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.

More...

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=

Grape compound may block the formation of fat cells

Purdue University researchers have come up with the ability of a compound known as piceatannol (see structure)  to help prevent the formation of mature fat cells by blocking the pathways needed for their growth. Piceatannol is an analog of resveratrol, found in grapes and other fruit, which is converted to piceatannol in humans following its consumption.

Purdue assistant professor of food science Kee-Hong Kim and his associates tested piceatannol in cultured preadipocytes, which are immature fat cells. These cells pass through several stages before reaching maturity over a ten day or longer period. "These precursor cells, even though they have not accumulated lipids, have the potential to become fat cells," Dr Kim explained. "We consider that adipogenesis is an important molecular target to delay or prevent fat cell accumulation and, hopefully, body fat mass gain."

Dr Kim's team found that piceatannol bound to the preadipocytes' insulin receptors during their initial stage of fat cell formation, which blocked insulin's ability to control cell cycles and activate genes necessary for the further stages of adipogenesis. "Piceatannol actually alters the timing of gene expressions, gene functions and insulin action during adipogenesis, the process in which early stage fat cells become mature fat cells," Dr Kim stated. "In the presence of piceatannol, you can see delay or complete inhibition of adipogenesis."

"Our study reveals an antiadipogenic function of piceatannol and highlights insulin receptor and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis," the authors conclude.

Dr Kim hopes to test piceatannol in an animal model as well as find a way to prevent the compound from degrading so that enough is available to the body to prevent fat gain. "We need to work on improving the stability and solubility of piceatannol to create a biological effect," he added.

Ref : http://www.jbc.org/content/287/14/11566.abstract?sid=48fa8a22-7a4d-4561-9585-80d643245a89

Isis Initiates Phase 1 Study in Patients With Cancer With the First Generation 2.5 Antisense Drug, ISIS-STAT3Rx

 In continuation of my update on antisense drugs...

Isis Pharmaceuticals, Inc.  announced the initiation of a Phase 1 study of ISIS-STAT3Rx, a Generation 2.5 antisense drug designed to treat cancer.  ISIS-STAT3Rx specifically reduces the production of signal transducer and activator of transcription 3 (STAT3). Because STAT3 is over expressed in numerous types of cancers, ISIS-STAT3Rx has the potential to be broadly useful for both solid and liquid tumors.  The ISIS-STAT3Rx development plan is initially focused on key cancers where there is a high unmet medical need and a strong link to STAT3, such as hepatocellular carcinoma (HCC) and ovarian cancer.  Advancements in Isis' technology platform have resulted in the improved potency of Generation 2.5 antisense drugs creating opportunities for drugs like ISIS-STAT3Rx to be effective in the more difficult to treat types of cancer. 

 

"The role of STAT3 as a key factor critical for tumor cell growth and survival of cancer cells has made STAT3 widely viewed as an important target of interest," said David S. Hong, M.D., Assistant Professor, Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center.  "STAT3 is a well understood transcription factor involved in multiple survival mechanisms that intersect with the growth, metastasis and invasiveness of cancer. The ability to selectively inhibit STAT3 could allow us to effectively treat some of the most difficult to treat cancers."

 
Isis Initiates Phase 1 Study in Patients With Cancer With the First Generation 2.5 Antisense Drug, ISIS-STAT3Rx

Ref : http://ir.isispharm.com/phoenix.zhtml?c=222170&p=irol-newsArticle&ID=1691711&highlight=

Two-Drug Therapy Helped Kids With Type 2 Diabetes

Two-Drug Therapy Helped Kids With Type 2 Diabetes:  Children with type 2 diabetes may achieve better blood sugar control with a combination of two drugs, metformin and Avandia, than with metformin alone, a new study suggests. However, Avandia (rosiglitazone) was recently linked...