FAQ: Laboratory studies of HIV infection

7 facts about the study of the human immunodeficiency virus in a controlled environment

One of the most urgent problems of modern medicine - is the fight against HIV. The epidemic of the infection that leads to the disease called AIDS, captured almost all countries around the world. To date, a variety of attempts at least to limit the epidemic, to stop its spread by creating vaccines and subsequent vaccination, as well as other measures, in general, have not been successful.

When the last of the vaccine failed, adopted a consensus decision in the scientific community that we do not know the fundamental mechanisms of HIV infection, and it is the most important: to fight the infection, you need to start to understand the fundamental mechanisms of infection and on this basis to develop preventive measures. Therefore, my colleagues and I are exactly the fundamental problems of HIV infection. Why this virus is so successful from his point of view? Why deal with many other viruses, the virus remains unbeaten? To feed your immune system – buy Cyanocobalamin, Meldonium, Metaprot, IRS 19, Selank, Cerluten.

• 1.Strategy for HIV

The main reason for choosing a very successful from the point of view of the virus, of course, strategy. First, unlike the other virus infects precisely those cells that are designed to fight infection. Secondly, he chose the path of a successful sexual reproduction - is the preferred method for virus propagation. It is important that it not only infects the immune cells that are designed to fight it, and activated cells. That is, when the virus infects the other body, the immune system cells are activated and destroy the virus or virus infected cells. However, HIV attacks the activated cells, that is, the ones that are designed to destroy it - this is its advantage.

For a long time it seemed that the disease runs as follows: the virus infects a person, there are some mild symptoms, and then it disappears, and there is many months, sometimes even long-term latent phase. But then it turned out that it is not. The concept of latent phase appeared because based on a blood test sick patients. It turned out that during this phase, the virus disappears from the blood really, but it continues to multiply and destroy lymphoid tissue, lymph nodes, which are the centers of origin of the immune response to infection.

• 2.The study under controlled conditions

When it turned out, it became clear that it is necessary to study how these viruses do not proliferate in suspension in a laboratory or in the blood of a patient, namely in the tissue. Therefore, the group, which I direct, my colleagues and I have created such a laboratory system that allows you to learn in a controlled environment reproduction and pathogenesis of this virus in the lymph tissue. For a variety of both technical and ethical reasons, it is practically impossible to study how the virus replicates in the human patient tissue. A blood test can be taken without any consequences, but it is difficult to penetrate into the tissue and in many cases impossible.

From the history of medicine shows that most of the mechanisms of human diseases became clear when they were created or animals, or other laboratory models to study them, because science is necessary to control all the conditions for the study of any process. The man, of course, impossible. Animal models of HIV infection there is little, although there is a similar virus which infect monkeys, but unlike many other viruses, HIV infects human, and only a person.

We have created a system that consists of pieces of lymphatic tissue. To create it, you can take the operational material, for example, after a tonsillectomy or adenotomy when excised tonsils or adenoids. Basically cut the tonsils in children for indications of frequent colds. We take these pieces, we know how to cultivate them in the laboratory for two to three weeks, artificially infect them with HIV and see how the pathogenesis. In this way, we have some interesting data.

• 3.The use of a laboratory model

Also, this system is used for testing various antiviral drugs, because studies of HIV infection are very expensive. Any clinical trials require years of preparation, because the drug goes through various stages of testing before it is introduced even in healthy volunteers to toxicity testing. Our system allows without any problems related to ethics, with the permissions view in preclinical trials as the drug acts on the virus.

In addition, this system is very useful and provides a lot of information about the virus, transmission, experts say, that is how the virus is transmitted from an infected person to a healthy, for example from a man to a woman. We have a system that allows you to cultivate, such as the cervix, where the infecting virus transmission from man to woman sexually.

• 4.Co-infection with HIV and herpes

We got a lot of interesting results, in particular, the process of contracting the virus. HIV infects activated immune cells, some of them are moving to this state if a virus infection, but can be activated and infection by other viruses. That is why other pathogens, even not as terrible as HIV, herpes viruses such as for a healthy person, do not pose a danger, activate immune system cells, thus creating a new target for HIV infection.

• 5.The defeat of the immune response system of control

HIV "invented" a cunning strategy: it infects cells, and they begin to secrete special substances - cytokines that activate neighboring cells. Therefore, a neighboring cell, which until then had been alone and therefore could not be infected with HIV, it becomes a target for the virus. Thus HIV infection paves the way for himself and distributed in the tissues. In addition, HIV infection, and infection associated virus, activating the cells to cause the production of so-called interleukins. Interleukins - is soluble substances which are allocated among the cells are absorbed by the other during the normal immune response. It is very difficult, "degenerate" system, it can be replaced with some other interleukins, and they regulate the normal immune response. This complex system of interleukins varies under the influence of HIV infection like a sick man, and the chronically sick.

We have found for example that one odd elevated cytokine in semen of men with HIV, which is called interleukin-7. Why he's raised - it is unknown.

Knowing the nature of this virus, it is possible to think that he does nothing in vain. Most likely, the entire cytokine system is a sick man changes the virus in their favor, otherwise evolution would not let him be so successful. Perhaps more pathogenic viruses are selected than if it was without interleukin. It was found that the IL facilitates the transfer of the virus and infection of cervical tissue.

We conducted a simple experiment: if you take the tissue of the cervix of healthy women and infecting her with HIV in a Petri dish, add to the interleukin-7, the infection is much more efficient. On the basis of this work, we have the following hypothesis: maybe men with elevated IL-7 is easier to infect their partners than those who have less interleukin.

• 6.Resistance to HIV infection

Linked to this is a big problem: there are a pair of "husband - wife" recruited for clinical trials, which consist in constant communication, not change each other, but without knowing it, and do not take precautions, the men can be infected by a virus, and a woman for a few years, often many years, did not become infected. When it is found, we thought that these women have some protection mechanism and, perhaps, it will be able to play all the others. Long studied, but nothing special in these women is not found.

In light of our research, we think that the absence of infection, transmission from these men consists precisely in the fact that they have the cytokines that promote infections violated. At the moment this is only a hypothesis, which may be incorrect.

• 7.Treatment of co-infection of HIV and herpes

As already mentioned, the herpes viruses help accompany HIV infection and transmission. For quite a long time for people infected and the virus, and the other, prescribed therapy against the herpes virus, since it is clear that a single disease rather than two. In this case, registers opened in the 70's standard drug acyclovir - this is the most effective tool against the herpes virus. Acyclovir acts on several herpes viruses, including the one that usually accompanies HIV - 2 herpes virus.

we can study the mechanism of interaction of viruses in the laboratory for the study of HIV. When we started to infect tissue slices immunodeficiency virus, and herpes virus, we would like to reproduce the effect of acyclovir on the system in a controlled laboratory case. It turned out that this is possible: the use of acyclovir inhibits herpes viral infection and leads to suppression of HIV. Since we can carry out the control in our system, it was found that acyclovir can without herpes 2 directly affect HIV infection.

We are now conducting clinical trials, they are far from complete, so can not be recommended for the treatment of acyclovir, but it is one of the examples where laboratory system allows you to open that actually it would be impossible to open, studying human. Nobody can allow research on human beings, and rightly so. Also, this situation is an example of a controlled laboratory system allows you to discover the mechanisms of interaction of the virus, viral pathogenesis, which are needed to fight the virus and the development of preventive methods.

Immune activation and human disease

Biologist Dr. Doping tells about the general theory of medicine, the immune system and HIV infection. How does the immune activation? What parameters characterize the process? As immune activation contributes to the emergence of viral diseases?

All modern natural science came out of the history of natural philosophy - medieval science, which is not divided on the nature of the different departments and studied it as a whole. Over time, science divided into physics, chemistry, medicine, and biomedicine, as they say. And for some reason they have gone very different ways. Physics has sought to unite his theories and the idea of physics - try within a unified theory to explain all the phenomena of our world.

Medicine has gone a completely different way: she began to concentrate around certain diseases, which led to a very large specialty medicine. For example, ophthalmologists know little about the heart diseases, people who deal with heart disease, atherosclerosis, little is known about infectious diseases, people who deal with infectious diseases, little is known about the various pathologies of pregnancy and so on.

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Last general theory of biology - is the cell theory, which was developed over 150 years ago, and since then, particularly the general theory was not. And now we are seeing the development, the development of the theory, which is the first in many years, the general theory of medicine - it is a theory of how different diseases occur and what unites them.

Different diseases in different areas accompanied by the phenomenon of immune activation. In the days of Pasteur and many years later, the immune system is considered as a system that protects us from flying around the bacteria, viruses, and if, God forbid, a virus or a bacterium entered the body, the immune system is activated and destroys them. Then everything goes back to the previous level before the next infection, unless the infection is not lethal. It turned out that this is not the case.

The immune system often does not come back, and, moreover, in our body there are many viruses and bacteria that live permanently, without threatening our health, but from time to time are activated. Thus, the immune system how to maneuver in the army: it happens all the time training. When a person becomes infected with what some viruses, bacteria - becomes inflamed. We all know that such inflammation when, for example, it appears on the skin. Inflammation is associated with lymphocyte activation, reproduction, leukocyte traffic to areas of infection occurs redness, increased vascular permeability - we are faced with the same life. Then it all goes. Sometimes it becomes chronic. The so-called chronic inflammation is characterized by the production of a number of soluble substances and activation of certain cells.

There is a phenomenon that is now clear - easier activation of the immune system. This inflammation is not without chronic inflammation, but something less than that, the weaker. It turned out that it is accompanied by various diseases, and in different areas have experts understand that this immune activation strongly contributes to the development of the disease. It's like a second key to the safe. One key - is directly etiological agent that causes, say, HIV - HIV is.

The second key - immune activation, which is the engine of infection and possibly without this disease and would not develop.

This is not new idea. New is that experts in different areas do not know how widely this view, which captures different areas. In various areas, this idea appeared at different times. For example, with heart disease, atherosclerosis can be traced to the Rudolf Virchow, the classics of science of the last century, in other areas, she appeared in the 90s, or more recently.

We are engaged in the study of immune activation. It has a number of very specific measured parameters: appearance molecules called immune activation markers on lymphocytes, occurrence of vesicles, cells which produce other cells and transmit the information signal (in which the RNA and protein), and several other parameters. This immune activation was common to many illnesses. We examined the immune activation with different peers. In particular, immune activation in atherosclerosis we explore Moscow with prominent experts in the field of heart disease, cardiologists Alexander V. Shpektorov Jurevna and Elena Vasilyeva. We will explore this in different disorders of pregnancy - there is a violation of pregnancy called preeclampsia, is very common, often leading to the death of the fetus - an outstanding American expert Roberto Romero and several other diseases.

The clearest example that shows why the immune activation is the driving force of infection - HIV infection. Immunodeficiency virus, by definition, causes immunodeficiency. Long thought that this immune deficiency, because the virus kills some important cells. Really. But it turned out that the driving force of HIV immune activation is because the virus infects mainly immuno-activated cells continue to activate immune-cells that are not infected, and thus the infection develops.

Why this immune activation is such an important show experiments on monkeys. There is a similar virus in monkeys, called simian immunodeficiency virus. There are monkeys, macaques, which are infected with the virus laboratory, and they have a disease similar to the little disease that causes HIV in humans. And there are monkeys that are infected but not ill with the disease. At first thought, that they do not become infected - it turned out to be infected. I think that they have an immune system that prevents the spread of the virus. It turned out that it is not. The only difference in monkeys that did not suffer in spite of being infected with the virus - the fact that their system ignores the virus, it is not immuno-activate live quietly, without paying attention to the virus. This is an important proof in mathematics, almost absolute proof that immune activation is the driving force of this infection.

Even in the field of cancer it was found that immune activation plays a major role. Long thought - and it is true - that cancer cells appear in our body all the time, but for the time being the immune system of their catches, destroys, and most of us do not get sick with cancer, especially at a young age. And then she at some point as it passes the cell, and then there is cancer. But even then, in solid tumors a lot of activated lymphocytes, which are thought to be struggling with this tumor.

It's all true, but it turned out that this immune activation have the opposite part: it contributes to the development of cancer. Specifically, cancer cells proliferate under the influence of factors that produce immuno-activate cells. Cancer cells that broke away from the main tumor, can not find a place for metastasis should be attached somewhere other tissues, and this contributes to immune activation. It prepares such soil to a cell in the village and began to invade the tissue. In addition, within a large tumor substances enough to feed it, and tumors produce factors inducing the growth of blood vessels that grow into the tumor and thus it is fed.

The vascular ingrowth is also a consequence of the immune activation of the local system.

Thus, immune activation contributes to some of its frequent occurrence of tumors. The same can be said about the eye disease - related macular degeneration - the destruction of the retina when the retina tissue sprout n undeformed vessels, of which the fluid flows and destroys the retina. This is a very common disease, especially among the elderly, when the stain occurs.

All these factors together, all of the research in different areas suggest that immune activation is one of the main aspects of various diseases. This relates to diabetes, Alzheimer's disease, to various other diseases. As any new discovery of factors that cause the disease, it may be a target for therapy, and in some areas are already making attempts to suppress the immune activation in the hope that it suppresses the disease. Of course, to suppress the need to very carefully to develop this very neat drug, because, if not suppress the immune system, we get sick, die from diseases that are now our system is struggling. However, such attempts have already been, and in some areas they are quite promising.

Cell death and its use in medicine

Biologist Dr. Doping tells about active and passive processes of cell death, necrosis, and ways of dealing with cancer. How is apoptosis? What diseases can lead to cell death? Why in different cells and tissues of different forms of death work?

The process of cell death can be active or passive. Passive process - when the injured cells are not able to repair damage to their own and must be somehow eliminated as many tissues within the body. Active process - this is when the cell realizes that it has fulfilled its function, and that should be allowed to operate other cells. A typical example of such an active process - embryogenesis or differentiation.

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The population of cells in any tissue is governed by three processes. The first - a cell division, when their number increases; second - differentiation when the number of cells increases or decreases depending on the tissue; and third - this cell death. These processes are responsible for the proper functioning of tissues and organs. If we take the average weight of a person (70 kg) - every day we lose about 1 kg of our weight. This is a normal physiological process. The most actively dying cells - this intestinal epithelial cells over a lifetime they change almost 4,000 times. If the cells do not die, for 70 years of life, we have produced 30 km of the intestine.

The dead cells in the body should be eaten either macrophages or neighboring cells. This is very important because if there is no inflammation, which is dangerous for the tissues and body. Very few cells simply die, many of them commit suicide, it is in certain and necessary conditions. There are two physiological state. The first - when a lot of cells are killed, leading to loss of homeostasis. Second - this is when there is no cell death, or it defective, and then the amount of accumulated cells. Both situations are abnormal, and there are plenty of diseases associated with cell death. Depending on how much or little of cells killed in the same organ may cause such situation exactly the opposite of the disease.

Abdominal surgery

Surgeon Dr. Doping tells about division by emergency and planned surgery, the most common operations and the history of surgical instruments.

The abdomen - it's belly. Accordingly, abdominal surgery - an operation on the abdominal organs. Abdominal organs - that is all that is from the diaphragm to the pelvis. Accordingly, all found in the digestive organs of the abdominal cavity. In addition, we consciously feel about another part of the authorities, who are in the retroperitoneal space - is the kidney, pancreas. Furthermore, the pelvic organs - a uterus, appendages in women, prostate in men bladder. So it's a huge amount of vital organs, which provide our peaceful existence.

Abdominal surgery is divided into emergency and planned. With emergency surgery all probably familiar with. Most hospitals performing surgery on an emergency basis, all first aid and hospitals accept patients. It's no secret that most private diseases are: acute pancreatitis, acute appendicitis, cholecystitis, intestinal obstruction, incarcerated hernia, bleeding from duodenal ulcers and stomach. Accordingly, this group of diseases, which I have described, which arise suddenly, just in those patients who are filling up most of the emergency rooms and operating the hospitals involved in emergency surgery in the abdominal cavity.

Do not forget about the injury, which is related to exceptional occurrences, catastrophes, leading to damage of the abdominal cavity, to the intra-abdominal bleeding, and without immediate surgery is inevitable ruin. Accordingly, a large number of patients arrives daily at various hospitals. This is probably the main contingent, and a larger percentage of transactions in most general hospitals - is emergency surgery.

Planned operations. What it is? That can wait, you can explore. This gastric disease, duodenal ulcer disease, chronic. Liver disease, tumors, metastatic lesions. Disease and intestinal tumors in most cases. In this situation there is no urgency. But if we do not remove the diseased organ, the tumor will continue to grow, there may be metastases in other parts of the body, and the patient, unfortunately, is no future for radical treatment. Therefore, elective surgery involves correction of those diseases that do not happen quickly, but prolonged their existence will lead either to a deterioration in the quality of life, or to a reduction in its duration. To improve immune system and the quality of our life - buy Meldonium, Prednisolon, Peptides (Cytomax) Bonomarlot, Vladonix for prevention cancer.

Therefore, elective surgery can be divided into surgery in the abdominal cavity in benign diseases. What is most often done for benign diseases? This gastric ulcer and duodenal ulcer. It is true that in the past was much more of these operations. Now there was a drug therapy, so the frequency of these operations has decreased significantly. Benign tumors of the gastrointestinal tract, liver, duodenum, stomach, small intestine and colon surgery subject. With regard to malignant diseases. One of the major problems of our society - a malignant disease. Not yet found ways of treating malignant diseases without surgery. Yes, there are a number of diseases that are cured by chemotherapy, but this applies mainly to hematologic diseases. When we talk about cancer of the abdominal cavity, the only option is radical - it is removing them. Therefore, in most cases, this is accomplished in oncology institutions in the oncologic dispensary or in the hospitals, where there is a license to cancer care. Cancer care requires a holistic approach: in addition to the operations required chemotherapy, radiation therapy, that is, a scalpel is not enough. What is the difference between benign from malignant disease? That benign do not give metastases, rarely progresses. Malignant tend to recur, to metastasize, ie screenings tumors in other organs. So now the direction of scientific research - is the search for effective drugs to stabilize or, on the contrary, recourse cure these tumors in combination with surgery. Therefore, a single operation is not enough, it supplemented by chemotherapy, radiotherapy, chemoradiotherapy, that is, using combined methods of treatment.

If we talk about specialization within the abdominal surgery, ie the abdominal cavity, the recently observed specialization even within the abdominal cavity. In particular, surgery of the liver, pancreas and biliary tract require special preparation, and it is called, hepatologists, surgeons, hepato-pancreatobiliary surgery. Surgeons performing surgery on the stomach, esophagus, intestines, called the surgeons, gastroenterologists. Those doctors who are engaged in operations on the colon and rectum are called Coloproctology. And each of this profession is very serious and requires very serious skills, so they are isolated within the abdominal surgery. Now it is to be a universal surgeon heavier and heavier. Yes, in emergency surgery, we have no other choice. It is necessary, when damaged many organs or emergency situation, to operate all. But when we talk about complex diseases, cancer or benign lesions of the abdominal cavity, depending on their localization is very clearly specialize everyone who is engaged in one or another section of abdominal surgery.

Abdominal surgery is quite young Surgery, because associated with the introduction of anesthesia, with the understanding that such an infectious process after surgery, therefore, to perform operations on the abdominal organs (this abdominal surgery) began only in the second half of the XIX century. Why? Because it is at the end of the first half of the XIX century, in 1848, the famous American dentist Morton proposed using ether anesthesia. With ether patient medical immersed in a dream. And with anesthesia, disconnection of consciousness and pain sensitivity, the opportunity to perform in such difficult areas. Prior to that, no one could touch the abdominal cavity, so the operations are performed in historical perspective on the limbs. Yes, sporadic operation, that is random, but it can not even be called an operation. Clearly, combat injury, the field of battle, the front abdominal wall is injured, guts out - they do then? All the submerged inside, and if the patient was not fortunate and penetrating internal injuries and abdominal bleeding, some of them survived. And wholly mortality, that is, all died until such time as surgeons have not learned somehow to anesthetize a person - and this opportunity came just in the middle of the XIX century, and boldly could be under anesthesia introduced into the abdominal cavity, to sew up wounds . Therefore, the first operation, if we talk about liver operations began in 1871, when on the battlefield German military surgery Bruns first sewed liver injury and the patient, wounded soldier, survived. This is the first written record about the operation of the liver.

By the end of XIX century there were operations on the stomach. Everyone is familiar with such names as Billroth, Roux, Kocher, because we still carry out operations under their names, for example: gastric resection Billroth I, Billroth II or bowel resection, isolated intestine loop by Roux, Kocher maneuver. That is, many methods are still used around the world, called the names of those surgeons who at the end of XIX - early XX century proposed a certain operation. They could never do that, if there was no anesthesia.

In addition, the introduction of asepsis, antisepsis, ie decontamination of instruments and surgical field, which introduced the English surgeon Lister at the end of the XIX century with the help of carbolic acid - a poison, we say, but then it saved hundreds of lives. Prior to that, there is nothing decontaminated surgeons believed that the dirtier the hem of the surgeon and his surgical coat, so he is more experienced. And many patients die from hospital-acquired infections, called nosocomial fever, and is nothing more than an infection.

Very important was the discovery of penicillin by Fleming. In 1943, Americans began to use the antibiotic on the battlefield, and hundreds of thousands of victims were rescued with the help of antibiotics is in wounds of the abdomen. And of course, without a parallel open surgery could not be developed, so to achieve in other areas are widely allowed to develop heart surgery, in the 50s there were heart-lung machine. The discovery in the field of immunology and survival of tissue transplantation has allowed to develop successfully. Neurosurgery is now at a very high level, because besides knowledge of the neurophysiology of pain relief during surgery on the brain are now allowed to perform unique operations to remove tumors from remote areas.

Besides, now increasingly incorporated minimally invasive technology. What it is? This implementation of major surgery, but because of the small access using video-surgery: laparoscopy, robotic surgery. That is often when talking about robotic surgery, the surgeon sits outside of the surgical field, the console, in the form of 3D, he sees the surgical field and can absolutely precisely, that is, with great precision, to intervene surgically in the distance. It is theoretically possible from a different city to carry out these operations.

Thus, the prospects of abdominal surgery is very interesting. They relate primarily to the introduction of new minimally invasive technologies, when this technique allows from small accesses to remove large pieces that have demanded more access, with a large increase and, consequently, with fewer complications. This is a quick rehabilitation of patients after surgery and rapid inclusion in the public process after seemingly complex operations such as liver resection, the removal of the pancreas. I'm not talking about the other operations, such as the esophagus, stomach and so on.

Thus, the opening in the adjacent areas of scientific achievements in other areas: in low-temperature physics, high temperature, robotic engineering, anesthesiology, critical care medicine, pharmacology - allow surgery, particularly abdominal and achieve greater heights and achieve success in those cases where, for example, a few years ago it was impossible to achieve effective treatment of a disease.

The evolutionary role of tumors

The biologist Dr. Doping speaks about a chronic state of cancer, their role in the evolution and oncogenesis.

Cancer problem is one of the major public health problem, because until now a very high percentage of people dying from cancer. In addition, cancer patients have very severe punishment. Modern science is unable to do something, do something to help, some types of cancer even manages to heal. But the overall picture is that we are not winning the battle.

At the end of 1960, Nixon announced the program of struggle with cancer, after they flew to the moon. We had to fill the vacuum aspirations, so the United States announced the so-called virus cancer program. As a result, the program first viruses have been identified which cause leukemia in humans. If we, the human civilization, did not, we would not have identified the AIDS virus, because it turned out that the AIDS virus is related to leukemia virus. And all of the technologies that have been acquired in the study of leukemia virus during this decade of the 1970s, were then applied to HIV. Now Obama has recently announced another, so to speak, the fight against cancer, with cancer, because the task is not finished, that describes the problem.

Now let's go to the other side. Why the problem is not solved, because it spent a lot of money, but it does not work? Earlier there was this idea that it is necessary to find a "golden bullet" (the idea suggested Kuchta) that will solve all our problems. But it turns out, is not a "golden bullet". Among oncologists maturing idea that seems to be the tumor did not win, so we must somehow try to live with it, that is, cause swelling in controlled chronic condition. All this shows that it is necessary to work not only on specifics - on specific medications and some technology, but also on the paradigm, the general view. It turns out that this kind of demand stimulates our thinking, that is what I will continue to tell you, by itself comes to mind, but it proves popular, because the old paradigm does not work.

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Now I will talk about the evolutionary role of tumors, which in itself seems a little strange - the evolutionary role of tumors, tumor role in the progressive evolution. If we begin to understand, it will not be very strange. Firstly, the majority of tumors do not kill the organism. We are still accustomed to hearing about malignant tumors, from which people die. It turns out that in humans and animals have also benign tumors, other tumors that do not kill the organism. Their more than 50%. Such tumors exist and they may be involved in biological processes. Furthermore, there is a discharge inherited tumors that may be involved in the evolution.

In comparative oncology studied for two hundred years. It tumors in various representatives of the living world - mostly animal, of course, but also in plants, too, are tumors. It turns out that no matter studied, everywhere find the tumor, and a feeling that the tumor has spread throughout the phylogenetic tree. If they are so widespread, then the question arises: what is the place they occupy in the evolution?

There is a maxim which has made a well-known geneticist of Russian origin Dovzhansky: "Nothing in biology makes sense except in the light of evolution." Therefore, if there is such a widespread phenomenon as a tumor, then they should be considered in the light of evolution. I explain that it's not crazy, it's not a whim. Many directors work with the classics only in order to emphasize some the feature. Create a Evolutionary theory of the role of the tumor - is not a whim, but a consequence of the biological way of thinking.

The next group of evolutionary arguments for the role is tumors that oncogenes and tumor-suppressor gene that control tumors too widespread. It turns out that they are very ancient, almost the most ancient genes in humans and other animals. It turns out that the cellular oncogenes and tumor suppressor gene, is also very old, perhaps the oldest of genes after "household" in animals. Another very interesting fact is called the convergence of signaling pathways and oncogenesis. What it is? It turns out that certain oncogenes play a role in normal development, and the development of normal signaling pathways play a role in oncogenesis. The question then arises: swelling - a part of the development?

On this basis, I first conjectured in the world (and so now all this so kind), which suggests that tumors can indeed play a role in the evolution of organisms, providing a redundant cell masses for the expression of an evolutionary new genes. And there is a word "redundant cell masses" and "evolutionary new genes." It can be measured, especially evolutionary new genes. I'll tell you how we measured.

Firstly, we measured before, found several examples already described as a paradoxical when tumors indeed played a role in the evolution. These include, for example, nodules of leguminous plants (plant is an example, but nonetheless). The nodules that resemble tumors are fixing nitrogen, so they have turned to the new authorities in legumes.

On the other hand, many of voles in the stomach has macro-villi which arise from malignant papillomatosis and kill these voles. However, they manage to leave offspring. And other burrowing rodents based on these malignant villous benign macro-villi emerged, playing a role in symbiogenesis with some bacteria that help to ferment cellulose.

A further example of this kind is the placenta, which took place in the history of placental several times. As a result of various independent infection by retroviruses, which become endogenous retroviruses endogenous retroviral genes were involved in placental development. And the placenta is the organ that has a number of tumor characteristics (I counted about 12). The brightest tumor symptoms of placenta - is the invasiveness and metastasis, that is a normal organ that behaves like a tumor, and the people who study the placenta, ask the question: "What is the placenta differs from the tumor?" It turns out that regulation, that is, the placenta is so well regulated that it differs from this tumor. But if it is output from the regulation, it becomes malignant.

Why do we need new hypotheses, new theory? They must somehow explain what is happening, what is around us, and they need to predict. In addition, we are his theory to explain something, explaining all the paradoxes, of which I have just told, we also predicted something. We have formulated two very non-trivial predictions. The first of these - the fact that tumors may be selected to function in an organism. Second prediction - that are activated in tumors start working evolutionarily new genes.

To prove the first prediction, we have been working with goldfish. One of them we are still alive and is a symbol. She has a beautiful cap on his head, that lvinogolovki, Oranda - they have such cute education in mind, in fact, and so they were selected. When I saw them, I knew immediately what it is: a tumor. We did histology, and, indeed, it looks like a benign tumor. To definitively prove this, we conducted a two-year experiment looked at the development of a hundred fishes, followed all the stages of development of the tumor and make an unambiguous conclusion that the cap goldfish is a benign tumor. Then it turns out that the breeders and a half thousand years, the fish were taken on a benign tumor. Every possible artificial selection with a benign tumor, in the same way natural selection can work in nature with different types of tumors. This is a very non-trivial result.

Another group of the results we have obtained in the proof of the existence of genes with dual specificity, evolutionarily new, expressed in tumors. When dealing with an evolutionary new genes we studied the specificity of their expression. Y genes, which are known to be expressed in tumors, we determined the evolutionary novelty. We showed in both cases that, indeed, there is a large group of genes, which we have called the evolutionarily new, expressed in tumors, in English HSEER (Human Specifically Expressed Evolution Removal). We have shown in the past their work, which is not only individual genes (which we have described about 12 pieces), but whole classes of genes may be evolutionarily novel. Many of them occur mainly in the human, that is, it is an evolutionary new human genes, which have almost absolute specificity of expression in the tumor.

FAQ: Methods of treating Cancer

6 facts about cell mutations, targeted therapies and approaches to cancer treatment.

Cancer is known to mankind for a long time. It is a disease in which the treatment throughout the history of mankind is practically unable to achieve any success. With the advent of antibiotics people almost forget the terrible infections from plague and ending with syphilis. However, as the world population ages, the probability for each of us to meet growing cancer in life. Unfortunately, despite the hundreds of billions of dollars that have been spent in the developed world since the late '80s, and decades of research, we do not see a significant breakthrough in the treatment of cancer. The increase in life expectancy of cancer patients was not due to the fact that there were revolutionary therapies for the last 20-30 years, but mainly because the cancer began to be diagnosed at an earlier stage. The problem is that the medicine can diagnose the disease at a phase where no treatment after a year in the number of cancer cells will be such that the weight or volume of the tumor will be measured already hundreds grams.To improve the quality of our life - buy Prednisolon, Meldonium, Peptides (Cytomax) Bonomarlot, Vladonix for prevention cancer.

• 1.Genetic Background

The human body, like any animal organism comprises genes in its genome, which are used for cancer of the development. At first glance, this seems illogical. In order to grow from a single cell and become a human being, you must use the mechanisms that are at a mature age are dangerous or unnecessary. In particular, in order to prevent rejection of the fetus in the mother, the embryo cells learn to deceive her immune system, posing as "their own", and thus prevent the mother's immune system to destroy the embryo. This explains a lot of pathologies. This favorable evolution of the acquisition, but the same genes being activated in adulthood, can help a cancer cell to trick the immune system and prevent the destruction of cancer cells.

• 2.Age-related causes of cancer

In fact, the body of each adult healthy person - millions of cancer cells that are in balance with the body, and continuously determined cells of the immune system are destroyed. However, with age, the number of possible errors in the execution of the genetic program begins to grow, and at some point the amount of stress is greater than the possibility of damage control systems. At this point, the cancer cells are knocked loose. The danger lies in the fact that all signs are cells of the same organism. At first, they have almost the same genetic code as all other human cells, and it does not allow the protective systems to quickly identify them.

• 3.Mutation of cancer cells

Cancer cells begin to rapidly mutate, and new copies of the genome fight against the body's defense systems. New forms of these cells, which are absolutely not similar to the original cell or any other cells to the patient. Studies show that cancer swollen the same patient is not one type of cancer, and many species. In fact, it is not about how to deal with any one disease, but to fight with different, quite unlike forms of the disease. In this sense, there is no one disease - cancer. There are many different forms of cancer, and even in the case of each patient simultaneously realized very many different forms of cancer. It is for this reason that effective cancer control devices, except for surgery and very aggressive forms of chemotherapy or radiation therapy, has been invented.

• 4.Lack of anti-cancer therapies

Another complicating factor is that the immune system is a major defense against human cancer. Cells of the immune system and tumor cells divide rapidly, and most of the therapies aimed at the destruction of rapidly dividing cells, at the same time lead to the destruction or suppression of immune functions. Thus, many treatment leads to the fact that the body gets strong toxicological damage and simultaneously suppressed immunity. We are talking about the fact that a lot of money in a very expensive hospital during the life of the patient increases less than a year.

• 5.Possibilities of targeted therapies

In this regard, the question arises: where to find a reason for the hope that cancer will ever be healed? Rapid progress can not be expected, but recent studies provide some hope. We must look for ways to distinguish between cancer cells and healthy people and come up with Targeted, specific therapies that allow the immune system to either recognize or specifically destroy those cells that are not strongly resemble the cells of healthy tissue.

In this way, in recent years there has been considerable progress. In particular, certain types of cancer could develop targeted agents, which allow to operate against a very specific genes activated only in cancer cells. Thus, in recent years has made significant strides in pediatric oncology, where the percentage of surviving patients was significantly increased. Also it managed to get a great response ( "response of patients") in some forms of cancer, such as breast cancer. specific markers have been developed, which allowed to identify the patient population for which certain specific tools would be useful, and get a very high percentage of cure in specific categories, even for small groups of patients.

This approach has some advantages, but has some drawbacks. In order to apply a tablet or therapy genotyped individuals have first, and then determine that, for example, only 2% of the 100% of people will be able to respond to this therapy. It is extremely difficult clinical research in oncology. If only a percentage or a few percent of the entire population of patients respond to this drug, the pharmaceutical companies largely disappears the reason for which they are developing these drugs. After all, if the number of patients will be measured in tens or hundreds of thousands, this drug will receive the status of "Orphan Drug» (orphan drug), only work for a very small group of patients, which is unlikely to be able to create effective demand, in order to recoup the research.

Currently, biotechnology will likely move in the direction of the search universal mechanism that will effectively inhibit cancers using these or other unique arrangements. As the embryo is cheating mother's immune system in order to stay alive and cancer cells using this mechanism to control immunity. The destruction of this mechanism will not bring any damage to healthy cells, but is likely to help immunity or some means of immune therapy to cope with cancer. In 2013, in the second phase for the first time showed the success of GSK drug companies, which managed to get the immune-boosting drugs, raised its forecast for the survival of patients in combination with different forms of therapy or independently.

• 6.Glycolysis as a source of energy

It is known that cancer cells use an entirely different way of breathing. When the immune system is trying to kill a particular cell of the organism, cell death occurs through the destruction of the mitochondria - a special organelle of the cell, which is responsible for energy production. Those cancer cells that were able to shut down the mitochondria, or get rid of it, obviously, can not be killed in this way, so after a few weeks or months after the onset of a cancerous disease in humans, almost all cancer cells breathe without mitochondria, using a completely different mechanism for energy It called "glycolysis". Glycolysis is ineffective, so it does not use the normal cells. Drugs that would cut out glycolysis, would be able to leave the cancer cells are starved and kill them either alone or in combination with other drugs. It is in this way recently in preclinical and early phase clinical trials, progress has been made with the drugs that control various forms of cancer metabolism.

So far there is no evidence other than animal testing, that this approach or an approach that is associated with immune therapy, will allow us to ever talk about the possibility of treatment of cancer patients. However, the fact that the attempts of the past dozen years to develop a drug to target a narrow group of people against specific markers the researchers once again start to move towards a universal anti-cancer drugs with a wide effect, allows us to hope that sooner or later the disease will be controlled.

What will be the new diagnostic device for cancer?

The biologist Dr. Doping tells about the occurrence of mutations in the body, the mechanism of repair and Sequencing of a new generation.

As we know, in the future, everything is possible. Take a normal mobile phone. He no longer is just a phone, this device is very far away from the device with a tube and drive that we remember from childhood. The mobile phone includes a camera, a video camera, a calculator, a timer, notebook and more. The same can happen with the device engaged in cancer diagnostics. But is it possible to create a fundamentally new device that would replace any existing and would give some new paradigm for cancer diagnosis? Presumably, this is possible.

Cancer Diagnosis - is a very broad topic. When it comes to the early detection of the fact that a person somewhere is starting to develop a malignant tumor, obviously, such a device would be examined blood samples and other body fluids, to analyze the accumulation of mutations in the case of exceeding a certain threshold among them would trigger an alarm. We are talking about mutations, because in cancer spoil repair mechanisms, mechanisms that contain the DNA of the cell in order. That is, when any damage occur - and they happen all the time - that the repair mechanisms eliminate them. Imagine that the cleaners' strike began at the airport. This will lead to the fact that the airport will become a net into the cloaca. The same happens with the genome of cancer cells. repair system in some way derived from the game, or "intentionally" or accident under the influence of any adverse factors of the environment. This addition to the neat and attractive mechanism for maintaining genome stops working, and the genome becomes literally a dump, which is an accumulation of a huge number of mutations.

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Thus, it turns out that cancer cells contain more mutations than normal. Cancer cells rapidly grow and die, as our immune system fights them. Furthermore, by virtue of the tumor tissue growth mechanism in some cells lack the resources they clog more successful, fast-breeding blatant and colleagues, and they are killed and their genome fragments enter the blood, urine, and so forth. Therefore, the blood present in the DNA fragments of dead cancer cells. And if blood exceeded the threshold mutant variants of DNA molecules, it may be a signal that something is wrong in the body. I venture to suggest that this leads not only cancer but also inflammation, chronic infections, and so on. But in any case, the detection of an increased number of mutations in the DNA will indicate that it is necessary to concentrate on finding some internal problems of the body.

After that the entire body must be systematically explored. For this kind of device can be constructed which will report on where it is a tumor. After that, obviously, you need some way to understand what the this tumor, take a sample of biological material for laboratory tests, which are already very complex and quite effective. For this purpose, you can use a third device that is precisely right from the source of tumor development, however small it may be, to take a sample of biological material. At the moment it is very difficult, and in some cases take the material is simply impossible. Further biomaterial to be analyzed by a variety of laboratory tests, which immediately will give answers to all questions. This may be the fourth device.

In any case the principle of universal early diagnosis, it seems to me, it can be built on an analysis of a large array of DNA molecules. This modification of DNA analysis techniques, as I think is the most promising direction in this area. This does not mean that in the future will be used necessarily subsidiaries approaches to those that exist today. Most likely, it will be some fundamentally new technological processes to examine the DNA faster and cheaper. Very important Vitamin B12 is essential for DNA synthesis.

In general, DNA analysis methods are developing very quickly. Thus, the methods of large-scale and relatively inexpensive determination of the structure of DNA became known in 2005, and began to be used widely since 2008-2009. Although interest in this topic in the world is huge, but the development of technology, unfortunately, has slowed in recent years, and not on scientific and technical reasons. Branch production sequencing (devices for the determination of the structure of DNA) and the new generation of reagents was virtually monopolized by a few manufacturers, which led to the fact that prices on the read nucleotide (analog of bits of information) some time ago actually stopped falling. This is a completely unacceptable situation, despite the fact that progress is running ahead by leaps and bounds. Apparently, this is due to the fact that large companies to monopolize the market, busy buying up competing technologies in the early stages of development and do not allow the expansion of the competitive field. Thus, the technology, which could oust them simply do not reach its final incarnation.

Why there is a hangover?

Chemist Dr. Doping tells about human physiology and reaction to alcohol.

A hangover is due to alcohol consumption. The more alcohol, the stronger the hangover. It is believed that the primary mechanism of alcohol hangover - a violation of water-salt balance and dehydration of the brain that causes headaches. These symptoms are easily cropped and folk remedies, for example, ibuprofen. However, besides the actual alcohol hangover is caused by its metabolites, mainly acetaldehyde. The fact that a complete breakdown of alcohol in the body, if simplistic, two-stage: alcohol dehydrogenase oxidizes alcohol to acetaldehyde and then acetaldehyde is aldehyde dehydrogenase oxidizes to carbon dioxide, acetic acid and water.

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With regular consumption of alcohol the body synthesizes a lot of alcohol and alcohol very quickly oxidized man slightly drunk and able to drink a lot of alcoholic beverages, while maintaining control and practically no feeling of euphoria. However, for unknown at the moment science reasons aldehyde synthesis is rarely enhanced. As a result, people who had been drinking a lot, aldehyde undergoes a hangover, that is poisoning acetaldehyde. It is characterized by: palpitations and arrhythmia, irrational longing and fear, the swelling and redness of the face, the inability to accurately motility, psychological depression, persisting two or three days, and sleep disorders. Unfortunately, as acetaldehyde - a strong carcinogen. I think the one who finds a way to activate the aldehyde dehydrogenase, will receive the Nobel Prize.

The progress of these biochemical processes determines the individual sensitivity to alcohol. If the decay is slower alcohol than the oxidation of acetaldehyde, the presence of acetaldehyde in the blood will be minimized. Hangover will not grow. And when, on the contrary, some people like more resistant to alcohol and not get drunk even objectively large doses of alcohol (0.5-0.7 liters of strong alcohol and more), acetaldehyde accumulates and provides terrible hangover without prior intoxication.

Nanochemistry in cancer treatment

Chemist Dr. Doping tells about new drugs for the treatment and diagnosis of cancer and the role of nanoparticles of metals and metal oxides in biomedicine.

About 8 million people die each year from cancer. Most of the time men and women are diagnosed with lung cancer, the second place are cancer of the prostate and breast. The development of therapies invested huge funds, the efforts of scientists and pharmaceutical companies. Market of anticancer drugs is about $ 70 billion, 3% of which is occupied by the Russian market. But most of the therapies of cancer remains ineffective.

Why is the existing drugs are ineffective?

Medicines that we try to use in medical practice, for the most part are low molecular weight organic compounds. These are small molecules of about one nanometer, with a number of unpleasant features. They are very poorly soluble in body fluids, that is their rather difficult to introduce in a human body. Also, the drug may exit from the body before therapeutic effect will give the molecule of sufficiently small, it passes quickly through the bodies and outputted. In addition, the drug can not always overcome a number of biological barriers and penetrate into the tumor tissue. Of course, the drug can act on non-target tissue, that is, not to where we want to send our product. Medication must overcome a number of biological barriers (e.g., blood-brain barrier to treat central nervous system).

Another problem is drug delivery. When we start working with anticancer drugs, there is one feature: they are often non-specific, non-selective. That is, after the introduction into the body, they are distributed throughout the body and very rarely get in sufficient quantities in this or that place.

Targeted Drug Delivery

Scientists around the world began to think, how to make sure that the drug was delivered targeted, dot. For this there are two ways. The first - "sew" to the drug, a chemotherapeutic anticancer drugs known organic molecule, which will be responsible for delivery. It is known that our liver cells, prostate, brain, kidneys and other organs have on their surface markers that are specific only for that body. By this token, you can pick up a molecule. It may already be known in the nature of the molecule can be synthesized new compounds can be used antibodies, peptides. Then, if you make a medicine with this molecule, it will be delivered exactly where needed.

Next, the researchers want to add additional functionality to this system, so we can not only deliver and treat, but also, for example, to diagnose. Ideally, a single material can immediately diagnose the injury and start the healing process. Then the researchers drew attention to nanoparticles of metals and metal oxides.

Nanoparticles of metals and metal oxides in medicine

What are the nanoparticles? Most often it is 'beads' size of 10 to 100 nm. They can be functionalized drug outside. So we arrive at the delivery by passive transport. The low molecular weight drug (due to the fact that a small molecule) is very rapidly excreted. The particles have different properties: they are big enough and the circulation increases considerably.

It is not necessarily to take the nanoparticles of metals or metal oxides. For these purposes, you can take the polymer particles (liposomes, micelles) - these drugs are, but they are out of date. Then there are metal particles and metal oxide particles.

First, they act as drug carrier. Second, due to their size they will accumulate in the tumor. Third, due to the fact that this metal or metal oxide, it becomes possible to control them and use them, including for diagnostic purposes. For example, the nanoparticles based on iron oxides. This small magnets, which respond to an external magnetic field. What gives? The idea is simple: the drug is administered intravenously, apply a magnet to the affected tissue or organ and the drug accumulates in the desired location.

Unfortunately, this technology has not gone to the hospital due to a number of problems: the blood flow velocity, the depth of the tumor, the magnetic field direction, and so on. However, such particles can be very effectively used in other field - this contrast agents.

The contrast agents for diagnostic

Small magnets are visible in MRI (magnetic resonance imaging). MRI - one of the best non-invasive diagnostic methods, including cancer pathologies. Magnetic beads are visible in MRI, the tumor is very good contrast. Initially, five types of contrast agents used to diagnose liver. But with only one left over time. It turned out, they are toxic to the liver, although deposits. Not immediately, but over time after the accumulation of certain contrast agents started to allocate reactive oxygen species, damaging the liver.

The nanoparticles based on iron oxides themselves ideal contrast agent, even though the problems with toxicity, they are much better than what is used today in clinics. For example, derivatives of gadolinium are actively used - Gadovist, Magnevist. Gadolinium, as a heavy metal, is highly toxic. A magnetic particles, in principle, non-toxic, if solved the problem a long accumulation in the liver and long elimination from the body.

Early diagnosis by using magnetic particles

The ideal contrast agent should be smaller than the conventional large contrast agents in clinical 100-200 nm. small balls (40-50 nm) is necessary to make and to cover something that our body will not be perceived as an alien. For example, human serum albumin - blood protein, with which nanoparticles may be modified. This technology has not decided to apply to the liver, for which and so is the contrast agents, and for the brain.

Glioblastoma multiforme - it is a heavy brain tumor, which is difficult to diagnose in the early stages. It was found that the magnetic particles are excellent contrast agents for glioblastoma multiforme. They are absolutely non-toxic. After five minutes, the particles accumulate in the brain, which makes carrying out tests in the clinic is very effective: entered - in five minutes already can be carried out. While all the main results obtained in the rat, but it launched a full-fledged pre-clinical testing of the contrast agent. To improve immune system - buy Prednisolon, Bonomarlot, Ovagen, Endoluten.

Preclinical tests include full-scale study of toxicity, including genetic toxicity, immunotoxicity, cardiac, reproductive, ie toxicity, delayed in generation. Of course, efficiency. Already it is clear that the method can be used for breast cancer. By 2017, in the presence of a partner from the pharmaceutical business, which will be able to produce experimental batches to begin clinical trials on humans. Then, the world's first contrast agent based on the magnetic particles will be created.

Side effects of chemotherapy

New developments in drugs against cancer are necessary because traditional chemotherapy many shortcomings. Tumor cells, with the exception of rare types of cancer, mainly very aggressive. They divide rapidly and, accordingly, they must be taken from the external environment to supply a lot of vitamins and other substances. Tumor cells themselves need to pump medium. That is exactly what acts chemotherapy: rapidly dividing cells will absorb all the drugs that you have in the bloodstream.

In classical anticancer drug, is actively used in the clinic today, a series of platinum (cisplatin, carboplatin, oxaliplatin) side effects - nephrotoxicity and neurotoxicity. There are so many products with cardiotoxicity. The main problem is that the non-selective drugs many side effects. Chemotherapy is very aggressive, it quickly kills the tumor. Even if we assume that it has no side effects, due to the fact that the body gets a lot of degradation products of tumor cells, the body will be poisoned. Therefore, constantly we are looking for more effective treatments.

Cell Death

The biologist Dr. Doping tells about programmed cell death, the role of caspases and cell death in plants. How the process of apoptosis occurs? What are the enzymes responsible for cell death? What are the ways of apoptosis program development? And some studies have practical significance of programmed cell death?

In a multicellular organism most of the cells does not live throughout the life of this organism. Of course there are neurons that live their entire lives, they were formed in infancy, as they then exist. The majority of the cells live for a certain time, then dies. The process of death is very complex, orderly and must take place intelligently.

The cell can not just die, fall apart, because then the decay products will destroy everything. She has to die so as not to damage the surrounding cells. Therefore, the process of cell death is very hard-coded. There are special proteins in which the cell itself is very intelligently kills. The process of cell death is usually called "programmed cell death".

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There are several variants of programmed cell death. Most currently investigated in a process called "apoptosis". The main feature consists in apoptosis that occurs in the nucleus of the compaction of chromatin. The cell does not swell, it is, on the contrary, it is compressed slightly and then falls apart into small fragments and these fragments are captured by cells, macrophages, which digested remnants of dead cells.