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Articles from this Volume

 
Review Article

Mark C Ledesma, Brittney Jung-Hynes, Travis L Schmit, Raj Kumar, Hasan Mukhtar,
and Nihal Ahmad
 
Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men globally. Selenium and vitamin E are essential components of the human diet and have been studied as antioxidants and/or potential agents for a variety of human diseases. The Selenium and Vitamin E Cancer Prevention Trial (SELECT) is a phase III, randomized placebo-controlled human trial to investigate the PCa chemopreventive effects of selenium, vitamin E, or their combination. The SELECT, that involved 35,533 men and an intended follow-up of up to 12 years is the largest clinical chemoprevention trials ever. Ledesma et al. review the unsuccessful outcomes of the SELECT in detail in this article. They suggest that an improved understanding of selenium and vitamin E biology may facilitate the discovery of these doses and formulations. 

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Posted by MolMed Editor on Feb 9, 2011 12:00 AM CST
Review Article

Akihisa Matsuda, Asha Jacob, Rongqian Wu, Mian Zhou, Jeffrey M Nicastro, Gene F Coppa, and Ping Wang

 
Sepsis and ischemia-reperfusion (I/R) injury are among the leading causes of disability and death in the surgical intensive care setting. During both conditions, there is a large pro-inflammatory response generated by the body, which leads to increased apoptosis and necrosis. Milk fat globule-EGF factor VIII (MFG-E8), which is mainly produced by macrophages and dendritic cells, serves as a bridging molecule between apoptotic cells and macrophages. It has been shown that the levels of MFG-E8 are decreased in experimental sepsis and I/R injury models. Matsuda et al. have summarized the work done with MFG-E8 in these models and provide good evidence that the morbidity and mortality associated with sepsis and I/R injury may be attenuated by MFG-E8, and may be developed as a potential therapy in the clinical setting. 

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Posted by MolMed Editor on Feb 8, 2011 12:00 AM CST
Review Article

Gerd G Gauglitz, Hans C Korting, Tatiana Pavicic, Thomas Ruzicka, and Marc G Jeschke
 
When normal wound healing goes awry, excessive scarring can result and thereby significantly decrease a patient's quality of life. In the developed world alone, 100 million patients develop scars following such events as burn injury, lacerations, abrasions, surgery, piercings and vaccinations. The development of keloids and hypertrophic scars - both fibroproliferative disorders – is not well understood owing to an absence of effective human clinical models and an incomplete definition of the complex cell and molecular mechanisms involved. In this review, Gauglitz et al. summarize the pathophysiology underlying keloid and hypertrophic scar formation and discuss established treatments and novel therapeutic strategies.

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Posted by MolMed Editor on Feb 7, 2011 12:00 AM CST
Ilya V Ulasov, Suvobroto Nandi, Mahua Dey, Adam M Sonabend, and Maciej S Lesniak
 
Malignant gliomas tend to be highly refractory to traditional cancer treatments, such as chemotherapy. The most commonly used therapeutic agent, temozolomide (TMZ), is thought to have limited efficacy in part because of the presence and activity of CD133+ cancer stem cells. Ulasov et al. argue that SHH and Notch signaling may be important for maintenance of CD133+ glioma cells and that these pathways could enhance glioma cell resistance to TMZ. The authors found that Notch and SHH activity in CD133+ cells was indeed enhanced by TMZ exposure. They also demonstrate increased efficacy of TMZ therapy in the presence of pharmacological antagonism of Notch and SHH pathways. Since this primary treatment modality currently has a modest effect in only a subset of patients, these findings might lead to markedly improved therapies for glioma patients.

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Supplementary Data PDF
Posted by MolMed Editor on Feb 6, 2011 12:00 AM CST
J William Lindsey, Sandeep K Agarwal, and Filemon K Tan
 
Multiple sclerosis (MS), an inflammatory and demyelinating disease of the central nervous system, is thought to be immune-mediated. A key characteristic of MS is fluctuating disease activity, with clinical relapses separated by remissions. The immunologic events leading to relapse are not well defined, and a better understanding of these events may lead to new treatment strategies. Here, Lindsey et al. utilized microarrays to investigate gene expression of T and non-T cells in relapsing and remitting MS patients. They found 71 genes with expression differences between the relapsing and remitting samples. Observed changes in gene expression suggest an activation of non-T cells and changes in function of T cells in MS relapse. A better understanding of the events underlying relapse may lead to new treatment approaches for MS.

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Posted by MolMed Editor on Feb 5, 2011 12:00 AM CST
Suhail Akhtar, Xiaoling Li, Elizabeth J Kovacs, Richard L Gamelli, and Mashkoor A Choudhry
 
Approximately one million burn injuries are reported every year in the U.S. and nearly half of those occur in individuals who are under the influence of alcohol. Evidence suggests burn patients intoxicated at the time of injury are more susceptible to infection and carry a higher mortality rate. Interleukin-18 (IL-18) has been shown to play a key role in neutrophil recruitment to the intestine and lungs following alcohol intoxication and burn injury. In this work, Akhtar et al. examined an experimental model of alcohol intoxication and burn injury to determine if burn injury influences neutrophil apoptosis and whether IL-18 plays a role in this setting. Their findings suggest IL-18 delays neutrophil apoptosis by modulating pro-and antiapoptotic proteins. This research indicates therapies designed to inhibit IL-18 release may decrease neutrophil survival and lessen injury.

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Posted by MolMed Editor on Feb 4, 2011 12:00 AM CST
Eric Pasmant, Julien Masliah-Planchon, Pascale Lévy, Ingrid Laurendeau, Nicolas Ortonne, Béatrice Parfait, Laurence Valeyrie-Allanore, Karen Leroy, Pierre Wolkenstein, Michel Vidaud, Dominique Vidaud, and Ivan Bièche
 
Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder affecting 1 in 3000 individuals worldwide. While most patients have a small mutation in the NF1 gene, approximately 5% of patients have an NF1 microdeletion, encompassing 18 additional genes. NF1-microdeleted patients exhibit a more severe phenotype than general NF1 patients and have an increased risk of developing malignant peripheral nerve sheath tumors (MPNSTs). Pasmant et al. postulate this may be due to inactivation of a second tumor suppressor gene located in the microdeletion region. The authors investigated the expression profile of 18 genes located in the NF1 microdeletion region in NF1 patients. Several genes which may lead to an increased risk of malignancy in NF1 patients were identified. Two genes were significantly downssregulated in MPNST biopsies and cell lines indicating potential involvement in increased malignancy in these patients. Future studies will be aimed at further understanding this mechanism.

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Supplementary Data PDF
Posted by MolMed Editor on Feb 3, 2011 12:00 AM CST
Naoki Fujita, Mamoru Nakanishi, Jun Mukai, Yuuji Naito, Takafumi Ichida,Masahiko Kaito, Toshikazu Yoshikawa, and Yoshiyuki Takei
 
Chronic hepatitis C (CHC) is among the leading causes of chronic liver disease worldwide with severity varying from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Although combination therapy has been established as an effective therapy for chronic hepatitis C virus infection (HCV), 20% of patients are non-virological responders. Mechanisms responsible for resistance have not been fully elucidated and it is difficult to predict treatment response prior to therapy initiation. Here, Fujita et al. use a ProteinChip array coupled with SELDI-TOF/MS to investigate the global serum protein profile of chronic HCV patients treated with combination therapy. Results indicate differences between responders and non-virological responders and indicate protein profile analysis may be useful for predicting treatment response. This data aids in understanding the mechanisms underlying resistance and may lead to development of more effective antiviral therapies in CHC patients.

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Posted by MolMed Editor on Feb 2, 2011 12:00 AM CST
Chun Xi Liu, Qin Hu, Yan Wang, Wei Zhang, Zhi Yong Ma, Jin Bo Feng, Rong Wang, Xu Ping Wang, Bo Dong, Fei Gao, Ming Xiang Zhang, and Yun Zhang
 
Diabetic nephropathy is clinically characterized by proteinuria and progressive renal insufficiency. Current standards of treatment include angiotensin-converting enzyme (ACE) inhibitors, which block the pathogenic role of the renin-angiotension system. Reduced expression of ACE2 in kidneys of diabetic patients suggests this enzyme plays a role in diabetic nephropathy. Here, Liu et al. examined the renoprotective effects of ACE2 gene transfer in an experimental model of diabetic nephropathy. The authors show ACE2 exerts a renoprotective effect similar to that of ACE inhibition. This data suggests further studies into ACE2 gene targeting and therapy are warranted as potential avenues of research for the treatment of diabetic nephropathy.

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Supplementary Data PDF
Posted by MolMed Editor on Feb 1, 2011 12:00 AM CST
Shuchen Gu, Natalia Papadopoulou, Omaima Nasir, Michael Föller, Konstantinos Alevizopoulos, Florian Lang, and Christos Stournaras
 
Cancer biology is, by necessity, focused on cell survival and cell migration. Cell signaling molecules, such as membrane androgen receptors (mARs), may serve as crucial relays informing cancer cells to stop dividing and to begin apoptosis. In this article, Gu et al. examined the role of mAR activation in the context of the pro-survival PI-3 kinase/Akt pathway in vitro and in vivo. They found that upon mAR stimulation, PI-3K and Akt activity were decreased with a concomitant increase in apoptosis. They also demonstrate that mAR activation reduces intestinal tumor incidence in mice. These studies may ultimately result in the development of anti-tumorigenic strategies based on specific mAR activation.

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Supplementary Data PDF
Posted by MolMed Editor on Jan 9, 2011 12:00 AM CST
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