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Aminopterin
Aminopterin (or 4-aminopteroic acid), the 4-amino derivative of folic acid, is an antineoplastic drug with immunosuppressive properties often used in chemotherapy. Aminopterin is a synthetic derivative of pterin. Aminopterin works as an enzyme inhibitor by competing for the folate binding site of the enzyme dihydrofolate reductase. Its binding affinity for dihydrofolate reductase effectively blocks tetrahydrofolate synthesis. This results in the depletion of nucleotide precursors and inhibition of DNA, RNA, and protein synthesis. It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities. Uses Discovered by Yellapragada Subbarow, the drug was first used by Sidney Farber in 1947 to induce remissions among children with leukemia. Aminopter ...
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Sidney Farber
Sidney Farber (September 30, 1903 – March 30, 1973) was an American pediatric pathologist. He is regarded as the father of modern chemotherapy for his work using folic acid antagonists to combat leukemia, which led to the development of other chemotherapeutic agents against other malignancies. Farber was also active in cancer research advocacy and fundraising, most notably through his establishment of the Jimmy Fund, a foundation dedicated to pediatric research in childhood cancers. The Dana–Farber Cancer Institute is named after him. Early life He was born in Buffalo, New York, to Jewish parents Simon and Matilda (Goldstein) Farber. He was the third of 14 children. He was the younger brother of the noted philosopher and University of Buffalo professor Marvin Farber (1901–1980). Farber graduated from University at Buffalo, The State University of New York, or SUNY Buffalo, in 1923. Farber Hall, built in 1953 on the South Campus of SUNY Buffalo, is named for him. In the ...
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HAT Medium
HAT Medium (hypoxanthine-aminopterin-thymidine medium) is a selection medium for mammalian cell culture, which relies on the combination of aminopterin, a drug that acts as a powerful folate metabolism inhibitor by inhibiting dihydrofolate reductase, with hypoxanthine (a purine derivative) and thymidine (a deoxynucleoside) which are intermediates in DNA synthesis. The trick is that aminopterin blocks DNA ''de novo'' synthesis, which is absolutely required for cell division to proceed, but hypoxanthine and thymidine provide cells with the raw material to evade the blockage (the "salvage pathway"), provided that they have the right enzymes, which means having functioning copies of the genes that encode them. The enzyme dihydrofolate reductase, which produces tetrahydrofolate (THF) by the reduction of dihydrofolate, is specifically blocked by aminopterin. THF, acting in association with specific proteins, can receive single carbon units that are then transferred to specific targets. ...
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Methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leukemia, lung cancer, lymphoma, gestational trophoblastic disease, and osteosarcoma. Types of autoimmune diseases it is used for include psoriasis, rheumatoid arthritis, and Crohn's disease. It can be given by mouth or by injection. Common side effects include nausea, feeling tired, fever, increased risk of infection, low white blood cell counts, and breakdown of the skin inside the mouth. Other side effects may include liver disease, lung disease, lymphoma, and severe skin rashes. People on long-term treatment should be regularly checked for side effects. It is not safe during breastfeeding. In those with kidney problems, lower doses may be needed. It acts by blocking the body's use of folic acid. Methotrexate was first made in 19 ...
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Monoclonal Antibodies
A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies can have monovalent affinity, binding only to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody-secreting plasma cell lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one monoclonal antibody to two epitopes. It is possible to produce monoclonal antibodies that specifically bind to virtually any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in biochemistry, molecular biology, and medicine. Monoclonal antibodies are being used on a clinical level for both the diagnosis and thera ...
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Yellapragada Subbarow
Yellapragada Subba Rao (12 January 1895 – 8 August 1948) was a pioneering Indian biochemist who discovered the function of adenosine triphosphate (ATP) as an energy source in the cell, developed methotrexate for the treatment of cancer and led the department at Lederle laboratories in which Benjamin Minge Duggar discovered chlortetracycline (Aureomycin) in 1945. A student of Madras Medical College, his elder brother and younger brother both died due to tropical sprue in the span of 8 days. He subsequently discovered folic acid as a cure for tropical sprue. He discovered methotrexate, a chemotherapy drug still used today and also used for rheumatoid arthritis, and diethylcarbamazine (DEC), the only effective drug for treating filariasis. Most of his career was spent in the United States. Despite his isolation of ATP, Subbarao did not gain tenure at Harvard though he would lead some of America's most important medical research during World War II. He is also credited ...
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Hybridomas
Hybridoma technology is a method for producing large numbers of identical antibodies (also called monoclonal antibodies). This process starts by injecting a mouse (or other mammal) with an antigen that provokes an immune response. A type of white blood cell, the B cell, produces antibodies that bind to the injected antigen. These antibody producing B-cells are then harvested from the mouse and, in turn, fused with immortal B cell cancer cells, a myeloma, to produce a hybrid cell line called a hybridoma, which has both the antibody-producing ability of the B-cell and the longevity and reproductivity of the myeloma. The hybridomas can be grown in culture, each culture starting with one viable hybridoma cell, producing cultures each of which consists of genetically identical hybridomas which produce one antibody per culture (monoclonal) rather than mixtures of different antibodies (polyclonal). The myeloma cell line that is used in this process is selected for its ability to grow i ...
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Congenital Malformation
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional disorders in which problems exist with how a body part works. Functional disorders include metabolic and degenerative disorders. Some birth defects include both structural and functional disorders. Birth defects may result from genetic or chromosomal disorders, exposure to certain medications or chemicals, or certain infections during pregnancy. Risk factors include folate deficiency, drinking alcohol or smoking during pregnancy, poorly controlled diabetes, and a mother over the age of 35 years old. Many are believed to involve multiple factors. Birth defects may b ...
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Dana–Farber Cancer Institute
Dana–Farber Cancer Institute is a comprehensive cancer treatment and research institution in Boston, Massachusetts. Dana–Farber is the founding member of Dana–Farber/Harvard Cancer Center, Harvard's Comprehensive Cancer Center designated by the National Cancer Institute, and one of the 15 clinical affiliates and research institutes of Harvard Medical School. As of 2021, Dana–Farber is ranked the #3 cancer hospital in the world. Two Nobel laureates in Physiology or Medicine are among its past and present faculty. Dana–Farber's research discoveries include the development of the highly successful Gleevec to treat chronic myeloid leukemia. Overview Dana–Farber employs more than 4,855 full-time and part-time people, 529 faculty, and has annual gross revenues of about $1,733,386,000. All faculty and postdoctoral research fellows at Dana–Farber hold the equivalent academic positions concurrently at Harvard University. There are more than 523,425 adult and pediatric pat ...
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Leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ''leukemia cells''. Symptoms may include bleeding and bruising, bone pain, fatigue, fever, and an increased risk of infections. These symptoms occur due to a lack of normal blood cells. Diagnosis is typically made by blood tests or bone marrow biopsy. The exact cause of leukemia is unknown. A combination of genetic factors and environmental (non-inherited) factors are believed to play a role. Risk factors include smoking, ionizing radiation, petrochemicals (such as benzene), prior chemotherapy, and Down syndrome. People with a family history of leukemia are also at higher risk. There are four main types of leukemia— acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and chr ...
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Folic Acid
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and storage. Folate is required for the body to make DNA and RNA and metabolise amino acids necessary for cell division. As humans cannot make folate, it is required in the diet, making it an essential nutrient. It occurs naturally in many foods. The recommended adult daily intake of folate in the U.S. is 400 micrograms from foods or dietary supplements. Folate in the form of folic acid is used to treat anemia caused by folate deficiency. Folic acid is also used as a supplement by women during pregnancy to reduce the risk of neural tube defects (NTDs) in the baby. Low levels in early pregnancy are believed to be the cause of more than half of babies born with NTDs. More than 80 countries use either mandatory or voluntary fortific ...
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Protein Biosynthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critical functions as enzymes, structural proteins or hormones. Protein synthesis is a very similar process for both prokaryotes and eukaryotes but there are some distinct differences. Protein synthesis can be divided broadly into two phases - transcription and translation. During transcription, a section of DNA encoding a protein, known as a gene, is converted into a template molecule called messenger RNA (mRNA). This conversion is carried out by enzymes, known as RNA polymerases, in the nucleus of the cell. In eukaryotes, this mRNA is initially produced in a premature form ( pre-mRNA) which undergoes post-transcriptional modifications to produce mature mRNA. The mature mRNA is exported from the cell nucleus via nuclear pores to the cytoplasm ...
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Pterin
Pterin is a heterocyclic compound composed of a pteridine ring system, with a "keto group" (a lactam) and an amino group on positions 4 and 2 respectively. It is structurally related to the parent bicyclic heterocycle called pteridine. Pterins, as a group, are compounds related to pterin with additional substituents. Pterin itself is of no biological significance. Pterins were first discovered in the pigments of butterfly wings (hence the origin of their name, from the Greek ''pteron (πτερόν)'', wing) and perform many roles in coloration in the biological world. Chemistry Pterins exhibit a wide range of tautomerism in water, beyond what is assumed by just keto-enol tautomerism. For the unsubstituted pterin, at least five tautomers are commonly cited. For 6-methylpterin, seven tautomers are theoretically predicted to be important in solution. The pteridine ring system contains four nitrogen atoms, reducing its aromaticity to the point that it can be attacked by nucl ...
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