Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment

Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.Magnus Zethoven, Luciano Martelotto, Andrew Pattison, Blake Bowen, Shiva Balachander, Aidan Flynn, Fernando J. Rossello, Annette Hogg, Julie A.Miller, Zdenek Frysak, Sean Grimmond, Lauren Fishbein, Arthur S. Tischler, Anthony J. Gill, Rodney J. Hicks, Patricia L. M. Dahia, Roderick Clifton-Bligh, Karel Pacak, Richard W. Tothil

A signature predicting poor prognosis in gastric and ovarian cancer represents a coordinated macrophage and stromal response

10.1158/1078-0432.CCR-13-3049Clinical Cancer Research20102761-2772CCRE

Época de nascimento sobre a composição regional e tecidual da carcaça de cordeiros da raça Texel Birth season on regional and tissue carcass composition in Texel breed lambs

Foram avaliados os efeitos de épocas alternativas de nascimento sobre a composição regional e tecidual da carcaça em ovinos. Quarenta e nove cordeiros machos não-castrados da raça Texel, nascidos em duas épocas (agosto e novembro), foram mantidos em regime de pastagem e abatidos com média de idade de 129 e 164 dias, respectivamente. Previamente aos abates foi feita a avaliação da produção forrageira do campo pelo método Botanal. Foram verificadas melhores condições forrageiras para os cordeiros nascidos em agosto, que apresentaram maior peso e proporção na maioria dos cortes, assim como menor proporção de músculo na paleta e perna; apresentando maior conteúdo de tecido adiposo na maioria dos cortes da carcaça. Para os cordeiros nascidos em novembro, ocorreu maior relação músculo:gordura e músculo:osso na paleta e na perna, assim como maior relação músculo:gordura no costilhar. As condições nutricionais são responsáveis pelas diferenças nos pesos e rendimentos dos cortes, assim como na composição tecidual da carcaça, em cordeiros mantidos em regime de pasto, viabilizando o uso de época alternativa de nascimentos para incrementar a oferta de animais para o abate.<br>The effect of alternative birth season on regional and tissue carcass composition of sheep was evaluated. Forty nine (49) Texel intact male lambs, born in two seasons (August and November), were kept under grazing and slaughtered with an average age of 129 and 164 days, respectively. Prior to slaughter forage production was measured using Botanal method. Lambs born in August had more favorable forage conditions, showing higher body weight and proportion in the majority of cuts, as well as lower proportion of shoulder and leg muscles showing higher adipose tissue content in the majority of carcass cuts. For lambs born in November, a higher muscle:fat and muscle:bone rate in shoulder and leg, as well as a higher ribcut muscle:fat rate. Nutritional conditions are responsible for differences in weights and cuts yields, as well as for the tissue carcass composition, in lambs maintained under grazing regime, making feasible the use of alternative birth periods to increase animal offer for slaughter