Diabetes: Possible Therapies
In former study, intake of coffee, both caffeinated and decaffeinated, and tea has been associated with a decreased chance of type two diabetes mellitus. Presently, according to a meta-analysis issued in the December 2009 release of Archives of General Medicine, a high consumption of coffee is linked up with a decreased risk of diabetes mellitus.
Research workers from the University of Sydney in Commonwealth of Australia and their co-workers looked for relevant researches concerning the connection between coffee, decaf, or tea and diabetes mellitus between 1966 and July 2009. They discovered 18 researches accounting on the connection between coffee apply and diabetes mellitus, which included data on about 458,000 partakers. They also discovered six researches on the link between decaf and diabetes mellitus and seven researches on the connection between tea and diabetes mellitus. The research workers discovered that multiplied coffee apply was linked to lessened diabetes mellitus chance, with every another cup of coffee adding to a 7 percent decrease in the excess chance of diabetes mellitus.
Similar important opposite connections were discovered with decaf and tea and risk of diabetes mellitus. While this meta-analysis advises a protective action of coffee, decaf, and tea against the chance of diabetes mellitus, these discoveries need to be validated in randomized clinical tests.
Research workers from the University of Sydney in Commonwealth of Australia and their co-workers looked for relevant researches concerning the connection between coffee, decaf, or tea and diabetes mellitus between 1966 and July 2009. They discovered 18 researches accounting on the connection between coffee apply and diabetes mellitus, which included data on about 458,000 partakers. They also discovered six researches on the link between decaf and diabetes mellitus and seven researches on the connection between tea and diabetes mellitus. The research workers discovered that multiplied coffee apply was linked to lessened diabetes mellitus chance, with every another cup of coffee adding to a 7 percent decrease in the excess chance of diabetes mellitus.
Similar important opposite connections were discovered with decaf and tea and risk of diabetes mellitus. While this meta-analysis advises a protective action of coffee, decaf, and tea against the chance of diabetes mellitus, these discoveries need to be validated in randomized clinical tests.
Companies Marketing Unapproved Topical Drugs Containing Ibuprofen Receive FDA Warning
The US Food and Drug Administration has written to eight companies marketing over-the-counter (OTC) topical drugs containing the pain reliever ibuprofen and other active ingredients to warn them that they are breaking the law because their drugs are unapproved.
In a press statement released on Thursday, the federal agency said the companies should have applied for approval before marketing their drugs.
The names of the companies and their associated products are:
* Progressive Emu, Inc: Emuprofen.
* BioCentric Laboratories, Inc: BioEntopic 15% Ibuprofen Crème.
* Core Products International, Inc: Ibunex Topical Ibuprofen.
* Geromatrix Health Products: LoPain AF 15% Ibuprofen Crème.
* MEKT LLC: IB-RELIEF.
* Ridge Medical Products: Profen HP.
* Meditrend, Inc. dba Progena Professional Formulations: IbuPRO-10 Plus.
* Wonder Laboratories: IBU-RELIEF 12.
The FDA has warned them that they may not continue to market their products without agency approval and has asked them to explain in writing within 15 days how they will address these violations and stop them happening again.
While the FDA allows some OTC drugs to be marketed without first obtaining agency approval, ibuprofen is not one of them because it is not included in any OTC drug monograph, that is the regulations that set out what is required in the drug's labelling, formulations and indications.
"Companies wishing to market OTC drugs that do not meet the monograph requirements can submit and receive approval of a new drug application," said the FDA statement.
Deborah M. Autor, director of the Office of Compliance at the FDA's Center for Drug Evaluation and Research (CDER) said:
"These companies have an obligation to the public to demonstrate to the FDA that their products are safe and effective, and they have failed to do so."
While orally administered ibuprofen has been approved as a safe and effective treatment for pain and inflammation, there are no approved applications for topical ibuprofen products, explained the FDA.
Also, while the agency has proposed to add orally administered ibuprofen to the applicable OTC monograph, it has never proposed adding topical ibuprofen.
Topical ibuprofen products are often promoted it as a "safer" alternative to oral ibuprofen, which is described as having long term side effects such as stomach ulcers and cardiovascular problems. However, the FDA stated that:
"These safety claims for topical ibuprofen have not been reviewed by the FDA, nor has the agency evaluated what side effects might be associated with such products."
Source: FDA.
In a press statement released on Thursday, the federal agency said the companies should have applied for approval before marketing their drugs.
The names of the companies and their associated products are:
* Progressive Emu, Inc: Emuprofen.
* BioCentric Laboratories, Inc: BioEntopic 15% Ibuprofen Crème.
* Core Products International, Inc: Ibunex Topical Ibuprofen.
* Geromatrix Health Products: LoPain AF 15% Ibuprofen Crème.
* MEKT LLC: IB-RELIEF.
* Ridge Medical Products: Profen HP.
* Meditrend, Inc. dba Progena Professional Formulations: IbuPRO-10 Plus.
* Wonder Laboratories: IBU-RELIEF 12.
The FDA has warned them that they may not continue to market their products without agency approval and has asked them to explain in writing within 15 days how they will address these violations and stop them happening again.
While the FDA allows some OTC drugs to be marketed without first obtaining agency approval, ibuprofen is not one of them because it is not included in any OTC drug monograph, that is the regulations that set out what is required in the drug's labelling, formulations and indications.
"Companies wishing to market OTC drugs that do not meet the monograph requirements can submit and receive approval of a new drug application," said the FDA statement.
Deborah M. Autor, director of the Office of Compliance at the FDA's Center for Drug Evaluation and Research (CDER) said:
"These companies have an obligation to the public to demonstrate to the FDA that their products are safe and effective, and they have failed to do so."
While orally administered ibuprofen has been approved as a safe and effective treatment for pain and inflammation, there are no approved applications for topical ibuprofen products, explained the FDA.
Also, while the agency has proposed to add orally administered ibuprofen to the applicable OTC monograph, it has never proposed adding topical ibuprofen.
Topical ibuprofen products are often promoted it as a "safer" alternative to oral ibuprofen, which is described as having long term side effects such as stomach ulcers and cardiovascular problems. However, the FDA stated that:
"These safety claims for topical ibuprofen have not been reviewed by the FDA, nor has the agency evaluated what side effects might be associated with such products."
Source: FDA.
Popular Breast Cancer Drug Used With Certain Antidepressants Puts New Jersey Women At Risk
A new analysis finds that women in New Jersey who take the breast cancer drug tamoxifen in conjunction with certain popular antidepressants may be at a higher risk for a breast cancer recurrence.
In May, Medco Health Solutions, Inc. (NYSE: MHS) and Indiana University School of Medicine released a study revealing that women using tamoxifen to prevent a recurrence of breast cancer who also use certain selective serotonin reuptake inhibitors (SSRI), for example Prozac(R) (fluoxetine), Paxil(R) (paroxetine) and Zoloft(R) (sertraline), have up to twice the chance of having a recurrence of the disease.
In a separate New Jersey-specific analysis, Medco found that among nearly 2,000 tamoxifen patients in the state during 2008, 12 percent were also taking SSRIs, including those that could put them in the at-risk population.
"We've been aware that certain antidepressants, known as CYP2D6 inhibitor drugs, block the activation of tamoxifen chemically, but this evidence shows that these drugs are putting women in New Jersey and across the nation at a much higher risk for recurrent breast cancer," said Dr. Milayna Subar, National Practice Leader for Medco's Oncology Therapeutic Resource Center located at Medco's Willingboro, N. J. pharmacy. "Women taking tamoxifen along with an SSRI should speak with their doctor immediately to discuss modifications to their medication regimen to ensure they are getting the full benefit of their tamoxifen therapy."
Approximately 500,000 women take tamoxifen in the U.S., with 80,000 new patients starting on the treatment annually. Nearly 30 percent of women taking tamoxifen also use an antidepressant. Based on estimates from the Centers for Disease Control and Prevention, New Jersey is among the states with the highest breast cancer incidence and death rate in the country.
The study by Medco and Indiana University School of Medicine that was presented at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO). It was the largest study to-date looking at how these drugs impact breast cancer recurrence rates when taken with tamoxifen.
Antidepressants are often prescribed when women receiving tamoxifen are depressed, or to treat hot flashes -- a common side effect of the breast cancer drug. Paxil, Prozac and Zoloft are among a group of antidepressant drugs known as CYP2D6 inhibitors. These drugs prevent the CYP2D6 enzyme from working properly, and cause less of the active form of tamoxifen, called endoxifen, from being produced, making the drug less effective at preventing breast cancer. Women taking tamoxifen along with certain SSRIs have a 2-fold increased risk of breast cancer recurrence compared to women not taking these drugs together.
Tamoxifen
Tamoxifen is one of the oldest and most widely used treatments for reducing the risk of breast cancer recurrence among women with estrogen-dependent tumors. The drug works by blocking the estrogen receptors in the breast cells and can reduce the risk of a breast cancer recurrence by up to 50 percent. It's the only anti-estrogen available for prevention of breast cancer recurrence in pre-menopausal women and is one of several anti-estrogens used to treat post-menopausal breast cancer patients.
Medco Therapeutic Resource Center(R) in Willingboro, N.J.
Willingboro, New Jersey is home to the world's largest automated pharmacy and is the current site of the Medco Therapeutic Resource Center (TRC) for oncology patients. Medco's TRCs focus on the specialized treatment of patients with chronic and complex conditions, including centers for cardiovascular diseases, diabetes, immunologic and pulmonary conditions. Nearly half of the company's 2,600 pharmacists are specialists deployed across the TRCs where they provide disease-specific therapy management for those patients who account for 96 percent of pharmacy spending and 75 percent of this country's medical costs.
About Medco
Medco Health Solutions, Inc. (NYSE: MHS) is pioneering the world's most advanced pharmacy(R) and its clinical research and innovations are part of Medco making medicine smarter(TM) for more than 60 million Americans.
With more than 20,000 employees dedicated to improving patient health and reducing costs for a wide range of public and private sector clients, and 2008 revenue exceeding $51 billion, Medco ranks 45th on the Fortune 500 list and is named among the world's most innovative, most admired and most trustworthy companies.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that may cause results to differ materially from those set forth in the statements. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the risks and uncertainties that affect our business, particularly those mentioned in the Risk Factors section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission.
Source: Medco Health Solutions, Inc
In May, Medco Health Solutions, Inc. (NYSE: MHS) and Indiana University School of Medicine released a study revealing that women using tamoxifen to prevent a recurrence of breast cancer who also use certain selective serotonin reuptake inhibitors (SSRI), for example Prozac(R) (fluoxetine), Paxil(R) (paroxetine) and Zoloft(R) (sertraline), have up to twice the chance of having a recurrence of the disease.
In a separate New Jersey-specific analysis, Medco found that among nearly 2,000 tamoxifen patients in the state during 2008, 12 percent were also taking SSRIs, including those that could put them in the at-risk population.
"We've been aware that certain antidepressants, known as CYP2D6 inhibitor drugs, block the activation of tamoxifen chemically, but this evidence shows that these drugs are putting women in New Jersey and across the nation at a much higher risk for recurrent breast cancer," said Dr. Milayna Subar, National Practice Leader for Medco's Oncology Therapeutic Resource Center located at Medco's Willingboro, N. J. pharmacy. "Women taking tamoxifen along with an SSRI should speak with their doctor immediately to discuss modifications to their medication regimen to ensure they are getting the full benefit of their tamoxifen therapy."
Approximately 500,000 women take tamoxifen in the U.S., with 80,000 new patients starting on the treatment annually. Nearly 30 percent of women taking tamoxifen also use an antidepressant. Based on estimates from the Centers for Disease Control and Prevention, New Jersey is among the states with the highest breast cancer incidence and death rate in the country.
The study by Medco and Indiana University School of Medicine that was presented at the 2009 Annual Meeting of the American Society of Clinical Oncology (ASCO). It was the largest study to-date looking at how these drugs impact breast cancer recurrence rates when taken with tamoxifen.
Antidepressants are often prescribed when women receiving tamoxifen are depressed, or to treat hot flashes -- a common side effect of the breast cancer drug. Paxil, Prozac and Zoloft are among a group of antidepressant drugs known as CYP2D6 inhibitors. These drugs prevent the CYP2D6 enzyme from working properly, and cause less of the active form of tamoxifen, called endoxifen, from being produced, making the drug less effective at preventing breast cancer. Women taking tamoxifen along with certain SSRIs have a 2-fold increased risk of breast cancer recurrence compared to women not taking these drugs together.
Tamoxifen
Tamoxifen is one of the oldest and most widely used treatments for reducing the risk of breast cancer recurrence among women with estrogen-dependent tumors. The drug works by blocking the estrogen receptors in the breast cells and can reduce the risk of a breast cancer recurrence by up to 50 percent. It's the only anti-estrogen available for prevention of breast cancer recurrence in pre-menopausal women and is one of several anti-estrogens used to treat post-menopausal breast cancer patients.
Medco Therapeutic Resource Center(R) in Willingboro, N.J.
Willingboro, New Jersey is home to the world's largest automated pharmacy and is the current site of the Medco Therapeutic Resource Center (TRC) for oncology patients. Medco's TRCs focus on the specialized treatment of patients with chronic and complex conditions, including centers for cardiovascular diseases, diabetes, immunologic and pulmonary conditions. Nearly half of the company's 2,600 pharmacists are specialists deployed across the TRCs where they provide disease-specific therapy management for those patients who account for 96 percent of pharmacy spending and 75 percent of this country's medical costs.
About Medco
Medco Health Solutions, Inc. (NYSE: MHS) is pioneering the world's most advanced pharmacy(R) and its clinical research and innovations are part of Medco making medicine smarter(TM) for more than 60 million Americans.
With more than 20,000 employees dedicated to improving patient health and reducing costs for a wide range of public and private sector clients, and 2008 revenue exceeding $51 billion, Medco ranks 45th on the Fortune 500 list and is named among the world's most innovative, most admired and most trustworthy companies.
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that may cause results to differ materially from those set forth in the statements. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the risks and uncertainties that affect our business, particularly those mentioned in the Risk Factors section of the Company's Annual Report on Form 10-K and Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission.
Source: Medco Health Solutions, Inc
New Drug Hope For Advanced Melanoma
Early results of a trial found that a new drug that targets a genetic mutation found in over half of melanoma cases and some other cancers caused tumors to shrink and patients to live around 6 months longer without their disease getting worse, including those whose cancer had spread to the liver, lung and bone.
The results of the phase I trial on the experimental drug PLX4032 were released earlier this week at the American Society of Clinical Oncology conference in Orlando, Florida. The drug is being developed by Roche and Plexxikon.
Principal investigator Dr Keith T Flaherty, assistant professor at the Abramson Cancer Center of the University of Pennsylvania, said that:
"PLX4032 has shown both tumour shrinkage and delay in tumour progression in patients whose tumours harbour a BRAF mutation, as well as improved quality of life for symptomatic patients."
"Seven years after BRAF mutations were first identified we have validation that this mutation is a cancer driver and therapeutic target," he said, adding that he and his co-investigators were very excited about this new development, especially for their melanoma patients for whom there are few treatment options.
The gene mutation also occurs in about 10 to 15 per cent of colorectal tumors and 8 per cent of other solid tumors, said the researchers.
The trial showed that patients treated with PLX4032 had a median progression free survival of at least six months, including those with advanced metastatic cancer that had spread to other organs such as liver, lungs and bone. Current treatments usually give patients with advanced stage melanoma about two months extra life before their disease progresses.
The researchers also found that:
* PLX4032 was well tolerated at therapeutic doses.
* Nine mutation-positive melanoma patients showed partial responses and four mutation-positive melanoma patients showed minor responses.
* Disease control lasted up to 14 months with continuous therapy, with many responding patients still receiving treatment.
* A small group of patients without the BRAF mutation did not respond to treatment, and progression-free survival was less than two months, consistent with historical data.
* Drug-related adverse events included rash and photosensitivity and were classified as mild in grade.
Roche also reported that:
"Serious adverse events, including diagnosis of cutaneous squamous cell carcinoma, were observed in some patients after chronic treatment; however the safety profile has been warranted favourable for this population and the trial authorised to proceed to the next stage of investigation."
PLX4032 targets and destroys cancer cells that carry the BRAF mutation.
BRAF is a gene that plays an important role in cell growth and division. The mutation, however, leads to uncontrolled cell growth and division which then causes 60 per cent of melanomas, the most deadly form of skin cancer, and about 8 per cent of all solid tumors.
Roche told the press they expect the new drug's "potency and selectivity" will lead to a treatment that is "both effective and well tolerated".
Roche and its partner Plexxikon are also working on a companion diagnostic that will help identify which patients have the BRAF mutation.
The companies are now planning the next stage: bigger trials and a registration programme starting later this year.
If this goes well, they will launch a tissue-based companion diagnostic test, which the companies describe as "another step forward in personalising cancer treatment".
The two companies want to extent the use of PLX4032 for other cancers that harbour the BRAF mutation, and they are also developing the companion diagnostic test to select patients for clinical trials and then later for treatment with the drug.
Malingnant melanoma is the most serious form of skin cancer and about 160,000 people worldwide every year are diagnosed with it.
It is treatable if caught early, but once it has spread to other organs, the patient's prospects are not good. Fewer than 2 per cent of patients with systemic metastases live more than two years.
Roche said the results on the new drug represent not only a step forward in understanding how to treat malignant melanoma but they also represent:
"A significant advance in the use of biomarkers and diagnostic tools and the potential benefits of tailoring cancer treatment to individual patients."
The results of the phase I trial on the experimental drug PLX4032 were released earlier this week at the American Society of Clinical Oncology conference in Orlando, Florida. The drug is being developed by Roche and Plexxikon.
Principal investigator Dr Keith T Flaherty, assistant professor at the Abramson Cancer Center of the University of Pennsylvania, said that:
"PLX4032 has shown both tumour shrinkage and delay in tumour progression in patients whose tumours harbour a BRAF mutation, as well as improved quality of life for symptomatic patients."
"Seven years after BRAF mutations were first identified we have validation that this mutation is a cancer driver and therapeutic target," he said, adding that he and his co-investigators were very excited about this new development, especially for their melanoma patients for whom there are few treatment options.
The gene mutation also occurs in about 10 to 15 per cent of colorectal tumors and 8 per cent of other solid tumors, said the researchers.
The trial showed that patients treated with PLX4032 had a median progression free survival of at least six months, including those with advanced metastatic cancer that had spread to other organs such as liver, lungs and bone. Current treatments usually give patients with advanced stage melanoma about two months extra life before their disease progresses.
The researchers also found that:
* PLX4032 was well tolerated at therapeutic doses.
* Nine mutation-positive melanoma patients showed partial responses and four mutation-positive melanoma patients showed minor responses.
* Disease control lasted up to 14 months with continuous therapy, with many responding patients still receiving treatment.
* A small group of patients without the BRAF mutation did not respond to treatment, and progression-free survival was less than two months, consistent with historical data.
* Drug-related adverse events included rash and photosensitivity and were classified as mild in grade.
Roche also reported that:
"Serious adverse events, including diagnosis of cutaneous squamous cell carcinoma, were observed in some patients after chronic treatment; however the safety profile has been warranted favourable for this population and the trial authorised to proceed to the next stage of investigation."
PLX4032 targets and destroys cancer cells that carry the BRAF mutation.
BRAF is a gene that plays an important role in cell growth and division. The mutation, however, leads to uncontrolled cell growth and division which then causes 60 per cent of melanomas, the most deadly form of skin cancer, and about 8 per cent of all solid tumors.
Roche told the press they expect the new drug's "potency and selectivity" will lead to a treatment that is "both effective and well tolerated".
Roche and its partner Plexxikon are also working on a companion diagnostic that will help identify which patients have the BRAF mutation.
The companies are now planning the next stage: bigger trials and a registration programme starting later this year.
If this goes well, they will launch a tissue-based companion diagnostic test, which the companies describe as "another step forward in personalising cancer treatment".
The two companies want to extent the use of PLX4032 for other cancers that harbour the BRAF mutation, and they are also developing the companion diagnostic test to select patients for clinical trials and then later for treatment with the drug.
Malingnant melanoma is the most serious form of skin cancer and about 160,000 people worldwide every year are diagnosed with it.
It is treatable if caught early, but once it has spread to other organs, the patient's prospects are not good. Fewer than 2 per cent of patients with systemic metastases live more than two years.
Roche said the results on the new drug represent not only a step forward in understanding how to treat malignant melanoma but they also represent:
"A significant advance in the use of biomarkers and diagnostic tools and the potential benefits of tailoring cancer treatment to individual patients."
Selecting Anti-Hepatitis B Virus Agents For Drug-Resistance Patients
HBV infection may lead to acute liver disease, chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma. Over 350 million people worldwide are estimated to be infected chronically by HBV and are therefore at risk of liver failure, cirrhosis, or hepatocellular carcinoma. The principal treatment for chronic hepatitis B (CHB) involves the use of interferon alpha (IFN-a) or nucleoside analogs. In vitro analysis of clinical HBV isolates is currently difficult for lacking of HBV cellular culture model
A research article published in the World Journal of Gastroenterology addresses this. The research team led by Prof. Yin-Ping Lu from Union Hospital of Tongji Medical College reportd a useful strategy to select anti-HBV agents for drug-resistance patients. The full-length HBV genomic DNA from chronic hepatitis B patients were amplified by polymerase chain reaction (PCR). The amplified HBV DNA fragments were inserted into an universal HBV expression vector respectively. The recombinant plasmids containing 1.1 copies of HBV genome were transient transfected into Huh7 cells and antiviral susceptibility of lamivudine and adefovir were analyzed in vitro model system. Furthermore, the antiviral susceptibility of adefovir in vivo were observed subsequently.
Eight clinical HBV isolates form different individual with lamivudine-resistance were cloned into HBV expression vector, and recombinant plasmids were transcient transfected into Huh7 cells. The results indicated that HBV genome of clinical HBV isolates could effectively replicate and be expressed in Huh7 cells. Adefovir but not lamivudine inhibited HBV replication both in vitro and in vivo.
The novel method described in this article enables rapidly selecting of anti-HBV agents in clinic and will be useful in future studies of antiviral therapy for chronic hepatitis B.
A research article published in the World Journal of Gastroenterology addresses this. The research team led by Prof. Yin-Ping Lu from Union Hospital of Tongji Medical College reportd a useful strategy to select anti-HBV agents for drug-resistance patients. The full-length HBV genomic DNA from chronic hepatitis B patients were amplified by polymerase chain reaction (PCR). The amplified HBV DNA fragments were inserted into an universal HBV expression vector respectively. The recombinant plasmids containing 1.1 copies of HBV genome were transient transfected into Huh7 cells and antiviral susceptibility of lamivudine and adefovir were analyzed in vitro model system. Furthermore, the antiviral susceptibility of adefovir in vivo were observed subsequently.
Eight clinical HBV isolates form different individual with lamivudine-resistance were cloned into HBV expression vector, and recombinant plasmids were transcient transfected into Huh7 cells. The results indicated that HBV genome of clinical HBV isolates could effectively replicate and be expressed in Huh7 cells. Adefovir but not lamivudine inhibited HBV replication both in vitro and in vivo.
The novel method described in this article enables rapidly selecting of anti-HBV agents in clinic and will be useful in future studies of antiviral therapy for chronic hepatitis B.
How Drug That Blocks Cholesterol Absorption From The Diet Works
A new study in the June issue of Cell Metabolism, a Cell Press publication, sheds light on the action of the drug ezetimibe (trade name Zetia), which is used to treat high cholesterol. Ezetimibe is unique among cholesterol-lowering drugs in that it works by cutting the amount of cholesterol taken in from the diet rather than by blocking cholesterol's manufacture in the body.
Earlier studies had suggested that ezetimibe acts on an intestinal and liver protein recently found to play a critical role in cholesterol absorption. Now, the researchers reveal how that protein known as Niemann-Pick C1-like 1 (NPC1L1) carries cholesterol into the cell. They also show that ezetimibe bars NPC1L1's entry into the cell, thereby keeping cholesterol at bay.
"This is a breakthrough in terms of understanding how cholesterol is absorbed," said Bao-Liang Song of Shanghai Institutes for Biological Sciences. "Now we see how NPC1L1 is recycled between the cell surface and vesicles [inside the cell] and how it takes in cholesterol."
The findings might also have important implications for the search for new cholesterol absorption inhibitors, he added. "If we can uncover the players, we can try to identify new small molecules to interfere with the process."
Despite its bad reputation as a major risk factor for coronary heart disease, cholesterol is an essential component of most biological membranes and is the precursor for synthesis of steroid hormones and bile acids produced by the liver to break down fat. Almost every kind of mammalian cell can synthesize cholesterol, but the process is an energy-intensive one. Therefore, mammals including humans obtain significant amounts of cholesterol from their diets.
Four years ago, scientists identified NPC1L1 as a critical player in cholesterol's absorption. Researchers also found that mice lacking NPC1L1 stop responding to ezetimibe. While there were clues that the drug interacts directly with the cholesterol absorption protein, the details remained unclear.
Song's group now finds that cholesterol specifically encourages cells to engulf and internalize NPC1L1 in a process known as endocytosis. In that process, part of the cell membrane pinches off to form a vesicle containing the protein.
By preventing NPC1L1's entry into the cell, the researchers showed they could dramatically reduce the amount of cholesterol taken up by cells. Ezetimibe accomplishes that by preventing NPC1L1 from incorporating into vesicles.
Although ezetimibe can dramatically decrease blood cholesterol concentrations in some people, it is barely effective in others, the researchers said.
" Therefore," Song said, "there is an urgent need for more cholesterol uptake inhibitory drugs. Our work provides the molecular basis for developing additional cholesterol absorption inhibitors. Moreover, the cell-based assay that we have established can potentially be used to screen for novel inhibitors of NPC1L1 endocytosis, which will block cholesterol uptake eventually."
Earlier studies had suggested that ezetimibe acts on an intestinal and liver protein recently found to play a critical role in cholesterol absorption. Now, the researchers reveal how that protein known as Niemann-Pick C1-like 1 (NPC1L1) carries cholesterol into the cell. They also show that ezetimibe bars NPC1L1's entry into the cell, thereby keeping cholesterol at bay.
"This is a breakthrough in terms of understanding how cholesterol is absorbed," said Bao-Liang Song of Shanghai Institutes for Biological Sciences. "Now we see how NPC1L1 is recycled between the cell surface and vesicles [inside the cell] and how it takes in cholesterol."
The findings might also have important implications for the search for new cholesterol absorption inhibitors, he added. "If we can uncover the players, we can try to identify new small molecules to interfere with the process."
Despite its bad reputation as a major risk factor for coronary heart disease, cholesterol is an essential component of most biological membranes and is the precursor for synthesis of steroid hormones and bile acids produced by the liver to break down fat. Almost every kind of mammalian cell can synthesize cholesterol, but the process is an energy-intensive one. Therefore, mammals including humans obtain significant amounts of cholesterol from their diets.
Four years ago, scientists identified NPC1L1 as a critical player in cholesterol's absorption. Researchers also found that mice lacking NPC1L1 stop responding to ezetimibe. While there were clues that the drug interacts directly with the cholesterol absorption protein, the details remained unclear.
Song's group now finds that cholesterol specifically encourages cells to engulf and internalize NPC1L1 in a process known as endocytosis. In that process, part of the cell membrane pinches off to form a vesicle containing the protein.
By preventing NPC1L1's entry into the cell, the researchers showed they could dramatically reduce the amount of cholesterol taken up by cells. Ezetimibe accomplishes that by preventing NPC1L1 from incorporating into vesicles.
Although ezetimibe can dramatically decrease blood cholesterol concentrations in some people, it is barely effective in others, the researchers said.
" Therefore," Song said, "there is an urgent need for more cholesterol uptake inhibitory drugs. Our work provides the molecular basis for developing additional cholesterol absorption inhibitors. Moreover, the cell-based assay that we have established can potentially be used to screen for novel inhibitors of NPC1L1 endocytosis, which will block cholesterol uptake eventually."
Sexual Function Of Prostate Cancer Survivors Improved By Cialis
In the first randomized trial of its kind, Tadalafil, a drug typically prescribed for erectile dysfunction in men, has been proven to increase the sexual function of prostate cancer survivors, according to a study released today from the International Journal of Radiation Oncology*Biology*Physics, the official journal of ASTRO.
Prostate cancer is the most commonly diagnosed cancer in men, with an estimated 235,000 Americans expected to be diagnosed with it this year. In its early stage, prostate cancer can be treated with surgery and radiation therapy or a combination of the two. With more advanced cancer, treatment options can vary.
The walnut-sized prostate is located near the tubes that carry urine and semen. After treatment, some patients report trouble achieving an erection sufficient for sexual activity, also called erectile dysfunction or ED. In this study, doctors wanted to test whether the drug Tadalafil, which sells under the brand name Cialis, would help prostate cancer survivors with ED who were treated with three-dimensional conformal radiation therapy (3D-CRT). This is the first randomized, placebo-controlled, double-blind trial to examine Tadalafil's lasting effect in treating patients who have ED after radiation therapy for prostate cancer.
Nearly 360 patients were treated for prostate cancer at the Erasmus MC-Daniel den Hoed Cancer Center in The Netherlands between 1998 and 2002. Among them, 60 patients complaining of erectile dysfunction after radiation therapy were included. Patients were eligible if they were treated with 3D-CRT at least 12 months before the study entry, agreed not to use any other treatment for ED and agreed to make at least one sexual intercourse attempt every week during the 12-week trial. Patients were given an initial 4-week course of no treatment at all; however, patients had to attempt sexual activity at least once a week in this 4-week period.
Patients were given 20mg of Tadalafil or a placebo for 6 weeks. Patients were allowed to take the drug or placebo at-will with no restrictions on food or alcohol, but no more than once per day. The men were instructed that the drug would be effective for as long as 36 hours after dosing. After the first 6-week period of the trial, participants were moved onto alternative treatment; patients who were given placebo were switched to Tadalafil and vice versa.
Doctors found that successful intercourse was reported in 48 percent of the survivors who took Tadalafil versus the 9 percent of the men who were given placebo. There was also a reported improvement of the quality of erections in 67 percent of the patients versus only 20 percent of the placebo group.
"Fortunately, prostate cancer is a very curable disease with most patients living at least five years after diagnosis. Now that we've proven we can beat the disease, it's imperative that we work to help maintain the quality of life for the men who survive it, including preserving their sexual function," said Luca Incrocci, M.D., Ph.D., lead author of the study. Dr. Incrocci is a radiation oncologist at the Erasmus MC-Daniel den Hoed Cancer Center in The Netherlands. "This study proves that the drug Cialis is effective in helping men maintain their sexual health."
Prostate cancer is the most commonly diagnosed cancer in men, with an estimated 235,000 Americans expected to be diagnosed with it this year. In its early stage, prostate cancer can be treated with surgery and radiation therapy or a combination of the two. With more advanced cancer, treatment options can vary.
The walnut-sized prostate is located near the tubes that carry urine and semen. After treatment, some patients report trouble achieving an erection sufficient for sexual activity, also called erectile dysfunction or ED. In this study, doctors wanted to test whether the drug Tadalafil, which sells under the brand name Cialis, would help prostate cancer survivors with ED who were treated with three-dimensional conformal radiation therapy (3D-CRT). This is the first randomized, placebo-controlled, double-blind trial to examine Tadalafil's lasting effect in treating patients who have ED after radiation therapy for prostate cancer.
Nearly 360 patients were treated for prostate cancer at the Erasmus MC-Daniel den Hoed Cancer Center in The Netherlands between 1998 and 2002. Among them, 60 patients complaining of erectile dysfunction after radiation therapy were included. Patients were eligible if they were treated with 3D-CRT at least 12 months before the study entry, agreed not to use any other treatment for ED and agreed to make at least one sexual intercourse attempt every week during the 12-week trial. Patients were given an initial 4-week course of no treatment at all; however, patients had to attempt sexual activity at least once a week in this 4-week period.
Patients were given 20mg of Tadalafil or a placebo for 6 weeks. Patients were allowed to take the drug or placebo at-will with no restrictions on food or alcohol, but no more than once per day. The men were instructed that the drug would be effective for as long as 36 hours after dosing. After the first 6-week period of the trial, participants were moved onto alternative treatment; patients who were given placebo were switched to Tadalafil and vice versa.
Doctors found that successful intercourse was reported in 48 percent of the survivors who took Tadalafil versus the 9 percent of the men who were given placebo. There was also a reported improvement of the quality of erections in 67 percent of the patients versus only 20 percent of the placebo group.
"Fortunately, prostate cancer is a very curable disease with most patients living at least five years after diagnosis. Now that we've proven we can beat the disease, it's imperative that we work to help maintain the quality of life for the men who survive it, including preserving their sexual function," said Luca Incrocci, M.D., Ph.D., lead author of the study. Dr. Incrocci is a radiation oncologist at the Erasmus MC-Daniel den Hoed Cancer Center in The Netherlands. "This study proves that the drug Cialis is effective in helping men maintain their sexual health."
Enhancement Drugs And Healthy People
Healthy people are more willing to take drugs to enhance traits that are not fundamental to their identity.
According to a new study in the Journal of Consumer Research, people's willingness to take a pill or drug depends on whether the trait the drug promises to enhance is one they consider fundamental.
Authors Jason Riis (NYU, Harvard Business School), Joseph P. Simmons (Yale University), and Geoffrey P. Goodwin (Princeton University) examine the moral dilemmas that arise as technologies develop that not only cure disease but also enhance already-healthy people. As many young people without diagnosed disorders or deficits take Ritalin or Adderall to improve concentration or anti-depressants to lift their moods, this study examines what makes healthy people willing to take pills.
The researchers determined that people do not feel comfortable using a pill to enhance a trait they believe to be fundamental to their identity. But less-fundamental traits, including concentration, are more acceptable targets.
"We suggest that people's willingness to take psychological enhancements will largely depend on beliefs about whether those enhancements will alter characteristics considered fundamental to self-identity," the authors write.
During a series of studies, the researchers found that young people were less likely to agree to take a drug to increase their social comfort than one that increased their ability to concentrate. The most common reason participants said they wouldn't want to take a pill was because it would "fundamentally change who I am."
Not surprisingly, the marketing message affected participants' responses. When the researchers tested different advertising taglines, they found that participants responded more positively to a drug promising to help them become "more than who you are," than one that would allow them to become "who you are."
"Together, this research converges to highlight the importance of identity expression and preservation in governing the choices and lives of consumers," write the authors.
According to a new study in the Journal of Consumer Research, people's willingness to take a pill or drug depends on whether the trait the drug promises to enhance is one they consider fundamental.
Authors Jason Riis (NYU, Harvard Business School), Joseph P. Simmons (Yale University), and Geoffrey P. Goodwin (Princeton University) examine the moral dilemmas that arise as technologies develop that not only cure disease but also enhance already-healthy people. As many young people without diagnosed disorders or deficits take Ritalin or Adderall to improve concentration or anti-depressants to lift their moods, this study examines what makes healthy people willing to take pills.
The researchers determined that people do not feel comfortable using a pill to enhance a trait they believe to be fundamental to their identity. But less-fundamental traits, including concentration, are more acceptable targets.
"We suggest that people's willingness to take psychological enhancements will largely depend on beliefs about whether those enhancements will alter characteristics considered fundamental to self-identity," the authors write.
During a series of studies, the researchers found that young people were less likely to agree to take a drug to increase their social comfort than one that increased their ability to concentrate. The most common reason participants said they wouldn't want to take a pill was because it would "fundamentally change who I am."
Not surprisingly, the marketing message affected participants' responses. When the researchers tested different advertising taglines, they found that participants responded more positively to a drug promising to help them become "more than who you are," than one that would allow them to become "who you are."
"Together, this research converges to highlight the importance of identity expression and preservation in governing the choices and lives of consumers," write the authors.
Sixth Annual Gastrointestinal Cancers Symposium Press Program Announced
The sixth annual Gastrointestinal (GI) Cancers Symposium Press Program will highlight research on the prevention, screening and treatment of GI cancers. Study authors will discuss four notable studies in an embargoed presscast (press briefing via live webcast) on Tuesday, January 13 from 12:00-1:30 PM (EST).
Featured research includes:
- Findings from an economic model assessing the potential cost savings associated with KRAS gene testing in patients with metastatic colorectal cancer, and using gene status to guide use of the targeted therapy cetuximab (Erbitux)
- A randomized, placebo-controlled study evaluating whether octreotide LAR, a drug used to inhibit hormone secretion, can delay tumor growth in patients with rare metastatic neuroendocrine midgut tumors
- A study exploring the use of epidermal growth factor gene variations to predict risk of esophageal cancer in patients with gastroesophageal reflux disease (GERD)
- A study examining the use of DNA mismatch repair genes to determine clinical outcomes for pancreatic cancer patients, which have the potential to identify patients who are most likely to benefit from more aggressive care
This year's Symposium will take place from January 15 through January 17, 2009, at the Moscone West Building in San Francisco, CA, and will feature more than 500 abstracts on a variety of gastrointestinal cancers including cancers of the esophagus, stomach, hepatobiliary, pancreas, small bowel, colon, and rectum. These cancers are diagnosed in approximately 263,000 people in the U.S. every year.
In addition to the presscast, a working newsroom will be available onsite at the meeting for reporters. Experts will be available for comment and perspective upon request.
Four leading medical specialty societies co-sponsor the three-day, multidisciplinary symposium including the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Therapeutic Radiology and Oncology (ASTRO) and the Society of Surgical Oncology (SSO).
Featured research includes:
- Findings from an economic model assessing the potential cost savings associated with KRAS gene testing in patients with metastatic colorectal cancer, and using gene status to guide use of the targeted therapy cetuximab (Erbitux)
- A randomized, placebo-controlled study evaluating whether octreotide LAR, a drug used to inhibit hormone secretion, can delay tumor growth in patients with rare metastatic neuroendocrine midgut tumors
- A study exploring the use of epidermal growth factor gene variations to predict risk of esophageal cancer in patients with gastroesophageal reflux disease (GERD)
- A study examining the use of DNA mismatch repair genes to determine clinical outcomes for pancreatic cancer patients, which have the potential to identify patients who are most likely to benefit from more aggressive care
This year's Symposium will take place from January 15 through January 17, 2009, at the Moscone West Building in San Francisco, CA, and will feature more than 500 abstracts on a variety of gastrointestinal cancers including cancers of the esophagus, stomach, hepatobiliary, pancreas, small bowel, colon, and rectum. These cancers are diagnosed in approximately 263,000 people in the U.S. every year.
In addition to the presscast, a working newsroom will be available onsite at the meeting for reporters. Experts will be available for comment and perspective upon request.
Four leading medical specialty societies co-sponsor the three-day, multidisciplinary symposium including the American Gastroenterological Association (AGA) Institute, the American Society of Clinical Oncology (ASCO), the American Society for Therapeutic Radiology and Oncology (ASTRO) and the Society of Surgical Oncology (SSO).
Study Links ADHD Drugs To Sudden Death In Children
A new study by researchers in the US suggests there may be a link between the use of stimulant drugs for attention-deficit hyperactivity disorder (ADHD) and sudden cardiac death in healthy children, but the US Food and Drug Administration (FDA), who funded the study with the National Institute of Mental Health, said because of its limitations, parents and carers should not stop giving children such medication on the basis of this study but should discuss any concerns with their prescribing doctor.
The study was the work of lead author Dr Madelyn S Gould of Columbia University, New York, New York, and colleagues, and is published in the 15 June issue of the American Journal of Psychiatry.
In the case-control study, using state-based mortality data from 1985 to 1996, Gould and colleagues compared the use of stimulant drugs in 564 healthy children aged 7 to 19 from across the US who died suddenly and most likely due to sudden cardiac disturbance with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents.
The primary measure of exposure was the presence of stimulant medication as noted in the medical examiner records, toxicology reports and death certificates. The stimulants involved were amphetamine, dextroamphetamine, methamphetamine, and methylphenidate.
The results showed that out of the 564 healthy children who died suddenly, 10 (1.8 per cent) were taking stimulants, specifically methylphenidate (better known in the US under its brand name of Ritalin). This compared with only 2 children (0.4 per cent) in motor vehicle accident comparison group, only one of whom was taking Ritalin (methylphenidate).
Logistical regression, a tool commonly used by epidemiologists, showed a statistically significant link between stimulant use and sudden unexplained death in a primary analysis. This result was supported qualitatively in a further "comprehensive series of sensitivity analyses", wrote the authors, who concluded that:
"This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents."
"Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment," they added.
In a Safety Communication released on 15 June, the FDA said that:
"The FDA can not conclude that the data in the study affect the overall risk-benefit profile of stimulant medications used to treat ADHD in children."
What they are saying is they are not going to change their advice about the risks versus the benefits of the medication because of the study's limitations, which they say include:
* The significant time lag between when the deaths occurred and when the data was collected.
* The different circumstances around each death that may have affected how well family members and/or carers may have remembered details of any medication the deceased child had been using.
* Sudden unexplained death in a child would be more likely to initiate a post-mortem inquiry than a death due to blunt force trauma in a motor vehicle accident.
* The low frequency of stimulant medication use by the children in both the study and the control groups.
When scientists highlight a study's limitations they are in effect saying that another study looking at the same things might reach a different result if it didn't have those limitations.
With subjects as serious as this, and with parents and carers rightly concerned about what to do about any ADHD medication their children have been prescribed, it is important that research in the service of public health produces results that are robust and reliable, so a small study like this one really needs to be confirmed by more research, preferably with a larger study, especially if there are concerns about its limitations.
In fact, the FDA is already co-sponsoring another larger study that is looking at the link between increased risk of heart attack, stroke and other cardiovascular problems and use of stimulant medication by children, the results of which are expected to come out later this year.
Dr Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research told the press:
"The FDA continues to review drug safety information for stimulant medications used to treat ADHD so that we can give health care professionals and families the most up-to-date drug safety information available."
The federal agency urged doctors to follow the current prescribing information that accompanies the product label, which recommends that young and adult patients being considered for ADHD treatment:
"Work with their health care professional to develop a treatment plan that includes a careful health history for cardiovascular disease in the child and his or her family."
Such preparation should include a physical exam that pays particular attention to the cardiovascular system, and should consider screening tests such as electrocardiogram and echocardiogram, depending on the patient's history and whether it suggests possible risk factors for heart disease.
The study was the work of lead author Dr Madelyn S Gould of Columbia University, New York, New York, and colleagues, and is published in the 15 June issue of the American Journal of Psychiatry.
In the case-control study, using state-based mortality data from 1985 to 1996, Gould and colleagues compared the use of stimulant drugs in 564 healthy children aged 7 to 19 from across the US who died suddenly and most likely due to sudden cardiac disturbance with a matched group of 564 young people who died as passengers in motor vehicle traffic accidents.
The primary measure of exposure was the presence of stimulant medication as noted in the medical examiner records, toxicology reports and death certificates. The stimulants involved were amphetamine, dextroamphetamine, methamphetamine, and methylphenidate.
The results showed that out of the 564 healthy children who died suddenly, 10 (1.8 per cent) were taking stimulants, specifically methylphenidate (better known in the US under its brand name of Ritalin). This compared with only 2 children (0.4 per cent) in motor vehicle accident comparison group, only one of whom was taking Ritalin (methylphenidate).
Logistical regression, a tool commonly used by epidemiologists, showed a statistically significant link between stimulant use and sudden unexplained death in a primary analysis. This result was supported qualitatively in a further "comprehensive series of sensitivity analyses", wrote the authors, who concluded that:
"This case-control study provides support for an association between the use of stimulants and sudden unexplained death among children and adolescents."
"Although sudden unexplained death is a rare event, this finding should be considered in the context of other data about the risk and benefit of stimulants in medical treatment," they added.
In a Safety Communication released on 15 June, the FDA said that:
"The FDA can not conclude that the data in the study affect the overall risk-benefit profile of stimulant medications used to treat ADHD in children."
What they are saying is they are not going to change their advice about the risks versus the benefits of the medication because of the study's limitations, which they say include:
* The significant time lag between when the deaths occurred and when the data was collected.
* The different circumstances around each death that may have affected how well family members and/or carers may have remembered details of any medication the deceased child had been using.
* Sudden unexplained death in a child would be more likely to initiate a post-mortem inquiry than a death due to blunt force trauma in a motor vehicle accident.
* The low frequency of stimulant medication use by the children in both the study and the control groups.
When scientists highlight a study's limitations they are in effect saying that another study looking at the same things might reach a different result if it didn't have those limitations.
With subjects as serious as this, and with parents and carers rightly concerned about what to do about any ADHD medication their children have been prescribed, it is important that research in the service of public health produces results that are robust and reliable, so a small study like this one really needs to be confirmed by more research, preferably with a larger study, especially if there are concerns about its limitations.
In fact, the FDA is already co-sponsoring another larger study that is looking at the link between increased risk of heart attack, stroke and other cardiovascular problems and use of stimulant medication by children, the results of which are expected to come out later this year.
Dr Janet Woodcock, director of the FDA's Center for Drug Evaluation and Research told the press:
"The FDA continues to review drug safety information for stimulant medications used to treat ADHD so that we can give health care professionals and families the most up-to-date drug safety information available."
The federal agency urged doctors to follow the current prescribing information that accompanies the product label, which recommends that young and adult patients being considered for ADHD treatment:
"Work with their health care professional to develop a treatment plan that includes a careful health history for cardiovascular disease in the child and his or her family."
Such preparation should include a physical exam that pays particular attention to the cardiovascular system, and should consider screening tests such as electrocardiogram and echocardiogram, depending on the patient's history and whether it suggests possible risk factors for heart disease.