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The journey of resveratrol from yeast to human

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The journey of resveratrol from yeast to human Abstract The natural polyphenolic compound resveratrol was first discovered in the 1940s. In the recent years, this compound received renewed interest as several findings implicated resveratrol as a potent SIRT1 activator capable of mimicking the effects of calorie restriction, and regulating longevity in lower organisms. Given the worldwide increase in age-related metabolic diseases the beneficial effects of resveratrol on metabolism and healthy aging in humans are currently a topic of intense investigation. Resveratrol (3,5,4'-trihydroxystilbene) was first isolated from the roots of white hellebore ( Veratum grandiflorum O. Loes ) in 1940 [ 1 ], and later, in 1963 from the roots of  Polygonum Cupsidatum , a plant used in traditional Chinese and Japanese medicine [ 2 ]. However, the first real interest in this compound came when in 1992 resveratrol was postulated to explain some of the cardio-protective effects of red wine [ 3 ] and w

Internal ribosome entry site of bFGF is the target of thalidomide for IMiDs development in multiple myeloma

Internal ribosome entry site of bFGF is the target of thalidomide for IMiDs development in multiple myeloma ABSTRACT Although new analogues of immunomodulatory drugs (IMiDs) are being developed for MM, the molecular mechanism of these drugs remains unclear. In the current study, we used MM cell lines as a model to investigate the molecular mechanism of thalidomide and to compare its potency with IMiDs such as pomalidomide. We determined that thalidomide did not inhibit cell proliferation of RPMI8226 and U266 MM cells, whereas pomalidomide showed a significant inhibitory effect on these two MM cell lines. Interestingly, we further demonstrated that although thalidomide down-regulated bFGF translation through the inhibition of IRES even at 0.1 µg/ml, pomalidomide did not have a similar affect bFGF levels. A colony formation assay demonstrated that thalidomide and the bFGF knock-down clones caused a significant reduction in the clonogenic ability of MM cells, and treatment with exogenous

Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma - reasons and consequences

Upregulation of the miR-17-92 cluster and its two paraloga in osteosarcoma - reasons and consequences ABSTRACT Osteosarcomas (OS) are aggressive bone tumors characterized by complex karyotypes with highly variable structural and numerical chromosomal aberrations. Although several genes and pathways commonly altered in malignant tumors have also been identified in OS, the molecular pathogenesis and driving genetic events eventually leading to tumor development are still poorly understood. The microRNA (miRNA) cluster 17-92 and its two paraloga 106a-363 and 106b-25 are known to have diverse oncogenic properties and have been shown to be constantly upregulated in several established OS cell lines. In this study we analyzed a series of 75 well characterized pretherapeutic OS samples for their expression of cluster-related miRNAs and correlated our findings with clinico-pathological parameters including prognosis, metastases and response to neoadjuvant therapy. Interestingly, higher express

Cutting the brakes and flooring the gas: how TMEPAI turns TGF-β into a tumor promoter

Cutting the brakes and flooring the gas: how TMEPAI turns TGF-β into a tumor promoter ABSTRACT In normal or nonmalignant cells, TGF-β inhibits cellular proliferation through activation of the SMAD-dependent canonical signaling pathway. Recent findings demonstrate that the protein TMEPAI1 can block the cytostatic effects of the canonical TGF-β signaling pathway, while activating cellular proliferation through the noncanonical, SMAD-independent TGF-β signaling pathway. As TMEPAI1 shows increased expression in the poor prognosis basal and HER2 intrinsic subtypes of breast cancer, these findings point to a new avenue of targeted therapy with considerable therapeutic potential.  http://www.impactjournals.com/Genes&Cancer/index.php?abs=34 impact factor  When people refer to modern medicine, accuracy plays one of the most significant roles and people’s lives are literally dependent on it. Hence, any researches related to medicine are required to comply with the highest standards. The pro

STAT activation status differentiates leukemogenic from non-leukemogenic stem cells in AML and is suppressed by arsenic in t(6;9)-positive AML

STAT activation status differentiates leukemogenic from non-leukemogenic stem cells in AML and is suppressed by arsenic in t(6;9)-positive AML ABSTRACT Acute myeloid leukemia (AML) is characterized by an aberrant self-renewal of hematopoietic stem cells (HSC) and a block in differentiation. The major therapeutic challenge is the characterization of the leukemic stem cell as a target for the eradication of the disease. Until now the biology of AML-associated fusion proteins (AAFPs), such as the t(15;17)-PML/RARα, t(8;21)-RUNX1/RUNX1T1 and t(6;9)-DEK/NUP214, all able to induce AML in mice, was investigated in different models and genetic backgrounds, not directly comparable to each other. To avoid the bias of different techniques and models we expressed these three AML-inducing oncogenes in an identical genetic background and compared their influence on the HSC compartment  in vitro  and  in vivo . These AAFPs exerted differential effects on HSCs and PML/RARα, similar to DEK/NUP214, indu

DEPTOR is linked to a TORC1-p21 survival proliferation pathway in multiple myeloma cells

DEPTOR is linked to a TORC1-p21 survival proliferation pathway in multiple myeloma cells ABSTRACT We investigated the mechanism by which gene silencing of the mTOR inhibitor, DEPTOR, induces cytoreductive effects on multiple myeloma (MM) cells. DEPTOR knockdown resulted in anti-MM effects in several MM cell lines. Using an inducible shRNA to silence DEPTOR, 8226 MM cells underwent TORC1 activation, downregulation of AKT/SGK activity, apoptosis, cell cycle arrest and senescence. These latter cytotoxic effects were prevented by TORC1 paralysis (Raptor knockdown) but not by over-expression of AKT activity. In addition, DEPTOR knockdown-induced MM death was not associated with activation of the unfolded protein response, suggesting that enhanced ER stress did not play a role. In contrast, DEPTOR knockdown in 8226 cells induced p21 expression, independent of p53, and p21 knockdown prevented all of the cytotoxic effects following DEPTOR silencing. DEPTOR silencing resulted in p21 upregulatio

Taurolidine cooperates with antineoplastic drugs in neuroblastoma cells

Taurolidine cooperates with antineoplastic drugs in neuroblastoma cells ABSTRACT Neuroblastoma is the most common extracranial tumor in childhood. Outcome of stage 4 disease remains poor and the development of novel therapeutic approaches is thus urgently needed. Taurolidine (TRD), originally invented to avoid catheter infections, has shown to exhibit antineoplastic activity in various cancers. The growth of neuroblastoma cell lines is inhibited by TRD as recently demonstrated. Further analysis disclosed a significant negative growth effect of TRD on the four neuroblastoma cell lines SH-EP TET21N, SK-N-AS, SK-N-BE(2)-M17 and SK-N-SH. Detected IC 50  (51-274 µM; 48 h) are promising and correspond to clinically- achievable plasma levels. Apoptosis was induced (76-86%; 48 h) in a time- dependent manner mediated by a simultaneous activation of the intrinsic and extrinsic pathways. This was confirmed by cleavage of caspases -3, -8 and -9 and abrogation of apoptosis by pan-caspase inhibition

Career Mikhail Blagosklonny

Mikhail Blagosklonny From Wikipedia, the free encyclopedia Jump to navigation Jump to search Mikhail Blagosklonny Alma mater First Pavlov State Medical University of St. Peterburg Scientific career Fields Anti-aging medicine ,  oncology Institutions New York Medical College Roswell Park Cancer Institute Mikhail Blagosklonny  is a scientist who studies  cancer  and  aging . He is an adjunct faculty member at the  Roswell Park Cancer Institute  in  Buffalo, New York . [1] Contents 1 Career 2 Rapamycin and aging 3 Editorial activities 4 References Career [ edit ] Blagosklonny earned both his  M.D.  in internal medicine and his  PhD  in experimental medicine and cardiology from the  First Pavlov State Medical University of St. Petersburg . [ citation needed ]  He was appointed associate professor of medicine at  New York Medical College , Valhalla, NY in 2002 before taking a position as a senior scientist at Ordway Research Institute ( Albany, New York ). Blagosklonny held this position un