Jul
27
2018

Modified Poliovirus Effective Against Brain Cancer

A clinical trial found modified poliovirus effective against brain cancer. 61 patients with glioblastoma, the most deadly brain cancer there is, have been enrolled in this trial since 2012.

Glioblastoma treatment with genetically modified poliovirus

Dr. Gromeier, one of the lead cancer researchers at Duke University, Durham, North Carolina has done animal experiments. Unlike poliovirus, he found that genetically modified poliovirus was harmless for the central nervous system and yet he found modified poliovirus effective against brain cancer. This genetically modified poliovirus was attacking glioblastoma cells in cell cultures and in human brains. Dr. Annick Desjardins, a co-author of the study explained that the researchers had to take a piece of RNA away from the poliovirus and replace it with a neutral piece of RNA. This way it is still attracted to the numerous poliovirus receptors, which are expressed on many human cancers. The genetic sequence that allows poliovirus to reproduce in normal cells was taken out with the genetic modification. An inert RNA piece from the rhinovirus, the cause of the common cold was replacing this.

Effect of the genetically modified poliovirus

This way the modified poliovirus is no longer destroying nervous tissue. But the virus can still multiply in the glioblastoma cells, release toxins and kill these cancer cells.

Dr. Bryan Choi is a fellow in the Cellular Immunotherapy Program at Massachusetts General Hospital Cancer Center. He also works at the Department of Neurosurgery at Harvard Medical School. Although he was not part of this study he stated that this study was a giant step forward. “Perhaps the most promising aspect is the ability for this genetically modified virus to not only directly kill brain cancer cells, but to release tumor antigens,” Choi said. Antigens are toxic substances that stimulate the immune system to mount an immune response against the cancer. This immunotherapeutic effect is an important aspect of this new treatment modality.

Some human statistics of the pilot study showing modified poliovirus effective against brain cancer

Here are the highlights.

  1. 21% of the poliovirus patients are still alive three years after treatment; this compares to just 4% of the control patients who only received chemotherapy.
  2. The average survival time for the 61 patients who have received the genetically modified poliovirus therapy was 12.5 months. This compares with 11.3 months for a control group of matched patients. These had received standard treatment (chemotherapy).
  3. Some patients were much better responders than others. A 20-year old man a 60-year-old man survived 69 months (nearly 6 years). They are still alive today. This was unthinkable of in the past for patients with glioblastoma.

Repeat modified poliovirus therapy for glioblastoma recurrence

Dr. Darell D. Bigner, a co-author of the study, a professor of pathology and emeritus director observed the following. Some patients experienced initial reduction of the glioblastoma, and when the cancer came back they received repeat modified poliovirus treatments. To the surprise of the investigators the tumors shrank again and again. This was never the case with conventional chemotherapy. Once a glioblastoma is chemotherapy-resistant, chemotherapy will not work again.

Experience with modified poliovirus therapy

  1. In this trial treatment for glioblastoma started with implanting a catheter right into the center of the glioblastoma. An infusion of the engineered poliovirus followed, a process that could take up to 6.5 hours. Removal of the catheter was next.
  2. In the beginning researchers used higher doses of the genetically engineered poliovirus. Some people developed severe inflammation causing seizures, which needed treatment. Confusion and language difficulties were also side effects. Others developed pronounced nausea. The researchers decided to lower the dosage of the genetically engineered poliovirus, and the patients still had good clinical results.
  3. “We are presently enrolling in a phase 2 trial combining the genetically modified poliovirus with one dose of chemotherapy,” Desjardins said. “We are also enrolling in a trial for pediatric brain tumor patients.” In addition studies using genetically engineered poliovirus against breast cancer and against skin cancer are also in the planning stage.
  4. There are other new approaches where there the doctor injects the photosensitizer indocyanine into breast cancer tissue. Next the doctor points a laser beam near the infrared frequency of light to the cancer area. You find details about this procedure here.
Modified Poliovirus Effective Against Brain Cancer

Modified Poliovirus Effective Against Brain Cancer

Conclusion

A new approach to treating glioblastoma, one of the deadliest brain cancers, has shown promising results. A genetically engineered poliovirus is no longer making the person sick with polio, but instead destroys glioblastoma cells and prolongs patients’ lives. Some patients lived up to 6 years while controls lived less than one year. The effect of this new treatment occurs from the release of toxins within the glioblastoma cancer. This leads to cancer cell death and the release of these toxins. The immune system receives stimulation to recognize and destroy the remaining glioblastoma cells. At this point the basic steps of this new therapy are in place.

Future direction of research

But the same method will one day likely be in use for other cancers. There are plans for new clinical trials to examine this further. The researchers also want to test cure rates of a combination of chemotherapy and genetically engineered poliovirus therapy. This will answer the question whether the combination treatment will be better than genetically engineered poliovirus therapy alone.

Feb
08
2014

Sugar As A Cause Of Cancer

It has been known for a long time that cancer cells can survive without the ordinary aerobic pathways of energy production. They can get energy from a metabolic pathway, which bypasses normal cell metabolism (aerobic glycolysis). But many attempts of designing a cancer therapy to exploit this difference have so far been unsuccessful.

This Mayo Clinic website even explains that it would be a myth that cancer would grow better with sugar. The following pieces of research question this myth.

Sugar makes cancer grow faster (activates oncogenes) in fruit flies

In this study from the Icahn School of Medicine at Mount Sinai in New York City fruit flies were used as an animal model. You may ask, why fruit flies; we are not fruit flies, we are humans! As incredible as it sounds, on a cellular level our cell metabolism and the cell metabolism of fruit flies is identical. But the generation time of fruit flies is much shorter and results can be seen in days and weeks. To achieve the same in human trials would take months and years. Also, researchers could breed a strain of fruit flies that was susceptible to develop tumors. When they were fed sugar, the fruit flies developed insulin resistance within a short time. This model was chosen by the researchers as it is known for some time that in humans insulin resistance from diabetes, obesity, and other metabolic diseases leads to a higher risk of developing breast cancer, liver cancer, colon cancer and pancreatic cancer. The researchers wanted to sort out what the metabolic advantage of the cancer cells was under these conditions.

The researchers found that the sugar in the diet activated silent cancer causing genes (called “oncogenes)” in the fruit flies that in turn helped to promote insulin resistance and the development of tumors. Because of the insulin resistance sugar could not enter into the normal body cells, but the tumor was using up all of the sugar allowing the tumor cells to multiply at a rapid rate. The end result was that the sugar from the diet fed the cancer cells directly making them grow faster. Interestingly, when these flies that had developed tumors on a high sugar diet were switched to a high protein/low sugar diet, the tumors stopped growing and were contained.

In this fruit fly example the researchers were subsequently able to block cancer cell growth by special cancer suppressing drugs (acarbose, pyrvinium and an experimental drug AD81), which were given in combination. 90% of the flies given the triple-drug treatment survived to adulthood while control flies not treated with this regimen all died of their tumors.

Although this model was only done in fruit flies and one could question whether or not this was relevant to what is happening in human cancer patients, the following piece of research puts this fear to rest.

Sugar As A Cause Of Cancer

Sugar As A Cause Of Cancer

Human breast cancer cell study in vitro

In January 2014 the American Society for Clinical Investigation published a collaborative study between the Lawrence Berkeley National Laboratory, Berkeley, California, CA and the Hokkaido University Graduate School of Medicine, Japan, which used human breast cells in tissue culture showing that sugar could cause breast cancer.

The original papers of this US/Japanese research team are quite technical and I do not expect you to understand this link where it is published. I posted it for those who want in depth information. The researchers used a simple tissue culture model where they could observe tumor growth in cell cultures under the microscope using a gel where the breast tissue samples were placed side by side with normal breast cells that served as controls. The cell cultures of both normal cells and malignant cells were obtained from the same reduction mammoplasty tissue samples. This way the cell cultures mimicked a situation as close to the reality of what is going on in a woman’s body when breast cancer develops.

The normal breast epithelial cells were seen in culture to get organized as a roundish cell formation (an acinus formation) while the cancer cells were growing as irregular cell clumps. This visual effect was reproducible and is depicted in the paper. With high sugar concentrations in the growth medium breast cancer cells multiplied at a faster rate, not so the normal cells. But some normal cells underwent a transformation into abnormal and cancerous cell types. On the other hand, when sugar concentrations were severely restricted, morphological changes took place where cancer cells slowed down their growth or stagnated while some of them even changed into the normal cell formation (acinus formation). Using various known oncogene stabilizers the investigators could show that the same effect was noted as with the low sugar concentration in the growth medium.

The investigators tested whether other cell lines of breast cancer would show similar results as to the effects of sugar feeding or restriction. They were able to show that high sugar feeding activated cancer cells, no matter where the cancer cell lines originated. The authors discussed that metformin, which is known to control the metabolism in diabetic patients and lowers blood sugar levels, has also been shown to calm down growth of cancer (due to stopping oncogene stimulation), which improves the survival rates of many different cancer types in diabetic patients; it also reduces the risk of developing cancer in those who are taking metformin.

Other investigators have shown in mouse experiments that an impressive lowering of cancer rates could be achieved with low carb diets.

Human evidence for cancer causation and cancer prevention

Several clinical studies seem to indicate that there is a higher cancer rate in diabetics where insulin resistance can lead to activation of cancer producing genes (called oncogenes) and cause various cancers. In this link colorectal cancer and pancreatic cancer are discussed in relationship to diabetes and insulin resistance. High glycemic foods (sugar, starchy foods) were associated with breast cancer, colorectal cancer and endometrial cancer. The majority of trials showed this association although not all. The more obese patients were, the more pronounced the insulin resistance was and the more the relationship to these cancers became apparent. A diet that is high in starchy foods like potatoes, rice and bread is causing pancreatic cancer as was shown by researchers at the Dana-Faber Cancer Institute, Brigham and Women’s Hospital and Harvard School of Public Health. High glycemic diets have shown to cause colorectal cancer, diabetes and being overweight. The Standard North American Diet (SAD) is a pathway to many chronic illnesses due its high load in refined carbohydrates. Ironically the abbreviation for it is “SAD”, which in my opinion reflects adequately its sad influence on health and well being. We know now that sugar and starchy foods lead to insulin overproduction, which in turn causes the metabolic syndrome (also known as “insulin resistance”). This causes the immune system to weaken and fat to be deposited as visceral fat in the stomach area. Visceral fat is metabolically very active as it secretes cytokines like tumor necrosis factor alpha (TNF alpha), COX-2 enzymes and others. Insulin and growth factors from the visceral fat gang up together with the elevated blood sugar, which activates tumor-producing genes (oncogenes) to cause cancer.

While cancer rates are higher in patients with insulin resistance, they were lower in patients who did have normal insulin levels. It is important to concentrate your efforts on normalizing weight, which will normalize insulin sensibility and avoid the development of cancer. Sugar avoidance and avoidance of cereals and starchy foods will help you achieve this goal.

Conclusion

Although the idea that sugar could cause cancer has been around since 1924 (Dr. Warburg), it has taken up to now to be proven in animals and humans.

The purpose of this blog was to show how there is a connection between the consumption of sugar and starchy foods and various cancers in man. Animal experiments are useful in suggesting these connections, but many clinical trials including the Women’s Health Initiative have shown that these findings are also true in humans. It is insulin resistance due to sugar and starch overconsumption that is causing cancer.

We are now in a position to know why people who consume a low carb diet, develop less cancer than people who consume a high carb diet. I have followed such a low carb diet (also known as low-glycemic index food diet) since 2001 and find it easy to follow. However, I do not dispute that it takes some discipline to change the old way of eating to the new one. The benefits are definitely worth it: you are feeling well now and you are staying well as you age.

More information about hyperinsulinism that can cause breast cancer: http://nethealthbook.com/cancer-overview/breast-cancer/causes-breast-cancer/

Last edited Nov. 7, 2014

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Apr
01
2013

My Experience With Cancer Research

April is cancer awareness and fundraising month. I thought it would be interesting to analyze what’s going on behind the scenes of cancer research. I was a cancer researcher for over 3 years at the Ontario Cancer Institute (OCI) from 1972 to 1975 and I will share some insider experiences here.

1. Publish or perish

We were told by our supervisors to “publish or perish”. In other words all the experiments we did needed to fit into the larger picture the group was working on, and the results should be different and interesting and most of all publishable. There had to be significant differences between experimental groups and controls, so that publishers of medical journals would accept them for publication. There were often two or three manuscript revisions where the content was “massaged” (proper wording, comparing or opposing the results with other publications) so that it was considered “publishable”.

2. Fund raising awareness

One of the major fund sources for cancer research in Canada was the MRC (Medical Research Council of Canada), which has been replaced by the Canadian Institutes of Health Research (CIHR) in 2000. Without money there is no cancer research, so everybody was aware of the policies and expectations of the fund source.

3. Mouse model versus human tissue based research

I was working in the immunology section of the biophysics department, where basic medical research at the OCI is done. In this department much research had already been performed separating cell populations in a mouse model to determine what cell types were needed to initiate an immune response. The B cells in mammals are antibody-producing cells of the immune system that protect from viruses. T cells are thymus-processed cells that turn into killer cells, which can attack parasites and also cancer cells. I was working in this area. We did cell separation experiments where the cells were separated according to cell size and collected in vials. Subsequently remixing experiments were done to find out what cell types were needed to mount an immune response to a mouse tumor cell line as targets. I started questioning whether a mouse model would be the appropriate model to study human cancer biology. But this was not met with approval, as the “holy grail” was that what worked in a mouse model (mouse mammalian cells) should also work in the human situation (human mammalian cells).

My Experience With Cancer Research

My Experience With Cancer Research

4. Non-medical researchers in cancer research

This is a thorny issue, but a reality. My immediate supervisor in cancer research had a PHD in physics, which was perfect for sorting out density issues for cell separation experiments. His colleague and co-chair of the immunology department had a PHD in biology, which was a good fit for mouse experiments. Both of them felt somewhat insecure when I asked probing questions about relevance of mouse experiments for the human cancer condition. As I needed to publish my experiments, which were done under the supervision of these supervisors, I had to quiet down and concentrate on the mouse model the team was working on. For a while this could even be exciting as we were studying the cell interaction between macrophages and T cells to mount a cell-mediated immune response.

5. Regulation of the cancer research industry

After playing with cell cultures for 2 ½ years it was time for me to reach out to get a job in the cancer research field or else go back to medicine. In1975 there was no equal opportunity legislation in place that would have protected me as a landed immigrant from discrimination. The reality in 1975 was that only Canadian born physicians who attended a Medical School in Canada could become a director of a cancer research facility in Canada. The rules for me (I had left Germany right after my rotating internship) were that I had to go through further medical training and pass the Canadian licensing exam (LMCC), which I did eventually at McMaster University in Hamilton, Ontario. One final attempt to shed light on my options was an interview with the “big boss” at the Ontario Cancer Institute at the time, a physician cancer researcher, Dr. Ernest A. McCulloch, for whom I had great respect. He was a sharp thinker and had vision, and he was a fellow physician. I asked him what he would do on the long-term, if he was in my place. He said that in the long-term with my medical background it would be a lot more satisfying for me to get back into medicine and practice medicine. However, he wanted me to go on for another 1 or 2 years and publish more papers together with my supervisors. I decided for myself right there that I would leave cancer research and I prepared quietly for my exit. Within a short time I got a position to work as an intern at a hospital at McMaster University and in the spring of 1978 I passed the LMCC (licensing) exam. As a fully licensed physician in Canada I was no longer interested in “slave work” in cancer research. I also left the cold winters of Ontario behind and went to the west, to British Columbia.

6. Future vision of medical cancer research

Research has come a long way. Recently I came across a new breast cancer protocol, which is non-toxic, without chemotherapy and without radiation. It is so unconventional that the US research team, aware of the politics in the US, decided to do the initial trials in the Caribbean. I wrote a blog about this new breast cancer treatment protocol, which I believe will become the future standard for breast cancer therapy and perhaps even for other cancers.

In Germany and Switzerland there is an alternative breast cancer treatment with a non-toxic plant-based chemotherapy involving mistletoe extracts. It has a dual action, namely a chemotherapeutic effect, but at the same time an immune system stimulating effect. Here is a study going back to 2001, which is still relevant. There was a 40% long-term survival benefit in the Iscador group when compared to a control group without treatment. Normally, oncologists would jump at such an excellent chemotherapeutic agent as even chemotherapeutic agents that show a 25% beneficial survival effect would be considered a good treatment option. However, as the medication is a simple mistletoe extract and cannot be patented, Big Pharma is not interested in marketing this. As a result cancer treatment protocols in Europe are significantly different from those in North America.

In the future I would expect that non-toxic treatment methods for any type of cancer will be more successful than any chemotherapeutic or radiation treatment approaches as both interfere with the immune function, which is what will kill the patient at the end. As cancer is a disease where the immune system fails, cancer patients need to be shown how to stimulate their immune system, as this is the only thing, which can control cancer on the long-term.

You will hear more about epigenetic switches as often a cancer producing substance will turn off a gene (epigenetic switch) and this causes cancer.  Remove what throws that switch into the off position or introduce a healing agent that resets the switch and the cancer will get eliminated.

7. Prevention of cancer

The most powerful cancer preventatives are found in herbs, spices, vitamins and minerals. Did you know that curcumin, derived from the Indian spice turmeric, prevents a number of cancers? Similarly, vitamin D3 at high enough doses (4000 to 5000 IU per day) has been shown to prevent cancers. Linus Pauling showed long time ago that vitamin C at high enough dose would be an antioxidant and would stimulate the immune system and thereby be a cancer preventative. It works together with a detoxifying antioxidant, glutathione in the liver to neutralize any free radicals, which are aggressive chemicals that cause cancer. There are many other vitamins and minerals that I have explained elsewhere, which are needed together with organic food to give you the building blocks for a stable cell metabolism. This in turn will strengthen the immune system to defend you from toxins of the environment. A simple step like a daily exercise routine can cut your cancer risk down to 50% compared to those who elect to not exercise. Did I mention the importance of quitting smoking and cutting out alcohol? The “quit smoking” part has been known for some time. I learnt about cancer being caused by smaller doses of alcoholic beverages over a long period of time at the Anti-Aging conference in Las Vegas in December 2011. First I thought it would be a big deal to quit alcohol entirely. But since I have quit the modest few drinks per month that I thought I would miss, I actually have not missed them at all! I strongly believe in cancer prevention, so quitting alcohol completely was only one small step in this overall objective. In view of the recent statement by the WHO that 70% of all deaths are caused by smoking and drinking of alcoholic beverages, it behooves us to change our lifestyles, if we are at all interested in a healthy long life.

Conclusion

From reading about cancer research now, nothing has changed in cancer research circles since the time when I was part of it. Basic cancer research involving animal experiments is necessary. But in my opinion cancer research should be more human-centered using human cell lines in culture and using clinical trials. Ultimately cancer research needs to invent and develop new non-toxic cancer therapies to cure cancer patients.

More on cancer in general and on specific cancers: http://nethealthbook.com/cancer-overview/

Last edited Nov. 6, 2014

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Nov
22
2012

New Breast Cancer Treatment

For decades the dogma in medicine has been that any kind of cancer, including breast cancer would be treated with surgery, radiotherapy and/or chemotherapy. However, the 5-year survival rates were disappointing as this table shows. In the 1980’s the idea of adjuvant treatments for cancer came up and one of the popular methods was hyperthermia treatment. Cancer cells of a variety of cancers were found to be very heat sensitive, but the limiting factor in treating with hyperthermia systemically was the fact that   bone marrow cells were found to be very heat sensitive, which limited this application. With respect to breast cancer a review of data pooled from 5 trials showed that there was an 18% survival advantage due to the added step of hyperthermia in addition to radiotherapy. With radiotherapy alone a group of advanced breast cancer patients had a 5-year survival of 41%, but a comparable group treated with a combination of radiotherapy and hyperthermia had a survival of 59%.

Let’s back track for a moment and ask what breast cancer is. In the past we thought it developed out of one mutated cell, a breast cancer cell that would multiply into a clone of cells, which would first grow locally and then spread as metastases throughout the body at a later time. Unfortunately further research has shown that breast cancer can simultaneously occur in several spots in one breast or even in both breasts. The spreading of the cell clones to distant areas can occur very early on, but cells can lay dormant for years and start growing again at a time when the immune system is weak. With these facts in mind it can readily be seen that surgery cutting out a “local breast lump” will not be successful in the long term as a treatment of breast cancer, even when radiotherapy treatment is added to sanitize the local lymph glands of local cancer metastases.  Adding chemotherapy to eradicate distant metastases may  sound like a good idea, but chemotherapy is very toxic to bone marrow cells and to the immune cells that are supposed to kill the last breast cancer cells. As a result, chemotherapy has its own problems. Medical researchers had to start thinking outside of the box to discover a breakthrough in breast cancer treatment.

Fast forward to 2012. We still need a breast cancer treatment method that is non-toxic, that kills the breast cancer cells and that ensures that there will be no recurrences in the future.

New Breast Cancer Treatment

New Breast Cancer Treatment

This new treatment method is called “laser-assisted immunotherapy“, and it is being studied in a pilot study right now. 62.5% of end stage breast cancer patients had a response rate, something that has never been achieved before. The systemic side-effects of hyperthermia are overcome by heating only locally and directing the laser beam to the diseased tissue. The quality of the Laser beam is close to the infrared frequency of light . This is amplified by injecting the FDA approved compound indocyanine green, which absorbs more heat from the laser beam right in the cancer cells where it is needed for local hyperthermia treatment. The immune cells and the bone marrow cells are not harmed. The killed cancer cells release the cancer antigens that the immune system could not recognized before, as the immune cells were suppressed by suppressor T lymphocytes. With this added immune booster which is called “glycated chitosan” the cancer patients’ immune cells(called “killer T lymphocytes”)  are now being stimulated and are in a position to eradicate the last trace of cancer cells anywhere in the body. This is similar to a vaccination procedure that takes place within the body of the cancer patient. The T lymphocytes remember the surface antigen of the cancer cells that were killed. As a result the same type of tumor will never reoccur in that person’s life. It also takes care of the dilemma of the past that sometimes more than one cell type clone was found among the biopsy material of a cancer patient.

At this point the trial has not reached the 5 year mark of survival. Only 15 patients of the total of 45 patients have so far been enrolled. But 80% of the 15 patients have survived 2.5 years, which is unheard of with stage IV (late stage) breast cancer. In an experimental breast cancer model in rats where laser assisted immunotherapy was first shown to be effective, there was 100% survival of the treated group. However, it was noted that it was essential that all three components of the new treatment modality were followed. The protocol for the human pilot study therefore is as follows:

1. After placement of an anesthetic in the tumor area the indocyanine green is injected into the tumor (placement of the photosensitizer).

2. The laser beam near infrared frequency of light is applied in the tumor area (or over the palpable metastases). This application takes about 10 to 12 minutes and two courses are given over two weeks. An option of a third course within one year may be considered, but did not have to be done so far.

3. The adjuvant immune booster (glycated chitosan) is injected into and underneath the tumor right after the laser treatment is finished.

This triple therapy is the secret to the success of the new breast cancer treatment as each step is augmenting the other steps resulting in a complete destruction of the breast cancer and an active immunization against any of the residual cancer cells.

At this point the offshore Caribbean breast cancer treatment pilot study has been chosen to bypass frustrating FDA slow-downs in the US. But I suspect that proper protocols in a much bigger randomized US based study will follow the obvious successes in these late stage breast cancer cases. New cancer therapies are urgently needed. They are typically introduced by treating “incurable” (late stage) patients first. We are about 2 1/2 years away from the completion of this pilot study so that 5-year cures rates can be compared to older studies with the conventional cancer treatment approach. I am convinced that this new approach will not only help breast cancer patients,  but will also help prostate cancer patients and pancreas cancer patients (these three come to mind as they all are glandular cancers). Surgery for the removal of lymph gland metastases in prostate cancer patients and breast cancer patients using laser assisted surgery with indocyanine green stained lymphatic tissue has already been pioneered. It also opens up possibilities of modifying the method to suit other types of cancers.

More information about breast cancer: http://nethealthbook.com/cancer-overview/breast-cancer/

Last updated Nov. 6, 2014