Monday, March 13, 2023

6-Gingerol

6-Gingerol





6-Gingerol is the bioactive ingredient in raw ginger that inhibits arginase and helps convert M2 (tumor-protecting) macrophages into a M1 (tumor-attacking) phenotype. This is an important area of immune resistance and immune checkpoint failure. Also, Lo Russo, et al. showed that macrophages might be an important mechanism that resulted in hyperprogression (rapid cancer growth) with the treatment of PD-1/PD-L1 inhibitors. Hyperprogression is a major concern with this type of immune checkpoint therapy as it results in reduced survival that is actually caused by the therapy when patients are treated with drugs such as Keytruda and Opdivo.



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Friday, March 10, 2023

PULSED ELECTRIC FIELD ACTIVATES THE IMMUNE SYSTEM BETTER THAN RADIOFREQUENCY ABLATION

PULSED ELECTRIC FIELD ACTIVATES THE IMMUNE SYSTEM BETTER THAN RADIOFREQUENCY ABLATION





There have been several studies of the pulsed electric field (PEF) where tumor response was slowly verified in cancer patients. It was possible to demonstrate a better response in the immune system compared to traditional radiofrequency ablation (RFA) in a murine model, this shows a stronger immune cytokine profile and a better tumor response than radiofrequency thermal ablation for volumes of compatible ablation.

Understanding the differences in the post-ablation biological cascade between thermal ablation and PEF, which does not rely on thermal processes to kill cells. To understand the differences between those two methods we looked at cellular cytokine expression, immune cell infiltration, and tumor response (including contralateral rechallenge).” Regardless of not removing 100 percent of the tumor, the immune system is still activated. “.

While RFA-treated tumors showed immune cells to accumulate at the border of the treatment tumor zone, PEF-treated tumors showed immune cell infiltration throughout the tumor, thus PEF-treated tumors were found to have recruitment of dendritic cells than RFA-treated tumors,” according to Dr. Pastori. In addition, an increase in circulating adaptive immune cells is observed in the blood of PEF-treated mice. This observation was inversely related to volume tumor: increased numbers of adaptive immune cells generated lower tumor volumes in PEF-treated mice.”

The findings show that not all ablation modalities are treated equally: “Local administration of PEF demonstrates a systemic response, greater suppression of tumor growth, and possibly greater synergy with checkpoint inhibitor immunotherapy compared with traditional RFA,” said Dr. Pastori

The potential to generate a systemic immune response from local therapy opens up several new avenues for treatment. “For example, in patients with suspected metastatic disease, EPF could be administered at the time of diagnostic biopsy to synergize and potentially improve response to standard pharmacotherapeutic agents while avoiding a second procedure. Additionally, some patients may experience abscopal effects triggered by the mechanism of PEF cell destruction and the resulting antigen release and immune stimulation that acts systemically to produce off-target beneficial effects.”

Reference

Powers, M. P. (2023, 5 marzo). Pulsed electric field activates immune

system better than radiofrequency ablation. IR Quarterly. http://irq.sirweb.org/sirtoday/PEF-activaties-immune/



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Thursday, March 9, 2023

Beta Glucans

Beta Glucans





Beta glucans, also known as Β-glucans, are polysaccharides that come from the cell walls of oats, barley, mushrooms, yeast, bacteria, and fungi. They bind to immune receptors and can attract immune cells into the tumor environment. Depending on where they are derived, B-glucans can have different effects. It is still unclear which source of B-glucans is superior, if any. Theoretically the oat/barley-based B-glucans may have an advantage, but that still is not fully proven. No matter the source, all types of B-glucans seem to have immune enhancing properties. They are able to decrease regulatory cells and increase immune-stimulating cytokines, which can help “turn up the heat” in the tumor microenvironment. Since a cold tumor microenvironment is a major reason for immunotherapy failure, B-glucans have the potential to boost the response of immunotherapy.
As I had mentioned before, the potential list of natural substances that may be immune-stimulating is exhaustive. I selected some of the ones that I thought have the most evidence and potential, without being too overwhelming. A patient can only take so many supplements and medications.
Now that you know about a few immune enhancing supplements, we have to discuss some of the darker side of immunotherapy, adverse reactions. Thankfully we can use intra-tumoral injection to minimize these side effects, while maximizing success and reducing cost.



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Wednesday, March 8, 2023

HOW BREAST CANCER CELLS CAN REPROGRAM IMMUNE CELLS TO ASSIST IN METASTASIS

HOW BREAST CANCER CELLS CAN REPROGRAM IMMUNE CELLS TO ASSIST IN METASTASIS





Natural killer (NK) cells, which are a type of immune cells, have been found to limit metastasis by inducing the death of cancer cells, although metastasis continues in patients anyway, i.e., they keep escaping to other parts of the body.

Scientists continue to analyze the interactions between NK cells and invading breast cancer cells in their labs and have discovered that metastatic breast cancer cells can reprogram NK cells so that they stop killing cancer cells and instead place, help in metastasis.

Metastatic disease is the main cause of death from breast cancer, so it is necessary to know how and why this occurs in our body. The right way would be to prevent or reverse the reprogramming of natural killer cells in patients, it could be a new way to stop metastasis and reduce mortality from breast cancer”.

These studies have shown that NK cells selectively target the cells that initiate the metastatic process and how cancer cells trick the immune system into helping them,” says Ewald, lead author of the study, and co-director of the Cancer Invasion Program. and Metastasis at the Johns Hopkins University Kimmel Cancer Center and professor of cell biology at the Johns Hopkins University School of Medicine.

Dr. Elizabeth Jaffee is deputy director of the Johns Hopkins Kimmel Cancer Center; Co-Director, Skip Viragh Center for Pancreatic Cancer Clinical Research and Patient Care; associate director, Bloomberg-Kimmel Institute for Cancer Immunotherapy; and the Dana and Albert “Cubby” Broccoli Professor of Oncology.

Using molecular profiling and computational analyzes developed by Dr. Joel Bader, professor of biomedical engineering at the Johns Hopkins Institute for Basic Biomedical Sciences and Institute for Genetic Medicine, and Hildur Knútsdóttir, a fellow in the laboratory of Bader, Ewald said they were able to map every suspected molecular interaction between immune cells and cancer cells – and identify the ones that likely regulate this communication.

“As predicted, when we blocked these inhibitory signals, the NK cells continued to be the ‘good guys’ and continued to clean up the cancer cells,” says Ewald. “We are excited that this approach could be used to prevent metastasis formation, and we are also testing whether this approach could be used to reactivate an immune response to an existing metastasis.”

The researchers say the process could also be applied to other types of cancer.

Immunotherapies that target NK cells could also potentially be used alongside existing immunotherapies that stimulate T cells to fight cancer.

Reference

ecancer. (2020, 13 julio). Las células del cáncer de mama pueden

reprogramar las células inmunes para ayudar en la metástasis. https://ecancer.org/es/news/18166-las-celulas-del-cancer-de-mama-pueden-reprogramar-las-celulas-inmunes-para-ayudar-en-la-metastasis



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Tuesday, March 7, 2023

Anacardic acid

Anacardic acid





It is known that drugs used in chemotherapy can destroy cancer cells and normal cells, giving numerous side effects such as myelosuppression and leukopenia. In recent years, supplementation with herbal plants or natural compounds has been studied to complement cancer treatment and help protect your body from the harm this therapy can cause, such as curcumin (previously discussed) and Anacardic acid.

Anacardic acid found in cashew nuts and shell oil shows immunomodulatory and antitumor activity with minimal or no secondary effects. It is used in traditional medicine to treat mainly gastrointestinal disorders in Mexico. The many effects of Anacardic Acid include cytotoxic, antibacterial, and antiproliferative activities in different cancer cell lines and autologous cancer models.

It can also potentially protect against oxidative and inflammatory disorders in the lungs. Bokyung Sung et demonstrated in a study that Anarcardic acid down-regulates the expression of NK-KB-dependent gene products involved in cell proliferation, anti-apoptosis, invasion, and angiogenesis. It also potentiates apoptosis induced by TNF and chemotherapeutic agents having potential as an anticancer agent.

A study by the National Polytechnic Institute in Mexico demonstrated that Anarcardic acid could reduce the toxic effects of chemotherapeutic agents such as 5-FU and Carboplatin on bone marrow and leukocytes. These may be a consequence of the immunomodulatory effect of salicylic acid, which can also be combined with other antineoplastic agents to increase the effect and achieve higher tumor reduction ratios in patients, increasing their survival rate and quality of life.

https://doi.org/10.3390/molecules26113241

https://ashpublications.org/blood/article/111/10/4880/24271/Anacardic-acid-6-nonadecyl-salicylic-acid-an

https://doi.org/10.1182/blood-2007-10-117994



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Monday, March 6, 2023

Sulforaphane

Sulforaphane





Sulforaphane is obtained from cruciferous vegetables, such as broccoli. It is necessary to have enzymatic production of sulforaphane, which is generated when myrosinase converts glucoraphanin into sulforaphane. So, when you are looking for this as a supplement, you will want the activated form. Castro, et al. published a study in Cancer Prev Res, March 2019 that reported sulforaphane suppressed breast cancer stem cells. In regards to sulforaphane there may be some contradicting aspects when it comes to the immune response. Some studies suggest it inhibits TGF-B, which can reduce immune suppression in advanced cancers. A study by Johler, et al., Cancer Immunol Immunother, Dec 2016 showed that sulforaphane inhibits macrophage migration inhibitory factor (MIF) that can help cancer escape the immune system. Also, inhibiting MIF with sulforaphane can result in a decrease in MDSCs, which should further help the anti-cancer immune response. However, the authors, Liang, et al. published a study in AdvBiolRegul, Jan 2019 discussing how sulforaphane may be a “doubled-edged sword” when it comes to cancer immunotherapy. They state that sulforaphane acts pro-oxidatively in human T cells, which can inhibit their activation and tumor killing functions. Clearly, it is hard to say if it is best to take the good with the bad in regards to sulforaphane. In general, I feel the benefits mayoutweigh the negatives, but we certainly need more studies.



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Friday, March 3, 2023

Cannabis Products

Cannabis Products





Certainly you cannot delve too far into alternative and natural treatments for cancer without running into people saying that marijuana cures cancer. I have many patients who have tried cannabis products, but I have not personally run into any that were cured from using them. I wanted to know where these people who have been cured are. I attended somemeetings with people discussing all the benefits of cannabis. The stories they described sounded promising, at least in the way they tell them to the lay public. But I did not see the real evidence. Many of the cancers they were citing great benefits for are ones that people can generally live with for many years, if not a decade or more. So, stating that a person was still alive after one year of cannabis use was not the results I was looking for.

In regards to the immune response, research has shown that there are receptors in the immune system for compounds found in cannabis called cannabinoids. There are two receptors, CB1 and CB2. CB2 is found on immune cells. In an article published by Rieder, et al. May 20, 2009 in the journal of Immunobiology, called “Cannabinoid-induced Apoptosis in Immune Cells As a Pathway to Immunosuppression,” they describe that cannabis inhibits the immune system and increases regulatory cells. These are not good things when it comes to cancer. So, how can there be all this information out on the internet that cannabis cures cancer, or at least helps? Certainly it seems helpful with symptoms of cancer, but that does not mean it makes cancer better.

In my research I found that there was a general overall lack of good studies on this topic. At the European Society of Medical Oncology, September 2017; Taha, et al. presented a poster titled “The effect of cannabis use on tumor response toNivolumab in patients with advanced malignancies.” In their study there were some concerning results related to cannabis use and cancer, showing patient using cannabis with the immunotherapy Nivolumab had a greater than 50% reduction of their response rate (37.5% versus 15.9%).

On the positive side, there have been animal studies with CBD and a human study with THC directly injected into tumors that have had some promising results. Also, cannabis is a complex mixture, containing numerous compounds. It is verypossible that specific isolated extracts may have benefits. We still have a lot to learn in regards to cannabis products and the treatment of cancer. Our group plans to conduct further studies looking at the immune response from intra-tumoral injection of cannabis extracts. However, it does seem clear that cannabis products can help with certain cancer-related symptoms, but this is more for palliation and not for actual treatment of the cancer.



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