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Biomedical subjects

Mark S Peterson

Publications and source records attributed to Mark S Peterson.

12 recordsLinked to original sources
PubMed2006

Repression of cap-dependent translation attenuates the transformed phenotype in non-small cell lung cancer both in vitro and in vivo.

Aberrant hyperactivation of the cap-dependent protein synthesis apparatus has been documented in a wide range of solid tumors, including epithelial carcinomas, but causal linkage has only been established in breast carcinoma. In this report, we sought to determine if targeted disruption of deregulated cap-dependent translation abrogates tumorigenicity and enhances cell death in non-small cell lung cancer (NSCLC). NSCLC cell lines were stably transfected with either wild-type 4E-BP1 (HA-4E-BP1) or the dominant-active mutant 4E-BP1(A37/A46) (HA-TTAA). Transfected NSCLC cells with enhanced translational repression showed pronounced cell death following treatment with gemcitabine. In addition, transfected HA-TTAA and HA-4E-BP1wt proteins suppressed growth in a cloning efficiency assay. NSCLC cells transduced with HA-TTAA also show decreased tumorigenicity in xenograft models. Xenograft tumors expressing HA-TTAA were significantly smaller than control tumors. This work shows that hyperactivation of the translational machinery is necessary for maintenance of the malignant phenotype in NSCLC, identifies the molecular strategy used to activate translation, and supports the development of lung cancer therapies that directly target the cap-dependent translation initiation complex.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Reducing the effects of dredged material levees on coastal marsh function: sediment deposition and nekton utilization.

Dredged material levees in coastal Louisiana are normally associated with pipeline canals or, more frequently, canals dredged through the wetlands to allow access to drilling locations for mineral extraction. The hydrologic impact on marshes behind the levee is of concern to coastal resource managers because of the potential impact on sediment transport and deposition, and the effect on estuarine organism access to valuable nursery habitat. This study examined the effects of gaps in dredged material levees, compared to continuous levees and natural channel banks, on these two aspects of marsh function. Field studies for sediment deposition were conducted biweekly for a year, and nekton samples were collected in spring and fall. Variation in nekton density among study areas and landscape types was great in part because of the inherent sampling gear issues and in part because of differences in characteristics among areas. Nekton densities were generally greater in natural compared to leveed and gapped landscapes. Differences in landscape type did not explain patterns in sediment deposition. The gaps examined appear to be too restrictive of marsh flooding to provide efficient movements of floodwaters onto the marsh during moderate flooding events. The "trapping" effect of the levees increases sediment deposition during extreme events. Gapping material levees may be an effective method of partially restoring upper marsh connection to nekton, but this method may work best in lower elevation marshes where nekton use is greater.

Disaster Planning↗
PubMed2005

Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP.

Cap-dependent translation is initiated by the binding of eIF4E to capped mRNA (m(7)GpppN). We have prepared a small library of 7-methyl guanosine nucleoside and nucleotide analogs and evaluated their ability to inhibit eIF4E binding to 7-methyl GTP with a competitive eIF4E binding immunoassay. 5'-H-Phosphonate derivatives in which the 2'- and 3'-riboside hydroxyls were tethered together by an isopropylidene group were shown to be a new class of inhibitors of eIF4E binding to capped mRNA.

3T3 Cells↗
PubMed2004

Translation initiation factor 4E blocks endoplasmic reticulum-mediated apoptosis.

Eukaryotic translation initiation factor 4E (eIF4E) is the mRNA cap-binding protein required for translation of cellular mRNAs utilizing the 5' cap structure. The rate-limiting factor for mRNA recruitment to ribosomes, eIF4E is a major target for regulation of translation by growth factors, hormones, and other extracellular stimuli. When overexpressed, eIF4E exerts profound effects on cell growth and survival, leading to suppression of oncogene-dependent apoptosis, causing malignant transformation and conferring tumors with multiple drug resistance. We found previously that overexpressed eIF4E interdicts the apoptotic pathway induced by growth factor withdrawal and cytotoxic drugs by selectively activating the expression of Bcl-X(L), thus preventing mitochondrial release of cytochrome c. In this study, we examined the impact of ectopic eIF4E expression on apoptosis mediated by the endoplasmic reticulum (ER). Here we show that eIF4E rescued cells from the ER stressors brefeldin A, tunicamycin, thapsigargin, and the Ca(2+) ionophore A23187. In addition, we found that cells rescued from Ca(2+) ionophore-triggered apoptosis did not release calcium from their ER nor did they translocate caspase-12 from the ER to the cytoplasm. These data lend strong support to the concept that eIF4E functions as a pleiotropic regulator of cell viability and that integration of critical organelle-mediated checkpoints for apoptosis can be controlled by the cap-dependent translation apparatus.

3T3 Cells↗
PubMed2003

Measuring responses to simulated predation threat using behavioral and physiological metrics: the role of aquatic vegetation.

An organism's daily activities are affected by predation and predation risk that have behavioral and physiological costs, which translate into long-term population and community consequences. We tested the hypothesis that the perception of predation risk from sand seatrout, Cynoscion arenarius, affects the behavior, and immediate and intermediate physiological responses of longnose killifish, Fundulus majalis. We further hypothesized that prey responses change if prey are buffered by artificial submerged aquatic vegetation (SAV), a potential refuge from predators. Experiments were conducted to quantitatively estimate the behavior, plasma cortisol (PC) concentration, mass-specific oxygen consumption, and short-term growth rate changes relative to full, partial, and no visual exposure to the predator. The partial visual exposure treatment involved the use of artificial SAV. Our results indicate that there are significant behavior and physiological responses of longnose killifish to predation threat. Longnose killifish in the full visual and partial exposure treatments displayed different behaviors than the control treatments by shifting towards the rear of the aquaria. In addition, longnose killifish in the full visual exposure compared to the partial exposure and the control treatments responded by exhibiting an elevation of PC and mass-specific oxygen consumption rate, and through decreased short-term growth. These responses were less intense in the partial exposure, when artificial SAV was present. The significance of this study is that it examines a suite of responses from cellular to the whole-organism level as they are affected by predation threat and modified by the presence or absence of artificial SAV.

Animals↗
PubMed2003

Helical CT screening for hepatocellular carcinoma in patients with cirrhosis: frequency and causes of false-positive interpretation.

OBJECTIVE: The purpose of our study was to determine the specificity of helical CT for depiction of hepatocellular carcinoma in a population of patients with cirrhosis. SUBJECTS AND METHODS: Single-detector helical CT screening was undertaken in 1329 patients with cirrhosis who were referred for transplantation. The patients underwent one or more helical CT examinations over 30 months and were followed up for an additional 19 months or until transplantation. We predominantly used unenhanced and biphasic contrast-enhanced techniques with infusions of 2.5-5.0 mL/sec. Four hundred thirty patients underwent transplantation within this period. Liver specimens were sectioned at 1-cm intervals, with direct comparison of imaging and pathologic findings and histologic confirmations of all lesions. Prospective preoperative helical CT reports were used for the primary data analysis. A retrospective unblinded review was undertaken to determine characteristics of false-positive lesions diagnosed as hepatocellular carcinoma. RESULTS: Thirty-five patients (8%) had false-positive diagnoses for hepatocellular carcinoma based on helical CT. Twenty of these patients (5%) showed hypoattenuating lesions seen during one of the three helical CT examination phases. Fifteen patients (3%) had hyperattenuating lesions seen during the arterial phase. Among the 15 hyperattenuating lesions, CT revealed the causes to be transient benign hepatic enhancement (n = 3), hemangiomas (n = 2), fibrosis (n = 2), peliosis (n = 1), volume averaging (n = 1), low-grade dysplastic nodule (n = 1), or undetermined (n = 5). Of the 20 hypoattenuating lesions, the causes were shown to be fibrosis (n = 8), focal fat (n = 4), infarcted regenerative nodules (n = 2), regenerative nodules (n = 1), fluid trapped at the dome of the liver (n = 1), hemangioma (n = 1), or undetermined (n = 3). Follow-up helical CT in 13 (72%) of 18 patients allowed a change in the diagnosis of hepatocellular carcinoma to a finding of no cancer present. CONCLUSION: Helical CT screening for hepatocellular carcinoma in patients with cirrhosis has a substantial false-positive detection rate. Although most of lesions were hypoattenuating, a few hyperenhancing arterial phase lesions were proven not to be hepatocellular carcinoma. An awareness of imaging characteristics and follow-up imaging can help radiologists avoid a mistaken diagnosis in many patients.

Adolescent↗
PubMed2002

Translation factor eIF4E rescues cells from Myc-dependent apoptosis by inhibiting cytochrome c release.

Eukaryotic translation initiation factor 4E (eIF4E) markedly reduces cellular susceptibility to apoptosis. However, the mechanism by which the translation apparatus operates on the cellular apoptotic machinery remains uncertain. Here we show that eIF4E-mediated rescue from Myc-dependent apoptosis is accompanied by inhibition of mitochondrial cytochrome c release. Experiments achieving gain and loss of function demonstrate that eIF4E-mediated rescue is governed by pretranslational and translational activation of bcl-x as well as by additional intermediates acting directly on, or upstream of, the mitochondria. Thus, our data trace a pathway controlling apoptotic susceptibility that begins with the activity state of the protein synthesis machinery and leads to interdiction of the apoptotic program at the mitochondrial checkpoint.

Animals↗
PubMed2002

Imaging the spectrum of biliary tract disease.

An understanding of underlying biliary pathology and the corresponding subtle changes reflected at imaging can greatly improve imaging accuracy in evaluating the biliary tract. The optimal demonstration of biliary tract imaging findings requires attention to specific imaging and contrast techniques, regardless of the modality used.

Bile Duct Neoplasms↗
PubMed2002

Intrahepatic biliary anatomy of living adult liver donors: correlation of mangafodipir trisodium-enhanced MR cholangiography and intraoperative cholangiography.

OBJECTIVE: The purpose of our study was to assess the usefulness of mangafodipir trisodium-enhanced MR cholangiography for evaluating intrahepatic biliary anatomy of adult living liver donors and to correlate the results with intraoperative cholangiography. CONCLUSION: Mangafodipir trisodium-enhanced MR cholangiography accurately shows the biliary anatomy in the livers of donors. Noninvasive preoperative evaluation of the biliary anatomy in donor candidates is important for the detection of common anatomic variants that may require alternative graft-harvesting surgery.

Adult↗