Combination therapy may be better than radiotherapy alone to treat aggressive brain cancer

It is known that radiotherapy is effective in damaging brain tumors, but radiotherapy does not fully kill the tumor because the cancer cells can repair themselves and keep living.  Researchers at Sidney Kimmel Cancer Center are now testing a combination of radiotherapy and a drug called panobinostat that makes the cancer cells unable to repair themselves. The researchers are testing the combination on aggressive, recurrent brain cancer.  They feel that panobinostat makes radiotherapy much more effective.

Currently, there is no standard treatment for gliomas other than radiation.  Most patients will not live very long.  The efficacy of panobinostat is hopeful for improving survival rates.

Panobinostat was approved for use in 2015 for treatment of multiple myeloma, and now it is being tested to treat other cancers. It is a histone deacetylase inhibitor; it works by modifying RNA to change protein production and turns off RAD51 (a DNA repair enzyme) which upsets cancer growth.

Researchers found that the highest doses of panobinostat were well tolerated and improved survival.  Overall, researchers found that this cancer drug was very safe and that there is promise to treat other drugs.

The question I will pose is:  If the drug works by changing protein production and turning off DNA repair enzymes, wouldn’t you think it would cause bad side effects?  Yet it was shown to be very safe at even the highest doses.

 

 

Wenyin Shi, Joshua D. Palmer, Maria Werner-Wasik, David W. Andrews, James J. Evans, Jon Glass, Lyndon Kim, Voichita Bar-Ad, Kevin Judy, Christopher Farrell, Nicole Simone, Haisong Liu, Adam P. Dicker, Yaacov R. Lawrence.Phase I trial of panobinostat and fractionated stereotactic re-irradiation therapy for recurrent high grade gliomas. Journal of Neuro-Oncology, 2016; DOI:10.1007/s11060-016-2059-3

DNA ‘Trojan horse’ smuggles drugs into resistant cancer cells – Cells mistake DNA casing for food, consume drugs and die

Researchers at Ohio State University are working on a new method to treat resistant cancer cells.  Since the cancer cells are resistant, they are no longer affected by the cancer drugs the patient has been taking.  However, when researchers encapsulated one of the resistant drugs in DNA, the resistant cells mistook the drug for food, ate it, and died.  This technique is called “DNA Origami” and it has only been used to treat solid tumors, never before used to treat drug-resistant leukemia cells.

The researchers have been testing this method in mice, and hope to move onto humans within a few years.  The researchers are studying acute myeloid leukemia (AML) that is resistant against the drug daunorubicin.  When daunorubicin enters an AML cell, the cell recognizes them and pumps them back out through openings in the cell wall, much like a sump pump.

The new method they are exploring hiding is like a “trojan horse” becuase daunorubicin is hid inside a DNA shell that can bypass the pumps so they can’t eject the drug from the cell.  The drug accumulates and then causes the cell to die.

There is also hope to tailor these structures to make them deliver drugs selectively to cancer cells and not to other parts of the body where they can cause side effects.

DNA origami nanostructures have great potential for drug delivery.  The drug the researchers were studying in this research worked by going into the cancer cell’s DNA and preventing it from replicating.

 

The question I will ask is:  Knowing that DNA origami has been used to treat solid tumors but never before leukemia, do you think this cancer treatment method will work in other types of cancers? Why or why not?

 

 

 

Patrick D. Halley, Christopher R. Lucas, Emily M. McWilliams, Matthew J. Webber, Randy A. Patton, Comert. Kural, David M. Lucas, John C. Byrd, Carlos E. Castro. DNA Origami: Daunorubicin-Loaded DNA Origami Nanostructures Circumvent Drug-Resistance Mechanisms in a Leukemia Model (Small 3/2016). Small, 2016; 12 (3): 307 DOI:10.1002/smll.201670014

New front opens in battle against stroke – Medicinal approach cuts recurrence risk by 24 percent in stroke patients

Medical scientists discovered that an already-known drug showed to reduce the risk of stroke or heart attack by almost a quarter in patients who had previously suffered a stroke or mini-stroke!  The drug is pioglitazone, which some of you know is used to treat diabetes.  Pioglitazone works by making the body less insulin resistant, and researchers found that insulin resistance puts you at a risk for heart attack and stroke.

The typical drugs to treat stroke are blood thinners and anticoagulants.  Statins and blood pressure medications may also help in some cases.  It is unusual for a diabetes drug to be used to treat heart attack or stroke.

Blood thinners, statins, and blood pressure management medications have all been shown to significantly reduce the risk for stroke.  However, researchers wanted to explore another risk factor:  insulin resistance, also called “pre diabetes.”

Researchers showed that insulin resistance was associated with a higher risk of stroke and heart attack.  Therefore, they tested pioglitazone, a diabetes drug that can help reduce insulin resistance.

The results of the five-year, double-blind trial of pioglitazone versus a placebo, was that the team found that patients receiving the drug had 24% fewer incidents of either stroke or heart attack.  This is important because pioglitazone may now be used to prevent diabetes as well as heart attack / stroke.

My question is:  Knowing the side effects of pioglitazone, would you been willing to reccommend this medication as a preventative measure? For example, if the patient has a family history of heart attack / stroke, but has not had one?  Do you think the side effects outweigh the benefit of taking the drug as a preventative measure?

 

 

Walter N. Kernan, Catherine M. Viscoli, Karen L. Furie, Lawrence H. Young, Silvio E. Inzucchi, Mark Gorman, Peter D. Guarino, Anne M. Lovejoy, Peter N. Peduzzi, Robin Conwit, Lawrence M. Brass, Gregory G. Schwartz, Harold P. Adams, Leo Berger, Antonio Carolei, Wayne Clark, Bruce Coull, Gary A. Ford, Dawn Kleindorfer, John R. O’Leary, Mark W. Parsons, Peter Ringleb, Souvik Sen, J. David Spence, David Tanne, David Wang, Toni R. Winder. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. New England Journal of Medicine, 2016; 160217112012002 DOI: 10.1056/NEJMoa1506930

Study suggests sildenafil may relieve severe form of edema in swimmers

Swimmers and divers who are prone to pulmonary edema in cold water (which can be deadly), could benefit from a dose of sildenafil, which is more commonly known by its brand name, Viagra®.

We all know that sildenafil can be used to treat erectile dysfunction in men, but it is also used to treat pulmonary arterial hypertension.  It works by dilating blood vessels.  In cold water swimmers and divers, their blood vessels rapidly constrict; this can lead to pooling of blood in the heart and lungs.

Athletes and swimmers with SIPE (swiming-induced pulmonary edema) cough up blood, have trouble breathing, and have low blood oxygen.  The symptoms may go away over 24 hours, but the condition can be fatal.

Researchers put 10 SIPE-susceptible athletes into a pool that mimicked the conditions that trigger SIPE.  They then compared those 10 athletes to 20 other athletes who had no history of SIPE.  The SIPE-susceptible athletes had higher pulmonary arterial pressure and pulmonary artery wedge pressure during the underwater exercise.

When the SIPE susceptible athletes were given sildenafil and performed the same exercises, their pressures were no longer as elevated.

In the words of Moon, one of the researchers, the conclusion of the study is that “It appears that the drug, which dilates the blood vessels, could be creating more capacity in the blood vessels in the arms and legs, reducing the tendency for blood to redistribute to the thorax, and therefore reducing the high pressure in the pulmonary vessels.”

This can be a promising lead on a drug that can make swimming/diving possible for people who are prone to SIPE.

The question I will pose is:  Is it better to take drugs as a preventative measure, or to take them after symptoms have developed?

 

 

Richard E. Moon, Stefanie D. Martina, Dionne F. Peacher, Jennifer F. Potter, Tracy E. Wester, Anne D. Cherry, Michael J. Natoli, Claire E. Otteni, Dawn N. Kernagis, William D. White, and John J. Freiberger. Swimming-Induced Pulmonary Edema: Pathophysiology and Risk Reduction With Sildenafil. Circulation: Journal of the American Heart Association, February 2016 DOI:10.1161/CIRCULATIONAHA.115.019464

Appalachia continues to have higher cancer rates than the rest of US, but gap is narrowing

Appalachia, a region of the US that contains Pittsburgh (Appalachia stretches from New York to Mississippi and contains 25 million people), has higher cancer rates than the rest of the nation; contributing factors are higher tobacco use, lower socioeconomic status, and patient health care utilization.

In 2007, the CDC’s National Program of Cancer Registries (NPCR) published a study that showed higher cancer rates in Appalachia between 2001 and 2003; however, the study had some shortcomings.  A more thorough study was done between 2004 and 2011, and it contained data from both Appalachian populations and non-Appalachian populations.  This study was able to analyze 100% of the US population by using data from the National Program of Cancer Registries (NPCR) and data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program.

The data from the Appalachian population was divided into three groups:

  • residents from three regions (counties in the north, central, and south Appalachia)
  • by gender, race (black and white)
  • by Appalachian Regional Commission-designated economic status (distressed, at-risk, transitional, competitive, and attainment

This was then compared with data on the non-Appalachian population, and the results showed that “the cancer incidence rates were elevated among Appalachians regardless of how they were categorized.”

Even though Appalachia has a higher incidence of cancer as compared to the rest of the country, the gap is narrowing (with the exceptions of cancers of the oral cavity and pharynx, larynx, lung and bronchus, and thyroid).  It is promising to note that the gap between Appalachia and non-Appalachia has narrowed since 2007.

This study is important because it shows the importance of screening for cancers and diseases for at-risk populations.  It also shows the importance of lifestyle.  For example, not using tobacco products will make you less at risk for cancer.  And if you do use tobacco products, it is important to be screened for cancers more regularly since you are more at risk.

The question I will pose is:  What initiatives can we take to decrease the rate of cancer in Appalachia?

 

Reda J. Wilson, A. Blythe Ryerson, Simple D. Singh, and Jessica B. King.Cancer Incidence in Appalachia, 2004–2011. Cancer Epidemiol Biomarkers Prev, February 2016 DOI: 10.1158/1055-9965.EPI-15-094

Long-term benefits of ‘senolytic’ drugs on vascular health in mice

Since cardiovascular disease is the leading cause of death in the US, it is a popular research topic.  Researchers at the Mayo Clinic discovered significant improvements in the vascular systems of mice after repeated treatments of removing senescent cells (cells that are damaged and no longer function properly). They did this by using senolytic drugs to clear these damaged cells from the body.

This is the first study to show regular and continual clearance of senescent cells improves age-related vascular conditions, and that this method may be applicable in a human population.  If so, it would greatly reduce cardiovascular disease and death.

This study looked at the impact that these senolytic drugs (dasatinib and quercetin) had on blood vessels in mice over a three month period.  A separate set of mice had plaque buildup in their vessel walls, and after being treated with these drugs, it was found that calcifications were reduced on the interior of vessel walls, thus improving vascular health.

The research team is hoping that one day, removal of senescent cells will be a normal part of therapy along with traditional management of cardiovascular risk factors.

The question I will pose is:  Is removal of senescent cells as effective as drugs used to treat plaque buildup?  If it is not, is it worth investing time and money in?

 

 

Carolyn M. Roos, Bin Zhang, Allyson K. Palmer, Mikolaj B. Ogrodnik, Tamar Pirtskhalava, Nassir M. Thalji, Michael Hagler, Diana Jurk, Leslie A. Smith, Grace Casaclang-Verzosa, Yi Zhu, Marissa J. Schafer, Tamara Tchkonia, James L. Kirkland, Jordan D. Miller. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell, 2016; DOI: 10.1111/acel.12458

Allergy shots effective for baby boomers suffering from seasonal allergies

In recent years, there has been an increased number of people suffering from allergies, especially people who are “baby boomers.” A new study shows that immunotherapy, or allergy shots, reduced symptoms by 55% after three years of therapy, and decreased the amount of medication needed for relief of symptoms by 64%.

This study is important because it was thought that allergy shots would be not as effective in the older population, since they have an aging immune system, but the data shows that allergy shots are still very effective.

This study is also important because older people tend to have chronic diseases, and it makes it difficult to manage allergies.  Additionally, hay fever is more common in patients over age 65.

The study was published in the Annals of Allergy, Asthma and Immunology.  The patients were 60 people who suffered from hay fever, aged 65 to 75 years.  The 60 people were sorted into two groups.  The first group received allergy shots over three years, and the second group received placebo.  The research showed that the allergy shots were extremely effective in the older population.

The question I will pose is:  Is it more beneficial for someone to receive three years of consistent allergy shots? Or is it more beneficial to take an allergy pill to manage symptoms?  Also, if the shots only reduce symptoms by 55% after three years, is it really worth the time and cost?

 

 

Andrzej Bozek, Krzysztof Kolodziejczyk, Anna Krajewska-Wojtys, Jerzy Jarzab. Pre-seasonal, subcutaneous immunotherapy: a double-blinded, placebo-controlled study in elderly patients with an allergy to grass. Annals of Allergy, Asthma & Immunology, 2016; 116 (2): 156 DOI:10.1016/j.anai.2015.12.013

Diabetes drug shown to help body rebuild after heart attack

Since heart disease is the leading cause of illness in diabetic patients, researchers have decided to explore the effects that a diabetes drug, metformin, has on the heart.

The study was funded by the Diabetes Research and Wellness Foundation, Queen Elizabeth Hospital Diabetes Charity, Newcastle University and King Abdulaziz University.

Researchers used stem cells from the umbilical cord to construct a model simulating a heart attack in a lab.  They found three discoveries:

  1. New blood vessel formation is essential to heart attack recovery, and that metformin helps new blood vessels to form.
  2. The research also shows that during a heart attack, there is a lack of oxygen in the presence of high glucose levels, and metformin reverses that process.
  3. It was also found that metformin affects several genes that are important in the growth of new blood vessels.

Since not all diabetic patients can take metformin, it is hopeful that this discovery will lead to research and development of new drugs, since there is a better understanding of how metformin works.  There is also demand for improved treatment for diabetic patients so that they may survive a heart attack.

This study is significant because the research can instantly make a difference in treatments by offering a new approach to heart disease in diabetic patients.  The study is also the first report describing the effect of the physiological concentration of metformin as seen in patients.

Going forward, it is hopeful that clinical trials will be started to further investigate metformin’s effect on heart attack recovery in patients.

The question I will pose is: Since biguanides work in similar ways, do you think that other biguanides will help in heart attack recovery?

 

Sherin Bakhashab, Fahad W. Ahmed, Hans-Juergen Schulten, Ayat Bashir, Sajjad Karim, Abdulrahman L. Al-Malki, Mamdooh A. Gari, Adel M. Abuzenadah, Adeel G. Chaudhary, Mohammed H. Alqahtani, Sahira Lary, Farid Ahmed, Jolanta U. Weaver. Metformin improves the angiogenic potential of human CD34 cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction. Cardiovascular Diabetology, 2016; 15 (1) DOI:10.1186/s12933-016-0344-2

High-dose influenza vaccine in older adults

Older adults (those over age 65) are more greatly affected by illnesses/infections than the younger population. This is due to changes in immunity and immunosenesence during aging. For this reason, the older population benefits more from a high-dose flu shot.

Antibody levels correlate to vaccine effectiveness, and older patients have lower antibody levels. 31 studies found that older adults were 2-4 times less likely to produce sufficient protection against influenza.

Fluzone High Dose is am HD trivalent influenza vaccine from Sanofi Pasteur. It gained FDA approval in 2009. A report showed that the HD vaccine resulted in a 24.2% improvement in older adults as compared to the standard (SD) vaccine. This shows that the HD vaccine prevents influenza more in older adults. Another study comparing the effectiveness of the HD and SD vaccines was performed in a long-term care facility; researchers concluded that the geometric mean titers for those who received the HD vaccine were significantly higher than for those who received the SD vaccine.

Medicare data supported the same viewpoint. Over the 2012-2013 influenza season, investigators identified 929,730 individuals who received the HD influenza vaccine and 1,615,545 individuals who received the SD influenza vaccine. Results showed that those who received the HD influenza vaccine were 22% less likely to have influenza infections as well as 22% less likely to be admitted to the hospital for influenza. However, a study at the Veteran’s Administration showed no differences in hospitalization rates for HD and SD groups.

The HD flu shot is safe. The phase II and III studies “noted some increase in reported adverse events, but not at a level that merited concern.” The most common adverse reaction was pain at the injection site. “The relative risk of developing at least one serious adverse event after receiving the HD versus SD influenza vaccine was 0.92.”

Although the cost of the HD vaccine is about twenty dollars higher than the SD vaccine, the HD vaccine is associated with cost-savings in the long run. By preventing influenza, it results in less hospital visits and less medicine. It reduces medical costs by about $120 on average.

In summary, both the SD and the HD flu shots are appropriate for adults. The HD flu shot has shown greater efficacy in the older population, and is associated with cost savings. It is important for patients to get their flu shot annually and to get vaccinated well before flu season, since antibodies that provide protection to the body may take 2 weeks or more after vaccination to form.

The question I will pose is:  Can the HD flu shot be given to younger adults as well? And if not, why?

 

Wang JM, Orly V, Joseph AZ. High-dose influenza vaccine in older adults. Journal of the American Pharmacist’s Association. 2016;56:95-97  http://www.japha.org/article/S1544-3191(15)00014-X/fulltext