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Years and Volumes

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Articles from this Volume

Rong Wu, Salvatore J Coniglio, Amanda Chan, Marc H Symons, and Bettie M Steinberg

Recurrent respiratory papillomas (RRP) are epithelial tumors of the airway caused by human papillomaviruses. Papilloma cells overexpress the epidermal growth factor receptor (EGFR) and signal transduction pathways linked to EGFR are altered in papilloma cells contributing to abnormal differentiation.  Cyclooxygenase-2 (COX-2) expression is elevated in respiratory papilloma tissues and requires EGFR and phosphatidylinositol 3-kinase (PI3K) activity.  However, the EGFR-Mek-Erk pathway plays no role in induction of COX-2 in papilloma cells, suggesting that one or more other pathways is involved in these cells.  Wu et al. (143-150) postulated that a Rac1-dependent pathway may play a role in the induction of COX-2 in papilloma cells.  Results show that Rac1 is overexpressed in papilloma cells, that overexpression is due to increased EGFR signaling and that Rac1 mediates induction of COX-2 in part through activation of p38.  This pathway is specific to papilloma cells and does not function in normal laryngeal cells.  A detailed understanding of this mechanism may lead to therapeutic targets for recurrent respiratory papillomas.


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Posted by Leah Caracappa on Mar 2, 2007 12:00 AM CST
Veronika Miskolci, Janet Rollins, Hai Yen Vu, Chandra C Ghosh, Dennis Davidson, and Ivana Vancurova

Increased activation of the transcription factor NF-kB in neutrophils has been associated with the pathogenesis of sepsis, acute lung injury (ALI), bronchopulmonary dysplasia (BPD) and other neutrophil-mediated inflammatory disorders. Despite recent progress in analyzing early NF-kB activation in human neutrophils, mechanisms of NF-kB activation in persistently stimulated neutrophils remain unknown. Persistent NF-kB activation is believed to be involved in the host response to sepsis and the pathogenesis of ALI and BPD. Miskolci et al. (134-142) analyzed NF-kB activation and expression of IkB and NF-kB proteins during neutrophil stimulation with inflammatory signals for prolonged periods. Data suggest that NF-kB is persistently activated in human neutrophils during neutrophil-mediated inflammatory disorders. This persistent NF-kB activity may represent one of the underlying mechanisms for the continuous production of pro-inflammatory mediators. Understanding the mechanisms regulating initiation and persistence of NF-kB activation in human neutrophils may provide new information for the development of early detection and safer therapies for ALI, BPD, sepsis and other neutrophil-mediated inflammatory disorders.

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Posted by Leah Caracappa on Mar 1, 2007 12:00 AM CST
Donato Gemmati, Federica Federici, Gianluca Campo, Silvia Tognazzo, Maria L Serino, Monica De Mattei, Marco Valgimigli, Patrizia Malagutti, Gabriele Guardigli, Paolo Ferraresi, Francesco Bernardi, Roberto Ferrari, Gian L Scapoli, and Linda Catozzi

Despite recent developments, the frequency of adverse cardiac events after myocardial infarction (MI) remains a significant clinical problem.  Recent studies and case reports have shown the coagulation factor XIII (FXIII) plays a beneficial role in myocardial healing after infarction and improves survival in mice and humans.  Low circulating levels of FXIII were associated with the worst clinical outcome after myocardial infarction.  Common FXIII gene variants, such as FXIIIA-V34L and FXIIIB-H95R significantly influence the molecule activity.  To evaluate the relationship between the two gene variants and survival in patients after myocardial MI, Gemmati et al. (112-120) PCR-genotyped a cohort of 560 MI cases for the V34L and H95R and monitored follow-up. The authors conclude that the FXIII L34-allele improves survival after MI in all groups analyzed, potentially through the L34- associated higher activity with positive effects on myocardial healing and recovered functions. These results pave the way for the manipulation of FXIII molecules to improve myocardial healing, recovery of functions, and survival after infarction.

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Posted by Leah Caracappa on Feb 6, 2007 12:00 AM CST
Simona Vittorini, Simona Storti,  Maria Serena Parri, Alfredo Giuseppe Cerillo, and Aldo Clerico

Human conotruncal heart defects are congenital heart defects affecting cardiac outflow.  The cardiac neural crest, which consists of a specific neural cell crest population, is responsible for the morphogenesis of the outflow region of the developing heart and conotruncal heart defects are due to alterations in this area.  Abnormal calcium sensitivity of the contractile apparatus and a depressed L-type calcium current have been observed in animal models of conotruncal heart defects.  Here, Vittorini et al. (105-111), analyzed the relationship between congenital heart defects and myocardial calcium handling in humans by analyzing gene expression of proteins (SERCA2a, PLN and SLN) and receptors (RyR2) involved in calcium handling.  Data suggest a complex mechanism aimed to enhance the intracellular calcium reserve in children affected by tetralogy of Fallout, a conotruncal heart defect.  Results of this study indicate that the use of array technology may be a beneficial approach for future investigations allowing for a better understanding and identification of integrated messages.

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Posted by Leah Caracappa on Feb 5, 2007 12:00 AM CST
Naoki Fujita, Ryosuke Sugimoto, Masaki Takeo, Naohito Urawa, Rumi Mifuji,Hideaki Tanaka, Yoshinao Kobayashi, Motoh Iwasa, Shozo Watanabe, Yukihiko Adachi, and Masahiko Kaito

Iron is required for metabolic processes and is tightly regulated in all organisms.  Excess iron deposition in the liver is known to be hepatotoxic, may exacerbate liver injury and be resistant to interferon-based therapy in patients with chronic hepatitis.  Hepatic iron overload has become more common among patients with end-stage liver disease due to hepatitis and little is known regarding this mechanism.  Hepcidin, exclusively synthesized in the liver is thought to be a key regulator of iron homeostasis and is induced by infection and inflammation.  Here, Fujita et al. (97-104) measured gene expression of hepcidin in liver samples from patients with various liver conditions and assessed the relationship with clinical, hematological, histological and etiological findings.  Analysis revealed that hepcidin may play a pivotal role in the pathogenesis of iron overload in patients with chronic hepatitis C.  Management of hepcidin levels may prove to be beneficial for patients with chronic hepatitis C.

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Posted by Leah Caracappa on Feb 4, 2007 12:00 AM CST
Vittorio Di Maso, Claudio Avellini, Lory Crocè, Gianluca Tell, Natalia Rosso, Franco Quadrifoglio, Laura Cesaratto, Erika Codarin, Giorgio Bedogni, Carlo Beltrami, and Claudio Tiribelli

Hepatocellular carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the third cause of cancer-estimated deaths.  Its development is generally the final event of long-standing liver disease.  The molecular events related to hepatocarcinogenesis have not been well described although a strong body of evidence suggests a critical role for reactive oxygen species (ROS).  Increased levels of ROS promote oxidative stress damage and may be involved in the development of HCC.  Apurinic apyrimidinic endonuclease/redox effector factor 1 (APE/Ref-1) is a regulator of cellular response to oxidative stress conditions and is involved in transcriptional regulation and base excision repair.  Here, Di Maso et al. (89-96) assess the expression of APE1/Ref-1 in hepatocellular carcinoma and surrounding liver cirrhosis.  Results indicate a possible role of APE1/Ref-1 over-expression in the development of HCC and indicate that the sub-cellular localization of APE1/Ref-1 in HCC tissue might be used as a prognostic marker for this wide spread disease.

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Posted by Leah Caracappa on Feb 3, 2007 12:00 AM CST
Galatea Kallergi, Dimitris Mavroudis, Vassilis Georgoulias and Christos Stournaras

The development of metastasis in cancer is one of the most important factors determining the long-term outcome of the disease.  Studies have shown that the detection of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) represents a strong and independent predictive and prognostic factor for a decreased disease-free period and overall survival.  Several markers have been used to detect CTCs in the peripheral blood of patients with breast cancer.  However, analysis of activated signaling kinases in CTC’s, implicated in cellular transformation, migration and survival has not been addressed.  Here, Kallergi et al. (79-88) used immunofluorescence microscopy to analyze expression of the kinases FAK and PI-3 in peripheral blood from 45 breast cancer patients’ CTC’s. The findings provide strong evidence that micrometastatic cells express activated signaling kinases, which may regulate migration mechanisms, supporting the presumption of their malignant and metastatic nature.  Analysis of phosphorylated FAK in peripheral blood may represent a new marker for the detection of micrometastatic cells in breast cancer patients as well as a target for therapy.

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Posted by Leah Caracappa on Feb 2, 2007 12:00 AM CST
Laura Mulvey, Alamelu Chandrasekaran, Kai Liu, Sara Lombardi, Xue-Ping Wang, Karen J Auborn, and Leslie Goodwin

The risk of breast cancers is inversely proportional to the amount of cruciferous vegetables in one’s diet. High levels of estrogen have been shown to increase the risk of breast cancer, and diindolylmethane (DIM), a biologically active phytochemical derived from cruciferous vegetables, is a promising agent for the prevention of estrogen-sensitive cancers. In order to better understand the complexity of gene regulation by DIM and estradiol (E2), Mulvey et al. (69-78) analyzed gene expression using microarray profiling and quantitative real time PCR in a breast cancer cell line.  The interplay of DIM and E2 was reflected in the expression of a subset of genes in which the combination of DIM and E2 acted either additively or antagonistically to alter gene expression.  An understanding of these interactions and the subsequent changes in gene expression which occur enhance present knowledge regarding DIM and its use in the prevention of estrogen-sensitive cancers.

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Posted by Leah Caracappa on Feb 1, 2007 12:00 AM CST
Emily Baechler, Jason Bauer, Catherine Slattery, Ward Ortmann, Karl Espe, Jill Novitzke, Steve Ytterberg, Peter Gregersen, Timothy Behrens, and Ann Reed

Juvenile and adult dermatomyositis (DM) are rare autoimmune diseases belonging to the group of idiopathic inflammatory myopathies characterized by proximal muscle weakness and muscle inflammation.  Although the cause is unknown, it is believed that a combination of genetic and environmental factors contribute to the disease. Expression of interferon (IFN)-regulated genes is elevated in affected muscle tissue from patients with DM but it has not yet been determined if this signature extends to the peripheral blood in DM.  Here, Baechler et al. (59-68) perform global gene expression profiling of peripheral blood cells from adult and juvenile DM patients and healthy controls.  Investigation of IFN-regulated transcripts revealed a striking IFN signature present in most DM patients studied. Additionally, the transcript and serum protein IFN signatures were associated with disease activity.  These data suggest that the IFN signature in peripheral blood may be a useful marker for DM disease activity and a practical alternative to invasive muscle biopsy.

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Table S1   Table S2

 

Posted by Leah Caracappa on Jan 6, 2007 12:00 AM CST
Christopher J Edwards, Jeffrey L Feldman, Jonathan Beech, Kathleen M Shields, Jennifer A Stover, William L Trepicchio, Glenn Larsen, Brian MJ Foxwell, Fionula M Brennan, Marc Feldmann, and Debra D Pittman

Rheumatoid arthritis (RA) is a chronic inflammatory disease causing synovial joint damage, disability and a shortened life expectancy.  An awareness of the destructive potential of RA has lead to more aggressive use of disease-modifying anti-rheumatic drugs.  Currently, diagnosis of RA may take several weeks and factors used to predict a poor prognosis are not always reliable.  Recent studies have demonstrated that unique gene expression changes can be identified in peripheral blood mononuclear cells (PBMCs) from patients with cancer, multiple sclerosis and lupus.  Gene expression analysis has been applied to synovial tissue to define molecularly distinct forms of RA, however, extracting tissue from a synovial joint is invasive and clinically impractical.  Here, Edwards et al. (40-58) performed a global gene expression analysis on PBMCs from RA patients and normal volunteers.  Ten genes with increased expression in RA PBMCs compared with controls, mapped to a RA susceptibility locus.  These results suggest that analysis of RA peripheral blood at the molecular level may provide a set of candidate genes that could yield an easily accessible gene signature to aid in early diagnosis and treatment.

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Posted by Leah Caracappa on Jan 5, 2007 12:00 AM CST
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