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Crenolanib
Crenolanib besylate (CP-868,596-26 or AR-868,596-26, 4-piperidinamine, 1- -[(3-Methyl-3-oxetanyl)_methoxy.html" ;"title="-[5-[(3-Methyl-3-oxetanyl) methoxy">-[5-[(3-Methyl-3-oxetanyl) methoxy1H-benzimidazol-1-yl 8-quinolinyl]-, monobenzenesulfonate) is an investigational inhibitor being developed by AROG Pharmaceuticals, LLC. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer, including acute myeloid leukemia (AML), gastrointestinal stromal tumor (GIST), and glioma. Crenolanib is an orally bioavailable benzamidazole that selectively and potently inhibits signaling of wild-type and mutant isoforms of class III receptor tyrosine kinases (RTK) FLT3 (FMS-like Tyrosine Kinase 3), PDGFR α (Platelet-Derived Growth Factor Receptor), and PDGFR β. Unlike most RTK inhibitors, crenolanib is a type I mutant-specific inhibitor that preferentially binds to phosphorylated active kinases with the ‘DFG in’ conformation motif. B ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDGFR
Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes. Mechanism of action The PDGF family consists of PDGF-A, -B, -C and -D, which form either homo- or heterodimers (PDGF-AA, -AB, -BB, -CC, -DD). The four PDGFs are inactive in their monomeric forms. The PDGFs bind to the protein tyrosine kinase receptors PDGF receptor-α and -β. These two receptor isoforms dimerize upon binding the PDGF dimer, leading to three possible receptor combinations, namely -αα, -ββ and -αβ. The extracellular region of the receptor consists of five immunoglobulin-like domain ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may include feeling tired, shortness of breath, easy bruising and bleeding, and increased risk of infection. Occasionally, spread may occur to the brain, skin, or gums. As an acute leukemia, AML progresses rapidly, and is typically fatal within weeks or months if left untreated. Risk factors include smoking, previous chemotherapy or radiation therapy, myelodysplastic syndrome, and exposure to the chemical benzene. The underlying mechanism involves replacement of normal bone marrow with leukemia cells, which results in a drop in red blood cells, platelets, and normal white blood cells. Diagnosis is generally based on bone marrow aspiration and specific blood tests. AML has several subtypes for which treatments and outcomes may vary. The fir ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Myelodysplastic Syndrome
A myelodysplastic syndrome (MDS) is one of a group of cancers in which immature blood cells in the bone marrow do not mature, and as a result, do not develop into healthy blood cells. Early on, no symptoms typically are seen. Later, symptoms may include feeling tired, shortness of breath, bleeding disorders, anemia, or frequent infections. Some types may develop into acute myeloid leukemia. Risk factors include previous chemotherapy or radiation therapy, exposure to certain chemicals such as tobacco smoke, pesticides, and benzene, and exposure to heavy metals such as mercury or lead. Problems with blood cell formation result in some combination of low red blood cell, platelet, and white blood cell counts. Some types have an increase in immature blood cells, called blasts, in the bone marrow or blood. The types of MDS are based on specific changes in the blood cells and bone marrow. Treatments may include supportive care, drug therapy, and hematopoietic stem cell transplantati ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Stromal
Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any organ, for example in the uterine mucosa (endometrium), prostate, bone marrow, lymph node and the ovary. They are cells that support the function of the parenchymal cells of that organ. The most common stromal cells include fibroblasts and pericytes. The term ''stromal'' comes from Latin , "bed covering", and Ancient Greek , , "bed". Stromal cells are an important part of the body's immune response and modulate inflammation through multiple pathways. They also aid in differentiation of hematopoietic cells and forming necessary blood elements. The interaction between stromal cells and tumor cells is known to play a major role in cancer growth and progression. In addition, by regulating local cytokine networks (e.g. M-CSF, LIF), bone marrow stromal cells have been described to be i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Mitogen-activated Protein Kinase Kinase
Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a dual-specificity kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK). MAP2K is classified as . There are seven genes: * (a.k.a. MEK1) * (a.k.a. MEK2) * (a.k.a. MKK3) * (a.k.a. MKK4) * (a.k.a. MKK5) * (a.k.a. MKK6) * (a.k.a. MKK7) The activators of p38 (MKK3 and MKK6), JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways. The acronym MEK derives from MAPK/ERK Kinase. Role in melanoma MEK is a member of the MAPK signaling cascade that is activated in melanoma. When MEK is inhibited, cell proliferation is blocked and apoptosis (controlled cell death) is induced. See also * Signal transduction * MAP kinase * MAP kinase kinase kinase * MAP kinase kinase kinase kinase Mitogen-activated protein kinase kinase kinase kinase (MAP4K) is a family of proteins involved in cellular signal transduction. * MAP4K1 (aka HPK1) * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dermatofibrosarcoma Protuberans
Dermatofibrosarcoma protuberans (DFSP) is a rare locally aggressive malignant cutaneous soft-tissue sarcoma. DFSP develops in the connective tissue cells in the middle layer of the skin (dermis). Estimates of the overall occurrence of DFSP in the United States are 0.8 to 4.5 cases per million persons per year. In the United States, DFSP accounts for between 1 and 6 percent of all soft tissue sarcomas and 18 percent of all cutaneous soft tissue sarcomas. In the Surveillance, Epidemiology and End Results (SEER) tumor registry from 1992 through 2004, DFSP was second only to Kaposi sarcoma. Presentation Dermatofibrosarcoma protuberans begins as a minor firm area of skin most commonly about to 1 to 5 cm in diameter. It can resemble a bruise, birthmark, or pimple. It is a slow-growing tumor and is usually found on the torso but can occur anywhere on the body. About 90% of DFSPs are low-grade sarcomas. About 10% are mixed, containing a high-grade sarcomatous component (DFSP-FS) ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDGFB
Platelet-derived growth factor subunit B is a protein that in humans is encoded by the ''PDGFB'' gene. Function The protein encoded by this gene is a member of the platelet-derived growth factor family. The four members of this family are mitogenic factors for cells of mesenchymal origin and are characterized by a motif of eight cysteines. This gene product can exist either as a homodimer (PDGF-BB) or as a heterodimer with the platelet-derived growth factor alpha (PDGFA) polypeptide (PDGF-AB), where the dimers are connected by disulfide bonds. Clinical significance Mutations in this gene are associated with meningioma. Reciprocal translocations between chromosomes 22 and 17, at sites where the ''PDGFB'' and ''COL1A1'' genes are respectively located or, alternatively, an abnormal small supernumerary ring chromosome merge these two genes to form a ''COL1A''-''PDGFB'' fusion gene. This fusion gene greatly overproduces PDGFB and is considered responsible for causing the develop ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chronic Myelomonocytic Leukemia
Chronic myelomonocytic leukemia (CMML) is a type of leukemia, which are cancers of the blood-forming cells of the bone marrow. In adults, blood cells are formed in the bone marrow, by a process that is known as haematopoiesis. In CMML, there are increased numbers of monocytes and immature blood cells (blasts) in the peripheral blood and bone marrow, as well as abnormal looking cells (dysplasia) in at least one type of blood cell. CMML shows characteristics of a myelodysplastic syndrome (MDS); a disorder that produces abnormal looking blood cells, and a myeloproliferative neoplasm (MPN); a disorder characterised by the overproduction of blood cells. For this reason, CMML was reclassified as a MDS/MPN overlap disorder in 2002. For a diagnosis of CMML, the World Health Organization (WHO) states that the blood monocyte count must be >1x109/L, no Philadelphia chromosome or mutations in the PDGFRA or PDGFRB gene should be present, the blast count must be 10% and 1x109/L is essential for a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDGFRB
Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the ''PDGFRB'' gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies. Gene The ''PDGFRB'' gene is located on human chromosome 5 at position q32 (designated as 5q32) and contains 25 exons. The gene is flanked by the genes for granulocyte-macrophage colony-stimulating factor and Colony stimulating factor 1 receptor (also termed macrophage-colony stimulating factor receptor), all three of which may be lost together by a single deletional mutation thereby causing development of the 5q-syndrome. Other genetic abnormalities in ''PDGFRB'' lead to various forms of potentially malignant bone marrow disorders: small deletions in and chromosome translocations causing fusions between ''PDGFRB'' and any one of at least 30 genes can cause Myeloproliferative neoplasms that commonly involve eosinophilia, eosinophil-induced organ injury, and possible progressio ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
DIPG
Diffuse midline glioma (DMG), previously called Diffuse Intrinsic Pontine Glioma (DIPG) is a fatal tumour that arises in the brainstem; most commonly in the pons or thalamus. DMG is believed to be caused by genetic mutations that cause epigenetic changes in cells of the developing nervous system, resulting in a failure of the cells to properly differentiate. Currently, the standard of care is fractionated external beam radiotherapy, as the tumour location precludes surgery, and chemotherapy has shown to be ineffective, however the estimated survival post-diagnosis remains only 9-15 months. Diagnosis Like most brainstem tumors, diagnosing diffuse intrinsic pontine glioma usually involves non-invasive brain imaging like MRI, in addition to neurologic physical exam. Biopsies and other procedures are very uncommon. Similar to DIPG, diffuse midline gliomas (DMG) often fall into similar categories for both diagnosis and treatment as DIPG and are often categorized together. More rece ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pons
The pons (from Latin , "bridge") is part of the brainstem that in humans and other bipeds lies inferior to the midbrain, superior to the medulla oblongata and anterior to the cerebellum. The pons is also called the pons Varolii ("bridge of Varolius"), after the Italian anatomist and surgeon Costanzo Varolio (1543–75). This region of the brainstem includes neural pathways and tracts that conduct signals from the brain down to the cerebellum and medulla, and tracts that carry the sensory signals up into the thalamus.Saladin Kenneth S.(2007) Anatomy & physiology the unity of form and function. Dubuque, IA: McGraw-Hill Structure The pons is in the brainstem situated between the midbrain and the medulla oblongata, and in front of the cerebellum. A separating groove between the pons and the medulla is the inferior pontine sulcus. The superior pontine sulcus separates the pons from the midbrain. The pons can be broadly divided into two parts: the basilar part of the pons (ventral ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gliomas
A glioma is a type of tumor that starts in the glial cells of the brain or the spine. Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours. Signs and symptoms Symptoms of gliomas depend on which part of the central nervous system is affected. A brain glioma can cause headaches, vomiting, seizures, and cranial nerve disorders as a result of increased intracranial pressure. A glioma of the optic nerve can cause visual loss. Spinal cord gliomas can cause pain, weakness, or numbness in the extremities. Gliomas do not usually metastasize by the bloodstream, but they can spread via the cerebrospinal fluid and cause "drop metastases" to the spinal cord. Complex visual hallucinations have been described as a symptom of low-grade glioma. A child who has a subacute disorder of the central nervous system that produces cranial nerve abnormalities (especially of cranial nerve VII and the lower bulbar ner ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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