Monday, August 30, 2010
This PLX4032 trial represents the first evidence that a treatment that targets activating BRAF mutations can induce significant tumor regressions in patients," said Dr. K. Peter Hirth, CEO of Plexxikon. He adds that "these data are particularly encouraging, with responses observed at all sites of disease, including challenging visceral lesions in the bone, liver and small bowel and they are hopeful that PLX4032 will provide similar benefit to these patients so urgently in need of effective therapies."..
Ref : http://www.nejm.org/doi/full/10.1056/NEJMoa1002011
Saturday, August 28, 2010
Thursday, August 26, 2010
"Although MTX is considered the standard of care in RA, both as a monotherapy and in combination with other RA treatments, the dosing and maximal therapeutic benefit of MTX is limited by well-documented tolerability issues, long-term safety concerns and variable bioavailability," commented Dr. Simon Pedder, president and CEO of Chelsea Therapeutics. "Given that CH-4051 is metabolically stable and that all of our preclinical and clinical work suggests enhanced absorption, dramatically increased potency and improved tolerability over MTX, we believe CH-4051 will be safe and highly efficacious in a historically treatment-resistant patient population."
Wednesday, August 25, 2010
Ref : http://www.asm.org/images/Communications/chagas%20-%20aac.pdf
Sunday, August 22, 2010
"The findings provide hope that such an approach will someday help the 33 million people worldwide who currently live with HIV," Mansky said.
Saturday, August 21, 2010
Endothelial Function Improvement With Dietary (Cocoa) Flavanols in Patients With Coronary Artery Disease....
A new study by UCSF cardiologists and researchers lead by Dr. Yerem Yeghiazarians found that high concentrations of cocoa flavanols decrease blood pressure, improve the health of blood vessels and increase the number of circulating blood-vessel-forming cells in patients with heart disease. The findings indicate that foods rich in flavanols such as cocoa products, tea, wine, and various fruits and vegetables have a cardio-protective benefit for heart disease patients.
Flavanols are phytonutrient compounds that are found naturally in apples, grapes, tea, cocoa and cherries, which account for the antioxidant effect provided by red wine and green tea. The study found a protective effect from a cocoa drink with 375 mg of flavanols, but according to researchers, a standard or recommended dosage has not yet been defined to achieve optimal health benefit.
The UCSF team has shown for the first time that one of the possible mechanisms of flavanol's benefit is an increase in the circulation of so-called angiogenic cells in the blood. These cells, also known as early endothelial progenitor cells, are critical for the repair process after vascular injury, and perform function and maintenance roles in the endothelium. Endothelium is the thin layer of cells that line the interior wall of blood vessels.
In the current study, the benefit seen from the two-fold increase in circulating angiogenic cells was similar to that achieved by therapy with statins and with lifestyle changes such as exercise and smoking cessation. The benefit demonstrated with cocoa flavanol therapy occurred in addition to the medical regimen already being taken by study participants.
"Our data support the concept that dietary flavanols at the levels provided -- in tandem with current medical therapy -- are safe, improve cardiovascular function, and increase circulating angiogenic cells, which have previously been shown to correlate positively with long-term cardiovascular outcomes" said Yeghiazarians.
Though long-term trials examining the effects of high-flavanol diets on cardiovascular health and function are warranted, but these early findings help us understand how these compounds impact the function of damaged blood vessels...
Ref : Yerem Yeghiazarians et.al., J. Am. Coll. Cardiol., July 13, 2010; 56: A20.
Tuesday, August 17, 2010
"Both 28- and 48-week boceprevir regimens significantly increased sustained virologic response rates which is the best definition of a cure we have compared to the 48 week control," said Dr. Kwo. "The 48-week treatment arm with 4 weeks of peg interferon lead-in and 44 weeks of peg interferon, ribavirin, and boceprevir led to the largest improvement over the control group ever reported. That's very impressive."
Researchers conclude that, best results were reported for the 103 patients who were treated for four weeks with the standard two drug regiment, followed by 44 weeks of the three-drug regimen including boceprevir: 75 percent of these patients tested negative for evidence of the virus six months after the end of treatment.
As per the lead researcher, Dr. Kwo, based on this phase 2 study, it appears that if this drug receives final approval approximately two-thirds of patients will be able to be treated successfully with 28 weeks of treatment and one-third will need 48 weeks of treatment, though this will require confirmation from the phase 3 trials, from which preliminary results were recently released.
Friday, August 13, 2010
"Etoricoxib was also associated with fewer side effects and thus overall patient satisfaction with pain medication," the researchers write...
Thursday, August 12, 2010
Herbal extracts include the extracts from turmeric root, saw palmetto berry, grape skin, pomegranate, pumpkin seed, pygeum bark, sarsaparilla root, green tea, and Japanese knotweed. Hence, it is rich in natural polyphenols, including quercetin, resveratrol, epigallocatechin gallate (EGCG), and ellagic acid, which have previously demonstrated anticancer potential. The unique formula contains 3 medicinal mushrooms grown on an herbal-enhanced medium. The mushrooms included are Phellinus linteus, Ganoderma lucidum, and Coriolus versicolor, each with known anticancer properties.
Researchers claim that, ProstaCaid was designed based on constituents that exhibit antiprolifetaive, antioxidant, and apoptotic activities; however, its efficacy and the mechanisms of action are yet to be examined. Researchers looked at the effectiveness of the preparation in suppressing several types of prostate cancer cell lines in culture and attempt to delineate the mechanism of action for justification in pursuing animal to determine efficicacy invivo.
Researchers conclude that, the anticancer activity of ProstaCaid may be ascribed to its polyphenolic flavonoids and curcuminoids derived from various herbs as well as other supplements, such as DIM. The preparation contains supplements such as quercetin (15%), Curcuma longa root extract complex with enhanced bioavailability (BCM-95; 20%), DIM (3%), and resveratrol (0.2%). Some of these components have shown a strong doseand time-dependent growth inhibition and apoptotic death in prostate cancer cells; 25 mM of quercetin inhibited about 50% PC3 cell growth for 72 hours. At 24 hours, 50 mM and 100 mM quercetin induced G2/M arrest and apoptosis, manifested by the decrease in G2/M-related protiens.
Researchers summarise that, ProstaCaid has anti-cancer activities in both AD and AI prostate cancer cells at very low concentrations (25 mg/mL). It also suggests that ProstaCaid inhibits cell growth and survival, at least through the inhibition of AKT and MAPK signaling. The effect on AI cell lines is especially of importance as there is presently no curative therapy for hormone refractory prostate cancer.
Researchers postulate that ProstaCaid may affect activity of Cdc2/cyclin B1 kinase by reducing this complex formation. Cdc2 could be dephosphorylated by Cdc25C and become inactive or be phosphorylated by protein kinase, such as Wee1, and then converted into an inactive form. They also suggest that more studies are needed in the future to test it and to define its upstream events in PC3 cells.
Ref : Jun Yan and Aaron E. Katz, Integr Cancer Ther 2010 9: 186
Tuesday, August 10, 2010
Monday, August 9, 2010
"This analysis of the PINNACLE study opens the door for additional research into targeted approaches to VELCADE treatment."..
The PINNACLE trial was a Phase II, open-label, single-arm, multicenter study of 155 patients with relapsed/refractory MCL and was the basis of the 2006 approval of VELCADE for the treatment of patients with relapsed/refractory MCL who had received one prior therapy. The overall response rate in the trial was 31 percent, with a median duration of response of 9.3 months; the CR rate was 8 percent, with a median duration of response of 15.4 months.
The Goy analysis used archived tumor samples from 73 patients who participated in the PINNACLE trial. The biopsies were examined for biomarkers associated with poor prognosis in MCL or those regulated by the proteasome. The biomarker levels were then compared to the effect of VELCADE on patients, according to response rates including overall survival and time to progression...
Ref : http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsArticle&ID=1434934&highlight=
Saturday, August 7, 2010
A chemical compound called Galanin, that boosts the action of a molecule normally produced in the brain may provide the starting point for a new line of therapies for the treatment of epileptic seizures, according to a new study by scientists at "The Scripps Researcher Institute".
"This compound really provides a new angle for developing drugs to treat seizures," says Scripps Research Assistant Professor Xiaoying Lu..
Galanin is a peptide, a fragment of a protein, produced in the brain to regulate a variety of functions, such as pain, memory, addition, mood, and appetite. In the late 1990s, researchers discovered that galanin is also a potent anticonvulsant.
Recent research suggests that when seizures occur the brain steps up production of galanin, possibly as a way to protect itself against the seizures. As a result, mice engineered to lack galanin are more susceptible to developing seizures.
Because galanin seems to play a role in reducing seizures, several groups of researchers, including those at Scripps Research, have been working to develop drugs that target the galanin system. The first category of such compounds consists of synthetic molecules that mimic galanin's functions (called agonists) and include Galnon, developed by Bartfai's group. Galnon and other galanin agonists have been shown to act as anticonvulsants when given to animals that were rendered prone to developing seizures. But these agonists have several drawbacks as potential therapeutic agents. For one thing, because Galnon acts relativly broadly, it may have unwanted side effects.
Interestingly, now Lu, Roberts, Bartfai, and colleagues at Scripps Research have now designed a compound that targets the galanin system but, unlike the previous agonists, is more selective in its action. The compound, dubbed CYM2503, binds to one of the three receptors for galanin on nerve cells, the galanin receptor type 2 (GalR2). On its own, CYM2503 has no effect on GalR2, but when galanin also binds to the receptor, CYM2503 boosts galanin's function.
The researchers tested the effects of CYM2503 on mice and rats that had received a chemical causing them to have seizures. The animals that received CYM2503 took longer to get the seizures and, when they did, the seizures lasted for a shorter time. Most importantly, when the researchers looked at the animals after 24 hours, the rats that had been treated with CYM2503 had a dramatically higher survival rate than those that had not.
This mechanism of action, modifying a receptor's function, is common to many successful drugs that have been developed for the treatment of a number of conditions, including epilepsy, hyperparathyroidism, and AIDS, but not yet for drug candidates targeting galanin system.
Because CYM2503 only works when galanin, a natural molecule, is also present, the researchers predict it will have fewer side effects than drugs that work on their own. This study provides the first evidence that modulating the GalR2 receptor is an effective strategy for treating seizures, thus opening the door for the development of drugs that target this mechanism.
"It is a double breakthrough" . "The compound is a first new mode-of-action anticonvulsant and it represents a new mechanism of molecular action." Also based on the known functions of the GalR2 receptors, it may also work in treating depression and in protecting the brain from damage," says Lu...
Wednesday, August 4, 2010
As per the claim by the researchers, this drug did not cause weight loss or neurological side effects, which rimonabant does, but did have effects on levels of glucose and fats in the blood that should reduce the risk of the serious health consequences of obesity.
The authors therefore hope that this approach of targeting only peripheral CB1R can be translated into the clinic to reduce health risks in obese patients..
Tuesday, August 3, 2010
The mollusks use a deadly dose of conotoxins (peptide toxins, e.g., α/ω-conotoxin peptides) that disrupt myriad biological functions. The mollusks inject into passing prey with hypodermic-needle-like teeth that shoot from their mouths like harpoons.
Within the conotoxin brew are several peptides that relieve tough-to-treat neuropathic pain just as well as morphine does but without its addictive properties. Although scientists have tried to turn such compounds into pain relievers, they've been hamstrung with problems administering such drugs. The pain reliever Prialt (see structure, Ziconotide), a synthetic version of ω-conotoxin MVIIA, but it must be injected directly into the spinal cord with a surgically implanted pump.
Now interestingly, scientists in Australia lead by Prof. David Craik (Institute for Molecular Bioscience at the University of Queensland), have managed to engineer a conotoxin that can be taken orally. Researchers found that, by linking the N-terminus of α-conotoxin Vc1.1—a compound derived from Conus victoriae—to its C-terminus, they could make the 16-residue peptide orally active. In the cyclized peptide, which is known as α-conotoxin cVc1.1, the protein's head and tail are tethered by a string of six amino acids—two alanines flanked on each side by two glycines. Prof. Craik says he chose the linker because it was inexpensive, wouldn't add any functionality to the molecule, and would be easy to characterize with nuclear magnetic resonance. In tests with rats, the cyclized peptide proved to be as potent a painkiller as gabapentin, the most popular drug for neuropathic pain, even though the conotoxin-based peptide was administered at a dose that is less than 1% of the dose typically given for gabapentin (other orally prescribed peptide is Ciclosporin a immunosuppressant).
Craik's group has shown that cyclizing larger peptides can make them orally available. His team's analysis of the protein database shows that up to 25% of all proteins have their ends within 10 Å of one another a distance that could easily be spanned with linkers of six to 10 amino acids.
"All you need is for the ends to be roughly close to one another," Prof. Clark says.
Craik says the cyclization also enhances hydrogen bonding across the entire molecule, making it resistant to the endopeptidases that attack a protein's interior amino acids. He says it's sort of like a zipper: "A zipper can be regarded as a series of hydrogen bonds all interlocking together, and when you zip it all up, you've got a beautiful set of coordinated hydrogen bonds. But you've still got two ends, and when you pull apart those two ends of the zipper, then the first hydrogen bond goes, then the next, and then the next. Craik has discovered several other examples of cyclic peptides, which he calls cyclotides (C&EN, April 19, 2004, page 40). He's hoping to use their structural features to guide the engineering of other peptides, as he did with α-conotoxin cVc1.1 At the moment, Craik is trying to raise funds so enough preliminary experiments can be done to file an Investigational New Drug Application. "The most challenging aspect has been just raising the money to get it commercialized," he says. "Pharmaceutical companies are always a little nervous about peptides. We need more success stories so that they'll see peptides not only as fantastic leads but also as potential drugs."...
Ref : http://www3.interscience.wiley.com/journal/123500852/abstract
Monday, August 2, 2010
Phenolic compounds (chlorogenic & neo-chlorogenic acids) in peaches, plums kill breast cancer cells..
Byrne and Dr. Luis Cisneros-Zevallos originally studied the antioxidants and phytonutrients in plums and found them to match or exceed the blueberry which had been considered superior to other fruits in those categories.
"These extracts killed the cancer cells but not the normal cells," Cisneros-Zevallos said...
As per the claim by the researchers, two specific phenolic acid components - chlorogenic and neochlorogenic ( structures, source :ChemBlink) - were responsible for killing the cancer cells while not affecting the normal cells. Researchers add that the two compounds are very common in fruits, the researchers said, but the stone fruits such as plums and peaches have especially high levels. The team said laboratory tests also confirmed that the compounds prevented cancer from growing in animals given the compounds.
"So this is very, very attractive from the point of view of being an alternative to typical chemotherapy which kills normal cells along with cancerous ones," Byrne claims..
Researchers conclude that, phenolic acids present (chlorogenic- left above structure and neo-chlorogenic acids-right below structure) have potential as chemopreventive dietary compounds because of the relatively high growth inhibition exerted on the estrogen-independent MDA-MB-435 breast cancer cell line and low toxicity exerted in the normal MCF-10A cells.
Dr. Byrne plans to examine more fully the lines of the varieties that were tested to see how these compounds might be incorporated into his research of breeding plums and peaches. Dr. Cisneros-Zevallos will continue testing these extracts and compounds in different types of cancer and conduct further studies of the molecular mechanisms involved. Hope they come up with substantial results to support their claim....