Cyclopamine In Smoothened Receptor
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Cyclopamine In Smoothened Receptor
Cyclopamine (11-deoxojervine) is a naturally occurring chemical that belongs in the family of steroidal alkaloids. It is a teratogen isolated from the corn lily (''Veratrum californicum'') that causes fatal birth defects. It prevents the embryonic brain from separating into two lobes (an extreme form of holoprosencephaly), which in turn causes the development of a single eye (cyclopia). The chemical was named after this effect, as it was originally noted by Idaho lamb farmers who contacted the US Department of Agriculture after their herds gave birth to cycloptic lambs in 1957. It then took more than a decade to identify the corn lily as the culprit. Later work suggested that different rain patterns caused the sheep to graze differently, impacting the amount of corn lily ingested by pregnant sheep. The poison interrupts the sonic hedgehog signaling pathway during development, thus causing birth defects. Discovery and naming In 1957, Idaho sheep ranchers contacted the US Depart ...
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Steroidal Alkaloid
Steroidal alkaloids have organic ring backbones which feature nitrogen-based functional groups. More specifically, they are distinguished by their tetracyclic cyclopentanophenanthrene backbone that marks their close relationship with sterols. They fall in two major categories: Solanum alkaloids and Veratrum alkaloids. A Steroidal alkaloid has also been found in ''Chonemorpha fragrans'' (Frangipani vine), 'chonemorphine' was used to treat intestinal infections in Wistar rats. (Chatterjee DK et al (1987) Parasitol Res 74, 1, 30-33). ''Solanum'' alkaloids These compounds generally appear as their corresponding glycoside in plants of the genus ''Solanum''. ''Solanum'' includes plants like potatoes, tomatoes, and various nightshades Starting with cholesterol, the biosynthesis of these compounds follow a similar general mechanism including hydroxylation, oxidation, and transamination before differentiating. Alkaloids found in these plants include chaconine, solanine, solasodine, tom ...
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Mechanism Of Cyclopamine Metabolism
Mechanism may refer to: *Mechanism (engineering), rigid bodies connected by joints in order to accomplish a desired force and/or motion transmission *Mechanism (biology), explaining how a feature is created *Mechanism (philosophy), a theory that all natural phenomena can be explained by physical causes *Mechanism (sociology), a theory that all social phenomena can be explained by the existence of a deterministic mechanism * "The Mechanism", song by Disclosure * ''The Mechanism'' (TV series), a Netflix TV series See also *Machine *Machine (mechanical) *Linkage (mechanical) *Mechanism design, the art of designing rules of a game to achieve a specific outcome *Mechanism of action, the means by which a drug exerts its biological effects *Defence mechanism, unconscious mechanisms aimed at reducing anxiety *Reaction mechanism, the sequence of reactions by which overall chemical change occurs *Antikythera mechanism, an ancient Greek analog computer *Theory of operation A theory of op ...
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Sonidegib
Sonidegib (INN), sold under the brand name Odomzo, is a medication used to treat cancer. Sonidegib is Hedgehog signaling pathway inhibitor (via smoothened antagonism). Approvals and indications It was approved for medical use in the United States and in the European Union in 2015 It is indicated for the treatment of adults with locally advanced basal-cell carcinoma that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy. Pharmacology Sonidegib is administered by mouth. Common side effects include muscle spasms, hair loss, fatigue, abdominal pain, nausea, headache, and weight loss. Sonidegib binds to and inhibits smoothened to inhibit activation of the Hedgehog pathway. Sonidegib is primarily metabolized by CYP3A and is eliminated hepatically. Development It has been investigated as a potential treatment for: * Pancreatic cancer * Breast cancer * Basal cell carcinoma of the skin * Small cell lung cancer * Med ...
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Vismodegib
Vismodegib (trade name Erivedge ) is a drug for the treatment of basal-cell carcinoma (BCC). The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma . The drug was developed by the biotechnology/pharmaceutical company Genentech. Indication Vismodegib is indicated for patients with basal-cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation. Mechanism of action The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents t ...
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Functional Analog (chemistry)
In chemistry and pharmacology, functional analogs are chemical compounds that have similar physical, chemical, biochemical, or pharmacological properties. Functional analogs are not necessarily structural analogs with a similar chemical structure. An example of pharmacological functional analogs are morphine, heroin and fentanyl, which have the same mechanism of action, but fentanyl is structurally quite different from the other two with significant variance in dosage. File:Morphin - Morphine.svg, Morphine File:Heroin - Heroine.svg, Heroin File:Fentanyl2DCSD.svg, Fentanyl See also *Federal Analogue Act The Federal Analogue Act, , is a section of the United States Controlled Substances Act passed in 1986 which allows any chemical "substantially similar" to a controlled substance listed in Schedule I or II to be treated as if it were listed in ... References Chemical nomenclature Pharmacology {{pharma-stub ...
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Angiogenesis
Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splitting. Vasculogenesis is the embryonic formation of endothelial cells from mesoderm cell precursors, and from neovascularization, although discussions are not always precise (especially in older texts). The first vessels in the developing embryo form through vasculogenesis, after which angiogenesis is responsible for most, if not all, blood vessel growth during development and in disease. Angiogenesis is a normal and vital process in growth and development, as well as in wound healing and in the formation of granulation tissue. However, it is also a fundamental step in the transition of tumors from a benign state to a malignant one, leading to the use of angiogenesis inhibitors in the treatment of cancer. The essential role of angiogenesis in ...
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Stromal Cell
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term ''stromal'' comes from Latin , "bed covering", and Ancient Greek , , "bed". Stromal cells are an important part of the body's immune response and modulate inflammation through multiple pathways. They also aid in differentiation of hematopoietic cells and forming necessary blood elements. The interaction between stromal cells and tumor cells is known to play a major role in cancer growth and progression. In addition, by regulating local cytokine networks (e.g. M-CSF, LIF), bone marrow stromal cells have been described to be ...
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Multiple Myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include amyloidosis. The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, and certain chemicals. There is an increased risk of multiple myeloma in certain occupations. This is due to the occupational exposure to aromatic hydrocarbon solvents having a role in causation of multiple myeloma. Multiple myeloma may develop from monoclonal gammopathy of undetermined significance that progresses to smoldering myeloma. The abnormal plasma cells produce abnormal antibodies, which can cause kidney problems and overly thick blood. The plasma cells can also form a mass in the bone marrow or soft tissue. When one tumor i ...
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Glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness. The cause of most cases of glioblastoma is not known. Uncommon risk factors include genetic disorders, such as neurofibromatosis and Li–Fraumeni syndrome, and previous radiation therapy. Glioblastomas represent 15% of all brain tumors. They can either start from normal brain cells or develop from an existing low-grade astrocytoma. The diagnosis typically is made by a combination of a CT scan, MRI scan, and tissue biopsy. There is no known method of preventing the cancer. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The medication temozolomide is frequently used ...
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Rhabdomyosarcoma
Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle. Cells of the tumor are identified as rhabdomyoblasts. There are four subtypes – embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, pleomorphic rhabdomyosarcoma, and spindle cell/sclerosing rhabdomyosarcoma. Embryonal, and alveolar are the main groups, and these types are the most common soft tissue sarcomas of childhood and adolescence. The pleomorphic type is usually found in adults. It is generally considered to be a disease of childhood, as the vast majority of cases occur in those below the age of 18. It is commonly described as one of the small-blue-round-cell tumors of childhood due to its appearance on an H&E stain. Despite being relatively rare, it accounts for approximately 40% of all recorded soft tissue sarcomas. RMS can occur in any soft tissue site in the body, but is primarily found in t ...
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Medulloblastoma
Medulloblastoma is a common type of primary brain cancer in children. It originates in the part of the brain that is towards the back and the bottom, on the floor of the skull, in the cerebellum, or posterior fossa. The brain is divided into two main parts, the larger cerebrum on top and the smaller cerebellum below towards the back. They are separated by a membrane called the tentorium. Tumors that originate in the cerebellum or the surrounding region below the tentorium are, therefore, called infratentorial. Historically medulloblastomas have been classified as a primitive neuroectodermal tumor (PNET), but it is now known that medulloblastoma is distinct from supratentorial PNETs and they are no longer considered similar entities. Medulloblastomas are invasive, rapidly growing tumors that, unlike most brain tumors, spread through the cerebrospinal fluid and frequently metastasize to different locations along the surface of the brain and spinal cord. Metastasis all the way dow ...
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Basal Cell Carcinoma
Basal-cell carcinoma (BCC), also known as basal-cell cancer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raised area with ulceration. Basal-cell cancer grows slowly and can damage the tissue around it, but it is unlikely to spread to distant areas or result in death. Risk factors include exposure to ultraviolet light, having lighter skin, radiation therapy, long-term exposure to arsenic and poor immune-system function. Exposure to UV light during childhood is particularly harmful. Tanning beds have become another common source of ultraviolet radiation. Diagnosis often depends on skin examination, confirmed by tissue biopsy. It remains unclear whether sunscreen affects the risk of basal-cell cancer. Treatment is typically by surgical removal. This can be by simple excision if the cancer is small; otherwise, Mohs surgery is generally recomme ...
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