506 research outputs found

    Effects of Diabetes and Insulin on α-amylase Messenger RNA Levels in Rat Parotid Glands

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    Previous studies have shown that amylase levels are reduced significantly in the pancreas and parotid gland of diabetic rats and that insulin reverses this effect and increases the secretory protein levels. In the pancreas, these changes in amylase protein levels are accompanied by parallel changes in amylase mRNA levels. In the present study, the effects of diabetes and subsequent insulin treatments on contents (per cell) of amylase protein and its mRNA in parotid glands were compared in rats rendered diabetic with an injection of a beta-cell toxin, streptozotocin (STZ). Both amylase protein and its mRNA contents were reduced significantly in diabetic rats, compared with control rats, and this reduction was reversed following insulin injections of diabetic rats. In insulin-injected diabetic rats, amylase protein contents increased before a detectable increase in amylase mRNA levels was seen. The mRNA contents of a non-secretory protein, actin, did not change during diabetogenesis or subsequent insulin treatments. The reductions in parotid contents of amylase and its mRNA in diabetic rats and the reversal of these changes by insulin are similar to those changes that occur in the pancreas under the same conditions. However, the magnitude of these changes in parotid glands was much smaller than in the pancreas, and the effect of insulin on amylase mRNA synthesis was not as immediate as in the latter gland.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67977/2/10.1177_00220345900690081001.pd

    DC-SCRIPT is a novel regulator of the tumor suppressor gene CDKN2B and induces cell cycle arrest in ERα-positive breast cancer cells

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    Breast cancer is one of the most common causes of cancer-related deaths in women. The estrogen receptor (ERα) is well known for having growth promoting effects in breast cancer. Recently, we have identified DC-SCRIPT (ZNF366) as a co-suppressor of ERα and as a strong and independent prognostic marker in ESR1 (ERα gene)-positive breast cancer patients. In this study, we further investigated the molecular mechanism on how DC-SCRIPT inhibits breast cancer cell growth. DC-SCRIPT mRNA levels from 190 primary ESR1-positive breast tumors were related to global gene expression, followed by gene ontology and pathway analysis. The effect of DC-SCRIPT on breast cancer cell growth and cell cycle arrest was investigated using novel DC-SCRIPT-inducible MCF7 breast cancer cell lines. Genome-wide expression profiling of DC-SCRIPT-expressing MCF7 cells was performed to investigate the effect of DC-SCRIPT on cell cycle-related gene expression. Findings were validated by real-time PCR in a cohort of 1,132 ESR1-positive breast cancer patients. In the primary ESR1-positive breast tumors, DC-SCRIPT expression negatively correlated with several cell cycle gene ontologies and pathways. DC-SCRIPT expression strongly reduced breast cancer cell growth in vitro, breast tumor growth in vivo, and induced cell cycle arrest. In addition, in the presence of DC-SCRIPT, multiple cell cycles related genes were differentially expressed including the tumor suppressor gene CDKN2B. Moreover, in 1,132 primary ESR1-positive breast tumors, DC-SCRIPT expression also correlated with CDKN2B expression. Collectively, these data show that DC-SCRIPT acts as a novel regulator of CDKN2B and induces cell cycle arrest in ESR1-positive breast cancer cells

    Past decade above-ground biomass change comparisons from four multi-temporal global maps

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    Above-ground biomass (AGB) is considered an essential climate variable that underpins our knowledge and information about the role of forests in mitigating climate change. The availability of satellite-based AGB and AGB change (Delta AGB) products has increased in recent years. Here we assessed the past decade net Delta AGB derived from four recent global multi-date AGB maps: ESA-CCI maps, WRI-Flux model, JPL time series, and SMOS-LVOD time series. Our assessments explore and use different reference data sources with biomass re-measurements within the past decade. The reference data comprise National Forest Inventory (NFI) plot data, local Delta AGB maps from airborne LiDAR, and selected Forest Resource Assessment country data from countries with well-developed monitoring capacities. Map to reference data comparisons were performed at levels ranging from 100 m to 25 km spatial scale. The comparisons revealed that LiDAR data compared most reasonably with the maps, while the comparisons using NFI only showed some agreements at aggregation levels <10 km. Regardless of the aggregation level, AGB losses and gains according to the map comparisons were consistently smaller than the reference data. Map-map comparisons at 25 km highlighted that the maps consistently captured AGB losses in known deforestation hotspots. The comparisons also identified several carbon sink regions consistently detected by all maps. However, disagreement between maps is still large in key forest regions such as the Amazon basin. The overall AAGB map cross-correlation between maps varied in the range 0.11-0.29 (r). Reported AAGB magnitudes were largest in the high-resolution datasets including the CCI map differencing (stock change) and Flux model (gain-loss) methods, while they were smallest according to the coarser-resolution LVOD and JPL time series products, especially for AGB gains. Our results suggest that AAGB assessed from current maps can be biased and any use of the estimates should take that into account. Currently, AAGB reference data are sparse especially in the tropics but that deficit can be alleviated by upcoming LiDAR data networks in the context of Supersites and GEO-Trees

    Rearranged EML4-ALK fusion transcripts sequester in circulating blood platelets and enable blood-based crizotinib response monitoring in non-small-cell lung cancer

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    Purpose: Non-small-cell lung cancers harboring EML4-ALK rearrangements are sensitive to crizotinib. However, despite initial response, most patients will eventually relapse, and monitoring EML4-ALK rearrangements over the course of treatment may help identify these patients. However, challenges associated with serial tumor biopsies have highlighted the need for blood-based assays for the monitoring of biomarkers. Platelets can sequester RNA released by tumor cells and are thus an attractive source for the non-invasive assessment of biomarkers. Methods: EML4-ALK rearrangements were analyzed by RT-PCR in platelets and plasma isolated from blood obtained from 77 patients with non-small-cell lung cancer, 38 of whom had EML4-ALK-rearranged tumors. In a subset of 29 patients with EML4-ALK-rearranged tumors who were treated with crizotinib, EML4-ALK rearrangements in platelets were correlated with progression-free and overall survival. Results: RT-PCR demonstrated 65% sensitivity and 100% specificity for the detection of EML4-ALK rearrangements in platelets. In the subset of 29 patients treated with crizotinib, progression-free survival was 3.7 months for patients with EML4-ALK+ platelets and 16 months for those with EML4-ALK− platelets (hazard ratio, 3.5; P = 0.02). Monitoring of EML4-ALK rearrangements in the platelets of one patient over a period of 30 months revealed crizotinib resistance two months prior to radiographic disease progression. Conclusions: Platelets are a valuable source for the non-invasive detection of EML4-ALK rearrangements and may prove useful for predicting and monitoring outcome to crizotinib, thereby improving clinical decisions based on radiographic imaging alone
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