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Oncolytic Adenovirus
Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus. Of the many different viruses being explored for oncolytic potential, an adenovirus was the first to be approved by a regulatory agency, the genetically modified H101 strain. It gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer. Engineering of oncolytic adenovirus Adenoviruses have so far been through three generations of development. Some of the strategies for modification of adenoviruses are described below. Attenuation For adenovirus replication to occur, the host cell must be induced into S phase by viral proteins interfering with cell cycle proteins. The adenoviral E1A gene is responsible for inactivation of several proteins, including retinoblastoma, allowing entry into S-phase. The adenovirus E1B55kDa gene cooperates with another adenoviral product, E4ORF6, to inactivate p5 ...
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Adenovirus
Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953. They have a broad range of vertebrate hosts; in humans, more than 50 distinct adenoviral serotypes have been found to cause a wide range of illnesses, from mild respiratory infections in young children (known as the common cold) to life-threatening multi-organ disease in people with a weakened immune system. Virology Classification This family contains the following genera: * '' Atadenovirus'' * '' Aviadenovirus'' * '' Ichtadenovirus'' * '' Mastadenovirus'' (including all human adenoviruses) * '' Siadenovirus'' * '' Testadenovirus'' Diversity In humans, currently there are 88 human adenoviruses (HAdVs) in seven species (Human adenovirus A to G): * A: 12, 18, 31 * B: 3, 7, 11, 14, ...
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Antibody
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen. Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can ''tag'' a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. In contrast, the remainder of the antibody is relatively constant. It only occurs in a few varia ...
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Myositis
Myositis is a rare disease that involves inflammation of the muscles. This can present with a variety of symptoms such as skin involvement (i.e., rashes), muscle weakness, and other organ involvement. Systemic symptoms such as weight loss, fatigue, and low fever can also present. Causes Injury, medicines, infection, or an autoimmune disorder can lead to myositis. It can also be idiopathic. * Injury - A mild form of myositis can occur with hard exercise. A more severe form of muscle injury, called rhabdomyolysis, is also associated with myositis. This is a condition where injury to your muscles causes them to quickly break down. * Medicines - A variety of different medicines can cause myositis. One of the most common drug types that can cause myositis is statins. Statins are drugs that are used to help lower high cholesterol. One of the most common side effects of statin therapy is muscle pain. Rarely, statin therapy can lead to myositis. * Infection - The most common infectious c ...
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Hepatotoxicity
Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins), and herbal remedies (two prominent examples being kava, mechanism unknown, and comfrey, through its pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins. More than 900 drugs have been implicated in causing liver injury (see LiverTox, exter ...
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MicroRNA
MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRNAs base-pair to complementary sequences in mRNA molecules, then gene silence said mRNA molecules by one or more of the following processes: (1) cleavage of mRNA strand into two pieces, (2) destabilization of mRNA by shortening its poly(A) tail, or (3) translation of mRNA into proteins. This last method of gene silencing is the least efficient of the three, and requires the aid of ribosomes. miRNAs resemble the small interfering RNAs (siRNAs) of the RNA interference (RNAi) pathway, except miRNAs derive from regions of RNA transcripts that fold back on themselves to form short hairpins, whereas siRNAs derive from longer regions of double-stranded RNA. The human genome may encode over 1900 miRNAs, although more recent analysis suggests that ...
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Oncolytic Adenovirus Controlled By MicroRNA Response Element
An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune system responses. Oncolytic viruses also have the ability to affect the tumor micro-environment in multiples ways. The potential of viruses as anti-cancer agents was first realised in the early twentieth century, although coordinated research efforts did not begin until the 1960s. A number of viruses including adenovirus, reovirus, measles, herpes simplex, Newcastle disease virus, and vaccinia have been clinically tested as oncolytic agents. Most current oncolytic viruses are engineered for tumour selectivity, although there are naturally occurring examples such as reovirus and the senecavirus, resulting in clinical tria ...
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Antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. The term ''antigen'' originally referred to a substance that is an antibody generator. Antigens can be proteins, peptides (amino acid chains), polysaccharides (chains of monosaccharides/simple sugars), lipids, or nucleic acids. Antigens are recognized by antigen receptors, including antibodies and T-cell receptors. Diverse antigen receptors are made by cells of the immune system so that each cell has a specificity for a single antigen. Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as clonal selection. In most cases, an antibody can only react to and bind one specific antigen; in some instances, however, antibodies may cross-react and bind more than one antigen. ...
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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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Enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called ''enzymology'' and the field of pseudoenzyme analysis recognizes that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties. Enzymes are known to catalyze more than 5,000 biochemical reaction types. Other biocatalysts are catalytic RNA molecules, called ribozymes. Enzymes' specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the reaction ra ...
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Cyclooxygenase-2
Prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) (The HUGO official symbol is PTGS2; HGNC ID, HGNC:9605), also known as cyclooxygenase-2 or COX-2, is an enzyme that in humans is encoded by the ''PTGS2'' gene. In humans it is one of two cyclooxygenases. It is involved in the conversion of arachidonic acid to prostaglandin H2, an important precursor of prostacyclin, which is expressed in inflammation. Function PTGS2 (COX-2), converts arachidonic acid (AA) to prostaglandin endoperoxide H2. PTGSs are targets for NSAIDs and PTGS2 (COX-2) specific inhibitors called coxibs. PTGS-2 is a sequence homodimer. Each monomer of the enzyme has a peroxidase and a PTGS (COX) active site. The PTGS (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins in two steps. First, hydrogen is abstracted from carbon 13 of arachidonic acid, and then two molecules of oxygen are added by the PTGS2 (COX-2), giving PGG2. Second, PGG2 is reduced to ...
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Oesophageal Adenocarcinoma
Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include dysphagia, difficulty in swallowing and weight loss. Other symptoms may include odynophagia, pain when swallowing, a hoarseness, hoarse voice, Lymphadenopathy, enlarged lymph nodes ("glands") around the clavicle, collarbone, a dry cough, and possibly hemoptysis, coughing up or hematemesis, vomiting blood. The two main Histopathology, sub-types of the disease are esophageal squamous-cell carcinoma (often abbreviated to ESCC), which is more common in the developing world, and esophageal adenocarcinoma (EAC), which is more common in the developed world. A number of less common types also occur. Squamous-cell carcinoma arises from the squamous epithelium, epithelial cells that line the esophagus. Adenocarcinoma arises from glandular cells present in the lower third of the esophagus, often where they have already Intestinal metaplasia, transformed ...
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Integrin
Integrins are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, organization of the intracellular cytoskeleton, and movement of new receptors to the cell membrane. The presence of integrins allows rapid and flexible responses to events at the cell surface (''e.g''. signal platelets to initiate an interaction with coagulation factors). Several types of integrins exist, and one cell generally has multiple different types on its surface. Integrins are found in all animals while integrin-like receptors are found in plant cells. Integrins work alongside other proteins such as cadherins, the immunoglobulin superfamily cell adhesion molecules, selectins and syndecans, to mediate cell–cell and cell–matrix interaction. Ligands for integrins include fibronectin, vitronectin, collagen and laminin. Stru ...
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