Better approach to treating deadly melanoma identified

Dec. 19, 2012 ? Scientists at The University of Manchester have identified a protein that appears to hold the key to creating more effective drug treatments for melanoma, one of the deadliest cancers.

Researchers funded by Cancer Research UK have been looking at why new drugs called "MEK inhibitors," which are currently being tested in clinical trials, aren't as effective at killing cancer cells as they should be.

They discovered that MITF -- a protein that helps cells to produce pigment but also helps melanoma cells to grow and survive -- is able to provide cancer cells with a resistance to MEK inhibitors.

Dr Claudia Wellbrock and her team at the Wellcome Trust Centre for Cell-Matrix Research compared human melanoma cells that respond to the drug to cells that don't. They discovered that the cells that didn't respond to the drug contained higher levels of the protein SMURF2.

The researchers reduced the level of SMURF2 in the melanoma cancer cells and then treated the tumour with the MEK inhibitor. They found a 100 fold increase in the sensitivity of the cells to the drug. It appears that removing SMURF2 radically decreases the level of MITF in melanoma cells, making the MEK inhibitor a lot more powerful.

Using mice with tumours the team found that over a three week period there was a substantial decrease in tumour growth when the removal of SMURF2 was used in combination with MEK inhibitors.

Dr Wellbrock says: "Much of cancer research is now focussed on finding new drug combinations. It's recognised that cancers frequently find new ways to combat even the most novel and highly efficient drug treatments, so we are now focussing on targeting the mechanisms that allow the cancer cells to overcome the drug effects. We're very excited about the potential for this new approach that has proved to be so effective in our experiments."

One of the drawbacks of the MEK inhibitor drug is that it targets all cells. MEK (MAP/ERK kinase protein) is present in all cells but cancer cells have overactive MEK. This means the drug must be used in small doses and for a lengthy period to avoid harming healthy cells. By reducing SMURF2 to increase the drug's effectiveness smaller doses could be given over a shorter time period, reducing the level of toxicity in healthy cells.

Dr Wellbrock says: "If we can reduce the toxicity to all cells it will mean cancer treatments are less harmful to patients. It's vital that we improve the treatments for melanoma which is the fifth most common cancer in the UK. By the time many people are diagnosed with melanoma the cancer has already started to spread and advanced tumours can be highly resistant to conventional cancer treatments. The development of resistance to new drugs has also been a major drawback. If we can identify more potent and less toxic drug combinations to tackle melanoma then we could save thousands of lives."

This study was funded in part by Cancer Research UK and the results have been published in the Journal of the National Cancer Institute.

Talking about the research Dr Julie Sharp from the charity said: "Recently there have been some really exciting developments in treating melanoma -- but new approaches that tackle the problem of resistance are still needed. This type of research will be a key focus of the planned new Manchester Cancer Research Centre which will bring together a wide range of research expertise to revolutionise cancer treatment."

The next step for Dr Wellbrock will be to find a drug that can reduce the activity of SMURF2 in cancer cells. The Manchester research team are now screening drug libraries for an existing drug that may already be approved for use for a different illness.

It's hoped that identifying a drug to use in combination with MEK inhibitors will provide a much more powerful and ultimately more successful approach to treating melanoma.

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Story Source:

The above story is reprinted from materials provided by Manchester University.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

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Journal Reference:

1. M. P. Smith, J. Ferguson, I. Arozarena, R. Hayward, R. Marais, A. Chapman, A. Hurlstone, C. Wellbrock. Effect of SMURF2 Targeting on Susceptibility to MEK Inhibitors in Melanoma. JNCI Journal of the National Cancer Institute, 2012; DOI: 10.1093/jnci/djs471

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/khn6WUoD1fQ/121219082813.htm

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Video: Schiff: Fed Will Keep Printing Money Until Economy Collap...

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Source: http://video.msnbc.msn.com/cnbc/50226392/

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NHL lawsuit assigned to former federal prosecutor

NEW YORK (AP) ? The NHL's lawsuit against its players was assigned to a relatively new federal judge who is a longtime New York Yankees fan and a former federal prosecutor.

The sides didn't talk Sunday, the 92nd day of a lockout that is threatening to wipe out an entire NHL season for the second time in nine years. NHL players started voting on whether to have their union give up collective bargaining rights, a "disclaimer of interest" that could be a precursor to an antitrust suit.

The league argued in a 43-page suit Friday in federal court in Manhattan that the union's actions were a bargaining maneuver and asked that the lockout be declared legal. The case was assigned to U.S. District Judge Paul A. Engelmayer, who joined the bench in July 2011.

The 51-year-old is a graduate of Horace Mann School, Harvard College and Harvard Law School.

He spent a year between college and graduate school as a reporter for The Wall Street Journal. After clerking for Supreme Court Justice Thurgood Marshall, he had two stints in the U.S. Attorney's office in Manhattan, rising to chief of the major crimes unit. He also worked in the Solicitor General's office in Washington, D.C.

One of his more prominent cases occurred in 1999, when he led the prosecution of Lawrence X. Cusack III, convicted on 13 counts on mail and wire fraud stemming from the sale of forged documents claiming President John F. Kennedy paid hush money to keep secret an affair with Marilyn Monroe. Cusack was sentenced to 10 years, 3 months in prison and ordered to pay $7 million restitution.

Two years earlier, Engelmayer prosecuted a Los Angeles woman, Autumn Jackson, who was convicted of conspiracy and crossing state lines to commit a crime for threatening to tell tabloids she was Bill Cosby's out-of-wedlock child unless he paid her $40 million. Jackson was sentenced to 26 months in prison. Cosby denied he was Jackson's father but admitted having an affair with her mother and providing more than $100,000 in financial support.

Engelmayer worked from 2000-11 with the New York law firm now known as WilmerHale before he was nominated for the bench by President Barack Obama and confirmed by the Senate.

In his most notable decision thus far, Engelmayer ruled a provocative ad that equates Muslim radicals with savages is protected speech under the First Amendment. New York's Metropolitan Transportation Authority initially refused to run the ad, saying it was "demeaning."

Source: http://news.yahoo.com/nhl-lawsuit-assigned-former-federal-prosecutor-224303378--nhl.html

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Microscopic beauties found in a slimeball

Colonial rotifers get jiggy with it in a video entered in the Olympus BioScapes Digital Imaging Competition. Australian high-school teacher Ralph Grimm assembled the video from microscopic images.

By Alan Boyle

You might not think something wonderful can be found in a ball of slime ? but Ralph Grimm's prize-winning video of the creatures living in a bit of pond scum proves it's possible.

Grimm's microscopic view of a colony of rotifers, complete with googly eyespots, won first prize in this year's Olympus BioScapes Digital Imaging Competition. More than 2,000 pictures of tiny life-science subjects were submitted from all over the world ? and today Olympus announced that Grimm led the top-10 list. You can see all 10 prize-winners, plus a selection of the entries receiving honorable mentions, in our slideshow.

Grimm, a 45-year-old high-school teacher from the Australian town of Jimboomba, says he found the microscopic colony in a bit of drab-looking leaf debris that he dredged up from a pond on his property.?"They look very plain," Grimm told me. "They look like slimeballs. You wouldn't take notice unless you knew what you were looking for."

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Fortunately, Grimm knew exactly what he was looking for, thanks to his long-running passion for microscopy. He recalled that he got his first microscope as a gift at the age of 7. "Once I learned to use the instrument, I got hooked on it. It's followed me along all my life," he said.

When Grimm got the slimeball under his microscope and cranked the magnification to 200x, he couldn't believe his eyes. "I had never seen this species of rotifer before," he said. Rotifers are tiny animals that live primarily in fresh water and gobble up gunk. As I mentioned last year in an item about the critters, there's a good chance that you've swallowed down more than a few rotifers if you drink unfiltered tap water. Some might think they're icky, but Grimm thought they were so cool that he set aside everything else he had planned for the day.

"Forget about lunch. Don't worry about breakfast," he said. "This is how I spent the entire day, just filming." After capturing gigabytes' worth of pictures, Grimm figured he had a good entry for the Olympus contest. And he was right.

As the first-prize winner, Grimm is receiving $5,000 worth of Olympus camera and microscope equipment, plus an expense-paid trip to San Francisco to bask in his glory. Arlene Wechezak's picture of red algae earned her the $2,500 second prize, and Igor Siwanowicz won the $1,500 third prize.

Click through the top images from the 2012 Olympus BioScapes International Digital Imaging Competition, which features microscopic images of life science subjects

Siwanowicz's ultra-close-up view of a fern wasn't the only picture recognized by the judges: He also scored three honorable mentions for his beautiful portraits of a feathery amphipod appendage, a moth's curled-up proboscis and an oak lace bug.

Siwanowicz, a researcher at the Howard Hughes Medical Institute's Janelia Farm research campus in Virginia, uses a laser-scanning confocal microscope and a palette of pigments to bring out the details in his small-scale subjects.?"To our eyes, the specimens appear very different from the final image," Siwanowicz told me in an email. "Usually they are colorless, sometimes showing red hue, depending on the intensity of staining. The samples of invertebrate exoskeletons stained with Congo Red dye are very often bright red."

He assigns different colors to the different wavelengths given off when his subjects are illuminated. "Assignment of the color in the captured image to any given channel is purely arbitrary; however, I do assign blue to the channel recording light of the shortest wavelength, green and red in similar fashion, in the 'natural' order," he said. "Combining the three channels into one produces the whole palette of colors. That is the closest to real representation of colors achievable with this microscopic technique ? in effect, it is like the microscope had trichromatic?'vision,' just as we do."

Click through the slideshow to see what Siwanowicz is talking about?? and grab your red-blue glasses to see the 3-D effect in this bonus picture of the oak lace bug. If you're in need of some red-blue specs, stay tuned: We'll be running a 3-D glasses giveaway on the Cosmic Log Facebook page later today.

Igor Siwanowicz

This 3-D photomicrograph provides a frontal view of the oak lace bug, a common pest found in oak trees. Wear red-blue glasses to see the 3-D effect.

More small wonders:

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Alan Boyle is NBCNews.com's science editor. Connect with the Cosmic Log community by "liking" the log's?Facebook page, following?@b0yle on Twitter?and adding the?Cosmic Log page?to your Google+ presence. To keep up with Cosmic Log as well as NBCNews.com's other stories about science and space, sign up for the Tech & Science newsletter, delivered to your email in-box every weekday. You can also check out?"The Case for Pluto,"?my book about the controversial dwarf planet and the search for new worlds.

Source: http://cosmiclog.nbcnews.com/_news/2012/12/17/15958431-how-beauty-was-found-in-a-slimeball?lite

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Simple, inexpensive way to improve healing after massive bone loss

ScienceDaily (Nov. 21, 2012) ? Bones are resilient and heal well after most fractures. But in cases of traumatic injury, in which big pieces of bone are missing, healing is much more difficult, if not impossible. These so-called "large segmental defects" are a major clinical problem, and orthopaedic surgeons struggle to treat them, especially among the military in places like Afghanistan.

Now research led by investigators at Beth Israel Deaconess Medical Center (BIDMC) offers surgeons a new approach. Described online in a recent issue of the Journal of Bone and Joint Surgery, the results confirm that the bone healing process of large segmental defects is exquisitely sensitive to its mechanical environment and suggests that "reverse dynamization," a straightforward and inexpensive process, could help speed healing of these traumatic injuries.

"Bones are greatly influenced by their mechanical environment, which is why casts, rods, plates and screws are typically used to heal fractures -- with a great deal of success," explains senior author Christopher Evans PhD, Director of the Center for Advanced Orthopaedic Studies at BIDMC. "But until now, no one has examined the relevance of the mechanical environment to the healing of large segmental bone defects."

According to the American Association of Orthopaedic Surgeons (AAOS), these injuries are one of the most demanding surgical challenges faced by orthopaedic trauma surgeons. Often as large as 20 centimeters in length, large segmental defects can be complicated by regional soft-tissue loss, reduced vascularity, regional scarring and infection. The AAOS notes that an increased number of missions being conducted on foot in Afghanistan has led to an increase in this type of combat blast injury.

Changing levels of stiffness during bone healing is known as "dynamization." During standard dynamization, bone is first held rigidly in place by a mechanical intervention, or fixation device. Once healing has begun, the stiff rigidity is loosened to allow movement. "An 'external fixator' is placed on the outside of the skin and usually has a 'cross-bar' that determines the level of rigidity and can be adjusted to allow more or less motion," explains Evans, who is also the Maurice Edmond Mueller Professor of Orthopaedic Surgery at Harvard Medical School. Evans and his colleagues thought that how firmly or loosely injured bone is held together by mechanical interventions -casts, rods, plates and screws -- could impact these large segmental bone defects, just as it does for more minor fractures -- but with one big difference. The scientists changed stiffness levels in the opposite order -- hence, "reverse dynamization."

"Our laboratory has a lot of experience with a rat model of segmental defect healing, and we noticed that during the healing process, the defect first fills with cartilage, and then the cartilage turns to bone," says Evans. Technically known as "endochondral ossification" this process is well documented to occur in fracture healing. 'We knew from other previous work that the early formation of cartilage is helped when mechanical fixation is loose. We also knew that a subsequent increase in fixator stiffness would provide the rigidity needed for the ingrowth of blood vessels and other aspects of healing." Evans and his coauthors hypothesized that a period of loose "fixation" followed by a period of stiffened "fixation" would accelerate healing of large segmental defects. "If bones are allowed to move slightly, cartilage will form in the defect," he adds. "If the area is then held rigidly in place, the new cartilage will then turn to bone."

The team constructed external fixators capable of providing varying degrees of stiffness during the healing process. By implanting a growth factor called bone morphogenetic protein-2 on a collagen sponge, the scientists initiated healing of segmental defects in the femurs of 60 rats. Groups of the animals were then allowed to heal with either low-, medium-, or high-stiffness fixators. Healing also took place under conditions of reverse dynamization, in which the stiffness levels were changed from low to high after a period of two weeks. After eight weeks, the researchers assessed healing using various measures including radiographs, microscopic analyses, and mechanical tests.

The investigators found that when they looked only at unchanging stiffness, the low-stiffness fixator produced the best healing; however, by comparison, the reverse dynamization provided considerable improvement, leading to a marked acceleration in the healing process by all tests. Also, notes Evans, the bone mineral content and bone area of the defects healed by reverse dynamization were closer to normal, and the healed bone had greater mechanical strength.

"Our study confirms the exquisite sensitivity of bone healing to its mechanical environment," he notes. The next step, says Evans, will be to see if this therapy works in large animals, while also gathering more information about the biological mechanisms that are at play. But, he adds, moving these findings into a clinical setting should be relatively straightforward. "The nice thing about this approach is that it's simple and could be rapidly translated to human use if our proposed large-animal studies are successful. The regulatory hurdles should be minor." Furthermore, he adds, reverse dynamization might also be applicable to other situations for which bone healing is problematic. "Sometimes in smokers or individuals with diabetes, fractures heal poorly," he notes, adding that the same can be true when an infection is present.

Reverse dynamization is also an attractive option in terms of cost. "Often, strategies devised in the lab to solve clinical problems are far too complex and expensive to be translated into meaningful clinical use," notes study coauthor Mark Vrahas, MD, Chief of the Harvard Orthopaedic Trauma Service. "But if the promise of this strategy holds out, it will be inexpensive enough to be used even in developing countries, where the burden of severe injuries are particularly high."

In addition to Evans and Vrahas, study coauthors include BIDMC investigators Vaida Glatt, PhD, Alan Ivkovic, MD, PhD, and Fanjun Liu, MD, PhD; Micah Miller of Harvard Orthopedic Trauma Service, Harvard Medical School; Nicola Parry, DVM, of the Massachusetts Institute of Technology; and Damian Griffin, MD, of Warwick University Medical School, Coventry, UK.

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Story Source:

The above story is reprinted from materials provided by Beth Israel Deaconess Medical Center.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Vaida Glatt, Micah Miller, Alan Ivkovic, Fangjun Liu, Nicola Parry, Damian Griffin, MD; Mark Vrahas, Christopher Evans. Improved Healing of Large Segmental Defects in the Rat Femur by Reverse Dynamization in the Presence of Bone Morphogenetic Protein-2. J Bone Joint Surg Am, 2012 Nov 21;94(22):2063-2073 DOI: 10.2106/JBJS.K.01604

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/T5vhKnLPTvI/121121145617.htm

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Income Tax Rates FY 2012-13 / AT 2013-14 for Individual & HUF

RATES OF INCOME-TAX AS PER FINANCE ACT, 2012:

As per the Finance Act, 2012, income-tax rates Applicable for Assessment Year 2013-14 / Financial Year 2012-13 Applicable to Individual, HUF, is as follows :-

Rates of tax

A.? HUF &? Individual (Including Female Assessee )? who is of the age of sixty years or Less

Sl. No.	Total Income	Rate of tax
1	Where the total income does not exceed Rs. 2,00,000/-.	Nil
2	Where the total income exceeds Rs. 2,00,000 but does not exceed Rs. 5,00,000/-.	10 per cent of the amount by which the total income exceeds Rs. 2,00,000/-
3	Where the total income exceeds Rs. 5,00,000/- but does not exceed Rs. 10,00,000/-.	Rs. 30,000/- plus 20 per cent of the amount by which the total income exceeds Rs. 5,00,000/-.
4	Where the total income exceeds Rs. 10,00,000/-.	Rs. 1,30,000/- plus 30 per cent of the amount by which the total income exceeds Rs. 10,00,000/-

B. Rates of tax for every individual, resident in India, who is of the age of sixty years or more but less than eighty years at any time during the financial year:

Sl. No	Total Income	Rate of tax
1	Where the total income does not exceed Rs. 2,50,000/-.	Nil
2	Where the total income exceeds Rs. 2,50,000 but does not exceed Rs. 5,00,000/-.	10 per cent of the amount by which the total income exceeds Rs. 2,50,000/-
3	Where the total income exceeds Rs. 5,00,000/- but does not exceed Rs. 10,00,000/-.	Rs. 25,000/- plus 20 per cent of the amount by which the total income exceeds Rs. 5,00,000/-.
4	Where the total income exceeds Rs. 10,00,000/-.	Rs. 1,25,000/- plus 30 per cent of the amount by which the total income exceeds Rs. 10,00,000/-

C. In case of every individual being a resident in India, who is of the age of eighty years or more at any time during the financial year:

Sl. No	Total Income	Rate of tax
1	Where the total income does not exceed Rs. 5,00,000/-.	Nil
2	Where the total income exceeds Rs. 5,00,000 but does not exceed Rs. 10,00,000/-.	20 per cent of the amount by which the total income exceeds Rs. 5,00,000/-
3	Where the total income exceeds Rs. 10,00,000/-.	Rs. 1,00,000/- plus 30 per cent of the amount by which the total income exceeds Rs. 10,00,000/-

2.2 Surcharge on Income tax:

There will be no surcharge on income tax payments by individual taxpayers during FY 2012-13 (AY 2013-14).

2.3.1 Education Cess on Income tax:

The amount of income-tax shall be increased by Education Cess on Income Tax at the rate of two per cent of the income-tax.

2.3.2 Secondary and Higher Education Cess on Income-tax:

From Financial Year 2007-08 onwards, an additional surcharge is chargeable at the rate of one per cent of income-tax (not including the Education Cess on income-tax).

Education Cess, and Secondary and Higher Education Cess are payable by both resident and nonresident assessees.

Source: http://taxguru.in/income-tax/income-tax-rates-fy-201213-201314-individual-huf.html

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CDC: Meningitis outbreak growing, 14 people dead

WASHINGTON (AP) ? Federal health officials said they've tracked down more than 90 percent of the roughly 14,000 people who may have received contaminated steroid shots, urging anyone with early symptoms of potentially deadly meningitis to seek help fast.

Of the 170 people sickened in the outbreak, all but one have a rare fungal meningitis, and 14 have died, the Centers for Disease Control and Prevention said Thursday. One person identified by Michigan health officials received the steroid shot in the ankle and has an infection there. While the biggest concern is for people given the shots for back pain, the CDC said people who received the injections in joints should also be alert to signs of localized infection, including redness, pain, swelling and fever.

More than 50 vials of the steroid produced by a specialty pharmacy in Massachusetts, the New England Compounding Center, have been found contaminated with some sort of fungus, said Deborah Autor of the Food and Drug Administration. The investigation is continuing into how the contamination could have occurred.

But a Massachusetts official said Thursday that it appears the company violated state law governing how compounding pharmacies are supposed to work. They are not supposed to do large-scale production like a drug manufacturer, but to produce medication for patient-specific prescriptions, said Dr. Madeleine Biondolillo of the Massachusetts Department of Public Health.

"This organization chose to apparently violate the licensing requirements under which they were allowed to operate," she told reporters Thursday.

The pharmacy has recalled the steroid that was sent to clinics in 23 states, as well as everything else it makes.

Idaho becomes the 11th state to report at least one illness. The others are Florida, Indiana, Maryland, Michigan, Minnesota, New Jersey, North Carolina, Ohio, Tennessee and Virginia.

____

Stobbe reported from New York.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/bbd825583c8542898e6fa7d440b9febc/Article_2012-10-11-Meningitis%20Outbreak/id-62cdf6806b63410bac0e089501708727

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