RESUMO
The propeptide (LOX-PP) domain of the lysyl oxidase proenzyme was shown to inhibit the transformed phenotype of breast, lung and pancreatic cells in culture and the formation of Her2/neu-driven breast cancer in a xenograft model. A single nucleotide polymorphism (SNP, rs1800449) positioned in a highly conserved region of LOX-PP results in an Arg158Gln substitution (humans). This arginine (Arg)âglutamine (Gln) substitution profoundly impaired the ability of LOX-PP to inhibit the invasive phenotype and xenograft tumor formation. To study the effect of the SNP in vivo, here we established a knock in (KI) mouse line (LOX-PPGln mice) expressing an Arg152Gln substitution corresponding to the human Arg158Gln polymorphism. Breast cancer was induced in wild-type (WT) and LOX-PPGln female mice beginning at 6 weeks of age by treatment with 7,12-dimethylbenz(a)anthracene (DMBA) in combination with progesterone. Time course analysis of tumor development demonstrated earlier tumor onset and shorter overall survival in LOX-PPGln versus WT mice. To further compare the tumor burden in WT and LOX-PPGln mice, inguinal mammary glands from both groups of mice were examined for microscopic lesion formation. LOX-PPGln glands contained more lesions (9.6 versus 6.9 lesions/#4 bilateral). In addition, more DMBA-treated LOX-PPGln mice had increased leukocyte infiltrations in their livers and were moribund compared with DMBA-treated WT mice. Thus, these data indicate that the ArgâGln substitution in LOX-PP could be an important marker associated with a more aggressive cancer phenotype and that this KI model is ideal for further mechanistic studies regarding the tumor suppressor function of LOX-PP.
Assuntos
Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/genética , Carcinógenos/toxicidade , Proteínas da Matriz Extracelular/genética , Polimorfismo de Nucleotídeo Único/genética , Proteína-Lisina 6-Oxidase/genética , Animais , Biomarcadores Tumorais/genética , Carcinogênese/induzido quimicamente , Carcinogênese/genética , Linhagem Celular Tumoral , Genes Supressores de Tumor/efeitos dos fármacos , Xenoenxertos , Camundongos , Camundongos Endogâmicos C57BLRESUMO
The use of prostate-specific membrane antigen-positron emission tomography (PSMA-PET) is becoming more widespread for the diagnosis and management of prostate cancer. Here we report a case of oligometastatic renal cell carcinoma (RCC) to the testes diagnosed incidentally on PSMA-PET imaging. This case demonstrates the potential for diagnosis of nonprostate disease with PSMA-PET imaging, as well as the promising nature of PSMA-PET for the diagnosis and surveillance of RCC. In addition, this case report discusses the rare occurrence of oligometastatic RCC to the testis.
RESUMO
Legumes constitute one of the most important global groups of agricultural species, providing a major source of protein and oil for humans and animals as well as fixing nitrogen and improving the fertility of soils. Gene technology can assist plant improvement efforts in clovers (Trifolium spp.), aiming to improve forage quality, yield, and adaptation to biotic and abiotic stresses. An efficient and reproducible protocol for Agrobacterium-mediated transformation of a range of Trifolium species, using cotyledonary explants and different selectable marker genes, is described. The protocol is robust and allows for genotype-independent transformation of clovers. Stable meiotic transmission of transgenes has been demonstrated for selected transgenic clovers carrying single T-DNA inserts recovered from Agrobacterium-mediated transformation. This methodology can also be successfully used for 'isogenic transformation' in clovers: the generation of otherwise identical plants with and without the transgene from the two cotyledons of a single seed.