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Articles from this Volume

Adriana Ferreira and Eileen H Bigio

Tau dysfunction has been implicated in neuronal degeneration in several diseases known as tauopathies. The most common tauopathy is Alzheimer’s disease (AD). The pathological hallmark of these diseases is the presence of intracellular aggregates of hyperphosphorylated tau. In addition to phosphorylation, other posttranslational modifications might be involved in the mechanisms underlying tau pathology. Studies suggest the calpain-mediated generation of a 17 kDa neurotoxic tau fragment might be part of the pathobiology of AD, and perhaps, all tauopathies. Ferreira et al. investigated the presence of 17 kDa tau fragment in brain areas affected in AD and other tauopathies as well as the relationship between tau cleavage and tau aggregation in degenerating central neurons. Results provide insights into both the potential role of this fragment in tau aggregation and the role of enhanced phosphorylation in the generation of this fragment. This underlying mechanism might be part of a conserved pathologic process shared by multiple tauopathies.   

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Posted by Leah Caracappa on Jul 11, 2011 12:00 AM CDT

Sanela Kurtovic, Valentina Paloschi, Lasse Folkersen, Johan Gottfries, Anders Franco-Cereceda, and Per Eriksson

Thoracic aortic aneurysm (TAA) is a pathological widening of the aorta, resulting from degeneration of extra cellular matrix and loss of smooth muscle cells in the tunica media. Impaired regulation of the transforming growth factor-β (TGFβ) signaling pathway has been linked to TAA and differential splicing potentially influences the function of proteins. Kurtovic et al. investigated the occurrence of differential splicing in the TGFβ pathway associated with TAA in patients with bicuspid (BAV) and tricuspid (TAV) aortic valve. Using Affymetrix Human Exon arrays and multivariate techniques, they demonstrated that the two different types of aorta tissues, dilated and non-dilated show different alternative splicing patterns in TGFβ pathway with respect to TAV and BAV. Their results indicate that dilatation in patients with TAV has different underlying molecular mechanisms compared with BAV patients.

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Posted by Leah Caracappa on Jul 10, 2011 12:00 AM CDT

Minja J Pfeiffer, Frank P Smit, John PM Sedelaar, and Jack A Schalken

Since the survival and growth of prostate cancer (PCa) cells are driven by androgens, androgen deprivation therapy is the first line of treatment for advanced PCa. However, despite castration, cancer often recurs and may be considered castration resistant prostate cancer (CRPC). In this work, Pfeiffer et al. hypothesize that treatment-surviving, cancer-initiating cells along with the ability to metabolize steroids from precursors may be required in order for recurrent tumors to form. The authors assessed steroidogenic enzyme expression and stem cell markers during androgen depletion in a PCa cell line as well as in clinical samples. Enzymes involved in adrenal steroid metabolism, stem/progenitor cell markers, and the androgen receptor were found to be upregulated. This evidence links steroidogenesis with cancer initiating cells in PCa and indicates that therapies targeting adrenal steroid metabolism may prove effective in preventing tumor regrowth.

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Posted by Leah Caracappa on Jul 9, 2011 12:00 AM CDT

Qingdong Guan, Yanbing Ma, China-Li Hillman, Gefei Qing, Allan G Ma, Carolyn R Weiss, Gang Zhou, Aiping Bai, Richard J Warrington, Charles N Bernstein, and Zhikang Peng

Interleukin (IL)-12 and IL-23 both share the p40 subunit and are key cytokines in the pathogenesis of Crohn’s disease.  Guan et al. developed vaccines that develop specific antibodies against both cytokines and here, tested them in experimental models of colitis. Vaccinations resulted in significantly less body weight loss, diminished colon inflammation and fibrosis, as well as reduced levels of multiple pro-inflammatory cytokines. These findings suggest this vaccine may provide a potential approach for long-term treatment of Crohn’s disease.

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Posted by Leah Caracappa on Jul 8, 2011 12:00 AM CDT

Shahab Uddin, Zeenath Jehan, Maqbool Ahmed, Aisha Alyan, Fouad Al-Dayel, Azhar Hussain, Prashant Bavi, and Khawla S Al-Kuraya

Over 21,000 women are diagnosed with ovarian cancers annually in the US. Two-thirds will die of their disease. Cisplatin is the gold standard in treatment, however, cells acquire resistance leading to the patients’ demise. Previous research shows fatty acid synthanse (FASN) is overexpressed in breast, ovarian, colorectal, lung, prostate and thyroid cancer and the magnitude of expression is proportional with cancer aggressiveness and metastasis. Here, Uddin et al. used ovarian tumor samples and cell lines to investigate the FASN pathway, AKT signaling, apoptosis and cisplatin resistance. The authors found FASN overexpression was directly linked to AKT phosphorylation and protection from cisplatin-induced apoptosis. Treatment with an FASN inhibitor promoted apoptosis in cancer cells via a mitochondrial pathway. These results provide a molecular rationale to design novel therapies directed against FASN in combination with cisplatin in ovarian carcinomas.

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Posted by Leah Caracappa on Jul 7, 2011 12:00 AM CDT

Prasad S Adusumilli, Sepideh Gholami, Yun Shin Chun, Michael Mullerad, Mei Ki Chan, Zhenkun Yu, Leah Ben-Porat, Valerie W Rusch, and Yuman Fong

Cytology diagnosis combined with imaging-assisted staging aids cancer treatment decisions. However, cytology from bodily fluids or sputum is often difficult to interpret because reactive mesothelial cells mimic malignant cells and cytology in patients with advanced cancer rarely finds malignant cells. Here, Adusumilli et al. tested whether a modified herpes virus carrying an EGFP protein could detect rare cancer cells in body fluids. The presence of cancer cells were accurately identified by all observers irrespective of their experience with microscopy even at a concentration as low as one cancer cell in one million normal cells. This fluorescence assisted cytologic testing (FACT) method may save patients from morbidity of surgery for tissue diagnosis and eliminate the interobserver variability that often plaques the field of cytopathology.

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Posted by Leah Caracappa on Jul 6, 2011 12:00 AM CDT

Iris Gehrke, Rajesh Kumar Gandhirajan, Simon Jonas Poll-Wolbeck, Michael Hallek, and Karl-Anton Kreuzer

Chronic lymphocytic leukemia (CLL) cells accumulate in the body as a result of their anti-apoptotic nature. Although cells undergo rapid apoptosis in vitro, they survive longer in vivo. CLL cells receive survival signals from their microenvironment, however, the nature of these signals is not completely understood. Vascular endothelial growth factor (VEGF) is considered a pro-survival factor in CLL but its source and mechanism have not been clearly identified. Here, Gehrke et al. investigate the source of VEGF and its effect on the survival of CLL cells co-cultured on bone marrow stromal cells (BMSCs). Data showed VEGF derived from BMSCs, but not CLL cells, is involved in coculture-mediated survival support of CLL cells. These results suggest targeting VEGF signaling may be a promising approach to overcome CLL cell apoptotic resistance in their natural microenvironment.

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Posted by Leah Caracappa on Jul 5, 2011 12:00 AM CDT

Jingzhou Chen, Yi Shi, Ziyu Li, Hui Yu, Yu Han, Xiaojian Wang, Kai Sun, Tao Yang, Kejia Lou, Yan Song, Yinhui Zhang, Yisong Zhen, Guiguo Zhang, Ying Hu, Jiafu Ji, and Rutai Hui

Colorectal cancer (CRC) is a one of the most pervasive cancers worldwide.
The IC53 gene has been reported to be upregulated in colon adenocarcinoma cells. Here, Chen et al. hypothesize that IC53 can regulate colon cancer progression and that a variant in the gene could modify the incidence and onset of colon cancer. Their data indicate IC53 is a positive mediator for colon cancer progression and the variant may serve as a protective factor against the onset of colorectal cancer.

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Posted by Leah Caracappa on Jul 4, 2011 12:00 AM CDT

Sanjaya K Satapathy, Mahendar Ochani, Meghan Dancho, LaQueta K Hudson, Mauricio Rosas-Ballina, Sergio I Valdes-Ferrer, Peder S Olofsson, Yael Tobi Harris, Jesse Roth, Sangeeta Chavan, Kevin J Tracey, and Valentin A Pavlov

Obesity affects more than 50 million people in the United States and is a global epidemic.  Obesity and the associated metabolic syndrome increases the risk of developing type 2 diabetes, cardiovascular disease, respiratory diseases and osteoarthritis. Inflammation is thought to be an important contributor to obesity-associated pathological conditions. Satapathy et al. explored the use of galantamine, a clinically approved drug for Alzheimer's disease, to alleviate obesity-related inflammation and other complications. Results indicate galantamine can reduce inflammation, decrease body weight gain and abdominal adiposity, and alleviate hyperglycemia, hyperinsulinemia, hypercholesterolemia, insulin resistance and fatty liver. These results suggest a previously unexplored potential of galantamine in alleviating obesity and its associated complications.

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Posted by Leah Caracappa on Jul 3, 2011 12:00 AM CDT

Agnes Bergerat, Julius Decano, Chang-Jiun Wu, Hyungwon Choi, Alexey I Nesvizhskii, Ann Marie Moran, Nelson Ruiz-Opazo, Martin Steffen, and Victoria LM Herrera

Stroke is the third leading cause of death with high rates of morbidity among survivors. The unequivocal need for new therapeutic approaches would benefit from unbiased proteomic analyses of experimental models of spontaneous stroke in the prestroke stage. Using proteomic analysis, Bergerat et al. tested the putative changes in cerebral cortical microvessels (cMVs) preceding the onset of stroke in a stroke-prone model. The authors show cMV prestroke proteomic changes associated with age and stroke susceptibility. Their data indicate significant molecular changes in ischemic cerebral microvasculature in the prestroke stage, which could contribute to the observed model phenotype of microhemorrhages and post-ischemic hemorrhagic transformation. These pathways comprise putative targets for translational research of much-needed diagnostic and therapeutic approaches for stroke.

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Posted by Leah Caracappa on Jul 2, 2011 12:00 AM CDT
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