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ABSTRACT. Clinicopathological features of mammary gland tumors (MGTs) in 101 dogs were evaluated retrospectively. The incidence of histological malignancy in 60 small-and 41 other-breed dogs were 25% and 58.5%, respectively. In 82 epithelial MGTs, small-sized tumors (< 3 cm) or non-invasive tumors were predominant in small breeds. In multivariate survival analysis, small breed (p=0.048) and lower stage of tumor cell invasion (p=0.006) were significantly associated with longer survival time. These results suggest that the incidence of histological or biological malignancy in MGTs is lower in small-breed dogs than in others. KEY WORDS: canine, clinicopathological survey, mammary gland tumor.

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Background. Refractoriness of glioblastoma multiforme (GBM) largely depends on its radioresistance. We investigated the radiosensitizing effects of celecoxib on GBM cell lines under both normoxic and hypoxic conditions. Methods. Two human GBM cell lines, U87MG and U251MG, and a mouse GBM cell line, GL261, were treated with celecoxib or g-irradiation either alone or in combination under normoxic and hypoxic conditions. Radiosensitizing effects were analyzed by clonogenic survival assays and cell growth assays and by assessing apoptosis and autophagy. Expression of apoptosis-, autophagy-, and endoplasmic reticulum (ER) stressrelated genes was analyzed by immunoblotting. Results. Celecoxib significantly enhanced the radiosensitivity of GBM cells under both normoxic and hypoxic conditions. In addition, combined treatment with celecoxib and g-irradiation induced marked autophagy, particularly in hypoxic cells. The mechanism underlying the radiosensitizing effect of celecoxib was determined to be ER stress loading on GBM cells. Conclusion. Celecoxib enhances the radiosensitivity of GBM cells by a mechanism that is different from cyclooxygenase-2 inhibition. Our results indicate that celecoxib may be a promising radiosensitizing drug for clinical use in patients with GBM. Keywords:autophagy, celecoxib, ER stress, glioblastoma, hypoxia, radiosensitivity. G lioblastoma multiforme (GBM) is the most frequently occurring malignant tumor of the central nervous system. 1 Despite standard carecomprising maximum surgical resection, 60 Gy of conventional radiotherapy, and chemotherapy with temozolomide (TMZ), the median survival time among patients with GBM is 1 year. 2The molecular mechanisms underlying the initiation and progression of GBM reported to date fall into 2 categories: (i) primary GBM with increased epidermal growth factor receptor (EGFR) expression and mutation of the phosphatase and tensin homolog and (ii) secondary GBM that is transformed from benign glioma types with stepwise mutations in the p53 and retinoblastoma genes. It is known that these genetic alterations in GBM are significantly associated with clinical prognosis.1 It has also been reported that methylation of O6-methylguanine-DNA methyltransferase increases the susceptibility of GBM tumor cells to alkylating agents, such as TMZ, 3 and mutation in the isocitrate dehydrogenase 1 gene was recently reported to significantly affect the prognosis in patients with GBM. 4 On the basis of these findings, therapy that targets these specific molecules could be a promising approach for controlling GBM. One possible target is cyclooxygenase-2 (COX-2) because a positive association has been reported among the levels of COX-2, EGFR/EGFRvIII, and activated signal transducer and activator of transcription 3 (STAT3).5 COX-2 expression was reportedly increased in human GBM and was negatively correlated with clinical outcomes in patients. 6 Celecoxib, a nonsteroidal anti-inflammatory drug (NSAID), selectively inhibits This drug is used clinically both for patients with ...

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