PCNA levels in neuroblastoma are increased in tumors with an amplified N- myc gene and in metastatic stage tumors

N- myc oncogene amplification in neuroblastoma has been found to be significantly associated with advanced stage disease and tumor progression. However, there is a lack of data on tumors, regarding the relationship between N- myc gene amplification and proliferation activity. Proliferating cell nuclear antigen (PCNA) is a proliferation-induced 36 kD nuclear protein that is the auxiliary component of DNA polymerase δ. PCNA levels in tissues have been found to correlate with proliferative activity. We have examined PCNA levels in neuroblastomas in relation to N- myc gene amplification and tumor stage. Statistically, significantly higher levels of PCNA were observed in tumors with an amplified N- myc gene relative to tumors with a single gene copy. The highest levels of PCNA were observed in advanced stage tumors with an amplified N- myc gene. Treatment of neuroblastoma cells in culture with retinoic acid, which induces differentiation, resulted in a substantial decrease in PCNA. Our results suggest that PCNA levels may reflect differences in proliferative activity between neuroblastomas, related to stage of the disease and to N- myc gene copy number.[/p ]Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42581/1/10585_2004_Article_BF00880069.pd

Belt and Road Initiative in Central Asia: Anticipating socioecological challenges from large‐scale infrastructure in a global biodiversity hotspot

Until recently, China's Belt and Road Initiative (BRI) has overlooked many of the social and environmental dimensions of its projects and actions in favor of more immediate economic and sociopolitical considerations. The main focus of investments under BRI has largely been to improve transport, telecommunication, and energy infrastructures. However, in Central Asia, biodiversity is not only foundational for the livelihoods and socioeconomic wellbeing of communities, it also shapes people's culture and identities. Furthermore, ecosystem services derived from functioning landscapes bring enormous benefit for millions of people downstream through integrated and transboundary water systems. Already under pressure from climate-induced melting of glaciers, the fate of ecologically important areas is considered in light of the potential harm arising from large-scale linear infrastructure projects and related investments under China-led BRI. Following review of some of the anticipated impacts of BRI on mountain environments and societies in the region, we highlight several emerging opportunities and then offer recommendations for development programs—aiming fundamentally to enhance the sustainability of BRI investments. Leveraging new opportunities to strengthen partner countries’ priority Sustainable Development Goals and enhancing their agency in the selection of collaborations and the standards to use in environmental impact and risk assessments are recommended

Glutathione S-transferase GSTT1 genotypes and susceptibility to cancer: studies of interactions with GSTM1 in lung, oral, gastric and colorectal cancers

Allelism in glutathione S-transferase GSTM1 and GSTT1 has been suggested as a risk factor in various cancers. Accordingly, we describe a group of case-control studies carried out to identify associations between GSTT1 genotypes and susceptibility to lung, oral, gastric and colorectal cancers. The frequencies of the putatively high risk GSTT1 null genotype were not increased in the lung, oral or gastric cancer cases compared with controls but the frequency of this genotype was significantly increased (P = 0.0011, odds ratio = 1.88) in the colorectal cancer cases. No significant interactions between the GSTT1 and GSTM1 null genotypes were identified in the cancer groups studied. Indeed, no significant associations between GSTM1 genotypes and susceptibility were identified though further evidence was obtained that the protective effect of GSTM1*A and GSTM1*B is not equal. The data complement studies showing that GSTT1 null is associated with an increased susceptibility to total ulcerative colitis and suggests that this enzyme is important in the detoxification of unidentified xenobiotics in the large intestine