Sirtuins such as SIRT1 are conserved protein NAD(+)-dependent deacylases and thus their function is intrinsically linked to cellular metabolism. Over the past two decades, accumulating evidence has indicated that sirtuins are not only important energy status sensors but also protect cells against metabolic stresses. Sirtuins regulate the aging process and are themselves regulated by diet and environmental stress. The versatile functions of sirtuins including, more specifically, SIRT1 are supported by their diverse cellular location allowing cells to sense changes in energy levels in the nucleus, cytoplasm, and mitochondrion. SIRT1 plays a critical role in metabolic health by deacetylating many target proteins in numerous tissues, including liver, muscle, adipose tissue, heart, and endothelium. This sirtuin also exerts important systemic effects via the hypothalamus. This review will cover these topics and suggest that strategies to maintain sirtuin activity may be on the horizon to forestall diseases of aging.

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SIRT1 and other sirtuins in metabolism.

SIRT1 and other sirtuins in metabolism

Naturally occurring cancers in pet dogs and humans share many features, including histological appearance, tumour genetics, molecular targets, biological behaviour and response to conventional therapies. Studying dogs with cancer is likely to provide a valuable perspective that is distinct from that generated by the study of human or rodent cancers alone. The value of this opportunity has been increasingly recognized in the field of cancer research for the identification of cancer-associated genes, the study of environmental risk factors, understanding tumour biology and progression, and, perhaps most importantly, the evaluation and development of novel cancer therapeutics.

Translation of new cancer treatments from pet dogs to humans.

Tumors of the Skin and Soft Tissues

Histone posttranslational modifications represent a versatile set of epigenetic marks involved not only in dynamic cellular processes, such as transcription and DNA repair, but also in the stable maintenance of repressive chromatin. In this article, we review many of the key and newly identified histone modifications known to be deregulated in cancer and how this impacts function. The latter part of the article addresses the challenges and current status of the epigenetic drug development process as it applies to cancer therapeutics.

/pdf/histone-modifications-and-cancer-w2boj1xl6t.pdf

Histone Modifications and Cancer.

Mapping of Neurotrophins and their Receptors in the Adult Mouse Brain and their Role in the Pathogenesis of a Transgenic Murine Model of Bovine Spongiform Encephalopathy

Purpose
The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype.

/pdf/fdg-pet-imaging-of-ela1-myc-mice-reveals-major-biological-4ylckfllu9.pdf

FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours.

Cutaneous lymphomas can be divided into two major subgroups based on the absence or presence of epitheliotropism. Nonepitheliotropic lymphoma are usually of presumed B-cell origin, as indicated by numerous cell marker studies in human lymphomas. Epitheliotropic lymphoma, which generally refers to mycosis fungoides and its variants, is ofpresumed T-cell origin.) Mycosis fungoides is a tumor of thymus-derived lymphocytes that arises in the skin.5.6 It is slowly progressive, spreading to lymph nodes and internal organs late in the course of the disease.6 Mycosis fungoides has three characteristic histologic features? 1) the cutaneous cell infiltrate is pleomorphic, with plasma cells, eosinophils, and histiocytes accompanying the neoplastic T lymphocytes; 2) many of the neoplastic T lymphocytes have hyperchromatic and convoluted nuclei, and these cells have been named mycosis cells$ and 3) Pautrier’s microabscesses, small intraepithelial clusters of the proliferating tumor cell^,^.^ are present and are considered almost pathognomonic for mycosis fungoides. Diseases resembling mycosis fungoides have been described in the dog,) cat,) calf,’ and Syrian hamster (Mesocricetus a~ratus).~ In laboratory mice, a condition resembling pagetoid reticulosis has been recently described.’ This report presents a case of epidermotropic cutaneous T-cell lymphoma (mycosis fungoides) supported by immunohistochemical staining of CD3 antigen in a rat. A male Sprague-Dawley rat (Charles River Laboratories, Spain), a member of the untreated control group of a longterm (27 months) carcinogenicity study of 400 animals, showed at week 107 of life a circumscribed erythematous patch with scaling in the interscapular region. At 1 15 weeks, two additional patches appeared on the dorsum of the animal. These lesions progressed to smooth, solid plaques that were erythematous, scaly, alopecic, and ulcerated. The animal did not show pruritus nor any other physical alteration, and his body weight was not diminished. Hematologic parameters indicated a slight leucocytosis. Other hematologic parameters were in the normal range of the other rats of the group. The rat was euthanatized at the end of the study (1 17 weeks of age). At necropsy, samples from all organ systems and from the cutaneous lesions were immersion-fixed in 10% buffered formalin and embedded in paraffin. Sections of 4 pm thickness were cut and stained with hematoxylin and eosin (HE).

https://journals.sagepub.com/doi/pdf/10.1177/030098589403100319

Epidermotropic Cutaneous Lymphoma (Mycosis Fungoides) in an SD Rat

Late stage cathepsin C, CXCL13 and Ki-67 overexpression correlate with regional neuropathology in a BSE transgenic murine model.

Repeated, low-dose administration of streptozotocin (STZ) is widely used to induce insulin-dependent diabetes mellitus in mice. The authors adapted this method using neonatal mice and determined the long-term effects of STZ injection in the mice. After receiving intraperitoneal injections of STZ at postnatal day 3 (P3), P4 and P8, male and female mice were hyperglycemic by week 4. A clear sex difference was found, with blood glucose levels in STZ-treated males remaining higher than those in STZ-treated females until week 23. Whereas STZ-treated males remained hyperglycemic until week 23, STZ-treated females did not have significantly higher glucose levels than control mice after week 18. Additionally, STZ-treated mice had neoplastic lesions in their livers by week 4, with a progression in the severity of these lesions until week 24. The results confirm that, in addition to pancreatic beta cell toxicity, STZ has an oncogenic effect on the liver when administered to neonates.

R.M. Rabanal

Papers

Mapping of Neurotrophins and their Receptors in the Adult Mouse Brain and their Role in the Pathogenesis of a Transgenic Murine Model of Bovine Spongiform Encephalopathy

FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours.

Epidermotropic Cutaneous Lymphoma (Mycosis Fungoides) in an SD Rat

Late stage cathepsin C, CXCL13 and Ki-67 overexpression correlate with regional neuropathology in a BSE transgenic murine model.

Hyperglycemia and hepatic tumors in ICR mice neonatally injected with streptozotocin