Association of cetuximab with adverse pulmonary events in cancer patients: a comprehensive review

Compounds derived from biologic sources, or biologicals, are increasingly utilized as therapeutic agents in malignancy. Development of anti-cancer targeted therapies from biologics is increasingly being utilized. Cetuximab, a chimeric monoclonal antibody, is one such anti-cancer targeted therapeutic that has shown efficacy in quelling the rate of patient decline in colorectal, head/neck, and non-small cell lung cancer. However, due to the relatively recent addition of biologic compounds to the therapeutic arsenal, information related to adverse reactions is less well known than those seen in traditional chemotherapeutics. Dermatologic reactions have been demonstrated as the most frequent side effect cited during cetuximab therapy for malignancy; however, other effects may lead to greater morbidity. In general, pulmonary complications of therapeutics can lead to significant morbidity and mortality. The purpose of this review is to compile the various pulmonary side effects seen in patients treated with cetuximab for various malignancies, and to compare the incidence of these adverse reactions to standard therapies

Sirt1 Promotes a Thermogenic Gene Program in Bone Marrow Adipocytes: From Mice to (Wo)Men

Bone marrow adipose tissue (MAT) is influenced by nutritional cues, and participates in whole body energy metabolism. To investigate the role of Sirtuin1 (Sirt1), a key player in metabolism, in MAT, marrow adiposity was evaluated in inbred 5-month-old 129/Sv Sirt1 haplo-insufficient (Sirt1Δ/+) and wild type (WT) mice. Decreased expression of the thermogenic genes: Prdm16, Pgc1α, Foxc2, Dio2, and β3AR was detected in whole tibiae derived from Sirt1Δ/+ compared to WT female mice. Similarly, decreased expression of Prdm16 and Pgc1α was observed in primary bone marrow mesenchymal stem cell (BM-MSC) cultures obtained from Sirt1Δ/+ compared to WT female mice, suggesting a cell autonomous effect of Sirt1 in BM-MSCs. In vitro, Sirt1 over-expression in the mesenchymal embryonic fibroblast stem cell line C3HT101/2 increased Pgc1α and Prdm16 protein level. Similarly, pharmacologic activation of Sirt1 by SRT3025 increased Foxc2, Pgc1α, Dio2, Tfam, and Cyc1 expression while inhibition of Sirt1 by EX527 down-regulated UCP1 in C3HT101/2 cells. Importantly, in human femoral BM-MSCs obtained from female patients undergoing hip operations for fracture or osteoarthritis, Sirt1 activation by SRT3025 increased PGC1α mRNA and protein level. Blocking sclerostin, an inhibitor of the WNT pathway and a Sirt1 target, by the monoclonal humanized antibody (Sc-AbII), stimulated β3AR, PRDM16, and UCP1 gene expression, and increased PGC1α protein level. These results show that Sirt1 stimulates a thermogenic gene program in marrow adipocytes in mice and humans via PGC1α activation and sclerostin inhibition. The implications of these findings to bone health, hematopoiesis and whole body energy metabolism remain to be investigated.ISSN:1664-239

Superb fairy-wren males aggregate into hidden leks to solicit extragroup fertilizations before dawn

Female superb fairy-wrens Malurus cyaneus initiate extragroup fertilizations by forays to the territory of preferred males, just before sunrise, 2--4 days before egg laying. Over a prolonged breeding season, males advertise their availability to foraying females by singing during the dawn chorus. Here, we show that 1) males commence dawn advertisement at the same time of the year regardless of their quality or status; 2) subordinate males advertise by singing in close proximity to the dominant, or by using the dominant's song perch, despite inevitable punishment; 3) low-quality dominants and their helpers sing from the boundary of their own territory, which increases their proximity to attractive neighboring dominants; 4) each spatial cluster of males use a common dialect of a song that is implicated in extragroup choice, despite the ability of individual males to sing several dialects; and 5) there is leakage of paternity to lower-quality helpers and neighbors as a result of their "satellite" behavior. Collectively, these data suggest that Wagner's hidden lek hypothesis (Wagner RA, 1998. Hidden leks: sexual selection and the clustering of avian territories. In: Parker PG, Burley NT, editors. Avian reproductive tactics: female and male perspectives. Ornithological Monographs No. 49. Allen Press. p. 123--145) can be extended to birds that defend year-round all-purpose territories and that mating induced by parasitic behavior of low-quality satellites can be one explanation for polyandry in birds. Copyright 2009, Oxford University Press.