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  History and Principles of Chemotherapy, Biology tutorial

Introduction:

Chemotherapy is just a treatment of diseases with chemicals, but it is generally referred to as cancer treatment. Use of antibiotics in treatment of bacteria is referred to as antibacterial chemotherapy, therefore first chemotherapeutic agent utilized is arsephenamine used to treat syphilis. It was discovered in 1909.

History of Chemotherapy:

Paul Ehrlich considered being father of immunology and chemotherapy is reported to have laid down principles on which chemotherapy is based. First use of drugs to treat cancer was in early 20th century, when mustard gas was used as chemical warfare agent in World War 1. It was seen that individuals exposed to mustard gas had low white blood cell count, and similar compound nitrogen mustard was studied during World War II. Based on hematopoeisis properties of mustard gas, in December 1942 numerous patients with lymphomas were provided intravenous injection of mustard gas, and there was a temporary outstanding improvement in illness. It was also seen during a military operation in World War II, survivors of hundreds of people exposed to mustard gas after air raid by Germany on Italian harbor of Bari, had low white blood cell counts. This occurrence led scientists to begin thinking of other substances which would help in treatment of cancer, and first drug produced from this line of research is called as mustine. Also after World War II, folic acid was also discovered to be effective against treatment of leukaemia in children, by blocking definite chemical agents like aminopterin and amethopterin. In 1965, POMP regimen, that is combination of different drugs to fight against cancer, was discovered. Through the combination, long term remission of leukaemia was made possible in children. This discovery is recommended to be responsible for improvements made so far in field of chemotherapy and almost all successful chemotherapies are known to use combination approach. Recently is discovery of adjuvant therapy, whereby chemotherapy is applied to tumor at extremely early stage or application of chemotherapy to remaining cancer cells after removal of tumor by surgery. It was found that high doses of chemotherapy after surgery prevented cancer cells from returning. Another chemical agent 5- fluorouracil, DNA inhibitor was discovered to enhance rate of colon cancer when combined with surgery. Lot of chemicals were tested during 1970s, to fight against cancer and even till present moment, drugs utilized to treat malaria, plant extracts have all been used in treatment of cancer, and improvements have been recorded in certain places and areas. Nevertheless use of chemotherapy in fight against cancer is losing grounds based on couple of side effects joined to it.

Principles of chemotherapy:

Cancer is uncontrolled development of cells coupled with invasion, and is thought to be caused by genetic and environmental factors. Successful use of chemotherapy in treatment of cancer is based on mode of action of chemical agents used, and genetic constituents of the patients.

Process of Cell Division:

Several studies have shown that kinetics of cell growth verifies tumor growth characteristics, and also partially describes biological behavior and heterogeneity of tumors. In cell cycle, mitosis results in three subpopulations of daughter cells; non-dividing and terminally distinguished cells, continually proliferating cells and stem cells, that are resting cells and may be employed in cell cycle. These cells are also seen in tumors. There are four distinct phases in cell cycle division process, and they are G-phase, where preliminary synthetic procedure occurs which prepare cells for DNA synthetic phase, called as S-phase. In S-phase, specific protein signals control cell cycle and permit replication of genome where DNA contents become tetraploid. G2-phase is another resting stage for cells, before heading on to mitotic phase, which is M-phase. M-phase is characterized with chromosome condensation and separation, and cell division in two daughter cells. Studies reveal that variations in the development of tumor or cancer reflect the proportion of keenly dividing cells, the length of cell cycle and the rate of cell loss. Tumors have been seen to have the sigmoid shaped growth curve that recommends that tumors rate of growth increases at faster rate when the size is small, and growth decreases as the size increases.

Principles of Chemotherapy:

Cells targeted by chemical agents in chemotherapy are cells which have the indistinct capacity to reproduce themselves that are stem cells. Most chemical agents perform by impairing mitosis or modifying delicate mechanisms of cell division, efficiently targeting fast dividing cells, whereas ignoring slowly developing tumor cells. Few agents cause tumor cells to experience programmed cell death, called as apoptosis. As most chemical agents target cell division procedure, tumors with high growth fraction like aggressive lymphomas, acute myeloid leukaemia and Hodgkin's disease are more probable to be affected by chemotherapy as larger part of cells are undergoing cell division at any point in time. Indolent lymphomas likely to respond to chemotherapy at a extremely slow and modest pace. Tumors still at the young stage at affected more efficiently by chemotherapy, as mechanisms regulating cell growth are still very much preserved, as they are more distinguished. As tumor or cancer cells ages, they become less distinguished and growth becomes less regulated. Therefore tumor cells response to chemical agents or chemotherapy is low, and at this phase surgery or radiation becomes more very important than chemotherapy. Near centre of some solid tumors, there is absolute cessation of cell division, and in most cases chemical agents don't have access to core of tumor, so they are highly insensitive to chemotherapy. Targeting of rapidly dividing cells in cell division cycle by chemical agents, also leads to destruction of cells liable for hair growth and replacement of intestinal epithelium. These side effects have pressured researchers to find ways to recognize malignant cells, so that they can be exclusively targeted without causing further damage to patients. Imatinib, monoclonal antibody drug was recommended to have been developed to target Philadelphia chromosome, mainly observed in patients with specific forms of tumors. Efforts are on to recognize much more features to develop efficient treatment modalities.

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