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CRLX101
CRLX101 is an experimental approach to cancer chemotherapy that is under investigation in human trials. It is an example of a nanomedicine. The agent represents a nanoparticle conjugate that consists of a drug delivery molecule, namely a cyclodextrin-based polymer (CDP) and an anti-cancer compound ( camptothecin). It was developed by Mark E. Davis, professor of Chemical Engineering at the California Institute of Technology, and associates at Insert Therapeutics, Inc., now Calando Pharmaceuticals, Inc., hence the original name "IT-101". Its novel delivery mode allows the agent, and thus the toxic anti-cancer component, to be preferentially accumulated in cancer tissue. In turn, toxic side effect are expected to be reduced. The technology was licensed by Calando and Caltech to Cerulean Pharma, in 2009. Rationale Camptothecin (CPT), an alkaloid extract with poor water solubility from plants such as '' Camptotheca acuminata'', exhibits anti-cancer activity possibly due, at least in ...
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Camptothecin
Camptothecin (CPT) is a topoisomerase inhibitor. It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs. It was isolated from the bark and stem of ''Camptotheca acuminata'' (Camptotheca, Happy tree), a tree native to China used in traditional Chinese medicine. It has been used clinically more recently in China for the treatment of gastrointestinal tumors. CPT showed anticancer activity in preliminary clinical trials, especially against breast, ovarian, colon, lung, and stomach cancers. However, it has low solubility and adverse effects have been reported when used therapeutically, so synthetic and medicinal chemists have developed numerous syntheses of camptothecin and various derivatives to increase the benefits of the chemical, with good results. Four CPT analogues have been approved and are used in cancer chemotherapy today, topotecan, irinotecan, belotecan, and trastuzumab deruxtecan. Camptothecin has also ...
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Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of ...
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Alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar structure may also be termed alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and, more rarely, other elements such as chlorine, bromine, and phosphorus.Chemical Encyclopedia: alkaloids
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Alkaloids are produced by a large variety of organisms including , , Medicinal plant, plants, an ...
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City Of Hope National Medical Center
City of Hope is a private, not-for-profit clinical research center, hospital and graduate school located in Duarte, California, United States. The center's main campus resides on of land adjacent to the boundaries of Duarte and Irwindale, with a network of clinical practice locations throughout Southern California, satellite offices in Monrovia and Irwindale, and regional fundraising offices throughout the United States. City of Hope is best known as a cancer treatment center. It has been designated a Comprehensive Cancer Center by the National Cancer Institute. City of Hope has also been ranked one of the nation's Best Cancer Hospitals by ''U.S. News & World Report'' for over ten years and is a founding member of the National Comprehensive Cancer Network. City of Hope played a role in the development of synthetic human insulin in 1978. The center has performed 13,000 hematopoietic stem cell transplants as of 2016 with patient outcomes that consistently exceed national avera ...
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Clinical Trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietary choices, dietary supplements, and medical devices) and known interventions that warrant further study and comparison. Clinical trials generate data on dosage, safety and efficacy. They are conducted only after they have received health authority/ethics committee approval in the country where approval of the therapy is sought. These authorities are responsible for vetting the risk/benefit ratio of the trial—their approval does not mean the therapy is 'safe' or effective, only that the trial may be conducted. Depending on product type and development stage, investigators initially enroll volunteers or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary i ...
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Enhanced Permeability And Retention Effect
The enhanced permeability and retention (EPR) effect is a controversial concept by which molecules of certain sizes (typically liposomes, nanoparticles, and macromolecular drugs) tend to accumulate in tumor tissue much more than they do in normal tissues. The general explanation that is given for this phenomenon is that, in order for tumor cells to grow quickly, they must stimulate the production of blood vessels. VEGF and other growth factors are involved in cancer angiogenesis. Tumor cell aggregates as small as 150–200 μm, start to become dependent on blood supply carried out by neovasculature for their nutritional and oxygen supply. These newly formed tumor vessels are usually abnormal in form and architecture. They are poorly aligned defective endothelial cells with wide fenestrations, lacking a smooth muscle layer, or innervation with a wider lumen, and impaired functional receptors for angiotensin II. Furthermore, tumor tissues usually lack effective lymphatic drainage. Al ...
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Polyethylene Glycol
Polyethylene glycol (PEG; ) is a polyether compound derived from petroleum with many applications, from industrial manufacturing to medicine. PEG is also known as polyethylene oxide (PEO) or polyoxyethylene (POE), depending on its molecular weight. The structure of PEG is commonly expressed as H−(O−CH2−CH2)n−OH. Uses Medical uses * Pharmaceutical-grade PEG is used as an excipient in many pharmaceutical products, in oral, topical, and parenteral dosage forms. * PEG is the basis of a number of laxatives (as ''MiraLax''). Whole bowel irrigation with polyethylene glycol and added electrolytes is used for bowel preparation before surgery or colonoscopy. * PEG is used in medicines for treating disimpaction and maintenance therapy for children with constipation. * When attached to various protein medications or drug carriers, polyethylene glycol of suitable length slows down their clearance from the blood. * The possibility that PEG could be used to fuse axons is being ...
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Glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of alpha-helices in secondary protein structure due to its compact form. For the same reason, it is the most abundant amino acid in collagen triple-helices. Glycine is also an inhibitory neurotransmitter – interference with its release within the spinal cord (such as during a ''Clostridium tetani'' infection) can cause spastic paralysis due to uninhibited muscle contraction. It is the only achiral proteinogenic amino acid. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom. History and etymology Glycine was discovered in 1820 by the French chemist He ...
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Topoisomerase
DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. Topological issues in DNA arise due to the intertwined nature of its double-helical structure, which, for example, can lead to overwinding of the DNA duplex during DNA replication and transcription. If left unchanged, this torsion would eventually stop the DNA or RNA polymerases involved in these processes from continuing along the DNA helix. A second topological challenge results from the linking or tangling of DNA during replication. Left unresolved, links between replicated DNA will impede cell division. The DNA topoisomerases prevent and correct these types of topological problems. They do this by binding to DNA and cutting the sugar-phosphate backbone of either one (type I topoisomerases) or both (type II topoisomerases) of the DNA strands. This transien ...
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Camptotheca Acuminata
''Camptotheca'' (happy tree, cancer tree, or tree of life) is a genus of medium-sized deciduous trees growing to tall, native to southern China and Tibet. The genus is usually included in the tupelo family Nyssaceae, but sometimes included (with the tupelos) in the dogwood family Cornaceae. The name "happy tree" is a direct translation of the Chinese name xǐ shù (Simplified Chinese:喜树). There are two species: *''Camptotheca acuminata'' Decne. *''Camptotheca lowreyana'' S.Y.Li The bark and stems of ''C. acuminata'' contain the alkaloid camptothecin. Several chemical derivatives of camptothecin are under investigation for or used as drugs for cancer treatment, including irinotecan, topotecan, rubitecan. ''C. acuminata'' also contains the chemical compounds trifolin and hyperoside Hyperoside is a chemical compound. It is the 3-''O''-galactoside of quercetin. Natural occurrences Hyperoside has been isolated from ''Drosera rotundifolia'', from the Lamiaceae ''Stachys sp ...
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Insert Therapeutics
Insert Therapeutics, Inc., now Calando Pharmaceuticals, Inc., is a medical research company that uses nanobiotechnology specializing in therapeutic agents that are conjugated, to facilitate and enhance drug delivery. The small company was founded in 2000, is located in Pasadena, California, and is owned by Arrowhead Research Corporation. The conjugates consist of a cyclodextrin-containing polymer (Cyclosert) that acts as a drug delivery system, and a linked medication, such as a chemotherapeutic drug of already proven efficacy. The size of the polymer is designed to “fit” the specific target, as vessels in a neoplasm allow for leakage of different sizes of polymers, as in healthy tissue. The leaked conjugates are concentrated in the target area. As a result, chemotherapeutic activity is locally enhanced, while general side effects are decreased. At least one of their conjugates, IT-101, has been investigated in a clinical trial Clinical trials are prospective biomedi ...
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Chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to reduce symptoms ( palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that block extracellular signals (signal transduction). The development of therapies with specific molecular or genetic targets, wh ...
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