Synthesis produces new fungus-derived antibiotic

A fortuitous collaboration has led to the total synthesis of a recently discovered natural antibiotic. The laboratory recreation of a fungus-derived antibiotic, viridicatumtoxin B, may someday help bolster the fight against bacteria that evolve resistance to treatments in hospitals and clinics around the world.

As part of the process, Rice organic chemist K.C. Nicolaou and structural biologist Yousif Shamoo and their colleagues created and tested a number of variants of viridicatumtoxin B that could lead to the simplified synthesis of a new generation of more effective antibiotics.

The work reported this month in the Journal of the American Chemical Society (JACS) focused on a tetracycline discovered in 2008 by scientists who isolated small amounts from penicillium fungi. The yield wasn't nearly enough for extensive testing, but it provided a basis for the discoverers to analyze its structure through magnetic resonance imaging, Nicolaou said.

"We're inspired by molecules that are biologically active and have the potential to become medicines one day," he said.

The new discovery belongs to a class of antibiotics known as tetracyclines for their distinctive molecular structure. They proved potent  in  initial tests on
Gram-positive bacteria, so named for a staining technique to mark bacteria that are more susceptible to antibiotics than their Gram-negative counterparts.

The first tetracyclines, discovered in the late 1940s, ushered in a new class of
powerful antibacterial agents to treat high-mortality diseases,    among  them
anthrax and plague as well as such bacterial infections as chlamydia, syphilis
and Lyme disease.

To find new weapons, especially  against  "superbugs" that resist nearly all antibiotics, synthetic chemists pursue the complex  process  of  mimicking the
structures of effective natural molecules as they build drug candidates atom by atom.

"Tetracyclines are widespread antibiotics today, but bacteria are building resistance to a lot of them," Nicolaou said. "This new tetracycline is not plentiful in nature, so the only way we can make it available to study by biologists for its potential in medicine is to synthesize it in the laboratory."

Ref : http://pubs.acs.org/doi/abs/10.1021/ja506472u

Synthesis produces new fungus-derived antibiotic 

Experimental Drug Would Help Fight Ebola if Supply Increases, Study Finds - NYTimes.com

A new study provides strong evidence that the experimental drug given to two American aid workers stricken with Ebola in Africa really works and could make a difference in the current outbreak — if more of it could be produced.

In the study, all 18 monkeys exposed to a lethal dose of Ebola virus survived when given the drug, known as ZMapp, even when the treatment was started five days after infection, when the animals were already sick.

Moreover, the monkeys’ symptoms, such as excessive bleeding, rashes and signs of liver toxicity, eventually disappeared. By contrast, all three monkeys in the control group died.

Experts said these were the best monkey results reported to date for any Ebola drug, raising hopes that the drug will work in people.

Experimental Drug Would Help Fight Ebola if Supply Increases, Study Finds - NYTimes.com

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors

In continuation of my update on capsaicin

Researchers report that dietary capsaicin – the active ingredient in chili peppers – produces chronic activation of a receptor on cells lining the intestines of mice, triggering a reaction that ultimately reduces the risk of colorectal tumors....

Chili peppers for a healthy gut: Spicy chemical may inhibit gut tumors  

Pesticide DDT linked to slow metabolism, obesity and diabetes, mouse study finds -- ScienceDaily

A new study in mice is the first to show that developmental exposure to DDT increases the risk of females later developing metabolic syndrome -- a cluster of conditions that include increased body fat, blood glucose, and cholesterol.

Pesticide DDT linked to slow metabolism, obesity and diabetes, mouse study finds  

Researchers uncover how malaria parasite becomes resistant to fosmidomycin drug

Researchers have uncovered a way the malaria parasite becomes resistant to an investigational drug. The discovery, at Washington University School of Medicine in St. Louis, also is relevant for other infectious diseases including bacterial infections and tuberculosis.

The study appears July 24 in Nature Communications.

Many organisms, including the parasite that causes malaria, make a class of molecules called isoprenoids, which play multiple roles in keeping organisms healthy, whether plants, animals or bacteria. In malaria, the investigational drug fosmidomycin blocks isoprenoid synthesis, killing the parasite. But over time the drug often becomes less effective.

"In trials testing fosmidomycin, the malaria parasite returned in more than half the children by the end of the study," said senior author Audrey R. Odom, MD, PhD, assistant professor of pediatrics. "We wanted to know how the parasite is getting around the drug. How can it manage to live even though the drug is suppressing these compounds that are necessary for life?"

Fosmidomycin, an antibiotic, is being evaluated against malaria in phase 3 clinical trials in combination with other antimalarial drugs.

Using next-generation sequencing technology, the research team compared the genetics of malaria parasites that responded to the drug to the genetics of malaria parasites that were resistant to it. With this approach, Odom and her colleagues found mutations in a gene called PfHAD1. With dysfunctional PfHAD1, malaria is resistant to fosmidomycin.

"The PfHAD1 protein is completely unstudied," Odom said. "It's a member of a larger family of proteins, and there are almost no biological functions assigned to them."

In malaria parasites, Odom's team showed that the PfHAD1 protein normally slows down the synthesis of isoprenoids. In other words, when present, PfHAD1 is doing the same job as the drug, slowing isoprenoid manufacturing. Since isoprenoids are necessary for life, it's not clear why the organism would purposefully slow down isoprenoid production.

Ref : http://www.nature.com/ncomms/2014/140724/ncomms5467/full/ncomms5467.html

Researchers uncover how malaria parasite becomes resistant to fosmidomycin drug

Antifungal drug resistance evoked through RNAi-dependent epimutations

Microorganisms like bacteria and fungi can evade treatment by acquiring mutations in the genes targeted by antibiotics or antifungal drugs. These permanent mutations were once thought to be the only way for drug-resistant strains to evolve. Now a new study has shown that microorganisms can use a temporary silencing of drug targets -- known as epimutations -- to gain the benefits of drug resistance without the commitment.

Though the new mechanism was discovered in a fungus called Mucor circinelloides, it is likely to be employed by other fungi as well as bacteria, viruses and other organisms to withstand treatment with various drugs. The finding appears July 27, 2014, in Nature.

"This mechanism gives the organism more flexibility," said Joseph Heitman, M.D., Ph.D., senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine. "A classic, Mendelian mutation is a more permanent binding decision, like a traditional marriage. These epimutations are reversible, more akin to moving in together. If conditions change, it is easier to revert to the way things were."

The epimutations are so transient, in fact, that the researchers almost disregarded them. Cecelia Wall, a graduate student in Drs. Heitman and Maria Cardenas' labs, had been looking for mutations that would make the human fungal pathogen M. circinelloides resistant to the antifungal drug FK506 (also known as tacrolimus). This pathogen causes the rare but lethal fungal infection mucormycosis, an emerging infectious disease that predominantly affects individuals with weakened immune systems.

Ref:http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13575.html

Antifungal drug resistance evoked through RNAi-dependent epimutations

Flamel Technologies Announces FDA Approval of Vazculep

 Flamel Technologies (NASDAQ: FLML) today announced that the U.S. Food and Drug Administration (FDA) has approved the company's New Drug Application (NDA) for Vazculep (phenylephrine hydrochloride). Vazculep Injection is an alpha-1 adrenergic receptor agonist indicated for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia. Flamel expects to launch Vazculep in the next few months in 1 mL single use vials, and 5 mL and 10 mL pharmacy bulk package vials. The drug strength is the same in all vials at 10 mg/mL. Phenylephrine hydrochloride is used in operating rooms and is injected intravenously either as a bolus or in a dilute solution as a continuous infusion.

Flamel Technologies Announces FDA Approval of Vazculep

FDA Approves Beleodaq (belinostat) for Peripheral T-Cell Lymphoma

The U.S. Food and Drug Administration today approved Beleodaq (belinostat) for the treatment of patients with peripheral T-cell lymphoma (PTCL), a rare and fast-growing type of non-Hodgkin lymphoma (NHL). The action was taken under the agency’s accelerated approval program...

FDA Approves Beleodaq (belinostat) for Peripheral T-Cell Lymphoma

Protein once seen as promising anti-cancer compound helps to stabilize neural circuits

Researchers at UC San Francisco (UCSF) have discovered that endostatin, a protein that once aroused intense interest as a possible cancer treatment, plays a key role in the stable functioning of the nervous system.

A substance that occurs naturally in the body, endostatin potently blocks the formation of new blood vessels. In studies in mice in the late 1990s, endostatin treatment virtually eliminated cancer by shutting down the blood supply to tumors, but subsequent human clinical trials proved disappointing.

"It was a very big surprise" to find that endostatin, through some other mechanism, helps to maintain the proper workings of synapses, the sites where communication between nerve cells takes place, said Graeme W. Davis, PhD, Hertzstein Distinguished Professor of Medicine in the Department of Biochemistry and Biophysics at UCSF and senior author of the new study. "Endostatin was not on our radar."

Protein once seen as promising anti-cancer compound helps to stabilize neural circuits

FDA Approves Ryanodex for the Treatment of Malignant Hyperthermia

Eagle Pharmaceuticals, Inc. (“Eagle” or “the Company”) (Nasdaq:EGRX) today announced that the U. S. Food and Drug Administration (FDA) has approved Ryanodex (dantrolene sodium) for injectable suspension indicated for the treatment of malignant hyperthermia (MH), along with the appropriate supportive measures. MH is an inherited and potentially fatal disorder triggered by certain anesthesia agents in genetically susceptible individuals. FDA had designated Ryanodex as an Orphan Drug in August 2013. Eagle has been informed by the FDA that it will learn over the next four to six weeks if it has been granted the seven year Orphan Drug market exclusivity.

FDA Approves Ryanodex for the Treatment of Malignant Hyperthermia

High-dose fluticasone effective against eosinophilic esophagitis, study shows...

I continuation of y update on Fluticasone..

Results from a clinical trial show that high doses of the corticosteroid fluticasone propionate safely and effectively induce remission in many people with eosinophilic esophagitis (EoE), a chronic inflammatory disease of the esophagus characterized by high levels of white blood cells called eosinophils. However, some trial participants did not respond to fluticasone even after six months of high-dose treatments, providing evidence that certain people with EoE are steroid-resistant. By analyzing gene expression -- the degree to which certain genes are turned on or off -- in esophageal tissues, the scientists identified a cluster of genes that may help predict steroid responsiveness.

Ref :Read more

High-dose fluticasone effective against eosinophilic esophagitis, study shows

Bowel cancer breakthrough may benefit thousands of patients

Researchers at Queen's University have made a significant breakthrough that may benefit
patients with bowel cancer. 

Dr Sandra van Schaeybroeck and her team have discovered how two genes cause bowel cancer cells to become resistant to treatments used against the disease. The research, which was funded by Cancer Research UK, was published this month in the international journal CellReports.

The activity of the two genes, called MEK and MET, was uncovered when the researchers looked at all the different pathways and interactions taking place in bowel cancer cells.

Dr van Schaeybroeck and her group found that these bowel cancers switch on a survival mechanism when they are treated with drugs that target faulty MEK genes. But when the researchers added drugs that also block the MET gene, the bowel cancer cells died.

The team are now testing a new approach to target these two genes in the most aggressive forms of bowel cancer in a European Commission funded clinical trial that is being led by Dr van Schaeybroeck.

Bowel cancer breakthrough may benefit thousands of patients

Zydelig Approved for Three Types of Blood Cancer

 Zydelig (idelalisib) has been approved by the U.S. Food and Drug Administration to treat relapsed forms of blood cancer, including chronic lymphocytic leukemia (CLL), follicular B-cell non-Hodgkin lymphoma (FL) and small lymphocytic lymphoma (SLL), the FDA said Wednesday in a news release.

The approval for the three forms of blood cancer covers instances when the cancer returns despite treatment with at least one other therapy, the agency said.

The drug's label will include a boxed warning that the medication could cause liver toxicity, diarrhea, high blood sugar, elevated liver enzymes, high blood triglycerides [a blood fat] and inflammation of the colon (colitis). Other side effects noted during clinical testing included fever, fatigue, nausea, cough, pneumonia, abdominal pain, chills and rash.

Zydelig is marketed by Gilead Sciences, based in Foster City, Calif.

Zydelig Approved for Three Types of Blood Cancer 

New combination drug controls tumor growth, metastasis in mice...

Researchers at UC Davis, University of      Massachusetts  and Harvard  Medical  School  have
created a combination drug that controls both tumor growth and metastasis. By combining a COX-2 inhibitor, similar to Celebrex, and an epoxide hydrolase (sEH) inhibitor, the drug controls angiogenesis (blood vessel formation), limiting a tumor's ability to grow and spread. The study appears today in the journal Proceedings of the National Academy of Sciences.

"We've   been   studying  the  effects of  COX  and  sEH  inhibitors, both    by themselves  and in combination, for several years," said senior author and UC Davis Distinguished Professor Bruce Hammock. "We were surprised to find that the dual inhibitor was more active than higher doses of each compound, either individually or together. By combining the two molecules into one we got much greater potency against several diseases and completely unique effects in terms of blocking tumor growth and metastasis."

Both COX and sEH enzymes control lipid signaling, which has long been associated with inflammation, cell migration, proliferation, hypertension and other processes. COX inhibitors block production of inflammatory and pain-inducing lipids, while sEH inhibitors preserve anti-hypertensive, anti-inflammatory and analgesic compounds. Separate COX and sEH inhibitors were previously found to work together in reducing inflammation and neuropathic pain.

After testing individual COX-2 and sEH inhibitors, the team synthesized the drug (PTUTB), the first combined COX-2/sEH inhibitor. They then tested the dual inhibitor against human lung and breast tumors, both in vitro and in mice. They found that PTUTB blocked angiogenesis, inhibiting the proliferation of endothelial cells, which are critical to blood vessel formation. This in turn limited tumor growth and metastasis, reducing lung and breast tumor growth by 70 to 83 percent. 

In breast and lung cancers, the dual inhibitor blocked angiogenesis, which blocked the growth of solid tumors," said Hammock. "This represents a new mechanism to control blood vessel and tumor growth."

Robert Weiss, a co-author and professor of nephrology at UC Davis, added that the combination drug achieved the results with minimal side effects and no cardiovascular or gastrointestinal effects.

"This is particularly important when administering COX-2 inhibitors, which have well-known cardiovascular risks," he said. "However, the added sEH  inhibitor appears to block COX-2's side effects."

The research was initiated by first author Guodong Zhang when he was a postdoctoral fellow in the Hammock laboratory. Zhang previously demonstrated that sEH inhibitors improve the power of omega-3 fatty acid (fish oil) diets to reduce tumor growth and metastasis, and implicated epoxides of the dietary supplement DHA as the causative agent.

New combination drug controls tumor growth, metastasis in mice  

Liver Cancer Drug Fails to Live Up to Early Promise...

In continuation of my update on everolimus

Although it looked promising in early studies, the drug everolimus didn't improve survival for people with advanced liver cancer in its latest trial, a new study found.

The findings from the phase 3 clinical trial are disappointing because earlier research suggested that everolimus (Afinitor) prevented tumor progression and improved survival for in advanced liver cancer. Normally, these patients can expect a median overall survival of less than one year.

The only drug currently shown to significantly improve survival of advanced liver cancer patients is sorafenib (Nexavar). But that drug's benefits are temporary and the cancer eventually progresses, according to background information in the new study.

The current study included 546 adults with advanced liver cancer whose disease progressed during or after treatment with sorafenib, or who could not take sorafenib. The patients were divided into two groups, with 362 given everolimus and 184 given a placebo.

Liver Cancer Drug Fails to Live Up to Early Promise 

New Inhaled Drug Shows Promise Against Asthma, Allergies...........

A new inhaled medication has the potential to treat mild asthma and allergies by interrupting the production of an immune system protein that triggers allergic reactions, a new study reports.

The drug, quilizumab, targets the blood cells that produce a protein called immunoglobulin type E (IgE), that serves a key role in allergies.

Quilizumab lowered total levels of IgE in the blood of people with allergies and mild asthma, and kept them low for a month, researchers report in the July 2 issue of the journal Science Translational Medicine.

"The subjects who received the drug not only had a reduction in their total IgE level, it also seemed to block production of new IgE in response to the allergen they inhaled," said study co-author Dr. Jeffrey Harris, principal medical director of immunology, tissue growth and repair for the drug manufacturer Genentech, which produces quilizumab and funded the study.

However, one expert noted that the drug has yet to prove itself against moderate to severe asthma.

New Inhaled Drug Shows Promise Against Asthma, Allergies  

New Inhaled Drug Shows Promise Against Asthma, Allergies - Drugs.com MedNews

A new inhaled medication has the potential to treat mild asthma and allergies by interrupting the production of an immune system protein that triggers allergic reactions, a new study reports.

The drug, quilizumab, targets the blood cells that produce a protein called immunoglobulin type E (IgE), that serves a key role in allergies.

Quilizumab lowered total levels of IgE in the blood of people with allergies and mild asthma, and kept them low for a month, researchers report in the July 2 issue of the journal Science Translational Medicine.

"The subjects who received the drug not only had a reduction in their total IgE level, it also seemed to block production of new IgE in response to the allergen they inhaled," said study co-author Dr. Jeffrey Harris, principal medical director of immunology, tissue growth and repair for the drug manufacturer Genentech, which produces quilizumab and funded the study.

However, one expert noted that the drug has yet to prove itself against moderate to severe asthma.

New Inhaled Drug Shows Promise Against Asthma, Allergies  

Breast Cancer Drug May Help Women Fight a Leading Cause of Infertility: Study

Women with polycystic ovary syndrome have a better chance of getting pregnant if they take a breast cancer drug instead of the currently preferred medication, a new study suggests.

Polycystic ovary syndrome -- the most common cause of female infertility in the United States -- causes higher than normal levels of the male hormone androgen, infrequent periods and small cysts on the ovaries. It affects 5 to 10 percent of reproductive-age women, according to background information in the study.

Currently, doctors typically prescribe clomiphine (Clomid) to boost fertility for women with polycystic ovary syndrome. However, this new study suggests the drug letrozole (Femara) results in better ovulation, conception and birth rates.

"We found a simple and comparatively safe and vastly more effective treatment for [polycystic ovary syndrome]," said lead researcher Dr. Richard Legro, a professor of obstetrics and gynecology at Penn State University's College of Medicine in Hershey, Penn.

Clomiphine, which works by stimulating ovulation, has been the standard treatment for years, but has a high rate of multiple births, Legro said.

Letrozole, a treatment for breast cancer in postmenopausal women, works by blocking estrogen production, tricking the ovaries into producing more of the hormone, he explained.

The new study, funded by the U.S. National Institutes of Health, was published July 10 in the New England Journal of Medicine.

Breast Cancer Drug May Help Women Fight a Leading Cause of Infertility: Study - Drugs.com MedNews

First drug candidate from NIH program acquired by biopharmaceutical company

A drug candidate developed by researchers at the NIH’s National Center for Advancing Translational Sciences (NCATS) and its collaborators to treat sickle cell disease has been acquired by Baxter International’s BioScience business. The drug candidate, Aes-103, is the first specifically developed to target the underlying molecular mechanism of sickle cell disease. Baxter now will advance the clinical development activities required for regulatory approval and commercialization.

Sickle cell disease is a genetic blood disorder that affects millions worldwide, including approximately 100,000 people in the United States — among them, 1 in 500 African-Americans.

This is the first time a company has acquired a drug candidate developed with NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program resources. Baxter International recently acquired AesRx, LLC, Newton, Massachusetts — the TRND program collaborator — including Aes-103. TRND and AesRx researchers worked together to develop Aes-103 through a Phase II clinical trial to evaluate safety and effectiveness. The trial data indicated that Aes-103 significantly reduced patients’ pain. 

“This is a wonderful example of why NCATS was created,” said NIH Director Francis S. Collins, M.D., Ph.D. “The progress made thus far in the development of Aes-103 demonstrates NCATS’ catalytic role in bringing together the necessary players, whether academic, nonprofit or industry, to overcome obstacles to translation and advance badly needed treatments to patients.”

First drug candidate from NIH program acquired by biopharmaceutical company

New Amyloid Reducing Compound Could Be a Preventive Measure Against Alzheimer’s | Neuroscience News Research Articles | Neuroscience Social Network

New Amyloid Reducing Compound Could Be a Preventive Measure Against Alzheimer’s | Neuroscience News Research Articles | Neuroscience Social Network



Ref : http://onlinelibrary.wiley.com/doi/10.1002/ana.24149/abstract;jsessionid=9F003DBC49DC78B99E15FC97CC073CFA.f01t03

New Drug May Boost Survival for Advanced Prostate Cancer Patients: Study - Drugs.com MedNews

A pill that blocks male hormone activity can improve survival and delay the need for chemotherapy in men with advanced prostate cancer, a new clinical trial has found.

Men who took a daily dose of the drug enzalutamide started chemotherapy nearly a year and a half later than men who received a placebo, even though their prostate cancer had spread to other parts of their bodies, said senior study author Dr. Tomasz Beer, deputy director of the Knight Cancer Center at Oregon Health and Science University.

New Drug May Boost Survival for Advanced Prostate Cancer Patients: Study

New Drug May Treat Constipation Caused by Strong Painkillers - Drugs.com MedNews

A new drug holds promise as a safe and effective treatment for constipation caused by prescription narcotic painkillers, new research states.

Constipation is a common side effect experienced by patients taking these powerful medications for chronic pain. When laxatives failed to provide relief, two phase 3 trials found the once-daily drug naloxegol could help.

"The studies showed rapid and sustained improvement for these patients, without compromising their pain management," study author Dr. William Chey, a gastroenterologist and professor of internal medicine at the University of Michigan Health System, said in a university news release.

The U.S. Food and Drug Administration, as well as health agencies in Canada and Europe, are reviewing the drug for possible approval.

Naloxegol (structure) was specifically designed to treat constipation caused by the narcotic painkillers that are often used to treat chronic health issues, such as osteoarthritis and back pain. These medications ease patients' pain by binding to certain receptors in the brain, but they also bind to receptors in the bowel, which raises the risk of constipation.

Naloxegol works by preventing the painkillers from binding to receptors in the bowel, but not the brain, according to the news release.

One of the new studies involved 652 people. The other study included 700 participants. The patients were randomly assigned to receive one 12.5 milligram (mg) or one 25 mg dose of naloxegol daily, or an inactive placebo.

New Drug May Treat Constipation Caused by Strong Painkillers 

Green tea could reduce pancreatic cancer risk: Study explains how

A study recently published online by the journal, Metabolomics, offers an explanation that researchers say could open a new area of cancer-fighting research. The study reports that EGCG, the active biologic constituent in green tea, changed the metabolism of pancreatic cancer cells by suppressing the expression of an enzyme associated with cancer, LDHA.

The researchers also found an enzyme inhibitor, oxamate, which is known to reduce LDHA activity, operated in the same manner: It also disrupted the pancreatic cancer cells metabolic system.

"Scientists had believed they needed a molecular mechanism to treat cancer, but this study shows that they can change the metabolic system and have an impact on cancer," said Wai-Nang Lee, MD, corresponding author of the study and a Los Angeles Biomedical Research Institute (LA BioMed) lead researcher. "By explaining how green tea's active component could prevent cancer, this study will open the door to a whole new area of cancer research and help us understand how other foods can prevent cancer or slow the growth of cancerous
cells."

Using sophisticated metabolic profiling methods, the researchers found EGCG disrupted the balance of "flux" throughout the cellular metabolic network. Flux is the rate of turnover of molecules through a metabolic pathway. The researchers found the EGCG disrupted this balance in the same manner that oxamate, a known LDHA inhibitor, did.

Based on this finding, they concluded that both EGCG and oxamate reduced the risk of cancer by suppressing the activity of LDHA, a critical enzyme in cancer metabolism, thereby disrupting the balance in the cancer cells metabolic functions.

Green teacould reduce pancreatic cancer risk: Study explains how  

New drug for non-Hodgkin lymphoma, chronic lymphocytic leukemia passes early test

The drug,
alisertib or MLN8237, inhibits the enzyme aurora A kinase, which is known to be
very active during cell division. The present study, published in the journalInvestigational
New Drugs, looks at the safety, tolerability, and preliminary success of
alisertib in treating non-Hodgkin lymphoma (NHL) and chronic lymphocytic
leukemia (CLL).

"An advantage with this drug is it is oral and very effective in a significant number of patients with aggressive lymphoma when used at that dose for 7  days out a 21 day cycle," said hematologist Swaminathan Iyer, M.D., who led the multi-site study. 

Drugs commonly used to treat NHL and CLL are chemotherapeutic drugs and some biological targeted agents such as the monoclonal antibodies rituximab, ofatumumab and obinutuzumab with varying degrees of success.

Although about 1/2 of patients participating in the phase I study experienced side effects most of which were manageable events, Iyer said that is not unusual for such
biologic (non chemotherapy) drugs.

"The side effects were fairly tolerable in this study," Iyer said. "We would like to see more information from a larger group of patients to fully understand the drug's safety and tolerability for those experiencing the middle-to-later stages of these diseases."

Iyer and his group recommend 50 mg, twice-daily doses of alisertib for the advanced phase trials of the drug, which Iyer says has begun enrollment. Alisertib is not yet approved for general medical use by the FDA. Its impact on T cell lymphoma is being investigated in a separate, phase III trial for a specific type of  lymphoma called the T cell lymphomas. Houston Methodist is a participating study site for that project. Initial phase II reports in these T cell lymphomas showed a 57% response, the highest ever noted for any single agent in this disease entity.

New drug
for non-Hodgkin lymphoma, chronic lymphocytic leukemia passes early test  

Leptin also influences brain cells that control appetite, researchers find -- ScienceDaily

Twenty years after the hormone leptin was found to regulate metabolism, appetite, and weight through brain cells called neurons, Yale School of Medicine researchers have found that the hormone also acts on other types of cells to control appetite...

Published in the June 1 issue of Nature Neuroscience, the findings could lead to development of treatments for metabolic disorders such as obesity and diabetes. "Up until now, the scientific community thought that leptin acts exclusively in neurons to modulate behavior and body weight," said senior author Tamas Horvath, the Jean and David W. Wallace Professor of Biomedical Research and chair of comparative medicine at Yale School of Medicine. "This work is now changing that paradigm."

Leptin, a naturally occurring hormone, is known for its hunger-blocking effect on the hypothalamus, a region in the brain. Food intake is influenced by signals that travel from the body to the brain. Leptin is one of the molecules that signal the brain to modulate food intake. It is produced in fat cells and informs the brain of the metabolic state. If animals are missing leptin, or the leptin receptor, they eat too much and become severely obese.

Leptin's effect on metabolism has been found to control the brain's neuronal circuits, but no previous studies have definitively found that leptin could control the behavior of cells other than neurons.

To test the theory, Horvath and his team selectively knocked out leptin receptors in the
adult non-neuronal glial cells of mice. The team then recorded the water and food intake, as well as physical activity every five days. They found that animals responded less to feeding reducing effects of leptin but had heightened feeding responses to the hunger hormone ghrelin.

"Glial cells provide the main barrier between the periphery and the brain," said Horvath. "Thus glial cells could be targeted for drugs that treat metabolic disorders, including obesity and diabetes."

Leptin also influences brain cells that control appetite, researchers find 

New therapy for pancreatic cancer patients shows promising results -- ScienceDaily

New therapy for pancreatic cancer patients shows promising results 

A Cinical trial conducted by researchers at the Virginia G. Piper Cancer Center Clinical Trials, a partnership between Scottsdale Healthcare and the Translational Genomics Research Institute (TGen), showed that a new drug called MM-398 (below structure), given in combination with 5-flourouracil (5FU) and leucovorin, produced a significant overall survival rate in patients with advanced, previously-treated pancreatic cancer.

FDA Approves Incruse Ellipta...

GlaxoSmithKline plc today announced that the US Food and Drug Administration (FDA) has approved Incruse Ellipta (umeclidinium) as an anticholinergic indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Umeclidinium is GSK’s first once-daily anticholinergic, a type of bronchodilator also known as a long-acting muscarinic antagonist (LAMA), and is contained in the Ellipta® inhaler. The FDA-approved strength is 62.5 mcg.

Following this approval by the FDA, it is anticipated that launch activities in the US will commence during the fourth quarter of 2014.

The phase III pivotal programme for umeclidinium included seven clinical studies which involved over 2,500 COPD patients treated with umeclidinium or placebo.

Incruse Ellipta (umeclidinium) Information from Drugs.com

FDA Approves Zontivity to Reduce the Risk of Heart Attacks and Stroke

The U.S. Food and Drug Administration  approved Zontivity (vorapaxar) tablets to reduce the risk of heart attack, stroke, cardiovascular death, and need for procedures to restore the blood flow to the heart in patients with a previous heart attack or blockages in the arteries to the legs.

Zontivity is the first in a new class of drug, called a protease-activated receptor-1 (PAR-1) antagonist. It is an anti-platelet agent, designed to decrease the tendency of platelets to clump together to form a blood clot. By decreasing the formation of blood clots, Zontivity decreases the risk of heart attack and stroke.

Like other drugs that inhibit blood clotting, Zontivity increases the risk of bleeding, including life-threatening and fatal bleeding. Bleeding is the most commonly reported adverse reaction in people taking Zontivity. The drug’s prescribing information (label) includes a Boxed Warning to alert health care professionals about this risk.

Zontivity must not be used in people who have had a stroke, transient ischemic attack (TIA), or bleeding in the head, because the risk of bleeding in the head is too great.

“In patients who have had a heart attack or who have peripheral arterial disease, this drug will lower the risk of heart attack, stroke, and cardiovascular death. In the study that supported the drug’s approval, Zontivity lowered this risk from 9.5 percent to 7.9 percent over a 3-year period – about 0.5 percent per year,” said Ellis Unger, M.D., director of the Office of Drug Evaluation I in the FDA’s Center for Drug Evaluation and Research.

FDA Approves Zontivity to Reduce the Risk of Heart Attacks and Stroke

Amrubicin promise for etoposide-naïve SCLC patients

Patients with chemotherapy-refractory small-cell lung cancer (SCLC) may benefit from treatment with the topoisomerase II inhibitor amrubicin, research from Japan suggests.

The 82 patients enrolled in the open-label, single-arm Japan Clinical Oncology Group Study JCOG0901 trial received amrubicin 40 mg/m2 for 3 days on a 21-day cycle, for a median of four cycles. All patients had already experienced no response, or progression, following treatment with at least one platinum-based regimen, with 51.2% previously treated with etoposide and 57.3% with irinotecan.

The overall response rate, defined as an independently assessed complete or partial response, was highly significant, at 32.9%, compared with a null hypothesis threshold of 10.0% or below. Median progression-free survival was 3.5 months and overall survival was 8.9 months, with over a third (35.7%) of patients alive 1 year later.

And amrubicin showed particular promise for patients who had not previously received etoposide, another type of topoisomere II inhibitor, say Haruyasu Murakami (Shizuoka Cancer Center) and colleagues.

Etoposide-naïve patients achieved an objective response rate of 45.0%, compared with 21.4% for those previously treated with the agent, a significant difference.

Both median progression-free survival and overall survival were also significantly higher in etoposide-naïve than pretreated patients, at 5.1 versus 2.9 months and 13.1 versus 7.9 months, respectively.

The reduced benefit of amrubicin found in patients previously treated with etoposide may be due to downregulation of topoisomerase II following the initial treatment, Murakami et al suggest in Lung Cancer.

Amrubicin promise for etoposide-naïve SCLC patients

Promising discovery in fight against antibiotic-resistant bacteria .....

Researchers at  the  University  of British  Columbia  have identified a small molecule  that prevents  bacteria from forming into biofilms, a frequent cause of infections. The anti-biofilm peptide works on a range of bacteria including many that cannot be treated by antibiotics...

Hancock and his colleagues found that the peptide known as 1018  consisting of just 12 amino acids, the building blocks of protein  destroyed biofilms and prevented them from forming.

Bacteria are generally separated into two classes, Gram-positives and Gram-negatives, and the differences in their cell wall structures make them susceptible to different antibiotics. 1018 worked on both classes of bacteria as well as several major antibiotic-resistant pathogens, including Pseudomonas aeruginosa, E. coli and MRSA.

"Antibiotics are the most successful medicine on the planet. The lack of effective antibiotics would lead to profound difficulties with major surgeries, some chemotherapy treatments, transplants, and even minor injuries," says Hancock. "Our strategy represents a significant advance in the search for new agents that specifically target bacterial biofilms."

Promising discovery in fight against antibiotic-resistant bacteria 

New details on microtubules and how the anti-cancer drug Taxol works

A pathway to the design of even more effective versions of the powerful anti-cancer drug Taxol has been opened with the most detailed look ever at the assembly and disassembly of microtubules, tiny fibers of tubulin protein that form the cytoskeletons of living cells and play a crucial role in mitosis. Through a combination of high-resolution cryo-electron microscopy (cryo-EM) and new methodology for image analysis and structure interpretation, researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) Berkeley have produced images of microtubule assembly and disassembly at the unprecedented resolution of 5 angstroms (Å). Among other insights, these observations provide the first explanation of Taxol's success as a cancer chemotherapy agent.

New details on microtubules and how the anti-cancer drug Taxol works  

Isis Pharmaceuticals reports positive data from ISIS-GCGRRx Phase 2 study in patients with type 2 diabetes

Isis Pharmaceuticals, Inc.  announced positive data from a Phase 2 study of ISIS-GCGRRx in patients with type 2 diabetes uncontrolled on stable metformin therapy. In this study, patients in the per protocol efficacy population treated with ISIS-GCGRRx achieved statistically significant reductions in measures of glucose control. The absolute mean reductions in hemoglobin A1c (HbA1c) were greater than 2 percentage points>Rx also experienced increased plasma GLP-1 levels. Isis will present additional detail from this study as a late-breaking abstract program at the American Diabetes Association 74th Scientific Sessions. In conjunction, Isis will host an investor event on June 15, 2014 at 7:00 a.m PT. 

"These results reported today represent the potential for a major advance in diabetes therapeutics. ISIS-GCGRRx employs a unique mechanism to treat patients with type 2 diabetes. It is well known that as type 2 diabetes progresses, dysregulated glucagon action becomes a more significant contributor to the disease. The ability of ISIS-GCGRRxto improve glycemic control without causing any clinically significant increases in blood pressure or lipids offers a significant advantage for both patients and treating physicians," said Robert Henry, M.D., chief, VA endocrinology & metabolism and professor of medicine in residence, University of California, San Diego School of Medicine. "The additional effect on increasing GLP-1 means that ISIS-GCGRRx treatment could help to preserve pancreatic function and enhance insulin secretion in diabetic patients."

Isis Pharmaceuticals reports positive data from ISIS-GCGRRx Phase 2 study in patients with type 2 diabetes