Victory Over Cancer : The Immune System and Genes Working Together
Exciting new discoveries reveal that at least two anti-cancer defense systems of the human body work in tandem with each other. When seeking alternative care for cancer, people often try to use various modes of healing. Often we conceptualize these various healing modalities as separate and distinct from each other. For example, we are used to thinking of the immune system having certain effects, and other healing systems of the body having their own separate effects. However, new discoveries of science tell us that the immune system cancer defenses and the genetic cancer defense mechanisms work together.
How Does The Body Fight Cancer?
What can we do to stimulate our natural healing forces to resist malignancy? Recent advances in medical science have revealed that the body has two primary weapons for fighting cancer. They are the immune system and the genes. However, this basic information was not understood until scientists began to unravel some of the deepest, darkest secrets of how cancer cells work. For many years, researchers were baffled by cancer. What exactly was the disease called cancer? How did the body fight cancer? The answers to these two crucial questions are now much better understood. This knowledge is giving new hope to cancer patients.
Cancer cells are now known to be the descendants of normal cells which changed into an unhealthy form. Cancer cells have many unique properties which allow them to be very strong, resilient, and resistant to attack by the immune system. The immune system serves as our primary defense against bacteria, viruses and other foreign invaders. Physicians specializing in natural health methods have long held that maintaining a healthy, vigorous immune system is important in patients battling cancer. Practitioners of the natural healing arts employ many types of herbs and nutrients in attempts to strengthen immune function. They look for evidence of immune system augmentation via tests such as immune cell counts, and by directly visualizing the living immune cells in action. It is quite fascinating and exciting to watch once sluggish immune cells turn into larger, more active forms. Special high-power microscopes allow us to see the immune system cells and to observe their activity levels.
Substances found in nature are often used by holistic practitioners for their anti-oxidant effects, or their purported ability to stimulate the immune system. However, some of these same items are also able to induce genetic healing in cancer. Case in point is NAC (N-acetylcysteine). Widely used for it's potential antioxidant and immuno-stimulative properties, NAC is also an inducer of genetic healing in malignancy. It seems likely that many more multi-role nutritional supplements will be discovered with time.
Natural Killer Cells
One of the primary objectives of immune system stimulation is to increase the number and vitality of Natural Killer Cells. Natural Killer (NK) Cells are large immune cells which have been shown to attack cancer cells and cells infected by viruses. NK Cells destroy their targets by releasing substances that damage the offending cell, leading to an immune response that eliminates the cell. If Natural Killer cells target and destroy cancer cells, why does cancer exist? Two theories help to elucidate this question. The first is that there are not enough NK cells, or that they are not activated to a level required for a potent anti-malignancy action. The other theory states that NK cells rarely know to kill malignant cells because the NK cells were not specifically programmed by the body to do so. New cancer vaccines are designed to "train" NK cells to attack cancer cells.
In addition to directly killing malignant cells by exuding a chemical, NK cells may also induce killing of cancer cells by causing a powerful gene response within the cancer cell itself. This gene response is known as apoptosis. Apoptosis is the self-destruction of malignant cells. The central control mechanisms of all cells, including cancer cells, are the genes. Genes reside within the center of every cell, and from there control all the functions and activities of the cell. Malignancy can only occur if the genes are changed in ways allowing the cell to transform into a cancer cell from a normal cell. Apoptosis is a gene response within the cancer cell that results in the cancer cell going through a program of self-destruction. Natural Killer cells seem to be able to cause this self-destruction. Other natural substances also are known to favor the self-destruction of cancer cells.
Alternative practitioners utilize many natural substances in an attempt to induce both immune and genetic healing forces against cancer. The two main genetic healing forces known to fight cancer are apoptosis and re-differentiation. Re-differentiation, the "R" in R-A Therapy is an inborn genetic system by which the cancer cell may be able to revert back to a normal, non-malignant condition under certain circumstances. The "A" in R-A therapy stands for apoptosis. Apoptosis is sometimes referred to as "cancer cell suicide". The two genetic healing mechanisms often go hand in hand with immune system augmentation, and are used in conjunction with many other alternative modalities.
The immune system and the body's gene defenses work together in an attempt to eliminate malignant cells. Many of the same natural substances which have long been used to stimulate the immune system have recently been shown to also help to induce our genetic healing mechanisms. Natural Killer cells, thought to be the single most powerful immune system agent to fight cancer, are thought to cause the death of malignant cells in part via their propensity to induce genes in the cancer cells that lead to the "self-destruction" of the selfsame cancer cells. The exciting new discovery that the body's two main defenses against cancer are closely related reveals to us the important role that natural therapies play, and engender hope for newer and better anti-cancer treatments.
Hyperthermia for Cancer
Is it possible to "cook" cancer into oblivion? Exciting new evidence indicates that this is sometimes a possibility! Cancer cells are much more sensitive to heat than are most normal cells of the body. Tumors need a blood supply, nutrients, and a normal body temperature if they are to thrive. When they are subjected to temperatures well above normal, in the 108 to 113 degree Fahrenheit range, they often die very rapidly. Achieving this potentially therapeutic body temperature for an adequate duration of time poses some safety problems. Our normal body temperature is 98.6 degrees, and fevers above 105 degrees are often dangerous. High temperatures may cause seizures since brain cells, like cancer cells, are sensitive to heat. How can this problem be overcome? There are several techniques now in use which help us to more safely use hyperthermia in cancer treatment.
The greatest recent advances in the field have come from new techniques that focus heating in a certain small area of the body. These devices are used to treat individual tumors or groups of tumors that are within a certain area. Depending upon the depth within the body, various modalities are utilized. For tumors on the surface of the skin or just below the surface, microwave heating may be utilized. Microwave is thought to be useful when tumors are at or near the surface of the body and not at a depth of more than 3 cm. Microwaves dissipate rapidly within the tissues of the body and are therefore unable to cause and adequate heating of malignant tissue that are located deep within the body. Tumors located to a depth of 8cm may be more amenable to treatment with ultrasound hyperthermia units. Sound waves are able to penetrate more deeply into the body. Another interesting fact about ultrasound hyperthermia is the ability of the technicians to focus the heat to a well-defined spot within the tissue to be treated. Therefore over-heating of adjacent non-malignant area can often be avoided. IRF, (Interstitial Radio Frequency) units employ the use of needles which are embedded into a tumor. The IRF unit then heats the needles, producing a targeted hyperthermia effect.
Whole body hyperthermia involves heating the patient to the maximum safe and tolerated level. Potential advantages of such a systemic and thorough hyperthermia include 1) there may be a general detoxification benefit and 2) there may be a greater likelihood of producing an effect against malignancy that is not found within the known tumors. Cancer is rarely confined to limited areas such as specific tumors. If it were, surgery would be curative if the tumors were removed. Unfortunately, this happens infrequently in most malignancies, since cancer cells often are present in areas other than known tumors. Whole body hyperthermia is most often induced via placing the patient in a sauna or whirlpool unit to employ the high specific heat of water to heat the body gradually and thoroughly. Some alternative therapies produce generalized fever. One of these is Iscador, the mistletoe extract. Proponents of mistletoe and related alternative modalities believe that at least a portion of the effect observed from these treatments derives from the increased whole body temperatures which occur.
It is interesting to note that hyperthermia was first seriously considered in modern cancer care after the observation, in the 1880's, that cancer patients who were subjected to high prolonged fever sometimes went into remission. This was observed in several febrile illnesses including poisonous spider bites and bacterial infections. A very famous old cancer therapy called BCG may, in part at least, produce an anti-cancer effect via the bacterial fever mechanism. Upon its introduction into medical practice, BCG was observed to produce meaningful medical benefits to cancer patients, and later became an approved medical treatment in the United States. BCG is now an FDA approved medicine based on a discovery many decades ago that this bacterial extract can induce a fever and sometimes lead to complete or partial cancer remissions. BCG today is utilized extensively in alternative medicine, as well as in conventional medicine for the treatment of bladder cancer.
Hyperthermia is truly a promising therapy option for the treatment of malignancy. It is expected that further research and more extensive experience by physicians utilizing hyperthermia will result in ever improving methods of using hyperthermia effectively and safely. It is crucial to note that the main drawback of whole body hyperthermia is that life is threatened at high temperatures. The brain, heart, and other crucial organs may be overwhelmed by the demands placed upon them by the abnormally elevated body temperatures. As is true with many therapies, proper monitoring by a qualified healthcare professional is wise.
Blood Sugar and Cancer
Cancer cells have a weakness that may allow us to detect and destroy tumors much better than in the past. The weakness is the need of malignant cells to use sugar as their primary energy source. Rapidly growing cancer cells "burn" a great deal of sugar each day. Without sugar to use as energy, cancer cells may become weak and vulnerable. The propensity of tumors to use sugar for energy allows us unique opportunities to 1) detect the tumors, 2) starve the tumors, and 3) make tumors more amenable to attack by medicines, vitamins, and herbs.
An exciting new advance in cancer detection is the PET scan (Positron Emission Tomography). PETs detect tumors by looking for areas within the patient in which blood sugar is being utilized in the rapid fashion characteristic of malignancy. In essence, the cancer cell's own need for sugar allows it to be "seen" on the PET scan. This allows for important advantages over older forms of cancer testing. PET scanners can detect much smaller tumors or aggregations of malignant cells than can CAT scans, bones scans, and X-Rays. PET scanners can tell us whether the cells within a tumor are still alive. This is quite important when a patient is being treated for cancer and the treating physician is trying to ascertain whether or not a mass visible on a CAT scan still contains living cancer cells. If the PET scan is negative, this indicates that the cancer cells within tumor have been successfully killed with the treatment. Prior to the advent of PET scans, doctors had to wait until the tumor shrank or disappeared in order to know that they were successful in their treatment.
Hypoglycemia therapy for cancer seeks to lower the blood sugar in an attempt to "starve" the tumors of their main food supply... sugar. Hypoglycemia means "low blood sugar". Some alternative medical clinics are using injections of insulin to profoundly lower the blood sugar of their cancer patients in an attempt to weaken or kill the cancer cells by depriving them of their main energy source. Dieticians and nutritionists well-versed in natural healing methods often advise their cancer clients to minimize foods that contain sugar, as well as foods that rapidly are converted by the digestive processes into blood sugar. They postulate that if a generally low level of sugar is maintained in the blood, then cancer may have more difficulty growing and developing. Foods that tend to easily and immediately raise blood sugar are those which contain sugar and simple carbohydrates. Products made of refined flour such as bread, cakes, and pasta are prime examples of simple carbs that readily increase the blood sugar levels. Whole grain precuts, nuts seeds, legumes and lean sources of protein, whether animal or vegetable sourced, tend to modulate blood sugar and fight high blood sugar from developing.
Seemingly to prove to us all how profoundly complex the human body truly is, some practitioners believe that temporarily causing an elevation in blood sugar may help them to fight cancer. The rationale is that at least two benefits may be gained from very short-term periods of elevated blood sugar levels, known in science as "hyperglycemia". Tests have revealed that tumors become internally more acidic when subjected to hyperglycemia. Some scientists believe that these periods of internal hyper-acidity within the tumors temporarily weaken the cancer cells, allowing a window of opportunity to open in which to attack them.
IPT, insulin potentiated therapy, uses a combination of hypo and hyperglycemia, plus herbs, vitamins, or medicines to treat cancer.
Genetic Healing in Cancer:
The Scientific Basis for R-A Therapy
Cancer is inherently a genetic disease. Mutations in the genes of normal cells are paramount in the process of carcinogenesis. Genes predisposing to cancer can be inherited. The genes within each cell instruct that cell as to its size, shape, and activity. The genes determine every major aspect of how a cell will present phenotypically, and the genes control the activity and functions of each cell. The genotype specifies the phenotype. Genetic factors are therefore paramount in both the development of cancer cells and also in determining what harmful activities the cancer cells will have within the body. The realization of the importance of genes in oncology has led scientists to begin experimenting with ways to influence cancer genes and to cause "genetic healing" in cancer.
Genetic healing can occur by many mechanisms. The best known of these mechanisms include 1) the direct incorporation of new "anti-cancer " genes into cancer cells, a concept which includes Telomerase gene therapy; 2) Re-differentiation; and 3) Apoptosis. Re-differentiation refers to the propensity of cancer cells to revert back to a normal, or perhaps simply to a "less-cancerous" state. This concept is premised upon the widely accepted theory that cancer cells derive from a cell that was once normal. The theory states that as the normal cell is placed under metabolic stress, it genetically mutates multiple times. Factors such as radiation, chemical toxins and others comprise the stressors which result in the step-by-step mutations. As each gene mutation occurs, the cell phenotypically becomes more abnormal. It is believed that this process occurs commonly in modern humans. Why then do not more cells become cancerous? The answer is thought to be the genetic checks and balances inherent within each cell.
Genetic checks and balances are the major safety mechanisms protecting us from developing cancer. Each of our cells is born with a natural endowment of genes and genetic pathways that are protective against carcinogenesis. Cell-cycle control genes monitor perturbations in the cell cycle and other genes scan for aberrations within the genetic code as the cell replicates itself via mitosis. These genes can stop an abnormal cell from replicating, and attempt to repair the genetic damage which we often call a mutation. The genes involved in re-differentiation and apoptosis are thought to be crucial in the monitoring and abatement of carcinogenesis. Interestingly, mutations in these protective genes are thought to be imperative if a mutating cell is to survive long enough to become a tumor. Re-differentiation genes may become active during the process of transformation of a normal cell into a malignant cell. They attempt to reverse the cell's progress down the genetic path towards malignancy and away from carcinogenesis. If the re-differentiation genes are successful, they will cause the mutating cell to take the same mutation steps backwards and thereby unravel the stepwise process of mutations which can lead to cancer.
Apoptosis genes also protect against mutagenesis. Apoptosis is the process by which our genes monitor if aberrations in the genetic code are occurring and then cause the cell to go through a process of self-destruction, if the genetic damage cannot be repaired. This process tends to delete cells which are mutating towards carcinogenesis. Many modern scientists believe that apoptosis, re-differentiation and cell cycle control genes are the most important inherent protective mechanisms against neoplasia.
This concept is the antithesis of another theory held widely by the public and by alternative medical practitioners. That theory holds that it is the immune system which primarily protects us from developing cancer. Many people assume that the immune system should know if a cell is dangerous to the body. However, there is little credible scientific evidence to suggest that the immune system has any way to detect cancer cells, or that the immune system is designed to attack cancer cells. The immune system is designed to protect the body from foreign invaders such as bacteria. Immunity senses whether each cell is a "self cell" or a foreign cell. Unfortunately, the markers of most cancer cells indicate to the immune system that it is a "self cell" and the immune system therefore ignores it. The so-called "immune surveillance system" against cancer is unlikely to have a significant impact to limit neoplastic growth and development. This, however, does not preclude the immune system from being coaxed into attacking cancer cells when medical treatments such as cancer vaccine therapy are administered, but it does argue against any natural inherent immune protection against carcinogenesis. The genetic protection mechanisms seem to have that role.
Fundamental to carcinogenesis is the destruction or impairment of the genes which encode the apoptotic and re-differentiation pathways. We would therefore expect that tumor cells would have these genes either eliminated, turned off or turned down. Cells which turn off or turn down their re-differentiation and apoptosis genes may potentially be prodded into turning these protective gene pathways back on. The process of re-differentiation may result in a partial reversion towards normalcy, in which case the cell simply becomes less cancerous. An active intra-cellular apoptotic mechanism results in an increased tendency of the mutating cell to sense that it has mutated, and then to self-destruct via complex genetic and cytosolic interaction.1 Although the exact mechanisms involved in the apoptotic pathways have not yet been fully elucidated, researchers are gradually revealing the intricacies involved in this life-saving process. One of the most important genes in this process is called p53. Apoptosis research has indicated that p53 induces the release of cytochrome c from the intermembrane space of mitochondria, and that Bax in the cytosol of the cell also plays a role.1
R-A Therapy is a concept of utilizing existing natural substances in an attempt to induce re-differentiation and apoptosis in cancer cells, or in cells undergoing malignant transformation. The concept of genetic healing and preventive mechanisms in oncology is in its infancy. None-the-less, there is credible scientific evidence that many natural substances may induce protective genetic mechanisms such as re-differentiation and apoptosis.
N-acetylcycteine is a very promising candidate for a natural substance which may induce apoptosis. N-acetylcysteine as a prominent component of the R-A Therapy regimen. Many recent scientific studies attest to the propensity of N-acetylcysteine to induce apoptosis and play other health-protective roles in the body. In alternative medicine, N-acetylcysteine is best known as an immune enhancer and antioxidant. However, in natural cancer therapy, its most important role may well be to induce genetic healing mechanisms. R-A Therapy relies upon the propensities of natural substances such as N-acetylcysteine to attempt the induction of genetic healing processes. N-acetylcysteine (NAC), along with another agent used in R-A Therapy known as dimercaptopropanol, have been shown to induce apoptosis in several cancerous (transformed) cell lines and several transformed tissue cultures.2 Interestingly, NAC and diemercaptopropanol did not induce the apoptotic "cell-suicide" program in normal cells. These two agents caused death of the transformed cells through apoptosis, but did not cause death in the normal non-malignant cells. The mechanisms of action described in this study included the elevated post-transcriptional expression of the p.53 gene via an increase of p.53 mRNA translation. The authors of the cited study postulate that "manipulating p53-dependant apoptosis with non-toxic antioxidants may have direct clinical application".
NAC has also been shown to affect the genes involved in cell-cycle control, one of the postulated genetic healing and genetic protective mechanisms against cancer. NAC was shown in a recent study to induce G(1) cell cycle prolongation and cyclin-dependent kinase inhibitors, causing the authors of the study to postulate that "taken together, these results suggest a potential novel molecular basis for chemoprevention by NAC."3 In another research paper, published in the International Journal of Biological Markers, the authors described NAC as "a cytoprotective drug that can prevent in vivo carcinogenesis."4 The same research paper showed evidence that NAC reduced the weight of the primary tumors studied (an indirect indication of cancer cell death), diminished the number of lung metastases, and reduced the formation of spontaneous metastases in mice. The researchers also found that NAC seems to have an anti-angiogenesis effect. They discovered that NAC strongly reduced the invasive activity of endothelial cells when subjected to angiogenic stimuli, and that NAC blocks gelatinase activity. An in vivo anti-angiogenesis activity was detected and reported by the authors from the oral administration of NAC. Perhaps the most interesting finding of this study to clinicians is the fact that NAC inhibited tumor latency, and that this effect was dose-dependant. The significance of this finding is that one of the important precepts of R-A Therapy is that high doses of natural substances should be administered in a way that best presents the highest possible dose directly to the cells. Intravenous administration of natural substances is therefore a very important part of the R-A Therapy concept.
NAC is postulated to have effects on the genes of cancer cells and also to serve as an antioxidant. These two seemingly separate roles may actually converge into one coherent anti-cancer mechanism of action as more research is done. Astrocytoma cells have been shown to proliferate in the presence of a strong pro-oxidant, but their proliferation was inhibited by the presence of NAC.5 Another study suggests that an inverse correlation exists between cellular lipid peroxidation and neoplastic transformation.6 The authors postulate that restoration of adequate antioxidant status in a cancer cell may modulate re-differentiation within the cell and inhibit cellular proliferation. Other more common anti-oxidants are also utilized in R-A Therapy. These include vitamins A, C, and E. A study in humans published in 1999 evaluated the role of both vitamin A and NAC in patients with cancer of the lungs and bronchial systems.7 A Scandinavian study elucidated the beneficial role of NAC, and the antioxidant vitamins A, C, and E to retard the growth and development of colorectal tumors.8 It is well-known that colorectal polyps may transform into colon cancer. The study found that of the 209 evaluated test subjects, 35.9% of the untreated controls developed polyps, whereas only 5.7% of the subjects supplemented with Vitamins A,C, and E, developed polyps. A furtherance of this study indicated preliminary data that those subjects who received NAC had a 40% reduction in polyps compared to controls.
Studies showing an effect to diminish proliferative growth of pre-cancerous lesions such as colon polyps may well also indicate direct anti-proliferative activity by the agent tested. Agents studied may also prove useful to prevent the development of cancer via genetic healing mechanisms that eliminate the cancerous cell during the transformation process, thereby sparing us the development of the matured disease of cancer. NAC was shown to decrease the proliferative index in a study of persons at risk for colon cancer.9 The proliferative index is thought to be a predictive biomarker for the risk of developing neoplastic disease.
The natural polyphenols are another group of natural substances utilized extensively in R-A Therapy. In the 1800's, homeopathy was the predominant form of medical care administered in the United States. The majority of MDs at that time primarily practiced homeopathy in their medical clinics. Homeopaths of that era cited homeopathic phenol as a leading medicine in cancer care. Modern research is once again bearing out the benefits of natural polyphenols in oncology. Green tea extract is rich in natural polyphenols and is used in RA Therapy. A study designed to evaluate and elucidate the cytotoxic effect of green tea polyphenols revealed a decrease in tumor cell viability in the presence of green tea extract and one of its component polyphenols known as epigallocatechin (EGC).10 The authors stated "Epidemiological studies suggest that the consumption of green tea may help prevent cancers in humans, and also breast and prostate cancers in animal models are reduced by green tea, and several mechanisms of action have been proposed for these effects."
Other members of the polyphenol family used in R-A Therapy include butyric acid, phenylic acidum, many forms of catechins, carbolic acidum, and components of the cruciferous vegetable family. Phenylehtylisocyanate and NAC were both studied to elucidate the anti-cancer role of the polyphenols and other natural components of the cruciferous vegetables.11 The study showed that these natural substances caused cytolysis of human prostate cancer cells when they were exposed to high doses of the agents and growth modulation which was dose-dependant at lower concentrations. The authors are quoted as stating... "There is growing evidence that thiol conjugates of isothiocyanates present in cruciferous vegetables are effective cancer chemopreventive and potentially active therapeutic agents." Butyrate was found to induce apoptosis in a cancer cell line normally resistant to undergoing apoptosis.12 The colon cancer cells were induced to undergo apoptosis induced by TNF-alpha and Fas ligating antibody. Butyrate was also found in the same study to influence reactive oxygen species.
Another two intriguing RATherapy components are alpha-lipoic acid and lecithinized ascorbic acid (PC-AS). Lipoic acid, like many medicinal natural substances, seems to have a plethora of potential beneficial mechanisms of actions and therapeutic uses. Normally thought of as an antioxidant, lipoic acid may also have a direct effect on the protective genetic apparatus of the cell. Alpha-lipoic acid exhibits inhibition of neoplasia in vitro.13 The authors of this study stated "alpha -lipoic acid is a potent thiol antioxidant which has been demonstrated to be efficacious in several oxidative stress models." Ascorbic acid, also known as vitamin C, has long been highly regarded in alternative cancer medicine for producing therapeutic benefit in cancer patients. A form of ascorbic acid to which lecithin has been covalently bonded revealed even greater effects in a recent study.14 Researchers found that PC-AS effectively inhibited murine pulmonary metastases, and that the potency of PC-AS was superior to that of ascorbic acid alone. They also showed evidence that NAC produced an additive inhibitory effect when combined with PC-AS.
Methods of inducing genetic healing in cancer, such as R-A Therapy, hold great promise for the future. Evidence of this is found in the recent activity of pharmaceutical firms and bio-technology companies to develop new products based on apoptosis and re-differentiation. One such example is a new drug now in FDA trials called "Aptosyn". Aptosyn is a man-made molecule derived from the arthritis drug Sulindac, which is found to have a propensity to induce apoptosis in cancer cells. Human clinical trials thus far seem promising. Genetic healing in cancer involves many healing mechanisms which may reasonably be referred to as "self healing" by the cancer cells themselves. It is probable that adding genetic healing mechanisms such as those found in R-A Therapy to other anti-cancer therapies will yield a far greater therapeutic benefit to patients than has thus-far been achieved in oncology.
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- Liu M, Wikonkal NM, Brash DE
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- Arora-Kuruganti P, Lucchesi PA, Wurster RD
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- Estensen RD, Levy M, Klopp SJ, Galbraith AR, Mandel JS, Blomquist JA, Wattenberg LW
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- Kennedy DO, Matsumoto M, Kojima A, Matsui-Yuasa, I
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Modulation of growth of human prostate cancer cells by the N-acetylcysteine conjugate of phenethyl isothiocyanate.
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- Giardina C, Boulares H, Inan MS
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