Frequency and causes of kangaroo-vehicle collisions on an Australian outback highway

Kangaroo-vehicle collisions are frequent on Australian highways. Despite high economic costs, detrimental effects on animal welfare, and potential impacts on population viability, little research has been done to investigate the impact of road mortality on kangaroo populations, where and why accidents occur, and how the collisions can be mitigated. We therefore collected data on species (Macropus rufus, M. giganteus, M. fuliginosus, M. robustus), sex and age of kangaroos killed on a 21.2-km bitumenised section of outback highway over 6 months in far western New South Wales, Australia. The spatial and temporal distribution of road-killed kangaroos was investigated in relation to the cover and quality of road-side vegetation, road characteristics, the density of kangaroos along the road, climatic variables and traffic volume. A total of 125 kangaroos were found killed on the road at a rate of 0.03 deaths km-1 day-1. Grey kangaroos of two species (M. giganteus, M. fuliginosus) were under-represented in the road-kill sample in comparison with their proportion in the source population estimated during the day. No bias towards either sex was found. The age structure of road-killed kangaroos was similar to age structures typical of source kangaroo populations. Road-kills mainly occurred in open plains country. In road sections with curves or stock races, road-kill frequencies were higher than expected. Greater cover and greenness of roadside vegetation at the verge probably attracted kangaroos to the road and variation in this vegetation affected the spatial distribution of road-kills. The temporal distribution of road-kills was positively correlated with the volume of night-time traffic. The probability of a kangaroo-vehicle collision increased exponentially with traffic volume. Results are discussed in relation to the potential for mitigation of kangaroo-vehicle collisions. © CSIRO 2006

Growth inhibition in clonal subpopulations of a human epithelioid sarcoma cell line by retinoic acid and tumour necrosis factor alpha.

Epithelioid sarcoma is a highly malignant soft tissue tumour that is refractory to conventional chemotherapy and irradiation. Since permanent cell lines of this tumour are extremely rare, in vitro data on compounds with significant antiproliferative effects are still lacking. Therefore, we investigated the effects of retinoic acid (RA) and tumour necrosis factor alpha (TNF-alpha) on tumour cell proliferation of three different clonal subpopulations (GRU-1A, GRU-1B, GRU-1C) derived from the same human epithelioid sarcoma cell line, GRU-1. In GRU-1A both RA (P=0.01) and TNF-alpha (P=0.002) exhibited highly significant and dose-dependent growth inhibitory effects, which could further be increased by a combined application of both compounds (P<0.006). GRU-1B proved to be sensitive to RA (P=0.006), whereas no response to TNF-alpha was observed. GRU-1C was resistant to both RA and TNF-alpha. The antiproliferative effect of TNF-alpha was mediated by TNF receptor 1(TNF-R1) and correlated positively with both the number of TNF-R1 per cell and receptor affinity. No correlation was detected between RA-induced growth inhibition and the expression pattern of the RA receptors (RARs) RAR-alpha, RAR-beta, and RAR-gamma. Plating efficiency, however, could exclusively be reduced by RA in GRU-1B, the only cell line expressing RAR-alpha. Taken together, these data are the first showing significant antiproliferative effects in human epithelioid sarcoma by RA and TNF-alpha. Whereas the TNF-alpha response seems to depend on the expression of TNF-R1, no simple correlation could be found between RA sensitivity and the expression pattern of RARs

Disturbed balance of expression between XIAP and Smac/DIABLO during tumour progression in renal cell carcinomas

Dysregulation of apoptosis plays an important role in tumour progression and resistance to chemotherapy. The X-linked inhibitor of apoptosis ( XIAP) is considered to be the most potent caspase inhibitor of all known inhibitor of apoptosis-family members. Only recently, an antagonist of XIAP has been identified, termed Smac/DIABLO. To explore the relevance of antiapoptotic XIAP and proapoptotic Smac/DIABLO for tumour progression in renal cell carcinomas (RCCs), we analysed XIAP and Smac/DIABLO mRNA and protein expression in the primary tumour tissue from 66 RCCs of all major histological types by quantitative real-time PCR, Western blot and ELISA. X-linked inhibitor of apoptosis and Smac/DIABLO mRNA expression was found in all RCCs. Importantly, the relative XIAP mRNA expression levels significantly increased from early (pT1) to advanced (pT3) tumour stages ( P = 0.0002) and also with tumour dedifferentiation ( P = 0.04). Western blot analysis confirmed the tumour stage-dependent increase of XIAP expression on the protein level. In contrast, mRNA and protein expression levels of Smac/DIABLO did not significantly change between early and advanced tumour stages or between low and high tumour grades. Consequently, the mRNA expression ratio between antiapoptotic XIAP and proapoptotic Smac/DIABLO markedly increased during progression from early ( pT1) to advanced ( pT3) tumour stages. Moreover, RCCs confined within the organ capsule ( pT1 and pT2) exhibited a significantly lower XIAP to Smac/DIABLO expression ratio when compared with RCCs infiltrating beyond the kidney ( pT3; P = 0.01). Thus, our investigation demonstrates that the delicate balance between XIAP and Smac/DIABLO expression is gradually disturbed during progression of RCCs, resulting in a relative increase of antiapoptotic XIAP over proapoptotic Smac/DIABLO, thereby probably contributing to the marked apoptosis resistance of RCC.OncologySCI(E)46ARTICLE71349-13579

Deficient activation of CD95 (APO-1/ Fas)-mediated apoptosis: a potential factor of multidrug resistance in human renal cell carcinoma

The pronounced resistance of human renal cell carcinoma (RCC) to anticancer-induced apoptosis has primarily been related to the expression of P-glycoprotein and effective drug detoxification mechanisms. Because the CD95 system has recently been identified as a key mediator of anticancer drug-induced apoptosis, we analysed the contribution of the CD95 system to chemotherapy-induced apoptosis in four newly established RCC cell lines. Here, we demonstrate that all RCC cell lines expressed CD95-receptor and -ligand. Exposure to agonistic anti-CD95 antibodies resulted in induction of apoptosis and significant (P< 0.05) reduction of cell number in three out of four cell lines, indicating that the essential components for CD95-mediated apoptosis were present and functionally intact in the majority of these RCC cell lines. Moreover, treatment of cultures with bleomycin or topotecan, a novel topoisomerase I inhibitor with little substrate affinity for P-glycoprotein, led to induction of apoptosis and significant (P< 0.05) dose-dependent reduction of cell number in all RCC cell lines. Both anticancer drugs also induced upregulation of CD95 ligand expression in all cell lines. Additionally, augmentation of CD95 receptor expression was found in three RCC cell lines, including one p53-mutated cell line, whereas another p53-mutated cell line showed no or only a weak CD95 receptor upregulation after exposure to topotecan or bleomycin, respectively. Despite this upregulation of CD95 receptor and ligand, antagonistic antibodies directed against CD95 receptors or ligands could not inhibit induction of apoptosis by topotecan and bleomycin in any cell line. Thus, although a functionally intact CD95 signalling cascade is present in most RCC cell lines, the anticancer drugs topotecan and bleomycin that induce upregulation of CD95 receptor and ligand fail to effectively activate CD95-mediated apoptosis. This deficient activation of CD95-mediated apoptosis might be an important additional factor for the multidrug resistance phenotype of human RCCs. © 2000 Cancer Research Campaig

X-linked inhibitor of apoptosis positive nuclear labeling: a new independent prognostic biomarker of breast invasive ductal carcinoma

<p>Abstract</p> <p>Background</p> <p>It's well recognized that X-linked inhibitor of apoptosis (XIAP) was the most potent caspase inhibitor and second mitochondria-derived activator of caspase (Smac) was the antagonist of XIAP. Experiments in vitro identified that down regulation of XIAP expression or applying Smac mimics could sensitize breast cancer cells to chemotherapeutics and promote apoptosis. However, expression status and biologic or prognostic significance of XIAP/Smac in breast invasive ductal carcinoma (IDC) were not clear. The present study aimed to investigate relationship among expression status of XIAP/Smac, apoptosis index (AI), clinicopathologic parameters and prognosis in IDC.</p> <p>Methods</p> <p>Immunohistochemistry and TUNEL experiment were performed to detect expression of XIAP, Smac, ER, PR, HER2 and AI in 102 cases of paraffin-embedded IDC samples respectively. Expression of XIAP/Smac were also detected in limited 8 cases of fresh IDC specimens with Western blot.</p> <p>Results</p> <p>Positive ratio and immunoscore of XIAP was markedly higher than Smac in IDC (<it>P </it>< 0.0001). It was noteworthy that 44 cases of IDC were positive in nuclear for XIAP, but none was for Smac. Expression status of Smac was more prevalent in HER2 positive group than negative group (<it>P </it>< 0.0001) and AI was positively correlated with HER2 protein expression (r_s= 0.265, <it>P </it>= 0.017). The present study first revealed that XIAP positive nuclear labeling (XIAP-N), but not cytoplasmic staining (XIAP-C), was the apoptotic marker correlated significantly with patients' shortened overall survival (<it>P </it>= 0.039). Survival analysis demonstrated that XIAP-N was a new independent prognostic factor except for patient age and lymph node status.</p> <p>Conclusion</p> <p>Disturbed balance of expression between XIAP and Smac probably contributed to carcinogenesis and XIAP positive nuclear labeling was a new independent prognostic biomarker of breast IDC.</p