The effects of surgery-induced immunosuppression and angiogenesis on tumour growth.

Surgical removal of primary tumours can help in the treatment of cancer but carries the risk of triggering the proliferation of dormant micrometastases. Many experimental and clinical studies have demonstrated that anti-angiogenic mechanisms and immune surveillance are essential to inhibit metastatic tumour cells from growing. As surgical stress often induces a reduction in anti-angiogenic factors in parallel with increases in angiogenic factors and suppression of immune surveillance during the post-operative period, new strategies for peri-operative immunostimulation and chemotherapy are required. This review summarises the factors and proposed mechanisms underlying the effects of surgery on immunosuppression and angiogenesis.

Prognostic utility of apoptosis index, Ki-67 and survivin expression in dogs with nasal carcinoma treated with orthovoltage radiation therapy.

Apoptosis, Ki-67 and survivin expression have been reported as prognostic values in human cancer treated with radiation therapy. The aim of this study was to evaluate the correlation between the outcome of canine nasal carcinomas treated with radiation therapy and these cancer markers. The apoptotic index (AI) was evaluated with TUNEL assays, and an immunohistochemical evaluation was performed on Ki-67 and survivin in 33 biopsy samples taken before treatment. Median survival times were estimated using Kaplan-Meier curves and the log-rank method. The AI ranged from 0 to 0.7%, and the percentage of Ki-67-positive cells defined as the proliferative index (PI) ranged from 0.8 to 77% in all samples. Neither the AI nor the PI had a significant relationship with survival time (P=0.056 and 0.211). Survivin expression was detected in 84.9% of samples of canine nasal carcinoma. Dogs with high survivin expression were associated with poorer response to treatment and had shorter survival times (P=0.017 and 0.031). Advanced-stage tumors were also significantly associated with a high level of survivin (P=0.026). Overexpression of survivin was shown to be an unfavorable prognostic factor in dogs with nasal carcinomas treated with radiation therapy.

The clock gene brain and muscle Arnt-like protein-1 (BMAL1) is involved in hair growth.

It is known that baldness caused by androgenetic alopecia is involved with androgen and the androgen receptor. Furthermore, it has been reported that testosterone secretion follows a circadian rhythm. Therefore, we hypothesized that a relationship exists between androgen-induced alopecia and biological rhythm. The mammalian circadian rhythm is controlled by several clock genes. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), one of the clock genes, is a transcription factor that plays central roles in the regulation of circadian rhythms. In this study, we investigated the influence of BMAL1 on hair follicle functions and hair growth. Mice deficient in BMAL1 expression exhibited a delay in hair regrowth after shaving. In hair follicles of mouse vibrissa, expression of Bmal1 and other clock genes was found to be rhythmic. Knockdown of BMAL1 in human follicle dermal papilla cells resulted in modulation of expression of several hair growth-related genes. Therefore, we concluded that expression of clock genes in hair follicles is linked to the circadian rhythm and that BMAL1 can regulate hair growth.

Peripheral lymphocyte subsets as a prognostic indicator of mortality and morbidity in healthy dogs.

To evaluate the relationship among immune status and increased morbidity and mortality, peripheral blood lymphocytes (CD3(+), CD4(+), CD8(+) and CD21(+) cells) from 32 healthy dogs over 8 years of age were analyzed. Twenty-five of the 32 dogs were followed-up for 3 years after the analysis; and 14 dogs were found to be diseased, and nine dogs died. There was no notable difference between the ages of the dogs that died compared with the ones that survived. The relative percentage of CD4(+) and the CD4(+):CD8(+) ratio decreased notably in dogs falling ill compared with healthy dogs. The relative percentage of CD3(+) lymphocytes showed a notable decrease in dogs that died within 3 years in comparison with dogs that survived. In a discriminant analysis of morbidity and mortality, most patients were correctly classified as diseased or not and surviving or dead, respectively. These results indicate that the immunophenotypes of peripheral blood lymphocytes in older dogs offer promise as parameters for evaluating mortality and morbidity.

Pathological classification of canine mammary tumor based on quantifying mRNA levels of hormonal receptors, SATB1, and Snail in tissue and fine needle biopsy samples.

Cytological diagnosis is not generally conclusive enough to identify histopathological malignancy in canine mammary tumors (CMTs). To establish cytological examination using fine needle biopsy (FNB) samples, gene expressions of hormonal receptors, human epidermal growth factor receptor 2 (HER2), and transcription regulators (Special AT-rich binding protein 1: SATB1 and Snail) were investigated in both tissue and FNB samples of CMTs. In tissue samples of malignant CMTs, especially invasive ones, low expressions of hormonal receptors and high expressions of SATB1 and Snail were detected. On discriminant analysis of tissue samples, 73.2% of CMTs were correctly classified according to histopathological examinations. In FNB samples of malignant CMTs, low expressions of hormonal receptors were detected. On discriminant analysis of FNB samples, 74.2% of CMTs were correctly classified according to histopathological examination. In conclusion, FNB gene expressions had a utility for diagnosis of CMTs malignancy in some degree. By researching more sensitive genes for malignant CMTs, the gene examination of FNB samples from CMTs will become a useful diagnostic tool that can be performed easily without anesthesia and could predict tumor malignancy and invasion prior to surgical removal.

Alterations of lymphocyte subpopulations in healthy dogs with aging and in dogs with cancer.

Changes in an individual's immune status are considered major contributing factors towards the morbidity of cancer and mortality of aging. To evaluate age-related changes in the immune status of dogs, the immunophenotypes (CD3, CD4, CD8 and CD21) of peripheral blood lymphocytes were measured in 160 healthy dogs aged from 1 to 17 years, and in 365 dogs with various tumors and at various stages. In healthy dogs, the absolute numbers of white blood cells, lymphocytes, and CD3(+), CD4(+) and CD21(+) lymphocytes decreased significantly with age. The relative percentages of lymphocytes and CD4(+) cells decreased significantly, while CD8(+) cells increased significantly with age. The CD4:CD8 ratio showed a significant age-related decrease. In contrast, dogs with tumors possessed significantly lower absolute numbers and relative percentages of all lymphocyte phenotypes, while the CD4:CD8 ratio was significantly higher than in age-matched controls. The relative percentages of CD3(+) and CD8(+) lymphocytes were significantly lower in dogs with distant metastases compared with dogs without metastases, and the CD4:CD8 ratio increased with advanced stage. These observations illustrate the significant changes in immune status with age and the presence of marked immunological defects in a large-scale study of dogs with advanced tumors.