Multitarget TB drug could treat other diseases, evade resistance -- ScienceDaily

A drug under clinical trials to treat tuberculosis could be the basis for a class  of broad-spectrum drugs that act against various bacteria, fungal infections and parasites, yet evade resistance, according to a study. The team determined the different ways the drug SQ109 attacks the tuberculosis bacterium, how the drug can be tweaked to target other pathogens from yeast to malaria  and how targeting multiple pathways reduces the probability of pathogens becoming resistant.

Led by U. of I. chemistry professor Eric Oldfield, the team determined the different ways the drug SQ109 attacks the tuberculosis bacterium, how the drug  can be tweaked to target other pathogens from yeast to malaria -- and how targeting multiple pathways reduces the probability of pathogens becoming resistant. SQ109 is made by Sequella Inc., a pharmaceutical company. 

"Drug resistance is a major public health threat," Oldfield said. "We have to make new antibiotics, and we have to find ways to get around the resistance problem. And one way to do that is with multitarget drugs. Resistance in many cases arises because there's a specific mutation in the target protein so the drug will no longer bind. Thus, one possible route to attacking the drug resistance problem will be to devise drugs that don't have just one target, but
two or three targets."

Oldfield read published reports about SQ109 and realized that the drug would likely be multifunctional because it had chemical features similar to those found in other systems he had investigated. The original developers had identified one key action against tuberculosis -- blocking a protein involved in building the cell wall of the bacterium -- but conceded that the drug could have other actions within the cell as well since it was found to kill other bacteria and
fungi that lacked the target protein. Oldfield believed he could identify those actions  and perhaps improve upon SQ109. 

"I was reading Science magazine one day and saw this molecule, SQ109, and I thought, that looks a bit like molecules we've been studying that have multiple targets," Oldfield said. "Given its chemical structure, we thought that some of the enzymes that we study as cancer and antiparasitic drug targets also could be SQ109 targets. We hoped that we could make some analogs that would be more potent against tuberculosis, and maybe even against parasites.

More : http://pubs.acs.org/doi/abs/10.1021/jm500131s

Multitarget TB drug could treat other diseases, evade resistance

Hepatitis C treatment cures over 90 percent of patients with cirrhosis...

Tweelve weeks of an investigational oral therapy cured hepatitis C infection in more than 90 percent of patients with liver cirrhosis and was well tolerated by these patients, according to an international study that included researchers from UT Medicine San Antonio and the Texas Liver Institute. Historically, hepatitis C cure rates in patients with cirrhosis (liver scarring) have been lower than 50 percent and the treatment was not safe for many of these patients.

Hepatitis C treatment cures over 90 percent of patients with cirrhosis  

New molecules working against Alzheimer's discovered -- ScienceDaily

New molecules working against Alzheimer's discovered  

Researchers of the Unit of Medicine Design and Molecular Topology (Department of Physics Chemistry) of the University of Valencia (UV) have discovered eight new active molecules against Alzheimer by a novel mechanism of action, different to the currently used medicines. The work has just been published in PLoS One.

Doxorubicin alone or with ifosfamide for treating soft tissue sarcoma? -- ScienceDaily

IN CONTINUATION OF MY UPDATE ON DOXORUBICIN

Dr. Ian Judson of the Royal Marsden Hospital in London and coordinator of this study says, "Our clinical trial was designed to compare combination treatment with doxorubicin and ifosfamide to treatment with doxorubicin alone, and our results show that the combination chemotherapy did not improve overall survival. So, if the goal of treatment is to control the disease, then administering doxorubicin alone is appropriate. On the other hand, if the goal is to shrink the tumor before another intervention or to relieve symptoms, then combination treatment is justifiable. The observed lack of improvement in overall survival points to the need for better treatments for patients with this disease."

For some thirty years, patients with soft tissue sarcomas have been treated with doxorubicin and ifosfamide, but few studies have directly assessed whether doxorubicin should be administered alone or in combination with ifosfamide. EORTC trial 62012 assessed whether the addition of ifosfamide to doxorubicin improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone.

Doxorubicin alone or with ifosfamide for treating soft tissue sarcoma?  

Small peptides as potential antibiotics -- ScienceDaily

Small peptides as potential antibiotics 

Eating fruits, vegetables linked to healthier arteries later in life

Women who reported consuming the most fruits and vegetables (eight to nine servings a day for a 2,000-calorie diet) in their 20s were 40 percent less likely to have calcified plaque in their arteries in their 40s compared with those who ate the least amount (three to four servings a day) during the same time period. This association persisted even after researchers accounted for other lifestyle behaviors, as well as for their current-day diets, further demonstrating the role dietary patterns at younger ages may play. 

"These findings confirm the concept that plaque development is a lifelong process, and that process can be slowed down with a healthy diet at a young age," Miedema said. "This is often when dietary habits are established, so there is value in knowing how the choices we make in early life have lifelong benefits."

Surprisingly, the same benefit did not hold true for men, which warrants further investigation.

"Several other studies have also suggested that a diet high in fruits and vegetables is less protective in men, but we do not have a good biological reason for this lack of association," Miedema said, adding that the study had less power to evaluate men (62.7 percent were female vs. 37.3 percent male).

The study included 2,508 participants from the ongoing government-sponsored Coronary Artery Risk Development in Young Adults (CARDIA) study, which is evaluating how heart disease develops throughout adulthood. CARDIA began in the mid-1980s with a group of men and women 18-30 years of age and has collected extensive data on medical, socioeconomic, psychosocial and behavioral characteristics.

Eating fruits, vegetables linked to healthier arteries later in life  

Oral cancer drug improves outcomes in women with resistant gynecologic cancers

PARP inhibitors prevent cancer cells from repairing themselves after experiencing DNA damage (for example from chemotherapy or radiation). Research has previously shown that veliparib is effective in combination with chemotherapy, but little data was available to indicate whether veliparib was effective as a single agent. Results of this multicenter trial suggest that it is.

"One criticism of the PARP drugs is they are not active in patients who have developed resistance to other therapies, but we found veliparib appears to be effective in some platinum-resistant patients with recurrent or persistent disease," said Robert L. Coleman, MD, lead author of the study and professor and vice chair of clinical research at the University of Texas MD Anderson Cancer Center, Houston. "Most of these patients have run out of treatment options, and it is very hopeful to potentially have another therapy to offer them."

In the study, 50 patients with BRCA gene mutations treated at one of 18 centers took veliparib by mouth twice a day. The median number of monthly treatment cycles was six (ranging from one to 22). Overall, 13 patients (26 percent) responded positively to the therapy, meaning the tumors shrank in size, including two patients in whom the tumors disappeared completely. In addition, disease was stabilized for more than four months in nearly half of the women (24).

"Patient recruitment can be a problem for many clinical trials, however, this one filled up very quickly, which reflects that women and their doctors understand that PARP inhibitors hold real promise," said Dr. Coleman.

Oral cancer drug improves outcomes in women with resistant gynecologic cancers

Peach extract prevents breast cancer metastasis in mice

AgriLife Research scientists say that the mixture of phenolic compounds present in the peach extract are responsible for the inhibition of metastasis, according to the study, which was this month published in the Journal of Nutritional Biochemistry.

“Cancer cells were implanted under the skin of mice with an aggressive type of breast cancer cells, the MDA-MB-435, and what we saw was an inhibition of a marker gene in the lungs after a few weeks indicating an inhibition of metastasis when the mice were consuming the peach extract,” said Dr.  Luis Cisneros-Zevallos, a food scientist for AgriLife Research in College Station. “Furthermore, after determining the dose necessary to see the effects in mice, it was calculated that for humans it would be equivalent to consuming two to three peaches per day.”

Ref : http://today.agrilife.org/2014/03/25/texas-researcher-peaches-inhibit-breast-cancer-metastasis-in-mice/

Peach extract prevents breast cancer metastasis in mice

Cancer treatment revolution potential with new drug

A new study at the University of Warwick, published today in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body's natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.

Called ZL105, the drug is a compound based on the precious metal iridium (organoiridium(III) complex [(η⁵-Cp^xbiph)Ir(phpy)(Cl)]). The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.

Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said "The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell 'power-house'. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects."

Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.

Study co-author Professor Peter J. Sadler said "Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments."

"Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.

"In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by
patients" argues Professor Sadler.

This research could also lead to substantial improvements in cancer survival rates. "Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells" said Dr Romero-Canelon.

Cancer treatment revolution potential with new drug

Natural plant compounds may assist chemotherapy

Plant compounds present in carrots and  parsley  may  one   day support  more  effective

delivery  of  chemotherapy  treatments,  new  research  has  found. Specific plant compounds are able to inhibit transport mechanisms in the body that select what

compounds are absorbed into the body, and eventually into cells.  These same transport 

mechanisms are known to interfere with cancer chemotherapy treatment.

Natural plant compounds may assist chemotherapy 

Adult cancer drugs show promise against an aggressive childhood brain tumor

Researchers relied on mice with group 3 medulloblastoma grown from patient tumors. The mice were developed in Roussel’s laboratory and are a powerful tool for testing the effectiveness of drugs against human tumors. Researchers used the mice to show that pemetrexed and gemcitabine worked against human group 3 tumors and that the drugs could be used in combination with existing chemotherapy agents to boost treatment effectiveness without undue risk. Cisplatin and cyclophosphamide were the other drugs used in this study.

“The finding provides a strong rationale for combination therapy with pemetrexed and gemcitabine for treatment of group 3 medulloblastoma,” Roussel said. Researchers found no evidence that mouse tumor cells develop resistance to the drugs.

Pemetrexed works by disrupting the ability of cancer cells to proliferate. Gemcitabine kills cells by triggering their suicide pathway. Researchers also found evidence the drugs work specifically against group 3 medulloblastoma. The drugs did not extend survival of mice with a different medulloblastoma subtype.

The study builds on previous St. Jude research that has helped to revolutionize understanding of the origins of medulloblastoma and laid the foundation for a new era of risk-based therapy. The goal is to maximize the likelihood of a cure and minimize long-term side effects. The approach combines clinical factors and the molecular markers associated with the different medulloblastoma subtypes to guide how radiation and chemotherapy are combined with surgery.

Adult cancer drugs show promise against an aggressive childhood brain tumor  

New combination drug therapy proves very effective in hepatitis C treatments

A new 12-week single tablet regimen of ledipasvir and sofosbuvir have proven to be highly effective in treating a broad range of patients with HCV genotype 1, a form of the virus found in up to 75 percent of infections, according to results unveiled today at the European Association for the Study of the Liver and published simultaneously online by the New England Journal of Medicine.

Between 94 percent and 99 percent of patients were cured of hepatitis C and results were similar in patients who have never been treated and for those who had previously been treated with a combination of peginterferon and ribavirin, the current course that carries sometimes significant side effects.

“Eliminating interferon and ribavirin from treatment regimens is expected to reduce the incidence and severity of adverse events, to simplify the treatment of patients with HCV infection and to provide an option for patients who are ineligible for the current interferon-based treatments,” said Nezam Afdhal, MD, the senior author of the studies, Director of the Liver Center at Beth Israel Deaconess Medical Center and a Professor of Medicine at Harvard Medical School.

Hepatitis C is an infectious disease primarily affecting the liver and which can lead to scarring and cirrhosis and is transmitted primarily through blood transfusions (prior to 1991), intravenous drug use, poorly sterilized medical equipment and sexual transmission.. After exposure 80 percent of patients develop a chronic hepatitis which can lead to cirrhosis, liver failure and liver cancer and hepatitis C is the most common cause for liver transplantation in the US.

Prior treatments have been with interferon which is an injectable cytokine released in response to viral infections. Interferon is combined with other antiviral agents and needs to be used for up to 48 weeks to cure hepatitis C. but is associated with number of side effects, including influenza-like symptoms depression and anemia. Many patients are ineligible for these interferon-based therapies.

“The real advances seen in the Ion trials is that the sofosbuvir-ledipasvir combination tablet enables us to treat almost all genotype 1 patients with a short duration of 8-12 weeks of treatment expanding the treatment pool and increasing the overall cure rate,” said Afdhal.

New combination drug therapy proves very effective in hepatitis C treatments

Statins could ease coughing in lung disease patients, study finds -- ScienceDaily

In continuation of my update on Statins

Common cholesterol-lowering drugs could provide relief to patients suffering from a chronic lung disease, a study has shown. The drugs -- known as statins -- were found to help alleviate the chronic coughing associated with the disease for some patients.

Statins could ease coughing in lung disease patients, study finds 

Researchers develop new eco repellent that stops mosquitoes from attacking humans

Researchers develop new eco repellent that stops mosquitoes from attacking humans

In the battle against malaria researchers at the University of Neuchâtel (Switzerland) have developed a new eco repellent that stops mosquitoes from attacking humans. A new mixture of extracted essential oils seems to be as effective in keeping off mosquitoes as common repellents like Deet for example. The advantage of the new substance: it is fully biodegradable and therefore comes also with fewer side effects.

The Swiss scientists who were conducting their studies within the European research project “ENAROMaTIC” are convinced that their discovery is just the beginning of a new wave of breakthroughs in this field. In the future, natural extracts of essential oils could play an important role in limiting the number of victims caused by disease-carrying insect vectors.

Research produces strong evidence for new class of antidepressant drugs | The University of Manchester

Galanin is a neuropeptide (a small protein) that was discovered and investigated over 30 years ago by various groups including the Swedish scientist Tomas Hokfelt. He is one of the senior authors of the paper published in the journal PNAS.

Professor Hokfelt and others made the fundamental discovery that neurones can release peptides alongside their classical transmitters and that galanin and noradrenaline are one such pair. Both have long been implicated in pain and stress and therefore depression but in the past it had been difficult to study peptides in humans.

The new research by scientists from Sweden, Hungary and the UK demonstrates that galanin is an important stress mechanism in the human brain that influences how sensitive or resilient people are to psychosocial stress.

Lead author Gabriella Juhasz, who is a Research Fellow at the University of Manchester and the Semmelweis University in Budapest, said: “Our research shows that some versions of the gene coding for galanin protect against the risk of depression and anxiety but only in people who have experienced early life neglect or trauma, or recent adverse events.

“Furthermore, the three genes for the three receptors through which galanin acts also influence the risk of depression in people experiencing early or recent life adversity. Crucially, all the galanin related genes are widely separated on different chromosomes and the odds are stacked against four random genes acting in the same way by chance.”

Results from the research indicate that although the results are statistically reliable, galanin effects modify the substantial effects of stress by only a few percent. Indeed the moderate overall genetic influence (about 35%) on depression is likely to be mediated by many small genetic effects interacting with each other and with psychosocial factors converging on stress mechanism in brain.

Co-author Professor Bill Deakin, from the University of Manchester, said: “The findings provide a strong reason to develop drugs that modify galanin functioning as a new class of antidepressant drug. And new drugs are badly needed as almost all commonly prescribed antidepressants act on serotonin and they are often not very effective.

“Our research confirms what previous reports have shown about the variation in the serotonin ‘transporter’ gene and how it influences the risk of depression. We found that the galanin effects are substantially greater than the effects of serotonin.”

Research produces strong evidence for new class of antidepressant drugs | The University of Manchester