Trial will evaluate resveratrol in Alzheimer's dementia

In continuation of my update on Resveratrol

Researchers at Georgetown University and 25 other U.S. academic institutions affiliated with the Alzheimer's Disease Cooperative Study will be conducting a phase II double-blinded, placebo-controlled trial that will test the effects of resveratrol in Alzheimer's disease patients. "This is the gold-standard for conducting a clinical study because it allows us to objectively determine if resveratrol is offering any benefits," stated Brigid Reynolds, NP, who is the lead researcher for the study's center at Georgetown.

The twelve-month trial, funded by the National Institute on Aging, will enroll men and women age 50 and over with mild to moderate dementia diagnosed as probable Alzheimer's disease and will require one caregiver or friend for each patient. Participants will be initially assigned to 500 milligrams resveratrol or a placebo daily, with dosage to be increased at 13 week intervals to a maximum of 1,000 milligrams twice per day. Lumbar punctures, brain magnetic resonance imaging (MRI) scans, and blood and urine tests will monitor the subjects' progress over the course of ten visits. The researchers hope to determine whether supplementation with resveratrol is helpful in delaying or altering the deterioration of memory and daily function that occurs in Alzheimer's disease.

"Most resveratrol studies showing any health benefits have been conducted in animal models, such as mice, and with doses that far exceed intake from sipping wine or nibbling on chocolate," stated R. Scott Turner, MD, PhD, who is the director of Georgetown University Medical Center's Memory Disorders Program and the national study's lead investigator. "With this clinical trial, we'll find out if daily doses of pure resveratrol can delay or alter memory deterioration and daily functioning in people with mild to moderate dementia due to Alzheimer's."

"During this study, we will also test whether resveratrol improves glucose and insulin metabolism in older individuals -- although those who already have diabetes will not be included in this study," he added....

Ref : http://explore.georgetown.edu/news/?ID=64145

Ebola, Marburg Virus Treatments Safe in Phase 1 Studies

In continuation of my update on antisense drugs and RNAi

AVI BioPharma Inc. announced positive safety results from the first five cohorts of Phase 1 single ascending dose trials of AVI-6002 and AVI-6003, AVI's lead drug candidates being evaluated for the treatment of the Ebola virus and Marburg virus.

Data were evaluated by an independent Data and Safety Monitoring Board (DSMB), which issued recommendations for both studies to progress as planned to the next highest dosing level after no safety concerns were identified. The Phase 1 single ascending dose trials are designed to characterize the safety, tolerability, and pharmacokinetics of each therapeutic candidate in healthy adult volunteers.

"We are very encouraged that these two drugs, which use our advanced PMOplus chemistry, have demonstrated a favorable safety profile through five cohorts in our dose-escalation studies,”says Chris Garabedian, president and chief executive officer of AVI BioPharma...

Ref : http://phx.corporate-ir.net/phoenix.zhtml?c=64231&p=RssLanding&cat=news&id=1619940

To date, 25 healthy human subjects (five per group) have been enrolled into five sequential dose groups in each of the two studies. Within each group, four subjects received the indicated dose of the therapeutic and one subject received placebo. For each group, safety, clinical laboratory and renal biomarker results through five days after treatment were reviewed by a DSMB. Subjects enrolled in the sixth group for the drug studies will receive 9.0 mg/kg of the therapeutic or placebo. Final, un-blinded safety and pharmacokinetic results for all subjects will be available upon completion of the trial.

Both candidates employ AVI's patented PMOplus technology that selectively introduces positive charges to its phosphorodiamidate morpholino oligomer (PMO) backbone to improve interaction between the drug and its target.

Tivozanib Improves RCC (renal cell carinomas) Survival

Tivozanib (see structure, AV-951) is an oral VEGF receptor tyrosine kinase inhibitor. It is undergoing clinical trial investigation for the treatment of renal cell carinomas. An oral quinoline urea derivative, tivozanib suppresses angiogenesis by being selectively inhibitory against vascular endothelial growth factor.

The positive results of this Phase 2 trial informed the design and implementation of TIVO-1, a pivotal Phase 3 clinical study in advanced RCC demonstrating tivozanib superiority over sorafenib in the primary endpoint of PFS in the first-line setting, top-line data from which were reported in January 2012.

“Current RCC therapies are associated with toxicities that can interfere with patients’ treatment regimens and impact treatment efficacy and activities of daily living,” said Dmitry A. Nosov, M.D., Ph.D., senior clinical researcher at the Blokhin Oncology Research Center, Moscow, Russian Federation, lead author of the Phase 2 study and TIVO-1 investigator.

“Despite recent progress in treating patients with RCC, patients and physicians would benefit from a new RCC treatment option that delivers both improved efficacy and a more tolerable safety profile. The combined tivozanib efficacy and safety data demonstrated in this Phase 2 study supports tivozanib as a potential advancement in the RCC treatment landscape.”

Based on the positive Phase 2 data and success of the TIVO-1 trial, AVEO and its collaborator Astellas Pharma Inc. are moving forward with plans for submitting the tivozanib NDA in RCC in the third quarter of 2012, with the MAA submission to follow.

“We believe that the efficacy and safety profile consistently demonstrated by tivozanib and recently validated in our Phase 3 TIVO-1 trial represent an important step forward in the treatment of patients who have advanced RCC,” said William Slichenmyer, M.D., Sc.M., chief medical officer, AVEO. “We are pleased with the opportunity to collaborate with tivozanib study investigators on publishing these positive Phase 2 data in the Journal of Clinical Oncology, and look forward to advancing our work with our global partners at Astellas to bring tivozanib to patients who can benefit from this therapy.”....

http://jco.ascopubs.org/content/30/14/1678.abstract?sid=1fe73024-e1cc-481f-acc3-1dc09b596f7f

Dalcetrapib Testing Halted..

A second experimental cholesterol medicine in a once-promising class of drugs meant to replace blockbusters such as Lipitor has failed in testing, casting doubt on whether any of the drugs will ever make it to pharmacies.

Swiss drugmaker Roche Holding AG said it has halted testing of its dalcetrapib (see structure), which the company had hoped would become a blockbuster, with eventual annual sales of more than $1 billion. The drug was in expensive late-stage patient testing as a treatment to raise HDL, or so-called good cholesterol, in heart disease patients.

Basel-based Roche said it decided to pull the plug on the recommendation of its independent data and safety monitoring board after an interim analysis, in a study called dal-OUTCOMES, found no "clinically meaningful" benefit.

Ref : http://www.roche.com/media/media_releases/med-cor-2012-05-07.htm

Positive Data from aripiprazole intramuscula for Schizophrenia Trial

Otsuka Pharmaceutical Co. Ltd. and H. Lundbeck A/S announced results from a Phase 3 clinical trial evaluating the efficacy, safety and tolerability of once-monthly aripiprazole (see structure) intramuscular (IM) depot formulation for the maintenance treatment of adults with schizophrenia. Trial results were presented in four poster presentations at the 2012 American Psychiatric Association (APA) Annual Meeting in Philadelphia. 

In a 52-week, double-blind, randomized, placebo-controlled study conducted by Otsuka Pharmaceutical Development & Commercialization, Inc. (OPDC), aripiprazole IM depot formulation significantly delayed time-to-impending relapse compared to placebo, the primary endpoint of the study (Hazard ratio = 5.03, p<0.0001). In addition, improvements in the symptoms [as measured by the Positive and Negative Syndrome Scale (PANSS) total score] were maintained throughout the study in patients treated with aripiprazole IM depot formulation, while patients who received placebo reported significantly worsening scores (mean change from baseline at week 52 was 1.4 for aripiprazole IM depot formulation compared to 11.6 for placebo; LOCF analysis, p<0.0001).

Canagliflozin Provided Substantial and Sustained Glycemic Improvements as Monotherapy and in Add-On Combinations in Adults with Type 2 Diabetes in Five Phase 3 Studies

Canagliflozin is an experimental drug being developed by Johnson & Johnson for the treatment of type 2 diabetes. It is an inhibitor of subtype 2 sodium-glucose transport protein (SGLT2), which is responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine..

More...

Lilly, Boehringer Ingelheim announce results from linagliptin Phase III trial on T2D

 In continuation of my update on Linagliptin

Results of the one Phase III study presented (Poster No. 999-P) showed that linagliptin was effective as an add-on therapy to basal insulin alone or in combination with metformin and/or pioglitazone in reducing blood glucose levels in adult patients with T2D, when compared to placebo as an add-on to these background therapies. Linagliptin demonstrated a placebo-adjusted reduction in HbA1c of 0.65% (p<0.0001) from a baseline HbA1c of 8.3% at 24 weeks without weight gain or additional risk of hypoglycaemia.  HbA1c is measured in people with diabetes to provide an index of blood glucose control for the previous two to three months. 

A post-hoc analysis from a second Phase III trial (Poster No. 1044-P) found that in hyperglycaemic patients on a background of metformin randomised to add linagliptin or glimepiride, a greater proportion of patients taking linagliptin achieved target HbA1c <7% without weight gain and/or hypoglycaemia than those taking glimepiride after 104 weeks (linagliptin 54% versus glimepiride 23%) while comparably improving blood glucose levels.

Ref : http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2012/09_june_2012_linagliptin1.html

Drug kills cancer cells by restoring faulty tumor suppressor

A new study describes a compound that selectively kills cancer cells by restoring the structure and function of one of the most commonly mutated proteins in human cancer, the "tumor suppressor" p53. The research, published by Cell Press in the May 15th issue of the journal Cancer Cell, uses a novel, computer based strategy to identify potential anti-cancer drugs, including one that targets the third most common p53 mutation in human cancer, p53-R175H. 

Restoring the function of mutant p53 with a drug has long been recognized as an attractive cancer therapeutic strategy," explains senior study author, Dr. Darren R. Carpizo, from The Cancer Institute of New Jersey. "However, it has proven difficult to find compounds that restore the lost function of a defective tumor-suppressor."

Using the National Cancer Institute's anticancer drug screen data researchers identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53^R175 mutant. Mechanistic studies reveal that NSC319726 (see structure) restores WT structure and function to the p53^R175 mutant. 

This compound kills p53^R172H knockin mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele-specific mutant p53-dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53^R175 mutant reactivator and as a lead compound for p53-targeted drug development.

Drug kills cancer cells by restoring faulty tumor suppressor

Combination of vaccine and letrozole effectively improves survival from breast cancer

In continuation of my update on Letrozole

Combination of vaccine and letrozole effectively improves survival from breast cancer: A vaccine that targets cancer cells in combination with the drug letrozole, a standard hormonal therapy against breast cancer, significantly increased survival when tested in mice, a team of UC Davis investigators has found.

Pungent Ingredient, piperine, in Black Pepper Targets Fat Cells

A preliminary new study suggests that the pungent component in black pepper known as piperine fights fat by blocking the formation of new fat cells.

If further studies confirm these effects, researchers say black pepper may offer a natural alternative for the treatment of fat-related disorders like obesity.

"Our findings suggest that piperine (see above structure), a major component of black pepper, inhibits fat cell differentiation ... thus leading to its potential use in the treatment of obesity-related diseases," writes researcher Ui-Hyun Park of Sejong University in Seoul, Korea 

Black Pepper the Fat Fighter....

Researchers say the benefits of black pepper and the black pepper plant have been known for centuries in traditional Eastern medicine, in which it is used to treat cholera, diarrhea, and other gastrointestinal issues.

In their study, researchers looked at the effects of piperine on gene expression in fat tissue in the lab and in computer models.

The results showed that piperine interfered with the activity of genes responsible for forming new fat cells.

Researchers say this benefit of black pepper sets up a chain reaction that helps keep the formation of fat in check in other ways as well.

"Overall, our results suggest that piperine could be a lead natural compound for the treatment of fat-related disorders," the researchers write.

Topical Gel (from Euphorbia peplus) Treats Precancerous Skin Condition, Actinic Keratosis

A new prescription gel may quickly treat a common precancerous skin condition called actinic keratosis, a new study shows.

The gel is derived from the sap of the Euphorbia peplus plant. This has long been used as a folk remedy for skin lesions.

The new gel, Picato (ingenol mebutate, see below structure), is applied once daily for two or three days, depending on the area being treated. Other available topical treatments must be used for several weeks, and often irritate the skin. Cryotherapy, or freezing the affected skin area, is also used but can sometimes leave a scar.

Because the new gel is only used for a few days, any irritation is usually short-lived. The short duration also makes people more likely to stay the course, another advantage, according to the study’s authors.

“The shorter application period is what makes ingenol mebutate a breakthrough in the treatment of actinic keratosis,” researcher Mark Lebwohl, MD, says in a news release. He is a professor and chair of the department of dermatology at Mount Sinai School of Medicine in New York City.

Experimental cholesterol drug, REGN727 (PCSK9 inhibitor) results called ‘game changing

In continuation on my update on drug discovery in the class of  Monoclonal antibodies

Researchers have known for some time that when the protein PCSK9, (below structure) which stands for proprotein convertase subtilisin/kexin 9, binds to LDL receptors on the liver, it compromises the organ’s ability to filter the bad cholesterol from the blood.

Too much LDL cholesterol circulating in the blood can lead to the thickening of artery walls, making them less flexible and therefore impairing their function and increasing the risk of heart disease.

In a phase one clinical trial, which is designed to determine if a drug is safe, researchers found that using a monoclonal antibody (lab-produced protein) called REGN727, was not only safe, but effectively blocked PCSK9 and therefore signficantly reduced bad cholesterol in healthy patients as well as those also taking the popular cholesterol-lowering drug Lipitor.

“Wars for PCSK9 are far bigger than the statin wars,” said Dr. Evan A Stein, lead author of the study and researcher at the Metabolic and Atherosclerosis Research Center in Cincinnati, Ohio. “This is a hot research area and everybody is so close together.”

The REGN727 study included three trial arms. Two arms used 72 healthy volunteers who were either injected with a single dose of the drug in increasing amounts to test for side effects, which is the purpose of a phase one clinical trial.  A third arm included 21 people with a family history of high cholesterol, and 30 people with nonfamilial high cholesterol. All of those subjects were also receiving treatment with the statin Lipitor.

A control group of subjects with nonfamilial high cholesterol was treated only with a special diet.  None of the subjects who received REGN727 discontinued the study because of adverse effects, and the subjects who received REGN727 had a striking reduction of 60 to 65%  in LDL cholesterol, according to Stein.

A PCSK9 inhibitor, Stein said, differs from statins “because it’s unlike any other drug. With statins you get toxicity – with these drugs we don’t see any side effects with the antibody.”

In an accompanying editorial, authors Dr. Stephen G. Young, and Loren G. Fong, Ph.D. write: “At this point, the status of PCSK9 therapeutics appears to be full speed ahead. Soon, we can expect more human trials in which investigators will dissect the properties of different PCSK9 antibodies and assess the effect of these agents.”

However, without long-term safety data and evidence that PCSK9 inhibitors truly help prevent heart disease, Young and Fong caution that it will remain unclear how important this class of drugs will be.

The cost of this drug will also play a role in determining which patients might use it, Fong and Young say.  But they also note that “patients who cannot tolerate statins could benefit greatly.”

Researchers also claim that,  the study methodology was thorough because it included people with high cholesterol as well as people with genetic familial high cholesterol, which is proven to be a result of impaired PCSK9 genetic function.

Researchers have known for some time that when the protein PCSK9, which stands for proprotein convertase subtilisin/kexin 9, binds to LDL receptors on the liver, it compromises the organ’s ability to filter the bad cholesterol from the blood.

Researchers conclude that, In three phase 1 trials, a monoclonal antibody to PCSK9 significantly reduced LDL cholesterol levels in healthy volunteers and in subjects with familial or nonfamilial hypercholesterolemia.

Ref : http://www.nejm.org/doi/full/10.1056/NEJMoa1105803

Soy Supplements Can Cool Hot Flashes

In continuation of my update on Soy...

Taking soy to relieve hot flashes has received mixed reviews over the years. Now, researchers who took another look at 19 published studies find that soy supplements may help, at least over time. Soy has been touted as an alternative treatment to hormone replacement therapy after HRT was linked to an increased risk of breast cancer.

“For many women with symptoms and especially with concerns about hormone replacement therapy, trying soy for six to 12 weeks to see if it relieves their symptoms could be a first line of treatment,” says Melissa Melby, PhD, a professor of medical anthropology at the University of Delaware.

Researchers conclude that, Soy isoflavone supplements, derived by extraction or chemical synthesis, are significantly more effective than placebo in reducing the frequency and severity of hot flashes. Additional studies are needed to further address the complex array of factors that may affect efficacy, such as dose, isoflavone form, baseline hot flash frequency, and treatment duration.


Ref : http://journals.lww.com/menopausejournal/Abstract/publishahead/Extracted_or_synthesized_soybean_isoflavones.98844.aspx

Lorcaserin Receives Positive Vote From FDA Advisory Committee

In continuation of my update on Lorcaserin

Lorcaserin Receives Positive Vote From FDA Advisory Committee:  

(FDA) Endocrinologic and Metabolic Drugs Advisory Committee voted 18 to 4, with one abstention, that the available data demonstrate that the potential benefits of lorcaserin outweigh the potential risks when used long-term in a population of overweight and obese individuals. Lorcaserin is an investigational drug candidate intended for weight management, including weight loss and maintenance of weight loss, in patients who are obese (BMI greater than or equal to 30) or patients who are overweight (BMI greater than or equal to 27) and have at least one weight-related co-morbid condition.

"The advisory committee's positive vote supports our belief in lorcaserin as a potential new treatment option for the medical management of overweight and obesity," said Jack Lief, Arena's President and Chief Executive Officer. "We will continue to work with the FDA as the agency completes its review of the lorcaserin new drug application."

In continuation of my update on curcumin,,,,

Curcumin, an active component of the Indian curry spice turmeric, may help slow down tumor growth in castration-resistant prostate cancer patients on androgen deprivation therapy (ADT), a study from researchers at Jefferson's Kimmel Cancer Center suggests. More

 Curry spice component may help slow prostate tumor growth

2 Drugs Better Than 1 to Treat Youth With Type 2 Diabetes

2 Drugs Better Than 1 to Treat Youth With Type 2 Diabetes: A combination of two diabetes drugs, metformin and rosiglitazone, was more effective in treating youth with recent-onset type 2 diabetes than metformin alone, a study funded by the National Institutes of Health (NIH) has found. Adding an intensive lifestyle intervention to metformin provided no more benefit than metformin therapy alone.

The study also found that metformin therapy alone was not an effective treatment for many of these youth. In fact, metformin had a much higher failure rate in study participants than has been reported in studies of adults treated with metformin alone.

The study found that treatment with metformin alone was inadequate for maintaining acceptable, long-term, blood glucose control in 51.7 percent of youth over an average follow-up of 46 months. The failure rate was 38.6 percent in the metformin and rosiglitazone group, a 25.3 percent reduction from metformin alone. In the metformin plus lifestyle group the failure rate was 46.6 percent.

A trial looking at curcumin and FOLFOX for advanced bowel cancer (CUFOX)

In continuation of  my update on curcumin

An upcoming clinical trial conducted by the Cancer Research UK and National Institute for Health Research Experimental Cancer Medicine Centre (ECMC) in Leicester, England will evaluate the effectiveness of curcumin, a compound that occurs in turmeric, as a means of improving the results of standard chemotherapy for metastatic colon cancer. The compound has been found to enhance chemotherapy's ability to kill colon cancer cells in previous research involving cell cultures. 

Doctors often treat bowel cancer that has spread with chemotherapy. The combination of chemotherapy they usually use is called FOLFOX. It is made up of the drugs folinic acid (leucovorin), fluorouracil (5FU) and oxaliplatin. But this doesn’t always work very well.  And it often causes side-effects such as numbness and tingling in hands and feet (peripheral neuropathy). This means the doctors sometimes need to lower the dose or even stop chemotherapy, so they are keen to improve treatment.

Curcumin is a plant extract found in the spice turmeric and is found in many everyday foods. We know from research that curcumin can help shrink tumours in the laboratory. It has also been used in several studies involving patients with a range of conditions, including cancer.

FDA AAC recommends approval of Pfizer’s tofacitinib for RA

In continuation of my update on  Tofacitinib...

FDA AAC recommends approval of Pfizer’s tofacitinib for RA: Pfizer Inc. the Arthritis Advisory Committee to the U.S. Food and Drug Administration (FDA) voted 8-2 to recommend approval of the investigational agent tofacitinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA). The Committee's recommendation will be considered by the FDA in its review of the New Drug Application (NDA) for tofacitinib. The FDA has provided an anticipated Prescription Drug User Fee Act (PDUFA) action date in August 2012. If approved by the FDA, tofacitinib would be the first new oral disease-modifying antirheumatic drug (or DMARD) for RA in more than 10 years and the first RA treatment in a new class of medicines known as Janus kinase (JAK) inhibitors..

Novartis Drug Pasireotide LAR Shows Superior Efficacy Compared to Sandostatin LAR in Phase III Trial of Patients With Acromegaly

Results of the largest Phase III study of acromegaly patients show the novel therapy pasireotide (SOM230 structure left below) long-acting release (LAR), was significantly more effective at inducing full biochemical control compared to the current standard medical therapy, Sandostatin® LAR® (octreotide/IM injection below right structure). 

Novartis Drug Pasireotide LAR Shows Superior Efficacy Compared to Sandostatin LAR in Phase III Trial of Patients With Acromegaly:  Patients on pasireotide (SOM230) LAR were 63% more likely to achieve full biochemical control than those on Sandostatin LAR, the current standard of care[1]  Acromegaly, a rare  endocrine disorder caused by excess growth hormone, can... 

Ref : http://www.novartis.com/newsroom/media-releases/en/2012/1609172.shtml

Positive Results from First of Two ATX-101 European Phase III Trials for Reduction of Submental Fat

KYTHERA,  announced the presentation of initial trial results from Study ATX-101-10-16, the first of two pivotal European Phase III clinical trials with ATX-101 (a first-in-class injectable drug being studied for the reduction of localized fat. ATX-101 is a proprietary formulation of deoxycholate (see below structure)  a well-studied endogenous compound that is present in the body), a facial injectable drug for the reduction of unwanted fat under the chin, or submental fat. V. Leroy Young, MD, FACS, presented the initial results at the American Society for Aesthetic Plastic Surgery (ASAPS) 45^th Annual Aesthetic Meeting in Vancouver, British Columbia, on May 4, 2012.

The ATX-101-10-16  trial met its pre-specified primary endpoints based on clinician and patient assessments. At the 2 mg/cm² dose, ATX-101 resulted in a statistically significant reduction of submental fat, relative to placebo, as measured using a 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) (mean of 0.90 vs. 0.22; p<0.001, week 24). Similarly, ATX-101 (2 mg/cm²) resulted in a statistically significant percentage of subjects, relative to placebo, achieving a pre-defined categorical change using a 7-point Subject Self Rating Scale (SSRS) (66.1 vs. 28.7; p<0.001, week 24).

Molecule Found That Inhibits Estrogen, Key Risk Factor for Endometrial and Breast Cancers

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a molecule, KLF15 (see structure) that inhibits the action of estrogen. This female hormone plays a key role in the growth, maintenance and repair of reproductive tissues and fuels the development of endometrial and breast cancers. The molecule, discovered in animal studies, could lead to new therapies for preventing and treating estrogen-related diseases in humans.

In studies involving rodents, Dr. Pollard discovered that a molecule called KLF15 (Kruppel-like transcription factor-15) controls the actions of estradiol and progesterone in the endometrium by inhibiting the production MCM2, a protein involved in DNA synthesis.

 

"Our findings raise the possibility that it may be possible to prevent or treat endometrial and breast cancer and other diseases related to estrogen by promoting the action of KLF15," said Dr. Pollard.

The paper, titled "KLF15 negatively regulates estrogen-induced epithelial cell proliferation by inhibition of DNA replication licensing," is coauthored by Sanhita Ray, Ph.D., a postdoctoral fellow at Einstein.

More....

Molecule Found That Inhibits Estrogen, Key Risk Factor for Endometrial and Breast Cancers

Flavonoid Compound Found in Foods and Supplements May Prevent the Formation of Blood Clots, Study Suggests...

A compound called  rutin (see structure - a quercetin derivative), commonly found in fruits and vegetables and sold over the counter a dietary supplement, has been shown to inhibit the formation of blood clots in an animal model of thrombosis.

 As per the researchers claim,

"Approximately half of all morbidity and mortality in the United States can be attributed to heart attack or stroke."..

The study focused on protein disulfide isomerase (PDI) which is found in all cells. Investigators in BIDMC's Division of Hemostasis and Thrombosis had previously shown that PDI is rapidly secreted from both platelets and endothelial cells during thrombosis, when a clot forms in a blood vessel, and that inhibition of PDI could block thrombosis in a mouse model.

"This was a transformative and unanticipated finding because it identified, for the first time, that PDI is secreted from cells in a live animal and is a potential target for preventing thrombosis," says Flaumenhaft. However, because intracellular PDI is necessary for the proper synthesis of proteins, the scientists had to identify a specific compound that could block the thrombosis-causing extracellular PDI -- without inhibiting the intracellular PDI.

They began by conducting a high-throughput screen of a wide array of compounds to identify PDI inhibitors. Among the more than 5,000 compounds that were screened, quercetin-3-rutinoside (rutin) emerged as the most potent agent. "Rutin was essentially the champion compound," says Flaumenhaft.

A bioflavonoid that is naturally found in many fruits, vegetables and teas including onions, apples and citrus fruits, rutin is also sold as an herbal supplement, having received a special designation for safety from the U.S. Food and Drug Administration (FDA). Surprisingly, studies of the rutin molecule demonstrated that the same part of the molecule that provides rutin with its ability to inhibit PDI also prevents the compound from entering cells."That finding explained how this compound can be both a potent inhibitor of PDI and a safe food supplement," says Flaumenhaft. "Our next questions were, 'Is this compound anti-thrombotic? Can it prevent blood clots?'"

Soybeans Soaked in Warm Water Naturally Release Key Cancer-Fighting Substance

In continuation of my update on Soy...

Hari B. Krishnan and colleagues explain that the substance, Bowman-Birk Protease Inhibitor (BBI) 9see the below structure), has shown promise for preventing certain forms of cancer in clinical trials. Those human tests resulted from evidence of BBI's beneficial effects, including indications that BBI derived from the large amounts of soybeans in traditional Japanese diets might underpin low cancer mortality rates in Japan. However, the current method of extracting BBI from soybeans is time-consuming and involves harsh chemicals. The scientists set out to see if there might be a greener and more environmentally friendly way of obtaining BBI.

They found that soybean seeds incubated in water at 122 degrees Fahrenheit naturally release large amounts of BBI that can easily be harvested from the water. The protein appeared to be active, with tests showing that it stopped breast cancer cells from dividing in a laboratory dish.

Sunscreen ingredient may be linked to endometriosis

                          (Picture source: Paper published)
Researchers have come with an interesting findings,  some sunscreens and other personal care products contain benzophenone (BP)-type ingredients that are very effective in blocking potentially harmful ultraviolet rays from the sun. Small amounts of BPs can pass through the skin and be absorbed into the blood, where they mimic the effects of estrogen. Endometriosis, which affects up to 1-in-10 women of reproductive age, needs estrogen to develop. Despite those facts, scientists until now had not checked for a connection between the use of BP sunscreens and the likelihood of being diagnosed with endometriosis.

Sunscreen ingredient may be linked to endometriosis

Ref : http://pubs.acs.org/doi/abs/10.1021/es204415a

Lenalidomide Shows Significant Benefit for Myeloma Patients, Phase III Study Suggests

In continuation of my update on lenalidomide...

Data from the first large U.S. study assessing the effectiveness of long-term "maintenance" therapy with lenalidomide for patients with multiple myeloma show that the drug significantly improves the time to progression and overall survival for patients with this often-deadly hematologic cancer. 

Among 460 patients aged 18 to 70 (median age 59), 321 were randomly assigned to the lenalidomide arm, and 229 to the placebo group. All participants had received prior autologous hematopoietic stem-cell transplantation and had stable (non-progressing) disease. The participants' assignments and responses to date were unblinded in December 2009 when the primary endpoint of the study (time to disease progression) showed a statistically significant difference between the two study groups. After January 2010, 86 of 128 eligible patients crossed over from the placebo arm to the active arm.

The researchers found that the therapy extended the time to disease progression by 19 months overall, even with the majority of placebo patients without progression crossing over to lenalidomide. The treatment was fairly well-tolerated particularly as compared to other treatments for multiple myeloma, such as thalidomide. There was more hematologic toxicity, particularly neutropenia, in the lenalidomide group. When the study data was analyzed again in October 2011, at a median follow-up of 34 months, 37% of participants receiving lenalidomide had disease progression or had died, compared to 58% of those in the placebo group.

"These findings fill a gap that existed previously in terms of data on whether maintenance therapy with lenalidomide prolongs the time to disease progression after initial therapy. We now have evidence that it does, in this and the two other lenalidomide studies that are presented in this issue of the Journal," said Dr. McCarthy. "This shows that patients with multiple myeloma now have options for prolonging the response to initial therapy. The next steps will be trying to improve on these responses by adding new agents that may prove even more effective in combination with lenalidomide following transplant."

Rexahn submits Phase II protocol for Archexin clinical study for ovarian cancer

In continuation of my update on Archexin (Archexin(R) was fromerly named as RX-0201, is  an oligonucleotide with 20 mers..c ompound that  inhibits the expression of human Akt-1.)...

Rexahn submits Phase II protocol for Archexin clinical study for ovarian cancer: Rexahn Pharmaceuticals, Inc., a clinical stage pharmaceutical company developing and commercializing potential best in class oncology and CNS therapeutics, today announced that it has submitted a Phase II protocol for the clinical study of Archexin as a treatment of ovarian cancer to the U.S. Food and Drug Administration (FDA).

Pfizer seeks FDA support for its new anti-rheumatoid arthritis pill

In continuation of my update on Tofacitinib

Pfizer seeks FDA support for its new anti-rheumatoid arthritis pill: Pfizer is waiting for the Food and Drug Administration to approve its new pill for rheumatoid arthritis (RA) - the first oral biologic for treating this ailment.

Botanical formula inhibits breast to lung cancer metastasis in mice

Botanical formula inhibits breast to lung cancer metastasis in mice: Scientists at Indiana University Health's Cancer Research Laboratory have found that a sophisticated botanical formula slows human breast cancer growth and inhibits breast to lung metastasis in mice. The formula contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum and Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus and Curcuma longa) and purified nutritional compounds, and showed no toxic side-effects.

Truvada deemed safe & effective in HIV infection risk reduction

Gilead Sciences Inc's Truvada pills are deemed  safe  and  effective  for  reducing the risk of HIV infection, U.S. regulators said on Tuesday. But they recommended a cautious approach for using the drug in efforts to prevent the virus that causes AIDS.

According to the Food and Drug Administration Truvada - a combination of Gilead's HIV drugs Emtriva (also known as emtricitabine see above structure), and Viread (or tenofovir see below left structure), which is already being used by patients with the human immunodeficiency virus, is well (left structure is that of  Tenofovir disoproxil fumarate)   tolerated overall by uninfected people and may prevent infection in high-risk individuals when used in combination with other strategies. The FDA acknowledged a strong correlation between the drug's efficacy at reducing HIV infection and the willingness of those taking it to adhere to the treatment.

Researchers speculated that women may require a higher dose of the drug to prevent infection. They also said the disappointing results may have resulted from women not taking the pills consistently. 

“We know that if the person doesn't take the medication every day they will not be protected,” said Dr. Rodney Wright, director of HIV programs at Montefiore Medical Center in New York and chairman of the AIDS Health Foundation. “So the concern is that there may not be adequate adherence to provide protection in the general population.” (right structure is Emtricitabine).

An outside panel of experts is scheduled to examine the FDA review documents on Thursday and make recommendations that U.S. health regulators will consider in deciding whether the drug should be used as a preventive treatment. Some experts have warned that the drug is only partly effective against HIV and that using it to prevent infection could cause protection from the virus to falter if patients fail to adhere to treatment.

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Black pepper compound fights fat

We know the that, black pepper has many medicinal benefits, like  curing illness such as constipation, diarrhea, earache, gangrene, heart disease, hernia, hoarseness, indigestion, insect bites, insomnia, joint pain, liver problems, lung disease, oral abscesses, sunburn, tooth decay, and toothaches. Now Korean researchers report that piperine (see structure below), a pungent compound found in black pepper (Piper nigrum), helps block the formation of new fat cells, a process known as adipogenesis.

"Adipogenesis is a well-organized process regulated by adipogenic transcription factors, such as peroxisome proliferator-activated receptor-gamma (PPAR-gamma), sterol regulatory element binding protein (SREBP) family, and CCAAT-enhancer binding protein (C/EBP) family," the authors write in their introduction. "Of these factors, PPAR-gamma has been focused on its role in adipocyte differentiation. In addition to being induced during adipogenesis, it is both necessary and sufficient for the process."

In addition to other benefits such as enhancing nutrient absorption in the digestive tract, black pepper has been found to reduce blood glucose and lipids. In the current study, Soo-Jong Um, Ji-Cheon Jeong and colleagues tested the effects of black pepper extract and piperine on cultured preadipocytes and found that both inhibited the cells differentiation into mature fat cells. Expression of the genes for PPAR-gamma, SREBP-1c and C/EBP-beta were all found to be decreased, as was the binding of PPAR-gamma to a coactivator known as CREB-binding protein following the administration of either treatment. Piperine was also shown to repress LXR-alpha, another transcriptional factor that is involved in the induction of adipogenesis as well as the synthesis of cholesterol and fatty acids.

"Taken together, our findings suggest that piperine, a major component of black pepper, inhibits fat cell differentiation by down-regulating the transcriptional activity of PPAR-gamma (and LXR-alpha) and suppressing the expression of PPAR-gamma (and LXR-alpha), thus leading to its potential use in the treatment of obesity-related diseases," the authors conclude.

Ref : http://pubs.acs.org/doi/abs/10.1021/jf204514a?prevSearch=%255BContrib%253A%2BSoo-Jong%2BUm%255D&searchHistoryKey=