Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following the development of the cyclotron in 1932, radio-isotopes became available for use in medicine both as tracer substances and therapeutic agents. The father of nuclear medicine, Dr J. H. Lawrence, pioneered their use in a range of disease states and found that radio-isotopes were of enormous value in the diagnosis and treatment of haemopoetic disease, particularly the myeloproliferative disorders. Radioactive phosphorus 32P emerged as the radio-isotope of choice for the myelosuppressive treatment of myeloproliferative disorders. This article also describes the use of radio-isotopes in the treatment of other disorders: chronic myeloid leukaemia, chronic lymphocytic leukaemia and myeloma, work that is now largely forgotten. All myeloproliferative disorders may evolve without treatment into myelodysplastic syndrome or blast-cell transformation. It is accepted that life is prolonged in myeloproliferative disorders treated with 32P or alkylating agents, yet both are leukaemogenic. The ideal form of treatment for polycythaemia vera is unknown and will remain so, for patients with this disorder often outlive their physician and achieve 90% of normal life expectation. 32P remains the treatment of choice for elderly patients with polycythaemia vera.
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PMID:Use of radioactive phosphorus in haematology. 937 45

Myeloproliferative diseases (MPD) include polycythemia vera (PV), essential thrombocythemia, agnogenic myeloid metaplasia, and chronic myelogenous leukemia. The focus of this report is on PV, which is characterized by an increase in red blood cells, granulocytes, and platelets. Complications associated with PV are an increased risk of thrombosis and abnormal bleeding. Phlebotomy to a hematocrit less than 45% is the mainstay of treatment for erythrocythemia, but may further increase the platelet count, necessitating the use of a platelet-lowering agent in conjunction with phlebotomy. Other treatment strategies include low-dose aspirin or other antithrombotic therapy and cytoreduction. Mounting evidence of the leukemogenicity and mutagenicity of radioactive phosphorus and alkylating agents, as administered using "conventional" regimens, has restricted the liberal use of these treatments. Three drugs have emerged as useful because of their efficacy in reducing the elevated platelet count: anagrelide, hydroxyurea (HU), and interferon alfa (IFN). It is clear that no single agent satisfies all the needs for cytoreduction that arise during the course of PV. Future protocols should be designed that draw on the large body of experience already gained with these drugs to transcend the limitations of single-agent therapy and to improve quality of life as well as survival. Semin Hematol 38(suppl 2):25-28.
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PMID:Current management in polycythemia vera. 1124 99

The reactions of 21-hydroxyprogesterone with Lawesson's reagent in toluene or [Formula: see text] gave four P-heterocyclic androst-4-ene derivatives (two tautomeric pairs): 4-(3-thioxoandrost-4-en-17[Formula: see text]-yl)-1,3,2-oxathiaphosphole-2- sulfide (2), 4-(3-thioxoandrost-4-en-17[Formula: see text]-ylidene)-1,3,2-oxathiaphospholane-2-sulfide (3), 4-(3-oxoandrost-4-en-17[Formula: see text]-yl)-1,3,2-oxathiaphosphole-2-sulfide (4), and 4-(3-oxoandrost-4-en-17[Formula: see text]-ylidene)-1,3,2- oxathiaphospholane-2-sulfide (5). The structures of all novel 17-substituted steroids were elucidated from their analytic and spectral data (HRMS, IR, 1D NMR and 2D NMR-HSQC, HMBC, NOESY, COSY). The detailed NMR analysis for all compounds revealed the presence of two pairs of signals in approx. 8:2 ratio indicating the existence of two diastereoisomers (a and b) with different configurations at the phosphorus atom. A parallel analysis of heteronuclear 2D [Formula: see text]-[Formula: see text] spectra (HSQC and HMBC) and homonuclear 2D spectra (NOESY and COSY) enabled complete [Formula: see text] and [Formula: see text] assignments of each isomer and provided evidence for the preferred configuration on phosphorus atom. Cytotoxic activity in vitro was tested against four tumor cell lines (human cervix carcinoma HeLa cells, chronic myelogenous leukemia K-562 and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compounds 3a,b and 4a,b showed a poor activity against HeLa and MDA-MB-453 cell lines, while against MDA-MB-361 cell line, all tested compounds exerted very weak cytotoxic effect. All compounds exerted moderate activity against K562 cells. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, and toxicity to brine shrimp Artemia salina were evaluated. All tested compounds showed strong antifungal activity.
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PMID:Synthesis, characterization and biological evaluation of some novel P-heterocyclic androst-4-ene derivatives. 2374 68

Tyrosine kinase inhibitors (TKIs) are at the forefront of molecular-targeted therapies for cancer. With the advent of imatinib for the treatment of chronic myelogenous leukemia, a new wave of small-molecule therapeutics redefined the oncologic treatment to become chronically administered medications with tolerable side-effect profiles compared with cytotoxic agents. Effects on bone mineral metabolism were observed during early imatinib treatment, in the form of hypophosphatemia with increased urinary phosphorus excretion. This finding led to detailed investigations of off-target effects responsible for changes in bone cell maturation, activity, and impact on bone mass. Subsequently, another BCR-Abl inhibitor (dasatinib), vascular endothelial growth factor (VEGF) inhibitors (sorafenib and sunitinib) as well as rearranged during transfection (RET) inhibitors (vandetanib and cabozantinib) were developed. Inhibition of bone resorption appears to be a class effect and is likely contributed by TKI effects on the hematopoietic and mesenchymal stem cells. As long-term, prospective, clinical outcomes data accumulate on these targeted therapies, the full extent of off-target side effects on bone health will need to be considered along with the significant benefits of tyrosine kinase inhibition in oncologic treatment.
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PMID:Effects of tyrosine kinase inhibition on bone metabolism: untargeted consequences of targeted therapies. 2447 55

Acute severe hypophosphatemia can be life threatening and is associated with mortality and impaired cardiac and respiratory function. Several conditions including decreased absorption or increased urinary phosphate excretion, shifts from the extracellular to intracellular compartments, and phosphate consumption by rapidly proliferating cells are known to induce moderate to severe acute hypophosphatemia. Although hypophosphatemia and/or phosphate depletion in patients with acute or chronic myeloid leukemia have been reported in the literature, hypophosphatemia due to acute lymphoblastic leukemia (ALL) is very rare. We report a case of history of ALL complicated by life-threatening hypophosphatemia manifesting as generalized muscle weakness, fatigue, acute shortness of breath, and difficulty in standing up and walking for 3 days. Serum inorganic phosphate levels were consistently low (0.06 mmol/L). The patient was hospitalized and thought to have a relapsed ALL.Anticancer agents and oral phosphate (660 mg twice daily) were administered. On the second day of treatment, the patient began to improve, and the patient gradually fully recovered within 5 days.We suggested that this hypophosphatemia was induced by a shift of phosphorus into leukemic cells that rapidly replicated in the tissues and excessive cellular phosphate consumption by rapidly proliferating cells. Serum phosphate levels should always be monitored,especially in suspected life-threatening manifestation in relapsed ALL.
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PMID:Life-threatening hypophosphatemia and/or phosphate depletion in a patient with acute lymphoblastic leukemia: a rare case report. 2526 44

The aim of the study is to assess the efficacy of seaweed for circular nutrient management to reduce eutrophication levels in the aquatic environment. We performed a comparative Life Cycle Assessment (LCA) of two reference waste management systems treating seaweed as biowaste, i.e. landfill disposal and combustion, and an alternative scenario using the seaweed Saccharina latissima as a resource for biobased fertilizer production. Life Cycle Impact Assessment (LCIA) methods were improved by using a cradle-to-cradle approach, quantifying fate factors for nitrogen and phosphorus loss from fertilized agriculture to the aquatic environment. We also differentiated between nitrogen- and phosphorus-limited marine water to improve the traditional freshwater impact category, making this indicator suitable for decision support in relation to coastal water management schemes. Offshore cultivation of Saccharina latissima with an average productivity of 150Mg/km(2) in Danish waters in 2014 was applied to a cultivation scenario of 208km(2). The bioresource scenario performs better than conventional biowaste management systems, delivering a net reduction in aquatic eutrophication levels of 32.29kgNeq. and 16.58kgPO4(3-)eq. per Mg (dry weight) of seaweed, quantified by the ReCiPe and CML impact assessment methods, respectively. Seaweed cultivation, harvest and reuse of excess nutrients from the aquatic environment is a promising approach for sustainable resource cycling in a future regenerative economy that exploits manmade emissions as a resource for closed loop biobased production while significantly reducing eutrophication levels in 3 out of 7 Danish river basin districts. We obtained at least 10% bioextraction of phosphorus manmade emissions (10%, 89% and >100%) and contributed significantly to local nitrogen reduction goals according to the Water Framework Directive (23%, 78% and >100% of the target).
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PMID:Bioextraction potential of seaweed in Denmark - An instrument for circular nutrient management. 2715 93

Since phosphorus (P) is a non-renewable element essential for life, it is extremely important to explore any potential supply of P, including that recovered from human excreta and urban wastewater. This study aimed to assess, using Life Cycle Assessment (LCA), whether recovering dissipated P by producing sludge-based phosphate fertilizer can be a suitable method to reduce P depletion. Environmental impacts of four scenarios of production of sludge-based phosphate fertilizers were compared to those of production of triple super phosphate, a mineral phosphate fertilizer used as a reference scenario. The novelty of this study was to estimate environmental impacts of sludge-based phosphate fertilizer production using a "product" LCA perspective instead of a "waste" LCA perspective. Consequently, upstream production of sludge was considered by allocating part of the environmental burdens of wastewater treatment to sludge production. Life Cycle Impact Assessment was performed using the CML-IA characterization method. Results indicated that sludge-based phosphate fertilizers appeared less environmentally friendly than mineral phosphate fertilizers, due to the contribution of the upstream burden of sludge production and P recovery. Finally, although P recovery helps preserve the mineral P resource, the overall assessment remains unfavorable for sludge-based products due to the low yields of P recovery, low P concentration of the sludge and the large amounts of energy and reactants needed to recover the P.
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PMID:Environmental impacts of phosphorus recovery from a "product" Life Cycle Assessment perspective: Allocating burdens of wastewater treatment in the production of sludge-based phosphate fertilizers. 3050 35

Phosphorus (P) is a non-renewable resource extracted from phosphate rock to produce agricultural fertilizers. Since P is essential for life, it is important to preserve this resource and explore alternative sources of P to reduce its criticality. This study aimed to assess whether fertilizing with sludge-based phosphate fertilizers (SBPF) can be a suitable alternative to doing so with fertilizers produced from phosphate rock. Environmental impacts of production and land application of SBPF from four recovery processes were compared to those of two reference scenarios: triple super phosphate (TSP) and sewage sludge. To avoid bias when comparing scenarios, part of the environmental burden of wastewater treatment is allocated to sludge production. The CML-IA method was used to perform life cycle impact assessment. Results highlighted that production and land application of SBPF had higher environmental impacts than those of TSP due to the large amounts of energy and reactants needed to recover P, especially when sludge had a low P concentration. Certain environmental impacts of production and land application of sewage sludge were similar to those of SBPF. Sensitivity analysis conducted for cropping systems highlighted variability in potential application rates of sewage sludge or SBPF. Finally, because they contain lower contents of heavy metals than sewage sludge or TSP, SBPF are of great interest, but they require more mineral fertilizers to supplement their fertilization than sewage sludge. Thus, SBPF have advantages and disadvantages that need to be considered, since they may influence their use within fertilization practices.
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PMID:Environmental performances of production and land application of sludge-based phosphate fertilizers-a life cycle assessment case study. 3177 34


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