Cancer Archives

Apr

2023

What you Must Know about Male Hormones

By Ray Schilling | andropause, Anti-aging medicine, Cancer, Diabetes, hair loss, heart attack, Infertility, prostate cancer, prostate hypertrophy, Stroke, testosterone

Dr. Pamela Smith, an anti-aging physician gave a talk about what you must know about male hormones. She spoke on Saturday, Dec. 10, 2022 at the Sands Conference Center of the Palazzo Hotel in Las Vegas. The title was “What you must know about male hormones”. She presented 199 slides, so the following can only be a brief summary of what she said. She started by saying that the term “male menopause” goes back in time to 1944. Other terms are andropause and late onset hypogonadism.

Different testosterone levels at different ages

It is important to realize that at age 20 the blood testosterone level is around 900 ng/dL, but this declines after age 30. It is 550 ng/dL at the age of 40. At the age of 50 the testosterone level is 350 ng/dL. And at the age of 70 the testosterone level has shrunk to 200 ng/dL or less. With this in mind, there are also seasonal variations with higher levels of testosterone occurring in summer and early fall, and low levels happening in winter and early spring. A healthy male produces the following male hormones: Testosterone, 5-6 mgs/day; Androstenedione, 3 mgs/day; DHT, 0.300 mgs/day; DHEAS, 50 mgs/day; and DHEA, 15 mgs/day.

Functions of testosterone

In other words, testosterone is the male hormone responsible for the male body characteristics. Every male body cell has testosterone receptors on it. Truly, this way testosterone is involved in protein manufacture and muscle maintenance. In fact, bone formation depends on testosterone and oxygen uptake as well. It is also controlling blood sugar together with insulin. In addition, normal sperm production depends on testosterone. To clarify, testosterone also regulates cholesterol and the immune system. By all means, it also helps to improve mood, is important for mental concentration and helps protect against Alzheimer’s disease. Finally, there is stimulation of platelets and megakaryocytes by testosterone, which makes blood clotting easier.

Symptoms of andropause

It must be remembered, towards the end of their 60’s many men get symptoms of tiredness, loss of energy and depression. Specifically, they may get a bad temper, present with irritability, anxiety and nervousness. Specifically, they complain of a loss of memory, loss of sex drive and libido. Certainly, their erections are getting weak or they lose them altogether. There is a decreased intensity of orgasm and they are gaining weight. All this should prompt their physician to have a total testosterone blood test done. When the testosterone level is less than 500 ng/dL the person should see their physician for replacement testosterone therapy.

Other signs of testosterone deficiency

There are other signs and symptoms of testosterone deficiency: backaches and joint pains, loss of fitness, being overstressed. In addition, testosterone-deficient males experience a decrease in job performance and a decline in physical fitness. They have bone loss, elevation of their blood cholesterol and an increased risk of heart disease. They often also have increased insulin resistance, diabetes and metabolic syndrome. Mortality in men with low testosterone is much higher than in controls with normal testosterone. Several dozens of literature references were provided to support the above statements.

Testosterone replacement and hormone balance

When a patient is on testosterone replacement, a digital rectal exam should be performed to check for the size of the prostate gland. A PSA should be done every year (in former prostate cancer patients every 3 months). PSA should stay below 4.0 ng/mL. If the PSA rises by 1.5 ng/mL in one year or by 0.75 ng/mL in two consecutive years, a urologist should be consulted to rule out prostate cancer.

Men produce small amounts of estrogens, which are important for memory function of the brain and for strong bones. Androgens and testosterone aromatize into estrogen via the enzyme aromatase in fatty tissue. There are a few reasons why aromatase increases: obesity, excessive alcohol intake, chronic inflammation and high insulin levels.

The following medications lower estrogen levels: phenobarbital, carbamepazine, trazodone, chlordiazepoxide and sulcrafate.

Side effects from elevated estrogen levels

Increased estrogen levels in males cause gynecomastia (colloquially called “beer tits”), decreased sex drive, heart attacks, strokes and benign prostate hypertrophy. Elevated estrogen levels also cause insulin resistance, rheumatoid arthritis and prostate cancer. Dr. Smith referenced all of these statements again with many literature quotations.

Dihydrotestosterone (DHT)

This metabolite of testosterone is 3-times stronger than testosterone. It is formed from testosterone by the enzyme 5-alpha reductase. It is responsible for the male-specific characteristics, the male genitalia and the prostate gland. Low levels of DHT cause reduced sexual function, decreased libido and weakened muscle function. On the other hand, elevated DHT causes male pattern baldness, hirsutism and benign prostate hypertrophy (BPH). There are two 5-alpha reductase inhibitors, namely finasteride and dutasteride, that clinicians use to lower elevated DHT levels. This can reduce the risk of prostate cancer by about 50%. Dr. Smith provided many literature quotations to support these statements.

Testosterone replacement therapy

Based on more than 3 dozen literature quotations Dr. Pamela Smith outlined the following:

Most men tolerated transdermal testosterone application very well.
Erectile dysfunction affects 1 in 5 older men.
Erectile dysfunction in association with low blood testosterone and low libido responds to transdermal application of testosterone very effectively.
It may take 14-25 weeks before transdermal testosterone treats erectile dysfunction successfully, more than 50% of men respond to this.
Testosterone replacement prevents beta amyloid precursor protein production, which increases memory and decreases the risk of Alzheimer’s development.
High stress produces high cortisol levels in the blood, which affect the hippocampus, where memory is located. Testosterone is neuroprotective, and it preserves memory.
Transdermal testosterone decreases coronary heart disease by relaxing coronary arteries. This prevents heart attacks and strokes.
Testosterone decreases inflammation and lowers LDL cholesterol.

More facts about testosterone replacement therapy

Testosterone lowers inflammatory cytokines and stimulates interleukin-10 production. This has anti-inflammatory and anti-atherogenic actions, which prevents heart attacks.
There was a reduction in mortality from heart attacks in the testosterone treated group of between 66% and 92%. In addition, 30 nonfatal strokes and 26 nonfatal myocardial infarctions occurred in the control group, but none in the testosterone group. Testosterone deficient heart failure patients responded very well to testosterone replacement therapy.
Prostate cancer or benign prostate hypertrophy do not increase with transdermal testosterone replacement therapy.

A Meta-analysis showed that older men with the highest risk for prostate cancer have the lowest testosterone blood levels.
Type 2 diabetics with a high insulin resistance respond well to testosterone replacement therapy. They increase insulin sensitivity and lower their blood sugars. This improvement peaks after 3 months and the effect stays for 12 months.

Further facts about testosterone replacement therapy

Testosterone replacement is safe. It provides significant benefits for erectile dysfunction, for muscle mass, prevention of Alzheimer’s disease, prevention of heart attacks and strokes. Testosterone treatment is for males above the age of 50, there is no cut-off for higher ages. There are many controlled clinical trials spanning over 70 years, which support all of what is presented here.
Testosterone can’t be taken orally, because it is rapidly metabolized in the liver. Instead, patients use transdermal testosterone gel or cream. Gels are commercially available and very expensive. Compounding pharmacies can provide testosterone creams for you, which are considerably cheaper and can be dosaged according to the patient’s needs. Testosterone esters in oil are available for subcutaneous or intramuscular injection twice per week. This ensured a steady testosterone level.

Improvements after testosterone replacement therapy

Timing of improvements: cholesterol reduction occurs by 12 months, for triglycerides it takes 22 months. Testosterone levels take 4 to 12 weeks to normalize. Fasting blood sugars and Hemoglobin A1C come own within 3 months with further improvements by 12 months. Sexual desire and energy are back to normal within 3 to 6 weeks.
It is important that you go for blood tests to measure testosterone levels every 3 months initially (blood level). If the levels are stable, the physician may decide to only order tests every 6 months.

What you Must Know about Male Hormones

Conclusion

The goal in the aging male is to maintain optimal male hormone levels. This achieves optimal health and prevents diseases of older age. First, it is important to preserve his erections, but at the same time testosterone replacement therapy prevents Alzheimer’s disease and memory loss. It also prevents heart attacks and strokes. Testosterone helps to preserve muscle mass. Hormone replacement therapy keeps lipids like cholesterol and triglycerides under control. Testosterone replacement reduces blood sugars and prevents type 2 diabetes mellitus. Replacement therapy also reduces elevated insulin levels. The end result is that testosterone replacement therapy maintains the health of the aging male.

Feb

2023

Common Nail Salon Tool Causes Skin Cancer

By Ray Schilling | Cancer, Skin Disorders

A recent publication in Nature Communications found that a common nail salon tool causes skin cancer. The researchers voiced concerns about the use of ultraviolet radiation from nail dryers with gel manicures. They were shown to cause DNA breaks in the exposed skin. The artificial nails require ultraviolet radiation to harden them. But the ultraviolet light hits the skin around the nails and of the fingers, which can be the first step in causing skin cancer.

Three stages in the development of skin cancer

In the 1970’s and 1980’s a lot of basic research using mouse models has been done about 3 stages of skin cancer development. Dr. Kripke was one of the pioneers in this field (see Ref. 1 and 2). However, it turned out later that the human skin is not identical to mouse skin and that human skin seems to be more resistant than that of inbred mice. Nevertheless, the basic concept that was researched then has held up to scrutiny over the ensuing decades. The development of skin cancer in man requires three steps.

1. Initiation

Initiators for skin cancer are UV light, tar, nitrogen mustard, psoralen to name a few. The DNA of skin cells undergoes some configurational changes, but when left alone it does not go on to cancer development.

2. Promotion

Common promoters for the development of skin cancer are: Ultraviolet light, phenol, anthralin, phorbol esters, benzoyl peroxide.

3. Carcinogenic effect

The role of carcinogens in skin cancer is not understood very well. However, the classical studies of scrotal cancer in chimney sweepers pointed to the importance of carcinogens in soot of chimneys (Ref.3). This is one of the first human examples for a carcinogen. Another carcinogen is arsenic. We do not know enough about long-term exposure to small amounts of carcinogenic compounds in drinking water or in polluted air. Other carcinogenic effects are excess radiation from X-rays or irritation from chronic inflammation (lupus lesions, burn scars, decubitus ulcers, chronic osteomyelitis). Repeated exposure to UV light also has carcinogenic effects on the skin by leading to DNA breaks. UV light exposure plays an important part in every step of skin cancer development.

More causes of skin cancer

Squamous cell cancer of the oral cavity and lip has been linked to chewing tobacco or betel nuts. There is also a link to certain viruses such as the human papillomavirus. This model for cancer development is applicable for many other cancers, if not for all forms of cancer. Many stabilizers and antimicrobial/antifungal substances such as parabens are also mild carcinogens. Many physicians warn their patients not to use parabens in tooth paste, cosmetics, shampoos, conditioners and body wash products. I agree with this opinion. Go to a health food store and get alternative products without parabens in it. Read labels! Numerous paraben-free products are also on the shelves of drugstores. If you read the word ”paraben”, leave the product on the shelf. Exposure to UV light and several sunburns in succession can also cause skin cancer.

Common nail salon tool causes skin cancer: further discussion

Ludmil B. Alexandrov holds dual titles as associate professor of bioengineering and cellular and molecular medicine at the University of California San Diego. He said: ”If you look at the way these devices are presented, they are marketed as safe, with nothing to be concerned about. But to the best of our knowledge, no one has actually studied these devices and how they affect human cells at the molecular and cellular levels until now.” Those who want to continue gel manicures, can use some precautions to minimize the risk of skin cancer. Use a sunblock that contains zinc and titanium on the skin of your fingers around the nails. This will block the damaging UV rays. But the safest way is to stop using nail dryers, which are necessary with gel manicures.

A common Tool in the Nail Salon may Damage your DNA and Cause Skin Cancer

Conclusion

We sometimes lose sight of what modern procedures can do to us. One example is the use of gel manicures that require exposure to UV light to harden the gel nail polish. Several layers are applied during a manicure session. Most people do not think that the accumulated exposure to UV light can lead to DNA breaks and eventually cause skin cancer. But dermatologists have noted that there is a direct link between the amount of UV light exposure and the risk to develop skin cancer later in life.

Prevention of UV light exposure

The logical conclusion is to stop using these applications of gel nail polish. However, if the person finds it difficult to abandon this manicure procedure, a compromise is to cover up the skin of your fingers with a sunblock that contains zinc and titanium. You can apply this to the skin of your fingers around the nails. To a certain extent this will block the damaging UV rays, but it is not a guarantee.

References

Kripke ML, Sass ER,eds.”Antigenicity of murine skin tumors induced by UV light”.JNCI 1974;53:1333-1336.
Kripke ML. “Immunology and photocarcinogenenis”. J. Am. Acad.Dermatol. 1986;14:149-155.
Potter M.”Percivall Pott’s contribution to cancer research”. NCI Monogr.1963;10:1.

Oct

2022

Plant-Based Meat Alternatives are Healthier

By Ray Schilling | Cancer, Cardiovascular disease, diet, food, Health, Nutrition, Obesity, Weight loss

A recent study showed that plant-based meat alternatives are healthier than the original meat dishes. This spread into various health websites on the Internet. One example is this one.

Some statistics about plant-based meat alternatives

Plant-based meat alternatives came to the market in the 1960’s. At that time, they consisted mainly of soy. Later textured vegetable protein joined soy products. Today they consist of pea protein, soy, potato, oils, various binders and flavorings to mimic the texture and flavor of meat.

The global plant-based meat market was about 5 billion USD last year. It is projected to increase by 19% from 2022 to 2030. The plant-based dairy alternatives market totaled 11 billion in 2020. The estimate is that this will grow to 32 billion in 2031.

How healthy are plant-based substitutes?

In the center of this discussion is the publication of Christopher J. Bryant from the Bath University in England. This publication reviewed 43 studies regarding plant-based substitutes regarding healthiness and environmental sustainability. In the following I am discussing the findings, particularly about health benefit of plant-based foods versus meat-based foods.

Problems with our current food consumption

There are several problems with human diseases that are transmitted from wildlife. HIV arouse from hunting of non-human primates. Rabies was transmitted in South America by vampire bats from cattle to humans. Early cases of severe acute respiratory syndrome (SARS) came from contact with wild life. Finally, bats transmitted the SARS coronavirus-like virus from wild animals and live animal markets to humans. Subsequently human to human transmission caused the spread of Covid all around the world as a pandemic.

Use of antibiotics in feedlots

In order to control diseases in closely kept animal feedlots farmers feed the livestock antibiotics. This helps to contain infections, but it also poses a grave problem to humans as antibiotics become more and more resistant. Superbugs developed this way. 18% of meat imported from China was contaminated with Salmonella. 88% of those exposed to contaminated meat were resistant to at least one antibiotic. But 58% were resistant to multiple antibiotics.

A Harvard study from Boston showed in 2020 that red meat and processed red meat consumption caused 15% more heart attacks compared to those who substituted the protein source with plant-based foods. The same study also noted that the heart attack rates were about 15% less for subjects who substituted meat with plant products in comparison to meat eaters.

Other results of the study

Several of the reviewed studies compared the nutritional profile of plant-based meat with the animal-based counterparts. Plant-based meat was significantly lower in saturated fat, and protein. However, they were significantly higher in fibre and salt. 40% of meat products were classified as ‘less healthy’. In comparison to that investigators assessed that only 14% of plant-based meat was ‘less healthy’. When saturated fat, sodium, sugar, and overall calorie content were tabulated, plant-based meat products compared favorably to meat. But salt content was often too high in plant-derived foods.

Plant-based burgers were much healthier than conventional beef-burgers, as they contained no cholesterol, less trans-fatty acids and less saturated fat. Vegetable-based food that contains pea protein is particularly valuable with regard to a high protein content.

Criticism of plant-based meat alternatives

At the present time many plant-based meat products have too much sugar and salt in it, but lack iron and vitamin B12. Various authors suggested that the food industry should add iron and vitamin B12 to their products and reduce the sugar and salt content.

Muscle synthesis

Mycoprotein is the active biochemical that builds up the protein of the muscle mass in man. Non-animal-derived dietary protein contains ample amounts of mycoprotein according to this publication. These authors investigated the ingestion of mycoprotein in a dose-response manner. They also measured insulin levels for 4 hours after ingestion of plant-derived mycoprotein. Insulin levels remain higher than normal for a sustained period.

Weight loss

A 2017 study showed that 40 grams of mycoprotein, which is the equivalent of 18 grams of protein was sufficient to lead to a robust muscle synthetic response. 60 g of mycoprotein (27 g protein) provided an optimal response regarding muscle synthesis. Gram for gram milk protein and mycoprotein were equivalent in amino acid bioavailability. Several studies examined weight loss following mycoprotein meals. One study found in overweight patients that chicken protein consumption was higher in comparison to consumption of plant mycoprotein. The mycoprotein consuming group chose to eat 10% less calories than the chicken control group.

Greenhouse gas emissions and other factors

The publication cited above also included a lot of findings regarding how plant-derived food saves greenhouse gas emissions and other facts. For instance, the pork supply chain requires 3.3-times more fertilizer and 1.6-times more pesticides than the production of plant-derived food. What this means is that plant-derived foods are more environmentally sustainable than animal products.

Plant-Based Meat Alternatives are Healthier

Conclusion

Plant-derived foods have improved in the past few decades. Pea-derived plant products are now equivalent in terms of protein content to milk and meat. By eating more plant-derived food people consume less meat, which helps the environment, but also benefits the person who eats it. We know that with the consumption of a certain amount of plant-derived food less people develop cardiovascular disease, diabetes and cancer. 40 grams of mycoprotein, which is the equivalent of 18 grams of protein was sufficient to lead to a robust muscle synthetic response.

Consumer beware

It is important to realize that not all is well with the list of “fake meat” and other highly processed plant-based products. Consumers must read the list of ingredients. If a product contains a laundry list of ingredients that not even an adult can pronounce and understand, it is very likely a highly processed food product that only pretends to be good for you. Should the sodium content be too high, steer away from it. High sugar content means that you put it back in the shelf. All in all, eating more plant-derived foods makes you healthier and improves the environment at the same time. But it is up to us to be discriminating colourful advertising from a nutritionally sound product.

Aug

2022

New Immunotherapy Approach against Cancer

By Ray Schilling | Cancer, immune system

A recent publication reported about a new immunotherapy approach against cancer. The model it dealt with was a very vicious brain cancer with the name glioblastoma. The results of this research were subsequently transferred to another vicious cancer, osteosarcoma, which is a form of bone cancer with a very poor prognosis. Researchers have to do further clinical experiments to establish this new immunotherapy in osteosarcoma patients. Physicians completed the following experiments and clinical studies.

Oncolytic virus Delta-24-RGD can lead to remission in glioblastoma patients

Researchers at the University of Navarra, Pamplona, Spain together with The University of Texas MD Anderson Cancer Center in the US investigated glioblastoma patients. They found that treatment of glioblastoma patients with oncolytic viruses Delta-24-RGD led to a greater than 3-year remission in 20% of cases. Normally, patients with a glioblastoma survive only 9 months on average. 12% had a greater than 95% reduction in the size of the tumor. This was a phase 1 clinical study with 37 patients who had recurrent malignant glioblastoma. The authors said: “Oncolytic adenoviruses are attractive therapeutic agents because they can kill tumor stem cells and induce cell death by several mechanisms, including direct lysis, expression of toxic proteins, induction of cytokines, and T-cell–mediated immunity.” The particular oncogenic virus that the researchers used was an adenovirus Delta-24-RGD.

Transferring glioblastoma results to a cure for osteosarcoma

The same researchers wanted to see whether the cure rates of treating patients with glioblastoma was transferable to other cancer patients. In particular they were interested in patients with osteosarcoma, which is a similarly vicious cancer. Advanced osteosarcoma has a survival rate of 27% after 5 years. The researchers first did experiments with a human osteosarcoma cell line in tissue culture and at the same time a murine osteosarcoma cell line. Later they tested the action of oncolytic viruses Delta-24-RGD in a mouse model.

Experiments with osteosarcoma cells in tissue culture

The advantage of such experiments is that you can control all the parameters easily in a Petri dish. But critics say that this is far removed from osteosarcoma behavior in humans. Researchers found that the oncolytic virus Delta-24-RGD killed many osteosarcoma cells in vitro. They also were able to insert a new gene into the oncolytic virus, which was equally effective in killing osteosarcoma cells. They called this virus Delta-24-ACT.

Curing osteosarcoma in a mouse model

Next the researchers tested effectiveness of the oncolytic viruses, Delta-24-ACT and Delta-24-RDG in mice. They injected osteosarcoma cells from tissue culture into the tibia of mice. Tumor growth was subsequently measured. The experimental groups were given two oncolytic virus infections, the control group did not. On day 10 and 18 the researchers could see that controls had faster growing tumors compared to the experimental groups. The experimental groups had less tumor side effects. And the experimental mice survived longer than the controls. Further research showed that the oncolytic viruses produced a 4-1BBL protein, which stimulated the animals’ immune system to fight the osteosarcoma.

New immunotherapy approach against cancer: Effector T cells

Researchers could prove that in mice treated with oncolytic viruses it was the special protein (4-1BBL) that stimulated T lymphocytes to become killer T cells. They in turn attacked the osteosarcoma cells.

New immunotherapy approach against cancer: The need for human research

Doing research in humans is more complicated than in a mouse model. But in order to improve survival rates in patients with osteosarcoma human research is absolutely essential. However, research is complex and the effects of oncolytic viruses is only in the 20% range with regard to increasing survival. This requires more research. It may be that instead of oncolytic viruses a stimulatory protein would arm T cells to become killer T cells that fight the cancer.

New Immunotherapy Approach against Cancer

Conclusion

Glioblastoma patients had a better survival after treatment with oncolytic viruses Delta-24-RGD. Researchers translated this type of research to another cancer, osteosarcoma. This also has a poor prognosis, Researchers did experiments in tissue culture and in a mouse model. They were able to show that oncolytic viruses produced a 4-1BBL protein, which stimulated the animals’ immune system to fight the osteosarcoma. Specifically, the protein armed T lymphocytes and turned them into killer T lymphocytes. These destroyed osteosarcoma cells in tissue culture or in the mouse model. It is encouraging to see positive results in a laboratory setting of a tissue culture. The step further in an animal experiment is also a positive achievement. More research will improve the cure rates of osteosarcoma. The effective treatment of osteosarcoma in humans is still far away! The next step is human research that shows improvements in patients’ survival rates.

May

2022

The Dirty Dozen and the Clean Fifteen

By Ray Schilling | Cancer, food, organic food

This article describes the dirty dozen and the clean fifteen.

The environmental working group (EWG) defined the “dirty dozen” as crops, which farmers pollute by repetitive spraying. Notably, this is a list of the 12 most insecticide-sprayed crops like strawberries, spinach, tomatoes and others. It is important to realize that in the last few years, the EWG added the 15 clean crops. For this reason, if you want to avoid toxins on your food you exchange the 12 dirty dozen for organically grown crops. Specifically, you can also rest assured that the pollution levels in your food is of no concern, when you add the “clean fifteen” since these crops are relatively non-polluted. By all means, I have used this shopping guide for over 10 years and always look for the yearly updates.

The dirty dozen

Here is the dirty dozen:

Strawberries
Spinach
Kale, collard & mustard greens
Nectarines
Apples
Grapes
Bells and hot peppers
Cherries
Peaches
Pears
Celery
Tomatoes

It is important to realize that certain agricultural methods lead to the insecticide contamination of the dirty dozen. It may come as a surprise that not only spinach, strawberries and cherries, but also apples, grapes, celery and tomatoes are very contaminated. I buy only organic equivalent versions of the dirty dozen.

The list of the clean fifteen

Here is the list of the clean fifteen:

Avocados
Sweet corn
Pineapple
Onions
Papaya
Sweet peas (frozen)
Asparagus
Honeydew melon
Kiwi
Cabbage
Mushrooms
Cantaloupe
Mangoes
Watermelon
Sweet potatoes

These are crops that you can buy and eat, because they are not contaminated with insecticide spray. There is a yearly update on the website, which informs you of any changes of the contaminated crops. So far little has changed over several years.

According to the CNN article cited in the beginning of this article 70% of the clean fifteen list have no detectable residues of pesticides. Just under 5% of this list had two or more pesticide residues. For this reason I would label those as relatively non- polluted.

Why pesticides are dangerous

Toxicity of pesticides depends on the chemical configuration. Some are more toxic than others. But in combination pesticides are much more toxic than each one of them alone. Some pesticides irritate the skin, others the eyes. Other chemicals are toxic to the nervous system and the hormone system. And on the long-term pesticides can cause cancer.

Specific toxins

DCPA http://extoxnet.orst.edu/pips/DCPA.htm is a general herbicide that farmers spray on several vegetable crops. It was banned by the European Union in 2009.
Nut and fruit tree farms use Chlorpyrifos, a pesticide, which farmers also spray on broccoli and cauliflower. The EPA banned this substance in February 2022. Chlorpyrifos contains an enzyme that causes neurotoxicity in children. It also causes neurodevelopmental effects in children.
Organophosphates block acetylcholinesterase, an enzyme that inactivates acetylcholine. Toxicity of organophosphates comes from poisoning with acetylcholine, which overstimulates muscles. https://en.wikipedia.org/wiki/Organophosphate_poisoning#Pathophysiology The brains of babies and children are very sensitive to the toxic effect of organophosphates.
A number of pesticides are endocrine-disrupting chemicals. This can have permanent or long-lasting effects on the reproductive development. https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NHEERL&dirEntryId=212273

Complaints of the industry about the EWG

The industry has repeatedly complained about the EWG that the publication of the dirty dozen would harm the sales of crops. But studies done by the EWG showed that only 1 in 6 consumers are buying less vegetables and fruit. Alexis Temkin, a toxicologist at the EWG with expertise in toxic chemicals and pesticides said: “The study actually shows that just over half of people surveyed said the ‘Dirty Dozen’ list made them more likely to buy fruits and vegetables.”

Here is what the consumer can do

Rinse fruit and vegetables before you serve it; this removes surface toxins
Buy food from a local farmer; you can enquire about his farming practices.
Buy produce in season; if you buy organic crops they are most reasonable are that time, and you can prepare or freeze the fruit and vegetables for future use.

The Dirty Dozen and the Clean Fifteen

Conclusion

The environmental working group (EWG) developed the concept of the 12 dirty dozen and the clean fifteen crops. The consumer needs to know the 12 dirty dozen, as he/she has to buy organic crops as a replacement for this. On the other hand, you can buy the 15 clean crops, but you first need to know what is on the list. Knowledge is power, and knowing about these crops ensures that you keep insecticides, fungicides and herbicides out of your body. This information is not only important for adults and youth, but particularly important for babies and small children. Chlorpyrifos, which was banned in February of 2022 in the US causes neurotoxicity in children. But it also causes neurodevelopmental effects in children. The cleaner the crops are that we eat, the healthier our bodies are.

Mar

2022

T-Cell Immunotherapy Cures Chronic Lymphocytic Leukemia

By Ray Schilling | Cancer, genetic marker, immune system, leukemia

T-cell immunotherapy cures chronic lymphocytic leukemia after 10 years. Researchers were able to use the blood of leukemia patients and modify immune cells to attack their cancer cells. Specifically, they introduced a chimeric antigen receptor into immune cells from patients in the lab. Subsequently they transfused the modified immune cells back into the leukemia patients. After 10 years researchers detected the same active cytotoxic T lymphocytes in both chronic lymphocytic leukemia patients, which contained the chimeric antigen receptor marker. This means that active cytotoxic lymphocytes, that also have the name of killer T cells, continued to eliminate any pathological cells from the lymphocytic leukemia patients.

The immune system explained

The immune system can respond with two major responses. The B lymphocytes originate from the bone marrow and turn into antibody producing plasma cells. With viruses this system works very well as it inactivates viruses that the immune system recognizes don’t belong into the body. The other branch of the immune system are the thymus-processed T cells. These are important to eradicate cancer cells. They are also called CD4 cells or cytotoxic T lymphocytes. Often tumor cells produce specific proteins that suppress the immune cells. But the researchers of these two chronic lymphocytic leukemia patients managed to introduce a chimeric antigen receptor into the CD4 cells that specifically targeted the leukemia cells. The immune system in these patients was working optimally and remained active for 10 years.

Some statistics regarding chronic lymphocytic leukemia

Here are some statistics of chronic lymphocytic leukemia (CLL). There were about 61,090 new cases of leukemia and 23,660 deaths from leukemia in 2021 in the US. Among these were 21,250 new cases of chronic lymphocytic leukemia (CLL). There were about 4,320 deaths from CLL. The average lifetime risk of getting CLL is 1 in 175 people or 0.5% of the population. The risk of getting CLL is slightly higher for men than women. CLL is a leukemia of older people, the average age at the time of diagnosis is 70 years. CLL is rare under the age of 40 and extremely rare in children.

Potential serious side effects of T-cell immunotherapy

Dr. David Porter, one of the authors of the study published in Nature said that this type of immunotherapy can have serious side effects. He added that therapies have become safer over the years. Oncologists are giving immunotherapies like the one which I described to hundreds and thousands of patients.

Here are the more common side effects.

The tumor lysis syndrome: when the tumor cells are all attacked at the same time, there is a lot of tumor cell destruction and the contents of the cells end up in the blood. This makes the patient rather sick for a few days. There can be serious electrolyte abnormalities that have to be countered with intravenous fluids. The toxins can also cause kidney damage, which physicians monitor closely.
Cytokine release syndrome: With this syndrome people develop a high fever, nausea, vomiting, much like a severe flu. They also develop muscle aches and joint pains. Patients can develop extremely low blood pressure. This occurs because fluid leaks into the lungs, which also causes problems breathing.
Neurologic toxicity: There can be a loss of speech and thought disturbances. Seizures can develop and the patients may turn comatose. Nevertheless most patients recover from this spontaneously.

Details of one case of CLL with successful treatment

Doug Olson was one of the patients who was studied in the publication in Nature. His original diagnosis was chronic lymphocytic leukemia when he was 49 years old. For 6 years he did not need much treatment. But then his leukemia flared up and chemotherapy got his CLL into remission for 5 years. Generally, leukemia behaves this way that treatment gets it into remission (meaning the leukemia is controlled). But on another occasion, it gets into a relapse, which means the leukemia flares up again. 11 years after the original diagnosis of the CLL there was a rapid decline due to another relapse. In a bone marrow biopsy 50% of the white blood cells were CLL and 50% were normal.

Infusion of CAR-T cells

He received his first infusion of CAR-T cells in September of 2010. Following this he became very sick and the oncologist hospitalized him for three days. One week later the oncologist could not find any more cancer cells in his body. But the cancer specialists were very reluctant to call it a cure at that time. Fast forward 10 years. And now there are still no cancer cells in Doug’s body. The blood analysis showed that active CAR-T cells are in Doug’s blood monitoring for him that no CLL cells reoccur. Now, 21 years after the initial diagnosis of his CLL the oncologists are convinced that the T-Cell Immunotherapy was what cured Doug.

Discussion

CLL is a special form of blood cancer. Chemotherapy has been successful in increasing survivor rates over the years. But the end of the patient with CLL comes from a final relapse of this leukemia form, which eventually no longer responds to chemotherapy. The researchers in this publication used a novel immunotherapy approach, where they introduced a chimeric antigen receptor into immune cells of patients in the lab. Subsequently they transfused this back into the leukemia patients.

T-cell Immunotherapy used surveillance T cells successfully

These modified immune cells became the “surveillance team” that eradicated new CLL cells and destroyed them on an ongoing basis. This immune therapy is getting rid of the last CLL tumor cell. The two cases described in this paper and investigated thoroughly after 10 years of immunotherapy intervention were completely free of CLL cells in their bone marrow biopsies. Two cases are not enough data, but it is a powerful result for a pilot study. Oncologists have to produce much larger clinical trials with more patients. This establishes that this new immunotherapy is superior to conventional chemotherapy and indeed prolongs survival compared to chemotherapy alone.

T-Cell Immunotherapy Cures Chronic Lymphocytic Leukemia

Conclusion

This pilot study showed that the immune system can be stimulated to suppress and eradicate leukemia (CLL) cancer cells. The authors introduced a chimeric antigen receptor into immune cells that were taken from patients. The researchers obtained blood samples. Then they introduced a chimeric antigen receptor into immune cells in the lab. Subsequently they injected these CAR-T cells back into the CLL patients. In these patients the CAR-T cells behaved like surveillance cells, which eradicated leukemia cancer cells on an ongoing basis. After 10 years of follow-up in two patients in this pilot study the clinicians could not find any CLL cancer cells in their bone marrows, but the CAR-T cells were still present. This type of study is encouraging as it is a model for immunotherapy of other cancers. It is a promising start, but obviously researchers need to do more studies to fine-tune cancer immunotherapy.

Sep

2021

Effects of a Plant-centered Diet on Cardiovascular Disease in Midlife

By Ray Schilling | Cancer, Cardiovascular disease, cholesterol, diet, exercise, heart attack, Mortality, Nutrition, olive oil, omega-3 fatty acids, Processed food

A study followed younger patients for 32 years looking for the effects of a plant-centered diet on cardiovascular disease in midlife. The researchers determined the heart attack and stroke rates when the participants were in their 50’s to 60’s. When on a plant-based diet cardiovascular disease rates fell by 52% compared to a control group with a meat containing diet. One subgroup changed the diet from a regular diet to a plant-based diet over 13 years. This reduced the risk ratio by 61% for heart attacks and strokes when assessed later.

Details of this study

There were 4946 adults as participants of this 32-year study. They were recruited in 1985 and 1986, at which time none of them had cardiovascular disease. The study completed in 2018. The results were published on Aug. 4, 2021. The researchers assessed the plant-centered diet quality using a tool with the name “A Priori Diet Quality Score” (APDQS). The higher the score, the higher the quality of the food. This means the person consumed nutritionally rich plant foods, limited amounts of high-fat meat products and less healthy plant foods.

Although a plant-rich diet consisted primarily of nutritionally rich plant foods, small amounts of animal products were also allowed. This involved low-fat dairy products, non fried poultry and steamed or grilled fish. This made the diet tastier and ensured that people would stick to this diet for decades.

Improvements of heart attack rates with plant-centered diet

After 32 years 289 cases of cardiovascular disease developed. The researchers compared participants with the highest food quintile to participants with the lowest food quintile. As mentioned, the risk for participants on a plant-based diet was 52% lower to get a cardiovascular disease. Moreover, a subgroup changed from a higher risk (fatter meals, meat, less vegetables) diet to a lower risk diet (lean fat, lean poultry, vegetables). Physicians followed this subgroup for 13 years and the risk ratio for heart attacks and strokes fell by 61%.

Comparison to other diet studies

There are other studies that looked at the effect of diet changes on the risk of developing heart disease. One such study examined 86 cross-sectional studies and 10 prospective studies in a meta-analysis. Vegetarian diets reduced deaths from heart attacks by 25% and brought down the incidence of total cancer rates by 8%. A vegan diet reduced the risk of total cancer by 15%.

In a study from the United Kingdom dated March 2019 several clinical trials were analyzed regarding non-diabetic populations. The question came up, what the effect of a Mediterranean diet was on cardiovascular disease incidence and mortality. The authors reviewed 30 RCTs (49 papers) with 12,461 randomized participants and seven ongoing trials. In one study the observation time was 46 months. A Mediterranean diet reduced the cardiovascular disease mortality by 65%!

Another study from Spain

Another study from Spain published in 2019 examined 7356 older adults (average 67 years) and followed them for 6.8 years. The investigators kept track of the physical activity and put everybody except the controls on a Mediterranean diet. The group on the lightest leisure-time physical activity consuming a Mediterranean diet had the lowest mortality. The all-cause mortality of this group was 73% lower than the control group.

What is so healthy about the Mediterranean diet?

Despite a wide variation between all the 15 countries bordering the Mediterranean Sea, there are common characteristics: an abundance of vegetables and fruit, along with nuts and legumes. Cereal products are largely whole grain. Olive oil is the principal fat source, and people eat fish, seafoods and poultry in moderation. They consume red meat rarely. Cheese and yogurt can be part of the diet, depending on the region.

The first clinical evidence supporting the health benefits of the Mediterranean diet came from the Lyon Heart Study. The researchers placed patients who had a heart attack either on the diet designed by the American Heart Association or a Mediterranean style diet. After a follow-up of 27 months, the group eating the Mediterranean diet had a reduction of heart attacks by 73% and a decreased mortality by 70% compared to the other group.

More detail on the ingredients of the Mediterranean diet

An analysis of the various foods of the Mediterranean diet shows the reasons for the health benefits clearly. The fats that people on a Mediterranean diet eat are heart-healthy monounsaturated fats like olive oil or fats that contain omega-3 fatty acids. They come from fish (tuna, salmon, trout, sardines) or from plant sources (walnuts, other tree nuts and flax seed).

As there is an emphasis on natural foods, the diet is extremely low in trans fatty acids (hydrogenated fats), which otherwise increases the risk for cardiovascular disease. As people consume more than 300g of vegetables per capita daily, the contents of antioxidants and other beneficial plant chemicals is much higher in comparison to Western diets. There are many individual components of the Mediterranean diet that contribute to the reduction of disease. This is particularly true for heart disease. It also is apparent, that there is not one single food or nutrient that is responsible for the health benefits. What matters are the interactive effects of all the nutrients that lead to the health benefits.

No processed food means healthier living

The practical application does not mean deprivation and starvation, but a move away from processed fats (margarine), baked goods (donuts, muffins, pastries), and high saturated fat snacks and trans fats (chips, crackers, cookies, pies). Food choices move towards those of fresh fruit and vegetables, nuts, fish, and olive oil. Portions or servings have to be adequate to maintain a healthy weight.

Mediterranean food is not the heaping plate of pasta with an afterthought of vegetables. It also is not the super-size fast food pizza with pepperoni and cheese. Mediterranean food incorporates fresh food rather than fast food. It entails a shift from large portions of red meat to smaller portions of fish, a transition from highly processed foods to ample helpings of dark green vegetables with a dose of olive oil. Low amounts of alcohol, especially red wine can make a meal enjoyable, which means that the limit is one drink per day for women, and two drinks per day for men. After dinner go for a walk!

Olive oil is one of the reasons why the Mediterranean diet is so healthy

In the past it was thought that the monounsaturated fatty acids in olive oil would be the reason why it is protective of the heart. However, newer studies have shown that it is the polyphenols and among these in particular hydroxytyrosol that lower blood pressure and protect you from hardening of the arteries.

A 2012 study from Spain has found that mortality from heart attacks was 44% lower than that of a control group who did not incorporate olive oil in their diet.

How polyphenols in olive oil work for you

Only two tablespoons of extra virgin olive oil per day protect you from heart disease. It does so by reducing the total cholesterol level in the blood as well as the LDL cholesterol level. When there is more polyphenol in olive oil (such as in extra virgin olive oil), the body produces more HDL, which is essential to extract oxidized LDL from arterial plaque. On top of that polyphenol rich olive oil increases the size of the HDL particles (these larger particles have the name HDL2), which are more efficient in extracting oxidized LDL from arterial plaques. A Sept. 2014 study in humans showed that higher polyphenol olive oil as found in extra virgin olive oil caused an increase in the more effective HDL2 particles. This cleans out plaques from arteries more effectively than the regular, cheaper olive oil.

Effects of a Plant-centered Diet on Cardiovascular Disease in Midlife

Conclusion

Several large, well-controlled studies showed that there are pronounced effects of a plant-centered diet on cardiovascular disease in midlife. Heart attack rates and mortality rates were reduced by 25% to 73% on a Vegan diet or a Mediterranean diet. When people combine a plant-centered diet with regular physical exercise they also live longer. One of the ingredients of a Mediterranean diet is extra virgin olive oil. It contains polyphenols that lower total and LDL cholesterol. It also increases the larger particles of HDL cholesterol with the name HDL2. HDL2 is more efficient in extracting oxidized LDL cholesterol from arterial plaques.

What you can eat on a plant-centered diet

A plant-centered diet incorporates fresh food rather than fast food. It entails a shift from large portions of red meat to smaller portions of fish, a transition from highly processed foods to ample helpings of dark green vegetables with a dose of olive oil. Instead of large portions of beef and sausages shift to seafood (tuna, salmon, trout, sardines), walnuts, other tree nuts and flax seed. The statistics clearly showed the effects of a plant-centered diet on cardiovascular disease in midlife with a reduction of heart attacks and mortality.

Some of the text above was published previously here.

Jun

2021

Being A Morning Person Can Prevent Depression

By Ray Schilling | Anxiety, Cancer, Cardiovascular disease, Circadian rhythm, coffee, depression, Gastrointestinal Disease, heart attack, Insomnia, Lung Disease, Mortality, neurological disease, telomeres

A British study concluded that being a morning person can prevent depression. It was reviewed also in CNN. The study used sleep data from 85,000 UK participants in the Great Britain Biobank Study. They wore wrist activity monitors that provided sleep data. Researchers compared the sleep data with the self-reported mood changes. They found that if the sleep pattern is misaligned with the circadian rhythm, those who are night owls are at a higher risk of developing mood disorders. The controls were those who were morning persons. They were not affected by the misalignment effect.

Normal sleep pattern

Natural sleep habit or the circadian rhythm starts between 10 PM and 11 PM and continues for 7 to 8 hours. Your hormones are replenished during your sleep. This helps your body’s hormones and the immune system to restore itself overnight.

“The health problems associated with being a night owl are likely a result of being a night owl living in a morning person’s world, which leads to disruption in their body’s circadian rhythms”. This is what sleep specialist Kristen Knutson said. She is an associate professor of neurology and preventive medicine at Northwestern University Feinberg School of Medicine.

Reclaim your natural sleep habit

The key is to learn to live within your circadian rhythm pattern. Caffeine is a powerful stimulant and will stop you from falling asleep. For this reason, it is best to avoid caffeine-containing beverages. If you cannot live without your favourite cup of java, switch to the decaffeinated version. Stop using LED lights (from TV, computers, tablets or smartphones) 2 hours prior to your bedtime. Use dark curtains and enjoy a comfortable bed. Maybe read that thriller, earlier in the day instead of making it your bedtime story. And do yourself a favour: you do not need the eleven o’clock news on TV! They will probably stop you from falling asleep. Go to sleep between 10PM and 11PM.

Children can have problems with sleep disturbances and depression

Another study published March 22, 2021 in the Jama Network showed that depression had an association with sleep disturbances in youth and children.

A meta-analysis of 16 publications looked at depression and disturbed sleep. It showed that depression was 1.5-fold higher in sleep disturbed youths/children compared to controls with a normal sleep pattern.

Other studies re. being a morning person can prevent depression

Another study with Dr. Knutson as the lead author appeared in 2018. The authors found that various health conditions, mood disorders and mortality were on the increase the more the sleep rhythm deviated from the circadian rhythm. Morning persons were protected from this effect. But night shift workers and night owls were at a higher risk of disease. Specifically, they found the following associations for evening types.

Evening types compared to morning types had a 1.94-fold risk of psychological disorders
The risk of diabetes was 1.30-fold for evening types
Neurological disorders had a 1.25-fold risk in evening types
Gastrointestinal/abdominal disorders occurred 1.23-fold more often in evening types
respiratory disorders were 1.22-fold more common in evening types
Evening types had a 10% increased risk of all-cause mortality

The researchers concluded that externally imposed timing of work and social activities has potentially serious health consequences.

Circadian misalignment responsible for disease

Dr. Knutson also said: “Circadian misalignment could also lead to inadequate sleep duration and quality, which could also impair mood and exacerbate mood disorders.”

In other words, circadian misalignment to circadian rhythm problems. This can cause mood disturbances, but eventually lead to the diseases listed above.

Evidence of health risks in night shifts workers

The medical literature is full of examples that the health of night shift workers is significantly affected by circadian misalignment. Here are a few examples.

1.Here is a random selection to illustrate the health risks of night shifts workers. A study from 2015 examined the sleep patterns of 315 shift nurses and health care workers in Iranian teaching hospitals. They found that 83.2% suffered from poor sleep and half of them had moderate to excessive sleepiness when they were awake.

2.This South Korean study examined 244 male workers, aged 20 to 39 in a manufacturing plant. Researchers compared blood tests from daytime workers to blood tests from night shift workers. They also obtained inflammatory markers like the C-reactive protein and leukocyte counts. Night shift workers had significantly higher values. The investigators concluded that shift workers have increased inflammatory markers. This is a sign of a higher risk of developing cardiovascular disease in the future.

Higher mortality and higher cancer risk in nighttime workers

3. A Swedish study found that white-collar shift workers had a 2.6-fold higher mortality over a control group of daytime white-collar workers.

4. Another study compared night workers in the age group of 45 to 54 with daytime workers and found a 1.47-fold higher mortality rate in the night shift workers.

5.In a study from China 25,377 participants were part of a study that investigated cancer risk in males with more than 20 years of night shift work. They had a 2.03-fold increased risk to develop cancer compared to males working day shifts. Women with night shift work in this study showed no effect with regard to cancer development.

Healthy telomeres with healthy sleep pattern

It is true that you can suffer multiple health problems, as all of your hormones depend on the resetting during your deepest sleep between 2AM and 4AM triggered by the nighttime melatonin response. Even your telomeres, the caps of chromosomes in every cell get shortened from too much stress and too little sleep.

One example of such a study comes from Milan, Italy. https://oem.bmj.com/content/75/Suppl_2/A480.1

In this 2018 study researchers compared 46 nurses who had worked in night shifts with 51 nurses working day shifts. Among the night shift workers breast cancer was common, but not among day workers.

Shortened telomeres, hypomethylation of BRC1 gene and p53 gene

In the night shift nurses from Milan there was hypomethylation of the breast cancer gene BRC1. There was also hypomethylation of the general cancer gene p53. At the same time significant telomere shortening occurred in night shift nurses who had worked night shifts for more than 15 years. This likely all worked together in causing night nurses to develop breast cancer more frequently.

Shortened telomeres mean a shortened life span. The reason for this is that people with shortened telomeres develop heart attacks, strokes and cancer. This is what shortens the life span. How do we avoid this risk? Go back to healthy sleep habits. As mentioned above it is best to start going to sleep between 10PM and 11PM and sleep for 7 to 8 hours. Night owls delay going to sleep by 2 to 3 hours.

Being A Morning Person Can Prevent Depression (click image to enlarge)

Conclusion

A publication in Molecular Psychiatry demonstrated that evening person (night owls) are more likely to develop depression. This is in comparison to morning persons. As discussed, other researchers showed that evening persons also can develop diabetes and neurological disorders. In addition, respiratory disorders and gastrointestinal disorders are more common in night owls as well. When it comes to mortality, evening persons have a 10% increase of mortality over morning persons. There is a large body of literature regarding diseases of night shift workers. Night Shift work is perhaps the most extreme example of a circadian misalignment. It leads to poor sleep, inflammation in the body, increased cancer risk and higher mortality compared to day shift workers.

Prevent telomere shortening

Even the telomeres get shortened in night owls and night shift workers. We can prevent problems like these by going to bed in time and sleeping according to our circadian rhythm. If you had a poor night’s sleep, make up for it with the help of an afternoon nap. Do not sleep all afternoon though; half an hour or one hour will be enough. Even a short, restful nap after coming home from work can restore your feeling of wellness.

Jan

2021

Review about Human Oncolytic Virus Research in 2020

By Ray Schilling | Cancer, immune system, Mortality

The British Medical Journal published a review about human oncolytic virus research in 2020. That is to say, the BMJ published this report in July 2020. On the negative side, the report is rather complex with many technical terms. With this in mind, I will keep it as simple as possible for this summary. Notably, oncolytic viruses are a new way of treating cancer. Adenovirus was the most common oncolytic virus in use by cancer research in the past 20 years. It must be remembered, researchers applied this to mainly melanoma and gastrointestinal cancers. In the past I discussed the use of oncolytic viruses in a related post.

History of licencing of oncolytic viruses

The first oncolytic virus was licenced in 2004 in Latvia. This was an RNA virus derived from the native ECHO-7 strain of a picornavirus, called Rigvir. This oncolytic virus was approved for treating melanomas.
Shortly after, in 2005, China approved a genetically modified adenovirus, H101 as an oncolytic virus. The approval was for the treatment of nasopharyngeal carcinoma combined with chemotherapy.
In 2015, the U.S. the FDA approved T-VEC (Talimogene laherparepvec), an attenuated herpes simplex virus, type 1. This new oncovirus encodes granulocyte-macrophage colony-stimulating factor (GM-CSF). This is effective for the local treatment of inoperable, recurrent melanoma. It works for cutaneous, subcutaneous and nodal lesions in patients with recurrent melanoma after initial surgery.

Review of 20 years of human oncolytic virus research

The investigators reported about 97 clinical trials with oncolytic viruses performed between 2000 and 2020. That is to say, this involved 3233 patients with cancer. Most of these trials were phase I (50.5%) trials. There were an additional 6.2% studies, which were phase I/II. 11.3% were phase II clinical trials and only 2.1% were phase III clinical trials. 29.9 % of the literature did not specify what type of trial the investigations were about. However, they likely belonged into the phase I category as they reported on first trials of a therapy on man.

*Oncolytic viruses derive from various types of viruses***

The number of studies that used a certain virus-derivative are included in brackets. It must be remembered that most of the studies dealt with six viruses: adenoviruses (30), herpes simplex virus (HSV-1) (23), reovirus (19), poxvirus (12), Newcastle disease virus (NDV) (5) and measles virus (3).

Stimulation of the immune system through GM-CSF

In 24 studies the researchers introduced GM-CSF transgene into an oncolytic virus. GM-CSF is a glycoprotein that is normally produced by granulocytes, a type of white blood cell. In this case, it stimulates dendritic cells, the precursors of T cells to produce killer T cells. Notably, this stimulates the immune system to better fight cancer.

Types of cancer targeted with oncolytic viruses

It is important to realize that the majority of the studies treated melanoma cases and gastrointestinal cancers. Namely, gastrointestinal cancers included esophageal cancer, gastric (stomach) cancer, colorectal cancer and pancreatic cancer. There were 30 studies involving melanomas with 1000 patients. There were 76 clinical trials regarding gastrointestinal cancers with 577 patients.

Moreover, other cancers where oncolytic viruses were studied were head and neck cancer (15 studies) breast and gynecological cancers (31 studies), genitourinary cancers (26 studies), and sarcomas (16 studies).

Other drugs given along with oncolytic viruses

It must be remembered that of the 97 total studies 62.9% were clinical trials where oncolytic viruses were the only therapy. In 37.1% of the studies physicians gave the oncolytic viruses along with cytotoxic chemotherapy, immunotherapy or radiotherapy.

Side effects of treatment with oncolytic viruses

The safety profile for treatment with oncolytic viruses appears to be tolerable. Fever was common, as were chills. Some patients reported nausea and vomiting, flu-like symptoms, fatigue and pain. But these symptoms disappeared within a few days.

Suppression of the bone marrow for a period of time was common, but more so when there was a combination of oncolytic viruses with chemotherapy. None of the patients transmitted viruses to household contacts or the healthcare team.

Antitumor activity in clinical trials with involvement of oncolytic viruses

An analysis of clinical responses to oncolytic virus therapy showed the following:

1% had disease control, which broke down as follows (items 2,3 and 4)
4% complete control (=cure)
7% partial control
12% stable disease
9% No response to treatment with oncolytic viruses

HSV-1 derived oncolytic viruses had the best response. The responses were not as good with adenovirus, reoviruses and with vaccinia viruses.

Discussion

Researchers of the BMJ publication analysed 97 clinical trials regarding oncolytic viruses over the past 20 years. This showed a number of points worth mentioning.

The goal of oncolytic virus therapy is to induce tumor cell death. Physicians could achieve this indirectly by stimulating the immune system. Oncolytic viruses can stimulate both the innate immune system and the tumor-specific adaptive immune response.
In the earlier years a lot of clinical trials investigated the safety of oncolytic viruses. But it became clear that oncolytic viruses were safe and fairly well tolerated.
Many clinical trials involved oncogenic viruses with GM-CSF recombinant genes. This gene makes the oncolytic virus produce the GM-CSF protein, which stimulates dendritic cells. The end result is that the immune system produces more killer T cells that attack cancer cells, which results in higher cure rates.

Conclusion

In a review researchers discussed the use of oncolytic viruses in cancer therapy over 20 years . Oncolytic viruses are derivatives mostly from adenoviruses, herpes simplex virus (HSV-1), reovirus, poxvirus, Newcastle disease virus (NDV) and the measles virus. In various clinical trials researchers found that disease control was achieve in only 21.1% of treated cases. There was a cure rate of 3.4%, but another 17.7% had partial control of the cancer or stable disease. But 78.9% of treated patients showed no response to treatment with oncolytic viruses. Obviously more research is necessary to improve the cure rates in cancer patients treated with oncolytic viruses. Clinical trials with combinations of immune checkpoint blockade and oncolytic virus therapy would also be helpful. All in all, oncolytic therapy is at this point not yet an effective form of treatment for cancer.

Jan

2021

Melatonin Is More Than a Sleeping Aid

By Ray Schilling | Alzheimer’s disease, Anti-aging medicine, Autism, autoimmune disease, Cancer, Cardiovascular disease, Circadian rhythm, Dementia, Diabetes, Health, heart attack, Heart Disease, Hormones, immune system, Inflammation, Insomnia, melatonin, Menopause, mitochondria, Multiple sclerosis, neurological disease, Osteoporosis, Parkinson’s disease, sleep, Stroke

Notably, the January 2021 issue of the Life Extension magazine informs you that melatonin is more than a sleeping aid. It contains an interview between Dr. Roman Rozencwaig and a Life Extension (LE) magazine reporter. It must be remembered that Dr. Rozencwaig dedicated much of his career to the healing effects of melatonin. Another keypoint is that in 1987 Dr. Rozencwaig published a paper together with two other researchers. Specifically, it showed that melatonin production by the pineal gland declines in older age. Markedly, they stated that this is the reason why people age and why diseases of aging develop. Another key point is that Dr. Rozencwaig also stated that taking oral melatonin can promote a healthier life.

Melatonin deficiency causing aging and various illnesses

With the aging process the pineal gland calcifies and melatonin production is steadily declining. Surely, along with this is a deterioration of the circadian hormone rhythm. Meanwhile, the neuroendocrine system in the brain gets disorganized. Accordingly, this causes various diseases to occur. To emphasize, Dr. Rozencwaig says that a proper balance between melatonin and neurotransmitters is what we need to maintain health and longevity. As a result, a daily intake of melatonin supports healthy aging and longevity.

The many clinical effects of melatonin

Oral melatonin tablets help you to fall asleep easier, particularly the population that is older than 60 years.

But besides that, melatonin has many other clinical effects.

Melatonin improves immunity, which improves resistance against infections. It helps also in cancer prevention
Melatonin maintains the circadian hormone rhythm by synchronizing pituitary and hypothalamic hormone production
It protects the brain and may prevent Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, autism, and others
Melatonin modulates anti-inflammatory cytokinins in different diseases

Dr. Rozencwaig mentioned that melatonin slows down the aging process. There are multiple intertwining reasons for this.

Melatonin’s actions against the aging process

Melatonin regulates gene expression. This means that some signs and symptoms of aging can be reversed through genetic switches
Because melatonin regulates the immune response, the body is more protected against viral, bacterial and parasitic infections
Melatonin helps to overcome chronic inflammation that produces cytokines
Melatonin is also liver-protective through stimulation of an enzyme (AMPK). This enzyme regulates cellular metabolism.
There are other processes that melatonin is involved in: energy metabolism by protection and restoration of mitochondria.
Melatonin protects against osteoporosis by balancing and regulating bone formation versus bone loss.

More actions of melatonin

An important function of melatonin is the stimulation of antioxidant enzymes like glutathione peroxidase and superoxide dismutase (SOD)
Melatonin regulates sirtuins, which are proteins that maintain cellular health. They protect you from obesity, type 2 diabetes, cancer, heart attacks and strokes, dementia and more
As already mentioned, melatonin is a neuroprotective agent and may prevent Alzheimer’s and dementia
Melatonin stimulates apoptosis of cancer cells.
Oral health and melatonin are related. Melatonin suppresses herpes infections and periodontal disease. Melatonin prevents oral cancers to a certain degree. In addition, dental implants survive better when melatonin is present in saliva.

Prevention of cognitive decline

Dr. Rozencwaig mentioned that melatonin stops much of the cognitive decline of aging. To achieve this the following processes take place.

Melatonin improves the sleeping pattern and increases the amount of REM sleep.
During sleep melatonin removes toxic amyloid and tau proteins. We know that with Alzheimer’s disease these are the proteins that accumulate in the brain.
Melatonin improves myelination of white matter in the brain. This prevents brain atrophy of old age.
The brain is metabolically very active and produces toxic free radicals. But melatonin is a strong antioxidant dealing with free radicals. Melatonin can cross the blood brain barrier and stimulates enzyme production to eliminate toxic reactive oxygen species.
Chronic inflammation also increases with age, but melatonin deals with this condition in the brain.
Here are 3 subtypes of melatonin receptors. The body integrates the multitude of actions of melatonin with the help of these receptors.

Melatonin Is More Than a Sleeping Aid

Conclusion

Melatonin is a powerful antioxidant that has many other useful protective qualities as explained. The body integrates various functions like anti-aging, anti-free radical activity, neuroprotection in the brain and more. Melatonin even synchronizes pituitary and hypothalamic hormone production. This helps to integrate the effect of melatonin, which benefits the body in many ways. Melatonin prevents Parkinson’s and Alzheimer’s disease, multiple sclerosis, autism, obesity, type 2 diabetes, cancer, heart attacks, strokes and dementia. Melatonin production deteriorates from the age of about 60 onwards. It is important to supplement with melatonin at nighttime from that age on. Usually, you only need small amounts of melatonin, between 1mg and 3 mg at bedtime. This prevents most of the serious diseases of old age, stimulates your immune system and lets you age gracefully.

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