Prognostic significance of tumor histology and four computed tomography (CT) staging methods was tested retrospectively in dogs from three treatment centers that underwent intent-to-cure-radiotherapy for intranasal neoplasia. Disease-free and overall survival times were available for 94 dogs. A grouping of anaplastic, squamous cell, and undifferentiated carcinomas had a significantly shorter median disease-free survival (4.4 mo) than a grouping of all sarcomas (10.6 months). Disease-free survivals were not significantly different, when all carcinomas were compared with all sarcomas. The published original and modified WHO staging methods did not significantly relate to either survival endpoint. A modified human maxillary tumor staging system previously applied to canine nasal tumors was prognostically significant for both survival endpoints; a further modified version of that CT-based staging system resulted in improved significance for both survival endpoints. Dogs with unilateral intranasal involvement without bone destruction beyond the turbinates on CT, had longest median survival (23.4 months); CT evidence of cribriform plate involvement was associated with shortest median survival (6.7 months). Combining CT and histology statistically improved prognostic significance for both survival endpoints over the proposed CT staging method alone. Significance was lost when CT stages were collapsed to < four categories or histopathology groupings were collapsed to < three categories.

No abstract

Estrogen is critical for skeletal homeostasis and regulates bone remodeling, in part, by modulating the expression of receptor activator of NF-κB ligand (RANKL), an essential cytokine for bone resorption by osteoclasts. RANKL can be produced by a variety of hematopoietic (e.g. T and B-cell) and mesenchymal (osteoblast lineage, chondrocyte) cell types. The cellular mechanisms by which estrogen acts on bone are still a matter of controversy. By using murine reconstitution models that allow for selective deletion of estrogen receptor-alpha (ERα) or selective inhibition of RANKL in hematopoietic vs. mesenchymal cells, in conjunction with in situ expression profiling in bone cells, we identified bone lining cells as important gatekeepers of estrogen-controlled bone resorption. Our data indicate that the increase in bone resorption observed in states of estrogen deficiency in mice is mainly caused by lack of ERα-mediated suppression of RANKL expression in bone lining cells.Estrogen is an important regulator of bone mass. The role of estrogen for bone homeostasis in humans is illustrated by the fact that estrogen deficiency is one of the major causes of postmenopausal osteoporosis 1 . Estrogen acts through two receptors, estrogen receptor-alpha (ERα) and -beta (ERβ), with ERα being more important for the regulation of bone metabolism 2 . Estrogen receptors are widely expressed in a variety of cells in bone and bone marrow. However, the actual target cell responsible for mediating the effects of estrogen on bone is still a matter of debate 3 . One of the most important downstream mediators of the action of estrogen on bone is the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) system. RANKL is an essential cytokine for osteoclast differentiation, activation, and survival 4, 5 . RANKL is produced by a variety of cells such as cells of the stromal cell lineage, activated T lymphocytes, but also B lymphocytes 5 . OPG is a soluble decoy receptor for RANKL which binds RANKL, and thereby inhibits osteoclastogenesis 6 . RANKL acts through the receptor RANK which is expressed in the cell membrane of osteoclasts and osteoclast precursor cells 7 . RANKL, RANK, and OPG are essential, non-redundant factors for osteoclast biology. Osteoclasts are entirely absent in RANK or RANKL deficient mice, leading to osteopetrosis, whereas OPG-deficient mice exhibit excessive bone resorption and severe osteoporosis 5,7,8 . RANKL exists in two biologically active forms, a membrane-bound form and a soluble form. Membrane-bound RANKL can be shed by matrix metalloproteinase 14 or by a disintegrin and metalloproteinase (ADAM) 10 9 resulting in soluble RANKL. In addition, soluble RANKL is produced by immune cells as a primary secreted form 5 . It is well established that sex steroids regulate the RANKL-OPG axis in osteoblast-like cells in vitro 10,11 . There is good evidence that OPG is regulated directly by sex hormones, whereas the sex steroid-mediated regulation of RANKL appears to be mainly indirect [10][11][12][13] . In vivo, o...

Our objective was to further characterize the late normal tissue complications developing after definitive irradiation of pelvic region tumors in dogs, and to search for prognostic factors. The medical records of dogs receiving definitive irradiation of the pelvic region between 1987 and 2005 were reviewed. The following criteria were established for inclusion: total dose > or =45 Gy, a portion of colon in the primary field, and a minimum of 6 months follow-up. Fifty-one dogs were identified. Prognostic factors evaluated included multiple descriptors of the patient, tumor and radiation treatment. One or more late complications were documented in 20 of 51 patients (39%). Complications were necrotic drainage/ulceration in the skin and subcutaneous tissues within the radiation field (n=7), chronic colitis (n=4), strictures (n=4), osteopenia (n=2), and one each rectal perforation, urinary bladder thickening, iliosacral osteosarcoma, pelvic limb edema, and perianal pain. Two prognostic factors were identified. There was an increase in complications in dogs with perineal tumors compared with other pelvic region sites (P = 0.04), and also in dogs with larger radiation fields (P = 0.04). The finding of an association of tumor site to complications may be a spurious finding and the association between field size and complications is not unexpected although absolute difference in field size between dogs with and without complications was small. There was no association between development of complications and survival. Based on the observed complication rate, consideration can be given to reducing dose per fraction in dogs receiving definitive pelvic region irradiation to <3 Gy.

Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m(-2) (range, 150-300 mg m(-2)) and 4 (range, 2-11), respectively. The overall median progression-free survival for all dogs was 259 days [95% confidence interval (CI95), 119-399 days]. The first progression-free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI95, 247-633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia.