Picking the Ideal Sin City Dental Services For Your Little Ones ...

As mentioned earlier, young children are direct receptors of their parent?s actions and emotions. In order for your child to stay calm, you will need to be doing the same. Although it can be tempting, avoid squeezing your child?s hand as the dentist begins inspecting and cleaning their teeth. Your child will instantly see this protective behavior as an indicator that something is wrong, and will not cooperate for the appointment.

Also avoid looking fearful during your child?s appointment, and use frequent positive encouragement to your child throughout. Another point worthy of mentioning is to avoid using the dentist, or any health care profession, for that matter, as a threat to your child. Your child?s safety and comfort are incredibly important for several reasons.

Going to the dentist can pose as a huge obstacle for many parents, but these next few tips should ease the mind of the parent and make them feel more confident in their ability to aid their child. You want your child to trust their dentist, not fear them. Having a phobia can prevent them from receiving the best care.

The first thing to know when taking children to the dentist is when the best time to do it is. It is recommended to take your child to the dentist for their first appointment promptly after they grow their first tooth. Being proactive and going during this time, rather than at the age of three, is a great step towards catching potential oral problems early on. The earlier an issue is observed, the earlier and faster it can be repaired by the dentist.

After the child?s first appointment, they should continue visiting the dentist once every six months, just as the parents should be doing. This will get everyone in the family in the habit of attending dentist?s appointments regularly, automatically creating a safe feeling for the child. Another point to keep in mind when dealing with your child?s first visit to the dentist is to watch the vocabulary used when describing the dentist?s office to your child.

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Munch This! ? Blog Archive ? Get a taste of Coconut Grove this ...

Featured, Food News. ? By Leoncio Alvarez on April 11, 2012 at 4:40 pm

One of the city?s more pocket-friendly food festivals will be?happening?this Saturday and Sunday. Great Taste of The Grove will take place April 14 and 15 from 11 a.m. to 7 p.m.

The Best of Taste and The Best of Presentation will be crowned on Sunday, presented by Channel 7?s Belkys Nerey. Panorama Restaurant is going four years strong and will be vying for the crown one more time this year. Each restaurant will be showcasing its best dish, according to Annabelle Bovet, of Belle Plume Communications. Against Panorama will be Bahama?s Specialty Food, Chart House, Jaguar Ceviche, Los Ranchos and Spartico from The Mayfair.

Introduced last year, the ?Sommelier Tasting Grove? and ?Connoisseur Spirits Lounge???will be offering guests the?opportunity to try some of the best wine and spirits around.

Come by for the food, drinks and the spectating. It is rumored that the very first ever Batman and James Bond cars will be displayed. And the kids can have fun in an adventure park.

General tickets are $5,with children under 12 free. ?Food and beverages will range from $1 ? $8. Peacock Park is located at 2820 MacFarlane Road.

Tags: bahama specialty food, chart house, food news, great taste of the grove, jaguar ceviche, los ranchos, miami news, panorama, spartico

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Joshua Ledet earns standing ovation on 'Idol'

In this April 4, 2012 photo released by Fox, Joshua Ledet performs on the singing competition series "American Idol," in Los Angeles. (AP Photo/Fox, Michael Becker)

In this April 4, 2012 photo released by Fox, Joshua Ledet performs on the singing competition series "American Idol," in Los Angeles. (AP Photo/Fox, Michael Becker)

In this April 4, 2012 photo released by Fox, Joshua Ledet performs on the singing competition series "American Idol," in Los Angeles. (AP Photo/Fox, Michael Becker)

In this undated image released by Fox, clockwise from left, "American Idol" contestants Skylar Laine, Phillip Phillips, Colton Dixon, DeAndre Brackensick, Elise Testone, Jessica Sanchez, Hollie Cavanagh and Joshua Ledet pose in Los Angeles. (AP Photo/FOX, Frank Micelotta)

In this undated image released by Fox, clockwise from left, "American Idol" contestants Skylar Laine, Phillip Phillips, Colton Dixon, DeAndre Brackensick, Elise Testone, Jessica Sanchez, Hollie Cavanagh and Joshua Ledet pose in Los Angeles. (AP Photo/FOX, Frank Micelotta)

(AP) ? Joshua Ledet ran ahead of the competition on "American Idol."

The booming 20-year-old singer from Westlake, La., had the Fox singing competition's judges on their feet Wednesday for his lively rendition of Bruno Mars' up-tempo tune "Runaway Baby." After Ledet's routine, which featured a horn section and go-go dancer, Randy Jackson told him it was "another unbelievable performance" and he's got everything going for him.

"You can sell a song like a work of art," beamed Steven Tyler.

Other singers who pleased the panel during the evening of tunes from 2010 to the present included 18-year-old country rocker Skylar Laine of Brandon, Miss., accompanying herself on guitar with Kellie Pickler's "Didn't You Know How Much I Loved You," and 16-year-old vocalist Jessica Sanchez of San Diego with Jazmine Sullivan's passionate "Stuttering."

"Jessica, every time I hear you sing, I forget where I am," Tyler said.

"Idol" mentor Jimmy Iovine laid down a gauntlet between 20-year-old rocker Colton Dixon, of Murfreesboro, Tenn., and 21-year-old pawn shop worker Phillip Phillips of Leesburg, Ga. Dixon delivered an emotional take on Skylar Grey's version of the Eminem and Rihanna hit "Love the Way You Lie," while Phillips failed to flourish with Maroon 5's "Give a Little More."

"It was just a little bit underwhelming for the Phillip Phillips I love," said Jennifer Lopez.

After landing in the bottom three last week, 28-year-old teacher Elise Testone, of Charleston, S.C., bounced back by closing the show with Lady Gaga's "You and I," and perfection continued to evade demure 18-year-old singer Hollie Cavanagh of McKinney, Texas. The show's judges weren't wowed by Cavanagh's rendition of Pink's "Perfect."

"It wasn't perfect, but it's a lot better than where you were last week," said Jackson.

Between the individual performances, the seven finalists paired up for two duets and a trio: Phillips and Testone got together for "Somebody That I Used to Know" by Gotye; Laine and Dixon crooned "Don't You Wanna Stay" by Jason Aldean and Kelly Clarkson; and Cavanagh, Ledet and Sanchez took on "Stronger" by first-season "Idol" champion Kelly Clarkson.

The finalist with the fewest viewer votes will face elimination Thursday.

___

Fox is a unit of News Corp.

___

Follow AP Entertainment Writer Derrik J. Lang on Twitter at http://www.twitter.com/derrikjlang .

___

Online:

http://www.americanidol.com

Associated Press

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How Web Hosting is Essential for Online Presence | Internet ...

web hosting
website hosting
cPanel hosting
The Internet gives chances for any person motivated enough to find a business of his own or ?try? something different, and the chances are endless. Have you ever dreamed of running your own internet site, your own piece with the ?dot com? pie? It all begins with a great idea, but to get a successful website launched and established it needs a bit of struggle. Anyone can generate a money making internet website with period, will, and the few bucks every month it takes to host it. And, like preparing a brick-and-mortar business, creating a website is often as much about expressing personalized development and providing the modern world with a service precisely as it is about earning a living.

So, to do business online you?ll want a internet site. Why? There are many answers to this question. Some of the most important reasons to establish a great world wide web presence are:

1. Improved reputation. It?s a idea that a professional, well-designed website contains a good impression on the customers?s trust inside your online shop. It shows you will be up-to-date and you like your clients by offering them a convenient method to contact you and to learn about your products and services. Using the World Wide Web looking for services and products is noticeably easier and quicker than searching personally through the Yellow Internet pages.

2. A 24/7 Worldwide presence. Your internet website is available for your potential customers round the clock, 7 days a week. With a web site, you open yourself up to a world of opportunity in reaching individuals who might not otherwise find you. When your offices are closed you will be sure that your website is ready to accept showcase your product or service and answer your clients?s queries.

3. A powerful gross sales tool. Your clients are able to reach your services and products in their own time. You can lower your expenses on printing costs for brochures, coupons, flyers, newsletters, and other mailings. Of course, a internet site doesn?t exclude the standard forms of marketing, but rather complements them.

But if you are here, chances are you already have a internet website or considering having one, so let?s proceed to another step: hosting a web site.

A internet website is basically a set of files linked via a navigation system. More complex internet site can have buttons, forms and extended functionality with a database to save e-mails, requests, products characteristics, or anything else. but in the terminate they come down to the same principle: a collection of file types. So, hosting a internet site may be the process of making those files available to the Internet users. To produce the website available on the Internet users you need:

A computer connected to the Internet where the files is going to be stored.
A software called web server (for example Apache Web Server) that will ?serve? the files on the visitors. A way to make the visitors find your site.

Why can?t you use your own computer to host your internet-site? It has already an Internet connection and that Apache/IIS Server shouldn?t be so hard to put. Well, i

Link to your article

Please use the following html code in pages of other websites (including your own) to link to your article. This in turn raises the popularity of your article, and the amount of visitors that will visit your website through the links on our website, and will also raise your Google search position.

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SmartGuard 300W, 4-in-1 Security system ... - Home Improvement

SmartGuard 300W, 4-in-1 Security system: Motion activated light+video camera+SD card memory+audio warning

SmartGuard 300W, 4-?n-1 Wellbeing system: Motion activated light+record camera+SD card memory+audio warning Facial appearance :

  • CUS list, inspected b? Intertek, (120watts ?nd 150watts ?r? ?l?? available)
  • 150 point wide angle motion detection, covers ?b??t 1500 square feet ?f semicircle area
  • 300 watts halogen lamps, hidden built-?n wellbeing camera ?nd audio warning alarm triggered via motion sensor
  • Simple t? install ???t l?k? ?n? outdoor light ?t entrances, patio, garage, porch, barn, etc
  • F?r outdoor ???, 2GB SD card INCLUDED, multiple working mode settings, product record: http://www.youtube.com/watch?v=l2N9Lqagbs0

Read more SmartGuard 300W, 4-?n-1 Wellbeing system: Motion activated light+record camera+SD card memory+audio warning details information fr?m original source page here.

SmartGuard 300W, 4-?n-1 Wellbeing system: Motion activated light+record camera+SD card memory+audio warning Description :

Proven effectiveness ?n situations fr?m th? city t? th? farm. Th?? 300W motion sensor wellbeing light ?? a self-contained wellbeing system, complete w?th record camera ?nd audio warning. Wh?n th? motion detector ?? triggered, th? floodlights come ?n, record ?t?rt? tape, ?nd ?n audio warning ?f ???r ?h???? sounds. Package includes a 2GB SD memory card (replaceable w?th SD cards up t? 32 GB), 300W halogen bulbs, ?nd back-up batteries. SD cards simply overwrite previous metaphors ?h??ld th? memory fill. Available audio warnings include two preprogrammed warnings ?nd two warnings ??? record yourself. SmartGuard ?? engineered f?r outdoor ???, ?? weather-proof, ?nd ideal f?r home, office, ?nd community wellbeing. Set time ?nd date using integrated LCD screen. Th?? unit ?? very simple t? install, ???t mount SmartGuard ?nt? ?n? outdoor light fixture around th? home ?r office ?? ??? w??ld ?n? outdoor light, such ?? above ???r garage, patio, outbuildings, ?nd entranceways.

Read ?ll SmartGuard 300W, 4-?n-1 Wellbeing system: Motion activated light+record camera+SD card memory+audio warning reviews fr?m consumer page here, ?r ??? ??n compare SmartGuard 300W, 4-?n-1 Wellbeing system: Motion activated light+record camera+SD card memory+audio warning price w?th Amazon US online store here.

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The Fundamentals of Good Business Management by ... - Mansmith

Malu Dy Buncio is
the Chief Business Development
Strategist of
Mansmith?and Fielders, Inc.


Over the last couple of years, I have been doing part-time consultancy with Mansmith & Fielders and have handled a great variety of clients. Clients in the broadcast and restaurant businesses, pharmaceutical, direct selling, gaming, and banking industries.? My focus has been business development and strategic planning.? Often I?m asked by clients, prior to the awarding of a project, ?How transferrable are your skill and experience to our business??? Often, I feel I?m typecast as a ?direct selling expert?.?There is a belief that direct selling is so unique that experience gained in this industry is not applicable to others.

What do I believe?? I believe that the fundamentals of good business management are universal.? This is what has allowed me to develop and facilitate strategic planning over a great variety of industries.

What do I mean by the fundamentals of good business practices?

Strategy Development.? Every business requires a road map.? As I am fond of saying, ?if you don?t know where you?re going, you will never get there.?? A business that is successful without a road map is either very small, has deep pockets (and therefore can afford to make expensive mistakes), or is led by a charismatic, entrepreneurial leader who knows instinctively what direction to take the organization.? However, once the business ceases to be small, runs out of cash, or loses the charismatic leader, the business begins to spin its wheels.? Growth is no longer sustainable.

Executional Excellence.? Another phrase I am fond of is ?Strategy is execution, execution, execution.?? It is not enough to have well-thought strategies.?It is far more important to have a well-thought-out plan for the execution of these strategies.?The larger and more complex a business is, the more detailed the plans for the execution of strategies must be.?As they say ?the devil is in the detail?.

People Management.? In my experience, there are two sides to people management. There is the technical, structural side where an organization must have processes in place to ensure that the organization is adequately staffed (numbers) and competent (quality). People management must be proactive.?By this I mean, you don?t recruit when there is a vacancy.? You protect critical and high potential employees.?You recruit, train, and develop for future needs.?The other side is the softer, yet equally important area of culture and corporate values.? Employees must understand what is and what is not acceptable?in the company they work for.

Leadership. Corporate culture and values are largely driven by the leader of an organization. There are formal leaders (by virtue of position) and informal leaders (those who influence).? Leadership is important particularly during times of turbulence and uncertainty. In times of crisis, it is not enough to manage a business, you have to lead.? There is an immense difference between managing and leading. We are all aware of how the leadership of Steve Jobs shaped Apple through good times and bad.? It will be interesting to see how the organization will develop post Steve Jobs.

Financial Management.? Even if you are a non-profit organization, a good, sound financial management is critical.? Goals must be achieved.? Controls must be in place.? Cash must flow.

Of course, there are ?hot buttons? that are unique to each industry or business.? They drive the business you are in.? Employees who possess the skill to execute them should be protected and nurtured. If a business is not built on the fundamentals of good business management, even those ?hot buttons? will not be enough to sustain growth.

Malu Dy Buncio is the Chief Business Development Strategist of Mansmith and Fielders, Inc., (www.mansmith.net). She will be conducting a seminar-workshop on May 29-30, 2012 entitled Strategic Planning. For inquiries on our programs, please call (63-2) 584-5858/412-0034, text 0918-81-168-88 or email?info@mansmith.net.

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Kristen Stewart's 'Snow White' Costume Revealed In Exclusive Behind-The-Scenes Look

From the moment we first laid eyes upon the visuals of "Snow White and the Huntsman," we had an idea that we were in for something special. That's a testament to the star power of Kristen Stewart, Chris Hemsworth and Charlize Theron, of course, but it also has a lot to do with the costuming [...]

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Why choose home health care? | Healthy Planning Style Care

Increasingly, families are making the decision to have health care provided in their own homes.? With 10,000 Americans turning 65 each day in 2011, the need for quality, affordable health care becomes an increased concern across the U.S. The aging baby-boomers ? it?s anticipated that by 2030 the number of people over 65 will exceed 70 million ? are now in a position where they need extra help with chronic conditions and daily activities, but don?t want to lose the independence and comfort of their homes.? In addition, the high costs of hospital and facility stays can cause a frightening financial burden.? While not everyone who needs health care assistance is a senior citizen ? like new mothers and singles living without family nearby ? the focus is often on the baby-boom generation.

There is scientific evidence that supports the belief that people heal faster and feel better when allowed to be at home.? Certainly the amount of germs and sources of infection are less when in a home environment over an institution.? The psychological benefits are undeniable; when asked, most people who are hospitalized with an illness ?just want to go home.?? This also allows family to stay with the person in need, providing them with the knowledge that they are still in the loop of their loved-one?s health issues.

Routine can be essential for physical and emotional well-being.? A home health care provider will help maintain the discipline of scheduled medications and therapies within a framework of personal routine.? Allowing a patient the comfort of keeping their normal, daily routine in their own home adds to the quality of life and sense of safety.? In addition, the health care provider can watch for changes in habits, attitudes, and demeanor that can be indicators of larger problems.? The emotional well-being extends to those who live with the patient, as it can be difficult to care for a family member with so many other demands ? like work or children ? that divide their time.? Lack of health care knowledge can put a strain on relationships between family members.? With the help of a trained home caregiver, family can enjoy being with each other while still getting the best attention to health issues.

Sometimes, it is the simple things that can mean a huge difference in the health of someone in need of care.? Having a health care provider come in a few times a week to fix a meal, assist with personal hygiene, and make sure that items are picked up for easy movement about the house can prevent illness or injury from poor nutrition, infection, or accidents.? This type of service is also very beneficial to new mothers or those recovering from surgeries, etc.

that are without the luxury of nearby family or friends to help during the first few weeks home.

An additional advantage to the comfort and health benefits is that it makes more economic sense to have a provider in your home.? Lengthy stays in a hospital or institution can add up to thousands of dollars very quickly, compounding the stress in your life.? By comparison, home health care is significantly cheaper, giving you more options with your health care dollar.

A home health agency is strictly regulated, meeting federal requirements and regulations to assure you that your home care provider is highly trained.? While they are not a substitute for a doctor?s care, they can be

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2 genetic deletions in human genome linked to the development of aggressive prostate cancer

[ Back to EurekAlert! ] Public release date: 9-Apr-2012
[ | E-mail | Share Share ]

Contact: Lauren Woods
law2014@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

Discovery of inherited-genetic variations may help assess a patient's risk of life-threatening disease before it strikes

NEW YORK (April 9, 2012 ) -- An international research team led by Weill Cornell Medical College investigators have discovered two inherited-genetic deletions in the human genome linked to development of aggressive prostate cancer. The findings, published online today in the Proceedings of the National Academy of Sciences (PNAS), indicate a man's risk of developing prostate cancer either triples or quadruples, depending on the genetic variant they inherit.

In the study, one genetic deletion is shown to affect the functioning of a known gene, while the other, found in a non-coding area of the genome once considered to be "junk DNA," seems to be regulating a cascade of genes. According to the lead co-authors, the study is potentially groundbreaking because it demonstrates that so-called copy number variations (CNVs) in either protein coding or non-coding areas of the human genome play a significant role in the development of cancer in general, and in aggressive prostate cancer, specifically.

"We used to think that only genes that made proteins were responsible for disease, but this study shows us that there is inherited information in the non-coding areas of the genome that appear to play a strong role in development of cancer," says study co-author, Dr. Mark A. Rubin, the Homer T. Hirst Professor of Oncology in Pathology at Weill Cornell Medical College. Other researchers have linked CNVs to Alzheimer's and Parkinson's disease, mental retardation, autism, schizophrenia and neuroblastoma, a type of brain cancer. "This study suggests there are other cancers that might be associated with CNVs," says Dr. Rubin. "It's an exciting new field of research."

"The study shows that copy number variations matter in cancer," says co-lead investigator, Dr. Francesca Demichelis, who is now an Assistant Professor at the Center of Integrative Biology at the University of Trento in Italy and an Adjunct Assistant Professor in the Institute for Computational Biomedicine at Weill Cornell Medical College.

The two genetic variants identified by the research team are not the only cause of aggressive prostate cancer, Dr. Demichelis says. "These variants likely collaborate with other factors early in a man's life leading to development of prostate cancer."

Prostate cancer affects one in six men during their lifetime, and family history is the strongest risk factor for prostate cancer. Because of the inheritable nature of the disease, for the study Weill Cornell researchers hunted to find DNA that is either significantly deleted or duplicated in the genome of patients with prostate cancer to compare it to men without the disease.

In this collaboration between Weill Cornell Medical College, the Brigham and Women's Hospital and Innsbruck University Hospital, researchers examined blood samples from a population of men from the Tyrol Early Prostate Cancer Detection Program in Austria. Since 1993, this program has been aggressively screening men, age 45-75, who live in the Tyrol region with prostate specific antigen (PSA) in order to detect prostate cancer as early as possible. The population includes men who developed prostate cancer as well as men with elevated PSA who have no prostate cancer based on a biopsy. In addition, researchers looked at the germline variation in these patients to see if there is a risk factor as to why some men with elevated PSA have prostate cancer and some men do not.

Molecular studies were performed in the U.S. on more than 1900 blood samples from Tyrolean men (867 unrelated cancer patients and 1,036 controls). Researchers discovered two CNVs that were significantly different between Tyrolean individuals with aggressive prostate cancer and those without cancer, and then reproduced that finding in another group of 800 U.S. patients. The researchers then tested the effect of the two variants in laboratory cells and discovered they increase the ability of cancer cells to grow and to invade.

Both of these variants are small deletions in DNA that lead to over-expression of genes, Dr. Demichelis says. She and her colleagues found that one gene that is over-expressed due to the variant deletion is MGAT4C, which leads to the ability of cells to grow and migrate. "A man with the variant is four times more likely to develop prostate cancer if he inherited this variant than if he did not," Dr. Demichelis says. "Interestingly, MGAT4C was found to be significantly over-expressed in metastatic versus localized prostate cancer," she adds.

The role of the other genetic variant, located in the "junk" region of the human genome, is not yet known, but the researchers believe it activates a cascade of other genes. They calculated a man is three times more likely to develop prostate cancer if he has inherited this variant.

The investigators calculated these two newly identified variants occur at a frequency of between 1.5-3 percent of the overall population, but are found at a significantly higher percentage in men diagnosed with aggressive prostate cancer. "For the gene coding variant, MGAT4C, we were able to analyze metastatic human samples where we observed that the high-risk gene is abundantly present," says Dr. Demichelis.

Now researchers are looking for other variants they hope to be able to build into a comprehensive DNA test to be used as a diagnostic tool to help clinicians identify men whose prostate cancer will likely progress to advanced stages. "We could also potentially use such a DNA test for chemoprevention if risk of developing aggressive prostate cancer is deemed to be high," says Dr. Demichelis. "This is the start of a new strategy. It would not replace PSA, but would identify other risk factors."

"In this new area of research, we are starting to appreciate that the differences in inherited genomic variants account not only for why we look different or respond in various ways to medication, but also for why we develop disease," Dr. Rubin says. "This is the first study to suggest these variants may account for susceptibility to cancer. This new line of research will also allow us to study the biology around prostate cancer initiation."

###

The study was supported in part by the Starr Cancer Consortium, the Early Detection Research Network from the National Cancer Institute, the Clinical and Translational Science Center, the Department of Defense and the National Human Genome Research Institute.

Other co-authors from Weill Cornell Medical College include: Chen X. Chen, Julie Huang, Samprit Banerjee, Dimple Chakravarty, Himisha Beltran, Olivier Elemento, Derek A. Oldridge, Naoki Kitabayashi, Sagit Goldenberg, David Soong, David S. Rickman, and Douglas S. Scherr. The study was a collaboration between Weill Cornell Medical College, Innsbruck Medical University, Austria: Helmut Klocker, Birgit Stenzel, Georg Schaefer, Wolfgang Horninger, Jasmin Bektic, and Georg Bartsch; Brigham and Women's Hospital and Harvard Medical School: Sunita R. Setlur, Jin Yun, Charles Lee and Helen Chen; University of Michigan Medical School: Arul M. Chinnaiyan, John T. Wei, and Javed Siddiquih; Dana-Farber Cancer Institute: Meredith M. Regan; and Beth Israel Deaconess Medical Center: Michale Kearney and Martin A. Sanda.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.


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?


AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.


[ Back to EurekAlert! ] Public release date: 9-Apr-2012
[ | E-mail | Share Share ]

Contact: Lauren Woods
law2014@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

Discovery of inherited-genetic variations may help assess a patient's risk of life-threatening disease before it strikes

NEW YORK (April 9, 2012 ) -- An international research team led by Weill Cornell Medical College investigators have discovered two inherited-genetic deletions in the human genome linked to development of aggressive prostate cancer. The findings, published online today in the Proceedings of the National Academy of Sciences (PNAS), indicate a man's risk of developing prostate cancer either triples or quadruples, depending on the genetic variant they inherit.

In the study, one genetic deletion is shown to affect the functioning of a known gene, while the other, found in a non-coding area of the genome once considered to be "junk DNA," seems to be regulating a cascade of genes. According to the lead co-authors, the study is potentially groundbreaking because it demonstrates that so-called copy number variations (CNVs) in either protein coding or non-coding areas of the human genome play a significant role in the development of cancer in general, and in aggressive prostate cancer, specifically.

"We used to think that only genes that made proteins were responsible for disease, but this study shows us that there is inherited information in the non-coding areas of the genome that appear to play a strong role in development of cancer," says study co-author, Dr. Mark A. Rubin, the Homer T. Hirst Professor of Oncology in Pathology at Weill Cornell Medical College. Other researchers have linked CNVs to Alzheimer's and Parkinson's disease, mental retardation, autism, schizophrenia and neuroblastoma, a type of brain cancer. "This study suggests there are other cancers that might be associated with CNVs," says Dr. Rubin. "It's an exciting new field of research."

"The study shows that copy number variations matter in cancer," says co-lead investigator, Dr. Francesca Demichelis, who is now an Assistant Professor at the Center of Integrative Biology at the University of Trento in Italy and an Adjunct Assistant Professor in the Institute for Computational Biomedicine at Weill Cornell Medical College.

The two genetic variants identified by the research team are not the only cause of aggressive prostate cancer, Dr. Demichelis says. "These variants likely collaborate with other factors early in a man's life leading to development of prostate cancer."

Prostate cancer affects one in six men during their lifetime, and family history is the strongest risk factor for prostate cancer. Because of the inheritable nature of the disease, for the study Weill Cornell researchers hunted to find DNA that is either significantly deleted or duplicated in the genome of patients with prostate cancer to compare it to men without the disease.

In this collaboration between Weill Cornell Medical College, the Brigham and Women's Hospital and Innsbruck University Hospital, researchers examined blood samples from a population of men from the Tyrol Early Prostate Cancer Detection Program in Austria. Since 1993, this program has been aggressively screening men, age 45-75, who live in the Tyrol region with prostate specific antigen (PSA) in order to detect prostate cancer as early as possible. The population includes men who developed prostate cancer as well as men with elevated PSA who have no prostate cancer based on a biopsy. In addition, researchers looked at the germline variation in these patients to see if there is a risk factor as to why some men with elevated PSA have prostate cancer and some men do not.

Molecular studies were performed in the U.S. on more than 1900 blood samples from Tyrolean men (867 unrelated cancer patients and 1,036 controls). Researchers discovered two CNVs that were significantly different between Tyrolean individuals with aggressive prostate cancer and those without cancer, and then reproduced that finding in another group of 800 U.S. patients. The researchers then tested the effect of the two variants in laboratory cells and discovered they increase the ability of cancer cells to grow and to invade.

Both of these variants are small deletions in DNA that lead to over-expression of genes, Dr. Demichelis says. She and her colleagues found that one gene that is over-expressed due to the variant deletion is MGAT4C, which leads to the ability of cells to grow and migrate. "A man with the variant is four times more likely to develop prostate cancer if he inherited this variant than if he did not," Dr. Demichelis says. "Interestingly, MGAT4C was found to be significantly over-expressed in metastatic versus localized prostate cancer," she adds.

The role of the other genetic variant, located in the "junk" region of the human genome, is not yet known, but the researchers believe it activates a cascade of other genes. They calculated a man is three times more likely to develop prostate cancer if he has inherited this variant.

The investigators calculated these two newly identified variants occur at a frequency of between 1.5-3 percent of the overall population, but are found at a significantly higher percentage in men diagnosed with aggressive prostate cancer. "For the gene coding variant, MGAT4C, we were able to analyze metastatic human samples where we observed that the high-risk gene is abundantly present," says Dr. Demichelis.

Now researchers are looking for other variants they hope to be able to build into a comprehensive DNA test to be used as a diagnostic tool to help clinicians identify men whose prostate cancer will likely progress to advanced stages. "We could also potentially use such a DNA test for chemoprevention if risk of developing aggressive prostate cancer is deemed to be high," says Dr. Demichelis. "This is the start of a new strategy. It would not replace PSA, but would identify other risk factors."

"In this new area of research, we are starting to appreciate that the differences in inherited genomic variants account not only for why we look different or respond in various ways to medication, but also for why we develop disease," Dr. Rubin says. "This is the first study to suggest these variants may account for susceptibility to cancer. This new line of research will also allow us to study the biology around prostate cancer initiation."

###

The study was supported in part by the Starr Cancer Consortium, the Early Detection Research Network from the National Cancer Institute, the Clinical and Translational Science Center, the Department of Defense and the National Human Genome Research Institute.

Other co-authors from Weill Cornell Medical College include: Chen X. Chen, Julie Huang, Samprit Banerjee, Dimple Chakravarty, Himisha Beltran, Olivier Elemento, Derek A. Oldridge, Naoki Kitabayashi, Sagit Goldenberg, David Soong, David S. Rickman, and Douglas S. Scherr. The study was a collaboration between Weill Cornell Medical College, Innsbruck Medical University, Austria: Helmut Klocker, Birgit Stenzel, Georg Schaefer, Wolfgang Horninger, Jasmin Bektic, and Georg Bartsch; Brigham and Women's Hospital and Harvard Medical School: Sunita R. Setlur, Jin Yun, Charles Lee and Helen Chen; University of Michigan Medical School: Arul M. Chinnaiyan, John T. Wei, and Javed Siddiquih; Dana-Farber Cancer Institute: Meredith M. Regan; and Beth Israel Deaconess Medical Center: Michale Kearney and Martin A. Sanda.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.


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