Tue, 4/12 4:55PM • 1:47:23
SUMMARY KEYWORDS
tumor, cancer, cells, patient, tumor microenvironment, treatment, nanoparticles, anti tumor, platelet, pnp, artemisinin, molecule, patel, immune system, pdl, receptor, present, immune response, cytokines, immune checkpoint
SPEAKERS
Bill Clearfield
00:23
Does Aaron
00:27
Dorito
00:32
inflation is hyperinflation. You’ll see inflation go down to all these been making the news because they were going to raise 50% in Europe,
00:42
parts of the United States as well. Dr. Phil
00:47
Ophea Hi there. How are you? Hi, how are you? Hello everyone. Hi well, okay, just the four of us so far. Dr. Burgess now. So
Bill Clearfield 01:02
so we were supposed to have a local judge here talking about legal stuff, but he had got a murder case at the last minute. So he’s going to be postponed a week. So I know Dr. Burgess is very upset about that.
01:20
Yeah. Hey, so as Dr. Patel is tonight, right?
01:24
Yeah, yeah, we were supposed to have a judge Egan Walker, who’s a district judge here in Reno. But he got a murder case at the last minute. He had to drop out. He said he couldn’t join us till 630. And I know that’s way past your bedtime, Johnny.
01:41
Yeah. So how’s everybody I was listening to Dr. Patel last night. She is so fat. Fantastic. Thank you
01:59
that’s what we like. So So I went to the AMG meeting in Florida last weekend and they spent four hours on not blocking estrogen for men on testosterone levels on testosterone. There are four different lectures on same thing. So I don’t know why. Going over over and over and over again again and again. So you know
02:31
why because you are not the in charge. You were not there to turn. I gave
02:37
the I don’t know if I gave the talk here to progesterone after hysterectomy. So no, I’m not in charge of that. Quite frankly, the thing that I am in charge of. I’ve had enough if that Las Vegas Strip. That was enough. So I think Dr. Burgess should take it over
03:01
to Dr. Zini and Dr. Patel. Lhasa he loves this kind of stuff.
03:10
Yeah, well,
03:11
the administrative stuff is different than than just doing the other stuff, which is educational, your your educational, as well as administrative.
03:28
There’s all sorts of bad actors in the administrative worlds. It’s just
03:34
Oh, I know that I know. I used to be in charge. I was of course director so I know what you’re talking about. And yeah, they all got their handout though. handout for what? If you show up you owe the money. Okay. So,
04:05
okay, so the guy said we were supposed to have judge Egan Walker, who’s local district judge here and I was going to have him give us a little talk on integrative medicine and the law so that we stay out of trouble. But he wasn’t able to make it to light late tonight. So he said he would be around next week. So we’ll do it next week.
04:33
Well, last night, Dr. Patel’s group and my wife are discussing their very thing. How do you get limb protect? How do you get legal protection? And are you protected? Questions? Well, I would assume no. Take the answer is no and then just take it from there. came down to one thing standard of care. Yeah, well,
05:02
we’re not doing the standard of care. We weren’t we wouldn’t be in this group. That’s the that’s
05:10
the standard of care is what group you belong to and what is the protocol of the group and exactly the group and peers are not the one in your town or in your city or in your state. But those who are practicing the medicine have this similar guide?
05:32
Yes. Yeah. But that would work only if we connected to Medical University. Yes. Right to have a CME and you have to have connected university like Dr. You can come up and write down on your website, that vitamin D is decrease the risk of cancer and you recommend it as a group, like the Canadian oncology society that and if you have many academies, writing on their website the same thing, then they will not be sending letters to the doctors telling them how you cannot say vitamin D, prevent cancer or protect, lower the risk of cancer, things like that. We need to and that’s why Dr. Sylvia here. And she can bring the law and all that things upfront and make it clear because I think doctors are unaware about those regulations and county regulations to fight back. You’re right about that. So,
06:44
okay, anybody
06:46
that’s gonna be that’s one person protect you from liability. But there are ways to decrease significantly decrease your liability and that’s what we’re looking at. Okay.
07:02
So, how about these fancy trusts and all this nonsense? Anybody have any of that kind of stuff? The combination they show, you know, we’ve had we’ve had the group come in many times to or to omit John, you know, the weather out of Chicago? Yeah, they’re selling a whole trust package and all of that. I mean, I have no idea what any of that stuff so the balance
07:29
just just to make it short, I lost $10 million in a trust because they thought it would protect the family. So when you do form a trust, you also incorporate other elements. So the three of us put in millions and not one of us received a penny. Well, those who never gave a penny receive millions. They have to be extremely careful with that stuff. I’m sure we’ll figure it out.
07:54
It’d be nice to figure it out beforehand, not after right.
07:58
In the meantime, we’re leaving the country and doing things out of the country. So we’ll see how that works to
08:05
Where are you going? Where are you going Bahamas?
08:08
Well, your friend in the Bahamas, Dr. Bethel, right.
08:12
Right. Let’s do that. I think he has a very nice clinic. He’s very open minded, very nice guy. I like him a lot. And he has a big land tear as well as nine acre of land on the beach, and it’s like a heaven there.
08:27
Yes, he’s here and we have a few other really top notch people on the Bahamas and I’m sure we can all work together. Well follow through and we’re also doing road town. But we’ll speak to that later.
08:43
Okay. Well, okay, it’s a little bit after five Dr. Patel’s. So
Bill Clearfield 08:52
again, thank you so much for participating and being part of our group and giving so much of yourself so I’m gonna let you introduce yourself. For those who don’t know you. Most everybody here is pretty much irregular from what I can see. So you’re on Dr. Patel, take it away.
09:10
Okay.
09:27
So those of you don’t know me. My name is Dr. Kalpana Patel and I am a practicing nurse Environmental Health Center buffalo. I’m president of the breast Environmental Health Center Buffalo and I am board certified in the environmental medicine, as well as for other boards. I am board certified including the board of American Academy of stem cell physicians, which was my last board certification few years ago. Whatever I do, usually I like to be board certified. So at least I am knowledgeable in the subject, what I am practicing. So in next few years so in next few years, we plan to have and maybe a surprise to Dr. Lhasa but an immuno oncology and and so the new horizon in the treatment of cancer and, and why I’m so much interested you will look at this epidemiology and you will know cancer is the second leading cause of deaths and out of the increase very out of two people at least one is going to get cancer by 2040 39.5% of men and women will be diagnosed with cancer at some point in their lifetimes. That was based on the statistics of 2015 to 2017. And cancer mortality was also projected to be very high and as a result the cost is likely to increase as population ages and more people have cancer as we know that it is the age related issue. If not more or less that old people have a higher incidence of cancer compared to the young ones. And we will be responsible for the payment in our national money granted medical care. Now if you look at the other statistics, that 2018 There were 810 point 1 million new cases versus 9.5 million cancer related deaths worldwide. So that means that out of two people, those who get cancer on is going to die. And that really stinks. But by 2040 that it even increases they anticipate 29 point 5 million will have cancer and cancer related deaths will increase to 16 point 4 million which is greater than 50%. So cancer rates are highest in the countries where population have the highest life expectancy. Also higher level of education and high standard of living. Most of the time this is true except in cervical cancer, where the reverse is true. The incidence rate is highest in the countries in which population ranks low on and the life expectancy as well. As standard of living and education. So now let’s look at the what are the most so solid tumors make up the 90% of newly diagnosed cancer cases. And how are they treated? They’re treated by surgery, chemotherapy and radiation. So surgery is touted as as a cure. But I think it is a illusion because the residual and metastatic disease remains a very significant issue. And
13:50
breast, prostate, lung and colorectal cancers accounted for nearly 50% of all new cancer cases in United States and responsible for almost 50% of deaths. Due to the cancer. So you have to know these four cancers really in detail because you are going to have 50% of newly diagnosed cancers are going to be any one of these four. And if you don’t provide the good treatment 50% of all deaths are due to these four cancers. So one has to be very cognizant of the fact that if they want to practice the immune oncology, they must have have a detailed knowledge, not about the cancer, but also about the immune system. Why the breast cancer most malignant tumor in women and median overall survival rate is very low. In standard therapies which are considered in the National Cancer index is unsuccessful. In greater than 50% of patients tumors relapse mortality increases. However, we doctors and patients, the doctors are not only doctors but we can be patients do and our patients. They’re all looking for effective therapies. What kind of therapies, therapies which are less toxic, having less side effects have improved tumor control and improved survival rate, improve longevity, as well as the quality of life. So now, as I mentioned before, cancer, we is a constant battle cancer between battle between the cancer cells and the immune cells. There’s an ongoing fight and if we can do something for this universal switch, and can switch it to the one way where the immune cells which are fighting we are empower them and teach them how to kill the cancer cells and when the race and that is the goal of the immune oncology. We are inundated with the data, which are sometimes very biased. And and this data, then support the new protocols and then then having a poor prognosis by that as that they can killing the cancer cells. They shut off the natural killer cells and eventually one dies because of the total tumor burden and malnutrition and other organ failure as a result. But 99% of the oncologists are wiping out the immune system with chemotherapy.
17:03
So then what happens that they are killing the thing that they are killing the single clone of mutated cells and cleaning them, killing them with the chemo using the maximum tolerated dose, remember, maximum tolerated dose that is being used in immunology that allergy and immunology that I practice for last 40 years. Now this maximum tolerated dose is done to improve our immune system, because the dollars in the immune system today become does not become very reactive. But here they are using to kill the cancer cells. That thing the cancer cell is a single clone of mutated cells, but that’s not so. So the treat we are treating the 1000s of clones of mutated malignant cells. However, we cannot treat with one drug because it results in a failure in greater than 50% of cases. So what do we learn? We are not going to use the maximum tolerated dose. We are not going to use the one drug treatment. We are going to use the multiple small doses. Our goal of the treatment is multiple drugs and other molecules which may be a natural molecules and use in the lowest dosages to kill the cancer cells and preserve the immune system. Our main goal has to its number one is preserved immune system and and as a result by empowering the immune system. We kill the cancer cells at the lower dosage of the drugs that we are using. And that has proved in the research that they are effective in killing the cancer. We activate the immune system all the time. That’s number two. And the mutations occur in all the base pairs of DNA. So whether it is genetic or epigenetic, but the the finally what happens is the mutation occurs in the pairs of DNA and if you have the blueprint of this DNA, which will be available in years to come and one can decide what type of treatment which drugs are going to be helpful and in this treatment. And so, so we know that cancer is at a molecular level. Cancer has no knowledge of where it is. It may be sitting in your thyroid or it may be sitting in the prostate or it may be sitting in the breast. But but it has. It’s no longer denoted by the organ because after all, it is the disease no matter where it sits. We have to look at the the immune status of the patient and also the immune status of the tumor. So now we are going to look at cancer and extracellular connective tissue matrix. And some of you might have been present at the Las Vegas academic conference. And you might have seen my this slide and I’m going to show you that our body is controlled by the local ground regulation communication system, which overall health depends on the balance optimal generalized homeostatic response or this ground regulation system. So it has three units of the ground regulation system, and these are the loose areolar. Here you see, this one is the organ cell. This one is the basement membrane and this one is the Ammar force, loosely areolar tissue which is made of proteoglycans glucosamine or glycans, and Vibrio necking and many other elements in particularly when we are discussing the case of cancer. But the predominant in the normal healthy people. It is it is the proteoglycans glycosaminoglycans and hyaluronic acid and very little fibronectin it also is collagen fibers. And elastin. And so, so, it has it this one makes the connective tissue matrix with this amorphous tissue is communicating system in a 40% of the body tissue surrounding every cell in every organ. And it varies from Oregon to organ like skein, 87% of the dermis and submucosa then testing is made of connective tissue matrix. So therefore, it is very important to understand that what is the basic ground regulation system of these different organs and how it is it is mutated modified in diseases. Then the another important aspect of the the ground regulation system is this is the there are three main connective tissue cells, which is the is it the fibroblasts, which is a very important it spits out the large amount of the Ammar first tissue like what we see here the ground substance and and also it has a cytokines chemokine etc. And then this one is the macrophage and these macrophages are important because they are versatile using the large amount of the dead cells and materials alike. And then there is a mast cells and basophils eosinophils leukocytes and lymphocytes and all different kinds of lymphocytes including the CD 48 th one th two type you know type and T regs as well as the th 17 sounds. Now, the third important part is these vascular pathway, which is the end vascular pathway which is the capillaries and similarly accompanied by the lymphatics underside, autonomic nerve endings and somatic nerve endings. So many times we we inject something in the connective tissue into the our intradermal injection or sub q injection. They a patient Sandaime react so instantly, it’s unbelievable the amount of reaction they may they may have through the autonomic response. So an autonomic response the signal goes from the connector to it and one may have neuro immune endocrine response. So one may have symptoms in the central nervous system peripheral nervous system, they can have cold hands, cold feet, their pinky fingers turn blue and many different kinds of reactions you may get. So whenever your patient is mentioning you about having colons and cold feet, think about the what is what is happening into the ground regulation system and what type of insights are there which are triggering this mechanism. Now let’s look at the what happens in the tumor. Because tumor microenvironment is very important. It has a different characteristic and it does not play a role in the maintenance of homeostasis, as I showed you before in the previous slide, that round regulation system is very important and it pays great role in obtaining and maintaining the homeostasis, the internal environment of the body. And tumors have a different kind of macro environment. So they their extracellular matrix is also rich in proteins. But some of these proteins are not expressed in a normal extracellular matrix in a normal individual, extracellular matrix and learn where cells support and protect the tumor.
25:48
In life in pancreatic ductal adenocarcinoma tumors surrounded by takes trauma. So physiologically immune cells are not able to reach to destroy tumor cells and or the chemo cannot reach another man’s outgrow our problem reaching the tumor and take extracellular matrix also keeps the T cells out as they cannot transfer very easily. And therefore we need the approaches to break down this fortress which is built by the TIC extracellular matrix and meaning that that we have to have a some system to take care of their fibroblast so their cells in their connective tissue matrix have unregulated growth is what type of cells do their hair as compared to a normal Strama. So stromal cells include cancer associated fibroblast cells of the immune system tumor vasculature, and lymphatic system parasites and adipocytes, parasites. So this network of fibroblast, which is a cancer associated fibroblasts represent a major cell population within these stromal compartment they’re involved in their structural and paracrine interactions between the other cells. And then what are the cells of the immune system? These are the T cells, T cells, B cells, natural killer cells, dendritic cells, but these these are the positive ones. And then there are myeloid derived suppressor cells, and tumor associated macrophages. They’re also called temes. And soluble growth factors, cytokines proteases, are also the part of that surrounding stromal components extracellular matrix can determine various phases of tumorigenesis even conferring the acquired drug resistance as it builds the fortress. Now, this is the diagram of the tumor microenvironment I have a better another really good diagram, but maybe in the future meeting, I’ll show you. So this is the blood vessel. These are the multiple tumor cells and this one is the T cell, the regulatory T cell. Now regulatory shell has a negative impact on the immune system. It works for the tumor, it were worked against the survival, and these are the natural killer cells. These are the T cells, these are activated T cells, these are inactivated T cells and these are the macrophages as you see that and, and then these are the stromal cells which we do see here. And so as I described before, they are very tight or maybe very loose depending upon how much of the matrix is present. Now, this is another diagram which shows you the cancer associated fibroblasts, there are large fibroblast and these are all the tumor cells which are seen in brown color and and then this yellow color is the myeloid derived suppressor cells, and they have also negative budget. They weren’t for the tumor, but having the negative effect on the destruction of the tumor. And then these are the dendritic cells and cancer associated fibroblasts, these are the dendritic cells. These are the neutrophils, these are the the again cancer associated fibroblasts, and these blue color ones are the million four sides. And these these are also the cancer associated fibroblasts. Very these are the parasites which you see over the normal blood vessels. But then when when these blood vessel grows out, as you see that it is very kinky, and then it branches out sometime there are a lot of hypoxic areas, and that that hypoxia
30:34
is favored. I mean, the tumor favors the hypoxia so that you understand that if you supply a large amount of oxygen, that oxygen has to read the tumor, and if your blood blood vessels are not too many, then there’s a problem in oxygenating the tumor unless you’re oxygenating with the hyperbaric oxygen. Now this is another another diagram of the tumor microenvironment showing the tumor in the center and then it started the year there we are going to start here with the antigen presenting cells which presents the tumor antigen to the the dendritic cells and then that goes and it goes to the T helper cells and and then have some reliefs of the cytokines. And again transformation occurs into the polarization of the direct cells. Now, direct cells really have blocking the disaffiliate and cytotoxic lymphocytes. Now also the mature myeloid derived suppressor cells have a negative effect or blocking effect on the cytotoxic T cell CDH. Sounds. Minor o majeure. The myeloid derived suppressor cells have also a negative feedback. It it goes and in MEK polarizes the macrophages instead of m two to m one and it promotes the what do we need it promotes the m two reprogramming and m two is what the tumor likes, but we do not we want polarization of m two m one. So remember that m one is very helpful for distraction of the tumor. Then the B cell usually secretes the IgM secretion via cell stimulation. And these are the direct cells which block the the receptors on the tumor and it has the inhibitory actor action on the natural killer cells. So, there are there are many other inflammatory cytokines like il six IL and PG do which also promote the formation of the T regs and including including il 12. This is another another diagram of the tumor microenvironment and as you see that is it is just full of lot of immune cells, but the immune cells have been disabled by the the CO stimulatory pattern of the immune system. Which is present in the tumor. So, now let’s look at the characteristic of macrophages tumor associated macrophages is they play a special role in cancer. It phagocytized is of the destroyed cells. It plays a great role in tissue remodeling and repair. It supports the tumor growth, remember it supports with tumor growth, and where does the signaling come signaling comes within the tumor and that the nodes the macrophages from from M mo to m to n it recruits the vasculature initiates the angiogenesis. And this the angiogenesis is there are many factors which initiates the angiogenesis besides the hypoxia and it plays the immunosuppressive role in tumor micro environment. So, in a pediatric brain Gedik ductal adenocarcinoma, tumor microenvironment is region macrophages and take extracellular matrix prevents the infiltration of T cells and thus prevents active killing of tumor cells. You for active killing of tumor cells you need large amount of natural killer cells Cytotoxic cells and in and not only that, but you need the activation activated cells to kill the tumor
35:32
okay
35:36
so now let’s look at the Cancer associated fibroblasts. They are distinct from the normal fibroblast, as they are derived from the heterogeneous population of cells like the mesenchymal sands, fibroblast, endothelial cells, smooth muscle cells, parasites adipocytes, in viral epithelial cells, they secrete proteases that are involved the integration of extracellular matrix to promote invasion and induce metastasis. So it also secrets the tumor supporting growth factors and cytokines. The growth factors are he parasite growth factor, which is also called ATF, IGF one, fibroblast growth factor, and TGF beta one. These growth factors directly interact with the malignant cells to promote tumor growth. Also, they secrete cytokines like TGF beta three FGF, seven and cscl to drown and thereby it induces the epithelial tumor cell transition to epithelial to mesenchymal transition. And this is one of the very important facts that we see in patients with the ovarian cancer and these promotes the invasion and metastasis. So when you have a patient with ovarian cancer, and if the biopsy report shows that there is a epithelial to mesenchymal transition, you actually know that this tumor is very invasive, and there must be a multiple metastasis. And no matter what you do that it is very hard to bring this tumor under control. It promotes the tumor growth by recruiting endothelial cells, and enhancing the tumor angiogenesis via secretion of the blue angiogenic factors, including il six VEGF stromal derived factor one and platelet derived growth factors and it this cancer associated fibroblasts also functionally modulate inflammatory response and thereby it mediates the innate immune cell recruitment to promote tumor angiogenesis and enhance tumor growth. So, sometime the innate immune response in cancer it has an adverse effect. So, there are multiple immunosuppressive molecules in tumor micro environment. And you got to understand that this is what protects the tumor and this is these are the weapons of the tumor to fight against the immune system. If you remember that, that that that’s a wonderful explanation. So, so, m m one what happens that m v one m one and one gets transferred to m two interferon gamma cannot induce its effects and proliferate the NK cells and also inflammation in their blood that defect is blocked NK cells and then that defect is blocked on interferon gamma. Then again, natural killer cells effect on the tumor is also blocked. So, IDEO is another another character, another component of the tumor that has inhibitory effect on CDH shells and direct cells are also have inhibitory effect on the CD itself. VEGF TGF beta, IL, Dan all have a negative effect including il six and here you will see that the natural killer T reg cells block the natural killer cells and and the dendritic cells. So that interaction with the tumor presenting antigen tumor antigen presenting APC cells cannot work between them and so angiogenesis also promoter. These are the immunogenic cells and the large amount of immuno evasive cancer cells and so, we do not want immuno evasive cells around us.
40:36
So, in summary, the inflammatory cytokines of tumor microenvironment TNF alpha, il six il X, and often upregulated, leaning to measure properties of cancer, such as angiogenesis and the matter stasis. However, il four il 13 and il 10 have been reported as the promoters of an anti inflammatory environment and adaptive immune response suppression. I LDN and TGF beta secretion polarizes the T cell to T reg cells. T regs are immunosuppressive cells and they are present sometime in a large amount in tumor microenvironment other immunosuppressive cells or tumor associated macrophages myeloid derived suppressor cells and they promote promote carcinogenesis. Metastasis, and also therapy resistance. Because when these tumor associated macrophages are very important in removing the the destroyed cells in some time they turn into the tumor resistance now this is a very important slide for you to remember. And you can go and look at it again and again and again. In so that you will understand that what are the consequences? What happens in the failure of the immune system and conquer the the cancer, the immune system plays a key role in eliminating tumor cells. Anti tumor response is often prevented by immune checkpoint molecules and what are the immune checkpoint molecules, these are the CO inhibitory molecules. This is the CTLA four molecule and this is the PD one receptor molecule. And they are important as well as there is also PDL one which is the another molecule which is associated as the regulators of enhanced immune response. These immune checkpoint mechanisms are often activated to suppress the anti tumor response and this is what happens in most of our patients that immune checkpoint have. Have a suppress separate I mean, immune checkpoint usually suppresses the anti tumor response and these anti tumor response therefore, several immune checkpoint inhibitors are needed. And there are the antibodies, peptides and small molecule drugs. So, if you have a PD one and this PD one receptor here, this PD one receptor has immunomodulatory effect in killing the cancer cell, but then when really one really one molecule even turns on by the PDL one leg and then it is activated and it is blocked completely in PD one one it activates, it suppresses the anti tumor response. So, you need the PD one immune checkpoint inhibitors which blocks the B one receptor. So, then PD one is disabled and as PD one is a disable, it can hear the entire tumor immune response. So, it is it is very, very important to understand that why do we need the antibodies because we want to these disable the other these about these receptors so that they do not have inhibitory when they are activated in inhibitory effect. So, immune checkpoint it’s the molecule in the immune system enhances or inhibits the immune responses. So, costimulatory immune checkpoint deliver the positive signals to T cells following their binding to ligands and receptors and on antigen presenting cells
45:29
going in Bidri immune checkpoints deliver negative signals to T cells upon interaction with their counterparts on a PC. So, they can inhibit immune responses, including PD one Pdl, one, release CTLA four and etc so the upregulation of coinhibitory immune checkpoints dampens the immune response downwards the tumor cells and facilitates the tumor to grow and evade the immune surveillance. So I think that there’s one is that very important to remember in some time, the you need to know not only that they are present when there is a biopsy specimen, you need to know that what how many leggins are PDL? One were on on that particular tumor tissue and Evie has a large number. Then then the insurance company would approve the use of the their checkpoint inhibitors so in cancer, the inhibitory immune checkpoints are often overexpressed on tumor cells as I discussed nontransformed cells within the tumor microenvironment and it dampens the immune system to mount an effective anti tumor response. PD one and PDL. One signaling induces the adaptive immune response in tumor micro environment. PDL, one is not expressed in normal cells, but interferon gamma, an inflammatory cytokine often stimulates the PDL one expression on various cell types in tumor microenvironment. And that’s why many times the patients have a very heavy PDL one expression and you need the inhibition inhibitor to antibody for PDL one. Similarly PD one PD one receptor on T shell acts as a dominant negative regulator of anti tumor T cell effector functioning by the engaging PDL one so MHC molecules are also on tumor cells, and they play a great role also in activation of the tumor. So what do we need to do is we need the immune checkpoint blockade and this is the current most promising approach in immuno oncology, activating the therapeutic anti tumor immunity and circumventing the immune resistance exhibited by the many tumors. So when chemotherapy doesn’t work, when when they are resistant to the many other treatments, or including the city city of Mesa, and that is the time you use the immune checkpoint blockade. Commonly used inhibitors for immunotherapy. Anti PD one monoclonal antibody CTLA four is exclusively expressed on T cells. It is a negative regulator of initial priming of T cells. It prevents the binding of CD 28 to co stimulatory molecule CDA T CDH. Six and of APC CTLA 4x Early in the immune response by inhibiting T cell activation. So therefore, we require anti CTLA four antibody called a plumbob. trade name of your ROI, which is IgG one monoclonal antibody, it negates the effects of negative regulation. So, in other words, if there is there is no surprise suppression of the immune system. The DCi keeps on working PD one is a Mindjack
49:58
point inhibitor AXA in the later stages of immune response. By turning off the antitumor T cell response. So these are more than our antitumor T cell response, but they act differently. Anti PD one checkpoint inhibitor nivolumab OPDIVO which is IgG for monoclonal antibody it negates the effect of negative regulation by PD one mediated immune inhibition. So, therefore, the dual inhibitors synergistically promote an anti tumor immune response by blocking complimentary mechanism and does the restores the patient’s own anti tumor immunity. It empowers the patient to destroy their own tumor
50:55
PDL one legan on APC plays a great role as a negative regulator of immune activity of T cell and anti PDL one antibody, which is known as a Keytruda which prevents binding to PD one receptors and thus dampens the negative regulation of anti tumor activity. Means promotes the activity antitumor activity. Now let’s look at the VEGF. It is an angiogenic factor and it increases the vascular supply to tumor not only that, but it also has the immunosuppressive effect. It decreases the number of T lymphocytes. It activates the immune checkpoint molecules and make them more mmm powers them so that they have negative regulation of the anti tumor activity machine meaning that it is going to promote the the tumor formation activity it increases the activity of tumor it inhibits the dendritic cells differentiation in cytotoxic T cells, it down regulates the MHC complexes, anti VEGF antibody ever seen is an anti angiogenic agent and it has a immunomodulatory effect when combined with immune checkpoint inhibitors. Now, let’s look at the immunotherapy and cancer. It is an effective therapeutic approach against cancer as it harnesses the power of immune cells and the body’s own immune system to destroy the tumor. However, they’re often associated with severe systemic side effects, when given by the intravenous route, in a maximum tolerated doses it benefits tumor expressing specific receptors in a subset of patient. Systemic administration of such immunotherapy can result in toxicities in lungs, GI tract and liver, endocrine, and neurologic systems. So now we are going to look at how can we deliver these potent immunotherapy agents in our body without causing severe side effects without delivering them in the maximum tolerated doses? Well, we have platelet nanoparticle delivery system. And so let’s look at the platelets and PNP delivery system in cancer. So platelets have a natural ability to bind to tumors and the components of tumor microenvironment. live lives have been implicated in tumor progression. It facilitates the metastasis by binding to the circulating tumor cells and hide them from detection makes them more immuno evasive. Now when the nanoparticles are delivered by the platelet membrane, and they clog it with the platelet membrane, so platelet membrane clogged nanoparticles, when delivered by the intratumoral injection, in the solid tumors, it is very facting plasma cell membrane of the human platelets has multiple proteins, glycoproteins and lipids. It has a platelet mimicking properties such as selective adherence to cells in the tumor microenvironment. Platelet cell membrane coating improves biocompatibility of nanoparticles to effectively interface with tumors through multimodal reactions. So, men these platelets are specially prepared and bear the membranes lysate are used and they coat and it enables the nanoparticles not just to bind, but bits retained at the tumor site
55:36
much longer than fully synthetic nanoparticles providing greater opportunity for encapsulated payloads. To accomplish their intended effect. So platelet membrane coated nanoparticles PNP R 848 in colon cancer, have been in research by the shallow therapeutics in that they use the this immune modulating molecule in the research to treat colorectal and breast cancer. They have been found to have a effective anti tumor response in in their mouse model, when administered by intact humoral injection PNP nanoparticles which are also dubbed as a PNP are 848 exhibited an impressive and that tumor immune response it is reported that concentration of nanometric lately nanoparticle is 1000 times higher when it is given by intratumoral injection as compared to given by the IV route. So, these shallow therapeutics how these are 48 that they’ve been using and to eradicate the tumor and also induce the sustain long term immunity. So mice were treated initially with PNP r 848. And they were D challenged not once but twice with increasing tumor burden. One goes down at the same time. I’m sorry, one. They will rechallenge not once but twice with increasing tumor burdens. They were able to completely reject and kill these tumors. Without any additional treatment. And this suggests that treatment with BNPL 848 has the potential to prevent future recurrence of the cancer. And this research I’m showing you is not I’m promoting this molecule because it’s not even available. But I’m just showing showing you that when you deliver the nanoparticle and close it with the platelet membrane and deliver as a platelet nanoparticle and induration to the tumor. It is not only treats the tumor eradicates the tumor and sustains the long term immunity. And as a result, when the tumor develops in any other organs, this long term sustained immunity is what persist and takes care of the tumor and it rejects the the development and progression of that tumor and in further slides, and I’ll show you what happens. So this is the patient who had colorectal cancer, I mean mouse study where there is a colorectal cancer and you see that this is the this the mouse which was treated with the PNP are 848 and there is 100% survival progression free survival and yours the control which is zero, and here is the free molecule of nano medicine and still it had a poor outcome. Then they use the pegylated which is a little bit long term acting and pegylated form but that did not have also very high survival rate. The only high survival rate was that when it was delivered by the cloaked by the platelet membrane, and platelet nanoparticle, then it was very high survival tumor progression free survival of colorectal cancer shown in this mouse model. Now does the effectiveness was established in aggressive metastatic breast cancer mouse model the same molecule and it significantly inhibits the tumor growth compared to the free drag and free loaded into purely synthetic particles.
1:00:08
In addition to meant with PNP R 848 was able to substantially reduce the number of metastatic nodes found in the mice in the different places, indicating that localized administration of PNP. Our 848 is able to induce a system wide, specific immune response against the tumor. So it was not just the localized effect, but it was the system by a specific immune response. And it was a sustained response. As as I showed in the previous slide that it had a sustained effect. So after a few months, even if the cancer develops it that it destroys the tumor, and here it shows the tumor growth inhibition and prevention of the macro stasis. So in this group, there was no matter stasis and here you see that in the tumor volume, the least amount of the tumor volume was in the PNP treated group. So nanoparticles are able to generate superior anti tumor immunity fact, compared to either free drug or pegylated. Nanoparticles due to their enhanced retention at the tumor site. I should I should say, not just the nanoparticle blood platelet cloak nanoparticles. So they increase their retention at the tumor site. And once you inject these BNB R 448 molecule into the tumor side, it is taken up by the resident antigen presenting cells and once taken up it releases its cargo which activates the antigen presenting cells and activated APCs then migrate to the nearest lymph node where they train other immune cells. T cells to recognize and fight the cancer some T cells return to the tumor site to battle the tumor while the others go into the circulation and surveil the body to eliminate any tumor cells that has escaped from the original tumor side. So it shows here this is the tumor and these BNB are 4d It was injected here. This is the underside housed by the APCs and then it goes into the resident APCs and this is the dendritic cell and then there’s the it has MHC two complex where the antigen is taken and then it goes into the natural killer cells, that NINE T cell and then it activates a activated APCs activate naive T cells hear that these APC gets activated once it is activated, it becomes the mature these T cells NINE T cells and then activated T cells goes into circulation into the tumor and activate the T cells in the tumor. It destroys the tumor. So activated T cells are the one which kills the tumor. So here the immune system is killing the tumor, but inactivated form drug delivery by modifying into nanoparticles, and then cloaking with the natural cell membrane represents an important advancement in nanomedicine. Metal results are achieved by combining both syntactic or natural nanoparticles and natural materials, the ability of PNP our 848 to retain the tumor side and promote a specific and sustained systemic anti tumor immune response is a promising step for the generalizable cure for cancer. And, and we do provide, we do not use we do not use any of the synthetic nanoparticles, we use the autoloaders platelets, we we process them to the platelet membrane and then also the the platelet lysate and also put our nanomedicine and again clothed them by their special procedure and and then we do that either by intravenous route or by
1:05:19
by air in the Interact humoral injection and then the follow that with the photosensitizing agent. We do that we also add that to our injection solution, and then we subject the patient to the beauty treatment photodynamic treatment is very essential as it creates the free radicals and a sustained killing occurs and enhances the cleaning activity and, and immune activation so let’s look at the entire tumoral immunotherapy and let nanoparticle so intratumoral immunotherapy is the emerging modality and treatment of solid tumors and all like receptors, agonist are used to elicit the immune response effectiveness of localized intangible delivery of TLR agonist, their single mode via platelet membrane coated nanoparticles showed antitumor responses. Thus, membrane coding provides a means of enhancing interactions with the tumor microenvironment and thereby maximizing the activity of our 848. So in detrimental administration enhances local immune activation and leads to complete tumor regression in a colorectal tumor model against the repeated tumori challenges in modulation of the tumor microenvironment occurs in high by engaging the toll like receptors and inhibiting tumor promoting immune signaling. Among the TLR seven, there is there is a receptor and predominantly they are expressed by macrophages, dendritic cells, natural killer cells and B cells. So, these DRL seven eight therapy leads to expansion of the tumor antigen specific city eight D cells. It is important for the development of the effective anti tumor immune response
1:07:50
systemic administration of TLR agonist, our 848 and other members of TLR seven agonist family when used in combination with the immune checkpoint inhibitors has proven advantages in treatment of squamous cell carcinoma, colon carcinoma, metastatic melanoma, pancreatic cancer and so on. But safety concerns are, are there as multiple intravenous doses oral administration of small molecular molecule TLR seven agonist causes the adverse events such as fever fatigue, headache, and hypertension, systemic administration that IV use leads to rapid depletion of leukocytes and transient local immune insufficiency. So localization of immuno stimulatory agents to the tumor microenvironment can convert it from a goal to a heart state, helping to kickstart the anti tumor immunity and all these references are available in one of the last slides I have provided me with this lecture. In order for interactive neural immunotherapies to be effective, it is necessary to confine the immune agonist payloads within the tumor site. direct injection of free drug has the potential for systemic leakage, and that can lead to reduce efficacy. So targeted intact humoral platelet nanoparticle cargo delivery is generally designed to be antigen specific. Now, this slide summarizes everything what we have discussed so far, that we showed you the total tumor volume is minimal with the PNP delivery system of this nanoparticle. Again, the progression free survival was also maximum with the use of the PNP molecule coated molecule, the total tumor volume is shown as minimal. Now this one is the specimen and in the control mouse and account control mouse you can just see that there was not much significant difference maybe 50%.
1:10:42
Exactly, exactly. Don’t enter into a situation where you’re so in other words, your pain uses
1:10:55
sorry, yes, go ahead.
1:10:58
So when it was treated by the free, are 848 Free, okay, it was not coated with anything. Then Then again the response was, was not significant as compared to the control. And then when neg pegylated nanoparticle R 848 was given for the prolonged recovery of the these nanoparticle again is the the size has reduced tumor tumor volume was did reduce, but not significantly. Whereas compared to little it nanoparticle delivered or for at 48 at the same there was none there is no tumor. So it is very important to understand. And that tumor wait they say it is reduced tumor nodules metastatic nodules were reduced. So, this shows the effectiveness when you give the molecule with the platelet clock membrane in an animal form, it is so effective when it is delivered by the entire tumor injection, which I’ll show you in my case presentation. So here is a 64 year old white male who was a retired painter has a recurrence of cancer of head and neck. Severe lightning face pain 10 out of 10 very sharp shooting unbearable pain, constant pain in other tumors in the neck. problem in swallowing difficulty in chewing fatigue unable to sleep well because of the pain. And he was against taking any of your as you mentioned that it was not effective and he did not want to have the LD and not work. So now this is 64 years or white male who was diagnosed to have metastatic stage four cancer squamous cell carcinoma of head and neck. He was operated in November of 2021. He was suggested to have chemotherapy and radiation after his surgery. Patients family did some research on this treatment protocol and decided not to go for it. They they were afraid of having more complication from radiation. Then they discuss this with their oncologist. Who told him that he has to recommend the protocol for his condition after listening to the patient, and regarding the side effects, what they have read and what happens. He he said that if he fails to do recommend the protocol, then he may lose his license. So that means that they are forced to tell that after the surgery, they have to go for chemo radiation. There’s nothing else that can be done. The patient was decided not to go for chemo and radiation. Now, let me go a little bit back into his history. In earlier part of the year, he had a problem, some growth in his temple area and in this temple area, they this growth continue to increase in the size. So they did it was seen by the physician and then was sent to the dermatologist and had biopsy done diagnosed as the sperm cell carcinoma. They recommended the most procedure patient’s family declined and they use the cura DERM that is the plant extract from Australia and of course the tumor disbanded and grow disappeared and left this hypo pigmented scar. But then, after they continued all the antioxidants and etc but then they few months later, they noticed that he developed some nodules under his check and in submandibular area and which completely kept on increasing in size and then it became like a forgetting mass before the manton saw the physician or then
1:15:43
decided to to have the surgery and then here you see that the surgery was done and then they put the flap here. So in January of 22nd 22 He got COVID-19 He was sick for three weeks. Subsequently he noted that pain was getting worse and tumor was growing back. Then he started to receive high dose vitamin C 50 grams twice a week. He continued to receive it but the tumors started growing fiercely. He was in he was his pain was 10 out of 10 and he was not able to sleep and they did not want to go for chemo radiation. So they were really concerned about what to do next. And then they brought him to my office. He was started after his examination and everything what they explained. He was given the IV artemisinin, and a high dose vitamin C as they both have a synergistic effect methylene blue ICG at the photosensitizing agent they were given him intravenously, and then the photodynamic therapy with hyperthermia was was delivered for about three visits while we were waiting to get a CT scan, as well as the board as many treatment had to be done. So following diagnostic CT scan of the chest in neck, he was started on immunotherapy treatment. He was continued on different IV therapies as well. We started him on a mistletoe immunotherapy. He continued to receive weekend IV therapies of ALA curcumin, as well as NAD he was receiving the polyphenols he was retrieving vitamin A vitamin D. He was receiving the methylene blue we started him on we started him on those that and then we started him on LDN so and and oral ala he was taking before even he came to our office. He was started on intratumoral injection of immunotherapy with BNP treatment three times a week and tumors were injected at multiple sites due to poor diffusion as was very hard tight and tumor. microenvironment was also hypoxic. He received 1/10 of the recommended dose of nivolumab which is the PD one receptor immune checkpoint inhibitor ever seen interferon gamma and many other ingredients including methylene blue ICG, followed by the PDT photodynamic treatment, along with the hyperthermia. He also received the IV treatment of the same and he was as he had enlarged lymph nodes in his chest, anterior and superior mediastinum lungs pleura in retroperitoneal. Area in upper abdomen within three treatments. His lightning pain disappeared within 10 days of treatment because we started his treatment on Thursday. If he started his treatment on on Monday probably he would have been better by following Monday. He has received a four weeks of treatment. Now, I would say five weeks of treatment but anyhow after four weeks of treatment is 50% reduction in his tumor mass. And in six weeks after five weeks of treatment, he was 60 to 70% better. Now he is under six weeks of his treatment.
1:19:56
So let me just show you his photograph. So this is the I showed you is photograph the tumor. How bad it was. Now he’s tumor here in the barricaded area has shrunk about 50% Here it is shrunk in submandibular area, then also posed to your regular area he has a large tumor which feels like cystic but must must be a very separated septic and and again he had also in a supraclavicular area. So this shows his pretreatment pictures and this shows his posttreatment pictures and you see that this this tumor was really prominent. This is a prac levy color versa and large tumor here and the large tumor was there. Now what you see is much more close up than what you see here. So his tumor is is there but it is much smaller than it was and the tumor in sub mandible area is considerably reduced and you don’t see the swelling like what you are seeing here anymore here and supraclavicular fossa it is smaller Jews. So now let me show you some of the articles which were there that squamous cell carcinoma of head and neck with tumor progression recurrence within six months of Latinum therapy was large and nivolumab significantly improved overall survival. The primary analysis demonstrated prolonged overall survival benefits versus the chemotherapy. Here, it mentions that the head and neck squamous cell carcinoma is the most common malignant cancer of head and neck in approximately 90% of the cases of head and neck tumor. local recurrence and distant metastasis are often observed after primary medical treatment with this patient had and once the disease becomes very, very invasive you with local recurrence, recurrent disease and metastases. The treatment is usually palliative chemotherapy and results are not very satisfactory. And so the new agents have been developed for the recurrent locally advanced and metastatic head and neck squamous cell carcinoma. These are the immune checkpoint inhibitors targeted PD one treatment and firstline gold standard is chemotherapy however, however, it is not not very effective. Many phase three studies are currently ongoing, evaluating the efficacy of combination treatment with anti CTLA four with anti PD one or anti PDL one very encouraging results have been demonstrated. But it is still a problem for the insurance company to accept that this is worse. And you have to just keep on looking for as many new articles as possible in order to treat your patients with the most current effective therapy and not what the insurance company approves. So now I want to show you why I gave patient they are demisting in the first artemisinin as you know it is a flavonoid which is present in the lives of our dementia and new plant. It is linked to the suppression of C 450 enzymes. However, it has also beneficial immunomodulatory activity. So in cancer cells, this effect includes broad inhibition by Shell cycle arrest which is very important for the metastatic cancer stimulation of apoptosis, inhibition of angiogenesis.
1:24:39
Disruption of cell migration, which makes the medicines and modulation of nuclear receptors fanciness and in down regulating the NF kappa B Moreover, artemisinin has a significant anti angiogenic, anti inflammatory and anti metastatic effects. Therefore, they are attractive for the cancer treatment. And another important thing that artemisinin reacts with the iron to form free radicals. In these free radicals are the one that kills the cancer cells. Research the other mechanisms, cancer cells require iron to proliferate, and so it is more susceptible to cytotoxic a pact of artemisinin than normal cells. And then the when the artemisinin tax transparent molecule is key when it gets endocytosed ion is released and reacts with artemisinin and formation of the free radical occurs in cancer cell and it kills the cancer cell. So the artemisinin tech transferrin is highly selective and potent in killing cancer cells. Thus, artemisinin tech iron carrying compounds could be developed into the powerful anti cancer drugs and we have found that in many of our patients that it is very, very effective
1:26:23
and I just want to show you one more thing that we are targeting angiogenesis, in squamous cell carcinoma head and neck, as you see here, the the this is the vascular supply and then anti angiogenic agents drives them up and it just very poor formation. So, in here, the immune activation occurs with the immune regulatory cell tumor invasion matters. This is occurs here but then when you provide the oxygenation, tumor perfusion and drug delivery increases and immune checkpoint inhibitors, intense dies again it shows the extracellular remodeling and how the tumor capillaries are providing the blood supply to the tumor. Okay, thank you for your patience and hope you go home with some Oreos. Wow that was excellent.
1:27:35
Can I see your references again
1:27:46
we’ll put them up on the on our website when we’ll have everything here. We have it recorded and Dr. Patel if you don’t mind this having your slides, put those up well, so
1:28:01
I have a thing that I would like to add here. I mean, what you’re doing is great. It’s an excellent, amazing phenomena. I think you’re the first in the world who are able to integrate everything that’s been published recently into practical patients, protocols, and I congratulate you for doing that. And what we need is some ultrasound imaging besides I saw that you have you know, it’s very clear, you’re able to show that those swelling of the lymph nodes are being deflated or decreased. But it will be good if we have those ultrasound imaging because that you can have more pictures about the progress of the treatment. And also seeing the change in those lymph nodes from the solid tumor into liquid because of the crisis. And that helps a lot to for the audience here and also for publications to show some imaging ultrasound but your presentation was great if we can make those pictures and start from now because you will continue will continue the same protocols for this patient. But if you start doing even with your ultrasound that you have a small one,
1:29:16
right right. I will just just no time you just don’t know what it is. Cheryl has been to my office she she knows it but I think I can I can help vision come on a weekend or something and I can do that. He’s got a busy I’m sorry what? I said you have a busy hub there. I mean, yeah, trafficking is is not too bad. But one patient is like the invasion so
1:29:53
so we have some questions for you Dr. Patel,
1:29:56
I just want to make sure that I forgot to mention that. We had used the metabolic blockade and these patients, meaning that metabolic pathways which are common to most of the tumors we have tried to create and and we know that the B 53 Gene, we were using the rice bran extract carabiners and yeah, we are in for and metformin, which is also multiple metabolic pathways. We he he’s also in Berberine he’s also on a is on my bags, and etc.
1:30:41
Okay, question is what type of mistletoe injectable do you use?
1:30:47
Well, I use the mistletoe Malley. When I’m doing the subcutaneous injection.
1:30:54
And what was the dose of methylene blue IV
1:30:57
methylene blue IV you can use anywhere from 25 to 50 milligram it’s very expensive. It’s very expensive. Okay, it’s like five bucks $1,600 to buy one box.
1:31:22
What if the cancer has no solid tumors and it’s blood based or deeper tumors such as pancreatic or liver tumors.
1:31:29
But then create a tumor? You know, when Dr. halachah has a center can be injected directly but until then we have to just go through the intravenous route
1:31:46
is there an IV version of platelet nanoparticle particle treatment?
1:31:50
We do the both we do intratumoral as well as the IV because you know, I have to still treat his metastatic lymph nodes although, you know, because the the tumor burden is so high. So we cannot just rely only on internet Ramallah injection and thinking that that’s going to take care of the sustain. I mean, they have shown in mouse model, but we don’t know what type of those we would require what type of conditions we will require beta, you know, looking at the clinical situation, we want to be more aggressive in the way we think that we want the dual delivery and that would be the India tumoral injection because his tumor load was very, very high which was extrinsic but the what we do not see except on the CT scan is that in Superior mediastinum anterior mediastinum and retroperitoneal nodes and we want to make sure that that retreat that the the beautiful part of the story is that the platelets are very attracted to the tumor cancer cell membrane. So so as a result, when you give intravenously it will seek out the tumor itself, just like the photosensitizing agents get concentrated in the tumor which has been shown in multiple models. So this way, we know that whatever we are injecting into the patient is going to go more into the tissue that bearing the organ or the lymph nodes wherever the tumor is. So like sometimes in pancreatic cancer, that that’s what we do. But pancreatic cancer is a very different animals because it’s not just the tumor, but but all the all the cytokines and the inflammatory cytokines what it does it it reduces the inflammation and then it invades the the intestines and the colon on particularly lying behind it. And so as a result, the patient develops the multiple obstructions and then in to treat that multiple obstruction. The physician the surgeons have become very, very aggressive. And then they the intestinal stent. And if you if you look at the intestinal stand, it’s nothing but the multiple wires put together make it as a net and introduce there. So I had one patient patient live longer than she will usually live but I mean, I don’t like to lose patient but I just saw that but at that time I did not have PNP treatment available. I was doing rest of the thing but I did not have a PNP and and we see that looking at that model, that even if you if you supply your medicine then in a narrow particle form, it’s are in a regulated form. It’s still not going to make that much difference the tumor load is still going to be there. And as long as the tumor load is there, the cytokines are present, T regs are there inflammation continues immune evasion is continues and as a result, you know we lose the game.
1:35:42
Okay, is there an IV version of platelet nanoparticle? We asked us you answered that right. Yeah. Right. Okay. What is your parameter to start detoxing in this patient?
1:35:53
Well, any patient you know, you it’s not like you you try to but the patient who came to me had all of that done. So I could just start but let’s say that this patient came to me and nothing he’s not done anything is not but he was on all seven prongs of the Environmental Medicine. And meaning that his environment was cleaner. His His food was clean. He was he was his son is organic farmer. They have organic farm and they were drinking glass bottles bring water. So and then he was on a gluten free diet. He was not eating much meat. He was only on a large amount of the smoothies, different smoothies and then the protein. He was not eating excessive protein and he was receiving. He was he had a lymphatic drainage in and he was not doing sauna but he his pain was so intolerable that he it was making his pain worse. So we just could not use the part of the sauna but but they were using other methods of detox.
1:37:19
When you use our Tennyson should you give iron with it since it uses
1:37:23
yeah usually takes the iron when when he leaves his house and then what’s the foundation use out of down patient but it’s about hour hour and a half some time I told them give about 45 minutes to one hour so whatever we can but yes he takes iron and then we give the artemisinin when when he’s not getting artemisinin, we are giving him the curcumin and ala so on a weekend from Friday, Saturday and Sunday he gets to La he gets three curcumin and one NAD
1:38:02
okay and then those of the iron
1:38:05
the dose of the iron is whatever we tell him take two capsules. I and we splice in it and we are giving him two capsules of that.
1:38:15
Do you give iron even if they’re not iron depleted?
1:38:19
No, no, no not and you can you can do that. I mean you know cancer loves iron. So we have to be it is like a double edged sword. But when you are using artemisinin, you got to use it.
1:38:32
That’s all the questions I have here.
1:38:34
Yeah, let’s activate the Artemis scene. And that’s the reason some of the studies they say don’t give Curcumin with artemisinin because iron chelation. Yeah, so first thing I think doctor, even doctor, I think metallic spray once before when a patient being aggressive. They knew too much on the patient, you may end up with your license. And that’s a big urgent case. Require even I ICU sometimes because of the electrolytes the service so you’re really when you are dealing with stage four cancer and you’re doing those protocols you have to be slow, and then progressively increasing your dosage or your frequency and be careful about tumor lysis.
1:39:20
That’s right, you know, moralize is your particularly when you give their very super high dose vitamin C along with some other other agents, you patients sometime shapes and has a trend. I mean, you know there’s like chills, and shakes. So what we tried to do is we aired calcium, and we tried calcium present gluconate versus calcium chloride and we can get him to like to be superior than casual glucan and, and and that has helped many patients. Again, when we are killing the cells, we want to make sure that patients hydration is good, because you don’t want kidneys shut down or you don’t want the other like severe electrolyte imbalance.
1:40:22
can you prevent the tumor lysis with daily IV hydration?
1:40:27
I think that not to be super aggressive is is the magical taking home message.
1:40:36
Okay. Okay. Anybody else any questions
1:40:40
regarding TLR receptor, the one that Dr. Patel is talking about the it’s been research of course the one that’s in that company was doing it the CLO therapeutic. I mean, TLA receptor agonist or antagonist are valuable there we’re using it. Now trick stone is one of them by missins are all TLA receptor with different modifiers. And so you can work on TLS receptor agonist and antagonist using FDA approved naltrexone or using peptides that we are using in cancer. Did you did you did that thymosin Alpha participation as well?
1:41:24
Yes, yes, yes. Yeah, I just unfortunately, I don’t know who’s listening. So I had to be careful about certain items.
1:41:33
Right. Now I understand that. Yeah, we can we can confident
1:41:39
that whoever is interested can can really we can move the seminar for them or something like that. So today conference and go over completely all different subjects and and discuss much in detail. So, this is just the overview, I mean, each each item can take a full hour. So, this is like what the lecture I have given you can be done into 16 sections without being being repeating anything like like Dr. Bill was talking about that on testosterone lecture for lectures almost repeated the same thing. But in our lecture, you won’t see that
1:42:32
our election, our lectures were better than the AMG ones. Tell you that we’re still waiting for the videos by the way. Yeah. So. Okay. Anybody else have any questions, comments?
Bill Clearfield 1:42:47
No. Training was just right at the bottom. Where can we train for platelet nanoparticles Dr. Patel and Hello, so that’s your study. That’s your valuate Yes, that’s right. And can we access studies for PNP?
1:43:07
Ah, yeah, there’s enough enough material you just have to dig deeper and deeper.
1:43:12
Okay. So, Dr. Nereo, you’re the one who asked this if you want I can get you their contact information. Okay. Thank you. Thank you. Anybody else have any? Any questions, comments? Okay. Okay.
1:43:39
You’re gonna have next week.
Bill Clearfield 1:43:40
Well, next week I have I have a judge Walker’s going to be here. He promised he was supposed to be here this week. We got Dr. Patel, you know, in the in the last hour, which we thank you so much for Dr. Patel.
1:43:54
Thank you.
Bill Clearfield 1:43:57
You’re here next week and then the 29th that’s the let’s see. That’s the 18th Is it? The next week or the 98th. And then the 26th. Dr. Jaron and I will be presenting our first project program together.
1:44:18
May, Dr. Sylvia again with physician autonomy thing because me and her we’re going to work on putting together a company or something. So if she can present here, again, to encourage the people about what we want to do, because it’s very critical to have a firm of lawyers protecting us defending us providing us with all this consent letters, and verifying all the protocols that we’re doing and making sure that it’s it’s lined up with the with the mainstream medicine with the regulations.
1:44:54
Okay, well, Doctor she’s not on right now. So Dr. Burgess I’m going to let Have you have ever get in touch with me. So may 3 I have Nisha Berman, who’s a good friend of mine. He’s from South Florida. He’s he’s written a treatise on hormones. We’re going to have him on May 3, and so may 10. Is my next open date. So as Dr. Cruz if she’s available then with Dr. Hasa. Do we get together?
1:45:28
Yeah, yeah, cuz I want to have her if she can do it on Monday for me next week. That’d be great for you, too. Okay. Well, we can have all the doctors ready for getting into our membership on moving this company forward. So
1:45:45
right okay, so So Dr. Burgess. We’ll we’ll have you passed that on for us. And anybody else have any comments, questions? Anybody else have any anything they’d like to present because like I said, I have endless Tuesday’s so we’re always looking for some for some speakers. So
1:46:08
it has come to my attention that Dr. Charles Gant, who is a holistic integrative psychiatrist for something like 3040 years, I believe. He just completed a book that deals with elements of balancing with the nature of the earth and basically this whole thing about regenerative soil and depletion. He’s an expert in integrative functional regenerative depletion, but it all comes back to the soil. And he has completed and he has just recently released a book on that. And Maria Fogarty was mentioning that he would be a great guy to have a chat.
1:46:46
I think you sent me his contact information, right? So
1:46:49
yeah, he’s, he’s a good guy, and he’s always helpful. He fit right in,
Bill Clearfield 1:46:53
so we’ll get in touch with him also. All right. Okay. Anybody else? Questions, comments? We got lots of thank yous and lots of great great, great class. Dr. Patel. So thank you. You’re always one of our favorites. Thank you.
1:47:11
Thank you very much. And good night, everybody.
1:47:14
Good night, everybody. Next week, same time, same station. We’ll see you here. Night night