TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells

The TP53induced glycolysis and apoptosis regulator (TIGAR) is the protein product of the p53 target gene, C12orf5. TIGAR blocks glycolysis and promotes cellular metabolism via the pentose phosphate pathway; it promotes the production of cellular nicotinamide adenine dinucleotide phosphate (NADPH), which leads to enhanced scavenging of intracellular reactive oxygen species, and inhibition of oxidative stressinduced apoptosis in normal cells. Our previous study identified a novel nucleoside analog that inhibited cellular growth and induced apoptosis in nasopharyngeal carcinoma (NPC) cell lines via downregulation of TIGAR expression. Furthermore, the growth inhibitory effects of cMet tyrosine kinase inhibitors were ameliorated by the overexpression of TIGAR in the NPC cell lines. These results indicate a significant role for TIGAR expression in the survival of NPCs. The present study aimed to further define the function of TIGAR expression in NPC cells. In total, 36 formalinfixed, paraffinembedded NPC tissue samples were obtained for the immunohistochemical determination of TIGAR expression. The effects of TIGAR expression on cell proliferation, NADPH production and cellular invasiveness were also assessed in NPC cell lines. Overall, TIGAR was overexpressed in 27/36 (75%) of the NPC tissues compared with the adjacent noncancer epithelial cells. Similarly, TIGAR overexpression was also observed in a panel of six NPC cell lines compared with normal NP460 hTert and Het1A cell lines. TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness of the NPC cell lines, whereas a knockdown of TIGAR expression resulted in significant inhibition of cellular growth and invasiveness. The expression of the two mesenchymal markers, fibronectin and vimentin, was increased by TIGAR overexpression, but reduced following TIGARknockdown. The present study revealed that TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness, and the maintenance of a mesenchymal phenotype, in NPC tissues.published_or_final_versio

Hybrid origin of "Bauhinia blakeana" (Leguminosae: Caesalpinioideae), inferred using morphological, reproductive, and molecular data

Bauhinia blakeana (Leguminosae subfam. Caesalpinioideae tribe Cercideae), or the Hong Kong Orchid Tree, is of great horticultural value. It is completely sterile and is shown here to be the result of hybridization between the largely sympatric species, B. purpurea and B. variegata. Although the analysis of patterns of morphological variation revealed only a few examples of phenotypic intermediacy, study of intersimple sequence repeat (ISSR) markers enabled unequivocal identification of the parental species due to the presence of additive inheritance of alleles and the absence of any bands that are unique to B. blakeana. Investigation of aspects of the reproductive biology of the taxa furthermore revealed that the parental species are largely xenogamous, have flowering periods that overlap seasonally and temporally, and share common pollinators. Evidence is provided to show that B. blakeana is not naturally stabilized and is only maintained horticulturally by artificial propagation. It is therefore recommended that the hybrid be regarded as a horticultural cultivar rather than a naturally occurring species; a new cultivar name, Bauhinia 'Blakeana', is accordingly validated.link_to_subscribed_fulltex

Floral biology, breeding systems and population genetic structure of three climbing bauhinia species (Leguminosae: Caesalpinioideae) in Hong Kong, China

The pollination ecology, breeding system and population genetic structure of three climbing Bauhinia species B. championii (4 populations, 23 individuals), B. corymbosa (2 populations, 25 individuals) and B. glauca (8 populations, 76 individuals) were studied in Hong Kong, southern China. We hypothesize that the climbing Bauhinia species will attract targeted pollinators to achieve out-cross success and high levels of self-incompatibility will be expected to maintain diversity, with local population expansion relying on vegetative propagation. All three species have inflorescences consisting of numerous small, pale, fragrant flowers, which show diurnal anthesis. Field observations revealed that all three species are predominantly pollinated by bees (particularly Apis mellifera) and butterflies (Graphium and Papilio species), although B. championii is also pollinated by wasps and flies. Bauhinia corymbosa and B. glauca have sucrose-dominant nectar, whereas B. championii has hexose-dominant nectar. In controlled-pollination experiments fruit and seed set were generally highest following artificial out-crossing. The index of self-incompatibility of B. championii is 1.07, indicating self-compatibility; B. corymbosa and B. glauca were obligately self-incompatible. The population genetic structure and variation of the Bauhinia species was investigated using ISSR markers. Generally the three species have moderate within-population (mean HS = 0.206) and high among-population genetic variation (mean GST = 0.284). No correlation exists between the geographical and genetic distance, possibly due to the small local population size. All three species showed high levels of heterozygosity as expected for predominantly out-crossing long-lived K-selected species. Copyright © 2009 Cambridge University Press.link_to_subscribed_fulltex

Increased expression of SPARC and SPARC-like 1 in relation to tumor angiogenesis in hepatocellular carcinoma

Background: Tumor angiogenesis, the growth of new blood vessels in tumor, is fundamental to tumor growth and metastasis of tumor cells. Our research group has identified two candidate genes for tumor angiogenesis, SPARC (Secreted Protein Acidic and Rich in Cysteine) and SPARC-like 1, in HCC through gene expression study using cDNA microarray technology. Objective: The aim of the present study was to quantify the expression of SPARC and SPARC-like 1 in HCC and to investigate the relationship between the expression of these genes and the increase in tumor angiogenesis in HCC. Methods: SPARC and SPARC-like 1 mRNA expression in HCC and nontumorous liver of 55 patients was quantitated by real-time RT-PCR. SPARC protein expression was assessed by immunohistochemical staining. The data were then correlated with the result of immunostaining for CD34, which is an endothelial cell marker for HCC angiogenesis. Result: Tumor SPARC mRNA level correlated significantly with tumor SPARC-like 1 mRNA level (p<0.001). Similarly, non-tumor SPARC mRNA level correlated significantly with non-tumor SPARC-like 1 mRNA level (p<0.001). This finding suggested that SPARC and SPARC-like 1 might be co-expressed. Further analysis using paired sample t test indicated that there was a significant difference between tumor and non-tumor SPARC mRNA level (mean 18.54 vs. 4.82, p<0.001). Likewise, there was a significant difference between tumor and non-tumor SPARC-like 1 mRNA level (mean 12.94 vs. 2.87, p<0.001). Immunohistochemical staining data indicated that tumor parenchymal SPARC protein expression was significantly correlated with tumor CD34 immunostaining (p<0.01). Similarly, tumor SPARC-like 1 mRNA expression was also significantly correlated with tumor CD34 immunostaining (p<0.05). Conclusions: Our results indicate that SPARC and SPARC-like 1 are overexpressed in HCC compared with nontumorous liver, and both genes may play a role in HCC angiogenesis

Quantitative correlation of serum levels and tumor expression of vascular endothelial growth factor in patients with hepatocellular carcinoma

Recent studies have suggested that serum levels of vascular endothelial growth factor (VEGF) may provide useful prognostic information in patients with various types of cancers. However, there has been a debate on whether serum VEGF level is a true reflection of tumor angiogenic activity in cancer patients. This debate originates from the finding that most VEGF in the serum is released from platelets during clotting. It has been postulated that platelet may serve the role of storage for circulating VEGF derived from the tumors. We conducted a study to clarify whether the platelet load of VEGF in the circulation correlates with tumor expression of VEGF. We measured quantitatively the serum VEGF 165 levels and tumor cytosolic VEGF 165 concentration by an ELISA and tumor VEGF 165 mRNA by real-time quantitative reverse transcription-PCR in 60 patients with hepatocellular carcinoma. Serum VEGF 165 levels correlated significantly with platelet counts (r = 0.662, P < 0.001). When corrected for platelet count, serum VEGF 165/platelet correlated significantly with tumor cytosolic VEGF 165 concentration (r = 0.447, P = 0.006), which in turn correlated with VEGF 165 mRNA expression in the tumors (r = 0.315, P = 0.020). Advancing tumor stage was associated with a significant increase in tumor cytosolic VEGF 165 concentration (P = 0.006), tumor VEGF 165 mRNA expression (P = 0.012), serum VEGF 165/platelet (P = 0.001), and serum VEGF 165 levels (P = 0.003). In conclusion, our data showed that the platelet load of VEGF in the circulation correlated positively with tumor VEGF expression. This study provides strong evidence that supports the use of serum VEGF level as an indirect estimate of tumor VEGF expression.link_to_subscribed_fulltex

SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma

Both Secreted Protein Acidic and Rich in Cysteine (SPARC) and Hevin are multifunctional matricellular glycoproteins. Recent experimental studies suggested that Hevin and SPARC together diminish angiogenesis, but their significance in hepatocellular carcinoma (HCC) remains unclear. This study aimed to correlate SPARC and Hevin expression with angiogenesis and clinicopathological features in HCC. SPARC and Hevin protein and mRNA expression in HCC specimens were assessed by immunostaining, immunoblotting, and quantitative reverse transcriptase-polymerase chain reaction. Tumour microvessel density (MVD) was assessed by CD34 immunostaining. The role of SPARC and Hevin in HCC was further assessed in an in vivo nude mice xenograft model. Both SPARC and Hevin mRNA levels were significantly higher in tumours than in non-tumourous livers. A significant correlation between tumour SPARC and Hevin mRNA levels was found. Moreover, SPARC protein localized in the tumour sinusoidal area correlated significantly with Hevin protein localized in HCC cells. Truncated forms of SPARC and Hevin proteins were detected in clinical samples. Truncated SPARC protein localized in the tumour sinusoidal area correlated significantly with tumour MVD. On the other hand, overexpression of full-length SPARC in tumour xenografts in athymic nude mice significantly delayed tumour growth, and this delay was related to a decrease in tumour angiogenesis. Expression of Hevin protein within HCC cells was related to the presence of tumour encapsulation and the absence of hepatitis B surface antigen in clinical samples. Overexpression of Hevin in tumour xenografts also significantly delayed tumour growth. In conclusion, this study has shown that SPARC and Hevin are upregulated in HCC compared with non-tumourous liver, and that they are inter-related at both mRNA and protein levels. Moreover, both SPARC and Hevin were related to HCC angiogenesis and tumour progression. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.link_to_subscribed_fulltex