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Anti-VEGF Agents
Anti–vascular endothelial growth factor therapy, also known as anti-VEGF () therapy or medication, is the use of medications that block vascular endothelial growth factor. This is done in the treatment of certain cancers and in age-related macular degeneration. They can involve monoclonal antibodies such as bevacizumab, antibody derivatives such as ranibizumab (Lucentis), or orally-available small molecules that inhibit the tyrosine kinases stimulated by VEGF: sunitinib, sorafenib, axitinib, and pazopanib (some of these therapies target VEGF receptors rather than the VEGFs). Both antibody-based compounds and the first three orally available compounds are commercialized. The latter two, axitinib and pazopanib, are in clinical trials. Bergers and Hanahan concluded in 2008 that anti-VEGF drugs can show therapeutic efficacy in mouse models of cancer and in an increasing number of human cancers. But, "the benefits are at best transitory and are followed by a restoration of tumour g ...
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Vascular Endothelial Growth Factor
Vascular endothelial growth factor (VEGF, ), originally known as vascular permeability factor (VPF), is a signal protein produced by many cells that stimulates the formation of blood vessels. To be specific, VEGF is a sub-family of growth factors, the platelet-derived growth factor family of Cystine knot, cystine-knot growth factors. They are important signaling proteins involved in both vasculogenesis (the ''De novo synthesis, de novo'' formation of the embryonic circulatory system) and angiogenesis (the growth of blood vessels from pre-existing vasculature). It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate such as in hypoxic conditions. Serum concentration of VEGF is high in bronchial asthma and diabetes mellitus. VEGF's normal function is to create new blood vessels during embryonic development, new blood vessels after injury, muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. It ...
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Lenvatinib
Lenvatinib, sold under the brand name Lenvima among others, is an anti-cancer medication for the treatment of certain kinds of thyroid cancer and for other cancers as well. It was developed by Eisai Co. and acts as a multiple kinase inhibitor against the VEGFR1, VEGFR2 and VEGFR3 kinases. Medical uses Lenvatinib is approved (since 2015) for the treatment of differentiated thyroid cancer that is either locally recurrent or metastatic, progressive, and did not respond to treatment with radioactive iodine (radioiodine). for Lenvima. In May 2016, the US Food and Drug Administration (FDA) approved it (in combination with everolimus) for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy. The drug is also approved in the US and in the European Union for hepatocellular carcinoma that cannot be removed surgically in patients who have not received cancer therapy by mouth or injection. Adverse effects Hypertension (high blood pressure) was the most ...
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Diabetes Mellitus
Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of the body becoming unresponsive to insulin's effects. Classic symptoms include polydipsia (excessive thirst), polyuria (excessive urination), polyphagia (excessive hunger), Weight loss#Unintentional, weight loss, and blurred vision. If left untreated, the disease can lead to various health complications, including disorders of the Cardiovascular disease, cardiovascular system, Diabetic retinopathy, eye, Diabetic nephropathy, kidney, and Diabetic neuropathy, nerves. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes. The major types of diabetes are Type 1 diabetes, type 1 and Type 2 diabetes, type 2. The most common treatment for ty ...
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Thiazolidinediones
The thiazolidinediones , abbreviated as TZD, also known as glitazones after the prototypical drug ciglitazone, are a class of heterocyclic compounds consisting of a five-membered C3NS ring. The term usually refers to a family of drugs used in the treatment of diabetes mellitus type 2 that were introduced in the late 1990s. As of 2024, there are two FDA-approved drugs in this class, pioglitazone and rosiglitazone. Mechanism of action Thiazolidinediones or TZDs act by activating PPARs (peroxisome proliferator-activated receptors), a group of nuclear receptors, specific for '' PPARγ'' (PPAR-gamma, PPARG). They are thus the PPARG agonists subset of PPAR agonists. The endogenous ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor binds to DNA in complex with the retinoid X receptor (RXR), another nuclear receptor, increasing transcription of a number of specific genes and decreasing transcription of others. The main effect ...
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Aflibercept
Aflibercept, sold under the brand names Eylea and Zaltrap among others, is a medication used to treat wet macular degeneration and metastatic colorectal cancer. It was developed by Regeneron Pharmaceuticals. It is an inhibitor of vascular endothelial growth factor (VEGF). Aflibercept is a recombinant fusion protein consisting of the extracellular domains of human VEGF receptor 1 and 2 fused to the Fc portion of human IgG1. By acting as a soluble decoy for the natural VEGF receptors, aflibercept inhibits their activation, thereby reducing angiogenesis. Medical uses Aflibercept (Eylea) is indicated for the treatment of people with neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and retinopathy of prematurity. Aflibercept (Zaltrap), in combination with fluorouracil, leucovorin, and irinotecan (known as FOLFIRI), is indicated for the treatment of people with metastatic colorect ...
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Off-label Use
Off-label use is the use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although most studies of off-label use focus on prescription drugs. Off-label use is very common and generally legal unless it violates ethical guidelines or safety regulations. The ability to prescribe drugs for uses beyond the officially approved indications is commonly used to good effect by healthcare providers. For example, methotrexate is commonly used off-label because its immunomodulatory effects relieve various disorders. However, off-label use can entail health risks and differences in legal liability. Marketing of pharmaceuticals for off-label use is usually prohibited. Indications and labeling laws An '' indication'' is when a drug is medically appropriate for a given condition; an approved indication is when a government drug regula ...
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Verteporfin
Verteporfin (trade name Visudyne), a benzoporphyrin derivative, is a medication used as a photosensitizer for photodynamic therapy to eliminate the abnormal blood vessels in the eye associated with conditions such as the wet form of macular degeneration. Verteporfin accumulates in these abnormal blood vessels and, when stimulated by nonthermal red light with a wavelength of 689 nm in the presence of oxygen, produces highly reactive short-lived singlet oxygen and other reactive oxygen radicals, resulting in local damage to the endothelium and blockage of the vessels.Verteporfin Verteporfin is also used off-label for the treatment of central serous retinopathy. Administration Verteporfin is usually injected intravenously into the largest arm vein. It is injected at a dose of 6 mg/m2 and light-activated. It is usually given 15 minutes before laser treatment. This dose can be repeated 4 times per year. Contraindications Porphyria : Patients with porphyria should not re ...
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Photodynamic Therapy
Photodynamic therapy (PDT) is a form of phototherapy involving light and a photosensitizing chemical substance used in conjunction with molecular oxygen to elicit cell death ( phototoxicity). PDT is used in treating acne, wet age-related macular degeneration, psoriasis, and herpes. It is used to treat malignant cancers, including head and neck, lung, bladder and skin. Advantages lessen the need for delicate surgery and lengthy recuperation and minimal formation of scar tissue and disfigurement. A side effect is the associated photosensitisation of skin tissue. Basics PDT applications involve three components: a photosensitizer, a light source and tissue oxygen. The wavelength of the light source needs to be appropriate for exciting the photosensitizer to produce radicals and/or reactive oxygen species. These are free radicals (Type I) generated through electron abstraction or transfer from a substrate molecule and highly reactive state of oxygen known as singlet oxygen ( ...
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Macular Degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred vision, blurred or vision loss, no vision in the center of the visual field. Early on there are often no symptoms. Some people experience a gradual worsening of vision that may affect one or both eyes. While it does not result in complete blindness, loss of central vision can make it hard to recognize faces, drive, read, or perform other activities of daily life. Visual release hallucinations, Visual hallucinations may also occur. Macular degeneration typically occurs in older people, and is caused by damage to the macula of retina, macula of the retina. Genetic factors and smoking may play a role. The condition is diagnosed through a complete eye exam. Severity is divided into early, intermediate, and late types. The late type is additionally divided into "dry" and "wet" forms, with the dry form making up 90% of cases. The difference between ...
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Ranibizumab
Ranibizumab, sold under the brand name Lucentis among others, is a monoclonal antibody fragment (Fab) created from the same parent mouse antibody as bevacizumab. It is an anti-angiogenic that is approved to treat the "wet" type of age-related macular degeneration (AMD, also ARMD), diabetic retinopathy, and macular edema due to branch retinal vein occlusion or central retinal vein occlusion. Ranibizumab was developed by Genentech and marketed by them in the United States, and elsewhere by Novartis, under the brand name Lucentis. Ranibizumab (Lucentis) was approved for medical use in the United States in June 2006, and in the European Union in January 2007. Medical uses In the United States, ranibizumab is indicated for the treatment of neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization. In the European Union, ranibizumab is indicated for t ...
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Targeted Therapy
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy (oncology), hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells (e.g. with traditional chemotherapy). Because most agents for targeted therapy are biopharmaceuticals, the term ''biologic therapy'' is sometimes synonymous with ''targeted therapy'' when used in the context of cancer therapy (and thus distinguished from chemotherapy, that is, cytotoxic therapy). However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy. Another form of targeted therapy involves the use of nanoengineered enzymes to bind to a tumor cell suc ...
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Vandetanib
Vandetanib, sold under the brand name Caprelsa, is an anti-cancer medication that is used for the treatment of certain tumours of the thyroid gland. It acts as a kinase inhibitor of a number of cell receptors, mainly the vascular endothelial growth factor receptor, the epidermal growth factor receptor, and the RET-tyrosine kinase. The drug was developed by AstraZeneca who later sold the rights to Sanofi in 2015. Medical use Vandetanib is used to treat medullary thyroid cancer in adults who are ineligible for surgery. Contraindications The V804M mutation in RET confers resistance to Vandetanib anti-RET activity. In people with moderate and severe hepatic impairment, no dosage for vandetanib has been recommended, as its safety and efficacy has not been established yet. Vandetanib is contraindicated in people with congenital long QT syndrome. Adverse effects Very common (present in greater than 10% of people) adverse effects include colds, bronchitis, upper respiratory tract ...
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