Olaparib
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Olaparib
Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers. In December 2014, olaparib was approved for use as a single agent by the European Medicines Agency (EMA) in the European Union and by the Food and Drug Administration (FDA) in the United States. Medical uses Olaparib is indicated to treat breast cancer, ovarian cancer, fallopian tube cancer, peritoneal cancer, pancreatic cancer, and prostate cancer. Side effects Side effects include gastrointestinal effects such as nausea, vomiting, and loss of appetite; fatigue; muscle and joint pain; and low blood counts such as anemia, with occasional leukemia. Somnolence was sometimes seen in clinical trials whi ...
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PARP Inhibitor
PARP inhibitors are a group of pharmacological inhibitors of the enzyme poly ADP ribose polymerase (PARP). They are developed for multiple indications, including the treatment of heritable cancers. Several forms of cancer are more dependent on PARP than regular cells, making PARP (PARP1, PARP2 etc) an attractive target for cancer therapy. PARP inhibitors appear to improve progression-free survival in women with recurrent platinum-sensitive ovarian cancer, as evidenced mainly by olaparib added to conventional treatment. In addition to their use in cancer therapy, PARP inhibitors are considered a potential treatment for acute life-threatening diseases, such as stroke and myocardial infarction, as well as for long-term neurodegenerative diseases. Medical uses Approved for marketing * Olaparib: In December, 2014, the EMA and US FDA approved olaparib as monotherapy (at 400 mg taken twice per day) for patients with germline BRCA mutated (gBRCAm) advanced ovarian cancer wh ...
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Ovarian Cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver. The risk of ovarian cancer increases with age. Most cases of ovarian cancer develop after menopause. It is also more common in women who have ovulated m ...
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Poly ADP Ribose Polymerase
Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in a number of cellular processes such as DNA repair, genomic stability, and programmed cell death. Members of PARP family The PARP family comprises 17 members (10 putative). They vary greatly in structure and function within the cell. * ''PARP1'', '' PARP2'', VPARP (''PARP4''), Tankyrase-1 and -2 (PARP-5a or ''TNKS'', and PARP-5b or ''TNKS2'') have a confirmed PARP activity. * Others include ''PARP3'', , ''TIPARP'' (or "PARP7"), ''PARP8'', , ''PARP10'', , ''PARP12'', , , and ''PARP16 (gene), PARP16''. Structure PARP is composed of four domains of interest: a DNA-binding domain, a caspase-cleaved domain (see below), an auto-modification domain, and a catalytic domain. The DNA-binding domain is composed of two zinc finger structural motif, motifs. In the presence of damaged DNA (base pair-excised), the DNA-binding domain will bind the DNA and induce a Allosteric regulation, conformational shift. It has been ...
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DNA Repair
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). This can eventually lead to malignant ...
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Merck & Co
Merck & Co., Inc. is an American multinational pharmaceutical company headquartered in Rahway, New Jersey, and is named for Merck Group, founded in Germany in 1668, of whom it was once the American arm. The company does business as Merck Sharp & Dohme or MSD outside the United States and Canada. Merck & Co. was originally established as the American affiliate of Merck Group in 1891. Merck develops and produces medicines, vaccines, biologic therapies and animal health products. It has multiple blockbuster drugs or products each with 2020 revenues including cancer immunotherapy, anti-diabetic medication and vaccines against HPV and chickenpox. The company is ranked 71st on the 2022 ''Fortune'' 500 and 87th on the 2022 ''Forbes'' Global 2000, both based on 2021 revenues. Products The company develops medicines, vaccines, biologic therapies and animal health products. In 2020, the company had 6 blockbuster drugs or products, each with over $1 billion in revenue: ''Keytruda'' ( ...
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Stephen Jackson (scientist)
Stephen Philip Jackson, FRS, FMedSci, (born 17 July 1962) is the Frederick James Quick Professor of Biology. He is a Senior Group Leader and Head of Cancer Research UK Laboratories at the Gurdon Institute. Education Professor Jackson was educated at the University of Leeds, graduating with a Bachelor of Science degree in Biochemistry in 1983. He then carried out his PhD research working with Jean Beggs on yeast RNA splicing at Imperial College London and Edinburgh University, earning his PhD in 1987. Research Following his PhD, Jackson carried out postdoctoral research with Robert Tjian at the University of California, Berkeley, where he developed an interest in the regulation of transcription. He returned to the UK in 1991 as a Junior Group Leader at the then Wellcome-CRC Institute, now the Gurdon Institute. Jackson's work has provided key insights into cellular processes that respond to DNA damage; processes fundamental to life and whose defects cause various diseases p ...
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Prostate Cancer
Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder. It is located in the hypogastric region of the abdomen. To give an idea of where it is located, the bladder is superior to the prostate gland as shown in the image The rectum is posterior in perspective to the prostate gland and the ischial tuberosity of the pelvic bone is inferior. Only those who have male reproductive organs are able to get prostate cancer. Most prostate cancers are slow growing. Cancerous cells may spread to other areas of the body, particularly the bones and lymph nodes. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty urinating, blood in the urine, or pain in the pelvis or back. Benign prostatic hyperplasia may produce similar symptoms ...
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Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ...
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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 chronic myeloi ...
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Complete Blood Count
A complete blood count (CBC), also known as a full blood count (FBC), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blood cells, red blood cells and platelets, the concentration of hemoglobin, and the hematocrit (the volume percentage of red blood cells). The red blood cell indices, which indicate the average size and hemoglobin content of red blood cells, are also reported, and a white blood cell differential, which counts the different types of white blood cells, may be included. The CBC is often carried out as part of a medical assessment and can be used to monitor health or diagnose diseases. The results are interpreted by comparing them to Reference ranges for blood tests, reference ranges, which vary with sex and age. Conditions like anemia and thrombocytopenia are defined by abnormal complete blood count results. The red blood cell indices can provide information about the ...
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Anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, the symptoms are often vague, such as tiredness, weakness, shortness of breath, headaches, and a reduced ability to exercise. When anemia is acute, symptoms may include confusion, feeling like one is going to pass out, loss of consciousness, and increased thirst. Anemia must be significant before a person becomes noticeably pale. Symptoms of anemia depend on how quickly hemoglobin decreases. Additional symptoms may occur depending on the underlying cause. Preoperative anemia can increase the risk of needing a blood transfusion following surgery. Anemia can be temporary or long term and can range from mild to severe. Anemia can be caused by blood loss, decreased red blood cell production, and increased red blood cell breakdown. Causes o ...
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BRCA Mutation
A ''BRCA'' mutation is a mutation in either of the ''BRCA1'' and ''BRCA2'' genes, which are tumour suppressor genes. Hundreds of different types of mutations in these genes have been identified, some of which have been determined to be harmful, while others have no proven impact. Harmful mutations in these genes may produce a hereditary breast–ovarian cancer syndrome in affected persons. Only 5–10% of breast cancer cases in women are attributed to ''BRCA1'' and ''BRCA2'' mutations (with ''BRCA1'' mutations being slightly more common than ''BRCA2'' mutations), but the impact on women with the gene mutation is more profound. Women with harmful mutations in either ''BRCA1'' or ''BRCA2'' have a risk of breast cancer that is about five times the normal risk, and a risk of ovarian cancer that is about ten to thirty times normal. The risk of breast and ovarian cancer is higher for women with a high-risk ''BRCA1'' mutation than with a ''BRCA2'' mutation. Having a high-risk mutation doe ...
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