] Humoral theory of Hippocrates
Until the 18th century, cancer was difficult to study: no suitable equipment was invented, the church prohibited autopsies, and the plague and smallpox took more lives and attracted attention. Therefore, from the ancient times, few records of malignant tumors have reached us, but still they are.
The first mention of cancer is found in the papyrus of Edwin Smith, a medical text of Ancient Egypt, which dates from the 16th century to ad. This papyrus can look through and read. Case number 45 describes malignant tumors. In the same place it is noted that there is no method of treatment.
Hippocrates (400 years before Christ) was the first to distinguish between benign and malignant tumors. He believed that the human body contains four humors, or liquids – blood, mucus, yellow and black bile – and any imbalance leads to diseases. It was believed that the cause of malignant tumors was the accumulation of black bile in a specific place. Hippocrates noted that without treatment, patients can live longer: black bile has spread through the body and can not be removed.
Of course, there is no black bile in the human body, but the idea of spreading the tumor through the body turned out to be correct. Malignant cells eventually separate from the tumor and give metastases.
Doctors and healers used humoral theory for more than 1300 years. During this period, autopsies were banned for religious reasons, which limited the study of tumors. Available methods of treatment in ancient times and the Middle Ages were surgery, moxibustion, bloodletting and rites.
The first surgical interventions
Surgery is one of the oldest branches of medicine. However, in medieval times, interventions did not always produce the desired results due to high blood loss, high risk of infection after surgery, and lack of antiseptics.
Roman physician Galen (130-200 Years of our era) wrote about the surgical treatment of breast cancer at an early stage, but did not consider this method effective for treating large and "hidden" tumors. He adhered to the humoral theory and assumed that black bile can not be removed from the body completely. This approach saved the lives of many people: in the Middle Ages, patients often died during surgery or because of complications after surgery.
The abolition of humoral theory
After the cancellation of the ban on autopsy In the 16th century, Andreas Vesalius compiled the first anatomical reference book of the human body, and a century later, Matthew Bailey described the structure of various pathologies. The humoral theory had to be reviewed, since scientists did not find any black bile.
In the 17th century, surgical methods of tumor removal began to develop. German surgeon Wilhelm Fabry during the operation to remove breast cancer cut the tumor together with enlarged lymph nodes, and the Dutch surgeon Adrian Helvetius performed a mastectomy, complete removal of the breast. A few years later, he wrote about one of the cases: "Since then, the patient has fully recovered. The pains completely stopped, the scars healed, and she enjoys the same state of health as before the cancer. "
In the 1850s, the German scientist Rudolf Virchow discovered in uncontrolled cell division tumors. He called this phenomenon neoplasia, and his main work "Cellular pathology" became the basis for understanding the causes of cancer development.
Anesthesia and antiseptic
In 1846 anesthesia was invented . This solved the problem with pain, because before that people had to undergo surgery in the mind. And in 1867 the French physician Joseph Lister discovered that ointment based on carbolic acid acts as an antiseptic and promotes wound healing after surgery.
Anesthesia and the first antiseptic have expanded the possibilities of surgery, and operations have been carried out everywhere. However, in some cases, tumors appeared again. Then surgeons began to expand the scope of interventions, which eventually led to the emergence of the radical surgery method.
Surgeon William Halstead thought that the more tissues removed during surgery, the less likely the relapse. The conclusion is not entirely correct, since malignant cells could spread throughout the body before the operation and metastasize to other tissues.
Only in the 1970s, during clinical trials, That less extensive operations are effective in the same way as radical ones. Unfortunately, by this time radical mastectomy gained great popularity and was considered almost the only true method of treatment of breast cancer.
In the 1990s surgeons minimized interventions in Healthy human tissue. Today, operations are divided into two types: open and minimally invasive. For open surgery, the doctor makes a large incision to remove the tumor, unhealthy tissue and, possibly, the lymph nodes.
For a minimally invasive operation, the doctor makes several small incisions, finds the tumor with a thin tube with a camera (laparoscope) and through another incision removes the tumor with instruments. After this operation, the patient is restored faster.
In the late 19th century, scientists drew attention to the ability of x-rays to kill malignant cells. Then no one had any idea how harmful the radiation was to healthy tissue.
X-rays were discovered in 1895, simultaneously with the development of radical surgery. A year after that, young doctor Emil Grubbe noticed how the skin and nails of people who worked with radiation sources are being destroyed. He suggested that the rays kill tumor cells and was the first who used radiation therapy to treat oncology.
The method quickly gained popularity: new clinics offering radiotherapy were opened in Europe and the US. It was effective in cases where the tumor did not spread to other organs.
The idea of using radiation was excellent, but it did not take into account two significant disadvantages of the X-ray tube: a non-uniform radiation flux and insufficient penetrating power. Most of the dose is absorbed by other tissues or dissipated. Thus, x-rays increase the number of mutations in healthy cells, which leads to the formation of new tumors. This option can not be considered an appropriate treatment.
In 1902, scientists Pierre and Marie Curie discovered the radioactive properties of radium. At first glance, this substance penetrated deeper than X-rays and gave more possibilities for treatment. For 10 years after the discovery of radium, many doctors and scientists who did not know about the dangers of radiation developed various malignant diseases. This continued until the first dosimeters and measurement standards for radioactive radiation appeared.
The electron accelerator and radioactive cobalt
In 1940, Donald Kerst assembled a betatron – a cyclic electron accelerator . The device emits particles that have high energy and penetrating power, so when using it, there are few scattered rays. In 1951 Swedish neurosurgeon Lars Lexell developed the device "Gamma Knife". It has several radiation sources of radioactive cobalt and gives a homogeneous beam of high energy. The betatron and gamma-knife have been successfully used to treat tumors today.
Radiation destroys DNA of cells directly or indirectly. In the second case, the water that is contained in the cells turns into free radicals – charged particles that damage DNA. Radiation does not disassemble which cells destroy, healthy or malignant, so the apparatus requires careful adjustment, so that the peak dose is at the desired depth.
Today, oncology uses X-ray Radiation, gamma rays and charged particles. They can enter the body and act on malignant cells through a special device or come from a radioactive material placed in the patient's body next to the tumor (brachytherapy).
There is also a third type of radiation therapy – systemic. The patient is given a radioactive liquid, for example iodine, which finds and kills tumor cells. But in this case it is difficult to take into account the exact amount of isotope that absorbs the body and the dose can be harmful.
Surgery and radiation therapy were used to treat solid tumors that develop not from the cells of the hematopoietic system. No one knew how to treat lymphomas and leukemia.
The idea of using toxic substances to treat these diseases arose after the First World War. At that time mustard gas was used as a chemical weapon. He burned the skin and mucous membranes, and also killed leukocytes: they were practically absent from the wounded.
Scientists wondered if mustard can cure lymphoma-a tumor of lymphatic tissue. In this disease, lymphocytes uncontrollably divide and disrupt the operation of lymph nodes and other organs, so the reduction of lymphocytes seemed the right solution. In 1942, after studies on animals, 10 doses of mustard gas were administered intravenously to a patient with lymphoma. The number of lymphocytes quickly fell, and the tumor diminished, but later began to grow again. This meant that the therapy worked, but the dose was not enough to fully recover.
Remission came about because the mustard gas is included in the group of alkylating agents that destroy the DNA of the cells and prevent them from dividing. But then they did not know anything about it yet.
Precursor of methotrexate
In 1947, a physician named Sidney Farber showed that the derivative of folic acid , Ametopterin, suppresses development of acute leukemia in children, which is characterized by uncontrolled division of white blood cells. This drug was a precursor of methotrexate, which is still used today.
The results of bone marrow biopsy of patients after the course of treatment with ametopterin were normal. Chemotherapy prolonged the life of children under 6 months, but then the disease returned. Farber did his best to find a cure that could cure leukemia completely. Then it was difficult to assume that several toxic substances should be used at once, and not just one.
In 1950, Gertrude Elion developed a 6-mercaptopurine (6-MP) preparation that was quickly approved for use in children with leukemia. After him, doctors again observed a brief remission.
Later, randomized clinical trials were conducted, during which it became clear that the use of two drugs instead of one prolongs remission and Improves prognosis.
In 1956, Dr. Min Chiu Lee clinically confirmed that a combination of four drugs cured metastatic choriocarcinoma in pregnant women. The National Institute of Oncology at first regarded these actions as aggressive and superfluous treatment of patients, and the scientist was suspended from work. Only then it became clear that only those women who had undergone Lee's complete course of survival survived.
In the 60s and 70s, scientists tried to use chemotherapy as an additional method of treating breast cancer after surgery. Surgeons were reluctant to go on clinical studies: no one wanted to deal with additional side effects in patients. But they were wrong.
In fact, any tumor is a systemic disease. Malignant cells spread throughout the body even in the early stages in the form of micrometastases. They remain in the body even after removal of the tumor, so local treatment methods are not enough. It is necessary to systematically influence the disease with the help of medicinal treatment. For example, adjuvant therapy (chemotherapy after surgery) can reduce the risk of recurrence and death.
Several studies have proven a positive result of adjuvant chemotherapy for the treatment of breast cancer and colorectal cancer. Also in 1974, a positive effect was shown in the case of metastatic testicular cancer, and chemotherapy was used to treat solid tumors.
Preparations for chemotherapy stop and slow down the division of cells. During the course of treatment, those cells that quickly divide are killed. It is not only malignant cells, but also healthy, which leads to side effects: hair loss, nausea, susceptibility to infections.
Immunotherapy is a relatively new type of cancer treatment. It is based on the use of drugs that train the cells of the patient's immunity. This became possible due to the discovery of the structure of DNA, the study of the characteristics of malignant cells and cells of the immune system.
In 1891, William Coley observed that the oncological patients who underwent scarlet fever or erysipelas had a remission. After that, he began to inject patients with the last stage of cancer with streptococcal bacteria. The tumor decreased, but the patients died from infection. Then Kohl heated the vaccine and injected patients with dead streptococci.
The result for that time was impressive: the patients recovered and lived for several years. However, the Kolya vaccine was not widely used. Scientists could not explain the mechanism, how bacteria act on the tumor, and the risk of infection was high. Chemo-and radiation therapy was much more interested in all.
In 1976, the BCG vaccine was successfully used to treat bladder cancer, which was used to prevent tuberculosis. It activates the immune system and helps the body fight this kind of cancer.
In 1975 Georges Keller and Cesar Milstein published an article on the method of obtaining a cell hybrid of a tumor cell And lymphocyte. Hybridom technology can detect antigens that are characteristic of tumors of certain tissues, get antibodies to them and use them for diagnosis and typing of tumors. Such antibodies are called monoclonal: they are produced by immune clone cells that originate from the same parent cell.
Other types of antibodies mark cancer cells so that the immune system is easier to locate and destroy them.
In the late 1990s, the FDA approved the first therapeutic monoclonal antibodies, rituximab and trastuzumab. The first for the treatment of lymphoma, and the second for breast cancer.
In 2010, Stephen Rosenberg announced the success of therapy with chimeric antigenic receptors. It is based on the genetic modification of the patient's T cells for the treatment of a malignant tumor.
Another method of immunotherapy is the introduction into the muscle or vein of cytokines, biologically active proteins that regulate the immune response. Interleukin-2 helps cells of the immune system to divide faster, and interferon – to fight against viral infections and malignant tumors.
Another promising area is the impact on immune control points that suppress the immune system response. Scientists have learned to block control points on T-cells, which helps the immune system to recognize and attack malignant cells. This method has already been approved by the FDA for the treatment of cancer.
Optimal treatment can be selected using molecular diagnostics. Scientists examine the patient's surgical material or biopsy to identify mutations in proto-oncogenes and suppressor genes. Набор мутаций индивидуален для каждой опухоли, поэтому лечение должно быть персонализированным. В следующий раз Атлас подробно расскажет о молекулярной диагностике.