TBL1XR1
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TBL1XR1
F-box-like/WD repeat-containing protein TBL1XR1 is a protein that in humans is encoded by the ''TBL1XR1'' gene. The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins that appear to have a regulatory function. It is believed that the WD40 repeats mediate protein–protein interactions, and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. Clinical significance Mutations in ''TBL1XR1'' cause Pierpont syndrome, which involves intellectual disability, a characteristic facial appearance and limb abnormalities. Mutations in ''TBL1XR1'' have been identified in lymphomas, including MYD88 wild-type Waldenstrom's macroglobulinemia. In prostate cancer, somatic copy-number gains (CNA) in ''TBL1XR1'' are present in around 15% of ...
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NAALADL2
N-Acetylated Alpha-Linked Acidic Dipeptidase Like 2 (NAALADL2) is a protein, encoded by the gene ''NAALADL2'' in humans. ''NAALADL2'' shares 25%–26% sequence identity and 45% sequence similarity with the glutamate carboxypeptidase II family which includes prostate cancer marker PSMA (''FOLH1''/''NAALAD1''). The NAALADL2 gene is a giant gene spanning 1.37 Mb which is approximately 49 times larger than the average gene size of 28 kb. Gene length is correlated with the number of transcript variants of a gene, as such, ''NAALADL2'' undergoes extensive alternative splicing and has 12 splice variants as defined by Ensembl. Function The current function of NAALADL2 is unknown. ''NAALADL2'' shows significant homology to N-acetylated alpha-linked acidic dipeptidase and transferrin receptors. While sharing some homology with the M28B metallopeptidase family, ''NAALADL2'' does not possess favoured amino acids at certain key positions that are highly conserved, and important for metallope ...
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WD40 Repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain. Structure WD40 domain-containing proteins have 4 to 16 repeating units, all of which are thought to form a circularised beta-propeller structure (see figure to the right). The WD40 domain is composed of several repeats, a variable region of around 20 residues at the beginning followed by a more common repeated set of residues. These repeats typically form a four stranded anti-parallel beta sheet or blade. These blades come together to form a propeller with the most common being a 7 bladed beta propeller. The blades interlock so that the last beta strand of one repeat forms with the first three of the next repeat to form the 3D blade structure. Function WD40-re ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid ...
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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 activatio ...
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Phosphoinositide 3-kinase
Phosphoinositide 3-kinases (PI3Ks), also called phosphatidylinositol 3-kinases, are a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. PI3Ks are a family of related intracellular signal transducer enzymes capable of phosphorylating the 3 position hydroxyl group of the inositol ring of phosphatidylinositol (PtdIns). The pathway, with oncogene PIK3CA and tumor suppressor gene PTEN, is implicated in the sensitivity of cancer tumors to insulin and IGF1, and in calorie restriction. Discovery The discovery of PI3Ks by Lewis Cantley and colleagues began with their identification of a previously unknown phosphoinositide kinase associated with the polyoma middle T protein. They observed unique substrate specificity and chromatographic properties of the products of the lipid kinase, leading to the discovery that this phosphoinositide kinase ha ...
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BCL6
Bcl-6 (B-cell lymphoma 6) is a protein that in humans is encoded by the ''BCL6'' gene. BCL6 is a master transcription factor for regulation of T follicular helper cells (TFH cells) proliferation. BCL6 has three evolutionary conserved structural domains. The interaction of these domains with corepressors allows for germinal center development and leads to B cell proliferation. The ''deletion'' of BCL6 is known to lead to failure to germinal center formation in the follicles of the lymph nodes, preventing B cells from undergoing somatic hypermutation. ''Mutations'' in BCL6 can lead to B cell lymphomas because it promotes unchecked B cell growth. Clinically, BCL6 can be used to diagnose B cell lymphomas and is shown to be upregulated in a number of cancers. Other BCL genes, including BCL2, BCL3, BCL5, BCL7A, BCL9, and BCL10, also have clinical significance in lymphoma. Normal Physiological Function Structure The protein encoded by the BCL6 gene is a zinc finger transcrip ...
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Neuroendocrine Tumor
Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine ( hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body. Although there are many kinds of NETs, they are treated as a group of tissue because the cells of these neoplasms share common features, such as looking similar, having special secretory granules, and often producing biogenic amines and polypeptide hormones. Classification WHO The World Health Organization (WHO) classification scheme places neuroendocrine tumors into three main categories, which emphasize the tumor grade rather than the anatomical origin: * well-differentiated neuroendocrine tumours, further subdivided into tumors with benign and those with uncertain behavior * well-differentiated (low grade) neuroendocrine carcinomas with low-grade malignant behavior * poorly differentiated (high grad ...
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Castrate-Resistant
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 sym ...
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Lymph Node
A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that include B and T cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles including cancer cells, but have no detoxification function. In the lymphatic system a lymph node is a secondary lymphoid organ. A lymph node is enclosed in a fibrous capsule and is made up of an outer cortex and an inner medulla. Lymph nodes become inflamed or enlarged in various diseases, which may range from trivial throat infections to life-threatening cancers. The condition of lymph nodes is very important in cancer staging, which decides the treatment to be used and determines the prognosis. Lymphadenopathy refers to glands that are enlarged or swollen. When inflamed or enlarged, lymph nodes can be ...
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Resection Margin
A resection margin or surgical margin is the margin of apparently non-tumorous tissue around a tumor that has been surgically removed, called " resected", in surgical oncology. The resection is an attempt to remove a cancer tumor so that no portion of the malignant growth extends past the edges or margin of the removed tumor and surrounding tissue. These are retained after the surgery and examined microscopically by a pathologist to see if the margin is indeed free from tumor cells. If cancerous cells are found at the edges the operation is much less likely to achieve the desired results. Residual tumour at the primary site after treatment (it does not address the surgical margin as commonly believed) is classified by the pathologist as (AJCC 8th Edition): * R0 - no cancer cells seen microscopically at the primary tumour site. * R1 - cancer cells present microscopically at the primary tumour site. * R2 - Macroscopic residual tumour at primary cancer site or regional lymph nodes. ...
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Cancer Staging
Cancer staging is the process of determining the extent to which a cancer has developed by growing and spreading. Contemporary practice is to assign a number from I to IV to a cancer, with I being an isolated cancer and IV being a cancer that has spread to the limit of what the assessment measures. The stage generally takes into account the size of a tumor, whether it has invaded adjacent organs, how many regional (nearby) lymph nodes it has spread to (if any), and whether it has appeared in more distant locations ( metastasized). The staging system is not applicable to astrocytoma, which is instead expressed as "grade I–IV". Grade IV astrocytoma, more commonly referred to as glioblastoma multiforme, is a universally fatal primary brain cancer most commonly seen in the seventh decade of life. TNM staging system Cancer staging can be divided into a clinical stage and a pathologic stage. In the TNM (Tumor, Node, Metastasis) system, clinical stage and pathologic stage are d ...
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Gleason Grading System
The Gleason grading system is used to help evaluate the prognosis of men with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prognosis and helps guide therapy. A Gleason score is given to prostate cancer based upon its microscopic appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 to 10, with higher numbers indicating greater risks and higher mortality. The system is widely accepted and used for clinical decision making even as it is recognised that certain biomarkers, like ACP1 expression, might yield higher predictive value for future disease course. The histopathologic diagnosis of prostate cancer has implications for the possibility and methodology of Gleason scoring. For example, it is not recommended in signet-ring adenocarcinoma or urothelial carcinoma of the prostate, and the sc ...
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