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Names | |
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Preferred IUPAC name 4,5,6,7-Tetrachloro-3′,6′-dihydroxy-2′,4′,5′,7′-tetraiodo-3H-spiro[[2]benzofuran-1,9′-xanthen]-3-one | |
Other names * C.I. 45440
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Identifiers | |
3D model (JSmol) | |
ChEMBL | |
ChemSpider | |
ECHA InfoCard | 100.021.813 |
EC Number |
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PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
C20H4Cl4I4O5 | |
Molar mass | 973.67 g/mol 1,017.65 g/mol (sodium salt) |
Pharmacology | |
S01JA02 ( WHO ) | |
Hazards | |
GHS labelling: | |
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Warning | |
H315, H319, H335 | |
P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, P501 | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Rose bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) is a stain. Rose bengal belongs to the class of organic compounds called xanthenes. [1] Its sodium salt is commonly used in eye drops to stain damaged conjunctival and corneal cells and thereby identify damage to the eye. The stain is also used in the preparation of Foraminifera for microscopic analysis, allowing the distinction between forms that were alive or dead at the time of collection.
A form of rose bengal is also being studied as a treatment for certain cancers and skin conditions. The cancer formulation of the drug, known as PV-10, is currently undergoing clinical trials for melanoma, [2] breast cancer. [3] and neuroendocrine tumors. The company also has formulated a drug based on rose bengal for the treatment of eczema and psoriasis; this drug, PV-10, is currently in clinical trials as well. [2]
Rose bengal was originally prepared in 1882 by Swiss chemist Robert Ghnem, as an analogue of fluorescein. [4] Rudolf Nietzki at the University of Basel identified the principal constituents of rose bengal as iodine derivatives of di- and tetra-chlorofluorescein. [5] The compound was originally used as a wool dye. [6] Its name derives from rose (flower) and Bengal (region); it is printed as rose bengal or Rose Bengal in the scientific literature. [7]
Despite its complicated photochemistry involving several species, [8] rose bengal is also used in synthetic chemistry as a visible light photoredox catalyst [9] and to generate singlet oxygen from triplet oxygen. The singlet oxygen can then undergo a variety of useful reactions, particularly [2 + 2] cycloadditions with alkenes and similar systems.
Rose bengal can be used to form many derivatives that have important medical functions. One such derivative was created so to be sonosensitive but photoinsensitive, so that with a high intensity focused ultrasound, it could be used in the treatment of cancer. The derivative was formed by amidation of rose bengal, which turned off the fluorescent and photosensitive properties of rose bengal, leading to a usable compound, named in the study as RB2. [10]
Salts of rose bengal include C20H2Cl4I4Na2O5 (CAS 632-69-9). This sodium salt is a dye, which has its own unique properties and uses. [11]
PV-10 (an injectable form of rose bengal) was found to cause an observable response in 60% of tumors treated, according to researchers in a phase II melanoma study. Locoregional disease control was observed in 75% of patients. Also confirmed was a "bystander effect", previously observed in the phase I trial, whereby untreated lesions responded to treatment as well, potentially due to immune system response. These data were based on the interim results (in 2009) of the first 40 patients treated in an 80-patient study. [3] [ needs update ]As of April 2016 [update] a phase-3 study of PV-10 as a single agent therapy for patients with locally advanced cutaneous melanoma (Clinical Trials ID NCT02288897) is enrolling patients. [2]
Rose bengal has been shown to not just prevent the growth and spread of ovarian cancer, but also to cause apoptotic cell death of the cancer cells. This has been proven in vitro, in order to prove that rose bengal is still a possible option in the treatment of cancer, and further research should be done. [12]
Rose bengal has been used to treat colon cancer. In one such study, [13] a protective immune response was generated from immunogenic cell death.
Rose bengal is also used in animal models of ischemic stroke (photothrombotic stroke models) in biomedical research. A bolus of the compound is injected into the venous system. Then the region of interest (e.g., the cerebral cortex) is exposed and illuminated by LASER light of 561 nm. A thrombus is formed in the illuminated blood vessels, causing a stroke in the dependent brain tissue. [14] [15]
Rose bengal has been used for 50 years to diagnose liver and eye cancer. Rose bengal dye is mixed with the homogenate of Brucella and pH of the solution is maintained at 3.8, and this dye is used to diagnose Brucellosis by agglutinating the suspected serum. Rose bengal is slightly irritating and toxic to the eye. [6] It has also been used as an insecticide. [16] [17]
Rose bengal is able to stain cells whenever the surface epithelium is not being properly protected by the preocular tear film, because rose bengal has been proven to not be able to stain cells because of the protective functioning of these preocular tear films. [18] This is why rose bengal is often useful as a stain in diagnosing certain medical issues, such as conjunctival and lid disorders. [19]
Rose bengal has been used for ocular surface staining to study the efficacy of punctal plugs in the treatment of keratoconjunctivitis sicca. [20]
Rose bengal is being researched as an agent in creating nano sutures. [21] Wounds are painted on both sides with it and then illuminated with an intense light. This links the tiny collagen fibers together sealing the wound. [22] [23] [24] Healing is faster and the seal reduces chances of infection. [25] [26]
Rose bengal is used to suppress bacterial growth in several microbiological media, including Cooke's rose bengal agar.
Rose bengal has been used as a protoplasm stain to discriminate between living and dead micro-organisms, particularly Foraminifera, since the 1950s when Bill Walton developed the technique. [27]
Rose bengal acetate can act as a photosensitiser and may have potential in photodynamic therapy to treat some cancers. [28]
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies. Immunotherapy is under preliminary research for its potential to treat various forms of cancer.
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).
Basal-cell carcinoma (BCC), also known as basal-cell cancer, basalioma or rodent ulcer, is the most common type of skin cancer. It often appears as a painless raised area of skin, which may be shiny with small blood vessels running over it. It may also present as a raised area with ulceration. Basal-cell cancer grows slowly and can damage the tissue around it, but it is unlikely to spread to distant areas or result in death.
Light therapy, also called phototherapy or bright light therapy is the exposure to direct sunlight or artificial light at controlled wavelengths in order to treat a variety of medical disorders, including seasonal affective disorder (SAD), circadian rhythm sleep-wake disorders, cancers, and skin wound infections. Treating skin conditions such as neurodermatitis, psoriasis, acne vulgaris, and eczema with ultraviolet light is called ultraviolet light therapy.
Melanoma is the most dangerous type of skin cancer; it develops from the melanin-producing cells known as melanocytes. It typically occurs in the skin, but may rarely occur in the mouth, intestines, or eye. In women, melanomas most commonly occur on the legs; while in men, on the back. Melanoma is frequently referred to as malignant melanoma. However, the medical community stresses that there is no such thing as a 'benign melanoma' and recommends that the term 'malignant melanoma' should be avoided as redundant.
A cancer vaccine, or oncovaccine, is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as therapeutic cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", being prepared from samples taken from the patient, and are specific to that patient.
Uveitis is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is described anatomically, by the part of the eye affected, as anterior, intermediate or posterior, or panuveitic if all parts are involved. Anterior uveitis (iridocyclitis) is the most common, with the incidence of uveitis overall affecting approximately 1:4500, most commonly those between the ages of 20-60. Symptoms include eye pain, eye redness, floaters and blurred vision, and ophthalmic examination may show dilated ciliary blood vessels and the presence of cells in the anterior chamber. Uveitis may arise spontaneously, have a genetic component, or be associated with an autoimmune disease or infection. While the eye is a relatively protected environment, its immune mechanisms may be overcome resulting in inflammation and tissue destruction associated with T-cell activation.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology and a growing subspecialty of oncology.
An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic viruses are thought not only to cause direct destruction of the tumour cells, but also to stimulate host anti-tumour immune system responses. Oncolytic viruses also have the ability to affect the tumor micro-environment in multiple ways.
Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and viral immunotherapy. These branches use three different types of treatment methods: gene overexpression, gene knockout, and suicide gene delivery. Gene overexpression adds genetic sequences that compensate for low to zero levels of needed gene expression. Gene knockout uses RNA methods to silence or reduce expression of disease-causing genes. Suicide gene delivery introduces genetic sequences that induce an apoptotic response in cells, usually to kill cancerous growths. In a slightly different context, virotherapy can also refer more broadly to the use of viruses to treat certain medical conditions by killing pathogens.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being 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. 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. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Uveal melanoma is a type of eye cancer in the uvea of the eye. It is traditionally classed as originating in the iris, choroid, and ciliary body, but can also be divided into class I and class II. Symptoms include blurred vision, loss of vision or photopsia, but there may be no symptoms.
Tumor-infiltrating lymphocytes (TIL) are white blood cells that have left the bloodstream and migrated towards a tumor. They include T cells and B cells and are part of the larger category of ‘tumor-infiltrating immune cells’ which consist of both mononuclear and polymorphonuclear immune cells, in variable proportions. Their abundance varies with tumor type and stage and in some cases relates to disease prognosis.
Oral pigmentation is asymptomatic and does not usually cause any alteration to the texture or thickness of the affected area. The colour can be uniform or speckled and can appear solitary or as multiple lesions. Depending on the site, depth, and quantity of pigment, the appearance can vary considerably.
Cancer treatments are a wide range of treatments available for the many different types of cancer, with each cancer type needing its own specific treatment. Treatments can include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy including small-molecule drugs or monoclonal antibodies, and PARP inhibitors such as olaparib. Other therapies include hyperthermia, immunotherapy, photodynamic therapy, and stem-cell therapy. Most commonly cancer treatment involves a series of separate therapies such as chemotherapy before surgery. Angiogenesis inhibitors are sometimes used to enhance the effects of immunotherapies.
Adoptive cell transfer (ACT) is the transfer of cells into a patient. The cells may have originated from the patient or from another individual. The cells are most commonly derived from the immune system with the goal of improving immune functionality and characteristics. In autologous cancer immunotherapy, T cells are extracted from the patient, genetically modified and cultured in vitro and returned to the same patient. Comparatively, allogeneic therapies involve cells isolated and expanded from a donor separate from the patient receiving the cells.
Racotumomab is a therapeutic cancer vaccine for the treatment of solid tumors that is currently under clinical development by Recombio, an international public-private consortium with the participation of the Center of Molecular Immunology at Havana, Cuba (CIM) and researchers from Buenos Aires University and National University of Quilmes in Argentina. It induces the patient's immune system to generate a response against a cancer-specific molecular target with the purpose of blocking tumor growth, slowing disease progression and ultimately increasing patient survival.
Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.
Talimogene laherparepvec, sold under the brand name Imlygic, is a biopharmaceutical medication used to treat melanoma that cannot be operated on; it is injected directly into a subset of lesions which generates a systemic immune response against the recipient's cancer. The final four year analysis from the pivotal phase 3 study upon which TVEC was approved by the FDA showed a 31.5% response rate with a 16.9% complete response (CR) rate. There was also a substantial and statistically significant survival benefit in patients with earlier metastatic disease and in patients who hadn't received prior systemic treatment for melanoma. The earlier stage group had a reduction in the risk of death of approximately 50% with one in four patients appearing to have met, or be close to be reaching, the medical definition of cure. Real world use of talimogene laherparepvec have shown response rates of up to 88.5% with CR rates of up to 61.5%.
Cellular adoptive immunotherapy is a type of immunotherapy. Immune cells such as T-cells are usually isolated from patients for expansion or engineering purposes and reinfused back into patients to fight diseases using their own immune system. A major application of cellular adoptive therapy is cancer treatment, as the immune system plays a vital role in the development and growth of cancer. The primary types of cellular adoptive immunotherapies are T cell therapies. Other therapies include CAR-T therapy, CAR-NK therapy, macrophage-based immunotherapy and dendritic cell therapy.
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