US Indian scientist ‘re-engineering’ tulsi "to control breast cancer"

US Indian scientist ‘re-engineering’ tulsi -  to  control breast cancer"

Led by an Indian-American, a team of scientists at a US university are genetically engineering tulsi or basil to enhance its pharmaceutical value, the institute said.

In his lab at the Owensboro facility, Chandrakanth Emani, Assistant Professor of Plant Molecular Biology at the Western Kentucky University and his students are genetically engineering the basil to produce more eugenol, a compound in basil that “has a very great pharmaceutical value because it's shown to  control breast cancer,” the University said in a statement.

“When you grind these basil leaves there is a compound called eugenol that comes out...Eugenol, when they put it on a plate where there are tumor cells, it stopped growth of the tumour cells. That was a proof of concept experiment which was done a long time back,” Prof Emani claimed.

“If I make it make higher and higher amounts of eugenol, that plant, basil plant, will be a storehouse of that anti-cancerous compound,” he said.

The next phase would be to test the compound as an effective cancer treatment. Prof Emani is also working to understand various basic cell functions.

Biology News

New Drug Combo Might Help Older, Sicker Patients With Leukemia

The research, led by German scientists, included nearly 800 older people (average age 73) who had been diagnosed with chronic lymphocytic leukemia. CLL is a cancer of the blood and bone marrow, the tissue inside bones in which blood cells are created.

The study was published online Jan. 8 in the New England Journal of Medicine. Study participants -- none of whom had received treatment for their illness before the start of the research -- were randomly assigned to one of three groups.

One group received an oral medication called chlorambucil (also known by the brand name Leukeran), the standard chemotherapy drug for older patients with CLL.

The second group received chlorambucil plus a drug called rituximab (Rituxan). This drug has been used effectively in combination with other forms of chemotherapy for more than a decade to treat younger, fitter patients with CLL, an expert said.

The third group received chlorambucil plus a new antibody drug called obinutuzumab. The rituximab and obinutuzumab were given intravenously.

The researchers, whose study was funded by the manufacturer of both obinutuzumab and rituximab, reported that the obinutuzumab-chlorambucil combination improved outcomes for the older CLL patients better than the other two treatment options.

The most common side effects for obinutuzumab are infusion reactions, low blood cell counts, fever, cough and musculoskeletal disorders, according to the manufacturer's website.

Dr. William Wierda, a professor in the department of leukemia at the University of Texas MD Anderson Cancer Center, said older patients don't tend to tolerate intensive chemotherapy with rituximab as well as younger patients. That has left older CLL patients with limited drug options, including chlorambucil, he said.

"We've been wanting to find a treatment that is effective and well tolerated in the elderly population," said Wierda, who was not involved with the new research. "A standard treatment for older patients with CLL has been chlorambucil, a type of chemotherapy that's been used for many years."

"The trial shows improvement in outcome remission rates and duration favoring patients who got chlorambucil and obinutuzumab," he said. "This was a head-to-head comparison of the two antibody arms of the study -- the rituximab and the obinutuzumab -- and obinutuzumab won out."

There also was an improvement in overall survival among the patients who received the obinutuzumab-chlorambucil combination treatment versus those who received chlorambucil alone, Wierda said.

New Drug Combo Might Help Older, Sicker Patients With Leukemia - Drugs.com MedNews

New Drug Combo Might Help Older, Sicker Patients With Leukemia - Drugs.com MedNews

Mekinist Plus Tafinlar Approved for Late-Stage Melanoma

The U.S. Food and Drug Administration on Friday approved Mekinist for use with another drug, Tafinlar, to treat advanced melanoma that is spreading or cannot be removed by surgery.

Melanoma is the most deadly form of skin cancer, accounting for an estimated 9,480 American deaths last year, the FDA said Friday in a news release. Mekinist (trametinib) is newly approved to be used in combination with Tafinlar (dabrafenib). Both drugs were first sanctioned in May 2013 to be used by themselves to battle advanced melanoma, the agency said.

The combination therapy is newly approved for people who have certain mutations in the BRAF V600E and V600K genes, the FDA said. About half of melanoma cases have the mutated genes.

The combination therapy was clinically evaluated in 162 people. Of those treated, 78 percent had their cancer shrink or disappear for an average of 10.5 months, the agency said.

Mekinist Plus Tafinlar Approved for Late-Stage Melanoma - Drugs.com MedNews

FDA Approves Anoro Ellipta to Treat COPD

A new inhaled drug to treat a serious lung condition called chronic obstructive pulmonary disease (COPD) has been approved by the U.S. Food and Drug Administration.

GlaxoSmithKline's Anoro Ellipta [Combination of umeclidinium bromide -(see structure-1 left) and vilanterol-structure-2 rightside below) is meant to be used once a day for long-term maintenance of airflow in patients with COPD. The lung disease makes breathing difficult and worsens over time.   

"Anoro Ellipta works by helping the muscles around the airways of the lungs stay relaxed to increase airflow in patients with COPD," Dr. Curtis Rosebraugh, director of the Office of Drug Evaluation II in the FDA's Center for Drug Evaluation and Research, said in an agency news release.

"The availability of new long-term maintenance medications provides additional treatment options for the millions of Americans who suffer with COPD," he added.

FDA Approves Anoro Ellipta to Treat COPD - Drugs.com MedNews

Farxiga Approved for Type 2 Diabetes - Drugs.com MedNews

In continuation of my update on Farxiga

Farxiga (dapagliflozin) has been approved by the U.S. Food and Drug Administration to treat adults with type 2 diabetes, the agency said Wednesday in a news release.

The drug, to be used for blood sugar control along with proper diet and exercise, is designed to prevent re-absorption of glucose by the kidneys. Type 2 diabetes affects some 24 million people, accounting for 90 percent of diabetes cases in the United States, the FDA said.

Farxiga Approved for Type 2 Diabetes - Drugs.com MedNews

Chinese herbal compound relieves inflammatory, neuropathic pain

Working with Chinese scientists, Olivier Civelli and his UC Irvine colleagues isolated a compound called dehydrocorybulbine (DHCB) from the roots of the Corydalis yanhusuo plant. In tests on rodents, DHCB proved to diminish both inflammatory pain, which is associated with tissue damage and the infiltration of immune cells, and injury-induced neuropathic pain, which is caused by damage to the nervous system. This is important because there are no current adequate treatments for neuropathic pain.

Moreover, the researchers found that DHCB did not generate the tolerance seen with continued use of most conventional pain relievers, such as morphine.

"Today the pharmaceutical industry struggles to find new drugs. Yet for centuries people have used herbal remedies to address myriad health conditions, including pain. Our objective was to identify compounds in these herbal remedies that may help us discover new ways to treat health problems," said Civelli, the Eric L. & Lila D. Nelson Chair in Neuropharmacology. "We're excited that this one shows promise as an effective pharmaceutical. It also shows a different way to understand the pain mechanism."

Study results appear in the Jan. 20 issue of Current Biology.

They are the product of a collaboration between two teams separated by the Pacific Ocean. As traditional Chinese medicine gains greater acceptance in Western medical practice, Xinmiao Liang at the Dalian Institute of Chemical Physics in China and his group have been working to create an "herbalome" of all the compounds in plant extracts that display pharmacological properties. The UC Irvine team suggested applying "reverse pharmacology"   a novel drug discovery approach that Civelli devised about 25 years ago   to the herbalome project.

Together they screened 10 traditional Chinese medicines known as analgesics, testing nearly 500 compounds for their pain-relief abilities. Only DHCB in corydalis induced a reproducible effect.

Corydalis is a flowering herbal plant that grows in Siberia, Northern China and Japan. People utilize its root extract to alleviate menstrual cramps, chest pain and abdominal pain. It's been previously studied for its analgesic properties, but this is the first time DHCB has been identified, extracted and tested.

Chronic neuropathic pain affects more than 50 million Americans, yet management of this pain remains a major clinical challenge due to the poor results and severe side effects of conventional analgesics. Civelli said that drawing upon traditional Chinese medical-herbal products could lead to a breakthrough treatment for these patients.

Chinese herbal compound relieves inflammatory, neuropathic pain

2 Pre-Surgery Drug Treatments Show Promise Against Aggressive Breast Cancer - Drugs.com MedNews

This pre-surgical drug therapy boosts the likelihood that no cancer cells will be found in breast tissue removed during either mastectomy or lumpectomy, according to two new studies.

The approach, called "neoadjuvant" chemotherapy, is being given to an increasing number of women with what's known as triple-negative breast cancer. Currently, the approach results in no identifiable cancer cells at mastectomy or lumpectomy in about-one third of patients, experts estimate. In such cases, the risk of a tumor recurrence becomes lower.

"Chemotherapy [before surgery] does work in triple-negative breast cancer. What we want to do is make it work better," said study researcher Dr. Hope Rugo.

Rugo is director of breast oncology and clinical trials education at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco.

Triple-negative cancers have cells that lack receptors for the hormones estrogen and progesterone. In addition, they don't have an excess of the protein known as HER2 on the cell surfaces. So, treatments that work on the receptors and drugs that target HER2 don't work in these cancers.

In two new studies, researchers got better results by adding drugs to the standard chemo regimen prior to surgery. However, both studies are phase 2 trials, so more research is needed.

Both studies are due to be presented Friday at the annual San Antonio Breast Cancer Symposium.

Rugo compared standard neoadjuvant therapy -- paclitaxel (Taxol, others), doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan, others) -- to standard therapy plus the drugs veliparib (investigational) and carboplatin (Paraplatin)....

2 Pre-Surgery Drug Treatments Show Promise Against Aggressive Breast Cancer - Drugs.com MedNews

Two-drug combo helps adolescents with ADHD, aggression

Prescribing both a stimulant and an antipsychotic drug to children with physical aggression and attention-deficit/hyperactivity disorder (ADHD), along with teaching parents to use behavior management techniques, reduces aggressive and serious behavioral problems in the children, according to a study conducted by researchers at The Ohio State University Wexner Medical Center….

For the "Treatment of Severe Childhood Aggression (TOSCA) Study," 168 children ages 6 to 12 who had been diagnosed with ADHD and displayed significant physical aggression were divided into two groups. All study participants received a psychostimulant drug called OROS methylphenidate (left structure) and their parents received behavioral parent training for nine weeks. The researchers called this treatment combination "basic" because both are evidence-based and have been shown to be helpful for improving both ADHD and aggression.

Researchers wanted to see if they could expand or augment this treatment by adding a second medication. If there was room for improvement at the end of the third week, a placebo was added for the "basic group," while the antipsychotic drug risperidone (right above structure)  was added for participants in the "augmented group."

Compared to the "basic group," the "augmented group" who received the stimulant drug and parent training plus risperidone showed significant improvement (on average with moderately better behavior) on the Nisonger Child Behavior Rating Form (NCBRF) Disruptive-Total Scale, the NCBRF Social Competence subscale and the Reactive Aggression part of the Antisocial Behavior Scale.

While there is always some risk with the addition of a second drug to the treatment package, the two drugs seemed to neutralize some of each other's potential side effects. For instance, children in the augmented group did not seem to have as much trouble falling asleep, once the risperidone was added, Aman said.

"We conducted this study because we viewed the combination of ADHD and significant physical aggression -- especially the aggression -- as a serious situation," Aman said. "It is not uncommon to use more than one medicine for other serious situations, such as when treating cancer or epilepsy for instance. Although doctors have often used stimulants and antipsychotics together in recent years, we did not have good evidence until now that they would work more effectively when carefully staged and given together."

Ref : http://dx.doi.org/10.1016/j.jaac.2013.09.022

Two-drug combo helps adolescents with ADHD, aggression

Malaria drug target raises hopes for new treatments

In a study published in Nature Chemistry, they show that blocking the activity of an enzyme called NMT in the most common malaria parasite prevents mice from showing symptoms and extends their lifespan. The team are working to design molecules that target NMT more potently, and hope to start clinical trials of potential treatments within four years.

A recent study estimated that 1.2 million people died from malaria in 2010. Although a variety of antimalarial drugs are available, some strains of the parasite are resistant to treatment. These strains are becoming more common, with treatment failures reported across multiple frontline drugs. If acute illness is cured, the parasite can remain dormant in the blood and return to cause illness later. Malaria vaccines have been researched intensively, but none have been introduced into clinical practice.

The new study shows that NMT is involved in a wide range of essential processes in the parasite cell, including the production of proteins that enable malaria to be transmitted between humans and mosquitoes, and proteins that enable malaria to cause long-term infection.

The researchers have tested a handful of molecules that block the activity of NMT in the parasite living inside human red blood cells, and in mice, but further refinement will be needed before a treatment is ready to be tested in humans.

Dr Ed Tate, from the Department of Chemistry at Imperial College London, who led the project, said: "The drug situation for malaria is becoming very serious. Resistance is emerging fast and it's going to be a huge problem in the future.

"Finding an enzyme that can be targeted effectively in malaria can be a big challenge. Here, we've shown not only why NMT is essential for a wide range of important processes in the parasite, but also that we can design molecules that stop it from working during infection. It has so many functions that we think blocking it could be effective at preventing long-term disease and transmission, in addition to treating acute malaria. We expect it to work not just on Plasmodium falciparum, the most common malaria parasite, but the other species as well.

Ref : http://www.nature.com/nchem/journal/vaop/ncurrent/full/nchem.1830.html

Malaria drug target raises hopes for new treatments

New role for milk: Delivering polyphenols with anti-cancer activity

Polyphenols found in tea manifest anti-cancer effects but their use is limited by poor bioavailability and disagreeable taste. A new study in the Journal of Dairy Science^® finds that when epigallocatechin gallate (EGCG), the major extractable polyphenol in green tea and the most biologically active, when diluted in skim milk or other milk complexes remains bioactive and continues to reduce colon cancer cell proliferation in culture at concentrations higher than 0.03 mg of EGCG/mL.

Ref : http://www.sciencedirect.com/science/article/pii/S002203021300859X

New role for milk: Delivering polyphenols with anti-cancer activity

Vemurafenib: Result unchanged despite new data

In continuation of my update on Vemurafenib

Longer survival, but also major side effects

The drug approved since February 2012 can be an option for adults whose melanoma cannot be removed by surgery or has formed secondaries (metastases) and in whose cancer a change (mutation) has occurred in a certain gene (BRAF-V600). G-BA had specified the drug dacarbazine as the appropriate comparator therapy.

In its first AMNOG assessment in June 2012, the Institute concluded that vemurafenib had major advantages in overall survival, but also major disadvantages in the form of side effects. Overall, this resulted in an indication of a considerable added benefit.

Vemurafenib: Result unchanged despite new data

Supramolecular high-aspect ratio assemblies with strong antifungal activity : Nature Communications : Nature Publishing Group

Efficient and pathogen-specific antifungal agents are required to mitigate drug resistance problems. Here we present cationic small molecules that exhibit excellent microbial selectivity with minimal host toxicity. Unlike typical cationic polymers possessing molecular weight distributions, these compounds have an absolute molecular weight aiding in isolation and characterization. However, their specific molecular recognition motif (terephthalamide-bisurea) facilitates spontaneous supramolecular self-assembly manifesting in several polymer-like properties. Computational modelling of the terephthalamide-bisurea structures predicts zig-zag or bent arrangements where distal benzyl urea groups stabilize the high-aspect ratio aqueous supramolecular assemblies. These nanostructures are confirmed by transmission electron microscopy and atomic force microscopy. Antifungal activity against drug-sensitive and drug-resistant strains with in vitro and in vivo biocompatibility is observed. Additionally, despite repeated sub-lethal exposures, drug resistance is not induced. Comparison with clinically used amphotericin B shows similar antifungal behaviour without any significant toxicity in a C. albicansbiofilm-induced mouse keratitis model.

Supramolecular high-aspect ratio assemblies with strong antifungal activity : Nature Communications : Nature Publishing Group

Low-fat fish oil changes cancer tissue in prostate cancer, study shows

Men with prostate cancer who ate a low-fat diet and took fish oil supplements had lower levels of pro-inflammatory substances in their blood and a lower cell cycle progression score, a measure used to predict cancer recurrence, than men who ate a typical Western diet, UCLA researchers found.

"We found that CCP scores were significantly lower in the prostate cancer in men who consumed the low-fat fish oil diet as compare to men who followed a higher fat Western diet," Aronson said. "We also found that men on the low-fat fish oil diet had reduced blood levels of pro-inflammatory substances that have been associated with cancer."

This study appears in the early online edition of Cancer Prevention Research, a peer-reviewed journal of the American Association for Cancer Research.

This study is a follow-up to a 2011 study by Aronson and his team that found a low-fat diet with fish oil supplements eaten for four to six weeks prior to prostate removal slowed the growth of cancer cells in human prostate cancer tissue compared to a traditional, high-fat Western diet.

That short-term study also found that the men on the low-fat fish oil diet were able to change the composition of their cell membranes in both the healthy cells and the cancer cells in the prostate. They had increased levels of omega-3 fatty acids from fish oil and decreased levels of the more pro-inflammatory omega-6 fatty acids from corn oil in the cell membranes, which may directly affect the biology of the cells, Aronson said.

"These studies are showing that, in men with prostate cancer, you really are what you eat," Aronson said. "The studies suggest that by altering the diet, we may favorably affect the biology of prostate cancer."

Ref : http://cancerpreventionresearch.aacrjournals.org/content/early/2013/10/29/1940-6207.CAPR-13-0261

Low-fat fish oil changes cancer tissue in prostate cancer, study shows

Molecule critical to healing wounds identified

Skin provides a first line of defense against viruses, bacteria and parasites that might otherwise make people ill. When an injury breaks that barrier, a systematic chain of molecular signaling launches to close the wound and re-establish the skin's layer of protection. 

A study led by researchers from the University of Pennsylvania's School of Dental Medicine and published in the Journal of Cell Biology now offers a clearer explanation of the role of one of the players in the wound-healing process, a molecule called FOX01. Contrary to what had been expected, FOX01 is critical to wound healing, providing researchers with a possible new target for drugs that could help speed that process for people with impaired wound healing.

Senior author Dana Graves is a professor in Penn Dental Medicine's Department of Periodontics and is vice dean for scholarship and research. He collaborated on the study with Penn's Bhaskar Ponugoti, Fanxing Xu, Chenying Zhang, Chen Tian and Sandra Pacio.

A critical element of wound healing involves the movement of keratinocytes, the primary cells comprising the epidermis, or the outer layer of skin. Previous research had found that FOX01 was expressed at higher levels in wounds, but scientists did not understand what role the molecule was playing. In other scenarios, such as in cancer cells, FOX01 promotes cell death and interferes with the cell reproduction, two actions that would seem to be detrimental to healing.

To investigate the role of FOX01 in wound healing, Graves and colleagues bred mice that lacked the protein in their keratinocytes and then observed the wound healing process in these mice compared to mice with normal FOX01.

"We thought that deleting FOX01 would speed up the wound-healing process," Graves said, "but in fact it had the opposite effect."

The mice that lacked FOX01 showed significant delays in healing. Whereas all wounds on control mice were healed after one week, all of the experimental mice still had open wounds.

Digging deeper into this counterintuitive finding, the researchers examined the effect of reducing FOX01 levels on other genes known to play a role in cell migration. They found that many of these genes were significantly reduced, notably TGF-β1, a critical growth factor in wound repair. When the team added TGF-β1 to cells lacking FOX01, the cells behaved normally and produced the proper suite of molecules needed for healing, indicating that FOX01 acts upstream of TGF-β1 in the signaling pathway triggered during the healing process.

Further experimenting revealed that mice lacking FOX01 had evidence of increased oxidative stress, which is detrimental to wound healing.

"The wound healing environment is a stressful environment for the cell," Graves said. "It appears that upregulation of FOX01 helps protect the cell against oxidative stress."

Molecule critical to healing wounds identified

Combinatory therapy may be effective in suppressing drug resistance in treatment of melanoma

"About 50 percent of melanomas are driven by mutations in the BRAF gene, and about 60-80 percent of these melanomas initially respond to BRAF inhibitors such as vemurafenib and dabrafenib, but most develop resistance within seven to eight months," said Dr. Lo. "Our goal is to study comprehensively how this cancer escapes from BRAF inhibitors, so we can design new treatment approaches to overcome this resistance.

"It is very exciting to see work funded under a Stand Up To Cancer Innovative Research Grant (IRG) yield these important results," stated Sherry Lansing, co-founder & member of the SU2C Council of Founders and Advisors. "We created the IRG program to enable some of the best and brightest young researchers across disciplines to think out of the box and attempt to make major breakthroughs in their field with bold research projects." The SU2C IRG program is one of two initial funding models created by SU2C to focus on groundbreaking translational research aimed at getting new therapies to patients quickly. IRG grants support work that incorporates new ideas and new approaches to solve critical problems in cancer research. Dr. Lo's grant was one of the initial 13 IRG grants awarded in December 2009. Thirteen additional IRG grants were awarded in April 2011. To date, SU2C has funded $19.42 million for IRG research.

"There are several types of resistance, and one of these studies focused on early resistance, because most melanomas respond to BRAF inhibitors partially, leaving behind tumors subject to further evolutionary selection and development of late resistance," said Lo. "We found that suppressing the BRAF-regulated MAPK signaling quickly led to an increase in PI3K-AKT pathway signaling [causing early resistance] in many but not all melanomas. In those that do not display this early adaptive response, certain tumor subclones with the 'right' genetic variants in the PI3K-PTEN-AKT pathway would then have selective growth advantage during BRAF inhibitor therapy and eventually contribute to acquired [late] resistance," he explained.

Lo and colleagues studied melanoma tumors from patients collected before and early during treatment with BRAF inhibitors, and found that there was an increase in the amount of the activated form of a protein called AKT, early on after the start of treatment. They further confirmed these findings using melanoma cells cultured in the laboratory. This increase in activated AKT was associated with various inhibitors that block MAPK signaling at different points along the pathway, such as BRAF and MEK inhibitors.

Combinatory therapy may be effective in suppressing drug resistance in treatment of melanoma