Insulin-Like Growth Factor II
Insulin-Like Growth Factor I
Somatomedins
Receptor, IGF Type 1
Intercellular Signaling Peptides and Proteins
Receptor, IGF Type 2
Epidermal Growth Factor
Insulin
Receptors, Somatomedin
Signal Transduction
Receptor, Insulin
Cells, Cultured
COUP Transcription Factor II
Cell Division
Receptor, Epidermal Growth Factor
Vascular Endothelial Growth Factor A
RNA, Messenger
Fibroblast Growth Factor 2
Receptors, Cell Surface
Transforming Growth Factor beta
Growth Substances
Insulin Resistance
Molecular Sequence Data
Platelet-Derived Growth Factor
Transforming Growth Factors
Fibroblast Growth Factors
Genomic Imprinting
Insulin-Like Growth Factor Binding Proteins
Base Sequence
Hepatocyte Growth Factor
Endothelial Growth Factors
Transforming Growth Factor alpha
Phosphorylation
Nerve Growth Factors
Glucose
Hexosephosphates
Insulin Receptor Substrate Proteins
Amino Acid Sequence
Vascular Endothelial Growth Factors
Hypoglycemia
Liver
Tumor Cells, Cultured
Insulin-Like Growth Factor Binding Protein 2
Placenta
Rhabdomyosarcoma
Wilms Tumor
Nerve Growth Factor
Gene Expression Regulation
Adipose Tissue
Insulin, Long-Acting
Gene Expression
Transfection
Protein Binding
Receptors, Fibroblast Growth Factor
Transforming Growth Factor beta1
Promoter Regions, Genetic
Receptors, Growth Factor
Prothrombin
Hemangiopericytoma
DNA
Insulin-like growth factors I and II are unable to form and maintain their native disulfides under in vivo redox conditions. (1/1873)
Insulin-like growth factor (IGF) I does not quantitatively form its three native disulfide bonds in the presence of 10 mM reduced and 1 mM oxidized glutathione in vitro [Hober, S. et al. (1992) Biochemistry 31, 1749-1756]. In this paper, we show (i) that both IGF-I and IGF-II are unable to form and maintain their native disulfide bonds at redox conditions that are similar to the situation in the secretory vesicles in vivo and (ii) that the presence of protein disulfide isomerase does not overcome this problem. The results indicate that the previously described thermodynamic disulfide exchange folding problem of IGF-I in vitro is also present in vivo. Speculatively, we suggest that the thermodynamic disulfide exchange properties of IGF-I and II are biologically significant for inactivation of the unbound growth factors by disulfide exchange reactions to generate variants destined for rapid clearance. (+info)Inhibition of angiogenesis induces chromaffin differentiation and apoptosis in neuroblastoma. (2/1873)
Inhibition of angiogenesis has been shown to reduce tumor growth, metastasis, and tumor microvascular density in experimental models. To these effects we would now like to add induction of differentiation, based on biological analysis of xenografted human neuroblastoma (SH-SY5Y, WAG rnu/rnu) treated with the angiogenesis inhibitor TNP-470. Treatment with TNP-470 (10 mg/kg s.c., n = 15) reduced the tumor growth by 66% and stereological vascular parameters (Lv, Vv, Sv) by 36-45%. The tumor cell apoptotic fraction increased more than threefold, resulting in a decrease in viable tumor cells by 33%. In contrast, the mean vascular diameter (29 microm) and the mean tumor cell proliferative index (49%) were unaffected. TNP-470-treated tumors exhibited striking chromaffin differentiation of neuroblastoma cells, observed as increased expression of insulin-like growth factor II gene (+88%), tyrosine hydroxylase (+96%), chromogranin A, and cellular processes. Statistical analysis revealed an inverse correlation between differentiation and angiogenesis. It is suggested that by inhibiting angiogenesis, TNP-470 induces metabolic stress, resulting in chromaffin differentiation and apoptosis in neuroblastoma. Such agonal differentiation may be the link between angiostatic therapy and tumor cell apoptosis. (+info)Dual role for transcription factor AP-2 in the regulation of the major fetal promoter P3 of the gene for human insulin-like growth factor II. (3/1873)
The human insulin-like growth factor II (IGF-II) gene contains four promoters that are differentially active during cell growth and development. Promoter 3 (P3) is the most active promoter in fetal and non-hepatic adult tissues. In addition to its expression during development, P3 is also the major promoter in many tumour tissues and IGF-II-expressing cell lines. Here we show that AP-2 has a dual function in P3 regulation in vivo as well as in vitro. In cells expressing low levels of endogenous AP-2, AP-2 overexpression activates P3, whereas P3 promoter activity is inhibited in cells containing abundant AP-2. Four potential AP-2-binding sites were identified in footprinting studies with recombinant AP-2. One of these AP-2-binding sites is located within the previously identified element P3-4 that contains two adjacent binding sites for IGF-II promoter-binding proteins IPBP3 and IPBP4/5. By applying binding competition assays and mutational analysis it is shown that AP-2 interferes with IPBP3 binding and transactivation in vivo as well as in vitro. Furthermore, AP-2 can bind additional elements in the proximal P3 promoter that also contribute to AP-2-mediated transactivation as shown by transient transfection assays. From these results we conclude that AP-2 is an important regulator in vivo and in vitro of IGF-II P3 activity. (+info)In-vitro fertilization and culture of mouse embryos in vitro significantly retards the onset of insulin-like growth factor-II expression from the zygotic genome. (4/1873)
In this study, the effect of in-vitro fertilization (IVF) and culture of mouse embryos in vitro on the normal expression of insulin-like growth factor-II (IFG-II) ligand and receptor was examined. The expression of IGF-II increased in a linear fashion at least up to the 8-cell stage of development. IGF-II expression in embryos collected fresh from the reproductive tract was significantly (P < 0.001) greater than in embryos fertilized in the reproductive tract and cultured in vitro (in-situ fertilized: ISF), and its expression was further reduced (P < 0.001) in IVF embryos at all development stages tested. The expression of IGF-II was significantly (P < 0.001) lower when embryos were cultured individually in 100 microl drops compared with culture in groups of 10 in 10 microl drops of medium. The addition of platelet activating factor to culture medium partially overcame this density-dependent decline of expression. Culture of ISF and IVF zygotes also caused the onset of new IGF-II mRNA transcription from the zygotic genome to be significantly (P < 0.001) retarded, until at least the 8-cell stage of development. This effect was greater (P < 0.05) for IVF than for ISF embryos. Neither IVF nor culture had any obvious effect on IFG-II/mannose-6-phosphate receptor (IGF-IIr) mRNA expression. (+info)Serum IGF-binding protein-6 and prostate specific antigen in breast cancer. (5/1873)
OBJECTIVE: Recent studies have demonstrated the presence of the IGF-binding proteins (IGFBPs) and prostate specific antigen (PSA), an IGFBP protease. in human breast tissue. We sought to investigate the differences in serum IGFs, IGFBP-1, -3 and -6, and PSA between patients with surgically proven breast cancer and patients with benign breast disease. DESIGN AND METHODS: Concentrations of IGFs, IGFBP-1, -3 and -6, and PSA were determined in the sera from 57 patients with breast cancer (CA), and 46 women with benign breast disease (BBD) using immunoassays for IGFs and IGFBPs and an ultrasensitive ELISA for PSA. RESULTS: The mean (+/- S.E.M.) serum IGFBP-6 level in the CA group, 127 (16) ng/ml, was statistically significantly lower than in the BBD group, 157 (10) ng/ml (P = 0.016). Patients with CA had an elevated geometric mean serum PSA level of 0.018 (range: 0.0015-0.107) ng/ml, compared with 0.007 (range: 0.0015-0.019) ng/ml in women with BBD (P = 0.025). Mean serum IGFBP-1 concentrations were significantly lower in the CA group, 16 (2) ng/ml, versus 37 (4) ng/ml in the BBD group (P = 0.001). Mean serum IGFBP-3 concentrations were also lower in the CA group versus the BBD group, at 1981 (65) ng/ml, versus 2603 (140) ng/ml (P = 0.002) respectively. In the CA group, statistically significant correlations between PSA and IGFBP-6 (r = 0.413; P = 0.001), and between PSA and IGFBP-1 (r = -0.329; P = 0.021) were seen. Differences in IGF-I and -II between the two groups were not statistically significant. CONCLUSION: Lower serum concentrations of IGFBP-6, -3 and -1, but higher PSA concentrations were seen in the breast cancer group, and collectively these would suggest that there is an increase in bioavailable IGF-I in breast cancer. (+info)HaCaT human keratinocytes express IGF-II, IGFBP-6, and an acid-activated protease with activity against IGFBP-6. (6/1873)
The insulin-like growth factor (IGF) system plays an important role in skin. HaCaT human keratinocytes proliferate in response to IGFs and synthesize IGF-binding protein-3 (IGFBP-3). Recently, IGFBP-6 was also identified by NH2-terminal sequencing, but it has not been identified by Western ligand blotting. In the present study, IGFBP-6 was detected in HaCaT-conditioned medium by use of immunoblotting and Western ligand blotting with 125I-labeled IGF-II. Proteolytic activity against IGFBPs, an important mechanism for regulation of their activity, was then studied. An acid-activated, cathepsin D-like protease that cleaved both IGFBP-6 and IGFBP-3 was detected. Although proteolysis did not substantially reduce the size of immunoreactive IGFBP-6, it greatly reduced the ability of IGFBP-6 to bind 125I-IGF-II as determined by Western ligand blotting and solution assay. HaCaT keratinocytes do not express IGF-I mRNA, but IGF-II mRNA and protein expression was detected. These observations suggest the possibility of an autocrine IGF-II loop that is regulated by the relative expression of IGF-II, IGFBP-3, and IGFBP-6, and IGFBP proteases in these keratinocytes, although demonstration of this loop requires further study. (+info)Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line. (7/1873)
The relationship between oestrogen (E2) and insulin-like growth factor-one (IGF-1) was examined in both tamoxifen-sensitive (MCF 7/5-21) and tamoxifen-resistant (MCF 7/5-23) subclones of the MCF 7 cell line. Both subclones were grown in defined, serum-free (SF) medium over a period of 7 days with the addition of E2 or IGF-1 or a combination of both agents. Growth of both MCF 7/5-21 and 7/5-23 cells was stimulated (245% and 350%, respectively) by E2. However, only the growth of MCF 7/5-23 cells was stimulated (266%) by IGF-1. A combination of E2 and IGF-1 significantly enhanced MCF 7/5-21 and 7/5-23 cell growth (581% and 695%, respectively). E2-induced IGF-1 receptor (IGF-1R) levels (as measured by 125I-IGF-1 binding and Northern analyses) in only MCF 7/5-23 cells. This effect was partially inhibited by tamoxifen. In medium containing serum, the growth of only the MCF 7/5-23 cells was significantly inhibited by the IGF-1R monoclonal antibody, alphaIR-3. The detection of E2-induced expression of IGF-2 using RT-PCR was demonstrated in the MCF 7/5-23 cells. These experiments indicate that E2 may sensitize tamoxifen-resistant MCF 7/5-23 cells to the growth stimulatory actions of IGF-2 via up-regulation of the IGF-1R and describes a cell-survival mechanism that may manifest itself as tamoxifen resistance. (+info)Inhibition of growth, production of insulin-like growth factor-II (IGF-II), and expression of IGF-II mRNA of human cancer cell lines by antagonistic analogs of growth hormone-releasing hormone in vitro. (8/1873)
Antagonistic analogs of growth hormone-releasing hormone (GHRH) suppress growth of various tumors in vivo. This effect is exerted in part through inhibition of the GHRH-GH-insulin-like growth factor (IGF)-I axis. Nevertheless, because autocrine/paracrine control of proliferation by IGF-II also is a major factor in many tumors, the interference with this growth-stimulating pathway would offer another approach to tumor control. We thus investigated whether GHRH antagonists MZ-4-71 and MZ-5-156 also act on the tumor cells directly by blocking the production of IGF-II. An increase in the IGF-II concentration in the media during culture was found in 13 of 26 human cancer cell lines tested. Reverse transcription-PCR studies on 8 of these cell lines showed that they also expressed IGF-II mRNA. Antagonists of GHRH significantly inhibited the rate of proliferation of mammary (MDA-MB-468 and ZR-75-1), prostatic (PC-3 and DU-145), and pancreatic (MiaPaCa-2, SW-1990, and Capan-2) cancer cell lines as shown by colorimetric and [3H]thymidine incorporation tests and reduced the expression of IGF-II mRNA in the cells and the concentration of IGF-II secreted into the culture medium. Growth and IGF-II production of lung (H-23 and H-69) and ovarian (OV-1063) cancer cells that express mRNA for IGF-II and excrete large quantities of IGF-II also was marginally suppressed by the antagonists. These findings suggest that antagonistic analogs of GHRH can inhibit growth of certain tumors not only by inhibiting the GHRH-GH-IGF-I axis, but also by reducing the IGF-II production and by interfering with the autocrine regulatory pathway. (+info)Insulin-like Growth Factor II (IGF-II) is a growth factor that is structurally and functionally similar to insulin. It is a single-chain polypeptide hormone, primarily produced by the liver under the regulation of growth hormone. IGF-II plays an essential role in fetal growth and development, and continues to have important functions in postnatal life, including promoting cell growth, proliferation, and differentiation in various tissues.
IGF-II binds to and activates the IGF-I receptor and the insulin receptor, leading to intracellular signaling cascades that regulate metabolic and mitogenic responses. Dysregulation of IGF-II expression and signaling has been implicated in several pathological conditions, such as cancer, growth disorders, and diabetes.
It is important to note that IGF-II should not be confused with Insulin-like Growth Factor I (IGF-I), which is another hormone with structural and functional similarities to insulin but has distinct roles in growth and development.
Insulin-like growth factor I (IGF-I) is a hormone that plays a crucial role in growth and development. It is a small protein with structural and functional similarity to insulin, hence the name "insulin-like." IGF-I is primarily produced in the liver under the regulation of growth hormone (GH).
IGF-I binds to its specific receptor, the IGF-1 receptor, which is widely expressed throughout the body. This binding activates a signaling cascade that promotes cell proliferation, differentiation, and survival. In addition, IGF-I has anabolic effects on various tissues, including muscle, bone, and cartilage, contributing to their growth and maintenance.
IGF-I is essential for normal growth during childhood and adolescence, and it continues to play a role in maintaining tissue homeostasis throughout adulthood. Abnormal levels of IGF-I have been associated with various medical conditions, such as growth disorders, diabetes, and certain types of cancer.
Somatomedins are a type of insulin-like growth factors (IGFs), specifically IGF-1 and IGF-2. They are peptide hormones that play an essential role in the regulation of growth, development, and metabolism in the human body. Somatomedins are primarily produced by the liver in response to stimulation by growth hormone (GH) and act as mediators of GH's effects on cell growth, differentiation, and survival. They also have important functions in glucose homeostasis, energy metabolism, and tissue repair. Somatomedins exert their actions by binding to specific receptors on the surface of target cells, leading to intracellular signaling cascades that regulate various cellular processes.
IGF-1R (Insulin-like Growth Factor 1 Receptor) is a transmembrane receptor tyrosine kinase that plays a crucial role in intracellular signaling pathways related to cell growth, differentiation, and survival. IGF-1R is primarily activated by its ligands, IGF-1 (Insulin-like Growth Factor 1) and IGF-2 (Insulin-like Growth Factor 2). Upon binding of the ligand, IGF-1R undergoes autophosphorylation and initiates a cascade of intracellular signaling events, primarily through the PI3K/AKT and RAS/MAPK pathways. These signaling cascades ultimately regulate various cellular processes such as glucose metabolism, protein synthesis, DNA replication, and cell cycle progression. Dysregulation of IGF-1R has been implicated in several diseases, including cancer, diabetes, and growth disorders.
Intercellular signaling peptides and proteins are molecules that mediate communication and interaction between different cells in living organisms. They play crucial roles in various biological processes, including cell growth, differentiation, migration, and apoptosis (programmed cell death). These signals can be released into the extracellular space, where they bind to specific receptors on the target cell's surface, triggering intracellular signaling cascades that ultimately lead to a response.
Peptides are short chains of amino acids, while proteins are larger molecules made up of one or more polypeptide chains. Both can function as intercellular signaling molecules by acting as ligands for cell surface receptors or by being cleaved from larger precursor proteins and released into the extracellular space. Examples of intercellular signaling peptides and proteins include growth factors, cytokines, chemokines, hormones, neurotransmitters, and their respective receptors.
These molecules contribute to maintaining homeostasis within an organism by coordinating cellular activities across tissues and organs. Dysregulation of intercellular signaling pathways has been implicated in various diseases, such as cancer, autoimmune disorders, and neurodegenerative conditions. Therefore, understanding the mechanisms underlying intercellular signaling is essential for developing targeted therapies to treat these disorders.
IGF-2 (Insulin-like Growth Factor 2) receptor is a type of transmembrane protein that plays a role in cell growth, differentiation, and survival. Unlike other receptors in the insulin and IGF family, IGF-2 receptor does not mediate the activation of intracellular signaling pathways upon binding to its ligand (IGF-2). Instead, it acts as a clearance receptor that facilitates the removal of IGF-2 from circulation by transporting it to lysosomes for degradation.
The IGF-2 receptor is also known as cation-independent mannose-6-phosphate receptor (CI-M6PR) because it can also bind and transport mannose-6-phosphate-containing enzymes to lysosomes for degradation.
Mutations in the IGF-2 receptor gene have been associated with certain types of cancer, as well as developmental disorders such as Beckwith-Wiedemann syndrome.
Epidermal Growth Factor (EGF) is a small polypeptide that plays a significant role in various biological processes, including cell growth, proliferation, differentiation, and survival. It primarily binds to the Epidermal Growth Factor Receptor (EGFR) on the surface of target cells, leading to the activation of intracellular signaling pathways that regulate these functions.
EGF is naturally produced in various tissues, such as the skin, and is involved in wound healing, tissue regeneration, and maintaining the integrity of epithelial tissues. In addition to its physiological roles, EGF has been implicated in several pathological conditions, including cancer, where it can contribute to tumor growth and progression by promoting cell proliferation and survival.
As a result, EGF and its signaling pathways have become targets for therapeutic interventions in various diseases, particularly cancer. Inhibitors of EGFR or downstream signaling components are used in the treatment of several types of malignancies, such as non-small cell lung cancer, colorectal cancer, and head and neck cancer.
Insulin is a hormone produced by the beta cells of the pancreatic islets, primarily in response to elevated levels of glucose in the circulating blood. It plays a crucial role in regulating blood glucose levels and facilitating the uptake and utilization of glucose by peripheral tissues, such as muscle and adipose tissue, for energy production and storage. Insulin also inhibits glucose production in the liver and promotes the storage of excess glucose as glycogen or triglycerides.
Deficiency in insulin secretion or action leads to impaired glucose regulation and can result in conditions such as diabetes mellitus, characterized by chronic hyperglycemia and associated complications. Exogenous insulin is used as a replacement therapy in individuals with diabetes to help manage their blood glucose levels and prevent long-term complications.
I'm sorry for any confusion, but "Mannosephosphates" is not a widely recognized or established term in medicine or biochemistry. It seems that this term may be a combination of "mannose," which is a type of sugar (monosaccharide), and "phosphates," which are compounds containing phosphorus. However, without more context, it's difficult to provide an accurate medical definition for this term.
In biochemistry, mannose can be linked to phosphate groups in various ways, such as in the context of mannose-1-phosphate or mannose-6-phosphate, which are involved in different metabolic pathways. If you could provide more information about where you encountered this term, I might be able to give a more precise definition or explanation.
Somatomedins are a group of insulin-like growth factor (IGF) that bind to specific receptors on the cell surface, known as "Somatomedin Receptors." These receptors, when bound by somatomedins, activate intracellular signaling pathways that promote cell proliferation and differentiation.
There are two main types of somatomedin receptors: IGF-1R (Insulin-like Growth Factor 1 Receptor) and IGF-2R (Insulin-like Growth Factor 2 Receptor). IGF-1R binds both IGF-1 and IGF-2 with high affinity, while IGF-2R has a higher affinity for IGF-2.
Abnormalities in somatomedin receptors have been implicated in various medical conditions, including cancer, growth disorders, and diabetes. For example, overexpression of IGF-1R has been observed in many types of cancer, leading to increased cell proliferation and resistance to apoptosis (programmed cell death). On the other hand, mutations in the IGF-1R gene have been associated with certain forms of dwarfism.
Therefore, understanding the role of somatomedin receptors in cell signaling and their involvement in various diseases is an active area of research in endocrinology and oncology.
Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.
The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.
Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.
An insulin receptor is a transmembrane protein found on the surface of cells, primarily in the liver, muscle, and adipose tissue. It plays a crucial role in regulating glucose metabolism in the body. When insulin binds to its receptor, it triggers a series of intracellular signaling events that promote the uptake and utilization of glucose by cells, as well as the storage of excess glucose as glycogen or fat.
Insulin receptors are composed of two extracellular alpha subunits and two transmembrane beta subunits, which are linked together by disulfide bonds. The binding of insulin to the alpha subunits activates the tyrosine kinase activity of the beta subunits, leading to the phosphorylation of intracellular proteins and the initiation of downstream signaling pathways.
Abnormalities in insulin receptor function or number can contribute to the development of insulin resistance and type 2 diabetes.
"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.
Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.
It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.
COUP-TFII, also known as Nuclear Receptor Related 1 Protein (NURR1), is a transcription factor that belongs to the steroid hormone receptor superfamily. It plays crucial roles in the development and function of the nervous system, particularly in the differentiation and survival of dopaminergic neurons, which are important for movement control and motivation. COUP-TFII regulates gene expression by binding to specific DNA sequences called response elements in the promoter regions of target genes. It has also been implicated in various physiological and pathological processes, including energy metabolism, inflammation, and cancer.
Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.
Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.
Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.
In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.
The Epidermal Growth Factor Receptor (EGFR) is a type of receptor found on the surface of many cells in the body, including those of the epidermis or outer layer of the skin. It is a transmembrane protein that has an extracellular ligand-binding domain and an intracellular tyrosine kinase domain.
EGFR plays a crucial role in various cellular processes such as proliferation, differentiation, migration, and survival. When EGF (Epidermal Growth Factor) or other ligands bind to the extracellular domain of EGFR, it causes the receptor to dimerize and activate its intrinsic tyrosine kinase activity. This leads to the autophosphorylation of specific tyrosine residues on the receptor, which in turn recruits and activates various downstream signaling molecules, resulting in a cascade of intracellular signaling events that ultimately regulate gene expression and cell behavior.
Abnormal activation of EGFR has been implicated in several human diseases, including cancer. Overexpression or mutation of EGFR can lead to uncontrolled cell growth and division, angiogenesis, and metastasis, making it an important target for cancer therapy.
Vascular Endothelial Growth Factor A (VEGFA) is a specific isoform of the vascular endothelial growth factor (VEGF) family. It is a well-characterized signaling protein that plays a crucial role in angiogenesis, the process of new blood vessel formation from pre-existing vessels. VEGFA stimulates the proliferation and migration of endothelial cells, which line the interior surface of blood vessels, thereby contributing to the growth and development of new vasculature. This protein is essential for physiological processes such as embryonic development and wound healing, but it has also been implicated in various pathological conditions, including cancer, age-related macular degeneration, and diabetic retinopathy. The regulation of VEGFA expression and activity is critical to maintaining proper vascular function and homeostasis.
Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.
Fibroblast Growth Factor 2 (FGF-2), also known as basic fibroblast growth factor, is a protein involved in various biological processes such as cell growth, proliferation, and differentiation. It plays a crucial role in wound healing, embryonic development, and angiogenesis (the formation of new blood vessels). FGF-2 is produced and secreted by various cells, including fibroblasts, and exerts its effects by binding to specific receptors on the cell surface, leading to activation of intracellular signaling pathways. It has been implicated in several diseases, including cancer, where it can contribute to tumor growth and progression.
Cell surface receptors, also known as membrane receptors, are proteins located on the cell membrane that bind to specific molecules outside the cell, known as ligands. These receptors play a crucial role in signal transduction, which is the process of converting an extracellular signal into an intracellular response.
Cell surface receptors can be classified into several categories based on their structure and mechanism of action, including:
1. Ion channel receptors: These receptors contain a pore that opens to allow ions to flow across the cell membrane when they bind to their ligands. This ion flux can directly activate or inhibit various cellular processes.
2. G protein-coupled receptors (GPCRs): These receptors consist of seven transmembrane domains and are associated with heterotrimeric G proteins that modulate intracellular signaling pathways upon ligand binding.
3. Enzyme-linked receptors: These receptors possess an intrinsic enzymatic activity or are linked to an enzyme, which becomes activated when the receptor binds to its ligand. This activation can lead to the initiation of various signaling cascades within the cell.
4. Receptor tyrosine kinases (RTKs): These receptors contain intracellular tyrosine kinase domains that become activated upon ligand binding, leading to the phosphorylation and activation of downstream signaling molecules.
5. Integrins: These receptors are transmembrane proteins that mediate cell-cell or cell-matrix interactions by binding to extracellular matrix proteins or counter-receptors on adjacent cells. They play essential roles in cell adhesion, migration, and survival.
Cell surface receptors are involved in various physiological processes, including neurotransmission, hormone signaling, immune response, and cell growth and differentiation. Dysregulation of these receptors can contribute to the development of numerous diseases, such as cancer, diabetes, and neurological disorders.
Transforming Growth Factor-beta (TGF-β) is a type of cytokine, which is a cell signaling protein involved in the regulation of various cellular processes, including cell growth, differentiation, and apoptosis (programmed cell death). TGF-β plays a critical role in embryonic development, tissue homeostasis, and wound healing. It also has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.
TGF-β exists in multiple isoforms (TGF-β1, TGF-β2, and TGF-β3) that are produced by many different cell types, including immune cells, epithelial cells, and fibroblasts. The protein is synthesized as a precursor molecule, which is cleaved to release the active TGF-β peptide. Once activated, TGF-β binds to its receptors on the cell surface, leading to the activation of intracellular signaling pathways that regulate gene expression and cell behavior.
In summary, Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine involved in various cellular processes, including cell growth, differentiation, apoptosis, embryonic development, tissue homeostasis, and wound healing. It has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.
Growth substances, in the context of medical terminology, typically refer to natural hormones or chemically synthesized agents that play crucial roles in controlling and regulating cell growth, differentiation, and division. They are also known as "growth factors" or "mitogens." These substances include:
1. Proteins: Examples include insulin-like growth factors (IGFs), transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and fibroblast growth factors (FGFs). They bind to specific receptors on the cell surface, activating intracellular signaling pathways that promote cell proliferation, differentiation, and survival.
2. Steroids: Certain steroid hormones, such as androgens and estrogens, can also act as growth substances by binding to nuclear receptors and influencing gene expression related to cell growth and division.
3. Cytokines: Some cytokines, like interleukins (ILs) and hematopoietic growth factors (HGFs), contribute to the regulation of hematopoiesis, immune responses, and inflammation, thus indirectly affecting cell growth and differentiation.
These growth substances have essential roles in various physiological processes, such as embryonic development, tissue repair, and wound healing. However, abnormal or excessive production or response to these growth substances can lead to pathological conditions, including cancer, benign tumors, and other proliferative disorders.
Insulin resistance is a condition in which the body's cells become less responsive to insulin, a hormone produced by the pancreas that regulates blood sugar levels. In response to this decreased sensitivity, the pancreas produces more insulin to help glucose enter the cells. However, over time, the pancreas may not be able to keep up with the increased demand for insulin, leading to high levels of glucose in the blood and potentially resulting in type 2 diabetes, prediabetes, or other health issues such as metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease. Insulin resistance is often associated with obesity, physical inactivity, and genetic factors.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.
Platelet-Derived Growth Factor (PDGF) is a dimeric protein with potent mitogenic and chemotactic properties that plays an essential role in wound healing, blood vessel growth, and cellular proliferation and differentiation. It is released from platelets during the process of blood clotting and binds to specific receptors on the surface of target cells, including fibroblasts, smooth muscle cells, and glial cells. PDGF exists in several isoforms, which are generated by alternative splicing of a single gene, and have been implicated in various physiological and pathological processes, such as tissue repair, atherosclerosis, and tumor growth.
Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.
Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.
Transforming growth factors (TGFs) are a family of cytokines, or signaling proteins, that play crucial roles in regulating various cellular processes, including cell growth, differentiation, apoptosis (programmed cell death), and extracellular matrix production. They were initially identified due to their ability to induce the transformation of normal cells into cancerous cells in vitro. However, they also have tumor-suppressive functions under normal conditions.
TGFs are divided into two main classes: TGF-α (Transforming Growth Factor-alpha) and TGF-β (Transforming Growth Factor-beta). TGF-α is a single polypeptide chain, while TGF-β exists as a dimer. Both TGF-α and TGF-β bind to specific transmembrane receptors on the cell surface, leading to the activation of intracellular signaling pathways that ultimately regulate gene expression.
TGF-β is a potent regulator of immune responses, fibrosis, and cancer progression. In the context of cancer, TGF-β can act as both a tumor suppressor and a promoter. Initially, TGF-β inhibits cell proliferation and induces apoptosis in normal cells and early-stage tumor cells. However, in advanced stages of cancer, TGF-β signaling can contribute to tumor progression by promoting angiogenesis (the formation of new blood vessels), invasion, metastasis, and immune evasion.
Dysregulation of TGF-β signaling has been implicated in various diseases, including fibrosis, autoimmune disorders, and cancer. Therefore, understanding the complex roles of TGFs in cellular processes is essential for developing targeted therapies to treat these conditions.
Fibroblast Growth Factors (FGFs) are a family of growth factors that play crucial roles in various biological processes, including cell survival, proliferation, migration, and differentiation. They bind to specific tyrosine kinase receptors (FGFRs) on the cell surface, leading to intracellular signaling cascades that regulate gene expression and downstream cellular responses. FGFs are involved in embryonic development, tissue repair, and angiogenesis (the formation of new blood vessels). There are at least 22 distinct FGFs identified in humans, each with unique functions and patterns of expression. Some FGFs, like FGF1 and FGF2, have mitogenic effects on fibroblasts and other cell types, while others, such as FGF7 and FGF10, are essential for epithelial-mesenchymal interactions during organ development. Dysregulation of FGF signaling has been implicated in various pathological conditions, including cancer, fibrosis, and developmental disorders.
Genomic imprinting is a epigenetic process that leads to the differential expression of genes depending on their parental origin. It involves the methylation of certain CpG sites in the DNA, which results in the silencing of one of the two copies of a gene, either the maternal or paternal allele. This means that only one copy of the gene is active and expressed, while the other is silent.
This phenomenon is critical for normal development and growth, and it plays a role in the regulation of genes involved in growth and behavior. Genomic imprinting is also associated with certain genetic disorders, such as Prader-Willi and Angelman syndromes, which occur when there are errors in the imprinting process that lead to the absence or abnormal expression of certain genes.
It's important to note that genomic imprinting is a complex and highly regulated process that is not yet fully understood. Research in this area continues to provide new insights into the mechanisms underlying gene regulation and their impact on human health and disease.
Insulin-like growth factor binding proteins (IGFBPs) are a family of proteins that bind to and regulate the biological activity of insulin-like growth factors (IGFs), specifically IGF-1 and IGF-2. There are six distinct IGFBPs (IGFBP-1 to IGFBP-6) in humans, each with unique structural features, expression patterns, and functions.
The primary function of IGFBPs is to modulate the interaction between IGFs and their cell surface receptors, thereby controlling IGF-mediated intracellular signaling pathways involved in cell growth, differentiation, and survival. IGFBPs can either enhance or inhibit IGF actions depending on the specific context, such as cell type, subcellular localization, and presence of other binding partners.
In addition to their role in IGF regulation, some IGFBPs have IGF-independent functions, including direct interaction with cell surface receptors, modulation of extracellular matrix composition, and participation in cell migration and apoptosis. Dysregulation of IGFBP expression and function has been implicated in various pathological conditions, such as cancer, diabetes, and cardiovascular diseases.
A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.
Hepatocyte Growth Factor (HGF) is a paracrine growth factor that plays a crucial role in various biological processes, including embryonic development, tissue repair, and organ regeneration. It is primarily produced by mesenchymal cells and exerts its effects on epithelial cells, endothelial cells, and hepatocytes (liver parenchymal cells).
HGF has mitogenic, motogenic, and morphogenic properties, promoting cell proliferation, migration, and differentiation. It is particularly important in liver biology, where it stimulates the growth and regeneration of hepatocytes following injury or disease. HGF also exhibits anti-apoptotic effects, protecting cells from programmed cell death.
The receptor for HGF is a transmembrane tyrosine kinase called c-Met, which is expressed on the surface of various cell types, including hepatocytes and epithelial cells. Upon binding to its receptor, HGF activates several intracellular signaling pathways, such as the Ras/MAPK, PI3K/Akt, and JAK/STAT pathways, which ultimately regulate gene expression, cell survival, and cell cycle progression.
Dysregulation of HGF and c-Met signaling has been implicated in various pathological conditions, including cancer, fibrosis, and inflammatory diseases. Therefore, targeting this signaling axis represents a potential therapeutic strategy for these disorders.
Endothelial growth factors (ECGFs or EGFs) are a group of signaling proteins that stimulate the growth, proliferation, and survival of endothelial cells, which line the interior surface of blood vessels. These growth factors play crucial roles in various physiological processes, including angiogenesis (the formation of new blood vessels), wound healing, and vascular development during embryogenesis.
One of the most well-studied EGFs is the vascular endothelial growth factor (VEGF) family, which consists of several members like VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor (PlGF). These factors bind to specific receptors on the surface of endothelial cells, leading to a cascade of intracellular signaling events that ultimately result in cell proliferation, migration, and survival.
Other EGFs include fibroblast growth factors (FGFs), hepatocyte growth factor (HGF), platelet-derived growth factor (PDGF), and transforming growth factor-beta (TGF-β). Dysregulation of endothelial growth factors has been implicated in various pathological conditions, such as cancer, diabetic retinopathy, age-related macular degeneration, and cardiovascular diseases. Therefore, understanding the functions and regulation of EGFs is essential for developing novel therapeutic strategies to treat these disorders.
Transforming Growth Factor-alpha (TGF-α) is a type of growth factor, specifically a peptide growth factor, that plays a role in cell growth, proliferation, and differentiation. It belongs to the epidermal growth factor (EGF) family of growth factors. TGF-α binds to the EGF receptor (EGFR) on the surface of cells and activates intracellular signaling pathways that promote cellular growth and division.
TGF-α is involved in various biological processes, including embryonic development, wound healing, and tissue repair. However, abnormal regulation of TGF-α has been implicated in several diseases, such as cancer. Overexpression or hyperactivation of TGF-α can contribute to uncontrolled cell growth and tumor progression by stimulating the proliferation of cancer cells and inhibiting their differentiation and apoptosis (programmed cell death).
TGF-α is produced by various cell types, including epithelial cells, fibroblasts, and immune cells. It can be secreted in a membrane-bound form (pro-TGF-α) or as a soluble protein after proteolytic cleavage.
Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.
In the context of medicine and pharmacology, "kinetics" refers to the study of how a drug moves throughout the body, including its absorption, distribution, metabolism, and excretion (often abbreviated as ADME). This field is called "pharmacokinetics."
1. Absorption: This is the process of a drug moving from its site of administration into the bloodstream. Factors such as the route of administration (e.g., oral, intravenous, etc.), formulation, and individual physiological differences can affect absorption.
2. Distribution: Once a drug is in the bloodstream, it gets distributed throughout the body to various tissues and organs. This process is influenced by factors like blood flow, protein binding, and lipid solubility of the drug.
3. Metabolism: Drugs are often chemically modified in the body, typically in the liver, through processes known as metabolism. These changes can lead to the formation of active or inactive metabolites, which may then be further distributed, excreted, or undergo additional metabolic transformations.
4. Excretion: This is the process by which drugs and their metabolites are eliminated from the body, primarily through the kidneys (urine) and the liver (bile).
Understanding the kinetics of a drug is crucial for determining its optimal dosing regimen, potential interactions with other medications or foods, and any necessary adjustments for special populations like pediatric or geriatric patients, or those with impaired renal or hepatic function.
Nerve Growth Factors (NGFs) are a family of proteins that play an essential role in the growth, maintenance, and survival of certain neurons (nerve cells). They were first discovered by Rita Levi-Montalcini and Stanley Cohen in 1956. NGF is particularly crucial for the development and function of the peripheral nervous system, which connects the central nervous system to various organs and tissues throughout the body.
NGF supports the differentiation and survival of sympathetic and sensory neurons during embryonic development. In adults, NGF continues to regulate the maintenance and repair of these neurons, contributing to neuroplasticity – the brain's ability to adapt and change over time. Additionally, NGF has been implicated in pain transmission and modulation, as well as inflammatory responses.
Abnormal levels or dysfunctional NGF signaling have been associated with various medical conditions, including neurodegenerative diseases (e.g., Alzheimer's and Parkinson's), chronic pain disorders, and certain cancers (e.g., small cell lung cancer). Therefore, understanding the role of NGF in physiological and pathological processes may provide valuable insights into developing novel therapeutic strategies for these conditions.
Glucose is a simple monosaccharide (or single sugar) that serves as the primary source of energy for living organisms. It's a fundamental molecule in biology, often referred to as "dextrose" or "grape sugar." Glucose has the molecular formula C6H12O6 and is vital to the functioning of cells, especially those in the brain and nervous system.
In the body, glucose is derived from the digestion of carbohydrates in food, and it's transported around the body via the bloodstream to cells where it can be used for energy. Cells convert glucose into a usable form through a process called cellular respiration, which involves a series of metabolic reactions that generate adenosine triphosphate (ATP)—the main currency of energy in cells.
Glucose is also stored in the liver and muscles as glycogen, a polysaccharide (multiple sugar) that can be broken down back into glucose when needed for energy between meals or during physical activity. Maintaining appropriate blood glucose levels is crucial for overall health, and imbalances can lead to conditions such as diabetes mellitus.
Hexose phosphates are organic compounds that consist of a hexose sugar molecule (a monosaccharide containing six carbon atoms, such as glucose or fructose) that has been phosphorylated, meaning that a phosphate group has been added to it. This process is typically facilitated by enzymes called kinases, which transfer a phosphate group from a donor molecule (usually ATP) to the sugar molecule.
Hexose phosphates play important roles in various metabolic pathways, including glycolysis, gluconeogenesis, and the pentose phosphate pathway. For example, glucose-6-phosphate is a key intermediate in both glycolysis and gluconeogenesis, while fructose-6-phosphate and fructose-1,6-bisphosphate are important intermediates in glycolysis. The pentose phosphate pathway, which is involved in the production of NADPH and ribose-5-phosphate, begins with the conversion of glucose-6-phosphate to 6-phosphogluconolactone by the enzyme glucose-6-phosphate dehydrogenase.
Overall, hexose phosphates are important metabolic intermediates that help regulate energy production and utilization in cells.
Insulin Receptor Substrate (IRS) proteins are a family of cytoplasmic signaling proteins that play a crucial role in the insulin signaling pathway. There are four main isoforms in humans, namely IRS-1, IRS-2, IRS-3, and IRS-4, which contain several conserved domains for interacting with various signaling molecules.
When insulin binds to its receptor, the intracellular tyrosine kinase domain of the receptor becomes activated and phosphorylates specific tyrosine residues on IRS proteins. This leads to the recruitment and activation of downstream effectors, such as PI3K and Grb2/SOS, which ultimately result in metabolic responses (e.g., glucose uptake, glycogen synthesis) and mitogenic responses (e.g., cell proliferation, differentiation).
Dysregulation of the IRS-mediated insulin signaling pathway has been implicated in several pathological conditions, including insulin resistance, type 2 diabetes, and certain types of cancer.
An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.
Vascular Endothelial Growth Factors (VEGFs) are a family of signaling proteins that stimulate the growth and development of new blood vessels, a process known as angiogenesis. They play crucial roles in both physiological and pathological conditions, such as embryonic development, wound healing, and tumor growth. Specifically, VEGFs bind to specific receptors on the surface of endothelial cells, which line the interior surface of blood vessels, triggering a cascade of intracellular signaling events that promote cell proliferation, migration, and survival. Dysregulation of VEGF signaling has been implicated in various diseases, including cancer, age-related macular degeneration, and diabetic retinopathy.
Hypoglycemia is a medical condition characterized by an abnormally low level of glucose (sugar) in the blood. Generally, hypoglycemia is defined as a blood glucose level below 70 mg/dL (3.9 mmol/L), although symptoms may not occur until the blood sugar level falls below 55 mg/dL (3.0 mmol/L).
Hypoglycemia can occur in people with diabetes who are taking insulin or medications that increase insulin production, as well as those with certain medical conditions such as hormone deficiencies, severe liver illnesses, or disorders of the adrenal glands. Symptoms of hypoglycemia include sweating, shaking, confusion, rapid heartbeat, and in severe cases, loss of consciousness or seizures.
Hypoglycemia is typically treated by consuming fast-acting carbohydrates such as fruit juice, candy, or glucose tablets to rapidly raise blood sugar levels. If left untreated, hypoglycemia can lead to serious complications, including brain damage and even death.
The liver is a large, solid organ located in the upper right portion of the abdomen, beneath the diaphragm and above the stomach. It plays a vital role in several bodily functions, including:
1. Metabolism: The liver helps to metabolize carbohydrates, fats, and proteins from the food we eat into energy and nutrients that our bodies can use.
2. Detoxification: The liver detoxifies harmful substances in the body by breaking them down into less toxic forms or excreting them through bile.
3. Synthesis: The liver synthesizes important proteins, such as albumin and clotting factors, that are necessary for proper bodily function.
4. Storage: The liver stores glucose, vitamins, and minerals that can be released when the body needs them.
5. Bile production: The liver produces bile, a digestive juice that helps to break down fats in the small intestine.
6. Immune function: The liver plays a role in the immune system by filtering out bacteria and other harmful substances from the blood.
Overall, the liver is an essential organ that plays a critical role in maintaining overall health and well-being.
'Tumor cells, cultured' refers to the process of removing cancerous cells from a tumor and growing them in controlled laboratory conditions. This is typically done by isolating the tumor cells from a patient's tissue sample, then placing them in a nutrient-rich environment that promotes their growth and multiplication.
The resulting cultured tumor cells can be used for various research purposes, including the study of cancer biology, drug development, and toxicity testing. They provide a valuable tool for researchers to better understand the behavior and characteristics of cancer cells outside of the human body, which can lead to the development of more effective cancer treatments.
It is important to note that cultured tumor cells may not always behave exactly the same way as they do in the human body, so findings from cell culture studies must be validated through further research, such as animal models or clinical trials.
Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.
Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.
The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.
Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.
Insulin-like Growth Factor Binding Protein 2 (IGFBP-2) is a protein that belongs to the insulin-like growth factor binding protein family. These proteins play a crucial role in regulating the bioavailability and activity of insulin-like growth factors (IGFs), particularly IGF-I and IGF-II, which are important for cell growth, differentiation, and survival.
IGFBP-2 has a high affinity for both IGF-I and IGF-II and functions to modulate their interaction with the IGF receptors. By binding to IGFs, IGFBP-2 can either prolong or shorten their half-life, influence their distribution, and control their access to cell surface receptors. This regulation is essential for maintaining proper growth and development, as well as for preventing uncontrolled cell proliferation and cancer progression.
In addition to its IGF-binding function, IGFBP-2 has also been shown to have IGF-independent effects on various cellular processes, including inflammation, apoptosis, and angiogenesis. These properties make IGFBP-2 a potential biomarker for several diseases, such as cancer, diabetes, and neurodegenerative disorders.
The placenta is an organ that develops in the uterus during pregnancy and provides oxygen and nutrients to the growing baby through the umbilical cord. It also removes waste products from the baby's blood. The placenta attaches to the wall of the uterus, and the baby's side of the placenta contains many tiny blood vessels that connect to the baby's circulatory system. This allows for the exchange of oxygen, nutrients, and waste between the mother's and baby's blood. After the baby is born, the placenta is usually expelled from the uterus in a process called afterbirth.
Rhabdomyosarcoma is a type of cancer that develops in the body's soft tissues, specifically in the muscle cells. It is a rare and aggressive form of sarcoma, which is a broader category of cancers that affect the connective tissues such as muscles, tendons, cartilages, bones, blood vessels, and fatty tissues.
Rhabdomyosarcomas can occur in various parts of the body, including the head, neck, arms, legs, trunk, and genitourinary system. They are more common in children than adults, with most cases diagnosed before the age of 18. The exact cause of rhabdomyosarcoma is not known, but genetic factors and exposure to radiation or certain chemicals may increase the risk.
There are several subtypes of rhabdomyosarcoma, including embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. The type and stage of the cancer determine the treatment options, which may include surgery, radiation therapy, chemotherapy, or a combination of these approaches. Early diagnosis and prompt treatment are crucial for improving the prognosis and long-term survival rates.
Wilms tumor, also known as nephroblastoma, is a type of kidney cancer that primarily affects children. It occurs in the cells of the developing kidneys and is named after Dr. Max Wilms, who first described this type of tumor in 1899. Wilms tumor typically develops before the age of 5, with most cases occurring in children under the age of 3.
The medical definition of Wilms tumor is:
A malignant, embryonal kidney tumor originating from the metanephric blastema, which is a mass of undifferentiated cells in the developing kidney. Wilms tumor is characterized by its rapid growth and potential for spread (metastasis) to other parts of the body, particularly the lungs and liver. The tumor usually presents as a large, firm, and irregular mass in the abdomen, and it may be associated with various symptoms such as abdominal pain, swelling, or blood in the urine.
Wilms tumor is typically treated with a combination of surgery, chemotherapy, and radiation therapy. The prognosis for children with Wilms tumor has improved significantly over the past few decades due to advances in treatment methods and early detection.
Nerve Growth Factor (NGF) is a small secreted protein that is involved in the growth, maintenance, and survival of certain neurons (nerve cells). It was the first neurotrophin to be discovered and is essential for the development and function of the nervous system. NGF binds to specific receptors on the surface of nerve cells and helps to promote their differentiation, axonal growth, and synaptic plasticity. Additionally, NGF has been implicated in various physiological processes such as inflammation, immune response, and wound healing. Deficiencies or excesses of NGF have been linked to several neurological disorders, including Alzheimer's disease, Parkinson's disease, and pain conditions.
'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.
Adipose tissue, also known as fatty tissue, is a type of connective tissue that is composed mainly of adipocytes (fat cells). It is found throughout the body, but is particularly abundant in the abdominal cavity, beneath the skin, and around organs such as the heart and kidneys.
Adipose tissue serves several important functions in the body. One of its primary roles is to store energy in the form of fat, which can be mobilized and used as an energy source during periods of fasting or exercise. Adipose tissue also provides insulation and cushioning for the body, and produces hormones that help regulate metabolism, appetite, and reproductive function.
There are two main types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is the more common form and is responsible for storing energy as fat. BAT, on the other hand, contains a higher number of mitochondria and is involved in heat production and energy expenditure.
Excessive accumulation of adipose tissue can lead to obesity, which is associated with an increased risk of various health problems such as diabetes, heart disease, and certain types of cancer.
Long-acting insulin is a type of insulin therapy used in the management of diabetes mellitus. It refers to a class of insulin products that have a prolonged duration of action, typically lasting between 18 and 24 hours or even up to 36 hours. This allows for once-or twice-daily dosing, providing a steady basal level of insulin to help control blood glucose levels throughout the day and night.
Examples of long-acting insulins include:
1. Insulin Glargine (e.g., Lantus, Toujeo, Basaglar)
2. Insulin Detemir (e.g., Levemir)
3. Insulin Degludec (e.g., Tresiba)
These insulins are designed to have a smooth and consistent release profile, minimizing the risk of hypoglycemia (low blood sugar) compared to older intermediate-acting insulins like NPH or lente insulin. However, individual responses to insulin may vary, and proper dosing, timing, and monitoring are essential for safe and effective use. Always consult with a healthcare professional for personalized advice on insulin therapy.
Gene expression is the process by which the information encoded in a gene is used to synthesize a functional gene product, such as a protein or RNA molecule. This process involves several steps: transcription, RNA processing, and translation. During transcription, the genetic information in DNA is copied into a complementary RNA molecule, known as messenger RNA (mRNA). The mRNA then undergoes RNA processing, which includes adding a cap and tail to the mRNA and splicing out non-coding regions called introns. The resulting mature mRNA is then translated into a protein on ribosomes in the cytoplasm through the process of translation.
The regulation of gene expression is a complex and highly controlled process that allows cells to respond to changes in their environment, such as growth factors, hormones, and stress signals. This regulation can occur at various stages of gene expression, including transcriptional activation or repression, RNA processing, mRNA stability, and translation. Dysregulation of gene expression has been implicated in many diseases, including cancer, genetic disorders, and neurological conditions.
Transfection is a term used in molecular biology that refers to the process of deliberately introducing foreign genetic material (DNA, RNA or artificial gene constructs) into cells. This is typically done using chemical or physical methods, such as lipofection or electroporation. Transfection is widely used in research and medical settings for various purposes, including studying gene function, producing proteins, developing gene therapies, and creating genetically modified organisms. It's important to note that transfection is different from transduction, which is the process of introducing genetic material into cells using viruses as vectors.
Protein binding, in the context of medical and biological sciences, refers to the interaction between a protein and another molecule (known as the ligand) that results in a stable complex. This process is often reversible and can be influenced by various factors such as pH, temperature, and concentration of the involved molecules.
In clinical chemistry, protein binding is particularly important when it comes to drugs, as many of them bind to proteins (especially albumin) in the bloodstream. The degree of protein binding can affect a drug's distribution, metabolism, and excretion, which in turn influence its therapeutic effectiveness and potential side effects.
Protein-bound drugs may be less available for interaction with their target tissues, as only the unbound or "free" fraction of the drug is active. Therefore, understanding protein binding can help optimize dosing regimens and minimize adverse reactions.
Fibroblast growth factor (FGF) receptors are a group of cell surface tyrosine kinase receptors that play crucial roles in various biological processes, including embryonic development, tissue repair, and tumor growth. There are four high-affinity FGF receptors (FGFR1-4) in humans, which share a similar structure, consisting of an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyrosine kinase domain.
These receptors bind to FGFs with different specificities and affinities, triggering a cascade of intracellular signaling events that regulate cell proliferation, differentiation, migration, and survival. Aberrant FGFR signaling has been implicated in several diseases, such as cancer, developmental disorders, and fibrotic conditions. Dysregulation of FGFRs can occur through various mechanisms, including genetic mutations, amplifications, or aberrant expression, leading to uncontrolled cell growth and malignant transformation. Therefore, FGFRs are considered promising targets for therapeutic intervention in several diseases.
Transforming Growth Factor-beta 1 (TGF-β1) is a cytokine that belongs to the TGF-β superfamily. It is a multifunctional protein involved in various cellular processes, including cell growth, differentiation, apoptosis, and extracellular matrix production. TGF-β1 plays crucial roles in embryonic development, tissue homeostasis, and repair, as well as in pathological conditions such as fibrosis and cancer. It signals through a heteromeric complex of type I and type II serine/threonine kinase receptors, leading to the activation of intracellular signaling pathways, primarily the Smad-dependent pathway. TGF-β1 has context-dependent functions, acting as a tumor suppressor in normal and early-stage cancer cells but promoting tumor progression and metastasis in advanced cancers.
Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.
Growth factor receptors are a type of cell surface receptor that bind to specific growth factors, which are signaling molecules that play crucial roles in regulating various cellular processes such as growth, differentiation, and survival. These receptors have an extracellular domain that can recognize and bind to the growth factor and an intracellular domain that can transduce the signal into the cell through a series of biochemical reactions.
There are several types of growth factors, including fibroblast growth factors (FGFs), epidermal growth factors (EGFs), vascular endothelial growth factors (VEGFs), and transforming growth factors (TGFs). Each type of growth factor has its own specific receptor or family of receptors.
Once a growth factor binds to its receptor, it triggers a cascade of intracellular signaling events that ultimately lead to changes in gene expression, protein synthesis, and other cellular responses. These responses can include the activation of enzymes, the regulation of ion channels, and the modulation of cytoskeletal dynamics.
Abnormalities in growth factor receptor signaling have been implicated in various diseases, including cancer, developmental disorders, and autoimmune diseases. For example, mutations in growth factor receptors can lead to uncontrolled cell growth and division, which is a hallmark of cancer. Therefore, understanding the structure and function of growth factor receptors has important implications for the development of new therapies for these diseases.
Prothrombin is a protein present in blood plasma, and it's also known as coagulation factor II. It plays a crucial role in the coagulation cascade, which is a complex series of reactions that leads to the formation of a blood clot.
When an injury occurs, the coagulation cascade is initiated to prevent excessive blood loss. Prothrombin is converted into its active form, thrombin, by another factor called factor Xa in the presence of calcium ions, phospholipids, and factor Va. Thrombin then catalyzes the conversion of fibrinogen into fibrin, forming a stable clot.
Prothrombin levels can be measured through a blood test, which is often used to diagnose or monitor conditions related to bleeding or coagulation disorders, such as liver disease or vitamin K deficiency.
Hypoglycemic agents are a class of medications that are used to lower blood glucose levels in the treatment of diabetes mellitus. These medications work by increasing insulin sensitivity, stimulating insulin release from the pancreas, or inhibiting glucose production in the liver. Examples of hypoglycemic agents include sulfonylureas, meglitinides, biguanides, thiazolidinediones, DPP-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists. It's important to note that the term "hypoglycemic" refers to a condition of abnormally low blood glucose levels, but in this context, the term is used to describe agents that are used to treat high blood glucose levels (hyperglycemia) associated with diabetes.
Insulin antibodies are proteins produced by the immune system that recognize and bind to insulin. They are typically formed in response to an exposure to exogenous insulin, such as in people with diabetes who use insulin therapy. In some cases, the presence of insulin antibodies can affect insulin absorption, distribution, metabolism, and elimination, leading to variable insulin requirements, reduced glycemic control, and potentially an increased risk of hypoglycemia or hyperglycemia. However, not all individuals with insulin antibodies experience clinical consequences, and the significance of their presence can vary between individuals.
Hemangiopericytoma is a rare type of soft tissue sarcoma, which is a cancer that develops from the cells that surround blood vessels. It specifically arises from the pericytes, which are cells that help regulate blood flow in capillaries. Hemangiopericytomas typically form in the membranes surrounding the brain and spinal cord (meninges), but they can also occur in other parts of the body such as the lungs, abdomen, or extremities.
These tumors usually grow slowly, but they can become aggressive and spread to other parts of the body (metastasize). Symptoms depend on the location of the tumor, but may include headaches, seizures, weakness, or numbness in the arms or legs. Diagnosis typically involves imaging tests like MRI or CT scans, followed by a biopsy to confirm the presence of cancer cells. Treatment usually consists of surgical removal of the tumor, often accompanied by radiation therapy and/or chemotherapy to help prevent recurrence or spread of the disease.
Deoxyribonucleic acid (DNA) is the genetic material present in the cells of organisms where it is responsible for the storage and transmission of hereditary information. DNA is a long molecule that consists of two strands coiled together to form a double helix. Each strand is made up of a series of four nucleotide bases - adenine (A), guanine (G), cytosine (C), and thymine (T) - that are linked together by phosphate and sugar groups. The sequence of these bases along the length of the molecule encodes genetic information, with A always pairing with T and C always pairing with G. This base-pairing allows for the replication and transcription of DNA, which are essential processes in the functioning and reproduction of all living organisms.
Beckwith-Wiedemann syndrome (BWS) is a genetic overgrowth disorder that affects several parts of the body. It is characterized by an increased risk of developing certain tumors, especially during the first few years of life. The symptoms and features of BWS can vary widely among affected individuals.
The medical definition of Beckwith-Wiedemann syndrome includes the following major criteria:
1. Excessive growth before birth (macrosomia) or in infancy (infantile gigantism)
2. Enlargement of the tongue (macroglossia)
3. Abdominal wall defects, such as an omphalocele (protrusion of abdominal organs through the belly button) or a diastasis recti (separation of the abdominal muscles)
4. Enlargement of specific internal organs, like the kidneys, liver, or pancreas
5. A distinctive facial appearance, which may include ear creases or pits, wide-set eyes, and a prominent jaw
Additional findings in BWS can include:
1. Increased risk of developing embryonal tumors, such as Wilms tumor (a type of kidney cancer), hepatoblastoma (a liver cancer), and neuroblastoma (a nerve tissue cancer)
2. Hypoglycemia (low blood sugar) in infancy due to hyperinsulinism (overproduction of insulin)
3. Asymmetric growth, where one side of the body or a specific region is significantly larger than the other
4. Ear abnormalities, such as cupped ears or low-set ears
5. Developmental delays and learning disabilities in some cases
Beckwith-Wiedemann syndrome is caused by changes in the chromosome 11p15 region, which contains several genes that regulate growth and development. The most common cause of BWS is an epigenetic abnormality called paternal uniparental disomy (UPD), where both copies of this region come from the father instead of one copy from each parent. Other genetic mechanisms, such as mutations in specific genes or imprinting center defects, can also lead to BWS.
The diagnosis of Beckwith-Wiedemann syndrome is typically based on clinical findings and confirmed by molecular testing. Management includes regular monitoring for tumor development, controlling hypoglycemia, and addressing any other complications as needed. Surgical intervention may be required in cases of organ enlargement or structural abnormalities. Genetic counseling is recommended for affected individuals and their families to discuss the risks of recurrence and available reproductive options.