Misplaced Pages

#539460

80-581: In 1984, the first prognostic indicator for advanced non-Hodkin's lymphoma was developed. An information theory guided, computer search and evaluation procedure entropy minimax was employed to discover the largest sub-groupings for which survival is as extreme as possible In the clinical trials analyzed retrospectively and containing a large fraction of patients not matching the 'good' - of 'good' (Karnofsky status >80 and 'A" Symptoms and SGOT <36 U/L), 'poor' (Karnofsky status <70 or Night sweats) and 'intermediate' (All Remaining) prognosis patterns identified,

160-516: A 50% mortality rate. There is no effective treatment against established cardiomyopathy caused by the drug as of 2010. The drug dexrazoxane , which is an iron chelator may be used to decrease the risk of doxorubicin's cardiotoxicity in certain cases. Another common and potentially fatal complication of doxorubicin is typhlitis , an acute life-threatening inflammation of the bowel. Additionally, some people may develop palmar plantar erythrodysesthesia (PPE), characterized by skin eruptions on

240-462: A compound similar in structure to doxorubicin was found to inhibit plasmepsin II, an enzyme unique to the malarial parasite Plasmodium falciparum . The pharmaceutical company GlaxoSmithKline (GSK) later identified doxorubicin in a set of compounds that inhibit parasite growth. Doxorubicin is also known to be fluorescent. This has often been used to characterize doxorubicin concentrations, and has opened

320-449: A continuous spectrum with a cutoff at maximum energy. The rest of the energy of each decay is carried off by an antineutrino which does not significantly interact and therefore does not contribute to the dose. Most energies of beta emissions are at about a third of the maximum energy. Beta emissions have much lower energies than what is achievable from particle accelerators, no more than few megaelectronvolts. The energy-depth-dose profile

400-493: A dose of 2  Gy radiation or greater. Chronic radiodermatitis occurs with chronic exposure to "sub-erythema" doses of ionizing radiation over a prolonged period, producing varying degrees of damage to the skin and its underlying parts after a variable latent period of several months to several decades. In the past this type of radiation reaction occurred most frequently in radiologists and radiographers who were constantly exposed to ionizing radiation, especially before

480-503: A higher therapeutic index , yet the cardiotoxicity remained. Doxorubicin and daunorubicin together can be thought of as prototype compounds for the anthracyclines . Subsequent research has led to many other anthracycline antibiotics, or analogs, and there are now over 2,000 known analogs of doxorubicin. By 1991, 553 of them had been evaluated in the screening program at the National Cancer Institute (NCI). In 2016 GPX-150

560-510: A pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby , rubis , describing the color. Clinical trials began in the 1960s, and the drug was successful in treating acute leukemia and lymphoma. However, by 1967, it was recognized that daunorubicin could lead to fatal cardiac toxicity. Researchers at Farmitalia soon discovered that changes in biological activity could be made by minor changes in

640-529: A reaction that follows recent administration of a chemotherapeutic agent and occurs with the prior radiation port, characterized by features of radiation dermatitis. Restated, radiation recall dermatitis is an inflammatory skin reaction that occurs in a previously irradiated body part following drug administration. There does not appear to be a minimum dose, nor an established radiotherapy dose relationship. "Alpha burns" are caused by alpha particles , which can cause extensive tissue damage if inhaled. Due to

720-577: A significant difference was found between the survival of patients with and those without a complete response to therapy. The authors concluded that trials using a patient mix weighted toward good prognosis will not find such a difference. In 1993, a retrospective analysis was performed on 2031 patients with aggressive non-Hodgkin's lymphoma, of all ages, treated with a doxorubicin -based chemotherapy regimen such as CHOP between 1982 and 1987. Several patient characteristics were analyzed to determine whether they were associated with differences in survival, and

800-481: A similar prognostic index predictive of outcome in advanced mantle cell lymphoma. There were four factors found to have independent prognostic relevance: age, performance status, LDH, and white blood cell count (WBC). The point values are assigned as follows: The sum of the allotted points correlates with the following risk groups: Doxorubicin Doxorubicin , sold under the brand name Adriamycin among others,

880-506: A skin reaction. Some reactions are immediate, while others may be later (e.g., months after treatment). Acute radiodermatitis occurs when an "erythema dose" of ionizing radiation is given to the skin, after which visible erythema appears up to 24 hours after. Radiation dermatitis generally manifests within a few weeks after the start of radiotherapy. Acute radiodermatitis, while presenting as red patches, may sometimes also present with desquamation or blistering. Erythema may occur at

SECTION 10

#1732863230540

960-414: Is spider veined and with underlying fibrosis . The burns may manifest at different times at different body areas. The Chernobyl liquidators ' burns first appeared on wrists, face, neck and feet, followed by chest and back, then by knees, hips and buttocks. Industrial radiography sources are a common source of beta burns in workers. Radiation therapy sources can cause beta burns during exposure of

1040-565: Is Accord Healthcare S.L.U. Zolsketil pegylated liposomal is a hybrid medicine of Adriamycin. It contains the same active substance as Adriamycin, but is available in a pegylated liposomal formulation. Zolsketil pegylated liposomal was approved for medical use in the European Union in May 2022. On 21 July 2022, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for

1120-520: Is a chemotherapy medication used to treat cancer . This includes breast cancer , bladder cancer , Kaposi's sarcoma , lymphoma , and acute lymphocytic leukemia . It is often used together with other chemotherapy agents . Doxorubicin is given by injection into a vein . Common side effects include hair loss , bone marrow suppression , vomiting , rash, and inflammation of the mouth . Other serious side effects may include allergic reactions such as anaphylaxis , heart damage , tissue damage at

1200-437: Is a pegylated (polyethylene glycol coated) liposome -encapsulated form of doxorubicin, developed to treat Kaposi's sarcoma . The polyethylene glycol coating results in preferential concentration of doxorubicin in the skin. However, this also results in a side effect called palmar plantar erythrodysesthesia (PPE), more commonly known as hand-foot syndrome. Following administration of this form of doxorubicin, small amounts of

1280-484: Is a skin disease associated with prolonged exposure to ionizing radiation. Radiation dermatitis occurs to some degree in most patients receiving radiation therapy, with or without chemotherapy. There are three specific types of radiodermatitis: acute radiodermatitis, chronic radiodermatitis, and eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy. Radiation therapy can also cause radiation cancer. With interventional fluoroscopy, because of

1360-418: Is a curve starting with a surface dose, ascending to the maximum dose in a certain depth d m (usually normalized as 100% dose), then descends slowly through depths of 90% dose (d 90 ) and 80% dose (d 80 ), then falls off linearly and relatively sharply though depth of 50% dose (d 50 ). The extrapolation of this linear part of the curve to zero defines the maximum electron range, R p . In practice, there

1440-430: Is a damage to the skin or other biological tissue and organs as an effect of radiation . The radiation types of greatest concern are thermal radiation , radio frequency energy, ultraviolet light and ionizing radiation . The most common type of radiation burn is a sunburn caused by UV radiation. High exposure to X-rays during diagnostic medical imaging or radiotherapy can also result in radiation burns. As

1520-516: Is a long tail of weaker but deep dose, called "bremsstrahlung tail", attributable to bremsstrahlung . The penetration depth depends also on beam shape, narrower beam tend to have less penetration. In water, broad electron beams, as is the case in homogeneous surface contamination of skin, have d 80 about E/3 cm and R p about E/2 cm, where E is the beta particle energy in MeV. The penetration depth of lower-energy beta in water (and soft tissues)

1600-479: Is about 2 mm/MeV. For a 2.3 MeV beta the maximum depth in water is 11 mm, for 1.1 MeV it is 4.6 mm. The depth where maximum of the energy is deposited is significantly lower. The energy and penetration depth of several isotopes is as follows: For a wide beam, the depth-energy relation for dose ranges is as follows, for energies in megaelectronvolts and depths in millimeters. The dependence of surface dose and penetration depth on beam energy

1680-466: Is also available in liposome -encapsulated forms as Doxil ( pegylated form), Myocet (nonpegylated form), and Caelyx, which are also given by intravenous injection. The FDA approved the first generic version of Doxil, made by Sun, in February 2013. Combination therapy experiments with sirolimus (rapamycin) and doxorubicin have shown promise in treating Akt -positive lymphomas in mice. Further,

SECTION 20

#1732863230540

1760-475: Is an indication of injury severe enough to cause chronic radiation dermatitis. Edema of dermal papillae , if present within 48 hours since the exposition, is followed by transepidermal necrosis . After higher doses, the malpighian layer cells die within 24 hours; lower doses may take 10–14 days to show dead cells. Inhalation of beta radioactive isotopes may cause beta burns of lungs and nasopharyngeal region, ingestion may lead to burns of gastrointestinal tract;

1840-411: Is clearly visible. Radiation burns are caused by exposure to high levels of radiation. Levels high enough to cause burn are generally lethal if received as a whole-body dose, whereas they may be treatable if received as a shallow or local dose. Fluoroscopy may cause burns if performed repeatedly or for too long. Similarly, X-ray computed tomography and traditional projectional radiography have

1920-592: Is commonly used to treat some leukemias and lymphomas , as well as cancers of the bladder , breast , stomach , lung , ovaries , thyroid , soft tissue sarcoma as well as aggressive fibromatosis (desmoid tumor), multiple myeloma , and others. Commonly used doxorubicin-containing regimens are AC (Adriamycin, cyclophosphamide ), TAC ( taxotere , AC), ABVD (Adriamycin, bleomycin , vinblastine , dacarbazine ), BEACOPP , CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine , prednisone ) and FAC ( 5-fluorouracil , adriamycin, cyclophosphamide). Its activity

2000-662: Is dependent on its cumulative dose, with an incidence about 4% when the dose of doxorubicin is 500–550 mg/m , 18% when the dose is 551–600 mg/m and 36% when the dose exceeds 600 mg/m . There are several ways in which doxorubicin is believed to cause cardiomyopathy, including oxidative stress due to iron accumulation, downregulation of genes for contractile proteins, and p53 -mediated apoptosis . Doxorubicin-induced cardiomyopathy typically results in dilated cardiomyopathy, with all four cardiac chambers being enlarged. This results in both systolic and diastolic dysfunction. Eventually, heart failure can result, which carries

2080-450: Is given prophylactically to neurosurgical patients who are receiving whole-brain therapy and systemic steroids. Radiation acne is a cutaneous condition characterized by comedo-like papules occurring at sites of previous exposure to therapeutic ionizing radiation, skin lesions that begin to appear as the acute phase of radiation dermatitis begins to resolve. Radiation recall reactions occur months to years after radiation treatment,

2160-461: Is inhibited by certain antioxidant plant extracts, for example Tragia volubilis aqueous extract. Doxil (see below) is used primarily for the treatment of ovarian cancer where the disease has progressed or recurred after platinum-based chemotherapy , or for the treatment of AIDS -related Kaposi's sarcoma . The most dangerous side effect of doxorubicin is dilated cardiomyopathy , leading to congestive heart failure . The rate of cardiomyopathy

2240-449: Is provided by clothing, especially shoes. The dose is further reduced by limited retention of radioactive particles on skin; a 1 millimeter particle is typically released in 2 hours, while a 50 micrometer particle usually does not adhere for more than 7 hours. Beta emissions are also severely attenuated by air; their range generally does not exceed 6 feet (1.8 m) and intensity rapidly diminishes with distance. The eye lens seems to be

2320-526: The Castle Bravo test was unexpectedly strong. A white snow-like dust, nicknamed by the scientists "Bikini snow" and consisting of contaminated crushed calcined coral , fell for about 12 hours upon the Rongelap Atoll , depositing a layer of up to 2 cm. Residents developed beta burns, mostly on the backs of their necks and on their feet, and were resettled after three days. After 24–48 hours their skin

2400-711: The Operation Upshot–Knothole , sheep as far as 50 miles (80 km) from the test site developed beta burns to their backs and nostrils. During underground nuclear testing in Nevada, several workers developed burns and skin ulcers, in part attributed to exposure to tritium . Beta burns were a serious medical issue for some victims of the Chernobyl disaster ; from 115 patients treated in Moscow, 30% had burns covering 10–50% of body surface, 11% were affected on 50–100% of skin;

2480-472: The genes required for DXR production, although not all of them have been fully characterized. In 1996, Strohl's group discovered, isolated and characterized dox A, the gene encoding the enzyme that converts daunorubicin into DXR. By 1999, they produced recombinant dox A, a cytochrome P450 oxidase , and found that it catalyzes multiple steps in DXR biosynthesis , including steps leading to daunorubicin. This

International Prognostic Index - Misplaced Pages Continue

2560-460: The photon energy , gamma radiation can cause deep gamma burns , with Co internal burns common. Beta burns tend to be shallow as beta particles are not able to penetrate deeply into a body; these burns can be similar to sunburn. Alpha particles can cause internal alpha burns if inhaled, with external damage (if any) being limited to minor erythema. Radiation burns can also occur with high power radio transmitters at any frequency where

2640-515: The DNA chain for replication, preventing the DNA double helix from being released and thereby stopping the process of replication . It may also increase quinone type free radical production, hence contributing to its cytotoxicity. The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to

2720-463: The above factors: The sum of the points allotted correlates with the following risk groups: Although the IPI has shown itself to be a useful clinical tool, widely used by oncologists and a mainstay of risk stratification in clinical trials for lymphoma, it should be kept in mind that it was developed prior to the use of rituximab , which is now included with anthracycline-based combination chemotherapy as of

2800-552: The aircraft carrier USS  Bairoko received beta burns, and there was an increased cancer rate. During the Zebra test of the Operation Sandstone in 1948, three men had beta burns on their hands when removing sample collection filters from drones flying through the mushroom cloud ; their estimated skin surface dose was 28 to 149 Gy, and their disfigured hands required skin grafts . A fourth man showed weaker burns after

2880-543: The beta burns may first manifest in 24–48 hours by itching and/or burning sensation that last for one or two days, sometimes accompanied by hyperaemia . After 1–3 weeks burn symptoms appear; erythema, increased skin pigmentation (dark colored patches and raised areas), followed by epilation and skin lesions . Erythema occurs after 5–15  Gy , dry desquamation after 17 Gy, and bullous epidermitis after 72 Gy. Chronic radiation keratosis may develop after higher doses. Primary erythema lasting more than 72 hours

2960-522: The body absorbs radio frequency energy and converts it to heat. The U.S. Federal Communications Commission (FCC) considers 50 watts to be the lowest power above which radio stations must evaluate emission safety. Frequencies considered especially dangerous occur where the human body can become resonant , at 35 MHz, 70 MHz, 80-100 MHz, 400 MHz, and 1 GHz. Exposure to microwaves of too high intensity can cause microwave burns . Radiation dermatitis (also known as radiodermatitis )

3040-567: The body. They can appear similar to sunburn. Unlike gamma rays, beta emissions are stopped much more effectively by materials and therefore deposit all their energy in only a shallow layer of tissue, causing more intense but more localized damage. On cellular level, the changes in skin are similar to radiodermatitis. The dose is influenced by relatively low penetration of beta emissions through materials. The cornified keratine layer of epidermis has enough stopping power to absorb beta radiation with energies lower than 70 keV. Further protection

3120-452: The combination resulted in unacceptable cardiotoxicity, including risk of cardiac failure manifesting as congestive heart failure (CHF). Published phase II study results have shown that Myocet, trastuzumab, and paclitaxel can safely be used concurrently without the cardiac risk, as measured by reduction in LVEF function, while still achieving superior tumor response. This finding is the basis for

3200-524: The dermis; modern radiotherapy electron beam accelerators take advantage of this. At yet higher energies, above 16 MeV, the effect does not show significantly anymore, limiting the usefulness of higher energies for radiotherapy. As a convention, surface is defined as the topmost 0.5 mm of skin. High-energy beta emissions should be shielded with plastic instead of lead, as high-Z elements generate deeply penetrating gamma bremsstrahlung . The electron energies from beta decay are not discrete but form

3280-431: The drug can leak from capillaries in the palms of the hands and soles of the feet. The result of this leakage is redness, tenderness, and peeling of the skin that can be uncomfortable and even painful. In clinical testing at 50 mg/m dosing every four weeks, half of people developed hand-foot syndrome. The rate of this side effect limits the dose of this formulation that can be given as compared with plain doxorubicin in

International Prognostic Index - Misplaced Pages Continue

3360-559: The earlier Yoke test. The Upshot–Knothole Harry test at the Frenchman Flat site released a large amount of fallout. A significant number of sheep died after grazing on contaminated areas. The AEC however had a policy to compensate farmers only for animals showing external beta burns, so many claims were denied. Other tests on the Nevada Test Site also caused fallout and corresponding beta burns to sheep, horses and cattle. During

3440-412: The epilation threshold for sheared sheep is between 23 and 47 Gy (2500–5000 rep ) and the threshold for normally wooled face is 47–93 Gy (5000–10000 rep), for thickly wooled (33 mm hair length) sheep it is 93–140 Gy (10000–15000 rep). To produce skin lesions comparable with contagious pustular dermatitis , the estimated dose is between 465 and 1395 Gy. The effects depend on both

3520-522: The factors that emerged as significant were, in addition to the Ann Arbor stage: age, elevated serum lactate dehydrogenase (LDH), performance status , and number of extranodal sites of disease. One point is assigned for each of the following risk factors: The sum of the points allotted correlates with the following risk groups: A simplified index can be used when comparing patients within an age group (i.e. 60 or younger, or over 60) and includes only 3 of

3600-557: The fallout particles from their skin did not develop skin lesions. The fishing ship Daigo Fukuryu Maru was affected by the fallout as well; the crew suffered skin doses between 1.7 and 6.0 Gy, with beta burns manifesting as severe skin lesions, erythema, erosions , sometimes necrosis, and skin atrophy . Twenty-three U.S. radar servicemen of the 28-member weather station on Rongerik were affected, experiencing discrete 1–4 mm skin lesions which healed quickly, and ridging of fingernails several months later. Sixteen crew members of

3680-468: The high skin doses that can be generated in the course of the intervention, some procedures have resulted in early (less than two months after exposure) and/or late (two months or more after exposure) skin reactions, including necrosis in some cases. Radiation dermatitis, in the form of intense erythema and vesiculation of the skin, may be observed in radiation ports. As many as 95% of patients treated with radiation therapy for cancer will experience

3760-628: The intensity and the energy of the radiation. Low-energy beta (sulfur-35, 170 keV) produces shallow ulcers with little damage to dermis, while cobalt-60 (310 keV), caesium-137 (550 keV), phosphorus-32 (1.71 MeV), strontium-90 (650 keV) and its daughter product yttrium-90 (2.3 MeV) damage deeper levels of the dermis and can result in chronic radiation dermatitis. Very high energies from electron beams from particle accelerators , reaching tens of megaelectronvolts, can be deeply penetrating. Conversely, megavolt-scale beams can deposit their energy deeper with less damage to

3840-523: The intercalation site, as evidenced by several crystal structures. By intercalation , doxorubicin can also induce histone eviction from transcriptionally active chromatin . As a result, the DNA damage response , epigenome and transcriptome are deregulated in doxorubicin-exposed cells. In the 1950s, an Italian research company, Farmitalia Research Laboratories, began an organized effort to find anticancer compounds from soil-based microbes. A soil sample

3920-493: The ionizing radiation interacts with cells within the body—damaging them—the body responds to this damage, typically resulting in erythema —that is, redness around the damaged area. Radiation burns are often discussed in the same context as radiation-induced cancer due to the ability of ionizing radiation to interact with and damage DNA , occasionally inducing a cell to become cancerous. Cavity magnetrons can be improperly used to create surface and internal burning. Depending on

4000-421: The keratin in the epidermal layer of the skin, external alpha burns are limited to only mild reddening of the outermost layer of skin. "Beta burns" —caused by beta particles —are shallow surface burns, usually of skin and less often of lungs or gastrointestinal tract , caused by beta particles, typically from hot particles or dissolved radionuclides that came to direct contact with or close proximity to

4080-598: The latter being a risk especially for grazing animals. Lost hair begins regrowing in nine weeks and is completely restored in about half a year. The acute dose-dependent effects of beta radiation on skin are as follows: According to other source: As shown, the dose thresholds for symptoms vary by source and even individually. In practice, determining the exact dose tends to be difficult. Similar effects apply to animals, with fur acting as additional factor for both increased particle retention and partial skin shielding. Unshorn thickly wooled sheep are well protected; while

SECTION 50

#1732863230540

4160-531: The liposomal encapsulation of the doxorubicin limits the cardiotoxicity. In theory, by limiting the cardiotoxicity of doxorubicin through liposomal encapsulation, it can be used safely in concurrent combination with other cardiotoxic chemotherapy drugs, such as trastuzumab . There is an FDA black box warning that trastuzumab cannot be used in concurrent combination with doxorubicin, only in sequential combination. Though concurrent combination of trastuzumab and doxorubicin in clinical studies found superior tumor response,

4240-411: The massive exposure was often caused by clothes drenched with radioactive water. Some firefighters developed beta burns of lungs and nasopharyngeal region after inhalation of massive amounts of radioactive smoke . Out of 28 deaths, 16 had skin injuries listed among the causes. The beta activity was extremely high, with beta/gamma ratio reaching 10–30 and beta energy high enough to damage basal layer of

4320-498: The medicinal product Celdoxome pegylated liposomal, intended for the treatment of metastatic breast cancer, advanced ovarian cancer, progressive multiple myeloma and AIDS-related Kaposi's sarcoma. The applicant for this medicinal product is YES Pharmaceutical Development Services GmbH. Celdoxome pegylated liposomal is a hybrid medicine of Adriamycin which has been authorized in the EU since 24 October 1979. Celdoxome pegylated liposomal contains

4400-407: The most common low-grade lymphoma, follicular lymphoma . The prognostic factors that emerged from this were: age, stage, number of lymph node areas involved, serum hemoglobin level, and serum LDH. One point is assigned for each of the following adverse prognostic factors: The sum of the points allotted correlates with the following risk groups: An effort was more recently undertaken to identify

4480-403: The most sensitive organ to beta radiation, even in doses far below maximum permissible dose. Safety goggles are recommended to attenuate strong beta. Careful washing of exposed body surface, removing the radioactive particles, may provide significant dose reduction. Exchanging or at least brushing off clothes also provides a degree of protection. If the exposure to beta radiation is intense,

4560-450: The ongoing phase III trial for FDA approval. Doxorubicin (DXR) is a 14- hydroxylated version of daunorubicin , the immediate precursor of DXR in its biosynthetic pathway. Daunorubicin is more abundantly found as a natural product because it is produced by a number of different wild type strains of Streptomyces . In contrast, only one known non- wild type species , Streptomyces peucetius subspecies cesius ATCC 27952,

4640-432: The palms of the hand or soles of the feet, swelling, pain, and erythema . Due to these side effects and its red color, doxorubicin has earned the nickname "red devil" or "red death." Chemotherapy can cause reactivation of hepatitis B , and doxorubicin-containing regimens are no exception. Doxorubicin and several chemotherapeutic drugs (including cyclophosphamide) can cause a loss of skin pigmentation . There

4720-494: The particles lodged between their toes as hoofed animals did not show problems with feet. About 350–600 cattle were affected by superficial burns and localized temporary loss of dorsal hair; the army later bought 75 most affected cows as the discolored regrown hair lowered their market value. The cows were shipped to Los Alamos and Oak Ridge, where they were observed. They healed, now sporting large patches of white fur; some looked as if they had been scalded. The fallout produced by

4800-589: The patients. The sources can be also lost and mishandled, as in the Goiânia accident , during which several people had external beta burns and more serious gamma burns, and several died. Numerous accidents also occur during radiotherapy due to equipment failures, operator errors, or wrong dosage. Electron beam sources and particle accelerators can be also sources of beta burns. The burns may be fairly deep and require skin grafts, tissue resection or even amputation of fingers or limbs. Radiation burns should be covered by

4880-539: The possibility of using the molecule as a theranostic agent. However, there are significant limitations, as doxorubicin's fluorescence spectrum is known to depend on a variety of factors, including the pH of the environment, solvent dielectric constant and others. Doxorubicin fluorescence is quenched by binding to DNA, and shielded by micelle encapsulation. It is also known to self-quench at high concentrations. In contrast, histone binding amplifies fluorescence. Radiation burn#Delayed effects A radiation burn

SECTION 60

#1732863230540

4960-557: The potential to cause radiation burns if the exposure factors and exposure time are not appropriately controlled by the operator. A study of radiation-induced skin injuries has been performed by the Food and Drug Administration (FDA) based on results from 1994, followed by an advisory to minimize further fluoroscopy-induced injuries. The problem of radiation injuries due to fluoroscopy has been further investigated in review articles in 2000, 2001, 2009 and 2010. Beta burns are frequently

5040-474: The release of photo-activated adriamycin with the aid of nanoporous optical antenna resulted in significant anti-cancer effect in MCF-7 breast cancer cells. In 2006, animal research coupling a murine monoclonal antibody with doxorubicin created an immunoconjugate that was able to eliminate HIV-1 infection in mice. There is some evidence for antimalarial activity for doxorubicin and similar compounds. In 2009,

5120-629: The result of exposure to radioactive fallout after nuclear explosions or nuclear accidents . Shortly after the explosion, the fission products have very high beta activity, with about two beta emissions per each gamma photon. After the Trinity test , the fallout caused localized burns on the backs of cattle in the area downwind. The fallout had the appearance of small flaky dust particles. The cattle showed temporary burns, bleeding, and loss of hair. Dogs were also affected; in addition to localized burns on their backs, they also had burned paws, likely from

5200-671: The same active substance as Adriamycin, but is available in a pegylated liposomal formulation. Celdoxome pegylated liposomal was approved for medical use in the European Union in September 2022. It is also known as hydroxydaunorubicin and hydroxydaunomycin. It is sold under a number of different brand names, including Adriamycin PFS, Adriamycin RDF, or Rubex. Doxorubicin is photosensitive, and containers are often covered by an aluminum bag and/or brown wax paper to prevent light from affecting it. Doxorubicin

5280-515: The same treatment regimen, thereby limiting potential substitution. Substitution would be desirable because liposome-encapsulated doxorubicin is less cardiotoxic than unencapsulated doxorubicin. This liposome-encapsulated form is also approved by the FDA for treatment of ovarian cancer and multiple myeloma. A non-pegylated liposomal doxorubicin, called Myocet, is approved in the European Union and in Canada for

5360-686: The site of injection, radiation recall , and treatment-related leukemia . People often experience red discoloration of the urine for a few days. Doxorubicin is in the anthracycline and antitumor antibiotic family of medications. It works in part by interfering with the function of DNA . Doxorubicin was approved for medical use in the United States in 1974. It is on the World Health Organization's List of Essential Medicines . Versions that are pegylated and in liposomes are also available; however, they are more expensive. Doxorubicin

5440-513: The skin, resulting in large area portals for infections , exacerbated by damage to bone marrow and weakened immune system . Some patients received skin dose of 400–500 Gy. The infections caused more than half of the acute deaths. Several died of fourth degree beta burns between 9–28 days after dose of 6–16 Gy. Seven died after dose of 4–6 Gy and third degree beta burns in 4–6 weeks. One died later from second degree beta burns and dose 1-4 Gy. The survivors have atrophied skin which

5520-477: The standard of care in B-cell lymphomas (the majority of non-Hodgkin's lymphomas). Rituximab has significantly improved the outcomes of lymphoma patients; and its effect on the prognostic value of the IPI is uncertain. Future development of a more rigorous prognostic index may thus be useful. Given the success of the IPI for intermediate grade lymphomas, an effort was undertaken to develop a similar prognostic index for

5600-510: The structure of the compound. A strain of Streptomyces was mutated using N -nitroso- N -methyl urethane, and this new strain produced a different, red-colored antibiotic. They named this new compound Adriamycin, after the Adriatic Sea , and the name was later changed to doxorubicin to conform to the established naming convention. Doxorubicin showed better activity than daunorubicin against mouse tumors, and especially solid tumors. It also showed

5680-528: The treatment of metastatic breast cancer in combination with cyclophosphamide , but it has not been approved by the FDA for use in the United States. Unlike Doxil, the Myocet liposome does not have a polyethylene glycol coating, and therefore does not result in the same rate of PPE. The minimization of this side effect may allow for one-for-one (1:1) substitution with doxorubicin in the same treatment regimen, thereby improving safety with no loss of efficacy. Like Doxil,

5760-553: The use of X-ray filters . Chronic radiodermatitis, squamous and basal cell carcinomas may develop months to years after radiation exposure. Chronic radiodermatitis presents as atrophic indurated plaques, often whitish or yellowish, with telangiectasia, sometimes with hyperkeratosis . Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy is a skin condition that occurs most often in women receiving cobalt radiotherapy for internal cancer. Radiation-induced erythema multiforme may occur when phenytoin

5840-445: The yield is poor. Since daunorubicin is produced by fermentation , it would be ideal if the bacteria could complete DXR synthesis more effectively. Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis . This inhibits the progression of topoisomerase II , an enzyme which relaxes supercoils in DNA for transcription . Doxorubicin stabilizes the topoisomerase II complex after it has broken

5920-443: The yield of DXR. This is of more than academic interest, because at that time DXR cost about $ 1.37 million per kg and current production in 1999 was 225 kg per annum. More efficient production techniques have brought the price down to $ 1.1 million per kg for the non liposomal formulation. Although DXR can be produced semi-synthetically from daunorubicin, the process involves electrophilic bromination and multiple steps, and

6000-615: Was granted orphan drug designation by US FDA. On 24 March 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zolsketil pegylated liposomal, intended for the treatment of metastatic breast cancer, advanced ovarian cancer, progressive multiple myeloma and AIDS-related Kaposi's sarcoma. The applicant for this medicinal product

6080-454: Was initially found to be capable of producing the more widely used doxorubicin. This strain was created by Arcamone et al. in 1969 by mutating a strain producing daunorubicin, but not DXR, at least in detectable quantities. Subsequently, Hutchinson's group showed that under special environmental conditions, or by the introduction of genetic modifications , other strains of Streptomyces can produce doxorubicin. His group also cloned many of

6160-465: Was isolated from the area surrounding the Castel del Monte , a 13th-century castle. A new strain of Streptomyces peucetius , which produced a red pigment, was isolated, and an antibiotic from this bacterium was effective against tumors in mice. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin , combining the name Dauni ,

6240-495: Was itching and burning; in a day or two the sensations subsided, to be followed after 2–3 weeks by epilation and ulcers. Darker-colored patches and raised areas appeared on their skin, blistering was uncommon. Ulcers formed dry scabs and healed. Deeper lesions, painful, weeping and ulcerated, formed on more contaminated residents; the majority healed with simple treatment. In general, the beta burns healed with some cutaneous scarring and depigmentation. Individuals who bathed and washed

6320-431: Was originally made from the bacterium Streptomyces peucetius . In the EU doxorubicin pegylated liposomal (as Caelyx) is indicated to treat breast cancer, ovarian cancer, and AIDS-related Kaposi's sarcoma. It is indicated to treat multiple myeloma in combination with bortezomib . Doxorubicin hydrochloride (as Myocet liposomal) is indicated to treat breast cancer in combination with cyclophosphamide . Doxorubicin

6400-592: Was significant because it became clear that all daunorubicin-producing strains have the necessary genes to produce DXR, the much more therapeutically important of the two. Hutchinson's group went on to develop methods to improve the yield of DXR, from the fermentation process used in its commercial production, not only by introducing dox A encoding plasmids , but also by introducing mutations to deactivate enzymes that shunt DXR precursors to less useful products, for example baumycin-like glycosides . Some triple mutants, that also over-expressed dox A, were able to double

#539460