointestinal cancer cells and tumors is an indicator of cell viability and a determinant of the peritoneal tumor burden and tested our hypothesis in relevant experimental models. Methods. MKN45 and LS174T models of human gastrointestinal cancer were treated with known mucin-depleting agents in vitro and in vivo, their mucin production was evaluated with Western blot immunohistochemistry, PAS staining and ELISA, and its correlation with cell viability and peritoneal tumor burden was analyzed. Results. A relationship was found between the viability of cancer cells and their mucin levels in vitro. In agreement, when treated animal models were categorized into low- and high-burden groups (based on the weight and number of the peritoneal nodules), tumoral mucin levels were found to be significantly higher in the latter group. Conclusions. Tumoral mucin is apparently among the factors that dictate the pattern and extent of the peritoneal spread of gastrointestinal cancer, where it allows for enhanced dissemination and redistribution. If further tested and validated, our hypothesis could lay the basis for the development of novel mucin-targeted strategies (AU)

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Tissue-based biomarkers predicting outcomes in metastatic colorectal cancer: a review

Although there have been recent advances in the treatment of metastatic colorectal cancer, particularly with systemic chemotherapy, new biological agents and surgical metastasectomy, the disease remains difficult to treat. To personalise the management of mCRC and optimise patient outcomes, it is vital to acquire a deeper understanding of its natural history and mechanisms behind disease progression. This may be achieved by extensive study of tumour biomarkers: proteins or genetic alterations within neoplastic cells or their surrounding stroma that may be used to predict patient outcomes, disease trajectory and response to various therapies. The discovery of mutant Kirsten-RAS in determining patients who may be refractory to anti-epidermal growth factor receptor treatments has reinvigorated and reiterated the importance of our attempts to individualise cancer care. While many biomarkers have been studied and shown promise in the setting of mCRC, they are, with the exception of K-ras testing not used currently in a clinical setting due to conflicting results, small patient samples and methodological variations. Larger, multi-centric studies with uniform methods of tumour marker study are required to effectively tailor systemic therapies and select appropriate candidates for surgical metastasectomy (AU)

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Influence of experimentally elevated testosterone on nest defence in dark-eyed juncos.

Testosterone affects the allocation of reproductive effort in male birds. Elevated testosterone causes male dark-eyed juncos, Junco hyemalis, to decrease care of dependant offspring, but this generalization is based largely on reduced provisioning rates by males treated with testosterone. Therefore, we used a predator model to explore the relationship between testosterone and nest defence, a more immediate measure of male parental effort. Control males (C-males) were more likely to respond within 10 min to a mount of an eastern chipmunk, Tamias striatus, placed at the nest than were testosterone-treated males (T-males). However, among males that did respond within 10 min, T-males initiated nest defence as fast as C-males and defended the nest with equal intensity. Females initiated nest defence more rapidly and struck the mount more often than their mates, regardless of the male's treatment. Overall, the decreased likelihood of T-males being present for nest defence (perhaps mediated by their large home ranges) may increase predation rates at their nests and represent an important cost of elevated testosterone levels. Copyright 1998 The Association for the Study of Animal Behaviour