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Inotuzumab Ozogamicin
Inotuzumab ozogamicin, sold under the brand name Besponsa, is an antibody-drug conjugate medication used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The medication consists of a humanized monoclonal antibody against CD22 ( inotuzumab), linked to a cytotoxic agent from the class of calicheamicins called ozogamicin. This drug was discovered by scientists collaborating at Celltech and Wyeth, and it was developed by Pfizer which had acquired Wyeth. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical use Inotuzumab ozogamicin is used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia. It is administered by intravenous infusion in a doctor's office or clinic. In studies in pregnant animals, the drug caused harm to the fetus at doses less than those used clinically, and so the drug has not been tested in pregnant women. Pregnant women should not take inotuzumab ozog ...
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Inotuzumab
Inotuzumab ozogamicin, sold under the brand name Besponsa, is an antibody-drug conjugate medication used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). The medication consists of a humanized monoclonal antibody against CD22 (inotuzumab), linked to a cytotoxic agent from the class of calicheamicins called ozogamicin. This drug was discovered by scientists collaborating at Celltech and Wyeth, and it was drug development, developed by Pfizer which had acquired Wyeth. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical use Inotuzumab ozogamicin is used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia. It is administered by intravenous infusion in a doctor's office or clinic. In studies in pregnant animals, the drug caused harm to the fetus at doses less than those used clinically, and so the drug has not been tested in pregnant women. Pregnant women should not take i ...
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CD22
CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases. CD22 is a sugar binding transmembrane protein, which specifically binds sialic acid with an immunoglobulin (Ig) domain located at its N-terminus. The presence of Ig domains makes CD22 a member of the immunoglobulin superfamily. CD22 functions as an inhibitory receptor for B cell receptor (BCR) signaling. It is also involved in the B cell trafficking to Peyer's patches in mice. In mice, it has been shown that CD22 blockade restores homeostatic microglial phagocytosis in aging brains. Structure CD22 is a transmembrane protein with a molecular weight of 140 kDa. The extracellular part of CD22 consists of seven immunoglobulin domains and the intr ...
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Liver Toxicity
Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins), and herbal remedies (two prominent examples being kava, mechanism unknown, and comfrey, through its pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins. More than 900 drugs have been implicated in causing liver injury (see LiverTox, externa ...
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Gemtuzumab Ozogamicin
Gemtuzumab ozogamicin, sold under the brand name Mylotarg, is an antibody-drug conjugate (a drug-linked monoclonal antibody) that is used to treat acute myeloid leukemia. The most common grade 3 and higher adverse reactions that occurred during Induction 1 and Intensification 2 in ≥ 5% of people who received gemtuzumab ozogamicin were infection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension. Medical uses In the United States, gemtuzumab ozogamicin is indicated for newly diagnosed CD33-positive acute myeloid leukemia (AML) for adults and children one month and older and for the treatment of relapsed or refractory CD33-positive AML in adults and children two years and older. Mechanism and side effects Gemtuzumab is a monoclonal antibody to CD33 linked to a cytotoxic agent from the class of calicheamicins ( ozogamicin). CD33 is expressed in most leukemic blast cells but also i ...
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Cell Nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support. The cell nucleus contains nearly all of the cell's genome. Nuclear DNA is often organized into multiple chromosomes – long stands of DNA dotted with various proteins, such as histones, that protect and organize the DNA. The genes within these chromosomes are structured in such a way to promote cell function. The nucleus maintains the integrity of genes and controls the activities of the cell by regulating gene expres ...
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Lysosome
A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane proteins, and its lumenal proteins. The lumen's pH (~4.5–5.0) is optimal for the enzymes involved in hydrolysis, analogous to the activity of the stomach. Besides degradation of polymers, the lysosome is involved in various cell processes, including secretion, plasma membrane repair, apoptosis, cell signaling, and energy metabolism. Lysosomes act as the waste disposal system of the cell by digesting used materials in the cytoplasm, from both inside and outside the cell. Material from outside the cell is taken up through endocytosis, while material from the inside of the cell is digested through autophagy. The sizes of the organelles vary greatly—the larger ones can be more than 10 times the size of the smaller ones. They were discov ...
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Endocytosis
Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. Endocytosis includes pinocytosis (cell drinking) and phagocytosis (cell eating). It is a form of active transport. History The term was proposed by De Duve in 1963. Phagocytosis was discovered by Élie Metchnikoff in 1882. Pathways Endocytosis pathways can be subdivided into four categories: namely, receptor-mediated endocytosis (also known as clathrin-mediated endocytosis), caveolae, pinocytosis, and phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is .... *Clathrin-mediated endocytosis is mediated by the production of smal ...
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B Cells
B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasma membrane where they serve as a part of B-cell receptors. When a naïve or memory B cell is activated by an antigen, it proliferates and differentiates into an antibody-secreting effector cell, known as a plasmablast or plasma cell. Additionally, B cells present antigens (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines. In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ where they were first discovered by Chang and Glick, which is why the 'B' stands for bursa and not bone marrow as commonly believed. B cells, unlike the other two classes of lymphocytes, T cells and ...
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Injection Site Reaction
Injection site reactions are allergic reactions that result in cutaneous necrosis that may occur at sites of medication injection, typically presenting in one of two forms, (1) those associated with intravenous infusion or (2) those related to intramuscular injection.James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . Intramuscular injections may produce a syndrome called livedo dermatitis. See also * Application site reaction * Vitamin K reactions * Skin lesion * List of cutaneous conditions Many skin conditions affect the human integumentary system—the organ system covering the entire surface of the body and composed of skin, hair, nails, and related muscle and glands. The major function of this system is as a barrier against t ... References Drug eruptions {{Cutaneous-condition-stub ...
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Jaundice
Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine. Normal levels of bilirubin in blood are below 1.0  mg/ dl (17  μmol/ L), while levels over 2–3 mg/dl (34–51 μmol/L) typically result in jaundice. High blood bilirubin is divided into two types – unconjugated and conjugated bilirubin. Causes of jaundice vary from relatively benign to potentially fatal. High unconjugated bilirubin may be due to excess red blood cell breakdown, large bruises, genetic conditions s ...
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Elevated Transaminases
In medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), may be an indicator of liver dysfunction. Other terms include transaminasemia, transaminitis, and elevated liver enzymes (though they are not the only enzymes in the liver). Normal ranges for both ALT and AST vary by gender, age, and geography and are roughly 8-40 U/L (0.14-0.67 μkal/L). Mild transaminesemia refers to levels up to 250 U/L. Drug-induced increases such as that found with the use of anti-tuberculosis agents such as isoniazid are limited typically to below 100 U/L for either ALT or AST. Muscle sources of the enzymes, such as intense exercise, are unrelated to liver function and can markedly increase AST and ALT. Cirrhosis of the liver or fulminant liver failure secondary to hepatitis commonly reach values for both ALT and AST in the >1000 U/L range. Elevated transaminases that persist less than six months are termed "acute" in na ...
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Leukopenia
Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of infection. Signs and symptoms Symptoms may include: * skin or mouth ulcers * sore throat * cough * difficulty in breathing * light-headedness * fever * chills * body aches. Leukopenia vs. neutropenia Neutropenia, a subtype of leukopenia, refers to a decrease in the number of circulating neutrophil granulocytes, the most abundant white blood cells. The terms ''leukopenia'' and ''neutropenia'' may occasionally be used interchangeably, as the neutrophil count is the most important indicator of infection risk. Agranulocytosis is an acute form of neutropenia. Causes Medical conditions Low white cell count may be due to acute viral infections, such as a cold or influenza. It has been associated with chemotherapy, radiation therapy, myelofibr ...
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