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Neuroendocrine Differentiation
Neuroendocrine differentiation is a term primarily used in relation to prostate cancers that display a significant neuroendocrine cell population on histopathological examination. These types of prostate cancer comprise true neuroendocrine cancers, such as Small-cell carcinoma, small cell carcinoma, carcinoid and carcinoid-like tumors, as well as prostatic adenocarcinoma exhibiting focal Neuroendocrine cell, neuroendocrine phenotype. __TOC__ Normal function Prostatic neuroendocrine cells, also known as endocrine-paracrine cells, are part of a larger regulatory cell population scattered throughout the whole organism, collectively known as diffuse neuroendocrine system or APUD cells. Neuroendocrine cells are present in all regions of the human prostate, most notably around the ducts, but also in the acinar epithelium and prostatic urothelium; there is a significant inter-individual variability. Two morphologic types have been described: the open type, extending slender apical processe ...
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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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Cholecystokinin
Cholecystokinin (CCK or CCK-PZ; from Greek ''chole'', "bile"; ''cysto'', "sac"; ''kinin'', "move"; hence, ''move the bile-sac (gallbladder)'') is a peptide hormone of the gastrointestinal system responsible for stimulating the digestion of fat and protein. Cholecystokinin, formerly called pancreozymin, is synthesized and secreted by enteroendocrine cells in the duodenum, the first segment of the small intestine. Its presence causes the release of digestive enzymes and bile from the pancreas and gallbladder, respectively, and also acts as a hunger suppressant. History Evidence that the small intestine controls the release of bile was uncovered as early as 1856, when French physiologist Claude Bernard showed that when dilute acetic acid was applied to the orifice of the bile duct, the duct released bile into the duodenum. In 1903 the French physiologist showed that this reflex was not mediated by the nervous system. In 1904 the French physiologist Charles Fleig showed that the ...
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Ki-67 (protein)
Antigen KI-67, also known as Ki-67, Ki-67 or MKI67 (Marker Of Proliferation Ki-67), is a protein that in humans is encoded by the ''MKI67'' gene (antigen identified by monoclonal antibody Ki-67). Function Antigen KI-67 is a nuclear protein that is associated with cellular proliferation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Furthermore, it is associated with ribosomal RNA transcription. Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis. Use as a marker of proliferating cells The Ki-67 protein (also known as MKI67) is a cellular marker for proliferation, and can be used in immunohistochemistry. It is strictly associated with cell proliferation. During interphase, the Ki-67 antigen can be exclusively detected within the cell nucleus, whereas in mitosis most of the protein is relocated to the surface of the chro ...
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Prostatic Acid Phosphatase
Prostatic acid phosphatase (PAP), also prostatic specific acid phosphatase (PSAP), is an enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer or other diseases. The highest levels of acid phosphatase are found in metastasized prostate cancer. Diseases of the bone, such as Paget's disease or hyperparathyroidism, diseases of blood cells, such as sickle-cell disease or multiple myeloma or lysosomal storage diseases, such as Gaucher's disease, will show moderately increased levels. Certain medications can cause temporary increases or decreases in acid phosphatase levels. Manipulation of the prostate gland through massage, biopsy or rectal exam before a test may increase the level. Its physiological function may be associated with the liquefaction process of semen.Page 1135-1136 in: Use in prostatic cancer prognosis Serum marker PSAP was used to monitor and assess progression of prostate cancer until the introduction of prostate sp ...
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Prostate-specific Antigen
Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the ''KLK3'' gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland. PSA is produced for the ejaculate, where it liquefies semen in the seminal coagulum and allows sperm to swim freely. It is also believed to be instrumental in dissolving cervical mucus, allowing the entry of sperm into the uterus. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders. PSA is not uniquely an indicator of prostate cancer, but may also detect prostatitis or benign prostatic hyperplasia. Medical uses Prostate cancer Screening Clinical practice guidelines for prostate cancer screening vary and are controversial, in part due to uncertainty as to whether the benefits o ...
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TP63
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the ''TP63'' (also known as the '' p63'') gene. The ''TP63'' gene was discovered 20 years after the discovery of the ''p53'' tumor suppressor gene and along with '' p73'' constitutes the ''p53'' gene family based on their structural similarity. Despite being discovered significantly later than ''p53'', phylogenetic analysis of ''p53'', ''p63'' and ''p73'', suggest that ''p63'' was the original member of the family from which ''p53'' and ''p73'' evolved. Function Tumor protein p63 is a member of the p53 family of transcription factors. p63 -/- mice have several developmental defects which include the lack of limbs and other tissues, such as teeth and mammary glands, which develop as a result of interactions between mesenchyme and epithelium. TP63 encodes for two main isoforms by alternative promoters (TAp63 and ΔNp63). ΔNp63 is involved i ...
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Cytokeratin
Cytokeratins are keratin proteins found in the intracytoplasmic cytoskeleton of epithelial tissue. They are an important component of intermediate filaments, which help cells resist mechanical stress. Expression of these cytokeratins within epithelial cells is largely specific to particular organs or tissues. Thus they are used clinically to identify the cell of origin of various human tumors. Naming The term ''cytokeratin'' began to be used in the late 1970s, when the protein subunits of keratin intermediate filaments inside cells were first being identified and characterized. In 2006 a new systematic nomenclature for mammalian keratins was created, and the proteins previously called ''cytokeratins'' are simply called ''keratins'' (human epithelial category). For example, cytokeratin-4 (CK-4) has been renamed keratin-4 (K4). However, they are still commonly referred to as cytokeratins in clinical practice. Types There are two categories of cytokeratins: the acidic type I cyt ...
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Human Chorionic Gonadotropin
Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation. The presence of hCG is detected in some pregnancy tests (HCG pregnancy strip tests). Some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a cancer diagnosis and, if high enough, paraneoplastic syndromes, however, it is not known whether this production is a contributing cause, or an effect of carcinogenesis. The pituitary analog of hCG, known as luteinizing hormone (LH), is produced in the pituitary gland of males and females of all ages. Various endogenous forms of hCG exist. The measurement of these diverse forms is used in the diagnosis of pregnancy and a variety of disease states. Preparations of hCG from various sources have also been used therapeutically, by ...
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Neurotensin
Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system. Neurotensin was first isolated from extracts of bovine hypothalamus based on its ability to cause a visible vasodilation in the exposed cutaneous regions of anesthetized rats. Neurotensin is distributed throughout the central nervous system, with highest levels in the hypothalamus, amygdala and nucleus accumbens. It induces a variety of effects, including analgesia, hypothermia and increased locomotor activity. It is also involved in regulation of dopamine pathways. In the periphery, neurotensin is found in enteroendocrine cells of the small intestine, where it leads to secretion and smooth muscle contraction. Sequence and biosynthesis Neurotensin shares significant sequence similarity in its 6 C-terminal amino acids with several other neuropeptides, including neuromedin N (which is derived ...
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Synaptophysin
Synaptophysin, also known as the major synaptic vesicle protein p38, is a protein that in humans is encoded by the ''SYP'' gene. Genomics The gene is located on the short arm of X chromosome (Xp11.23-p11.22). It is 12,406 bases in length and lies on the minus strand. The encoded protein has 313 amino acids with a predicted molecular weight of 33.845 kDa. Molecular biology The protein is a synaptic vesicle glycoprotein with four transmembrane domains weighing 38kDa. It is present in neuroendocrine cells and in virtually all neurons in the brain and spinal cord that participate in synaptic transmission. It acts as a marker for neuroendocrine tumors, and its ubiquity at the synapse has led to the use of synaptophysin immunostaining for quantification of synapses. The exact function of the protein is unknown: it interacts with the essential synaptic vesicle protein synaptobrevin, but when the synaptophysin gene is experimentally inactivated in animals, they still develop and ...
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Androgen Receptor
The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone in the cytoplasm and then translocating into the nucleus. The androgen receptor is most closely related to the progesterone receptor, and progestins in higher dosages can block the androgen receptor. The main function of the androgen receptor is as a DNA-binding transcription factor that regulates gene expression; however, the androgen receptor has other functions as well. Androgen-regulated genes are critical for the development and maintenance of the male sexual phenotype. Function Effect on development In some cell types, testosterone interacts directly with androgen receptors, whereas, in others, testosterone is converted by 5-alpha-reductase to dihydrotestosterone, an even more potent agonist for androgen receptor activation. T ...
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Adrenomedullin
Adrenomedullin (ADM or AM) is a vasodilator peptide hormone of uncertain significance in human health and disease. It was initially isolated in 1993 from a pheochromocytoma, a tumor of the adrenal medulla: hence the name. In humans ADM is encoded by the ''ADM'' gene. ADM is a peptide expressed by all tissues, and found in the circulation. A similar peptide named adreomedullin2 was reported in rats in 2004 which exhibits a similar function. Function Adrenomedullin may function as a hormone in the circulation control because it is found in blood in a considerable concentration. It was initially identified as a vasodilator, and some argued that it is the most potent endogenous vasodilatory peptide found in the body. Differences in opinion regarding the ability of AM to relax vascular tone may arise from the differences in the model system used. Other effects of AM include stimulating the growth of new blood vessels (angiogenesis) and increasing the tolerance of cells to oxidative ...
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