Experimental drug guadecitabine found safe in patients with colorectal cancer: Combination with standard chemotherapy shows promise in overcoming treatment resistance

In continuation of my update on guadecitabine (SGI-110)

In a small, phase I clinical trial, Johns Hopkins Kimmel Cancer Center researchers say they show for the first time that the experimental drug guadecitabine (SGI-110) is safe in combination with the chemotherapy drug irinotecan and may overcome resistance to irinotecan in patients with metastatic colorectal cancer. Results of the study are expected to be presented April 17 at the American Association for Cancer Research (AACR) Annual Meeting 2016 in New Orleans (abstract CT017).

Guadecitabine works to reverse a so-called epigenetic change in cancer cells known as methylation, which may alter genetic activity in cells in a way that can block the action of tumor-suppressing genes, pushing cells to become cancerous and resistant to therapy. By reversing this change in cancer cells, the drug restores cancer cells' vulnerability to drugs such as irinotecan.

The clinical trial included 22 patients with metastatic colorectal cancer who had been treated previously with irinotecan and whose disease was progressing. The patients were divided into four groups, each receiving different doses of guadecitabine in combination with irinotecan, over an average period of four months.

During the study, 15 patients had at least one imaging scan to retest the extent and location of their cancers -- with 12 patients experiencing stable disease -- for more than the four-month period, on average, and one patient experiencing a partial response to the treatment (measured as at least a 30 percent reduction in the size of the tumors.)

Although the study's main purpose was to test the safety rather than the effectiveness of guadecitabine doses, "we were very happy to see some patients who benefited from the combination of the therapies for many months to more than a year," says Nilofer Azad, M.D., professor of oncology at the Johns Hopkins University School of Medicine.

The study also showed signs that guadecitabine reduced methylation among the cancer cells. "We did see that giving a higher dose of the drug seemed to produce a better methylation response among patients," says Valerie Lee, M.D., a fellow at the Johns Hopkins Kimmel Cancer Center. "However, it seemed that patients were responding at all levels of the drug."

Among the side effects of the combined treatment, 16 patients experienced neutropenia, a low count of the infection-fighting white blood cells called neutrophils; five patients with neutropenia had fevers; three patients became anemic; and two patients developed thrombocytopenia, a lowered count of blood-clotting platelets. Other side effects included diarrhea (three patients), fatigue (two patients) and dehydration (two patients). There was one death during the study, possibly resulting from febrile neutropenia caused by the treatment.

The current study was based on previous studies in the laboratory of Nita Ahuja, M.D., director of the Sarcoma and Peritoneal Surface Malignancy Program and professor of surgery at the Johns Hopkins University School of Medicine, which showed that guadecitabine limited the growth of colorectal cancer cell lines when combined with irinotecan, says Azad.

The drug combination is being tested in an ongoing phase II clinical trial (NCT01896856) in a larger group of metastatic colorectal cancer patients at multiple institutions to determine the effectiveness of the dual therapy compared with chemotherapy regimens that do not include guadecitabine, says Azad.

Scientists leading the new study will also look for biomarkers in patients that could help determine which of them are most likely to benefit from guadecitabine and irinotecan. Lee says the research team will measure the amount of methylation in patients' cells when they begin their treatment and the presence of genes associated with irinotecan resistance, among other possible biomarkers.

In 2015, there were more than 130,000 people in the U.S. diagnosed with colon cancers. Five-year survival rates among people with localized colon cancers are more than 90 percent, but they are only 20 percent in those with metastatic cancer.

Guadecitabine is an experimental drug that has not been approved for use by the U.S. Food and Drug Administration. It is manufactured by Astex Pharmaceuticals, a supporter of the Johns Hopkins-led study. The research was also supported by the Van Andel Research Institute SU2C/AACR Epigenetics Dream Team.

Other scientists who contributed to the research include Judy Wang, Anup Sharma, Zachary Kerner, Stephen Baylin, Ellen Lilly, and Thomas Brown from Johns Hopkins; Anthony El Khoueiry from the University of Southern California; Henk Verheul and Elske Gootjes from Vrije Universiteit in the Netherlands; and Peter Jones from the Van Andel Research Institute.

Experimental drug guadecitabine found safe in patients with colorectal cancer: Combination with standard chemotherapy shows promise in overcoming treatment resistance 

Study demonstrates therapeutic potential of SOD-mimetic compound M40403 against Parkinson disease

Parkinson disease is a debilitating and incurable neurodegenerative disorder, affecting approximately 1-2% of people over sixty-five years old. Oxidative damage is considered to play a central role in the progression of Parkinson disease and strong evidence links chronic exposure to the pesticide paraquat with the incidence of the disease, most probably through the generation of oxidative damage.

In this work we demonstrated in human SH-SY5Y neuroblastoma cells the beneficial role of superoxide dismutase (SOD) enzymes against paraquat-induced toxicity, as well as the therapeutic potential of the SOD-mimetic compound M40403.

Having verified the beneficial effects of superoxide dismutation in cells, we then evaluated the effects using Drosophila melanogaster as in vivo model. Besides protecting against the oxidative damage induced by paraquat treatment, our data demonstrated that in Drosophila M40403 was able to compensate for the loss of endogenous SOD enzymes, acting both at a cytosolic and mitochondrial level. Because previous clinical trials have indicated that the M40403 molecule is well tolerated in humans, this study may have important implication for the treatment of Parkinson disease.

Study demonstrates therapeutic potential of SOD-mimetic compound M40403 against Parkinson disease: Parkinson disease is a debilitating and incurable neurodegenerative disorder, affecting approximately 1-2% of people over sixty-five years old. Oxidative damage is considered to play a central role in the progression of Parkinson disease and strong evidence links chronic exposure to the pesticide paraquat with the incidence of the disease, most probably through the generation of oxidative damage.

Cyclodextrin dissolves cholesterol crystals, reduces atherosclerotic plaques

In continuation of my update of cyclodextrin

Cardiovascular disease from atherosclerosis is one of the most common causes of death worldwide. Inflammation plays a crucial role in atherosclerosis and cholesterol crystals are considered to be early triggers in the development of the disease.

An international team has now found that cyclodextrin dissolves cholesterol crystals and reduces atherosclerotic plaques. This is a promising therapeutic approach for treating atherosclerosis. Their find was published in Science Translational Medicine.

Cyclodextrin works by reprogramming macrophages so that they do not cause such a strong inflammatory response in blood vessels that contain cholesterol crystals. The cyclodextrin also dissolves cholesterol crystals so that the cholesterol can be excreted from the body in urine. The result is prevention of plaque formation and even atherosclerotic plaque reduction in mice. Furthermore, when researchers used cyclodextrin to treat biopsies of plaques from human carotid arteries, they found similar results.

The study points to cholesterol crystals as a target for treatment of atherosclerosis, meaning that using cyclodextrin to dissolve the crystals could affect how the disease is treated.

The original idea for the test of cyclodextrin came from Chris Hempel, an American mother whose twin daughters are affected by a rare illness called Niemann-Pick Type C disease, in which cholesterol accumulates in the body. The children are being treated with cyclodextrin with promising results.

Ref : http://stm.sciencemag.org/content/8/333/333ra50

Cyclodextrin dissolves cholesterol crystals, reduces atherosclerotic plaques: Cardiovascular disease from atherosclerosis is one of the most common causes of death worldwide. Inflammation plays a crucial role in atherosclerosis and cholesterol crystals are considered to be early triggers in the development of the disease.

Valeant and Progenics Announce FDA Approves Relistor Tablets for the Treatment of Opioid-Induced Constipation in Adults with Chronic Non-Cancer Pain

In continuation of my update on Naltrexone

Valeant Pharmaceuticals International, Inc.  and Progenics Pharmaceuticals, Inc. today announced that the U.S. Food and Drug Administration has approved Relistor (methylnaltrexone bromide) Tablets for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain. Valeant expects to commence sales of Relistor Tablets in the U.S. in the third quarter of 2016.

"Opioid-induced constipation represents a long-lasting and potentially debilitating side effect of opioid therapy for millions of patients suffering from chronic pain," commented Joseph C. Papa, Chief Executive Officer of Valeant. "We believe Oral Relistor represents a new alternative treatment for OIC, and we look forward to introducing the more convenient oral formulation as soon as practicable."

"We are delighted that this milestone for Relistor has been achieved, and that patients suffering from OIC will have this new treatment option," said Mark Baker, Chief Executive Officer of Progenics. "We expect the market to be receptive to a more convenient oral tablet formulation of Relistor's well-established subcutaneous preparation. We would like to thank, in particular, Dr. Tage Ramakrishna and Dr. Robert Israel of Valeant for their work over many years in the clinical development of Relistor."

"Relistor has a unique mechanism of action that binds to mu-opioid receptors without impacting the opioid-mediated analgesic effects on the central nervous system," said Richard L. Rauck, MD, Medical Director, Center for Clinical Research, President, Carolinas Pain Institute, President of the Sceptor Pain Foundation of which he is a founding member, and Immediate Past President of the World Institute of Pain. "This represents a true breakthrough in the treatment of OIC, and addresses a large and growing need in the field of pain management." Today, the FDA approved Relistor Tablets (450 mg once daily) for the treatment of OIC in adults with chronic non-cancer pain. Previously, Relistor Subcutaneous Injection (12 mg and 8 mg) was approved in 2008 for the treatment of OIC in adults with advanced illness who are receiving palliative care and in 2014 for the treatment of OIC in adults with chronic non-cancer pain. About the Phase 3 Clinical Trial of Oral Relistor for OIC in Chronic Non-Cancer Pain (NCP) A randomized, double-blind, Phase 3 trial was conducted to evaluate once-daily dosing of 450 mg (n=200) methylnaltrexone (MNTX) tablets compared to placebo (n=201) in adults with chronic NCP. In the 450 mg treatment arm, MNTX tablets demonstrated statistically significant improvements in rescue-free bowel movement (RFBM) within 4 hours of administration over 28 days of dosing when compared to placebo treatment, achieving the primary endpoint. The 450 mg treatment group also achieved statistical significance for the first key secondary efficacy endpoint where a higher percentage of responders (i.e., had ≥3 RFBMs/week, with an increase of ≥1 RFBM/week from baseline for at least 3 of the 4 weeks) was observed with MNTX treatment as compared to placebo. Overall, efficacy of oral methylnaltrexone in this study was comparable to that reported in clinical studies of subcutaneous methylnaltrexone in subjects with chronic, non-cancer pain. The overall observed safety profile seen in patients treated with oral methylnaltrexone was comparable to placebo in this study.

Important Safety Information

Relistor (methylnaltrexone bromide) Tablets is contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie's syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using Relistor in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn's disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue Relistor in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with Relistor and consult their healthcare provider.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with Relistor. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using Relistor in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

Avoid concomitant use of Relistor with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal. The most common adverse reactions (≥ 12%) in adult patients with opioid-induced constipation and chronic non-cancer pain receiving Relistor tablets were abdominal pain, diarrhea, headaches, abdominal distention, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

About Relistor

Progenics has exclusively licensed development and commercialization rights for its first commercial product, Relistor, to Valeant. Relistor Tablets (450 mg once daily) is approved in the United States for the treatment of OIC in patients with chronic non-cancer pain. Relistor Subcutaneous Injection (12 mg and 8 mg) is a treatment for opioid-induced constipation approved in the United States and worldwide for patients with advanced illness and chronic non-cancer pain.

Added benefit of crizotinib drug for first-line treatment of advanced bronchial carcinoma not proven

In continuation of my update on crizotinib

The drug crizotinib (trade name: Xalkori) has been available since 2012 for patients with advanced non-small cell lung cancer (bronchial carcinoma) who have a high activity of the enzyme anaplastic lymphoma kinase (ALK) and have already received another treatment. In November 2015, the approval was extended to first-line treatment.

After its assessment in 2013, the German Institute for Quality and Efficiency in Health Care (IQWiG) therefore now reassessed the added benefit of the drug in comparison with the appropriate comparator therapy - and found out: An added benefit of crizotinib for the first-line treatment of advanced bronchial carcinoma is not proven.

Carboplatin only in advanced risk of cisplatin side effects

Advanced bronchial carcinoma can only be treated palliatively. The Federal Joint Committee (G-BA) specified several appropriate comparator therapies for this. Either cisplatin in combination with a third-generation cytostatic agent was to be used in the control arm, or - in case of an increased risk of cisplatin side effects - carboplatin with a third-generation cytostatic agent. Monotherapy with gemcitabine or vinorelbine was an alternative option for patients with already severe limitations.

Use of carboplatin attached to condition

The drug manufacturer did not use the latter option and only submitted data from a randomized study in which crizotinib was directly compared with cisplatin or carboplatin, each in combination with the cytostatic agent pemetrexed. Carboplatin is not approved for the treatment of advanced non-small cell lung cancer, but can be prescribed in so-called off-label use. This is only the case for patients with an advanced risk of cisplatin side effects, e.g. in neuropathy, hearing impairment or susceptibility to nausea, renal insufficiency or cardiac failure.

The only submitted study did not fulfil the condition

Almost half of the participants received carboplatin in the control arm of the PROFILE 1014 study; the criteria for this individual medical decision were not comprehensible. A large proportion of the patients in the control arm did not correspond to the criteria of the Pharmaceutical Directive for the off-label use of carboplatin. Patients with neuropathy, renal insufficiency or cardiac failure were excluded from participation in the study and only about two and six per cent of the participants had notable hearing impairment or nausea as accompanying disease.

Hence the control group of the study did not adequately represent the appropriate comparator therapy. The data submitted were therefore unsuitable for the derivation of an added benefit of crizotinib in comparison with this comparator therapy.

Added benefit of crizotinib drug for first-line treatment of advanced bronchial carcinoma not proven: The drug crizotinib (trade name: Xalkori) has been available since 2012 for patients with advanced non-small cell lung cancer (bronchial carcinoma) who have a high activity of the enzyme anaplastic lymphoma kinase (ALK) and have already received another treatment. In November 2015, the approval was extended to first-line treatment.

Zonisamide relieves myoclonus dystonia motor symptoms

A randomised crossover trial shows that zonisamide significantly improves motor symptoms and related disability in adults with myoclonus dystonia.

Myoclonus dystonia is very rare, and Marie Vidailhet (Hôpital Pitié-Salpêtrière, Paris, France) and co-researchers stress that their study "is the first controlled therapeutic trial to be conducted in this setting."

It involved 23 patients with myoclonus dystonia who were randomly assigned to receive the benzisoxazole derivative zonisamide (up to 300 mg/day) or placebo for a 6-week dose-escalation period followed by 3 weeks at the highest tolerated dose. After a 5-week washout period, the patients were switched to the other treatment.

From a baseline of 28 points on the Unified Myoclonus Rating Scale (UMRS) section 4, the severity of action myoclonus improved by a median of 5 points during the zonisamide treatment period relative to the placebo period. And from a baseline of 7 points on the UMRS section 5, myoclonus-related functional disability improved by a significant 2 points with zonisamide relative to placebo. Both of these differences were statistically significant.

Patients also had significantly improved dystonia, by 3 points on the Burke-Fahn-Marsden Dystonia Rating Scale, during zonisamide versus placebo treatment, although related disability was unaffected.

"Zonisamide may thus be considered as a therapeutic option for patients with mild to moderate [myoclonus dystonia] and for patients with severe forms who refuse or are not eligible for deep brain stimulation", write the researchers in Neurology.

They note that the benefits observed with zonisamide in their study are less than those reported for deep-brain stimulation.

Adverse events were reported by 83% of patients during the zonisamide treatment period and by 74% during the placebo period. Asthenia was more common during the zonisamide versus placebo phases (65 vs 17%), as were mood swings (35 vs 26%).

The researchers note that patients only received 9 weeks of treatment in their study, leaving the longer-term benefits and safety profile to be determined.

And they add that, because myoclonus dystonia "usually starts before age 10, the use of zonisamide in children will need to be addressed, although studies in epilepsy show that zonisamide is well-tolerated in this age group."

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

Zonisamide relieves myoclonus dystonia motor symptoms: A randomised crossover trial shows that zonisamide significantly improves motor symptoms and related disability in adults with myoclonus dystonia.

Common antihistamine may partially reverse damage to visual system in multiple sclerosis patients

A common antihistamine used to treat symptoms of allergies and the common cold, called clemastine fumarate, partially reversed damage to the visual system in people with multiple sclerosis (MS) in a preliminary study released today that will be presented at the American Academy of Neurology's 68th Annual Meeting in Vancouver, Canada, April 15 to 21, 2016.

The study involved people with MS and optic neuropathy, which is damage to the nerve that sends information from the eye to the brain. In people with MS, the immune system destroys myelin, the protective coating around the nerves, which then leads to damage along the nerves, slowing signals to and from the brain. Optic nerve damage is a common consequence of the disease.

"This study is exciting because it is the first to demonstrate possible repair of that protective coating in people with chronic demyelination from MS," said study author Ari Green, MD, of the Multiple Sclerosis Center at UC San Francisco, and a member of the American Academy of Neurology. "This was done using a drug that was identified at UCSF only two-and-a-half years ago as an agent with the potential to help with brain repair."

The five-month study involved 50 people with an average age of 40 who had MS for an average of five years and had mild disability. They all had evidence of a stable chronic optic neuropathy, meaning that they were not recovering from a recent optic neuritis.

Participants performed vision tests at the start and end of the study. For one test, called a visual evoked potential, the time for transmission of signal from the retina to the visual cortex was recorded. To be included in the study, participants had to have a delay in transmission time beyond 118 milliseconds in at least one eye and had to have evidence that they had an adequate number of nerve fibers to reinsulate. An improvement in the delay in transmission is considered a biomarker of myelin repair.

For the first three months of the study, people were given either the antihistamine clemastine fumarate or a placebo. For the second two months, those initially given the drug received the placebo and vice versa.

During the study, delays were reduced by an average of slightly less than two milliseconds in each eye per patient among those who received the antihistamine.

"While the improvement in vision appears modest, this study is promising because it is the first time a drug has been shown to possibly reverse the damage done by MS," said Green. "Findings are preliminary, but this study provides a framework for future MS repair studies and will hopefully herald discoveries that will enhance the brain's innate capacity for repair."

Common antihistamine may partially reverse damage to visual system in multiple sclerosis patients: A common antihistamine used to treat symptoms of allergies and the common cold, called clemastine fumarate, partially reversed damage to the visual system in people with multiple sclerosis (MS) in a preliminary study released today that will be presented at the American Academy of Neurology's 68th Annual Meeting in Vancouver, Canada, April 15 to 21, 2016.

Anti-inflammatory drugs may improve severity of depressive symptoms, study finds

Anti-inflammatory drugs similar to those used to treat conditions such as rheumatoid arthritis and psoriasis could in future be used to treat some cases of depression, concludes a review led by the University of Cambridge, which further implicates our immune system in mental health disorders.

Researchers from the Department of Psychiatry at Cambridge led a team that analysed data from 20 clinical trials involving the use of anti-cytokine drugs to treat a range of autoimmune inflammatory diseases. By looking at additional beneficial side-effects of the treatments, the researchers were able to show that there was a significant antidepressant effect from the drugs compared to a placebo based on a meta-analysis of seven randomised controlled trials. Meta-analyses of the other types of clinical trials showed similar results.

When we are exposed to an infection, for example influenza or a stomach bug, our immune system fights back to control and remove the infection. During this process, immune cells flood the blood stream with proteins known as cytokines. This process is known as systemic inflammation.

Even when we are healthy, our bodies carry trace levels of these proteins - known as 'inflammatory markers' - which rise exponentially in response to infection. Previous work from the team found that children with high everyday levels of one of these markers are at greater risk of developing depression and psychosis in adulthood, suggesting a role for the immune system, particularly chronic low-grade systemic inflammation, in mental illness.

Inflammation can also occur as a result of the immune system mistaking healthy cells for infected cells and attacking the body, leading to autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis and Crohn's disease. New types of anti-inflammatory drugs called anti-cytokine monoclonal antibodies and cytokine inhibitors have been developed recently, some of which are now routinely used for patients who respond poorly to conventional treatments. Many more are currently undergoing clinical trials to test their efficacy and safety.

The team of researchers carried out a meta-analysis of these clinical trials and found that the drugs led to an improvement in the severity of depressive symptoms independently of improvements in physical illness. In other words, regardless of whether a drug successfully treated rheumatoid arthritis, for example, it would still help improve a patient's depressive symptoms. Their results are published today in the journal Molecular Psychiatry.

Anti-inflammatory drugs may improve severity of depressive symptoms, study finds: Anti-inflammatory drugs similar to those used to treat conditions such as rheumatoid arthritis and psoriasis could in future be used to treat some cases of depression, concludes a review led by the University of Cambridge, which further implicates our immune system in mental health disorders.

Daily dose of coffee could help reverse non-alcoholic fatty liver disease

Adding coffee to the diet of people with non-alcoholic fatty liver disease (NAFLD) could help reverse the condition, according to a new study conducted in mice presented at The International Liver Congress 2016 in Barcelona, Spain.

The study found that a daily dose of coffee (equivalent to six cups of espresso coffee for a 70kg person) improved several key markers of NAFLD in mice that were fed a high fat diet. These mice also gained less weight than others fed the same diet without the dose of caffeine.

The scientists also showed how coffee protects against NAFLD by raising levels of a protein called Zonulin (ZO)-1, which lessens the permeability of the gut. Experts believe that increased gut permeability contributes to liver injury and worsens NAFLD. People suffering from NAFLD can develop scaring of the liver, also known as fibrosis, which can progress to a potentially life-threatening condition known as cirrhosis.

"Previous studies have confirmed how coffee can reverse the damage of NAFLD but this is the first to demonstrate that it can influence the permeability of the intestine," said Vincenzo Lembo, at the University of Napoli, Italy and study author. "The results also show that coffee can reverse NAFLD-related problems such as ballooning degeneration, a form of liver cell degeneration."

Researchers analysed three different groups of mice over a 12 week period. Group one received a standard diet, group two had a high fat diet and group three was given a high fat diet plus a decaffeinated coffee solution.

Coffee supplementation to a high fat diet significantly reversed levels of cholesterol (p<0.001), alanine aminotransferase (an enzyme which levels increase in the blood when the liver is damaged) (p<0.05), amount of fat in the liver cells (steatosis) (p<0.001) and ballooning degeneration (p<0.05). The combination of coffee and a high fat diet also reduced weight gain over time (p=0.028) in the mice. The study results suggest that coffee supplementation could cause variations in the intestinal tight junctions, which regulate the permeability of the intestine.

Daily dose of coffee could help reverse non-alcoholic fatty liver disease: Adding coffee to the diet of people with non-alcoholic fatty liver disease (NAFLD) could help reverse the condition, according to a new study conducted in mice presented at The International Liver Congress 2016 in Barcelona, Spain.

Willow herb extracts may be beneficial in treating multi-drug resistant bacterial and fungal infections

 

A common herb, Epilobi Hirsuti (see pic) could help reduce antibiotic doses and result in less severe side effects in treatments against multi-drug resistant microorganisms.

Although often considered a weed, due to its anti-inflammatory and antioxidant properties, willow herb has long enjoyed a solid reputation for easing problems of the prostate gland and urinary tract. New tests confirm that combining some of the commonly used antibiotics with great willow herb extracts may be beneficial in treating bacterial and fungal infections as well.

Many strains of bacteria are becoming resistant to even the strongest antibiotics, causing deadly infections and becoming a global health issue. In America alone this accounts for at least 23,000 deaths each year, as an abuse of antibiotics promotes the development of antibiotic-resistant bacteria. As more and more bacterial strains do not react to any of currently known antibiotics, scientists often turn to nature, screening for plant-derived compounds to identify new drug leads which would be able to control the populations of multi-drug resistant bacteria. An article published now online in Open Chemistry suggests that some of the willow herb extracts exert a synergistic effect with common antibiotics.

Using different solvents, the scientists from the National Institute of Chemical-Pharmaceutical R&amp;D, ICCF-Bucharest in Romania prepared a series of great willow herb extracts. They then screened the extracts - rich in phenolic acids and flavonoids -  for their antimicrobial effect against selected bacterial and fungal strains, to further test different concentrations of extracts along with a series of antibiotics for the possible effects of these combinations on the observed antimicrobial effect.

Interestingly enough, they were able to observe the synergistic effect on bacterial strains which were resistant to some of the commonly used antibiotics. The authors hence suggest that this development could lead to reducing the antibiotic doses, and consequently  to less severe side effects in therapies against multi-drug resistant microorganisms. Courtesy of the herbal healer, some bacterial or fungal infections can be treated with better effects when compared to a therapy based only on antibiotics, as it has potential to influence the antimicrobial effect of some common antibiotics and antibiotics may be co-administered with plant-derived compounds to potentiate their antimicrobial effect.

Ref : http://www.degruyter.com/view/j/chem.2016.14.issue-1/chem-2016-0004/chem-2016-0004.xml

Willow herb extracts may be beneficial in treating multi-drug resistant bacterial and fungal infections: A common herb could help reduce antibiotic doses and result in less severe side effects in treatments against multi-drug resistant microorganisms.

Intestinal bacteria can be used to reduce cancer risk, reveals UCLA study

Researchers have shown that various types of intestinal bacteria might be factors in both causing and preventing obesity, and in other conditions and diseases. Now, a UCLA study suggests that it could also potentially be used to reduce the risk for some types of cancer.

The research, published online April 13 in the peer-reviewed journal PLOS ONE, offers evidence that anti-inflammatory "health beneficial" gut bacteria can slow or stop the development of some types of cancer.

Ultimately, doctors might be able to reduce a person's risk for cancer by analyzing the levels and types of intestinal bacteria in the body, and then prescribing probiotics to replace or bolster the amount of bacteria with anti-inflammatory properties, said Robert Schiestl, professor of pathology, environmental health sciences and radiation oncology at UCLA and the study's senior author.

"It is not invasive and rather easy to do," he said.

Over millions of years, gut bacteria have evolved into both good and bad types: The good ones have anti-inflammatory properties and the bad ones promote inflammation. The human body typically contains about 10 trillion bacterial cells, compared with only 1 trillion human cells.

Schiestl and his colleagues isolated a bacterium called Lactobacillus johnsonii 456, which is the most abundant of the beneficial bacteria, and which has some pretty useful applications outside of medicine. "Since it is a Lactobacillus strain, it makes excellent yogurt, kefir, kombucha and sauerkraut."

In the UCLA study the bacterium reduced gene damage and significantly reduced inflammation — a critical goal because inflammation plays a key role in many diseases, including cancer, neurodegenerative diseases, heart disease, arthritis and lupus, and in the aging process.

Previous research led by Schiestl presented the first evidence of a relationship between intestinal microbiota and the onset of lymphoma, a cancer that originates in the immune system. The new study explains how this microbiota might delay the onset of cancer, and suggests that probiotic supplements could help keep cancer from forming.

For both studies, Schiestl and his team used mice that had mutations in a gene called ATM, which made them susceptible to a neurologic disorder called ataxia telangiectasia. The disorder, which affects 1 in 100,000 people, is associated with a high incidence of leukemia, lymphomas and other cancers.

The mice were divided into two groups — one that was given only anti-inflammatory bacteria and the other that received a mix of inflammatory and anti-inflammatory microbes that typically co-exist in the intestines.

In the Cancer Research paper, Schiestl and his team showed that in the mice with more of the beneficial bacteria, the lymphoma took significantly longer to form.

In the new study, the researchers analyzed the metabolites — molecules produced by the gut's natural metabolic action — in the mice's urine and feces. The scientists were surprised to find that the mice that were receiving only the beneficial microbiota produced metabolites that are known to prevent cancer. Those mice also had more efficient fat and oxidative metabolism, which the researchers believe might also lower the risk for cancer.

Intestinal bacteria can be used to reduce cancer risk, reveals UCLA study: Researchers have shown that various types of intestinal bacteria might be factors in both causing and preventing obesity, and in other conditions and diseases. Now, a UCLA study suggests that it could also potentially be used to reduce the risk for some types of cancer.

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring

In continuation of my update on dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa).

A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

But special attention must be given to the patient's age, kidney function and other factors before prescribing the new medications, according to a review article by neurologists at Loyola Medicine and Loyola University Chicago Stritch School of Medicine.

The report by Rochelle Sweis, DO and José Biller, MD, is published in the journal Current Treatment Options in Cardiovascular Medicine.

Atrial fibrillation (AFib) is the most common type of irregular heartbeat, and the prevalence is increasing as the population ages. In AFib, electrical signals that regulate the heartbeat become erratic. Instead of beating regularly, the upper chambers of the heart quiver and blood doesn't flow well. Blood clots can form, migrate to the brain and cause strokes. AFib is associated with a fivefold increase in the risk of stroke.

Blood thinning medications decrease the stroke risk by approximately 70 percent. For 60 years physicians have prescribed warfarin (Coumadin) and other blood thinners known as vitamin K antagonists. These medications have been proven to be effective in reducing the risk of blood clots and strokes. But they require continual monitoring and dose adjustments to ensure the drugs thin the blood enough to prevent clots, but not enough to increase the risk of major bleeding. Patients also must restrict their consumption of foods rich in vitamin K, such as spinach, Brussels sprouts, kale, parsley and green tea.

 

Warfarin

The new blood thinners include dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa). In the right patient population, the new drugs are a safe and effective option for treating atrial fibrillation, Drs. Sweis and Biller write.

Dabigatran         Rivaroxaban (BAY 59-7939)

Apixaban Edoxaban

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring: A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

Cholesterol-fighting drug molecule can kill prostate cancer cells

  

(Ro 48-8071 fumarate)

[4′-[6-(Allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate 

Standard treatment for prostate cancer can include chemotherapy that targets receptors on cancer cells. However, drug-resistant cancer cells can emerge during chemotherapy, limiting its effectiveness as a cancer-fighting agent. Researchers at the University of Missouri have proven that a compound initially developed as a cholesterol-fighting molecule not only halts the progression of prostate cancer, but also can kill cancerous cells.

"Cholesterol is a molecule found in animal cells that serves as a structural component of cell membranes. When tumor cells grow, they synthesize more cholesterol," said Salman Hyder, the Zalk Endowed Professor in Tumor Angiogenesis and professor of biomedical sciences in the MU College of Veterinary Medicine and the Dalton Cardiovascular Research Center. "Often, cancer patients are treated with toxic chemotherapies; however, in our study, we focused on reducing the production of cholesterol in cancer cells, which could kill cancer cells and reduce the need for toxic chemotherapy."

Currently, treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptors located in the cancer cells, which normally bind with hormones such as testosterone. Anti-hormone therapies, or chemical castration, also may be used in the fight against prostate cancer.

"Although tumor cells may initially respond to these therapies, most eventually develop resistance that causes prostate cancer cells to grow and spread," Hyder said. "Cholesterol also can contribute to the development of anti-hormone resistance because cholesterol is converted into hormones in tumor cells; therefore, these cholesterol-forming pathways are attractive therapeutic targets for the treatment of prostate cancer."

Using a compound developed by Roche Pharmaceuticals for the treatment of high cholesterol called RO 48-8071, Hyder and his team administered the molecule to human prostate cancer cells. They found that the compound was effective in reducing human prostate cancer cell growth. Subsequent studies also found that the compound caused cancer cell death.

Armed with this information, Hyder and the team then tested the results in mice with human prostate cancer cells. Following injection of the compound, Hyder found that the molecule was effective in reducing tumor growth.

These findings suggest that the potential cholesterol drug, when used in combination with commonly used chemotherapeutic drugs, could represent a new therapeutic approach in the fight against prostate cancer, Hyder said.

Cholesterol-fighting drug molecule can kill prostate cancer cells: Standard treatment for prostate cancer can include chemotherapy that targets receptors on cancer cells. However, drug-resistant cancer cells can emerge during chemotherapy, limiting its effectiveness as a cancer-fighting agent. Researchers at the University of Missouri have proven that a compound initially developed as a cholesterol-fighting molecule not only halts the progression of prostate cancer, but also can kill cancerous cells.

Traditional Chinese medicinal plant produces compounds that may help to kill human cancers

New research led by Professor Cathie Martin of the John Innes Centre has revealed how a plant used in traditional Chinese medicine produces compounds which may help to treat cancer and liver diseases.

The Chinese skullcap, Scutellaria baicalensis - otherwise known in Chinese medicine as Huang-Qin - is traditionally used as a treatment for fever, liver and lung complaints.

Previous research on cells cultured in the lab has shown that certain compounds called flavones, found in the roots of this plant, not only have beneficial anti-viral and anti-oxidant effects, but they can also kill human cancers while leaving healthy cells untouched. In live animal models, these flavones have also halted tumour growth, offering hope that they may one day lead to effective cancer treatments, or even cures.

As a group of compounds, the flavones are relatively well understood. But the beneficial flavones found in Huang-Qin roots, such as wogonin and baicalin, are different: a missing - OH (hydroxyl) group in their chemical structure left scientists scratching their heads as to how they were made in the plant.

Professor Cathie Martin, lead author of the paper published in Science Advances, explains: "Many flavones are synthesised using a compound called naringenin as a building block. But naringenin has this -OH group attached to it, and there is no known enzyme that will remove it to produce the flavones we find in Huang-Qin roots."

Working in collaboration with Chinese scientists, Cathie and her team explored the possibility that Huang-Qin's root-specific flavones (RSFs) were made via a different biochemical pathway. Step-by-step, the scientists unravelled the mechanism involving new enzymes that make RSFs using a different building block called chrysin.

"We believe that this biosynthetic pathway has evolved relatively recently in Scutellariaroots, diverging from the classical pathway that produces flavones in leaves and flowers, specifically to produce chrysin and its derived flavones," said Professor Martin.

"Understanding the pathway should help us to produce these special flavones in large quantities, which will enable further research into their potential medicinal uses. It is wonderful to have collaborated with Chinese scientists on these traditional medicinal plants. Interest in traditional remedies has increased dramatically in China since Tu Youyou was awarded the Nobel Prize for Medicine in 2015 for her work on artemisinin. It's exciting to consider that the plants which have been used as traditional Chinese remedies for thousands of years may lead to effective modern medicines."

Traditional Chinese medicinal plant produces compounds that may help to kill human cancers: New research led by Professor Cathie Martin of the John Innes Centre has revealed how a plant used in traditional Chinese medicine produces compounds which may help to treat cancer and liver diseases.

Palovarotene drug may prevent multiple musculoskeletal problems linked with FOP

We know that, Palovarotene (R-667, RO-3300074) is a highly selective retinoic acid receptor gamma (RAR-γ) agonist that is under investigation as a potential treatment for fibrodysplasia ossificans progressiva (FOP), an ultra-rare and severely disabling genetic disease characterized by extra-skeletal bone formation (heterotopic ossification or HO) in muscle and soft tissues. 

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Palovarotene is being developed by Clementia Pharmaceuticals and was granted Fast Track and orphan drug designations by the United States Food and Drug Administration for the treatment of FOP and Orphan Medicinal Product Designation by the European Medicines Agency (EMA) in 2014. Phase II clinical studies are currently underway

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New research in laboratory animals suggests that the drug palovarotene may prevent multiple skeletal problems caused by a rare but extremely disabling genetic bone disease, and may even be a candidate for use in newborn babies with the condition. Scientists at The Children's Hospital of Philadelphia, who previously repurposed the drug to prevent excess bone formation in animal models of fibrodysplasia ossificans progressiva (FOP), have extended that research in animals carrying the exact human disease-causing mutation.

In humans with FOP, an activating mutation in the ACVR1 gene triggers extraskeletal cartilage and bone formation and accumulation starting in early childhood. The extraskeletal bone occurs in muscles and other tissues where it does not belong. This pathological process, collectively called heterotopic ossification (HO), causes progressive loss of skeletal motion and hampers breathing and swallowing.

Currently untreatable and painful, FOP often causes death early in adulthood.

"This work represents a big step toward therapy," said co-study leader, Maurizio Pacifici, Ph.D., a developmental biologist and director of Orthopedic Research in the Division of Orthopedic Surgery at The Children's Hospital of Philadelphia (CHOP). "The mice used in this study were engineered to carry the human mutation that causes FOP, and the drug showed powerful and comprehensive benefits for skeletal growth and function in addition to inhibiting HO. If these results translate to humans, we may be able to treat children with FOP early in life, before the disease progresses."

The research appeared online March 12 in the Journal of Bone and Mineral Research.

Palovarotene drug may prevent multiple musculoskeletal problems linked with FOP: New research in laboratory animals suggests that the drug palovarotene may prevent multiple skeletal problems caused by a rare but extremely disabling genetic bone disease, and may even be a candidate for use in newborn babies with the condition.