|
Colibactin
Colibactin is a genotoxic metabolite produced by ''Escherichia coli'' and other ''Enterobacteriaceae'' ("enteric bacteria") believed to cause mutations leading to colorectal cancer and the progression of colorectal cancer, especially in early-onset colorectal cancers. Colibactin is a polyketide peptide that can form interstrand crosslinks in DNA. Colibactin is only produced by bacterial strains containing a polyketide synthase genomic island (''pks'') or ''clb'' biosynthetic gene cluster. About 20% of humans in high-income countries are colonized with ''E. coli'' that harbor the ''pks'' island. Colibactin forms DNA inter-strand cross-links by alkylation of adenine moieties on opposing DNA strands. It induces lytic development in certain bacteria that contain prophages. Colibactin has been previously demonstrated to have a characteristic mutational signature. The same mutational signature was discovered in several cohorts of colon cancer patients, and in smaller numbers of pati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Colorectal Cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal bleeding, blood in the stool, a change in bowel movements, weight loss, abdominal pain and fatigue. Most colorectal cancers are due to lifestyle factors and genetic disorders. Risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red meat, processed meat, and alcohol (drug), alcohol. Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of cases. It typically starts as a adenoma, benign tumor, often in the form of a colorectal poly ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Genotoxicity
Genotoxicity is the chemical property, property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with mutagenicity, all mutagens are genotoxic, but some genotoxic substances are not mutagenic. The alteration can have direct or indirect effects on the DNA: the induction of mutations, mistimed event activation, and direct DNA damage leading to mutations. The permanent, heritable changes can affect either somatic cells of the organism or germ cells to be passed on to future generations. Cells prevent expression of the genotoxic mutation by either DNA repair or apoptosis; however, the damage may not always be fixed leading to mutagenesis. To bioassay, assay for genotoxic molecules, researchers assay for DNA damage in cells exposed to the toxic substrates. This DNA damage can be in the form of single- and double-strand breaks, loss of excision repair, cross-linking, alkali-labile sites, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adenine
Adenine (, ) (nucleoside#List of nucleosides and corresponding nucleobases, symbol A or Ade) is a purine nucleotide base that is found in DNA, RNA, and Adenosine triphosphate, ATP. Usually a white crystalline subtance. The shape of adenine is complementary and pairs to either thymine in DNA or uracil in RNA. In cells adenine, as an independent molecule, is rare. It is almost always covalent bond, covalently bound to become a part of a larger biomolecule. Adenine has a central role in cellular respiration. It is part of adenosine triphosphate which provides the energy that drives and supports most activities in living cell (biology), cells, such as Protein biosynthesis, protein synthesis, chemical synthesis, muscle contraction, and nerve impulse propagation. In respiration it also participates as part of the cofactor (biochemistry), cofactors nicotinamide adenine dinucleotide, flavin adenine dinucleotide, and Coenzyme A. It is also part of adenosine, adenosine monophosphate, cy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Polyketides
In organic chemistry, polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (, or its reduced forms) and methylene () groups: . First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. Biotechnology has enabled discovery of more naturally-occurring polyketides and evolution of new polyketides with novel or improved bioactivity. History Naturally produced polyketides by various plants and organisms have been used by humans since before studies on them began in the 19th and 20th century. In 1893, J. Norman Collie synthesized detectable amounts of orcinol by ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alkylating Agents
Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting alkylation. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For upgrading of petroleum, alkylation produces a premium blending stock for gasoline. In medicine, alkylation of DNA is used in chemotherapy to damage the DNA of cancer cells. Alkylation is accomplished with the class of drugs called alkylating antineoplastic agents. Nucleophilic alkylating agents Nucleophilic alkylating agents deliver the equivalent of an alkyl anion ( carbanion). The formal "alkyl anion" attacks an electrophile, forming a new covalent bond ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thiazoles
Thiazole (), or 1,3-thiazole, is a 5-membered heterocyclic compound that contains both sulfur and nitrogen. The term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular formula C3H3NS. The thiazole ring is notable as a component of the vitamin thiamine (B1). Molecular and electronic structure Thiazoles are members of the azoles, heterocycles that include imidazoles and oxazoles. Thiazole can also be considered a functional group when part of a larger molecule. Being planar thiazoles are characterized by significant pi-electron delocalization and have some degree of aromaticity, more so than the corresponding oxazoles. This aromaticity is evidenced by the 1H NMR chemical shift of the ring protons, which absorb between 7.27 and 8.77 ppm, indicating a strong diamagnetic ring current. The calculated pi-electron density marks C5 as the primary site for electrophilic substitution, and C2-H a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Spiro Compounds
In organic chemistry, spiro compounds are compounds that have at least two molecular rings sharing one common atom. Simple spiro compounds are bicyclic (having just two rings). The presence of only one common atom connecting the two rings distinguishes spiro compounds from other bicyclics.For all four categories, see The specific chapters can be found aan respectively, same access date. For the description featuring adjacent atoms for all but the isolated category, see Clayden, op. cit. Spiro compounds may be fully carbocyclic (all carbon) or heterocyclic (having one or more non-carbon atom). One common type of spiro compound encountered in educational settings is a heterocyclic one— the acetal formed by reaction of a diol with a cyclic ketone. The common atom that connects the two (or sometimes three) rings is called the ''spiro atom''. In carbocyclic spiro compounds like spiro .5ndecane, the spiro-atom is a quaternary carbon, and as the ''-ane'' ending implies, these ar ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclopropanes
Cyclopropanes are a family of organic compounds containing the cyclopropyl group. The parent is cyclopropane (). Synthesis and reactions Most cyclopropanes are not prepared from the parent cyclopropane, which is somewhat inert. Instead, yclopropyl groups are often prepared by cyclization of 1,3-difunctional alkanes. An example of the former, cyclopropyl cyanide is prepared by the reaction of 4- chlorobutyronitrile with a strong base. Phenylcyclopropane is produced analogously from the 1,3-dibromide. A second major route to cyclopropanes entails addition of methylene (or its substituted derivatives) to an alkene, a process called cyclopropanation. Substituted cyclopropanes undergo the reactions associated with the cyclopropyl ring or the substituents. Vinylcyclopropanes are a special case as they undergo vinylcyclopropane rearrangement. Simple substituted cyclopropanes * Chlorocyclopropane * Cyclopropane carboxylic acid * Cyclopropyl amine * Cyclopropyl cyanide * Cycloprop ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mutagens
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in animals, such mutagens can therefore be carcinogens, although not all necessarily are. All mutagens have characteristic mutational signatures with some chemicals becoming mutagenic through cellular processes. The process of DNA becoming modified is called mutagenesis. Not all mutations are caused by mutagens: so-called "spontaneous mutations" occur due to spontaneous hydrolysis, errors in DNA replication, repair and recombination. Discovery The first mutagens to be identified were carcinogens, substances that were shown to be linked to cancer. Tumors were described more than 2,000 years before the discovery of chromosomes and DNA; in 500 B.C., the Greek physician Hippocrates named tumors resembling a crab ''karkinos'' (from which the w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bacterial Toxins
Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by ''Clostridium botulinum'' and less frequently by other ''Clostridium'' species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxins. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biolo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Indel
Indel (insertion-deletion) is a molecular biology term for an insertion or deletion of bases in the genome of an organism. Indels ≥ 50 bases in length are classified as structural variants. In coding regions of the genome, unless the length of an indel is a multiple of 3, it will produce a frameshift mutation. For example, a common microindel which results in a frameshift causes Bloom syndrome in the Jewish or Japanese population. Indels can be contrasted with a point mutation. An indel inserts or deletes nucleotides from a sequence, while a point mutation is a form of substitution that ''replaces'' one of the nucleotides without changing the overall number in the DNA. Indels can also be contrasted with Tandem Base Mutations (TBM), which may result from fundamentally different mechanisms. A TBM is defined as a substitution at adjacent nucleotides (primarily substitutions at two adjacent nucleotides, but substitutions at three adjacent nucleotides have been observed). In ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Adenomatous Polyposis Coli
Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the ''APC'' gene. The APC protein is a Down-regulation, negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the ''APC'' gene may result in colorectal cancer and desmoid tumors. ''APC'' is classified as a tumor suppressor gene. Tumor suppressor genes prevent the uncontrolled growth of cells that may result in cancerous tumors. The protein made by the ''APC'' gene plays a critical role in several cellular processes that determine whether a cell may develop into a tumor. The APC protein helps control how often a cell divides, how it attaches to other cells within a tissue, how the cell polarizes and the morphogenesis of the 3D structures, or whether a cell moves within or away from tissue. This protein also helps ensure that the chromosome number in cells produced through c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
