Archive for janeiro 9th, 2013

Cancer: Capitulo Dedicado ao Estudo desta Doença pela Matrix/DNA

quarta-feira, janeiro 9th, 2013

THE GUARDIAN

http://www.ucsdguardian.org/news-and-features/features/item/26200-the-up-and-coming-papers#.UO25l2-_B8E

The Up and Coming Papers (sôbre cancer e Aids)

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08 January 2013

The Unfolded Protein Response

A team of UCSD researchers, led by Navin R. Mahadevan at the Moores Cancer Center, found that nearly all tumor cells increase production of proteins used in growth and division through a mechanism called the unfolded protein response (UPR).

WIKIPEDIA – ( VER MAIS GOOGLE SEARCH) : The unfolded protein response (UPR) is a cellular stress response related to the endoplasmic reticulum. It is a stress response that has been found to be conserved between all mammalian species, as well as yeast and worm organisms. This article focuses on the mammalian response.

WIKIPEDIA – Integrated Stress Response (ISR)[1] is a cellular stress response common to all eukaryotes. ISR can be caused by cellular stresses and is often triggered by the activation of an eIF-2 kinase.

EIF-2 kinase

From Wikipedia, the free encyclopedia

Regulation of translation initiation via phosphorylation of Ser51 in eIF2’s α-subunit.[1]

eIF-2 is a kinase enzyme that phosphorylates eIF-2.[2]

There are four forms in mammals:

These are all responsible for the phosphorylation of the alpha subunit of eIF-2 at serine 51, one of the best-characterized mechanisms for down-regulating protein synthesis in eukaryotes in response to various cellular stress response‘s.

WIKIPEDIA: Retículo Endoplasmatico ( Ver tambem: http://micro.magnet.fsu.edu/cells/endoplasmicreticulum/endoplasmicreticulum.html

Retículo Endoplasmatico para MatrixDNA

Retículo Endoplasmatico para MatrixDNA

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In normal cells, proteins are folded, clumped together, and bent into different shapes in an intracellular structure called the endoplasmic reticulum (ER). When a cell is overworked, unfolded proteins pile up inside the ER and trigger a molecular signaling cascade that increases the overall activity of the cell, placing it in a stressed or “hyperactive” state.

Mahadevan and his colleagues found that nearly all cancer cells, which divide much more quickly than normal cells, use external signaling pathways to artificially trigger the UPR. Their work was published in the Nov. 18 issue of PLOS ONE, to little fanfare. However, on Jan. 4, a pharmaceutical company called Amicus Therapeutics announced that it had successfully tested a chaperonin-enzyme therapy for certain tumors. Chaperonin is one of the key proteins involved in the unfolded protein response, adding weight and importance to the UCSD team’s findings.

Enzymatic Explanations in Chronic Myeloid Leukemia

In early February 2012, a team of researchers headed by Michael Savona from UCSD found that a class of drugs called tyrosine kinase inhibitors (TKIs) was effective in treating chronic myeloid leukemia — cancer of the blood. Their findings were published in Volume 8 of Nature Reviews Cancer, and generated slight interest, having been cited six times in the following months.

However, this is likely to change in 2013. Tyrosine kinase inhibitors are a general class of compounds, and therefore can carry severe side effects. In a paper published in the Dec. 24 online edition of the Proceedings of the National Academy of Sciences, another team of UCSD researchers, led by Catriona Jamieson, M.D., Ph.D., reported that they had found the precise enzyme that is targeted by TKIs in chronic myeloid leukemia patients. This enzyme, an adenosine deaminase named ADAR1, is being characterized by the research team. More specific TKIs can be engineered to suit this enzyme, leading to more viable therapies for leukemia patients, a fact that has already begun to make these two research teams’ work more widely featured on the web.

As the specific ADAR1 inhibitors are developed in the coming year, the UCSD research teams’ work is likely to generate additional interest.

Keeping HIV in its Latent Phase

When a human being is infected with the human immunodeficiency virus, HIV, he or she can go for years without contracting acquired immunodeficiency syndrome — AIDS. There are a variety of reasons for this: the large number of white blood cells in the immune system and antiviral defense mechanisms in the bloodstream are both crucial. However, the most intriguing reason for the delay between HIV and AIDS may be the fact that for years, the HIV virus can replicate in the bloodstream in what is known as “latent phase” — a distinct structural form of the virus.

Last year, a team of researchers that included UCSD professor Leor Weinberger published a paper in the February issue of Cell Cycle outlining a possible mechanism for latency in HIV cells. These researchers found that BET bromodomain-targeting compounds, which are widely found in certain plants and microbes, are capable of activating transcription of DNA in HIV. At the time, however, their findings did not explain how and why HIV becomes activated in the human body and thus did not generate a particularly huge amount of interest.

However, the situation has now changed. A team of researchers at Hoffmann–La Roche, a pharmaceutical company, has found that BET bromodomain-targeting compounds are in fact secreted by mammals in small quantities in cells that have undergone a process known as acetylation in certain regions of their DNA.

Acetylation activates genes, and the La Roche researchers found that those that code for BET bromodomain-targeting compounds were found to be activated in certain fibroblasts, the tiny, often-overlooked cells that secrete the extracellular matrix, the glue that holds larger cells in a tissue together.

Given the new finding that BET bromodomain-targeting compounds are indeed secreted by human cells, the mechanism of HIV activation proposed by earlier by the UCSD research team now seems more likely. As such, the work is a good candidate to generate more buzz in 2013.