Esophagogastric Junctional Adenocarcinoma
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Esophagogastric Junctional Adenocarcinoma
Oesophagogastric junctional adenocarcinoma (OGJ adenocarcinoma) is a cancer of the lower part of the oesophagus with a rising incidence in Western countries. This disease is often linked to Barrett's oesophagus. The incidence of OGJ adenocarcinoma is rising rapidly in Western countries especially in recent decades, in contrast to the declining frequency of distal gastric adenocarcinoma. Treatment options for adenocarcinomas involving the oesophagogastric junction are limited and the overall prognosis is extremely poor, with a five-year survival rate of approximately 30% with surgery alone. Risk factors There are several established risk factors for OGJ adenocarcinoma. The biggest risk factors include gastroesophageal reflux disease (GERD) and Barrett's oesophagus. Other risk factors include smoking (with a twofold-increase) and obesity. Clinical features The clinical features of OGJ adenocarcinoma are variable depending on the extent of the tumor. Early stages are oftentime ...
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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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Microsatellite Instability
Microsatellite instability (MSI) is the condition of genetic hypermutability (predisposition to mutation) that results from impaired DNA mismatch repair (MMR). The presence of MSI represents phenotypic evidence that MMR is not functioning normally. MMR corrects errors that spontaneously occur during DNA replication, such as single base mismatches or short insertions and deletions. The proteins involved in MMR correct polymerase errors by forming a complex that binds to the mismatched section of DNA, excises the error, and inserts the correct sequence in its place. Cells with abnormally functioning MMR are unable to correct errors that occur during DNA replication and consequently accumulate errors. This causes the creation of novel microsatellite fragments. Polymerase chain reaction-based assays can reveal these novel microsatellites and provide evidence for the presence of MSI. Microsatellites are repeated sequences of DNA. These sequences can be made of units of 1 to 6 b ...
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Trastuzumab
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin. Common side effects include fever, infection, cough, headache, trouble sleeping, and rash. Other severe side effects include heart failure, allergic reactions, and lung disease. Use during pregnancy may harm the baby. Trastuzumab works by binding to the HER2 receptor and slowing down cell replication. Trastuzumab was approved for medical use in the United States in September 1998, and in the European Union in August 2000. It is on the World Health Organization's List of Essential Medicines. A biosimilar was approved in the European Union in November 2017, and in the United States in December 2018. Medical uses The sa ...
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HER2/neu
Receptor tyrosine-protein kinase erbB-2 is a protein that in humans is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently referred to as ''HER2'' (human epidermal growth factor receptor 2) or CD340 (cluster of differentiation 340). HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. But contrary to other member of the ERBB family, HER2 does not directly bind ligand. HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. In recent years the protein has become an important biomarker and target of therapy for approximately 30% of breast cancer patients. Name ''H ...
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ARID1A
AT-rich interactive domain-containing protein 1A is a protein that in humans is encoded by the ''ARID1A'' gene. Function ARID1A is a member of the SWI/SNF family, whose members have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodelling complex SWI/SNF, which is required for transcriptional activation of genes normally repressed by chromatin. It possesses at least two conserved domains that could be important for its function. First, it has an ARID domain, which is a DNA-binding domain that can specifically bind an AT-rich DNA sequence known to be recognized by a SWI/SNF complex at the beta-globin locus. Second, the C-terminus of the protein can stimulate glucocorticoid receptor-dependent transcriptional activation. It is thought that the protein encoded by this gene confers specificity to the SWI/SNF complex a ...
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SYNE1
Enaptin also known as nesprin-1 or synaptic nuclear envelope protein 1 (syne-1) is an actin-binding protein that in humans that is encoded by the SYNE1 gene. Function This gene encodes a spectrin repeat containing protein expressed in skeletal and smooth muscle, and peripheral blood lymphocytes, that localizes to the nuclear membrane. Enaptin is a nuclear envelope protein found in human myocytes and synapses, which is made up of 8,797 amino acids. Enaptin is involved in the maintenance of nuclear organization and structural integrity, tethering the cell nucleus to the cytoskeleton by interacting with the nuclear envelope and with F-actin in the cytoplasm. Structure Enaptin contains a coiled alpha-helical region and a large beta-sheet region in the upper part and at least four alpha-helices spliced together, indicating the similarity with collagen. The protein is made up of three main parts, as can be seen in the diagram: cytoplasmic (1-8746), anchor for type IV membrane pr ...
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TP53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often spoken of as, a single protein) are crucial in vertebrates, where they prevent cancer formation. As such, p53 has been described as "the guardian of the genome" because of its role in conserving stability by preventing genome mutation. Hence ''TP53'' ''italics'' are used to denote the ''TP53'' gene name and distinguish it from the protein it encodes is classified as a tumor suppressor gene. The name p53 was given in 1979 describing the apparent molecular mass; SDS-PAGE analysis indicates that it is a 53-kilodalton (kDa) protein. However, the actual mass of the full-length p53 protein (p53α) based on the sum of masses of the amino acid residues is only 43.7 kDa. This difference is due to the high number of proline residues in the protein, ...
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ESRRB
Estrogen-related receptor beta (ERR-β), also known as ESRRB or NR3B2 (nuclear receptor subfamily 3, group B, member 2), is a nuclear receptor that in humans is encoded by the ''ESRRB'' (Estrogen Related Receptor Beta) gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ... . Function ESRRB has been shown to be vital for the transition between a naïve pluripotent and primed pluripotent state in mammalian cells, and NANOG controls the expression of ESRRB in this scenario. References Further reading * * * * * * * * * * * * * {{Estrogen-related receptor modulators Intracellular receptors Transcription factors ...
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FGFR4
Fibroblast growth factor receptor 4 is a protein that in humans is encoded by the ''FGFR4'' gene. FGFR4 has also been designated as CD334 (cluster of differentiation 334). The protein encoded by this gene is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. The genomic organization of this gene, compared to members 1-3, encompasses 18 exons rather than 19 or 20. Although alternative splicing has ...
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HGF (gene)
Hepatocyte growth factor (HGF) or scatter factor (SF) is a paracrine cellular growth, motility and morphogenic factor. It is secreted by mesenchymal cells and targets and acts primarily upon epithelial cells and endothelial cells, but also acts on haemopoietic progenitor cells and T cells. It has been shown to have a major role in embryonic organ development, specifically in myogenesis, in adult organ regeneration, and in wound healing. Function Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor. Hepatocyte growth factor is secreted by mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial origin. Its ability to stimulate mitogenesis, cell motility, and matrix invasion gives it a central role in angiogenesis, tumorogenesis, and tissue regeneration. Structure It is secreted as a single inactive polypeptide and is c ...
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CR2 (gene)
Complement receptor type 2 (CR2), also known as complement C3d receptor, Epstein-Barr virus receptor, and CD21 (cluster of differentiation 21), is a protein that in humans is encoded by the CR2 gene. CR2 is involved in the complement system. It binds to iC3b (inactive derivative of C3b), C3dg, or C3d.Frank K, Atkinson JP (2001). "Complement system." In Austen KF, Frank K, Atkinson JP, Cantor H. eds. ''Samter's Immunologic Diseases, 6th ed. Vol. 1,'' p. 281-298, Philadelphia: Lippincott Williams & Wilkins, . B cells express CR2 receptors on their surfaces, allowing the complement system to play a role in B-cell activation and maturation. Interactions Complement receptor 2 interacts with CD19, and, on mature B cells, forms a complex with CD81 (TAPA-1). The CR2-CD19-CD81 complex is often called the B cell co-receptor complex,Abbas AK, Lichtman AH (2003). ''Cellular and Molecular Immunology, 5th ed.'' Philadelphia: Saunders, because CR2 binds to opsonized antigens through attache ...
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Somatic Mutation
A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline mutations, which can be passed on to the descendants of an organism, somatic mutations are not usually transmitted to descendants. This distinction is blurred in plants, which lack a dedicated germline, and in those animals that can reproduce asexually through mechanisms such as budding, as in members of the cnidarian genus ''Hydra''. While somatic mutations are not passed down to an organism's offspring, somatic mutations will be present in all descendants of a cell within the same organism. Many cancers are the result of accumulated somatic mutations. Fraction of cells affected The term somatic generally refers to the cells of the body, in contrast to the reproductive (germline) cells, which give rise to the egg or sperm. For example, in ...
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