• Mutations of the VHL gene are associated with Von Hippel-Lindau disease, which is characterized by hemangioblastomas of the brain, spinal cord and retina. (wikipedia.org)
  • Nonsense or deletion mutations of VHL protein have been linked to type 1 VHL with a low risk of pheochromocytoma (adrenal gland tumors). (wikipedia.org)
  • Mutations in the VHL gene increase the risk of developing tumors of the nervous system called paragangliomas or pheochromocytomas (a type of paraganglioma). (medlineplus.gov)
  • Other spontaneous mutations found in this condition, called somatic mutations, are acquired during a person's lifetime and are present only in the tumor cells. (medlineplus.gov)
  • The VHL gene mutations found in nonsyndromic paraganglioma or pheochromocytoma change single amino acids in the VHL protein or create an abnormally short protein. (medlineplus.gov)
  • The other VHL gene mutations that can cause familial erythrocytosis also change single amino acids in the VHL protein. (medlineplus.gov)
  • Mutations of the VHL gene are associated with Von Hippel-Lindau disease. (standardofcare.com)
  • Mutations leading to VHL loss of function result in a number of diseases including the VHL syndrome, an inherited disorder due to the germline VHL alterations. (standardofcare.com)
  • The disease is caused by mutations of the VHL gene on the short arm of the third chromosome (3p26-p25). (standardofcare.com)
  • In VHL disease, genetic mutations cause alterations to the pVHL protein, usually to the HIF1α binding site. (standardofcare.com)
  • We describe areas where major inroads were initially achieved by targeting angiogenesis and by unraveling pathways in the heterogeneous tumors of mesenchymal origin-spurred by the identification of c-Kit-activating mutations in GIST and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). (cancernetwork.com)
  • Here, in Part I, we describe areas where major inroads were initially achieved by targeting angiogenesis (central to the biology of renal cell carcinoma and hepatocellular cancer) and by unraveling pathways in the heterogeneous tumors of mesenchymal origin-spurred by the identification of c-Kit-activating mutations in gastrointestinal stromal tumors (GIST) and the regressions that ensued when tumors harboring these mutations were exposed to the tyrosine kinase inhibitor imatinib (Gleevec). (cancernetwork.com)
  • Either at genomic or at proteomic level, mutations have significant impact on normal gene or protein function, and human diseases could be associated with mutations like nonsynonymous single-nucleotide variations (nsSNVs) on amino acids. (hindawi.com)
  • Yet how gene mutations affect protein activities through posttranslational modification sites have not been widely studied. (hindawi.com)
  • Although data of both gene mutations and PTMs are increasing fast, the proteome-wide analysis on the relationship between damaged PTMs and human diseases is not well studied. (hindawi.com)
  • Cancer is a complex genetic disease caused by abnormal alteration (mutations) in DNA sequences that leads to dyregulation of normal cellular processes thereby driving tumor growth. (intechopen.com)
  • Herein we selected a Mendelian genetics form of familial cancer such as hereditary tumor syndromic endocrine neoplasias caused by highly penetrant germline mutations leading to pheochromocytoma-paraganglioma syndromes. (intechopen.com)
  • Multiple endocrine neoplasia syndrome type 1 (MEN-1), loss-of-function germline mutations in the tumor suppressor gene MEN1 increase the risk of developing pituitary, parathyroid and pancreatic islet tumors, and less commonly thymic carcinoids, lipomas and benign adrenocortical tumors. (intechopen.com)
  • In the case of multiple endocrine neoplasia type 2 (MEN 2), gain-of-function germline mutations clustered in specific codons of the RET proto-oncogene increase the risk of developing medullary thyroid carcinoma (MTC), phaeochromocytoma and parathyroid tumors. (intechopen.com)
  • Mutations in the tumor suppressor gene VHL cause the disease, which commonly manifests as a variety of tumors such as hemangioblastomas of the retina and brain as well as renal cell carcinoma. (eyewiki.org)
  • However, 20% of mutations are de novo, and diagnosis for patients with a negative family history is confirmed with the occurrence of two VHL-related tumors and at least one retinal hemangioblastoma [3] . (eyewiki.org)
  • For example, studies suggest that ccRCC is closely associated with tumor suppressor von-Hippel Lindau ( VHL ) gene mutations that lead to stabilization of hypoxia inducible factors (HIF-1 α and HIF-2 α , also known as HIF1A and EPAS1) in both sporadic and familial forms [ 5 , 6 ]. (hindawi.com)
  • Mutations in VHL cause von Hippel-Lindau disease, a disorder that results in cysts and benign tumors. (the-scientist.com)
  • Germline mutations in the VHL gene predispose individuals to a variety of tumors, including renal carcinoma, CNS hemangioblastoma, islet cell tumors of the pancreas, and pheochromocytoma. (nih.gov)
  • We have recently developed an improved method of detecting germline mutations in the von Hippel-Lindau disease tumor suppressor gene. (nih.gov)
  • We observed gain of functions in VHL mutations, thereby stabilizing HIF2α protein and reprograming HIF2α genome-wide target gene transcriptional programs. (biomedcentral.com)
  • Together, our findings highlight the crucial role of pVHL-HIF dysregulation in VHL disease and strengthen the clinical relevance and significance of the missense mutations of Ser65 residue in pVHL in the familial VHL disease. (biomedcentral.com)
  • For instance, it can be activated by oncogenic mutations of PTEN, VHL, the RAS/mitogen-activated protein kinase (MAPK) pathway and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. (spandidos-publications.com)
  • A single normal cell randomly acquires a series of mutations that allows it to proliferate and to be transformed into a cancer cell (i.e., founding clone), which initiates tumor progression and recurrence. (nature.com)
  • We have previously shown that tumor founding clone mutations are able to predict tumor recurrence. (nature.com)
  • Why and how it is replacing past approaches in the management of solid tumors is the subject of this two-part overview. (cancernetwork.com)
  • The situation with solid tumors is considerably more complex, and the evolution of targeted therapies for these cancers is still in its infancy. (cancernetwork.com)
  • At present, and for some years to come, the treatment of most solid tumors will continue to rely on a patchwork of empirically derived and newly introduced molecularly targeted agents. (cancernetwork.com)
  • They may include a cyst that contains a clear fluid, but solid tumors are as common as cystic ones. (medscape.com)
  • Hypoxia is the most common characteristic in the microenvironment of solid tumors because tumor progression and metastasis depend on the ability of cancer cells to initiate angiogenesis and ensure the delivery of oxygen and nutrients ( 11 , 12 ). (jcancer.org)
  • Different levels of viable cell inoculum density produced contrasting effects between 255 solid tumors as compared to 72 malignant. (shengsci.com)
  • The VHL syndrome, generally caused by hereditary allele inactivation plus a tissue somatic mutation, is characterized by the occurrence of malignancies and increased expression of oncogenic genes, including VEGF, that allow tumor development and progression. (standardofcare.com)
  • PURPOSE: Tumor hypoxia modifies treatment efficacy and promotes tumor progression. (ox.ac.uk)
  • During the progression of colitis, genetic alterations associated with mucosal permeability [ e.g. those in extracellular matrix protein 1 ( ECM1 ), cadherin 1 ( CDH1 ), and hepatocyte nuclear factor 4 alpha ( HNF4A )] have been observed and considered to confer the risk of severe UC ( 11 , 12 ). (iiarjournals.org)
  • The most relevant articles summarising existing knowledge on RCC genomics, including tumour cell evolution and progression, were selected for this review. (springer.com)
  • Hypoxia is an important micro-environmental factor in promoting tumor progression. (spandidos-publications.com)
  • We hypothesized that a preneoplastic field of inflammation, telomere shortening, and senescence underlies tumor progression in UC progressors. (shengsci.com)
  • Autosomal Dominant Polycystic Kidney Disease (ADPKD) Polycystic kidney disease (PKD) is a hereditary disorder of renal cyst formation causing gradual enlargement of both kidneys, sometimes with progression to renal failure. (msdmanuals.com)
  • The Von Hippel-Lindau tumor suppressor also known as pVHL is a protein that, in humans, is encoded by the VHL gene. (wikipedia.org)
  • Hydroxylation of HIF creates a binding site for pVHL (the protein product of the VHL gene). (wikipedia.org)
  • pVHL directs the polyubiquitylation of HIF1A, ensuring that this protein will be degraded by the proteasome. (wikipedia.org)
  • In types 1, 2A and 2B the mutant pVHL is defective in HIF regulation, while type 2C mutant are defective in protein kinase C regulation. (wikipedia.org)
  • The VHL gene is located on chromosome 3p35 and encodes the pVHL protein [6] [4] . (eyewiki.org)
  • Under normal conditions, von Hippel-Lindau tumor suppressor pVHL ubiquitinates HIF for degradation. (eyewiki.org)
  • However, a lack of pVHL such as in VHL disease or hypoxia leads to stabilization of HIF-α and increased expression of tumorigenic molecules such as vascular endothelial growth factor (VEGF), platelet- derived growth factor peptide (PDGF), and transforming growth factor (TGF-a) [4] . (eyewiki.org)
  • Immunofluorescence studies show Hs-CUL-2 to be a cytosolic protein that can be translocated to the nucleus by pVHL. (nih.gov)
  • Germline heterozygous mutation of the VHL tumor suppressor gene, located on 3p25.3, encoding VHL tumor suppressor protein (pVHL), has been identified as the leading cause of VHL disease. (biomedcentral.com)
  • pVHL is best known as the substrate-binding subunit of an E3 ubiquitin ligase, which binds the transcription elongation factors C and B (elongin C/B) forms the VCB complex, then interacts with Cullin-2 (CUL2) and the RING finger protein RBX1 forming the VCB-CR complex(3). (biomedcentral.com)
  • These VHL alterations lead to a predisposition to a somatic second hit, causing of a variety of tumors and fluid filled cysts, sporadic tumors, such as cerebellar hemangioblastoma, pheochromocytoma, clear cell renal cell carcinoma, familial erythrocytosis type two, that result in increased expression of HIF target genes. (standardofcare.com)
  • VHL disease encompasses various types of tumors, including retinal or central nervous system hemangioblastoma (RH or CNSH), clear cell renal cell carcinoma (RCC), pheochromocytoma (PHE), multiple pancreatic cysts or tumors (PCT), epididymal or broad ligament cystadenomas and endolymphatic sac tumor. (biomedcentral.com)
  • The unexpected finding of a retinal or CNS hemangioblastoma or the diagnosis of a pheochromocytoma should prompt a search for other associated VHL disease features, as many of these patients may have the diagnostic criteria for VHL disease. (medscape.com)
  • Von Hippel-Lindau (VHL) disease is an autosomal dominant genetic neoplastic disorder caused by germline mutation or deletion of the VHL gene, characterized by the tendency to develop multisystem benign or malignant tumors. (biomedcentral.com)
  • von Hippel-Lindau (VHL) disease, or von Hippel-Lindau syndrome, is a rare genetic disorder characterized by visceral cysts and benign tumors in multiple organ systems that have subsequent potential for malignant change. (medscape.com)
  • VHL disease is characterized by retinal capillary hemangiomas (also called benign vascular hamartomas). (medscape.com)
  • The mutation increases the overall risk for affected children to develop cancer or a number of benign tumors, especially at younger ages. (choa.org)
  • DICER1 syndrome, also known as DICER1-pleuropulmonary blastoma familial tumor predisposition syndrome, is a condition in which an individual is born with genetic changes that predispose him or her to develop benign and malignant tumors during childhood, through adolescence and, rarely, as an adult. (choa.org)
  • Pheochromocytomas are a feature of von Hippel-Lindau syndrome, but they and other paragangliomas can also occur nonsyndromically (without the other signs and symptoms of the syndrome). (medlineplus.gov)
  • As in von Hippel-Lindau syndrome, when the VHL protein is altered, the HIF-2α protein is not broken down, and instead builds up in cells. (medlineplus.gov)
  • The Von Hippel-Lindau syndrome (VHL) is a dominantly inherited hereditary cancer syndrome. (standardofcare.com)
  • The VHL syndrome is inherited by one mutation in the VHL protein that causes the protein's normal function to be lost or altered. (standardofcare.com)
  • Von Hippel-Lindau Syndrome (VHL) is a rare, autosomal dominant, familial neoplastic disease that affects the central nervous system and multiple organs such as the kidneys, pancreas, adrenals, and reproductive organs. (eyewiki.org)
  • They include tuberous sclerosis complex, Sturge-Weber syndrome , von Hippel-Lindau disease, and neurofibromatosis. (medscape.com)
  • Through the analysis of hereditary kidney cancer syndromes, many important novel genes have been discovered such as the VHL gene responsible for Von Hippel-Lindau syndrome, and several previously known genes were re-discovered to have new essential functions including MET which is mutated in hereditary papillary renal cell carcinoma, and FH , the gene responsible for hereditary leiomyomatosis renal cell carcinoma. (kumamoto-u.ac.jp)
  • A novel tumor suppressor gene FLCN was identified in 2002 as the gene responsible for another hereditary kidney cancer syndrome, Birt-Hogg-Dubé syndrome. (kumamoto-u.ac.jp)
  • Marfan Syndrome, porphyria, von Hippel-Lindau syndrome, osteogenesis imperfecta and Charcot-Marie-Tooth Disease are a few of the numerous genetic diseases associated with chromosome 3. (mc1-r.com)
  • The genetic changes that cause this syndrome are found in the DICER1 gene, a tumor suppressor gene. (choa.org)
  • Not all individuals with a diagnosis of DICER1 syndrome will develop tumors or cancer. (choa.org)
  • VHL disease is an autosomal dominant disease with a prevalence of 1 in 36,000 in the United States. (renalandurologynews.com)
  • The autosomal dominant form of polycystic kidney disease (ADPKD) is the most common life-threatening monogenic disease, affecting 12 million people worldwide. (basicmedicalkey.com)
  • Topology of autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) proteins polycystin-1, polycystin-2, and fibrocystin/polyductin (FPC) are shown. (basicmedicalkey.com)
  • VHL disease is inherited in an autosomal-dominant Mendelian pattern. (medscape.com)
  • In addition, VHL-mutated tumors showed an unexpected overexpression of EglN3 mRNA that did not lead to significantly different EglN3 protein levels. (nih.gov)
  • Mus musculus von Hippel-Lindau tumor suppressor (Vhl), mRNA. (genscript.com)
  • Pretreatment of murine myoblast (C2C12) cells with octyl-D-carnosine or carnosine enhanced HIF-1α protein expression, VEGF mRNA levels and VEGF release under hypoxic conditions. (frontiersin.org)
  • mRNA amounts correlated favorably with mRNA degrees of AB-hydrolase domain name made up of-5, an activator of ATGL, and adversely with mRNA degrees of lipid droplet proteins, perilipin, and Suggestion47 in human being subcutaneous adipose cells. (bioskinrevive.com)
  • Further analysis revealed that celastrol inhibited HIF-1α protein synthesis, without affecting the expression level of HIF-1α mRNA or degradation of HIF-1α protein. (spandidos-publications.com)
  • Sporadic mutation in the second copy of the VHL protein can lead to carcinomas, in particular hemangioblastomas affecting the liver and kidneys, renal and vaginal clear cell adenocarcinomas. (standardofcare.com)
  • According to the World Health Organization classification of tumors of the nervous system, hemangioblastomas are classified as meningeal tumors of uncertain origin. (medscape.com)
  • Asymptomatic lesions that sometimes are encountered in patients with multiple hemangioblastomas may be safely observed with frequent MRI scans to rule out tumor enlargement. (medscape.com)
  • [ 16 ] Cerebellar hemangioblastomas are frequently referred to as Lindau tumors because Swedish pathologist Arvid Vilhelm Lindau first described them in 1926. (medscape.com)
  • Clinical hallmarks of VHL disease include the development of retinal and central nervous system (CNS) hemangioblastomas (blood vessel tumors), pheochromocytomas , multiple cysts in the pancreas and kidneys, and an increased risk for malignant transformation of renal cysts into renal cell carcinoma. (medscape.com)
  • Nevertheless, when we compared VHL tumors with SDHB cases, which often exhibit a malignant behavior, we found that HIF-1α target genes showed a predominant activation in the VHL PCCs. (nih.gov)
  • Expression data from 67 HIF target genes was sufficient to cluster SDHB and VHL tumors into two different groups, demonstrating different pseudo-hypoxic signatures. (nih.gov)
  • This heterodimer of HIF is a transcription factor that activates genes that encode for proteins such as vascular endothelial growth factor (VEGF) and erythropoietin, proteins that are both involved in angiogenesis. (wikipedia.org)
  • The VHL protein likely plays a role in other cellular functions, including the regulation of other genes and control of cell division. (medlineplus.gov)
  • On the other hand, therapeutic concentrating on of PHDs to induce a pseudohypoxic (activation of HIF and focus on genes in normoxia) condition is under energetic clinical advancement in the framework of anemia and various other diseases concerning hypoxia (33,34). (bioskinrevive.com)
  • EXPERIMENTAL DESIGN: We performed linear discriminant analysis, a machine learning algorithm, on the NCI-60 cancer cell line microarray expression database to identify a gene profile that best distinguish cell lines with high Von-Hippel Lindau (VHL) gene expression, an important regulator of hypoxia-related genes, from those with low expression. (ox.ac.uk)
  • In hypoxic conditions, or in the presence of a deactivating VHL mutation HIF1alpha and other protein players initiate transcription of pro angiogenic genes. (the-scientist.com)
  • The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks. (hindawi.com)
  • In addition, a PPI network can be modeled as an undirected graph, where vertices represent proteins and edges represent interactions between proteins, to prioritize disease associated genes or pathways and to understand the modus operandi of disease mechanisms [ 9 , 10 ]. (hindawi.com)
  • 14 ] combined PPI and gene expression data to construct tissue-specific PPI networks for 60 tissues and used them to prioritize disease genes. (hindawi.com)
  • Mechanistic investigations demonstrated the key role of the identified genes in the balance between death and survival of tumor cells. (biomedcentral.com)
  • Key tumor suppressing genes on chromosome 3 encode apoptosis mediator RASSF1, cell migration regulator HYAL1 and angiogenesis suppressor SEMA3B. (mc1-r.com)
  • This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently, whereas it did not affect the expressions of HIF-1β and topoisomerase-I (topo‑I). Furthermore, celastrol prevented hypoxia-induced expression of HIF-1 target genes for vascular endothelial growth factor (VEGF) and erythropoietin (EPO). (spandidos-publications.com)
  • HIFs are necessary for tumor growth because most cancers demand high metabolic activity and are only supplied by structurally or functionally inadequate vasculature. (wikipedia.org)
  • HIF is necessary for tumor growth. (standardofcare.com)
  • The VHL tumor suppressor deactivates angiogenesis in an interesting oxygen sensing pathway. (the-scientist.com)
  • The Von Hippel-Lindau (VHL) tumor-suppressor protein is not functional in about 90% of patients with clear cell renal cell carcinoma, leading to accumulation of HIF proteins inside the tumor cell. (ascopost.com)
  • Dr. Choueiri reported results in the dose-expansion cohort comprising 55 patients with previously treated advanced clear cell renal cell carcinoma who received MK-6482 at 120 mg/d and were treated until progressive disease or unacceptable toxicity. (ascopost.com)
  • Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and accounts for approximately 60% to 70% of all renal tumors [ 1 ]. (hindawi.com)
  • The main action of the VHL protein is thought to be its E3 ubiquitin ligase activity that results in specific target proteins being 'marked' for degradation. (wikipedia.org)
  • Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells. (medlineplus.gov)
  • The process of the degradation of the hypoxia-inducible factors (HIFs) that mainly regulate oxygen and iron dependent activity of enzymes require DHL tumor suppressor. (standardofcare.com)
  • The main action of the VHL protein is ubiquitin ligase activity resulting in protein degradation. (standardofcare.com)
  • PHDs hydroxylate conserved prolyl residues from the HIF-1 and HIF-2 subunits, hence marketing their binding towards the von Hippel Lindau (VHL) tumor suppressor proteins, which goals HIF isoforms for proteasomal degradation in normoxia (21C24). (bioskinrevive.com)
  • The VHL protein sequenced by this gene was found to complex with the hypoxia-inducible factor (HIF-1) to promote the degradation of HIF-1. (renalandurologynews.com)
  • The modified HIF-1α interacts with Von Hippel-Lindau (VHL), which is part of the E3 ubiquitin ligase complex targeting HIF-1α for 26S proteasomal degradation. (spandidos-publications.com)
  • Retinal hemangioblastoma, fundus photo A-C, Fluorescein Angiography D. A. Observe the tortuous and dilated artery (feeder) and vein exiting through optic nerve head (draining), as well as the protruding retinal tumor with orange-yellow color present in the B. peripheral and C. optic nerve, with macular traction. (eyewiki.org)
  • Low power image-A. This retinal tumor shows high vessel density with thick walls (arrow) and cyst containing proteinaceous material (asterisk) High power image-B. The stromal cells are foamy and vacuolated (arrowheads) with many small channels resembling capillaries (arrows). (eyewiki.org)
  • phaos = light, literally meaning "tumor of lenses" after the retinal hamartomas that would eventually be recognized as part of constellation of findings now recognized as tuberous sclerosis complex. (medscape.com)
  • Von Hippel-Lindau disease can be split into two subtypes, Type 1 and Type 2, depending on the presence of pheochromocytomas [5] . (eyewiki.org)
  • Type 1 VHL has a low risk of pheochromocytomas, but both subtypes present with multiple organ tumors [5] . (eyewiki.org)
  • Metastatic pheochromocytomas and paragangliomas are rare and challenging tumors. (thieme-connect.com)
  • Fuhrman grading was first described in 1982 and has been used to both describe renal tumors and make prognoses. (renalandurologynews.com)
  • Diagnosis is confirmed with a positive familial history and at least one VHL-related tumor [3] . (eyewiki.org)
  • A diagnosis of familial VHL requires a positive family history of disease in addition to one VHL-associated tumor [3] . (eyewiki.org)
  • Through careful study of the cytogenetics of VHL patients, the gene at this locus was found to be a tumor suppressor gene associated with familial clear cell carcinomas as well as a large majority of sporadic RCC. (renalandurologynews.com)
  • Additionally, the nature of the mutation in the VHL protein leads to phenotypic manifestations in the pattern of cancer that develops. (wikipedia.org)
  • The mutation changes a single protein building block (amino acid) in the VHL protein, replacing the amino acid arginine with the amino acid tryptophan at position 200 (written as Arg200Trp or R200W). (medlineplus.gov)
  • This mutation disrupts the function of the VHL protein, particularly its ability to target HIF-2α to be broken down. (medlineplus.gov)
  • These genetic changes are thought to have similar effects on protein function to those of the Arg200Trp mutation. (medlineplus.gov)
  • The von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia and enhanced ventilatory sensitivity to hypoxia. (ox.ac.uk)
  • Early identification affected individuals with asymptomatic VHL disease-associated tumors and mutation carriers via genetic recognition and rational medical interventions would improve patients' survival rates and quality of life. (biomedcentral.com)
  • Hs-CUL-2 may be required for VHL function and, therefore, may be a candidate human tumor suppressor gene. (nih.gov)
  • Effects of tumor cell viability and inoculum density on growth parameters in the human tumor, soft-agar clonogenic assay. (shengsci.com)
  • Four hundred and forty-seven human tumor specimens were accessioned and processed for clonogenic assay, yielding 374 specimens, representing 23 different histiotypes, adequate for culture. (shengsci.com)
  • This, in addition to significant improvement in surgical approaches and microsurgical technique, has made hemangioblastoma, although dangerous, a potentially treatable and curable disease. (medscape.com)
  • The genetic hallmark of hemangioblastoma is loss of function of the von Hippel-Lindau (VHL) tumor suppressor protein. (medscape.com)
  • Hemangioblastoma is the most common primary adult intra-axial posterior fossa tumor. (medscape.com)
  • HIF1α and HIF2α play crucial roles in VHL disease, particularly with respect to ccRCC and hemangioblastoma. (biomedcentral.com)
  • The image below illustrates a hemangioblastoma of the retina as found in patients with VHL disease. (medscape.com)
  • In choosing the appropriate surgical approach to the tumor, one must take into consideration the position of the mass, the presence (or absence) of a large cystic component, associated hydrocephalus and surrounding edema, and the eloquence of neighboring neural and vascular structures. (medscape.com)
  • This protein complex has also been implicated in regulating a number of signaling pathways, including Wnt, mammalian target of rapamycin (mTOR), STAT3, cMET, phosphoinositide 3-kinase (PI3K)/AKT, G protein-coupled receptor (GPCR), and epidermal growth factor receptor (EGFR), as well as in the localization and activity of cystic fibrosis transmembrane conductance (CFTR). (basicmedicalkey.com)
  • FIGURE 339-1 Scheme of the primary cilium and cystic kidney disease proteins. (basicmedicalkey.com)
  • Both computed tomography (CT) and magnetic resonance imaging (MRI) will reveal large tumors expanding into the temporal bones for endolymphatic sac tumors (ELST) [7] . (eyewiki.org)
  • a protein component of a ubiquitin ligase complex) and hypoxia-inducible factors (a family of transcription factors activated by hypoxia). (lww.com)
  • The reasoning is that adrenal tumors might be responsible for many of the McCoys' notorious tempers. (the-scientist.com)
  • A total of 67% of patients received both prior anti-PD-1 (programmed cell death protein 1) and anti-VEGF (vascular endothelial growth factor) agents. (ascopost.com)
  • HIF-1 regulates production of multiple proteins, including vascular-endothelial growth factor (VEGF) and other cell regulatory proteins that are normally kept in check but which are significantly elevated in times of hypoxia, starvation, and stress. (renalandurologynews.com)
  • In heavily pretreated patients with metastatic disease, the objective response rate to single-agent MK-6842 was 24%, and responses were consistently seen across patients with favorable-, intermediate-, and poor-risk disease. (ascopost.com)
  • Four patients experienced grade 5 adverse events, all secondary to progressive disease. (ascopost.com)
  • The disease control rate was 80% in all patients, and high disease control rates were seen across all risk categories as follows: 100% in favorable-risk patients, 80% in intermediate-risk patients, and 70% in poor-risk patients. (ascopost.com)
  • Here, we investigated the relationship between osteopontin (OPN), tumor pO(2), and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). (ox.ac.uk)
  • The relationships between plasma OPN levels, tumor pO(2) as measured by the Eppendorf microelectrode, freedom from relapse (FFR), and survival in HNSCC patients were evaluated. (ox.ac.uk)
  • CONCLUSIONS: Plasma OPN levels appeared to correlate with tumor hypoxia in HNSCC patients and may serve as noninvasive tests to identify patients at high risk for tumor recurrence. (ox.ac.uk)
  • Loss of heterozygosity at a locus on chromosome 8 in a high percentage of tumors from patients with prostate carcinoma has been detected and the area of minimal deletion on chromosome 8p12-21 determined. (nih.gov)
  • A better understanding of locally advanced cervical cancer (LACC) is mandatory for further improving the rates of disease control, since a significant proportion of patients still fail to respond or undergo relapse after concurrent chemoradiation treatment (CRT), and survival for these patients has generally remained poor. (biomedcentral.com)
  • To identify specific markers of CRT response, we compared pretreatment biopsies from LACC patients with pathological complete response (sensitive) with those from patients showing macroscopic residual tumor (resistant) after neoadjuvant CRT, using a proteomic approach integrated with gene expression profiling. (biomedcentral.com)
  • Despite concurrent chemoradiation has significantly improved the rates of local and distant disease control for LACC patients, a significant proportion of patients still fail to respond or relapse, and therefore survival for these women has generally remained poor. (biomedcentral.com)
  • [ 2 ] Diagnosed in 50% of patients with VHL disease, these hemangiomas are composed of endothelial cells and pericytes. (medscape.com)
  • Tumors involving other organs and the CNS (brain, spinal cord) are present in 25% of patients with VHL disease. (medscape.com)
  • Cancer patients and tumor-bearing animals excrete high levels of modified purines and pyrimidines some of which, e.g. (shengsci.com)
  • Most patients carry a missing or damaged p53 gene, a tumor suppressor whose activity is impaired in almost 50% of all cancers. (nature.com)
  • Hence, pre-existing germline variants provide a profound constraint on the evolution of tumor founding clones and subclones and therefore have a contingent effect on the genetic makeup of tumor and presumably patient outcomes. (nature.com)
  • Sema4D is regulated by HIF-1 and plays a role in tumor-associated macrophage-induced metastatic behavior and is clinically significant in colon cancer ( 9 ). (jcancer.org)
  • Furthermore, studies have shown HIF-mediated Sema4D induction in the generation of the pro-angiogenic phenotype in oral squamous cell carcinoma (OSCC) and have determined its biological significance for tumor growth and vascularity ( 10 ). (jcancer.org)
  • However, their significance for tumor development has not been investigated. (shengsci.com)
  • To study the potential role in this metabolic shift of von Hippel-Lindau (VHL), a protein component of a ubiquitin ligase complex, the authors generated nephron progenitor cell-specific VHL knockout mice. (lww.com)
  • RBX2 is a potential drug target, the expression of which correlates with tumor staging, grading, and prognosis analysis. (bvsalud.org)
  • Endogenous interleukin-4 promotes tumor development by increasing tumor cell resistance to apoptosis. (shengsci.com)
  • Here, we found that endogenous IL-4 promotes tumor growth because neutralizing IL-4 by 11B1. (shengsci.com)
  • A nice linkurl:AP story;http://hosted.ap.org/dynamic/stories/H/HATFIELD_MCCOY_SECRET?SITE=PASTR&SECTION=HOME&TEMPLATE=DEFAULT talks about the hypothesis that much of the fuel for the famed Hatfield-McCoy feud might be attributed to Von Hippel-Lindau disease, a rare genetic disorder that predisposes those affected to highly-vascularized tumors. (the-scientist.com)
  • Tuberous sclerosis complex is a dominantly inherited genetic disorder in which tumors (usually hamartomas) develop in multiple organs. (msdmanuals.com)
  • Further accumulation of genetic changes confers invasiveness or metastatic potential on the tumor ( 6 , 7 ), and to date, several indicators have been identified to predict outcomes ( 7 , 8 ). (iiarjournals.org)
  • Other CNS neoplasms, including several tumors associated with von Hippel-Landau (VHL) disease, may present as histologic mimics, making diagnosis challenging. (medscape.com)
  • Definitive diagnosis of Von Hippel-Lindau disease occurs in one of two ways. (eyewiki.org)
  • Those without a family history require two or more VHL-associated tumors for diagnosis [3] . (eyewiki.org)
  • Diagnosis of VHL-associated tumors is more varied. (eyewiki.org)
  • Clinical diagnosis of VHL disease often relies on the presence of classical manifestations and family history. (biomedcentral.com)
  • The wide age range and pleiotropic manner in which VHL disease presents complicates diagnosis and treatment in affected individuals, as well as their at-risk relatives. (medscape.com)
  • Because VHL disease is a multiple-organ disease that widely varies in clinical presentation, various manifestations may lead to diagnosis. (medscape.com)
  • Recurrent, unabated ischemia is the underlying cause of tissue loss in peripheral arterial disease (PAD) or peripheral vascular disease (PVD). (frontiersin.org)
  • Carotid arteriogram demonstrates a vascular, dense, tumor filled from the anterior cerebral vessels and not involving the sagittal sinus. (medscape.com)
  • OBJECTIVES: Ubiquitination plays a vital role in controlling vascular inflammation, cellular protein quality control, and minimizing misfolded protein toxicity. (bvsalud.org)
  • Predominant involvement of the cerebellum and the spinal cord was noted, but the true incidence of this tumor was not discovered until noninvasive diagnostic imaging modalities, particularly magnetic resonance imaging (MRI), became more available. (medscape.com)
  • The tumor burden, combined with excessive catecholamine production, predispose to a broad spectrum of complications that range from spinal cord compression to any organ damage, all of which may lead to decreased quality of life and overall survival. (thieme-connect.com)
  • These compounds generally penetrate cell membranes, act on specific target proteins in cells, regulate intracellular signaling pathways, and cause some changes in cell phenotype. (chemscene.com)
  • In accordance, the aberrant expression of RBX2 will lead to dysregulation of many signaling pathways, which is crucial for tumor initiation and growth. (bvsalud.org)
  • Markedly, we found that suppression of HIF-1α accumulation by celastrol correlated with strong dephosphorylation of mammalian target of rapamycin (mTOR) and its effectors, ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E (eIF4E) and extracellular signal-regulated kinase (ERK), pathways known to regulate HIF-1α expression at the translational level. (spandidos-publications.com)
  • Pre-treatment tumor tissue biopsies were obtained during staging procedures, the joint assessment by surgeon and pathologist allowing an unequivocal identification of tumor area to be sampled. (biomedcentral.com)
  • Protein expression is influenced by many factors that may vary between experiments or laboratories. (genscript.com)
  • METHODS AND RESULTS: Stabilization of myocardial HIF-1 was achieved by pharmacological inhibition of prolyl hydroxylase (PHD) domain-containing enzyme using GSK360A or using cardiac-specific ablation of von Hippel-Lindau protein (VHL(fl/fl)) in mice. (ox.ac.uk)
  • Based on this function, the VHL protein is classified as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. (medlineplus.gov)
  • The VHL protein is also involved in the formation of the extracellular matrix, which is an intricate lattice that forms in the spaces between cells and provides structural support to tissues. (medlineplus.gov)
  • As has often been the case, hematologic malignancies have led the way in the introduction of this new generation of therapeutics-perhaps because of easy access to tumor samples for pharmacodynamics, and the narrow spectrum of cells of origin. (cancernetwork.com)
  • The protein enables cancer cells to live in the low-oxygen conditions found within tumors, and helps the body respond to cardiovascular. (the-scientist.com)
  • The VHL protein is found both in the nucleus and in the cytosol of transiently transfected cells. (nih.gov)
  • Type I tumors are more common and are composed of small cells characterized by their scanty basophilic cytoplasm and low nuclear grade. (renalandurologynews.com)
  • Notably, surgical treatment has also the potential advantage of removing chemoradioresistant residual tumor foci, with a higher local control and possibly better survival, since resistance of cancer cells to CRT remains a major therapeutic drawback. (biomedcentral.com)
  • Increased cAMP promotes protein kinase A activity, among other effectors, and, in turn, leads to cyst growth by promoting proliferation and fluid secretion of cyst-lining cells through chloride and aquaporin channels in ADPKD kidneys. (basicmedicalkey.com)
  • The foamy stromal cells between the capillaries stain positive for glial fibrillary acid protein and neuron-specific enolase. (medscape.com)
  • In vivo studies further confirmed the inhibitory effect of celastrol on the expression of HIF-1α proteins, leading to a decreased growth of Hep3B cells in a xenograft tumor model. (spandidos-publications.com)
  • The increase of interleukin-4 (IL-4) level in tumor environment and the up-regulation of IL-4 receptor (IL-4R) on tumor cells have been long observed. (shengsci.com)
  • This gene, often called a tumor suppressor gene, cannot protect cells from becoming cancerous when it isn't working properly. (choa.org)
  • With this purpose, 84 genetically characterized tumors were analyzed by means of transcriptional profiling. (nih.gov)
  • Masaya Baba and colleagues have been working on the clarification of the molecular function of FLCN by identifying its binding proteins and analyzing genetically engineered mouse models. (kumamoto-u.ac.jp)
  • The polycystic kidney diseases are a group of genetically heterogeneous disorders and a leading cause of kidney failure. (basicmedicalkey.com)
  • methylation at certain residues of histones can regulate gene expression [ 4 ], and glycosylation is responsible for targeting substrates and changing protein half-life [ 2 ]. (hindawi.com)
  • The oxygen-sensitive sign event that regulates HIF is certainly mediated by hydroxylase enzymes that regulate the proteins balance and consequent transcriptional activity of HIF (20). (bioskinrevive.com)
  • The PC1/2 protein complex may also directly regulate a number of cellular functions including the cell cycle, the actin cytoskeleton, planar cell polarity (PCP), and cell migration. (basicmedicalkey.com)
  • Understanding the proteins that regulate the 5-HT1A promoter will lead to insights on receptor regulation and provide new therapeutic targets relevant to depression, anxiety, obsessive compulsive disorder and other mental illnesses. (vdocuments.net)
  • William Kaelin, Jr. was in 1995 engaged in the study of the von Hippel-Lindau tumor suppressor gene, and after isolation of the first full-length clone of the gene showed that it could suppress tumor growth in VHL mutant tumorigenic cell lines. (nobelprize.org)
  • This process wrongly signals that there is a shortage of blood vessels and activates the formation of blood vessels, driving tumor growth. (ascopost.com)
  • These proteins act as growth suppressors. (msdmanuals.com)
  • Surgical problems include high tumor vascularity, vertebral artery control, and nerve root preservation. (medscape.com)
  • In the normal cell with active VHL protein, HIF alpha is regulated by hydroxylation in the presence of oxygen. (wikipedia.org)
  • This complex targets other proteins to be broken down (degraded) by the cell when they are no longer needed. (medlineplus.gov)
  • The coiled-coil domain is a structural motif found in proteins that are involved in a diverse array of biological functions such as the regulation of gene expression, cell division, membrane fusion and drug extrusion and delivery. (antikoerper-online.de)
  • We show that in the nephron BPGM is constitutively expressed, and up-regulated under conditions like acute kidney injury, clear cell renal carcinoma, or knock-out of the tumor suppressor von Hippel Lindau protein (VHL). (charite.de)
  • Clear cell RCC is associated with von Hippel-Lindau (VHL) disease. (renalandurologynews.com)
  • The Von Hippel-Lindau ( VHL ) tumour suppressor gene undergoes bi-allelic knockout in the vast majority of clear cell RCCs. (springer.com)
  • In our lab we utilize a variety of biochemical, biophysical and molecular biology methodologies to study the mechanism and significance of protein unfolding and misfolding. (tau.ac.il)
  • Our findings argue that senescence acts as a tumor suppressor mechanism that is abrogated during the transition from LGD to HGD in UC. (shengsci.com)
  • Further, our study demonstrates that repression of key effector proteins in the post-transcriptional miRNA pathway impairs primary cilium formation. (biomedcentral.com)
  • Glycine N-methyltransferase tumor susceptibility gene in the benzo(a)pyrene-detoxification pathway. (shengsci.com)
  • This disease involves multiple organ systems throughout the body, especially the heart, lungs, skin, and kidneys in addition to the central nervous system (CNS). (medscape.com)
  • Astrocytomas Astrocytomas are central nervous system tumors that develop from astrocytes. (msdmanuals.com)
  • RBX2 (RING box protein 2), also known as ROC2 (Regulator of Cullins 2), RNF7 (RING Finger Protein 7), or SAG (Sensitive to Apoptosis Gene) is a key component of the Cullin-RING-type E3 ubiquitin ligases (CRLs) and overexpressed in various human cancers. (bvsalud.org)
  • HIF-2α is one part (subunit) of a larger protein complex called HIF, which plays a critical role in the body's ability to adapt to changing oxygen levels. (medlineplus.gov)
  • and a second, previously identified and constitutively expressed and non-oxygen-regulated protein known as ARNT. (nobelprize.org)
  • Kaelin's 1999 study of the tumor-suppressor gene VHL, which helps control HIF, has been crucial for understanding cellular responses to changes in oxygen levels, according to a Harvard Medical School press release . (the-scientist.com)
  • The VHL protein has been shown to bind tightly and specifically to the Elongin B and C subunits and to inhibit Elongin (SIII) transcriptional activity in vitro . (nih.gov)
  • The autosomal recessive form of polycystic kidney disease (ARPKD) is rarer but affects the pediatric population. (basicmedicalkey.com)