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Bavituximab
Bavituximab (PGN401) is a human-mouse chimeric monoclonal antibody against phosphatidylserine, which is a component of cell membranes that is exposed when a cell is transformed into solid tumor cancer cell or dies, and when cells are infected with hepatitis C. The process of cell death is highly controlled and so there usually no immune response to phosphatidylserine but when bavituximab binds to it, the conjugate appears to stimulate an immune response in humans. Biology Phosphatidylserine is the most abundant anionic phospholipid in the cell's plasma membrane, and is usually positioned internally. However, during apoptosis and several pathological conditions including tumorigenesis or infection by some types of viruses, phosphatidylserine is flipped from an internal to an external position. When external, it can potentially be recognized by antibodies. As such, targeting external phosphatidylserine may be a strategy for novel broad-spectrum anti-viral therapies. Bavituxima ...
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Monoclonal Antibody
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 therapy ...
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Phosphatidylserine
Phosphatidylserine (abbreviated Ptd-L-Ser or PS) is a phospholipid and is a component of the cell membrane. It plays a key role in cell cycle signaling, specifically in relation to apoptosis. It is a key pathway for viruses to enter cells via apoptotic mimicry. Its exposure on the outer surface of a membrane marks the cell for destruction via apoptosis. Structure Phosphatidylserine is a phospholipid—more specifically a glycerophospholipid—which consists of two fatty acids attached in ester linkage to the first and second carbon of glycerol and serine attached through a phosphodiester linkage to the third carbon of the glycerol. Phosphatidylserine sourced from plants differs in fatty acid composition from that sourced from animals. It is commonly found in the inner (cytoplasmic) leaflet of biological membranes. It is almost entirely found in the inner monolayer of the membrane with only less than 10% of it in the outer monolayer. Introduction Phosphatidylserine (PS) is ...
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Chimera (protein)
Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this ''fusion gene'' results in a single or multiple polypeptides with functional properties derived from each of the original proteins. ''Recombinant fusion proteins'' are created artificially by recombinant DNA technology for use in biological research or therapeutics. '' Chimeric'' or ''chimera'' usually designate hybrid proteins made of polypeptides having different functions or physico-chemical patterns. ''Chimeric mutant proteins'' occur naturally when a complex mutation, such as a chromosomal translocation, tandem duplication, or retrotransposition creates a novel coding sequence containing parts of the coding sequences from two different genes. Naturally occurring fusion proteins are commonly found in cancer cells, where they may function as oncoprotein ...
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Malignant Transformation
Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as ''malignant degeneration'' of a previously existing benign tumor. Causes There are many causes of primary malignant transformation, or tumorigenesis. Most human cancers in the United States are caused by external factors, and these factors are largely avoidable. These factors were summarized by Doll and Peto in 1981, and were still considered to be valid in 2015. These factors are listed in the table. a Reproductive and sexual behaviors include: number of partners; age at first menstruation; zero versus one or more live births Examples of diet-related malignant transformation Diet and colon cancer Colon cancer provides one example of the mechanisms by which diet, the top factor listed in the table, is an external factor in cancer. The Western diet of African Americans in the United States is associated with a ye ...
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Solid Tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm can be benign, potentially ma ...
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Hepatitis C
Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, abdominal pain, and yellow tinged skin occurs. The virus persists in the liver in about 75% to 85% of those initially infected. Early on, chronic infection typically has no symptoms. Over many years however, it often leads to liver disease and occasionally cirrhosis. In some cases, those with cirrhosis will develop serious complications such as liver failure, liver cancer, or dilated blood vessels in the esophagus and stomach. HCV is spread primarily by blood-to-blood contact associated with injection drug use, poorly sterilized medical equipment, needlestick injuries in healthcare, and transfusions. Using blood screening, the risk from a transfusion is less than one per two million. It may also be spread from an infected mother to her ...
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Apoptosis
Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, DNA fragmentation, and mRNA decay. The average adult human loses between 50 and 70 billion cells each day due to apoptosis. For an average human child between eight and fourteen years old, approximately twenty to thirty billion cells die per day. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis is a highly regulated and controlled process that confers advantages during an organism's life cycle. For example, the separation of fingers and toes in a developing human embryo occurs because cells between the digits undergo apoptosis. Unlike necrosis, apoptosis produces cell fragments called apoptotic ...
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Lassa Fever Virus
''Lassa mammarenavirus'' (LASV) is an arenavirus that causes Lassa hemorrhagic fever, a type of viral hemorrhagic fever (VHF), in humans and other primates. ''Lassa mammarenavirus'' is an emerging virus and a select agent, requiring Biosafety Level 4-equivalent containment. It is endemic in West African countries, especially Sierra Leone, the Republic of Guinea, Nigeria, and Liberia, where the annual incidence of infection is between 300,000 and 500,000 cases, resulting in 5,000 deaths per year. As of 2012 discoveries within the Mano River region of west Africa have expanded the endemic zone between the two known Lassa endemic regions, indicating that LASV is more widely distributed throughout the tropical wooded savannah ecozone in west Africa. There are no approved vaccines against Lassa fever for use in humans. Discovery In 1969, missionary nurse Laura Wine fell ill with a mysterious disease she contracted from an obstetrical patient in Lassa, a village in Borno State, N ...
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Influenza
Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptoms begin from one to four days after exposure to the virus (typically two days) and last for about 2–8 days. Diarrhea and vomiting can occur, particularly in children. Influenza may progress to pneumonia, which can be caused by the virus or by a subsequent bacterial infection. Other complications of infection include acute respiratory distress syndrome, meningitis, encephalitis, and worsening of pre-existing health problems such as asthma and cardiovascular disease. There are four types of influenza virus, termed influenza viruses A, B, C, and D. Aquatic birds are the primary source of Influenza A virus (IAV), which is also widespread in various mammals, including humans and pigs. Influenza B virus (IBV) and Influenza C virus (ICV) pri ...
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Non-small Cell Lung Cancer
Non-small-cell lung cancer (NSCLC) is any type of epithelial lung cancer other than small-cell lung carcinoma (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively ( neoadjuvant chemotherapy) and postoperatively (adjuvant chemotherapy). Types The most common types of NSCLC are squamous-cell carcinoma, large-cell carcinoma, and adenocarcinoma, but several other types occur less frequently. A few of the less common types are pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma. All types can occur in unusual histologic variants and as mixed cell-type combinations. Nonsquamous-cell carcinoma almost occupies the half of NSCLC. In the tissue classification, the central type contains about one-ninth. So ...
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Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in the setting of chronic liver inflammation, and is most closely linked to chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol, aflatoxin, or pyrrolizidine alkaloids. Certain diseases, such as hemochromatosis and alpha 1-antitrypsin deficiency, markedly increase the risk of developing HCC. Metabolic syndrome and NASH are also increasingly recognized as risk factors for HCC. As with any cancer, the treatment and prognosis of HCC vary depending on the specifics of tumor histology, size, how far the cancer has spread, and overall health. The vast majority of HCC cases and the lowest survival rates after treatment occur in Asia and sub-Saharan Africa, in countries where hepatitis B infection is endem ...
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Monoclonal Antibodies For Tumors
Monoclonality refers to the state of a line of cells that have been derived from a single clonal origin. Thus "monoclonal cells" can be said to form a single clone. The term ''monoclonal'' comes from the Ancient Greek ''monos'', meaning "alone" or "single", and ''klon'', meaning "twig". The process of replication can occur ''in vivo'', or may be stimulated ''in vitro'' for laboratory manipulations. The use of the term typically implies that there is some method to distinguish between the cells of the original population from which the single ancestral cell is derived, such as a random genetic alteration, which is inherited by the progeny. Common usages of this term include: * Monoclonal antibody: A single hybridoma cell, which by chance includes the appropriate V(D)J recombination to produce the desired antibody, is cloned to produce a large population of identical cells. In informal laboratory jargon, the monoclonal antibodies isolated from cell culture supernatants of these ...
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