Breast Cancer Preventable and Reversible World Health News

Medical research discovers that breast cancer can be reversible and preventable. This is great news in the battle of cancer that many women are going through.

Study shows resistance is reversible

In dozens of experiments in mice and in human cancer cells, a team of Johns Hopkins scientists has closely tied production of a cancer-causing protein called TWIST to the development of estrogen resistance in women with breast cancer. Because estrogen fuels much breast cancer growth, such resistance — in which cancers go from estrogen positive to estrogen negative status — can sabotage anticancer drugs that work to block estrogen and prevent disease recurrence after surgery. Estrogen resistance develops in over half of women taking estrogen-blocking medications, such as tamoxifen, and exists from the start in many other women.

The Johns Hopkins-led team of cancer experts also reports that stalling TWIST production significantly reverses estrogen resistance.
“Now that we know TWIST has a major role in controlling estrogen resistance in breast cancer, we can investigate the value of anti-TWIST therapies and how they make possible postsurgical hormone therapy for all women who have had invasive breast cancer,” says senior study investigator and breast cancer biologist Venu Raman, Ph.D. “We suspect that TWIST production may be an underlying cause of estrogen resistance,” adds Raman, an associate professor in the Department of Radiology at the Johns Hopkins University School of Medicine and its Kimmel Cancer Center.

Estrogen resistance, Raman says, not only renders tamoxifen or aromatase inhibitors, such as anastrozole and letrozole, ineffective in women whose original estrogen receptor status was positive, but also rules out these standard treatment options for the one-quarter of women who at the time of their diagnosis already are estrogen receptor negative.

The latest findings of Raman and his team, to be published in the journal Oncogene online Nov. 7, are the first to demonstrate a detrimental link between TWIST activity and estrogen resistance. Previous work by Raman and others had shown that TWIST was more active in women with aggressive breast cancer and less active in women whose breast tumors were benign. But researchers had not yet established the direct connection to lowered levels of estrogen receptors.

In five separate cancerous cell lines grown in the laboratory, some from women with aggressive forms of breast cancer and the rest without, TWIST activity was shown in all cells to be strongly active where estrogen receptor activity was low. Further tests in human tissue samples showed the same result. In additional experiments in mice injected with breast cancer cells, researchers found that TWIST activation led to continuous and aggressive tumor growth despite tamoxifen therapy, while in mice tumors with low levels of TWIST, tumor growth waned within two months of treatment.

The new experiments are also believed to be the first to show that estrogen resistance is not a permanent condition, the researchers report. Halting TWIST production in two cell lines resulted in some return of anti-estrogen drug sensitivity. Almost 40 percent of cells tested reverted from being estrogen receptor negative to estrogen receptor positive, and some 30 percent of these cell receptors became tamoxifen sensitive, allowing the drug to target the cancerous cells.

Using Anabolic Steroids for Exercising will Damage Your Liver

If you enjoy exercising you should never use steroids to enhance your performance in any sport nor to enhance your body image; it is not worth it. You could damage your health permanently, your liver amongst other organs.

Patient Case:

A 32-year-old man presented with a seven-day history of nausea, vomiting, and jaundice associated with severe itching. He had no medical history of note and had not taken any prescribed medications for several years. He did not drink alcohol regularly and denied having used recreational drugs, although he eventually admitted having taken 5 mg a day of methandrostenolone for the first time in the previous two months. He stated that he took the drug to enhance his body image.
Blood tests on admission showed bilirubin 651 µmol/L (normal range 0 to 19), alanine aminotranferase 76 IU/L (0 to 45), alkaline phosphatase 262 IU/L (35 to 120), and international normalised ratio 1.3. An extended liver screen (including serological testing for hepatitis A, B, C, and E as well as for cytomegalovirus and Epstein-Barr virus, full autoantibody profile, and markers of metabolic liver diseases), abdominal ultrasonography, and magnetic resonance cholangiopancreatography failed to identify any alternative causes. Cholestasis induced by anabolic steroids was diagnosed clinically (after his history of use of anabolic steroids had been ascertained). He was initially treated with ursodeoxycholic acid and observed. He became severely hypertensive on day 2, needing treatment with amlodipine.

Full citation

Stem Cells and Spinal Cord Repair Research Programs Shut Down by Geron

The currents financial recession/depression has forced the Biotechnology firm Geron to discontinue its stem-cell research program and halt a pioneering clinical study in people with spinal-cord injury. This decision made many patients frustrated because they had tremendous hope that this laboratory study was going to help them in the future, but also affected many research workers for the firm who had to be let go.

Stem-Cells Biotechnology

For the past couple of decades, clinicians have watched the stem-cell field with a mixture of anticipation and skepticism. No group of patients has been more expectant than those with spinal cord injuries. Therapies for spinal cord injury have been promised almost since the dawning of the stem-cell field. The recent launch — and abrupt termination — of a phase 1 clinical trial for acute spinal cord injury by the biotechnology company Geron whetted the appetite, and then fueled the frustration, of these patients.

The New England Journal of Medicine

Wrinkles Off Eating Chia for Breakfast

Chia is very beneficial for anybody, but if you like cycling, you definitely want to get into eating chia, simply because it gives you energy, has Omega3, and helps your skin not to get so many wrinkles after hours of having been in the sun pedaling with the wind hitting your face.

Dolphins and Humans Brain Intelligence Increased by Teamwork

The average adult human’s brain weighs about 1.3 kilograms, has 100 billion or so neurons, and sucks up 20% of the oxygen we breathe. It’s much bigger than an animal our size needs. According to a new computer model, the brains of humans and related primates are so large because we evolved to be social creatures. If we didn’t play well with others, our brains would be puny.

The idea behind the so-called social intelligence hypothesis is that we need pretty complex computers in our skulls to keep track of all the complex relationships we have with each other—who’s a friend, who’s an enemy, who’s higher in the social ranks. Some studies have supported this idea, showing for example that bigger-brained primates tend to live in bigger social groups. The same appears to hold true for dolphins. But these studies only identified associations between brain and group size; they don’t show how evolution might have worked.

Since they didn’t have a few million years of time on their hands, Ph.D. student Luke McNally and colleagues at Trinity College Dublin simulated evolution on a computer. They started with 50 simple brains. Each had just three to six neurons. The researchers then made each brain challenge the others to one of two classic games: the prisoner’s dilemma or the snowdrift game.

In the prisoner’s dilemma, two people have been taken in for questioning by the police. If both keep their mouths shut, they’ll both be set free. If one sells out the other, the snitch will get off and the other will do a long stint in jail. If they tell on each other, both get shorter sentences. If the game lasts only one round, it’s better to turn in your accomplice. But over the long term, players can start remembering who’s done them a favor and learning to cooperate by maintaining their silence. In the snowdrift game, two people need to dig themselves out of a snowdrift. The best outcome for each player is to sit back while the other one digs, but digging cooperatively isn’t bad, either. In each game, a player’s only choice is whether to cooperate.

After playing one of the games, the brains reproduced asexually. Individuals that did better were programmed to be more likely to have offspring. Then all of the brains in the new generation had a chance to undergo a random mutation. The mutations could change the brain’s structure, number of neurons, or the strengths of the connections between those neurons. Each simulation ran for 50,000 generations, with 10 runs of the simulation for each of the two games.

From: ping.fm

Rivaroxaban Tx Symptomatic Pulmonary Embolism

BACKGROUND
A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism.

METHODS
In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.

RESULTS
Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups.

CONCLUSIONS
A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit–risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE

From: ping.fm

Best US Hospitals List 2011-2012

Just 17 of the nearly 5,000 hospitals evaluated for the 2011-12 rankings qualified. 

Rank	Hospital	Points	Specialties
1	Johns Hopkins Hospital, Baltimore	30	15
2	Massachusetts General Hospital, Boston	29	15
3	Mayo Clinic, Rochester, Minn.	28	15
4	Cleveland Clinic	26	13
5	Ronald Reagan UCLA Medical Center, Los Angeles	25	14
6	New York-Presbyterian University Hospital of Columbia and Cornell, N.Y.	22	12
7	UCSF Medical Center, San Francisco	20	11
8	Brigham and Women’s Hospital, Boston	18	12
9	Duke University Medical Center, Durham, N.C.	18	10
10	Hospital of the University of Pennsylvania, Philadelphia	17	12

The other 7 hospitals in the list

George Hincapie’s Varicose Veins in one leg

This is close up picture of the -one of my favorite procyclists of the modern era- varicose veins of George Hincapie’s legs.
Some people ask why would a cyclist get those varicose veins if he exercises a lot, well, in his case two factors to take in consideration: genetics first, second, it could have been the possibility of EPO abuse but not likely since he has them only in one leg.

Multiple Sclerosis Scientific Molecular Map

The molecular structure, described in the February 17, 2012 issue of the journal Science, is unique as the first-ever-to-be-determined lipid G protein-coupled receptor (GPCR). Molecules of this type play important roles in everything from cancer to metabolism, and this recent success should pave the way for researchers to establish the structures of other family members.
“There’s something special about the S1P1 receptor,” said Hugh Rosen, MD, PhD, a Scripps Research chemical biologist who co-led the work with Raymond Stevens, PhD, a structural biologist also from The Scripps Research Institute. “The biological consequences of even small changes with this receptor are profound. Understanding its structure provides clues about fundamental processes important in both health and disease.”
“Being able to finally look at a lipid GPCR and the occluded cell surface binding pocket was a surprise but explains many of the issues we wondered about,” said Stevens. “It is likely that other members of this subfamily will have a similar protein architecture.”
The study is a result of decades of research by the Stevens lab to develop methods to determine the structure of GPCRs, much work in the Rosen lab on the receptor biology and chemical tools to stabilize such molecules, and a multi-disciplinary collaboration between the two labs, which Rosen notes is one of the hallmarks of research at The Scripps Research Institute. The scientists acknowledge the support of the National Institutes of Health Common Fund as making the new findings possible.
“This work promises to underscore the importance of research collaboration to accelerate scientific discovery and development of new drug therapies,” said James M. Anderson, MD, PhD, director of the Division of Program Coordination, Planning, and Strategic Initiatives that guides the NIH Common Fund. “Combining structure-based analysis with small molecule screening serves as a model for effective drug design.”
Controlling Multiple Sclerosis

The new work reveals the structure of the S1P1 receptor, a protein embedded in the membranes of various cell types. When natural ligands such as the signaling lipid sphingosine 1-phosphate or potential drugs make specific interactions deep in receptor, portions of the receptor change shape to trigger cascades of chemical reactions inside the cell important to the maintenance of health.
Researchers have long known that S1P1 receptors play critical roles in controlling multiple sclerosis and other diseases. One way these receptors do this is by regulating the flow of certain white blood cells, or lymphocytes, out of lymph nodes.

This is critical because in patients with multiple sclerosis, auto-reactive lymphocytes attack the protective sheaths of nerve cells in the brain, causing malfunctions in the way the central nervous system transmits signals through the body. The S1P1 receptors are also involved in the progressions of harmful scarring and swelling in response to lymphocyte damages in the brain.
Gilenya, the first oral drug approved to treat multiple sclerosis, reduces this lymphocyte flow out of the lymph nodes in ways first identified by Rosen’s lab about 10 years ago. Based on a screening lead from the National Institutes of Health Molecular Libraries Small Molecule Repository, Rosen and Scripps Research Chemistry Professor Ed Roberts discovered and optimized other modulators of S1P1 receptors. This led to RPC-1063, a compound in clinical trials for multiple sclerosis by Receptos, a company co-founded by Rosen and Stevens.
Rosen’s lab has also shown that modulating S1P1 receptors can protect mice from a pandemic flu virus. This shows that the receptors may also be good drug development targets for other conditions tied to immune responses.
A Shifting Binding Pocket
The new study used the technique of x-ray crystallography to reveal the high-resolution three-dimensional image of the S1P1 receptor. The results provide scientists with important new details about the receptor’s mechanism of action.
One aspect of the receptor structure that is of particular interest is the binding pocket for the natural ligand or potential drugs that activate the receptor responses. The structure revealed how the binding pocket shifts to activate signaling. Understanding how that occurs makes it easier to identify additional compounds that might have effects in controlling the receptors.
With this structural information in hand, the scientists can now advance efforts to understand the specific chemical transformations that drive the cellular responses tied to multiple sclerosis and other diseases. “Better understanding always allows you to think about applications in a variety of ways that you might not have thought about before,” said Rosen. “This is an area that will keep us busy for many years to come.”
The S1P1 receptor structure has already yielded benefits, according to Michael Hanson, a scientist and director at Receptos, and lead author of the new paper. “The structure has helped us understand the details regarding receptor-ligand interactions for this receptor and structural data can be used more routinely for drug discovery projects of other GPCRs,” he said.

From: http://ping.fm/dGq3z

Researchers Gather for Shared Resources Fair and Drug Discovery Forum | Miller School of Medicine | University of Miami

The Miller Office of Research hosted two events this month at the Miller School for the research community – a Shared Resources Fair on the morning of February 17, and a Collaborative Research Exchange Forum (CREF) on drug discovery in the afternoon.

More than 200 researchers attended the third Shared Resources Fair, which featured nearly 50 posters with information about the varied core laboratories, facilities, and shared resources supporting discovery science, translational, and clinical research. Later, more than 50 faculty, staff, and students gathered at the Lois Pope LIFE Center for the forum to share information on drug discovery.

Led by Norma Sue Kenyon, Ph.D., the Martin Kleiman Professor of Surgery, Microbiology and Immunology, and Biomedical Engineering and senior associate dean for translational science, and Andrew Vinard, manager of biotechnology resources, the Core and Shared Facilities Office within the Miller Office of Research supports research excellence at the University. The fair was co-hosted by the Sylvester Comprehensive Cancer Center and the Wallace H. Coulter Center for Translational Research. Kenyon said events such as the Shared Resources Fair and the CREF reflect the University’s continuing support of its research community.

“The Miller School is committed to developing state-of-the art facilities, encouraging their use, and advancing scientific collaboration in areas of key importance to biomedical research,” said Kenyon, who is also director of the Coulter Center.

Claes Wahlestedt, M.D., Ph.D., professor of psychiatry and behavioral sciences and associate dean for therapeutic innovation, who led the drug discovery forum, added that topics like drug discovery especially benefit from an interdisciplinary team science approach.

“The Miller School has the expertise and laboratory resources needed to identify compounds that can be developed into the next generation of therapeutics,” Wahlestedt said

The CREF began with presentations and a panel discussion on:

• Chemoinformatics and drug discovery by Stephan Schürer, Ph.D., research assistant professor of molecular and cellular pharmacology and the Center for Computational Science’s lead scientist for chemoinformatics;

• Molecular oncology and drug discovery by Anthony Capobianco, Ph.D., professor of surgery and director of the Molecular Oncology Research Program, Division of Surgical Oncology;

• Cell biology and drug discovery by Glen Barber, Ph.D., chair of cell biology and anatomy, professor of medicine, and associate director of basic research at Sylvester.

Additional presentations and another panel discussion followed on these projects:

• Drug discovery at The Miami Project to Cure Paralysis by Vance Lemmon, Ph.D., the Walter G. Ross Distinguished Chair in Developmental Neuroscience and professor of neurological surgery;

• Peggy and Harold Katz Family Drug Discovery Center by Vineet Gupta, Ph.D., assistant professor of medicine, biochemistry and molecular biology, and the founding co-director of the Katz Center;

• Center for Therapeutic Innovation by Nagi Ayad, Ph.D., associate professor of psychiatry and behavioral sciences; and Shaun Brothers, Ph.D., research assistant professor of psychiatry and behavioral sciences.

From: http://ping.fm/TfYiU