Mycobacterium in olive oil for cancer treatment

Since then, they have been looking for ways to improve the immunotherapeutic activity of M. brumae through the design of different emulsions which can increase the homogeneity and stability, and therefore the efficacy, of the mycobacteria solutions when introduced into the body.

Researchers found a way to reduce the clumps produced naturally when mycobacteria cells, which possess a high content of lipids in their walls, are introduced into the usual aqueous solutions used for intravesical instillation in bladder cancer patients. This clumping may interfere with the interaction of the mycobacteria-host cells and negatively influence their antitumor effects.

Of the emulsions tested, the one based on olive oil induce a prominent immune response in both in vitro and in vivo experiments. Olive oil preserves the viability of the mycobacteria and provided higher anti-clumping rates, and this indicates favourable conditions for reaching the bladder.

According to Esther Julián, "these results highlight the potential of the olive oil-based emulsion as a promising delivery vehicle for the mycobacterial treatment of bladder cancer."

The work, recently published in the journal Scientific Reports, from the publishers of Nature, was conducted by scientists from the Department of Genetics and Microbiology of the Faculty of Biosciences, the Department of Animal Medicine and Surgery of the Faculty of Veterinary Medicine, and the Microbiology Service of the UAB, together with the Bacterial Infections and Antimicrobian Therapies group at the IBEC, Barcelona.

Is Avocado Good for Diabetes?

  

The humble avocado, shunned for years during the fat-free diet craze of the 1990s, may have finally hit its stride. No longer just for guacamole, this nutritious fruit is popping up as a healthy addition to various diet plans.

But can people with diabetes eat this food? It turns out that avocados are not only safe for people with diabetes, but they may be downright beneficial. Research shows that avocados offer many ways to help people manage their diabetes and improve their overall well-being.

Diet and diabetes

A healthy diet is critical for people with diabetes. The foods that they eat each day can have a considerable impact on how they feel and how well their diabetes is controlled.

In general, people with diabetes should eat foods that help control blood sugar levels and that offer health benefits such lowering blood pressure and cholesterol. This is one of the best ways to keep diabetes under control, avoid complications, and lead the healthiest life possible.

Avocados are an excellent choice for people with diabetes because they offer all these benefits - and possibly more.

Blood sugar control is critical for people who have diabetes. A physician or dietitian may advise patients to choose foods that are lower in carbohydrates and sugar. They may also recommend foods that help control blood sugar spikes. An avocado meets both of these requirements.

According to the United States Department of Agriculture, an average medium avocado has around 17 grams of carbohydrates. For comparison, an apple has 25 grams of carbohydrates and a banana has 27.

A 1-ounce serving, or about one-fifth of an avocado, contains only 3 grams of carbohydrates and less than 1 gram of sugar.

With so few carbohydrates, people with diabetes likely won't need to worry about an avocado raising their blood sugar levels.

Pairing an avocado with other foods may help reduce blood sugar spikes too. Its fat and fiber content takes longer to digest and slows the absorption of other carbohydrates in the process.

How much avocado can people with diabetes eat?

Before people make any significant changes to their diet, they should talk with their physician or dietitian. One of the things to consider is total calorie intake.

A whole avocado contains 250-300 calories, but a 1-ounce serving has only 50. People who are watching their calories in order to maintain or lose weight can still add avocado to their diet. This can be done by switching a serving of avocado for something else with a similar amount of calories like cheese or mayonnaise.

The American Diabetes Association (ADA) say people should pay attention to the type of fat they're eating more than the amount.

Specifically, people should strictly limit the unhealthy fats. This includes saturated fats and trans fats, often found in fatty meats, fried foods, processed and restaurant foods.

The ADA encourage people with diabetes to consider adding avocado into their diets due to its healthy fats.

Avocados and heart health

Avocados have fat and are calorie-dense, but this is not a reason for people with diabetes to avoid them.

The fats in avocados are mostly monounsaturated fatty acids (MUFAs), which have been shown to raise "good" HDL cholesterol. MUFAs can also lower levels of "bad" LDL cholesterol and fats called triglycerides, and reduce blood pressure.

Having healthy cholesterol, triglyceride, and blood pressure levels can reduce the risk of heart disease and stroke, according to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

People with diabetes are twice as likely to have heart disease and stroke as someone without diabetes, according to the NIDDK. More importantly, heart disease and stroke are the leading causes of death among people with diabetes.

There may be an additional reason that MUFAs are a ticket to better health when living with diabetes. A study published in the Journal of the American College of Nutrition suggests that these fats may help control blood sugar and insulin levels.

The researchers found this was particularly the case when replacing some carbohydrates in the diet with MUFAs. So besides being naturally low in sugar and carbohydrates, an avocado's healthy fats can help lower blood sugar levels even more.

Fiber, blood sugar levels, and feeling full

A medium avocado has an impressive 10 grams of fiber. For reference, men should get 30-38 grams of fiber per day, and women need 21-25 grams, according to the Academy of Nutrition of Dietetics.

Fiber is an important part of a healthy diet because it improves digestive health and keeps the bowels regular. It's particularly helpful for people with diabetes because it helps improve blood sugar levels.

A study in the Journal of the American Board of Family Medicine suggests that fiber can lower fasting blood sugar levels and hemoglobin A1C levels in people with diabetes.

Soluble fiber, which is present in avocados, may also improve cholesterol levels, according to a study in the American Journal for Clinical Nutrition. This is another way this fruit may help reduce the risk of heart disease.

Avocados may also help people feel fuller for longer. This can help people control their calorie intake without feeling hungry. A study in the Nutrition Journal found that eating half of an avocado with lunch increased levels of feeling full up to 5 hours later.

Is Avocado Good for Diabetes?

Is Okra Good for Diabetes?

According to a handful of recent studies, okra may reduce symptoms of diabetes - a group of diseases that includes type 1 diabetes, type 2 diabetes, and gestational diabetes.

 

Diabetes claimed the lives of 75,578 Americans in 2013, according to the United States Centers for Disease Control and Prevention (CDC). In 2014,8.5 percent of adults worldwide had the condition, the World Health Organization (WHO) report. By 2030, diabetes may be the seventh leading cause of death.

A number of factors increase a person's risk of developing diabetes, including a family history of the disease. Lifestyle factors also play a role, so doctors routinely recommend diet changes and increased exercise to reduce blood sugar levels.

Okra may help reduce blood sugar levels in some people with diabetes. Research into the effects of this seedy vegetable is still in the early stages, but the results are promising.

Okra thrives in temperate climates, producing large hibiscus-like flowers that eventually give rise to green seed pods. It is a member of the mallow family, which includes a number of other popular plants, including hibiscus, cocoa, and cotton.

Scientifically known as Abelmoschus esculentus, okra may have been grown as long ago as 2000 BCE in Egypt.

Okra's flavor is mild, and the entire seed pod can be eaten. This vegetable-like fruit also has a long history in traditional medicine.

Kew Royal Botanic Gardens report that in Eastern traditional medicine, okra leaves and fruit were used as pain relievers, moisturizers, and to treat urinary disorders. In Congolese medicine, okra is used to encourage a safe delivery during childbirth.

Can okra help with symptoms of diabetes?

Diabetes can often be well-managed with increasing a hormone called insulin and other medical therapies. However, some people with diabetes wish to avoid regular insulin injections. Others experience blood sugar dips and other unpleasant side effects, and diabetes medications do not work for everyone.

The possibility that a readily available seed pod could help control diabetes is an exciting one. But there is no evidence yet that okra can cure diabetes. So far, the research on okra has only looked at its effects on animals. Human bodies are similar to animals, but not all research on animals has worked out in humans.

Increased absorption of sugar by muscles

A 2005 study published in Planta Medica investigated the effects of okra on rats with diabetes. A substance called myricetin is present in okra and some other foods, including red wine and tea.

Researchers isolated myricetin from okra, then administered it to the rat. The treatment increased absorption of sugar in the rats' muscles, lowering their blood sugar.

A 2012 Food Science and Human Wellness review points to a number of other laboratory and animal studies that have linked myricetin to lower blood sugar. The study argues that myricetin may also reduce other risk factors for diabetes.

Reduction in blood sugar spikes after eating

A 2011 study published in ISRN Pharmaceutics found a link between okra and decreased blood sugar spikes after eating.

Researchers fed rats liquid sugar as well as purified okra through a feeding tube. Rats who consumed the okra experienced a reduction in blood sugar spikes after feeding. The study's authors think this is because the okra blocked the absorption of sugar in the intestines.

The study also explored possible interactions between okra and metformin, a drug that can reduce blood sugar in type 2 diabetes. Okra appeared to also block absorption of metformin. This suggests that okra could reduce the effectiveness of metformin, and should therefore not be eaten at the same time as the drug.

Lower blood sugar levels

A 2011 study published in the Journal of Pharmacy and Bioallied Sciences points to a link between eating okra and lower blood sugar. The researchers allowed the blood sugar of rats with diabetes to stay level for 14 days. They then gave the rats powdered okra peel extracts and seeds dosages of up to 2,000 milligrams per kilogram of body weight.

There were no poisonous effects linked with these relatively high doses of okra. The rats that ate okra had reduced blood sugar levels after up to 28 days of eating okra. The study ended on day 28, so it is unclear if the effects on blood sugar levels would have lasted longer.

Considerations for using okra

Few studies have linked okra to negative side effects, but some negative side effects are possible:

• Okra may make the drug metformin less effective.
• Okra is high in substances known as oxalates. Oxalates may increase the risk of kidney stones in people vulnerable to kidney stones.
• Okra can contain bacteria, pesticides, and other dangerous substances if it is not thoroughly washed. People should never consume rotten okra, frozen okra that is past its expiration date, or okra that has not been thoroughly washed.
• People with an okra allergy should not consume okra. Those with an allergy to other plants in the mallow family, such as hibiscus or cotton, may also be allergic to okra.
• Even if okra proves to be ineffective in fighting diabetes, it remains a safe snack for people with diabetes. A single serving of 100 grams contains just 30 calories, but offers a number of nutritional benefits:
  • Okra contains no saturated fats or cholesterol
  • Okra is rich in fiber, containing 9 percent of the recommended daily value (RDV)
  • Okra contains 8 percent of the RDV of calcium, 43 percent of the RDV of manganese, 10 percent of the RDV of iron and copper, and 44 percent of the RDV of vitamin K
  Okra is rich in protective substances known as antioxidants, including myricetin. According to the National Center for Complementary and Integrative Health, antioxidants may reduce oxidative stress, a process that damages cells in the body. Oxidative stress plays a role in the development of diabetes, as well as diseases such as:
  • Parkinson's disease
  • Alzheimer's disease
  • Cataracts
  • Macular degeneration
  • Heart and blood vessel disease
  • Cancer
  In addition to its antioxidant benefits, okra may also reduce tiredness. A 2015 study published in Nutrients found that substances found in okra seeds known as polyphenols and flavonoids could reduce fatigue.

Broccoli sprout extract may protect against oral cancer recurrence

It is the first study demonstrating that the extract protects against oral cancer, with the results of human, animal and laboratory tests reported in the journalCancer Prevention Research. This research is funded through Pitt's Specialized Program of Research Excellence grant in head and neck cancer from the National Cancer Institute.

"With head and neck cancer, we often clear patients of cancer only to see it come back with deadly consequences a few years later," said lead author Julie Bauman, M.D., M.P.H., co-director of the UPMC Head and Neck Cancer Center of Excellence. "Unfortunately, previous efforts to develop a preventative drug to reduce this risk have been inefficient, intolerable in patients and expensive. That led us to 'green chemoprevention'--the cost-effective development of treatments based upon whole plants or their extracts."

Cruciferous vegetables, such as broccoli, cabbage and garden cress, have a high concentration of the naturally occurring molecular compound sulforaphane, which previously has been shown to protect people against environmental carcinogens.

Dr. Bauman and her colleagues treated human head and neck cancer cells in the laboratory with varying doses of sulforaphane and a control, and compared them to normal, healthy cells that line the throat and mouth. The sulforaphane induced both types of cells to increase their levels of a protein that turns on genes that promote detoxification of carcinogens, like those found in cigarettes, and protect cells from cancer.

In a small preclinical trial, 10 healthy volunteers drank or swished fruit juice mixed with broccoli sprout extract for several days. The volunteers had no significant problems tolerating the extract and the lining of their mouths showed that the same protective genetic pathway activated in the laboratory cell tests was activated in their mouths, meaning that the sulforaphane was absorbed and directed to at-risk tissue.

Dr. Bauman also collaborated with senior author Daniel E. Johnson, Ph.D., professor of medicine at Pitt and a senior scientist in the UPCI Head and Neck Cancer Program, to see how the extract performed in mice predisposed to head and neck cancer. The mice who received the sulforaphane developed far fewer tumors than their counterparts who did not receive the extract.

The results of the mouse, human and lab studies have been so successful that Dr. Bauman has started a larger clinical trial in volunteers previously cured of head and neck cancer. These participants are taking capsules containing broccoli seed powder, which is more convenient to take regularly than the extract mixed with juice.

"Head and neck cancers account for approximately 3 percent of all cancers in the U.S., but that burden is far greater in many developing countries," said Dr. Bauman. "A preventative drug created from whole plants or their extracts may ease the costs of production and distribution, and ultimately have a huge positive impact on mortality and quality of life in people around the world."

Ref : http://cancerpreventionresearch.aacrjournals.org/content/early/2016/04/30/1940-6207.CAPR-15-0290

Broccoli sprout extract may protect against oral cancer recurrence  

Scientists streamline total synthesis of uncialamycin drug

A team led by Rice University scientists has improved the production of a potent anti-tumor antibiotic known as uncialamycin.

The Rice lab of synthetic chemist K.C. Nicolaou announced this month it had streamlined the total synthesis of uncialamycin to make it simpler to create novel variations of the molecule. Such variations could allow the substance, which is too toxic in its original form, to be made into useful drugs to fight cancer.

The new work by Nicolaou and colleagues appears in the Journal of the American Chemical Society.

Nicolaou's lab specializes in the synthesis of molecules found in nature with medicinal properties, but in amounts too small for testing or clinical use. The new process is scalable for bulk production, he said.

Uncialamycin is an enediyne, compounds defined by the presence of nine- and 10-member atomic rings in their structures. Two other enediynes, neocarzinostatin and calicheamicin, are or have been used as chemotherapy agents to treat leukemia and cancers of the liver and the brain.

"The 10-member ring is like the warhead of the molecule," Nicolaou said. "The ring undergoes the Bergman reaction, producing radicals that cut both strands of the DNA, rendering it difficult to repair by the cell. It's a Trojan horse that gets inside the cell and causes havoc."

The payoff has been a long time coming for Nicolaou and his colleagues who began investigating uncialamycin after it was isolated from a strain of streptomycete related to Streptomyces cyanogenus, a marine bacterium, in 2005. The lab reported the total synthesis of the molecule in 2007 and followed up in 2008 with a report on new synthetic versions and demonstration of its DNA-cleaving, antibiotic and cytotoxic capabilities.

He said the newly developed synthetic strategies and methods make it possible to synthesize a series of designed analogs of the molecule for biological evaluation. As part of the new study, the lab synthesized not only pure synthetic uncialamycin but also 13 variants of the molecule, with handles for attachment to cancer-cell-associated antibodies and other drug-delivery systems.

These were tested for their potency against lung, gastric, ovarian and multidrug-resistant cancer cell lines. Three of the variants showed "remarkably high potency against the tested cell lines," the researchers reported.

Nicolaou said the analogs proved stable enough to be used as payloads in antibody drug conjugates that combine a delivery system - an antibody capable of recognizing and targeting cancer cells - with the anti-cancer drug through a chemical linker that joins the two until they reach the target.

Ref : http://pubs.acs.org/doi/abs/10.1021/jacs.6b04339

Paclitaxel drug may promote cancer spread at low doses

In continuation of my update on paclitaxel

New research indicates that paclitaxel, which is the most commonly used chemotherapy for breast cancer, suppresses tumors when given at a certain dosage, but at low doses, it actually promotes cancer spread to the liver.

The findings suggest that lowering the dose of paclitaxel to reduce toxic side-effects is not a safe strategy.

"Paclitaxel and its analogous compounds are the first line agents widely used in clinical cancer chemotherapy. However, potential risks and reasonable treatment strategies of paclitaxel continue to be widely investigated," wrote the authors of The FEBS Journalstudy.

http://onlinelibrary.wiley.com/doi/10.1111/febs.13767/full

Increase in EPA/DHA omega-3 intake linked to lower risk of all-cause mortality

A recent meta-analysis in Scientific Reports supports a link between EPA and DHA omega-3 intake and a reduced risk of death by any cause. The meta-analysis included 11 studies involving 371,965 participants and 31,185 death events, with a subset of the studies being used for different analyses.

DHA   EPA

In the analysis of n-3 LCPUFA intake, there was a 9% reduced risk of all-cause death associated with high versus low omega-3 intake. In the dose-response analysis, an increase in EPA/DHA intake of 300 mg/day was associated with a 6% lower risk of all-cause mortality. These findings suggest that both dietary and circulating n-3 LCPUFA are shown to be significantly associated with reduced risk of all-cause mortality.

According to study author Manfred Eggersdorfer, "The meta-analysis of 11 prospective observational studies demonstrates that each 1% increment of omega-3s in total fatty acids in blood may be associated with a 20% decrease in risk of all-cause mortality. This is an important finding for the potential contribution of adequate omega-3 intake to public health."

Novel combination therapy shows strong response in phase 1 trial

In continuation of my update on Sorafenib, Premetrexed,  Vandetanib
"Though phase 1 studies are designed to evaluate the safety of a new therapy, we had strong preclinical evidence suggesting this novel drug combination could work against a variety of cancers, so we hoped that we would see a response in our patients in this early phase trial," said Andrew Poklepovic, M.D., lead investigator on the study. "With this trial, we established a safe dosing schedule, and we will now be testing the efficacy of the therapy in the phase 2 study."

The results of the clinical trial were recently published online by the journal Oncotarget (PMID: 27213589). The study enrolled 37 patients between October 2011 and December 2014. Of those patients, 36 received treatment and 33 were evaluated for response. One patient had a complete response, meaning all detectable traces of the tumor disappeared, while four patients had a partial response, which means that the tumor volume shrank by at least 30 percent. The therapy stabilized disease progression in an additional 15 patients, with some of these patients responding for up to a year. The therapy was found to be particularly active in breast cancer patients.

"Some dose-limiting toxicities associated with pemetrexed were observed in one cohort of patients, but those who were eligible were switched to the dosing schedule of the second cohort, which was found to safe and tolerable," says Poklepovic, medical oncologist and member of the Developmental Therapeutics research program at Massey as well as assistant professor in the Division of Hematology, Oncology and Palliative Care at the VCU School of Medicine.

The trial is based on pre-clinical research conducted by a team of Massey scientists led by Paul Dent, Ph.D., who is the Universal Corporation Chair in Cancer Cell Signaling and a member of the Cancer Cell Signaling research program at Massey, and Richard Moran, Ph.D., who recently retired after 22 years at Massey and more than four decades in the field. Pemetrexed was co-developed by Moran, and is now a first-line therapy for non-small cell lung cancer (NSCLC) and mesothelioma. Sorafenib is used to treat liver, kidney and thyroid cancer. In 2011, a research team led by Dent and including Moran discovered that the two drugs synergize to induce profound killing of cancer cells through a toxic form of autophagy, a process that normally re-cycles components of cells to provide energy for maintaining cell growth and survival. The drug combination hyper-activated the autophagy process within cancer cells, causing them to literally eat themselves to death (PMID: 21622715).

 Sorafenib  Pemetrexed

  Vandetanib    Lapatinib

The phase 2 study is not the only continuation of the research. Because the initial results of the phase 1 study were so promising, Dent started a new project to discover the best "third drug" that could act to further enhance the anti-cancer properties of the pemetrexed and sorafenib combination. This work has also recently been published in Oncotarget, and it showed that the combination therapy could be enhanced by a class of drugs known as ERBB1/2/4 inhibitors (PMID: 27015562).

"We discovered in mouse models of breast cancer that the drugs lapatinib and vandetanib significantly enhanced the anti-tumor effect of the pemetrexed and sorafenib therapy without any apparent toxicity to normal tissue. We made a nearly identical observation when adding the drug afatinib in experiments involving non-small cell lung cancer," says Dent. "Based on this data, we will be submitting a grant application to the National Cancer Institute for funding that will hopefully provide data that could allow us to open a future phase 1 trial testing the addition of an ERBB1/2/4 inhibitor to pemetrexed and sorafenib in patients with advanced solid tumors."

Dent was able to determine that ERBB1/2/4 inhibitors could increase the effectiveness of the combination therapy by using a novel technology called a multiplex assay. The multiplex assay is a broad, unbiased screening approach that allows researchers to simultaneously examine the levels of multiple hormones in the blood and determine the activities of enzymes in cancer cells. Using this technology, the researchers discovered that the enzyme ERBB1 was activated in response to the pemetrexed and sorafenib therapy.

"Unlike alternative methods where a certain degree of guesswork is required, the multiplex assay allowed us to observe exactly how the cancer cells responded to therapy," says Dent. "We were surprised to see that the enzyme ERBB1 was activated because it is ordinarily thought to protect cancer cells from chemotherapy. We went on to successfully use ERBB1/2/4 inhibitors as our third drug because of this unexpected data."

The multiplex assay provided Dent's team with such invaluable additional information about how the sorafenib and pemetrexed combination worked in the mouse models that they will now be using the assay in several of their clinical trials moving forward, including the new phase 2 trial of pemetrexed and sorafenib.

"The multiplex assay will allow us to track specific levels of hormones in the blood as patients undergo treatment, which could potentially give us a molecular 'fingerprint' of the point at which tumors develop resistance to the therapy," says Dent. "Ongoing preclinical experiments show that it could be possible to pinpoint exactly how the cancer cells are developing resistance to therapies, which might eventually allow oncologists to develop in real time a personalized therapy designed to overcome drug resistance in an individual patient's tumor."

Ref : http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=9434

More reasons to eat your broccoli

In continuation of my update on broccoli

University of Illinois researchers have identified candidate genes controlling the accumulation of phenolic compounds in broccoli. Consumption of phenolic compounds, including certain flavonoids, is associated with a lower risk of coronary heart disease, type II diabetes, asthma, and several types of cancer.

"Phenolic compounds have good antioxidant activity, and there is increasing evidence that this antioxidant activity affects biochemical pathways affiliated with inflammation in mammals. We need inflammation because it's a response to disease or damage, but it's also associated with initiation of a number of degenerative diseases. People whose diets consist of a certain level of these compounds will have a lesser risk of contracting these diseases," explains U of I geneticist Jack Juvik.

The researchers crossed two broccoli lines and tested their progeny in terms of total phenolic content and their ability to neutralize oxygen radicals in cellular assays. They then used a genetic technique called quantitative trait locus analysis to search for the genes involved in generating phenolics in the most promising progeny.

By identifying the genes involved in accumulating these compounds, the researchers are one step closer to breeding broccoli and related Brassica vegetables like kale and cabbage with mega-doses of phenolic compounds.

"It's going to take awhile," Juvik notes. "This work is a step in that direction, but is not the final answer. We plan to take the candidate genes we identified here and use them in a breeding program to improve the health benefits of these vegetables. Meanwhile, we'll have to make sure yield, appearance, and taste are maintained as well."

The good news is that phenolic compounds are flavorless and stable, meaning the vegetables can be cooked without losing health-promoting qualities.

Once these vegetables are consumed, the phenolic compounds are absorbed and targeted to certain areas of the body or concentrated in the liver. Flavonoids spread through the bloodstream, reducing inflammation through their antioxidant activity.

"These are things we can't make ourselves, so we have to get them from our diets," Juvik says. "The compounds don't stick around forever, so we need to eat broccoli or some other Brassica vegetable every three or four days to lower the risk of cancers and other degenerative diseases."