Posts Tagged ‘Development’

Foundation Medicine Appoints Gary Palmer, M.D., as Senior Vice President of Medical Affairs and Commercial Development

Foundation Medicine Appoints Gary Palmer, M.D., as Senior Vice President of Medical Affairs and Commercial Development
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Foundation Medicine, Inc., a personalized cancer diagnostics company that aims to bring comprehensive cancer genome analysis to routine clinical care, today announced the appointment of Gary Palmer, M.D., J.D., M.B.A., M.P.H. to the newly created position of senior vice president, medical affairs and commercial development. In this role, Dr. Palmer will drive …

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Key information about breast cancer risk and development is found in ‘junk’ DNA

Key information about breast cancer risk and development is found in ‘junk’ DNA
A new genetic biomarker that indicates an increased risk for developing breast cancer can be found in an individual’s “junk” (non-coding) DNA, according to a new study featuring work from researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech and their colleagues.

Read more on PhysOrg

ZIOPHARM Oncology Appoints Michael G. King, Jr. as Senior Vice President of Corporate Development & Communication

ZIOPHARM Oncology Appoints Michael G. King, Jr. as Senior Vice President of Corporate Development & Communication
ZIOPHARM Oncology, Inc. announced today that it has appointed Michael G. King, Jr., Senior Vice President of Corporate Development and Communication. In this newly established position, Mr.

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Q&A: Pfizer’s Mao Mao on Using Next-Generation Sequencing in Drug Development

Q&A: Pfizer’s Mao Mao on Using Next-Generation Sequencing in Drug Development
As next-generation sequencing becomes increasingly used in disease research, pharmaceutical companies are also looking to use the technology for drug development, to identify patients for clinical trials, and to find disease biomarkers.

Read more on GenomeWeb News

Celsion Receives Fast Track Designation For ThermoDox® Development Program To Treat Primary Liver Cancer

Celsion Receives Fast Track Designation For ThermoDox® Development Program To Treat Primary Liver Cancer
Celsion Corporation (Nasdaq: CLSN ), a leading oncology drug development company, today announced that the U.S. Food and Drug Administration (FDA) has designated the HEAT Study of its investigational drug, ThermoDox®, in combination with radiofrequency ablation (RFA), as a Fast Track Development Program.

Read more on PharmaceuticalOnline

Signs Of Breast Development In Girls – Breast Tenderness in Teenagers and Young Adults

Signs Of Breast Development In Girls

Can you remember back to when you were younger, to the time when you experienced breast tenderness? It’s not easy being a young woman growing up. There is a constant roller coaster ride of emotions to feel and experiences to go through. Hormones are erratic, skin problems seem continual and your moods are up, opps now they are down, no wait, they are up!

Breast tenderness is normal and common when young women are going through puberty. Often they ache, causing discomfort. Embarrassment can be felt by what is thought as the “overnight” growth of your breasts. “Honestly, I could swear they weren’t there yesterday!”. Getting used to your breasts developing, having breast tenderness, feeling uncomfortable, finding what bra is right for you, whilst going through possible confidence and self esteem issues, can be a huge ordeal!

My advice for teenage girls and young adult women, is to learn the basics and be breast aware. Find someone you can talk to about what you are feeling and going through. For young women aged 20, I would encourage you to start doing monthly breast self exam. Why wait until you are 40! The sooner you get into the regular habit of doing this, the quicker you will become familiar with your breasts. Please get past the embarrassment and weird feeling of doing breast self exam. You and your girlfriends need to have a discussion about the signs of breast cancer – you owe it to yourself to talk it over with them. Signs Of Breast Development In Girls

Learning how to do regular breast exam, you will no doubt discover that you are like many of us, and have lumpy breasts. Don’t panic and assume that your breast lump is breast cancer. More than likely, your lump or breast lumps you are feeling, are hormonal. That’s why by doing your breast self exam each month, you get to know how your breasts normally feel, and know when to do your exam. Most breast tenderness at a younger age is usually associated with your cycle, so be aware and don’t panic.

Young women also need to be aware of inflammatory breast cancer, which is a highly aggressive uncommon cancer, that does not have a breast lump. I am not trying to scare you girls, but do read up on inflammatory breast cancer so that you know the particular signs of breast cancer to look for.

For teenage girls, I think it’s never too early to start talking about womens health issues and breast cancer. Education is so important and in my opinion it is never to early to start raising awareness. Sow the seed of breast health into your teenagers mind. She may not pick up on it right now, but with support and encouragement, open discussions and education, she may end up being a young adult who starts doing regular monthly breast self exam. Yippee to that I say!

Oh by the way girls, please don’t roll your eyes with horror or boredom, if your mother or another female in your life has a breast talk with you. It is only because she cares! Signs Of Breast Development In Girls

Targeting Cancer Stem Cells: Therapeutic Strategies, Drug Development Pipeline, Biomarkers and Diagnostic Opportunities 2010

Cancer Stem Cell (CSC) research has accelerated in the last two years and considerable efforts are now being made to identify drug molecules that selectively target and destroy them. Today, 50 developmental molecules are being evaluated in the hope of targeting this subset of cancer cells. More than 40 companies and commercial groups are progressing these activities and around 20 drug-targeting strategies are being evaluated. Efforts are being made to target CSCs using novel single agents as well as combinations, based on new and established classes. This 2010 report gives a comprehensive update on current therapeutic and diagnostic development in this field, on the drug development pipeline and the most promising research areas in CSC characterisation. New therapeutic and diagnostic opportunities in this field are also presented.

Background: Many cancers contain a subset of stem-like cells believed to play a critical role in the development and progression of the disease. These cells, named Cancer Stem Cells (CSCs), have been found in leukaemia, myeloma, breast, prostate, pancreatic, colon, brain, lung and other cancers. Findings suggest that CSCs are able to “seed” new tumour formation and drive metastasis. CSCs also show resistance to a number of chemotherapy drug classes and radiotherapy – which may explain why it is difficult to completely eradicate cancer cells from the body, and why recurrence remains an ever-present threat. If these findings are confirmed in the clinic, the targeting of CSCs alongside the bulk of other cancer cells will offer a new paradigm in cancer therapeutics. Currently, there are more than 50 CSC R&D programmes in progress, around 50% of which are at Phases I-III. Patient data from the first clinical trials on CSC-targeting drugs are now being reported. More than two thirds of CSC R&D programmes are being taken forward by SME’s, and >90% of the patents in this field have been filed by Universities. Substantial opportunity for collaboration exists in this field, and this has lead to agreements between SMEs and number of international pharmaceutical companies.

Drug Pipeline: Approximately 20 different strategies, which are described in this report, are being pursued in the hope of discovering ways of selectively targeting CSCs. Recently for example, at the CTRC-AACR San Antonio Breast Cancer Symposium in December 2009, data were presented on the targeting of chemotherapy-resistant breast CSCs with the Merck compound MK-0752, a gamma-secretase inhibitor that targets the Notch pathway. In a study involving 35 women with advanced breast cancer, biopsies revealed reduced numbers of breast CSCs. In this particular case, it was suggested that combination therapies involving agents that also target the Notch pathway (believed to be important in CSC renewal) may offer more powerful strategies for killing resistant CSC populations.

Cancer Diagnostics: CSCs are believed to be causally linked to the development and metastatic spread of cancer. If this is confirmed in the clinic, this will place CSCs at the heart of cancer diagnostics and biomarkers. Scientists have identified a number of surface proteins, such as CD44, CD133 and many others, that may have important utility in both of these areas. A number of intracellular markers found in CSCs may also have diagnostic utility. These developments are described in this report. For example, CD133 mRNA levels in peripheral blood, measured using RT-PCR, have been found to predict colon cancer recurrence. There is a need for new methodologies that isolate and characterise circulating tumour cells (CTCs) in the blood, and can be applied to CSCs. CTC technologies using the EpCam marker to isolate these cells are able to predict breast and colon cancer recurrence. The adaption of these techniques, based on specific CSC phenotypes, may provide sensitive new methods for identifying CSCs in the body. If this is achieved, it will have important implications in therapeutic decision-making and monitoring.

This 2010 report gives a comprehensive and up-to-date review of global R&D on CSCs, and strategies to target them. This includes around 40 companies or commercially based research organisations (including 27 SMEs and 8 international pharmaceutical companies) that are progressing drug discovery activities, including drug pipeline (pre-clinical to Phase III), discovery strategy, candidate molecules, drug targets, clinical trials and related areas.

For more information on the report, kindly visit :
http://www.visionshopsters.com/product/3358/Targeting-Cancer-Stem-Cells-Therapeutic-Strategies-Drug-Development-Pipeline-Biomarkers-and-Diagnostic-Opportunities-2010.html

or email us your query at :

Cancer Stem Cell (CSC) research has accelerated in the last two years and considerable efforts are now being made to identify drug molecules that selectively target and destroy them. Today, 50 developmental molecules are being evaluated in the hope of targeting this subset of cancer cells. More than 40 companies and commercial groups are progressing these activities and around 20 drug-targeting strategies are being evaluated. Efforts are being made to target CSCs using novel single agents as well as combinations, based on new and established classes. This 2010 report gives a comprehensive update on current therapeutic and diagnostic development in this field, on the drug development pipeline and the most promising research areas in CSC characterisation. New therapeutic and diagnostic opportunities in this field are also presented.

Background: Many cancers contain a subset of stem-like cells believed to play a critical role in the development and progression of the disease. These cells, named Cancer Stem Cells (CSCs), have been found in leukaemia, myeloma, breast, prostate, pancreatic, colon, brain, lung and other cancers. Findings suggest that CSCs are able to “seed” new tumour formation and drive metastasis. CSCs also show resistance to a number of chemotherapy drug classes and radiotherapy – which may explain why it is difficult to completely eradicate cancer cells from the body, and why recurrence remains an ever-present threat. If these findings are confirmed in the clinic, the targeting of CSCs alongside the bulk of other cancer cells will offer a new paradigm in cancer therapeutics. Currently, there are more than 50 CSC R&D programmes in progress, around 50% of which are at Phases I-III. Patient data from the first clinical trials on CSC-targeting drugs are now being reported. More than two thirds of CSC R&D programmes are being taken forward by SME’s, and >90% of the patents in this field have been filed by Universities. Substantial opportunity for collaboration exists in this field, and this has lead to agreements between SMEs and number of international pharmaceutical companies.

Drug Pipeline: Approximately 20 different strategies, which are described in this report, are being pursued in the hope of discovering ways of selectively targeting CSCs. Recently for example, at the CTRC-AACR San Antonio Breast Cancer Symposium in December 2009, data were presented on the targeting of chemotherapy-resistant breast CSCs with the Merck compound MK-0752, a gamma-secretase inhibitor that targets the Notch pathway. In a study involving 35 women with advanced breast cancer, biopsies revealed reduced numbers of breast CSCs. In this particular case, it was suggested that combination therapies involving agents that also target the Notch pathway (believed to be important in CSC renewal) may offer more powerful strategies for killing resistant CSC populations.

Cancer Diagnostics: CSCs are believed to be causally linked to the development and metastatic spread of cancer. If this is confirmed in the clinic, this will place CSCs at the heart of cancer diagnostics and biomarkers. Scientists have identified a number of surface proteins, such as CD44, CD133 and many others, that may have important utility in both of these areas. A number of intracellular markers found in CSCs may also have diagnostic utility. These developments are described in this report. For example, CD133 mRNA levels in peripheral blood, measured using RT-PCR, have been found to predict colon cancer recurrence. There is a need for new methodologies that isolate and characterise circulating tumour cells (CTCs) in the blood, and can be applied to CSCs. CTC technologies using the EpCam marker to isolate these cells are able to predict breast and colon cancer recurrence. The adaption of these techniques, based on specific CSC phenotypes, may provide sensitive new methods for identifying CSCs in the body. If this is achieved, it will have important implications in therapeutic decision-making and monitoring.

This 2010 report gives a comprehensive and up-to-date review of global R&D on CSCs, and strategies to target them. This includes around 40 companies or commercially based research organisations (including 27 SMEs and 8 international pharmaceutical companies) that are progressing drug discovery activities, including drug pipeline (pre-clinical to Phase III), discovery strategy, candidate molecules, drug targets, clinical trials and related areas.

For more information on the report, kindly visit :
http://www.visionshopsters.com/product/3358/Targeting-Cancer-Stem-Cells-Therapeutic-Strategies-Drug-Development-Pipeline-Biomarkers-and-Diagnostic-Opportunities-2010.html

or email us your query at : info@visionshopsters.com
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The First Big Hitter in Genetic Development: Androgens

Make no mistake; nothing else mentioned in this book will help you grow like androgens, as they are the basic building block for increasing muscle size and strength. All other things only serve to enhance androgens. So whether you use a natural testosterone booster or a pro-hormone or real juice, you need the basics to build your genetic house. Androgens have been shown to create new muscle growth in multiple ways, both by increasing protein synthesis (filling up your muscle balloons) and increasing the differentiation of satellite cells (making more muscle balloons). That makes them the ultimate starting point for a genetic anabolic cocktail.

What are androgens? Quite simply they are testosterone and its derivatives, both legal and illegal. Guess when your body produces the most testosterone? You got it, puberty! That’s why you can gain mad muscle cells if you simply work out and eat right when you are in high school. Eating right is important because your body isn’t going to make new muscle cells if it doesn’t have the protein to fill up the ones it already has (which is why so many high school students work out without results). Growing muscle during puberty happens in the kitchen, not just the gym, but that is another book.

Androgens are the most potent muscle builders you can take. Luckily with our products you get the best of both worlds, increased androgen production without the negative side effects that SCARE the hell out of most people. You can start small and use something like Formadrol Extreme or you can jump up to our prohormones (Liquid Masterdrol and Methyl 1-D) or you can go the illegal route and hit juice (we don’t recommend this by the way). People doing our Trifecta Stack are routinely hitting 8-12lbs of muscle in a month without losing their gains. If you juice, you can probably increase that to 15-17lbs but when you grow that quickly, you rarely keep your gains. Slow, steady gains might not feel as exciting, but they are the way to build a body, not an ego! The combination of Stanolone (Liquid Masterdrol) plus Testosterone (Methyl 1-D) is a very powerful combination and gives you the ULTIMATE in safety and also gives REAL gains that you would see from a SANE steroid cycle, without the negatives!

So, how do you get a spike in androgens? Many ways… The first way is to use an herbal product that typically will trick your body into increasing output of Luteinizing Hormone. These were made popular with products like Tribulus

and have come a long way with the advent of newer ingredients like Long Jack? and others out on the market. Some of them, like Horny Goat Weed only

serve to boost sex drive and have not been shown to enhance testosterone production.

Another way is to use a natural testosterone booster like LG Sciences Formadrol Extreme?, which tricks your body into producing more testosterone by blocking estrogen in the body. This can give you levels above even the very highest natural range (a normal man ranges from 250 ng/dl of testosterone to 900 ng/dl). Formadrol Extreme? and similar products trick your body into producing more testosterone and can be very useful as a natural anabolic booster, getting your testosterone levels into the 1400ng/dl range. It is also great for Post Cycle Therapy after a steroid or pro-hormone cycle. They are also useful in combating gynecomastia, commonly called “bitch tits”.

The third way to boost your androgen levels is the use of pro-hormones. First made popular by “Andro”, pro-hormones use the basic building blocks of testosterone to force your body into producing more testosterone through the action of enzymes. The first generation of testosterone boosters, like Andro, had tons of side effects and didn’t work very well. Newer pro-hormones like 1-AD were better, but were still not up to the full value of a steroid cycle. The latest crop of pro-hormones, like Methyl-1-D? and Liquid Masterdrol by LG Sciences, reduce the side effects, prolong the half-life in the body and reduce conversion to unwanted, side effect producing by-products like Estrogen. The use of pro-hormones can give you testosterone levels that rival even the strongest steroids, raising your testosterone levels to 3000-3500 ng/dl if used properly.

Methyl-1-D? from LG Sciences is a pro-hormone that is formulated to reduce side effects, provide maximum safety and give you AMAZING results. It’s the real basis for our genetics-changing stack. For a more advanced stack, use Liquid-Masterdrol? along with Methyl-1-D? for the best possible combination of prohormones that hit both the more androgenic (Liquid Masterdrol?) and more anabolic (Methyl 1-D?) aspects of growth.

The fourth way to boost androgen levels is to use artificial illegal steroids to boost your testosterone levels above even the highest legal levels that pro-hormones can give. I am not here to make a value statement about steroids, but I am just pointing out the option to anyone that is in a foreign country that allows steroid use or is using androgens with a doctor’s prescription.

We highly suggest that you do not use illegal anabolic steroids for obvious reasons and we hope that you respect the law and your body by using natural substances that are safer alternatives. If you do use steroids however, we recommend that you do so safely, cycling off them for at least a month at a time, taking supplements like Fish Oil to cleanse your liver and reduce the chance of cardiovascular side effects. Now, that being said, steroids are obviously not that dangerous, since prescription compounds, such as Testosterone Gel, are being pushed as the next great development (never mind that the Testosterone Gels on the market are loaded with side effects including conversion to DHT which

aggravates the prostate and estrogen that can promote breast cancer, even in men). Once the root of all evil, steroids are suddenly completely safe and side effect free when turned into a prescription drug. Wake up people! Again, we don’t encourage you to use steroids, but if you do, please consider doing them safely (there is a section at the end of good supplements to take with steroids that will offer some nice protection from their side effects).

So, if you are going to do a cycle of steroids, this is the perfect time to add in some serious genetic expression supplements to maximize your growth. One of the funniest things I see is the juice crowd bashing the supplement crowd, when in reality someone on a cycle will probably benefit the most from proper supplementation.

Studies show that androgens do indeed cause genetic changes that can benefit powerlifters and bodybuilders.

Here you see how increasing testosterone through natural boosting, pro-hormones or illegal anabolic steroids can vastly increase satellite muscle cell expression. This is the first real pathway that the body uses to increase muscle size and the number of muscle cells. By increasing the raw number of satellite cells, testosterone is the foundation of our genetic altering arsenal.

Skeletal muscle morphology in power-lifters with and without anabolic steroids.

Eriksson A, Kadi F, Malm C, Thornell LE.

Department of Integrative Medical Biology, Section for Anatomy, Umea

University, 901 87 Umea, Sweden.

The morphological appearance of the vastus lateralis (VL) muscle from high-level power-lifters on long-term anabolic steroid supplementation (PAS) and power-lifters never taking anabolic steroids (P) was compared. The effects of long- and short-term supplementation were compared. Enzyme-immunohistochemical investigations were performed to assess muscle fiber type composition, fiber area, and number of myonuclei per fiber, internal myonuclei, myonuclear domains and proportion of satellite cells. The PAS group had larger type I, IIA, IIAB and IIC fiber areas (p<0.05). The number of myonuclei/fiber and the proportion of central nuclei were significantly higher in the PAS group (p or = 5 myonuclei. The results of AS on VL morphology in this study were similar to previously reported short-term effects of AS on VL. The initial effects from AS appear to be maintained for several years.

Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment.

Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.

Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus

lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression. AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis. Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nm testosterone and 30 nm dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression. These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.

That being said, we can safely increase testosterone using supplements and don’t need illegal anabolic steroids! Pro-hormones boost natural testosterone by giving you the building blocks for testosterone and other steroid hormones. Pro-hormones are the safest, most effective way to boost testosterone without using drugs. The second way is to use natural testosterone boosters. There are many on the market, like tribulus, long jack and others. The best combination is an anti-estrogen that tricks your body into producing more testosterone. There are many of these products on the market, but the latest generations are far more effective and have fewer or no negative effects on the body. Here is what some peer reviewed journal entries say about using testosterone to activate satellite cells:

Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy,young men.

Sinha-Hikim I, Roth SM, Lee MI, Bhasin S.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.

Testosterone (T) supplementation in men induces muscle fiber hypertrophy. We hypothesized that T-induced increase in muscle fiber size is associated with a dose-dependent increase in satellite cell number. We quantitated satellite cell and myonuclear number by using direct counting and spatial orientation methods in biopsies of vastus lateralis obtained at baseline and after 20 wk of treatment with a gonadotropin-releasing hormone agonist and a 125-, 300-, or 600-mg weekly dose of T enanthate. T administration was associated with a significant increase in myonuclear number in men receiving 300- and 600-mg doses. The posttreatment percent satellite cell number, obtained by direct counting, differed significantly among the three groups (ANCOVA P < 0.000001); the mean posttreatment values (5.0 and 15.0%) in men treated with 300- and 600-mg doses were greater than baseline (2.5 and 2.5%, respectively, P < 0.05 vs. baseline). The absolute satellite cell number measured by spatial orientation at 20 wk (1.5 and 4.0/mm) was significantly greater than baseline (0.3 and 0.6/mm) in men receiving the 300- and 600-mg doses (P < 0.05). The change in percent satellite cell number correlated with changes in total (r = 0.548) and free T concentrations (r = 0.468). Satellite cell and mitochondrial areas were significantly higher and the nuclear-to-cytoplasmic ratio lower after treatment with 300- and 600-mg doses. We conclude that T-induced muscle fiber hypertrophy is associated with an increase in satellite cell number, a proportionate increase in myonuclear number, and changes in satellite cell ultrastructure.

Androgen regulation of satellite cell function.

Chen Y, Zajac JD, MacLean HE.

Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia.

Androgen treatment can enhance the size and strength of muscle. However, the mechanisms of androgen action in skeletal muscle are poorly understood. This review discusses potential mechanisms by which androgens regulate satellite cell activation and function. Studies have demonstrated that androgen administration increases satellite cell numbers in animals and humans in a dose-dependent manner. Moreover, androgens increase androgen receptor levels in satellite cells. In vitro, the results are contradictory as to whether androgens regulate satellite cell proliferation or differentiation. IGF-I is one major target of androgen action in satellite cells. In addition, the possibility of non-genomic actions of androgens on satellite cells is discussed. In summary, this review focuses on exploring potential mechanisms through which androgens regulate satellite cells, by analyzing developments from research in this area.

Androgen receptor in human skeletal muscle and cultured muscle satellite cells: up-regulation by androgen treatment.

Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.

Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression. AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis. Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nm testosterone and 30 nm dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression. These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.

Testosterone action on skeletal muscle.

Herbst KL, Bhasin S.

UCLA School of Medicine, Charles R. Drew University, Los Angeles, California 90059, USA.

PURPOSE OF REVIEW: To highlight recent data demonstrating direct anabolic effects of androgens on the mammalian skeletal muscle and review the mechanisms by which testosterone regulates body composition. RECENT FINDINGS: Testosterone increases lean body mass and decreases fat mass in young men; the magnitude of the changes induced by testosterone in lean and fat mass are correlated with testosterone dose and the prevalent testosterone concentrations. Older men are as responsive to the anabolic effects of testosterone on the muscle as young men, but have increased frequency of adverse events with higher testosterone doses. This reciprocal change in lean and fat mass induced by androgens is best explained by the hypothesis that androgens promote the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibit adipogenesis through an androgen receptor mediated pathway. Resident muscle satellite cells increase in number with testosterone administration forming myoblasts leading to greater numbers of myonuclei in larger myofibers. Testosterone administration is associated with increased size of motor neurons. The roles of 5-alpha reduction and aromatization of testosterone into dihydrotestosterone and estradiol, respectively, in mediating testosterone effects on body composition are poorly understood. SUMMARY: Testosterone induces skeletal muscle hypertrophy by multiple mechanisms, including its effects in modulating the commitment of pluripotent mesenchymal cells. These changes in skeletal muscle lead to improved muscle strength and leg power; however, further studies are needed to determine the effects of testosterone on physical function and health-related outcomes in sarcopenia associated with aging and chronic illness.

Here you see how increasing testosterone through natural boosting, pro-hormones or illegal anabolic steroids can vastly increase satellite muscle cell expression. This is the first real pathway that the body uses to increase muscle size and the number of muscle cells. By increasing the raw number of satellite cells, testosterone is the foundation of our genetic altering arsenal.

Research and Markets: Triple Analysis: A Comprehensive Focus on Cancer Drug Development Strategies in Both Breast …

Research and Markets: Triple Analysis: A Comprehensive Focus on Cancer Drug Development Strategies in Both Breast …
DUBLIN—-Research and Markets has announced the addition of the “Triple Analysis: Breast Cancer, Lung Cancer and Peptides” report to their offering.

Read more on Business Wire via Yahoo! Finance

Research and Markets: Triple Analysis Focusing on Cancer Drug Development Strategies in Both Breast Cancer, Cancer …

Research and Markets: Triple Analysis Focusing on Cancer Drug Development Strategies in Both Breast Cancer, Cancer …
DUBLIN—-Research and Markets has announced the addition of the “Triple Analysis: Breast Cancer, Leukemia and Cancer Vaccines” report to their offering.

Read more on Business Wire via Yahoo! Finance