Monday, March 29, 2010

Two-drug combination destroys precancerous colon polyps....

A team of scientists at The University of Texas M. D. Anderson Cancer Center lead by Dr. Xiangwei Wu have come up with interesting finding i.e.,  a two-drug combination destroys precancerous colon polyps with no effect on normal tissue, opening a new potential avenue for chemoprevention of colon cancer. 

The regimen, tested so far in mouse models and on human colon cancer tissue in the lab, appears to address a problem with chemopreventive drugs - they must be taken continuously long term to be effective, exposing patients to possible side effects. 

The team found that a combination of Vitamin A acetate (RAc see  structure; source: Wikipedia) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), kills precancerous polyps and inhibits tumor growth in mice that have deficiencies in a tumor-suppressor gene. That gene, adenomatous polyposis coli (APC) and its downstream signaling molecules, are mutated or deficient in 80 percent of all human colon cancer.  

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent endogenous activator of the cell death pathway and functions by activating the cell surface death receptors 4 and 5 (DR4 and DR5). TRAIL is nontoxic in vivo and preferentially kills neoplastically transformed cells over normal cells by an undefined mechanism.

Interestingly, early experiments with APC-deficient mice showed that the two drugs combined or separately did not harm normal colon epithelial cells. Separately, they showed no effect on premalignant polyps called adenomas.

RAc and TRAIL together killed adenoma cells, causing programmed cell suicide know as apoptosis. RAc, researchers found, sensitizes polyp cells to TRAIL.

The scientists painstakingly tracked the molecular cascade caused by APC deficiencies, and found that insufficient APC sensitizes cells to TRAIL and RAc by suppressing a protein that blocks TRAIL.

APC-deficient mice were treated with 15 cycles of the RAc/TRAIL combination over six weeks. Others received either RAc or TRAIL and a control group received nothing. One month later, control mice and those treated with one of the drugs averaged between 35 and 42 polyps, while those receiving the combination averaged 10.

To test the combination’s potential as short-term therapy, APC-deficient mice were treated with two cycles of the combination in one week, causing a 69 percent polyp reduction two weeks later. A 10-fold increase in dose left treated mice with only 10 percent of the polyps found in controls.

A longer term test of relative survival using five treatments over four months improved survival from 186 days for controls to beyond 213 days for treated mice, with five of seven treated mice living more than eight months. Next, the researchers treated biopsy samples of normal tissue and tumor regions from patients with familial adenomatous polyposis – an inherited condition that inevitably leads to colon cancer if the colon is not removed. Treatment of normal tissue caused little cell death, while 57 percent of polyp cells were killed via apoptosis.

Targeted therapies today aim at blocking some aspect of the tumor that drives its growth, Wu said, whereas RAc and TRAIL together kill precancerous polyps outright. Since APC is deficient or mutated in other types of cancer, the combination therapy could become a more general drug.

Before human clinical trials can be considered, the team will conduct additional research to understand potential side effects and also will try to develop an injectable version of the combination, which is administered intravenously now..

Ref :

Sunday, March 28, 2010

Self-Poisoning of Mycobacterium tuberculosis by targeting GlgE in an a-glucan pathway...

In the past few years, extremely drug resistant strains of TB have arisen that can’t be eliminated by any drugs, so new strategies for attacking TB are urgently needed.

Now, researchers at Albert Einstein College of Medicine of Yeshiva University have found two novel ways of killing the bacteria that cause tuberculosis.

In searching for a new Achilles’ heel for M. tuberculosis, Dr. Jacobs and colleagues focused on an enzyme called GlgE. Previous research had suggested  that GlgE might be essential for the growth of TB bacteria.        (building polysaccharides) GlgE would also be an excellent drug target because there are no enzymes similar to it in humans or in the bacteria of the human gut.

Using genetic and biochemical approaches, William Jacobs and colleagues identified four enzymes involved in a pathway that converts a naturally-occurring sugar compound into polysaccharides called alpha-glucans. The scientists found that inactivating one of these enzymes, TreS, was not lethal to the bacteria, indicating that this pathway is not required for growth. 

However, inactivating GlgE was lethal, causing the buildup of toxic levels of the enzyme's sugar substrate, maltose-1-phosphate. In addition, the scientists found that the combined inactivation of TreS and an enzyme for an alternate alpha-glucan biosynthetic pathway was lethal, highlighting the important roles of alpha-glucan's in M. tuberculosis growth.

Sure enough, when the researchers inhibited GlgE, the bacteria underwent "suicidal self-poisoning": a sugar called maltose 1-phosphate accumulated to toxic levels that damaged bacterial DNA, causing the death of TB bacteria grown in Petri dishes as well as in infected mice.

The researchers discovered a second way of killing TB after observing a crucial connection between their novel alpha glucan pathway and a second pathway that also synthesizes alpha glucans. 

When the researchers knocked out one of the other enzymes in their novel pathway, the pathway's shutdown didn't kill the bacteria; similarly, inactivating an enzyme called Rv3032 in the second alpha glucan pathway failed to kill the microbes. But inactivating both of those enzymes caused what the researchers term synthetic lethality: two inactivations that separately were nonlethal but together cause bacterial death. 

Though the biological role of the GlgE pathway remains to be elucidated, GlgE and the alpha-glucan pathways more generally, are possible drug targets that can now be tested in in vivo models of tuberculosis infection....

"The bacteria that cause TB need to synthesize alpha glucans," notes Dr. Jacobs. "And from the bacterial point of view, you can't knock out both of these alpha glucan pathways simultaneously or you're dead. So if we were to make drugs against GlgE and Rv3032, the combination would be extremely potent. And since TB bacteria need both of those alpha glucan pathways to live, it's very unlikely that this combination therapy would leave behind surviving bacteria that could develop into resistant strains."

Ref :

Saturday, March 27, 2010

FDA approves Graceway Pharmaceuticals' NDA for Zyclara

We know that Imiquimod (structure - source -Drug Bank) is an   immune response modifier that acts as a toll-like receptor 7 agonist. Imiquimod is commonly used topically to treat warts on the skin of the genital and anal areas. Imiquimod does not cure warts, and new warts may appear during treatment. Imiquimod does not fight the viruses that cause warts directly, however, it does help to relieve and control wart production.

Graceway® Pharmaceuticals announced recently  that, FDA has approved the New Drug Application (NDA) for Zyclara™, determining it to be safe and effective for the treatment of clinically typical, visible or palpable actinic keratoses (AK).   

The new treatment can be used on large areas of skin, including the full face or balding scalp on a convenient, 6-week dosing cycle.Zyclara shares the same active ingredient as Aldara® (imiquimod) Cream, 5% and while both topicals are FDA-approved for the treatment of AK, there are notable differences between the two.  

Zyclara is indicated for daily use on an accelerated 6-week dosing cycle comprised of two weeks of daily treatment with Zyclara, two weeks of non-treatment, followed by two weeks of daily treatment with Zyclara. Aldara is not approved for daily use and its approved dosing regimen is for a full 16 weeks.  Additionally, Zyclara is indicated for use on larger areas of skin, the full face or balding scalp, while Aldara is restricted to a 25 cm2 area of skin. 

"Because AKs are pre-cancerous and can develop on skin frequently exposed to the sun, such as the face or balding scalp, an effective treatment that can be used on large areas of skin is beneficial," said Darrell Rigel, M.D., clinical professor of dermatology, New York University Medical Center. ....
Ref :

Friday, March 26, 2010

Mecamylamine may help to treat diabetic macular edema ......

We know that mecamylamine (see structure) has been used as a  ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. It is also sometimes used as an anti-addictive drug to help people stop smoking tobacco, and is now more widely used for this application than it is for lowering blood pressure. This effect is thought to be due to it blocking α3β4 nicotinic receptors in the brain.

Now researchers from the Wilmer Eye Institute of Johns Hopkins University School of Medicine in Maryland have come up with an interesting finding from an early-stage human clinical trials. i.e.,  the drug  'mecamylamine'  was safe and had biological effects in a type of diabetic eye disease, and may offer researchers a new approach to prevent and treat diabetic macular edema

Diabetic macular edema is a complication of a specific region of the retina in the eye, called the macula, that develops when small blood vessels become leaky such that fluid accumulates. Without treatment, diabetic macular edema can cause vision impairment, blurriness, or blindness.

As per the claim by the researcers,  approximately 40% of the participants showed significant improvement in overall vision and/or the thickness of the retina. The treatment also showed biological effects in the retina indicating that the drug was able to gain access to the retinal vessels.
"The safety and early signals of treatment effect arising from this study may create a strong interest in the development of multiple treatment options that are affordable and can be self-administered, helping to ease the burden of healthcare delivery and compliance," said Barbara Araneo, Director of Complications Research for JDRF. ...
Ref : 

Thursday, March 25, 2010

Methionine Aminopeptidases from Mycobacterium tuberculosis as Novel Antimycobacterial Targets ..

Suspecting that a particular protein in tuberculosis was likely to be vital to the bacteria's survival, Johns Hopkins scientists screened 175,000 small chemical compounds and identified a potent class of compounds that selectively slows down this protein's activity and, in a test tube, blocks TB growth, demonstrating that the protein is indeed a vulnerable target.
This class of chemical compounds attacks TB by inhibiting methionine aminopeptidase (MetAP), an essential enzyme found in organisms ranging from bacteria to humans, and that clearly has been conserved throughout evolution because of its important task of ensuring the proper manufacture of proteins.

Methionine aminopeptidase (MetAP) is a metalloprotease that removes the N-terminal methionine during protein synthesis. To assess the importance of the two MetAPs in Mycobacterium tuberculosis, researchers overexpressed and purified each of the MetAPs to near homogeneity and showed that both were active as MetAP enzymes in vitro. 
Researchers screened a library of 175,000 compounds against MtMetAP1c and identified 2,3-dichloro-1,4-naphthoquinone class of compounds as inhibitors of both MtMetAPs. It was found that the MtMetAP inhibitors were active against replicating and aged nongrowing M. tuberculosis. Overexpression of either MtMetAP1a or MtMetAP1c in M. tuberculosis conferred resistance of bacterial cells to the inhibitors. As per the claim by the researchers, knockdown of MtMetAP1a, but not MtMetAP1c, resulted in decreased viability of M. tuberculosis and they conclude  that MtMetAP1a is a promising target for developing antituberculosis agents.
The scientists cautioned that although the MetAP inhibitors prevent TB growth in test tubes, they have a long way to go before being declared safe and effective to treat TB patients...
"Judging from potency, a MetAP inhibibitor alone probably won't wipe out TB," Liu says. "TB is so hard to treat that the standard therapy involves a cocktail of multiple drugs; no single compound is powerful enough. Our hope is that someday an inhibitor of MetAP will become a new component to enhance the existing therapy."
Ref : Jun O. Liu, Chemistry & Biology, Volume 17, Issue 1, 29 January 2010, Pages 86-97

Tuesday, March 23, 2010

Clinical Data completes NDA submission for vilazodone.......

         Vilazodone (structure) is an antidepressant and anxiolytic of  the piperazine chemical class.

Clinical Data, Inc.   recently announced that the Company has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for vilazodone for the treatment of major depressive disorder (MDD). Vilazodone is a dual-acting potent and selective serotonin reuptake inhibitor and a 5-HT1A receptor partial agonist. The Company expects that the NDA submission, if accepted, will be subject to a standard review. 

This is a major milestone in the development of vilazodone and, if approved, its dual mechanism of action and safety profile will offer a new alternative for patients suffering from depression,” said Carol R. Reed, M.D..more...

Friday, March 19, 2010

Gemcitabine and cisplatin a promising combination for endometrial cancer...

In continuation of my update on cis-platin and its importance, I find this  info interesting to share with...

Gemcitabine (see structure) and cisplatin in combination have been investigated extensively in other disease sites, and synergism of the two agents has been confirmed in cell lines of human endometrial, ovarian, colon, lung and squamous cell head and neck carcinoma

Now researchers from The University of Texas M. D. Anderson Cancer Center , lead by Dr.Jubilee Brown, report from a small study of women with advanced or recurrent endometrial cancer, that gemcitabine and cisplatin, when used in combination, produced a response rate in fifty percent of patients.

The Phase II study of 20 patients found that the combination of gemcitabine and cisplatin, two drugs currently used to treat other types of cancer, limited the disease's progression, increasing progression-free survival while maintaining tolerable toxicity levels. It is believed that when administered together, gemcitabine helps overcome cell resistance to cisplatin, throwing tumor cells a potent one-two punch.

Findings demonstrated a 50 percent overall response rate, or improvement in disease. Additionally, the clinical benefit of the two-drug combination was 80 percent, as 16 of the 20 women experienced either an improvement or stabilization of disease. All side effects resulting from the therapy were manageable. Lead researcher, Dr. Brown concluded  that results from the study warrant investigation of the chemotherapy combination in a larger, definitive trial at multiple institutions.....

Ref :  Dr. Jubilee Brown,

Wednesday, March 17, 2010

Salsalate may be useful for the treatment of patients with type 2 diabetes .....

We know that Salsalate (see structure; source  is a  non-steroidal anti-inflammatory drug (NSAID) belonging to salicylates. It is used in the treatment of Osteo Arthritis and  Rheumatoid Arthritis. 

Now researchers from Harvard Medical School, lead by Dr. Allison Goldfine, have come up with interesting finding, i.e., Salsalate may be useful for the treatment of patients with type 2 diabetes as well. In a three-month trial of people with type 2 diabetes ,  those who took the drug showed significantly improved blood glucose levels. 

Starting off, the patients all had levels of hemoglobin A1C (a standard measurement that reflects blood sugar levels over several months) in the range of 7.0 to 9.5%. A significant number of those who took salsalate saw this number drop by 0.5%, a result that is in the range of several recently released diabetes therapeutics. Other tests related to glucose levels also showed substantial improvement.  

Overall the drug appeared to be safe and to be tolerated well by patients. The study included 108 individuals, aged from 18 to 75 years, at 17 clinical sites around the United States. Patients were randomly divided into four; three groups were each given differing amounts of salsalate in three daily doses, while the fourth received placebos. All patients continued with their current regimes for managing diabetes.

Though these preliminary findings  suggests  that,   salsalate may provide an effective, safe and inexpensive new avenue for diabetes treatment, however the researchers  want to complete the ongoing  additional studies so that they can further substantiate their claim........

Tuesday, March 16, 2010

Study provides better understanding of how mosquitoes find a host......

In continuation of my update on on developments in mosquito repellents ......

The potentially deadly yellow-fever-transmitting Aedes aegypti mosquito detects the specific chemical structure of a compound called octenol as one way to find a mammalian host for a blood meal, Agricultural Research Service (ARS) scientists report".......

Ref :

Monday, March 15, 2010

Eprotirome a promising addition to statin therapy ?

People with bad cholesterol have  risk of  future heart disease,  despite  cholesterol-lowering statin therapy. Now researchers from  Johns Hopkins have come up with interesting finding i.e.,  a drug that mimics the action of thyroid hormone [Eprotirome (new generic name for KB2115) structure source : chemBlink)  lowered cholesterol up to 32 percent in those already on statins, an effect equal to that expected from doubling the statin drug doses, without harmful side effects. 

Interestingly, the researchers caution that the results don't suggest that eprotirome will or should replace statins, which are the current gold standard for treating high LDL cholesterol.

However, the results of their small trial on 168 patients do suggest that eprotirome may eventually be a promising addition to statin therapy, a substitute for statins in people who can't tolerate their side effects, or a novel treatment for mixed dyslipidemia, a condition in which people have high levels of lipids other than cholesterol such as triglycerides or apolipoprotein B (apo B).

The researchers found that among the patients taking the 25, 50 or 100 mg doses of eprotirome reduced their LDL cholesterol levels by 22 percent, 28 percent, and 32 percent respectively, compared to only 6.5 percent in those taking placebo. Remarkably, they also found similar dose-related reductions in triglycerides, apo B, and Lp(a). They also found modest reductions in HDL cholesterol of approximately 3 percent.

As per the claim by the lead researcher Dr. Paul W. Ladenson,   'this drug represents a new class of medications that might offer hope to those at risk of future cardiovascular disease whose lipid profiles are not effectively altered with statin therapy, and perhaps for about a quarter of those who have tried statins but cannot tolerate their side effects'. Dr. Ladenson is a consultant to Karo Bio, maker of eprotirome.......

Ref :

Thursday, March 11, 2010

Positive phase III efficacy clinical trial for Fentanyl sublingual spray .....

INSYS Therapeutics, Inc. announced positive results from the pivotal phase III efficacy  trial for patients utilizing the Fentanyl Sublingual Spray (SL Spray) technology to treat breakthrough cancer pain.  The company claims that all primary and secondary endpoints were achieved in the study, and the drug is the first product to ever show statistically significant pain relief when measuring the summary of pain intensity difference at five minutes (SPID(5)) in a phase III breakthrough cancer pain trial using Fentanyl.

Dr. Richard Rauck, a principal investigator in the Phase III study observed,  the sublingual spray demonstrated very rapid, effective pain relief. Patients began to experience meaningful pain relief within five minutes. This observation was supported by the clinical research findings.  As claimed by the researchers, to date, no other transmucosal Fentanyl  (see the general structure) product has produced pain relief this quickly. This  finding is supported with continued pain relief at all subsequent time intervals. 

Hope this easy-to-use oral spray that can produce effective, potent and very rapid pain relief will be a tremendous advantage for the  patients who experience moderate to severe cancer breakthrough pain.....

Ref :

Wednesday, March 10, 2010

Japanese patent for Archexin (a novel anti-cancer drug)....

Rexahn Pharmaceuticals, Inc., a clinical stage pharmaceutical company commercializing potential best in class oncology and CNS therapeutics, announced that the Japanese Patent Office has issued a patent for its novel anti-cancer compound, Archexin. As per the claim by the company,  Archexin is a first in class, potent inhibitor of Akt protein kinase in the treatment of cancer. 

The AKT pathway is an important therapeutic target for cancer drug discovery as it functions as a main point for transducing extracellular and intracellular oncogenic signals. Moreover, alternations of the AKT pathway have been found in a wide range of cancers. Akt regulates signal processes of cell proliferation and survival, angiogenesis, and drug resistance in cancer. Archexin is being developed to treat solid tumors and has FDA Orphan drug designation for RCC, pancreatic, stomach, glioblastoma, and ovarian cancers. Archexin is in Phase II clinical development for pancreatic cancer as lead indication.

Archexin(R) was fromerly named as RX-0201, is  an oligonucleotide compound that  inhibits the expression of human Akt-1. I am really happy for this approval because, in my opinion this will boost the new field of drugs (ologonucleotides/antisense). I have covered some developments in this field, those interested can read earlier articles...

Tuesday, March 9, 2010

Combination therapy (Dutasteride & Tamsulosin) more effective for enlarged prostate...

Researchers from UT Southwestern Medical Center, lead by  Dr. Claus Roehrborn have come out with something interesting finding, i.e., two drugs  (Dutasteride, see left structure)  and Tamsulosin (see below structure) commonly prescribed for enlarged prostate yielded better results than either of the medicines alone.
The study, which included more than 4,800 men, is one of the first to compare single and combo medication regimens in such a large group.
 The first group of study participants received the drug dutasteride; the  second group received tamsulosin; and the third received a combination of the two medicines. Researchers found that, the combination therapy to be superior at reducing risk of BPH   progression   (25 % reduction in prostate volume). Interestingly, patients who received the combination therapy also showed a 50 percent reduction of prostate-specific antigen (PSA), a protein produced by both cancerous and noncancerous prostate tissue. 

Compared with tamsulosin alone, the combination of drugs reduced the incidence of acute urinary retention by 67 percent and reduced the need for BPH-related surgery by 70 percent.  They also  found  a 65 percent decrease in the relative risk of acute urinary retention or BPH-related surgery compared with tamsulosin alone and just over a 19 percent reduction compared with dutasteride alone.
Researchers conclude that  this research should provide physicians better information when they decide on a course of treatment for patients with BPH.....

Ref :

Monday, March 8, 2010

Presentations on Geron's Telomerase Inhibitor at AACR Special Conference

In continuation of my update on Geron's Telomerase Inhibitor..... Geron Corporation, announced several presentations at the American Association for Cancer Research (AACR) Special Conference on The Role of Telomeres and Telomerase in Cancer Research held in Fort Worth, TX between February 27th and March 1st. The conference comprised ten scientific sessions with over fifty oral presentations.

Geron scientists and collaborators presented recent data on the company's telomerase inhibitor, imetelstat sodium (GRN163L), And highlighted the drug's activity against cancer stem cells. As per the claim by the CMO & EVP, Stephen M. Kelsey,   the telomerase inhibitor is showing anti-cancer stem cell activity in a range of preclinical models. In Phase II trials of imetelstat starting this year Greron is targeting malignancies that are thought to be driven, at least in part, by cancer stem cells ....


Sunday, March 7, 2010

Maple Syrup and Maple water contain abscisic acid.....

It has recently been reported that maple syrup contains polyphenols  and shows ORAC (Oxygen Radical Absorbance Capacity, a unit of measurement for antioxidants developed by the NIH)  values which compare to commonly eaten fruits and vegetables such as broccoli. Now, further research on maple syrup and its original form, maple water, conducted by Dr Yves Desjardins and his colleagues (at  Institut des neutraceutiques et des aliments fonctionnels), has revealed that both products contain equally important quantities of terpenes, and in particular, abscisic acid (see structure), a phytohormone whose health benefits have only recently been discovered. 

Vegetable physiologists and botanical researchers have known about the physiological properties of abscisic acid in the vegetable kingdom for a long time, but its health benefits for humans has only recently come to light. Along with other effects, it is known to stimulate insulin release through pancreatic cells and to increase sensitivity of fat cells to insulin, which makes it a potent weapon against  metabolic syndrome and diabetes. So its good to see that maple products contain a whole host of complementary active elements. The sugar molecules which provide the energy and sweetness in maple products are inherently complemented by abscisic acid molecules because they encourage insulin homeostasis

The authors conclude that, further studies are obviously needed before one can more accurately understand how eating maple products affects insulin behavior......

Ref : Dr Yves Desjardins, (Emerging Topics in Health Effects of Fruits and Vegetables symposium which forms part of the 28th International Horticultural Congress in Portugal, August 22-27, 2010.)

Saturday, March 6, 2010

Oldest epilepsy drug (Ethosuximide) best for Children with "Petit Mal"....

Ethosuximide ( see structure)  is a succinimide anticonvulsant, used mainly in absence seizures. Ethosuximide is considered the first choice drug for treating absence seizures in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence drug Valproic acid. There is some controversy over the exact mechanism by which ethosuximide prevents absence seizures. While the view that ethosuximide is a T-type calcium channel blocker gained widespread support following its proposal, attempts to replicate the initial finding were inconsistent.

Now researchers, lead by Dr. Tracy A. Glauser, Director of Comprehensive Epilepsy Center at Cincinnati Children's Hospital Medical Center, have come up with an interesting finding, i.e., ethosuximide (Zarontin), one of the oldest anti-seizure medications  is most effective at controlling what is called absence or "petit mal" epilepsy, with the fewest side effects. Valproic acid (Valproate, Depakote) came second, and the newest drug, lamotrigine (Lamictal), was third.

The study included children aged 2.5 to 13 years, newly diagnosed with epilepsy and free of other problems, such as autism. They were randomly assigned to one of the three drugs. The study measured primarily whether they were free of seizures without intolerable side effects after 16 weeks, with a few children continuing for as long as 20 weeks. The study also measured how the drugs affected the children's ability to pay attention.

Ethosuximide prevented seizures in 53 percent of the children, slightly less than the 58 percent freedom-from-failure rate of valproic acid but significantly better than the 29 percent for lamotrigine. But only 33 percent of those taking the older drug had significant attention problems, compared to 49 percent of those taking valproic acid, the researchers found. 

Researchers conclude that, it was somewhat unexpected that the oldest of the drugs had as good an effect as the other and better side effects &  the study highlights the importance of looking not only at seizure control but also how the child does otherwise.......

Ref :

Friday, March 5, 2010

Cabazitaxel improves survival in patients with metastatic hormone-refractory prostate cancer....

Cabazitaxel (see structure), is an orally bioavailable semi-synthetic  derivative of the natural taxoid 10-deacetylbaccatin III with potential antineoplastic activity. Cabazitaxel binds to and stabilizes tubulin, resulting in the inhibition of microtubule depolymerization and cell division, cell cycle arrest in the G2/M phase, and the inhibition of tumor cell proliferation. Unlike other taxane compounds, this agent is a poor substrate for the membrane-associated, multidrug resistance (MDR), P-glycoprotein (P-gp) efflux pump and may be useful for treating multidrug-resistant tumors. In addition, cabazitaxel penetrates the blood-brain barrier (BBB).

Sanofi-aventis recently announced results from a Phase 3 trial which demonstrated cabazitaxel plus prednisone/prednisolone significantly improved overall survival and progression-free survival in patients with metastatic (advanced) hormone-refractory prostate cancer whose disease progressed following treatment with docetaxel-based chemotherapy. 

TROPIC (trial) was designed to assess patients with metastatic hormone-refractory prostate cancer whose disease had progressed following treatment with docetaxel-based chemotherapy. Results showed that the combination of cabazitaxel and prednisone/prednisolone significantly reduced the risk of death by 30%.

Researchers are  happy with these compelling results  and  hope that these results will provide new options and hope for patients with serious diseases, such as metastatic hormone-refractory prostate cancer.....

Ref :

Thursday, March 4, 2010

Pycnogenol counteracts kidney damage due to hyprtension...

Pycnogenol® is the patented trade name for a water extract of the bark of the French maritime pine (Pinus pinaster ssp. atlantica), which is grown in coastal southwest France.  Pycnogenol® contains oligomeric proanthocyanidins (OPCs) as well as several other bioflavonoids (catechin, epicatechin), phenolic fruit acids (such as ferulic acid and caffeic acid), and taxifolin. Procyanidins are oligometric catechins found at high concentrations in red wine, grapes, cocoa, cranberries, apples, and some supplements such as Pycnogenol.

Scientific evidence on its antioxidative capacity and protective action on the vascular system have been published in the most renowned scientific journals. Additional published findings have demonstrated Pycnogenol’s beneficial effects in cardiovascular health (reduces LDL), skincare (e.g., Melasma, erythema, Chronic venous insufficiency), cognitive function, diabetes health, inflammation, sports nutrition, asthma and allergy relief and menstrual disorders, among others.

Earlier research suggested that, supplementation of Pycnogenol® with  conventional diabetes treatment may lower glucose levels and improve endothelial function and may improve symptoms associated with diabetic microangiopathy.

Now researchers lead by Dr. Gianni Belcaro, have come up with an interesting finding.i.e.,  Pycnogenol®  counteracts kidney damage caused by hypertension, lowering urinary proteins and improving blood flow to the kidneys.

The randomized, controlled study conducted by the G D'Annunzio University in Italy investigated 55 hypertensive patients who showed early signs of impaired kidney function, as judged by elevated amounts of proteins found in their urine.  The patients were divided into two groups.  Both groups were treated with anti-hypertensive medication Ramipril and one group of 29 patients took Pycnogenol in addition to the Ramipril.

After six months of treatment with Ramipril, average protein levels decreased to 64 mg per 24-hour period, remaining well above an acceptable level.  Conversely, the group taking Pycnogenol® as an adjunct to Ramipril had an average of only 39 mg per 24-hour period, a decrease of nearly double compared with anti-hypertensive medication taken alone.

The study also found a statistically significant decrease in patients' blood pressure when taking Pycnogenol® in conjunction with Ramipril.  As per the clam by the researchers, the addition of Pycnogenol® decreased both systolic and diastolic pressures by an additional three to six percent.  Pycnogenol® was also found to lower the patients' elevated levels of inflammatory marker CRP, a blood protein associated with the risk for acute cardiovascular events such as heart attack, reducing values to a healthy level.

Researchers conclude that, Pycnogenol® as an adjunct to the medication produced significantly greater results, particularly for kidney function restoration  and Pycnogenol® continues to demonstrate its abilities as a natural solution for the complete cardiovascular system....

Ref :  Dr. Gianni Belcaro, March 2010, Journal of Cardiovascular Pharmacology...

Wednesday, March 3, 2010

Novel compound found effective against avian influenza virus (H5N1)....

Currently, two neuraminidase (NA) inhibitors, oseltamivir and zanamivir, which must be administrated twice daily for 5 days for maximum therapeutic effect, are licensed for the treatment of influenza. However, oseltamivir-resistant mutants of seasonal H1N1 and highly pathogenic H5N1 avian influenza A viruses have emerged. Therefore, alternative antiviral agents are needed.

Now  researchers from Japan,  lead by Yoshihiro Kawaoka,  have come up with a new neuraminidase inhibitor, R-125489, and its prodrug, CS-8958.  CS-8958 functions as a long-acting NA inhibitor in vivo (mice) and is efficacious against seasonal influenza strains following a single intranasal dose.

As per the claim by the researchers, R-125489 interferes with the NA activity of H5N1 viruses, including oseltamivir-resistant and different clade strains. A single dose of CS-8958 (1,500 µg/kg) given to mice 2 h post-infection with H5N1 influenza viruses produced a higher survival rate than did continuous five-day administration of oseltamivir (50 mg/kg twice daily).

Researchers conclude that, CS-8958 is a promising candidate for a new neuraminidase inhibitor to prevent and treat influenza patients infected with H5N1 and other subtype viruses... 

Ref : Yoshihiro Kawaoka et. al., PLoS Pathogens Feb., 2010

Tuesday, March 2, 2010

Baked rhubarb may help fight cancer....

Rhubarb (herbaceous perennial plants growing from short, thick rhizomes) is a  group of plants that belong to the genus Rheum in the family Polygonaceae.  They have large leaves that are somewhat triangular shaped with long fleshy petioles and small flowers. While the leaves are toxic, the plants have medicinal uses, but most commonly the plant's stalks (see picture, source : Wikipedia) are cooked and used in pies and other foods for their tart flavour.  A number of varieties have been domesticated for human consumption, most of which are recognised as Rheum x hybridum by the Royal Horticultural Society.

Rhubarb (stem & roots) has been used as a strong laxative (the two  - anthraquinones emodin and rhein are responsible). Rubarb has been used in traditional Chinese medicine & medieval Arabic and European prescriptions. The rhizomes ('roots') contain stilbene compounds (including rhaponticin) which seem to lower blood glucose levels in diabetic mice.

Now,  researchers from Biomedical Research Center at Sheffield Hallam University, lead by Dr. Nikki Jordan-Mahy, have come up with new findings. Researchers found that baking British garden rhubarb for 20 minutes dramatically boosted levels of anti-cancer chemicals called polyphenols. Previous research has shown that polyphenols selectively kill or prevent the growth of cancer cells.

This is the first study to examine the benefits of British rhubarb, specifically a variety grown in South Yorkshire. Earlier research has studied Oriental medicinal rhubarb, which has been used in traditional Chinese medicine for thousands of years. 

Baking and slow stewing offered the best maintenance of colour through preservation of anthocyanin and the highest antioxidant capacity. Baking for 20 min provided well-cooked rhubarb with the highest antioxidant capacity and the highest anthocyanin content, which is important for the aesthetic quality of the dish.  

As per the claim by the researchers, LC–MS analysis putatively identified over 40 polyphenol components in raw rhubarb (including anthraquinone, stilbene, anthocyanin and flavonol derivatives.) Baking caused selective effects on the stability of the different polyphenol components. Initially, the yield of all components increased but there was a drastic decline in the relative stability of anthraquinone aglycones with increasing cooking time and initial evidence for the turnover of other anthraquinone derivatives was obtained. Researchers now plan to study the effect of rhubarb's polyphenols on leukemia.....

Monday, March 1, 2010

Avosentan lower doses for Overt Diabetic Nephropathy ?

Avosentan (see structure) is a potent, selective endothelin A  receptor blocker and there is convincing evidence that the endothelin system contributes to diabetic nephropathy and cardiovascular disease. Many groups are working with this drug.  Now researchers from Schwabing General Hospital and KfH Kidney Centre, in Munchen, Germany have come out with interesting results, as per claim by the lead researcher, Dr.Johannes Mann, the drug avosentan substantially reduces urinary protein loss in people with type 2 diabetes and kidney disease, but the drug causes serious side effects.

Avosentan at either dose (25 & 50 mg) lowered patients' urinary protein excretion by 40%-50% (compared with less than 10% in patients taking placebo), individuals taking the drug experienced a high incidence of serious, sometimes life-threatening side effects. These included complications of fluid overload such as pulmonary edema, as well as congestive heart failure. In addition, there were more deaths in the groups taking avosentan (21 and 17) than in the group taking placebo

Dr. Mann noted that the findings from the ASCEND trial highlight the risks and potential benefits of endothelin antagonists in kidney disease patients with proteinuria and will help investigators design future studies to test the drugs' potential. Specifically, lower doses of avosentan may generate more positive results....

Ref : Mann J.F., et. al., J Am Soc Nephrol. 2010 Feb 18.