Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Juliusz Lempert was born in 1890 in Poland. A few years later the poor Jewish family emigrated to the United States. Lempert obtained his MD degree at Long Island Medical College, and soon after that established a small hospital of his own in Manhattan. Later he bought an old five-storey building and converted it into a new otological medical center, which he called Endaural Hospital. His life was rather difficult with the wave of antisemitism in the United States and the adversity which he encountered so many times. However his contribution to the microsurgical treatment of conductive deafness is immense. He elaborated and introduced a new method of mastoidectomy and, first of all, fenestration--a new one-stage surgical technique to be applied in cases of otosclerosis. This precise, sophisticated operation revolutionized surgical treatment. With a dentist's drill Lempert created a new window on the horizontal canal, in this way the sound wave could stimulate the inner ear. He was to call it "fenestration nov-ovalis". Lempert was never a member of any ENT society and worked in his hospital alone. When suddenly his only son was stricken with leukemia and died, Lempert was completely broken, and never returned to this work. The next blows were new operative methods of otosclerosis: stapes mobilisation introduced by Rosen and stapedectomy by Shea. He never accepted these new techniques. It was a painful experience for a surgical genius who had at so many times been hurt during his life. He could not believe that his fenestration was definitely gone. Lempert quickly deteriorated physically and mentally, and died in 1958.
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PMID:[Juliusz Lempert (1890-1959): the author of the fenestration technique]. 976 Jul 79

In three new approved indications (non Hodgkin's lymphoma, Hodgkin's lymphoma and acute lymphoblastic leukaemia) and in three previously existing indications (ovarian cancer, soft tissue sarcomas and osteogenic sarcomas), non comparative trials show that ifosfamide can induce tumour regression in patients who relapse after a first course of chemotherapy (sometimes containing cyclophosphamide). But clinical assessment has not yet formally demonstrated that this leads to a significant increase in survival time and/or quality of life, mainly because of toxicity. In cervical cancer, a new indication, a comparative trial shows higher tumour response rates with the ifosfamide + cisplatin combination than with cisplatin alone. However, the greater toxicity of the combination and the lack of any increase in survival must both be taken into account. In breast cancer and lung cancer comparative trials show no difference in efficacy between cyclophosphamide and ifosfamide, while toxicity may be worse with ifosfamide. Ifosfamide has no specific value in these approved indications. The same applied to ENT cancer, against which ifosfamide seems to have little activity.
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PMID:Ifosfamide: new idications-new dose strength. Limited evidence of effectiveness. 1018 82

Fibrin glue (FG) is one of the blood products known to be very useful for local hemostatic measure and as a medically valuable tool for adhesion, sealing, anastomosis, repair microvascular and nerve grafts in medical and surgical procedures. Before 1996, FG was used to a limited extent in Thailand due to the high cost. Technology for locally prepared FG was transferred to Bangkok International Hemophilia Training Center of the World Federation of Hemophilia (IHTC-WFH) in July 1996 by Prof. Uri Martinowitz and the late Prof. Henri Horoszowski. Since then FG has been widely used and proved to be very useful in Thailand. This paper reports 145 cases using low cost locally prepared FG at Ramathibodi Hospital during November 1996 to December 1997. A total of 145 cases with age range from 5 months to 73 years, which included 55 pediatrics and 90 adults, 100 males and 45 females. The amount of FG used was 1-80 ml per case. Clinical procedures included dental surgery (46), open heart surgery (35), ENT (28), orthopedic (13) including 2-3 joint correction in one session in 2 hemophiliacs, neurology (11), plastic repair (7), liver (2) and severe bleeding in dengue hemorrhagic fever (3). Forty-seven cases had hemostatic disorders. The result of local hemostatic, adhesive and sealant effect of FG was satisfactory with no complications. In open heart surgery, the amount of content in chest drain decreased and none required reopen-surgery to stop bleeding. Dental surgery was performed in 43 patients with bleeding disorders i.e. hemophilia, idiopathic thrombocytopenic purpura, leukemia, severe thrombocytopenia, patients on anticoagulant, etc. Only 3 cases (7%) required blood component compared to all of the 50 no-FG controlled cases (100%) that required blood component therapy. FG has proved to be very useful in many aspects i.e. minimizing blood product usage, decreasing medical workload, reducing medical cost and increasing patients' convenience and satisfaction in particular.
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PMID:Low cost locally prepared fibrin glue for clinical applications: reported of 145 cases. Committee of Bangkok International Hemophilia Training Center. 1073 May 18

Cladribine, an adenosine deaminase inhibitor, has been developed and launched by Ortho Biotech in collaboration with The Scripps Research Institute for the treatment of several neoplasms, including acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, cutaneos T-cell lymphoma, hairy-cell leukemia and non-Hodgkin's lymphoma. It was first launched in the US in February 1993. Ortho Biotech and The Scripps Research Institute have since been developing the compound for its potential use in multiple sclerosis (MS). In 1997, Ortho filed air NDA in the US for the use of cladribine in the treatment of relapsing-remitting and secondary progressive MS. An FDA drug advisory committee was planning to meet in January 1999 to discuss the NDA. However, Ortho cancelled the meeting. Following an FDA inspection during December 1998 and January 1999, the Scripps Clinic received a warning letter from the FDA in April 1999 regarding violations in the clinical studies of cladribine for MS, and Ortho withdrew the NDA after concluding that further clinical studies would be necessary. Cladribine has been known since the 1960s as an intermediate for the synthesis of 2-deoxynucleotides and its potential for the treatment of leukemia was disclosed in 1984. The Scripps Research Institute and the Johnson & Johnson group hold several patents claiming preparation methods (US 05208327), and additional indications, such as multiple sclerosis (WO-09316706) and rheumatoid arthritis (US-05310732). The associated patent, WO-09323508, is the only one among those patents that claims the use of unmodified cladribine for the treatment of leukemia, but it focuses particularly on a specific form of the disease, chronic myelogenous leukemia. Analysts at UBS Warburg predicted in October 2001, that the product would make US sales of $50 million in 2004 for its MS indication.
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PMID:Cladribine. Ortho Biotech Inc. 1189 41

Acute leukemia carries a poor prognosis, especially in older patients, emphasizing the need for novel therapies. Reasons for treatment failure include high rates of relapse and treatment-related toxicities. Farnesyltransferase inhibitors (FTIs), a new class of agents that can interfere with intracellular signaling, are good therapeutic candidates for study in these diseases, given the relatively high levels of the target enzyme, farnesyltransferase, expressed in bone marrow and by peripheral circulating lymphocytes. ZARNESTRA (formerly R115777, Ortho Biotech Oncology, Raritan, NJ) is an FTI that has clinical activity in solid tumors and antileukemic activity in vitro. In a phase I trial of Zarnestra in patients with high-risk leukemia (resistant or relapsed acute myeloid leukemia [AML] or acute lymphocytic leukemia [ALL], chronic myeloid leukemia [CML] in blast crisis, or AML in poor prognosis subgroups), patients experienced an overall response rate of 29%. Zarnestra was well tolerated with no dose-limiting toxicities through doses up to 900 mg twice daily. Assays measuring inhibition of farnesyltransferase activity showed a reliable inhibition at doses greater than 300 mg twice daily, and pharmacokinetic studies indicated that Zarnestra accumulated preferentially in the bone marrow in a dose-dependent fashion. These results suggest that Zarnestra should be studied further in patients with myeloid leukemia.
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PMID:Farnesyltransferase inhibitors and myeloid malignancies: phase I evidence of Zarnestra activity in high-risk leukemias. 1221 91

Nucleoside derivatives are currently used in the treatment of hematologic malignancies. Although intracellular events involved in the pharmacologic action of these compounds have been extensively studied, the role of plasma membrane transporters in nucleoside-derived drug bioavailability and action in leukemia cells has not been comprehensively addressed. We have monitored the amounts of mRNA for the 5 nucleoside transporter isoforms cloned so far (CNT1, CNT2, CNT3, ENT1, and ENT2) in several human cell types and in normal human leukocytes. We then examined the expression patterns of these plasma membrane proteins in patients with chronic lymphocytic leukemia (CLL) and correlated them with in vitro fludarabine cytotoxicity. Despite a huge individual variability in the mRNA amounts for every transporter gene expressed in CLL cells (CNT2, CNT3, ENT1, and ENT2), no relationship between mRNA levels and in vitro fludarabine cytotoxicity was observed. Fludarabine accumulation in CLL cells was mostly, if not exclusively, mediated by ENT-type transporters whose biologic activity was clearly correlated with fludarabine cytotoxicity, which reveals a role of ENT-mediated uptake in drug responsiveness in patients with CLL.
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PMID:Fludarabine uptake mechanisms in B-cell chronic lymphocytic leukemia. 1241 Dec 96

Tetrachloroethylene is used primarily as a dry cleaning agent, an industrial solvent for fats, oils, tars, rubber, and gums, and a metal degreasing agent. Tetrachloroethylene had antihelminthic uses, particularly for hookworms (1.6-8 g/60 kg), and was formerly used in combination with some grain protectants and fumigants. Toxicology and carcinogenesis studies of tetrachloroethylene (99.9% pure) were conducted by inhalation exposure of groups of 50 male and 50 female F344/N rats and B6C3F1 mice 6 hours per day, 5 days per week, for 103 weeks. The exposure concentrations used (0, 200, or 400 ppm for rats and 0, 100, or 200 ppm for mice) were selected on the basis of results from 13-week inhalation studies in which groups of 10 rats and 10 mice of each sex were exposed to tetrachloroethylene at 100-1,600 ppm for 6 hours per day, 5 days per week. During the 13-week studies, 1,600 ppm tetrachloroethylene was lethal to 20%-70% of the rats and mice and reduced the final body weights of survivors. In rats, tetrachloroethylene at 200-800 ppm caused minimal to mild hepatic congestion. In dosed male and female mice, minimal to mild hepatic leukocytic infiltration, centrilobular necrosis, bile stasis (400-1,600 ppm), and mitotic alteration (200-1,600 ppm) were produced. Tetrachloroethylene exposure also caused minimal renal tubular cell karyomegaly in mice at concentrations as low as 200 ppm. During the 2-year studies, exposure to tetrachloroethylene did not consistently affect body weight gains in either rats or mice. Exposure at 400 ppm tetrachloroethylene reduced the survival of male rats (control, 23/50; low dose, 20/50; high dose, 12/50). This reduced survival may have been related to an increased incidence of mononuclear cell leukemia. Tetrachloroethylene at both exposure concentrations reduced the survival of male mice (46/50; 25/50; 32/50), whereas exposure at 200 ppm reduced female mouse survival (36/50; 31/50; 19/50). Early deaths in mice may have been related to the development of hepatocellular carcinomas. Both concentrations of tetrachloroethylene were associated with increased incidences of mononuclear cell leukemia in male rats (28/50; 37/50; 37/50). In female rats, tetrachloroethylene increased the incidence of leukemia (18/50; 30/50; 29/50) and decreased the time to occurrence of the disease. Tetrachloroethylene produced renal tubular cell karyomegaly in male and female rats, renal tubular cell hyperplasia in male rats, and renal tubular cell adenomas or adenocarcinomas (combined) in male rats (1/49; 3/49; 4/50). The incidence of the renal tubular cell tumors was not statistically significant; these uncommon tumors have been consistently found at low incidences in male rats in other 2-year studies of chlorinated ethanes and ethylenes. One low dose male rat had a kidney lipoma, and another had a nephroblastoma. Four high dose male and two high dose female rats had gliomas of the brain, whereas one control male and one control female had this tumor. In male and female mice, tetrachloroethylene caused dose-related increases in the incidences of hepatocellular neoplasms. In males, tetrachloroethylene at 200 ppm increased the incidence of hepatocellular adenomas (11/49; 8/49; 18/50) and at both concentrations increased the incidence of hepatocellular carcinomas (7/49; 25/49; 26/50). In female mice, tetrachloroethylene at both concentrations increased the incidences of hepatocellular carcinomas (1/48; 13/50; 36/50). Tetrachloroethylene also produced renal tubular cell karyomegaly in both sexes of mice, and one low dose male mouse had a tubular cell adenocarcinoma. In these inhalation studies, there were no neoplastic changes in the respiratory tracts of either species, but there was an increase in the incidence of squamous metaplasia in the nasal cavities in dosed male rats (0/50; 5/50; 5/50). Tetrachloroethylene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of male Syrian hamster or male Sprague-Dawley rat liver S9. Tetrachloroethylene was not mutagenic in was not mutagenic in L5178Y/TK± mouse lymphoma cells with or without metabolic activation and did not induce sex-linked recessive lethal mutations in Drosophila melanogaster. Tetrachloroethylene did not induce sister-chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells in the presence or absence of metabolic activation. An audit of the experimental data was conducted for these 2-year studies on tetrachloroethylene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenicity of tetrachloroethylene for male F344/N rats as shown by an increased incidence of mononuclear cell leukemia and uncommon renal tubular cell neoplasms. There was some evidence of carcinogenicity of tetrachloroethylene for female F344/N rats as shown by increased incidences of mononuclear cell leukemia. There was clear evidence of carcinogenicity for B6C3F1 mice as shown by increased incidences of both hepatocellular adenomas and carcinomas in males and of hepatocellular carcinomas in females. Synonyms: carbon bichloride; carbon dichloride; ethylene tetrachloride; per; perc; perchlor; perchlorethylene; perchloroethylene; perk; tetrachlorethylene; 1,1,2,2-tetrachloroethylene Trade names: Ankilostin; Antisal 1; Dee-Solv; Didakene; Dow-Per; ENT 1860; Fedel-Un; Nema; Perclene; Percosolv; Perklone; PerSec; Tetlen; Tetracap; Tetraleno; Tetravec; Tetroguer; Tetropil
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PMID:NTP Toxicology and Carcinogenesis Studies of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4) in F344/N Rats and B6C3F1 Mice (Inhalation Studies). 1274 18

Nucleoside derivatives have important therapeutic activity in chronic lymphocytic leukaemia (CLL). Experimental evidence indicates that in CLL cells most of these drugs induce apoptosis ex vivo, suggesting that programmed cell death is the mechanism of their therapeutic action, relying upon previous uptake and metabolic activation. Although defective apoptosis and poor metabolism often cause resistance to treatment, differential uptake and/or export of nucleosides and nucleotides may significantly modulate intracellular drug bioavailability and, consequently, responsiveness to therapy. Two gene families, SLC28 and SLC29, encode transporter proteins responsible for concentrative and equilibrative nucleoside uptake (CNT and ENT, respectively). Furthermore, selected members of the expanding ATP-binding cassette (ABC) protein family have recently been identified as putative efflux pumps for the phosphorylated forms of these nucleoside-derived drugs, ABCC11 (MRP8) being a good candidate to modulate cell sensitivity to fluoropyrimidines. Sensitivity of CLL cells to fludarabine has also been recently correlated with ENT-type transport function, suggesting that, besides the integrity of apoptotic pathways and appropriate intracellular metabolism, transport across the plasma membrane is also a relevant event during CLL treatment. As long as nucleoside transporter expression in leukaemia cells is not constitutive, the possibility of regulating nucleoside transporter function by pharmacological means may also contribute to improve therapy.
Leukemia 2004 Mar
PMID:Nucleoside transporters in chronic lymphocytic leukaemia. 1473 75

Fludarabine is considered the treatment of choice for most patients with chronic lymphocytic leukemia (CLL). We have analyzed the role of plasma membrane transporters in nucleoside-derived drug bioavailability and action in CLL cells. Among the known plasma membrane transporters, we have previously observed a significant correlation between fludarabine uptake via ENT carriers and ex vivo sensitivity of CLL cells to fludarabine, although mRNA amounts of the equilibrative nucleoside transporters hENT1 and hENT2 do not show any predictive response to treatment. In this study, using polyclonal monospecific antibodies we have observed a significant correlation between the expression of hENT2 by Western blot and fludarabine uptake via hENT carriers and also with ex vivo sensitivity of CLL cells to fludarabine. These results suggest that the equilibrative nucleoside transporter hENT2 plays a role in fludarabine responsiveness in CLL patients.
Leukemia 2005 Jan
PMID:Equilibrative nucleoside transporter-2 (hENT2) protein expression correlates with ex vivo sensitivity to fludarabine in chronic lymphocytic leukemia (CLL) cells. 1551 Jan 96

Ortho-toluidine carcinogenicity has been tested in chronic experiments using mice, rats and dogs. Tumors were induced in 19% of mice (lung and kidney adenomas, leukemia), rats--40% (subcutaneous fat tumors, mammary fibroadenomas, leukemia, renal tumors and hepatic sarcoma). Bladder tumors developed in two dogs after 9 and 10 years of experiment. Both literature and experimental evidence point to o-toluidine as a hazard to humans.
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PMID:[Experimental study of ortho-toluidine carcinogenicity]. 1571 98


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