Fibroblastic Subtype has a Favourable Prognosis in Appendicular Osteosarcoma of Dogs.

Osteosarcoma (OS) is an aggressive malignant bone neoplasm that occurs mostly in the appendicular skeleton of dogs and people. OS is classified based on the presence of malignant stroma and the formation of extracellular matrix into osteoblastic, chondroblastic and fibroblastic forms. This study investigated the correlation between the three histological subtypes of canine OS and clinical outcome. Additionally, we examined whether there was any difference in the immunolabelling of desmin, S100 and neuron-specific enolase (NSE) between the three histological subtypes. Formalin-fixed and paraffin wax-embedded tissues from 87 dogs with primary OS were available for this study. The survival times were correlated with appendicular OS subtypes in dogs that were treated surgically, received adjuvant chemotherapy and had no pulmonary metastasis at the time of diagnosis. Dogs with an appendicular fibroblastic OS had significantly prolonged mean average survival times (546 ± 105 days) in comparison with dogs having appendicular osteoblastic (257 ± 48 days) or appendicular chondroblastic (170 ± 28 days) OS (P = 0.003, Log Rank). The results also revealed that the appendicular chondroblastic subtype is a significant indicator for poor prognosis in dogs compared with the fibroblastic or osteoblastic subtypes (P = 0.006, Cox regression). Moreover, the findings indicated that there was no significant correlation between the localization of desmin, NSE or S100 and histological subtypes. Importantly, dogs with appendicular fibroblastic OS were found to have a better prognosis when compared with dogs with other subtypes. This may suggest that histological subtypes of appendicular OS have diverse behaviour and could be used to categorize patients for risk-based assessment.

Immunohistochemical Validation of Spontaneously Arising Canine Osteosarcoma as a Model for Human Osteosarcoma.

Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents one of the primary bone tumours. It is the most common primary bone tumour in dogs and man. The characterization of an appropriate natural disease animal model to study human OS is essential to elucidate the pathogenesis of the disease. This study aimed to validate canine OS as a model for the human disease by evaluating immunohistochemically the expression of markers known to be important in human OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP), desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by all tumours, while desmin, S100 and NSE were expressed variably. The findings were similar to those described previously for human OS and suggest that canine OS may represent a useful model for the study of the human disease.

Canine Mixed Mammary Tumour as a Model for Human Breast Cancer with Osseous Metaplasia.

Canine mixed mammary tumours (CMMTs) and human metaplastic breast carcinomas (HMBCs) share several histopathological features and risk factors. In both species, these tumours display epithelial and stromal components. HMBCs are rare malignant tumours, but CMMTs are one of the most common mammary tumours in dogs and are more often benign than malignant. In this study, benign (n = 88) and malignant (n = 13) CMMTs were characterized using specific antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, cytokeratin AE1/AE3, vimentin, Ki67, E-cadherin and p63. Cartilage and bone matrices associated with benign and malignant CMMTs were characterized using specific antibodies against BMP4, Runx2, Sox9 and osteopontin. The current study suggested that CMMTs are of epithelial origin, but display a myoepithelial-like differentiation. The findings suggest key roles for Sox9, Runx2 and BMP4 in chondrogenesis and bone formation in CMMTs. The high expression of osteopontin in CMMTs appears to be unrelated to tumour malignancy.

Cardiac toxicity in breast cancer patients.

AIM: To asses cardiac toxicity post radiotherapy in left cancer breast patients with different fractionations. METHODS: This is a prospective randomized study conducted at Kasr El-Ainy Center of Clinical Oncology and Nuclear Medicine (NEMROCK). Cardiological assessment using RTOG toxicity criteria was done for left sided breast cancer patients after at least five years of conformal radiation therapy. There were two arms of radiation, conventional (50Gy/25sttt/5 Ws) and hypofractionation (42.5 Gy /16 fractions /3 1/5 weeks). RESULTS: Thirty patients were included in each arm. After a median follow up of 62 months (range 60 to 72), cardiac dysfunction developed more in the conventional arm but was insignificant (P value =0.36). Grade I & II toxicity was 83.3 vs 70% and grade III was 3.3% in the hypofractionated arm only. The rate of localregional tumor relapse at 5 years was similar (3.3%). CONCLUSION: Hypofractionated radiotherapy decreased cardiac toxicity though not statistically significant, however it is more cost effective and time consuming. KEYWORDS: breast cancer, cardiac toxicity, hypofractionation, Egypt.

Influence of certain calcium-channel blockers on some aspects of lorazepam-dependence in mice.

The effect of acute and chronic treatments of the calcium-channel blockers, isradipine, diltiazem and flunarizine in protecting against lorazepam dependence has been demonstrated in mice. Dependence was induced by twice-daily administration of lorazepam (1 mg kg-1) for 10 days, doubling the dose during the next 10 days. Withdrawal symptoms and changes in the noradrenaline, dopamine and 5-hydroxytryptamine content of different regions of the brain were observed after either 24-h withdrawal or flumazenil administration. Isradipine inhibited lorazepam withdrawal symptoms, the effect being accompanied in the 24-h withdrawal group by significant decreases in the noradrenaline and dopamine content of the thalamus and hypothalamus and in the noradrenaline content of the mid-brain. In the flumazenil-treated group isradipine produced significant decreases in mid-brain noradrenaline and dopamine levels and in the dopamine content of the thalamus and hypothalamus. Diltiazem did not, on the other hand, afford significant protection against lorazepam withdrawal symptoms and did not induce any significant change in the neurotransmitters studied. Flunarizine significantly inhibited lorazepam withdrawal symptoms, an effect accompanied by significant reduction in noradrenaline and dopamine levels in the thalamus and hypothalamus. Dopamine was also significantly reduced in the cerebral cortex. Similar effects were produced in the flumazenil-treated group, and the noradrenaline content was reduced in the medulla, pons and cerebellum. It was concluded that isradipine and flunarizine might be of value in ameliorating lorazepam withdrawal symptoms.

Certificated incapacity and unemployment in alcoholics.

Seventy-three male alcoholics permitted information to be obtained from official sources about time recorded as lost from work in receipt of sickness or unemployment benefits and about their weekly state insurance contributions. The average yearly time loss was 121-7 working days per person, comprising an average yearly loss through sickness of 86-1 and through unemployment of 35-6 working days respectively. By contrast the recorded national sickness loss for men in a comparable twelve months period averaged 15-9 working days per person. Thirteen alcoholics showed over five years, prolonged deficiency in work attendance. State benefits to the subjects, over twelve months during the early 1970s, totalled pounds 18,434.80. Diagnoses on their medical certificates underestimated incapacity from alcoholism.