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

We report a case of adult T-cell leukemia (ATL) with gastric involvement visualized by 111In-chloride scintigraphy. A 55-year-old male patient presented with upper abdominal pain and appetite loss. His barium gastric series showed multiple ulcerating polypoid tumors due to gastric involvement of ATL. These lesions accumulated 111In-chloride and were also avid for 67Ga-citrate. Although the mechanism of 111In-chloride accumulation is unknown, 111In-chloride scintigraphy may be useful in evaluating patients with ATL.
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PMID:Indium-111-chloride scintigraphy visualized gastric involvement in a case of adult T-cell leukemia. 1043 79

A 67 year old man with myelodysplasia was admitted as an emergency with a six week history of rectal bleeding and diarrhoea. Barium enema showed an irregular polypoid filling defect in the lateral wall of the proximal rectum near the rectosigmoid junction. Histology showed this to be a granulocytic sarcoma (extramedullary granulocytic leukaemia; chloroma) infiltrating the bowel. A low index of suspicion of this lesion results in an incorrect diagnosis in many such cases. A chloroacetate esterase immunoperoxidase stain will confirm the granulocytic nature of the tumour cells.
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PMID:Granulocytic sarcoma of the rectum: a rare complication of myelodysplasia. 1069 Jan 84

An apoptosis-inducing protein with molecular weight of 60 kDa has been purified from fetal bovine serum. The N-terminal amino acid sequence of this protein (e.g. I-P-L-D-P-V-A-G-Y-K) reveals that it is bovine fetuin, a fetal protein functioning to control embryogenesis. The apoptosis-inducing activity of fetuin is totally dependent on zinc. Depletion of zinc ion from fetuin or substitution of zinc ion by barium ion completely abolished the apoptosis-inducing activity of fetuin. Interestingly, while the fetuin isolated from fetal serum selectively induces apoptosis in cancer without affecting normal cells, the fetuin isolated from mature serum is completely inactive. This suggests that the biological activity of fetuin is under developmental regulation. In vivo, tumor animal model studies showed that fetuin enhanced survival by up to 141% in P388 leukemia animal model in mice. Fetuin was also found to inhibit prostate cancer formation in a PC-3 prostate cancer model in mice.
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PMID:Fetal fetuin selectively induces apoptosis in cancer cell lines and shows anti-cancer activity in tumor animal models. 1131 90

Amphotropic murine leukemia virus (MLV) can replicate in human cells and is a potential contaminant in vector preparations for human gene transfer studies. We have recently shown that replication of amphotropic MLV in specific human sarcoma and lymphoma lines is possible in the absence of the viral 75-bp transcription enhancer elements. Here, we have tested the replication of an amphotropic MLV, MLV-(MOA), and an enhancer-deficient mutant of this virus in human breast carcinoma-derived cell lines. The proviral expression plasmids use a cytomegalovirus (CMV) promoter for the initial transcription of virus RNA. We found that all cells analyzed are permissive for replication of MLV-(MOA). Enhancer-deficient virus is unable to replicate. However, in two lines the replication defect can be rescued by the spontaneous insertion of a CMV promoter and enhancer into the U3 region. This recombinant virus MLV-(RCMV) replicates with kinetics similar to that of MLV-(MOA) but is restricted to specific cell lines. The potential formation of RCMV recombinants during MLV vector preparation must be considered.
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PMID:Amphotropic murine leukemia virus replication in human mammary epithelial cells and the formation of cytomegalovirus-promoter recombinants. 1187 79

A 59-year-old man with a six-month history of chronic myelomonocytic leukemia (CMML) was admitted to the Kitasato University Hospital because of melena in September 2000. Colonofiberscopy and barium enema demonstrated an ulcerated tumorous lesion in the transverse colon. The histopathologic findings of the ulcer bed revealed diffuse infiltration of granulocytes at each stage of differentiation. The diagnosis of granulocytic sarcoma (GS) was made. Surgical resection was not indicated, because thrombocytopenia was hardly improved enough to allow surgery despite repetitive transfusion of platelet concentrates. CMML developed to refractory anemia with excess of blast in transformation in February 2001. Two courses of low dose cytarabine plus aclarubicin were ineffective on the GS in spite of a decrease in the peripheral blood blasts. Progression to acute myeloid leukemia eventually broke out, in July 2001. The patient died of leukemia complicated with pneumonia and intestinal obstruction. At present, nine cases of GS in the colon have been reported. However, these cases did not include CMML. This is the first report describing GS in the colon associated with CMML.
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PMID:[Granulocytic sarcoma of the colon in chronic myelomonocytic leukemia]. 1246 30

Barium chloride dihydrate, a white crystalline granule or powder, is used in pigments, aluminum refining, leather tanning and coloring, the manufacture of magnesium metal, ceramics, glass, and paper products, as a pesticide, and in medicine as a cardiac stimulant. Toxicology and carcinogenicity studies were conducted by administering barium chloride dihydrate (99% pure) in drinking water to F344/N rats and B6C3F1 mice for 15 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and mouse lymphoma cells. 15-DAY STUDY IN RATS: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm for 15 days, corresponding to average daily doses of 10, 15, 35, 60, or 110 mg barium/kg body weight to males and females. No chemical-related deaths, differences in final mean body weights, or clinical findings of toxicity were observed. Water consumption by male and female rats exposed to 2,000 ppm was slightly less (S16%) than controls during week 2. There were no significant differences in absolute or relative organ weights between exposed and control rats. No biologically significant differences in hematology, clinical chemistry, or neurobehavioral parameters occurred in rats. 15-DAY STUDY IN MICE: Groups of five males and five females received barium chloride dihydrate in the drinking water at concentrations of 0, 40, 80,173, 346, or 692 ppm for 15 days, corresponding to average daily doses of 5,10, 20, 40, or 70 mg barium/kg body weight to males and 5, 10, 15, 40, or 85 mg barium/kg body weight to females. No chemical-related deaths, differences in mean body weights or in water consumption, or clinical findings of toxicity were observed in mice. The relative liver weight of males receiving 692 ppm was significantly greater than that of the controls. The absolute and relative liver weights of females that received 692 ppm were significantly greater than those of the controls. No histopathologic evidence of toxicity was observed in mice. 13-WEEK STUDY IN RATS: Groups of 10 males and 10 females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 500, 1,000, 2,000, or 4,000 ppm for 13 weeks, corresponding to average daily doses of 10, 30, 65, 110, or 200 mg barium/kg body weight to males and 10, 35, 65, 115, or 180 mg barium/kg body weight to females. Three males and one female in the 4,000 ppm groups died during the last week of the study. The final mean body weights of male and female rats receiving 4,000 ppm were significantly lower (13% and 8%) than those of the controls. Water consumption by male and female rats in the 4,000 ppm groups was approximately 30% lower than that by the controls. No clearly chemical-related clinical findings of toxicity or neurobehavioral or cardiovascular effects were noted. Serum phosphorus levels in 2,000 and 4,000 ppm male and female rats were significantly higher than those in controls, but there were no biologically significant differences in hematology parameters or in serum sodium, potassium, or calcium levels. Renal tubule dilatation in the outer stripe of the outer medulla and cortex occurred in male and female rats receiving 4,000 ppm. 13-WEEK STUDY IN MICE: Groups of 10 males and 10 females received barium chloride dihydrate in the drinking water at concentrations of 0, 125, 500, 1,000, 2,000, or 4,000 ppm for 13 weeks, corresponding to average daily doses of 15, 55, 100, 205, or 450 mg barium/kg body weight to males and 15, 60, 110, 200, or 495 mg barium/kg body weight to females. Six males and seven females that received 4,000 ppm and one male that received 125 ppm died during the study. Final mean body weights of male and female mice receiving 4,000 ppm were significantly lower (>30%) than those of controls. Water consumption by male mice in the 4,000 ppm group was 18% lower than that by the controls; water consumption by other exposed groups of male and female mice was similar to thatd groups of male and female mice was similar to that by the controls. Clinical findings of toxicity were limited to debilitation in the surviving male and female mice receiving 4,000 ppm. The absolute and/or relative liver weights of mice receiving 1,000, 2,000, and 4,000 ppm were significantly lower than those of the controls. Multifocal to diffuse nephropathy characterized by tubule dilatation, regeneration, and atrophy occurred in 4,000 ppm male and female mice. 2-YEAR STUDY IN RATS: Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1,250, or 2,500 ppm for 104 (males) or 105 weeks (females), corresponding to average daily doses of 15, 30, or 60 mg barium/kg body weight for males and 15, 45, or 75 mg barium/kg body weight for females. The high dose of 2,500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4,000 ppm groups in the 13-week study. Survival, Body Weights, Water Consumption, and Clinical Findings: Two-year survival of exposed male and female rats was similar to that of the controls. The final mean body weights of male and female rats that received 2,500 ppm were (5% and 11%) lower than those of controls. Beginning as early as week 5, water consumption by male and female rats receiving 2,500 ppm was substantially lower than that by controls (male: 11% to 30%; female: 19% to 33%). There were no chemical-related clinical findings. Hematology and Clinical Chemistry: There were no chemical-related differences in hematology or clinical chemistry parameters in male or female rats. Special Studies: At the 15-month interim evaluation, the plasma barium concentrations (mg/ml) were significantly increased in males receiving 1,250 and 2,500 ppm and in all exposed groups of females (male: 0 ppm, 0.98; 500 ppm, 1.00; 1,250 ppm, 1.23; 2,500 ppm, 1.68; female: 0 ppm, 0.74; 500 ppm, 0.99; 1,250 ppm, 0.97; 2,500 ppm, 1.43). Barium levels in bone in rats from the 2,500 ppm groups were about 400 times greater than those in the controls. Pathology Findings: At the end of 2 years, there were no increased incidences of neoplasms or nonneoplastic lesions that could be attributed to barium chloride dihydrate. However, there were dose-related decreased incidences of adrenal medulla pheochromocytomas and mononuclear cell leukemia in male rats. 2-YEAR STUDY IN MICE: Groups of 60 males and 60 females received barium chloride dihydrate in the drinking water at concentrations of 0, 500, 1,250, or 2,500 ppm for 103 (males) or 104 weeks (females), corresponding to average daily doses of 30, 75, or 160 mg barium/kg body weight for males and 40, 90, or 200 mg barium/kg body weight for females. The high dose of 2,500 ppm was selected based on decreased final mean body weights, mortality, decreased water consumption, and chemical-related kidney lesions observed in the 4,000 ppm groups in the 13-week study. Survival, Body Weights, Water Consumption, and Clinical Findings: Two-year survival of male and female mice receiving 2,500 ppm was significantly lower than that of the controls due to renal toxicity. Final mean body weights of 2,500 ppm males and females were 9% and 12% lower than those of controls. Water consumption by male and female mice receiving barium chloride was similar to that by the controls. There were no chemical-related clinical findings. Hematology and Clinical Chemistry: There were no differences in hematology or clinical chemistry parameters measured at the 15-month interim evaluation. Special Studies: At the 15-month interim evaluation, plasma barium concentrations (mg/mL) were significantly increased in all exposed groups of mice (male: 0 ppm, 0.62; 500 ppm, 0.77; 1,250 ppm, 0.89; 2,500 ppm, 1.49; female: 0 ppm, 0.52; 500 ppm, 0.74; 1,250 ppm, 1.01; 2,500 ppm, 1.35). Pathology Findings: At the end of the 2-year study, there were increased incidences of nephropathy in male and female mice (male: 1/50, 0/50, 2/48, 19/50; female: 0/50, 2/53, 1/50, 37/54). There were no chemical-related increased incidences of neoplasms in male or female mice. The incidence of hepatocellular adenoma was significantly decreased in male mice receiving 2,500 ppm. GENETIC TOXICOLOGY: Barium chloride dihydrate was not mutagenic in Salmonella typhimurium strains TA97, TA98, TA100, TA1535, or TA1537, with or without exogenous metabolic activation (S9). It was mutagenic in L5178Y mouse lymphoma cells in the presence of S9, but it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells, with or without S9. CONCLUSIONS: Under the conditions of these 2-year drinking water studies, there was no evidence of carcinogenic activity of barium chloride dihydrate in male or female F344/N rats that received 500, 1,250, or 2,500 ppm. There was no evidence of carcinogenic activity of barium chloride dihydrate in male or female B6C3F1 mice that received 500, 1,250, or 2,500 ppm. There were chemical-related increased incidences of nephropathy in male and female mice.
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PMID:NTP Toxicology and Carcinogenesis Studies of Barium Chloride Dihydrate (CAS No. 10326-27-9) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies). 1261 99

We analyzed the TS-2 acute lymphoblastic leukemia (ALL) cell line that contains a t(1;19)(q23;p13.3) but lacks E2A-PBX1 fusion typically present in leukemias with this translocation. We found that the t(1;19) in TS-2 fuses the 19p13 gene DAZAP1 (Deleted in Azoospermia-Associated Protein 1) to the 1q23 gene MEF2D (Myocyte Enhancer Factor 2D), leading to expression of reciprocal in-frame DAZAP1/MEF2D and MEF2D/DAZAP1 transcripts. MEF2D is a member of the MEF2 family of DNA binding proteins that activate transcription of genes involved in control of muscle cell differentiation, and signaling pathways that mediate response to mitogenic signals and survival of neurons and T-lymphocytes. DAZAP1 is a novel RNA binding protein expressed most abundantly in the testis. We demonstrate that MEF2D/DAZAP1 binds avidly and specifically to DNA in a manner indistinguishable from that of native MEF2D and is a substantially more potent transcriptional activator than MEF2D. We also show that DAZAP1/MEF2D is a sequence-specific RNA-binding protein. MEF2D has been identified as a candidate oncogene in murine retroviral insertional mutagenesis studies. Our data implicate MEF2D in human cancer and suggest that MEF2D/DAZAP1 and/or DAZAP1/MEF2D contribute to leukemogenesis by altering signaling pathways normally regulated by wild-type MEF2D and DAZAP1.
Leukemia 2005 May
PMID:Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia. 1574 50

Voltage-gated K(+) channel activities are involved in regulating growth factor-stimulated cell proliferation in a variety of cell types. Here we report that suppression of a voltage-gated K(+) channel with 4-aminopyridine (4-AP), barium, and tetraethylammonium inhibited both EGF- and insulin-stimulated myeloblastic leukemia ML-1 cell proliferation in a concentration-dependent manner. Both MAPK/ERK and Akt pathways are known to mediate cell proliferative signals of a variety of growth factors including insulin. In serum-starved ML-1 cells, insulin rapidly stimulated phosphorylation of ERK1/2 and Akt, and the phosphorylation levels peaked approximately 30 min after treatment. Pretreatment of ML-1 cells with 4-AP potently and dose-dependently prevented phosphorylation of ERK1/2 and Akt. However, insulin-induced activation of the Akt pathway also played a role in promoting ML-1 cell proliferation. Flow cytometry analysis revealed that although ML-1 cells were primarily arrested at G(1) phase by serum starvation for 36 h, they reentered the cell cycle after treatment with serum or insulin for 24 h. However, concomitant 4-AP treatment was able to attenuate cell cycle progression in synchronized ML-1 cells stimulated with growth factors. Our results strongly suggest that a 4-AP-sensitive K(+) channel activity plays an important role in controlling proliferation of ML-1 cells by affecting the activation of multiple signal transduction processes induced by insulin.
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PMID:Insulin-activated, K+-channel-sensitive Akt pathway is primary mediator of ML-1 cell proliferation. 1580 56

The molecular basis governing functional behavior of human hematopoietic stem cells (HSCs) is largely unknown. Here, using in vitro and in vivo assays, we isolate and define progenitors versus repopulating HSCs from multiple stages of human development for global gene expression profiling. Accounting for both the hierarchical relationship between repopulating cells and their progenitors, and the enhanced HSC function unique to early stages of ontogeny, the human homologs of Hairy Enhancer of Split-1 (HES-1) and Hepatocyte Leukemia Factor (HLF) were identified as candidate regulators of HSCs. Transgenic human hematopoietic cells expressing HES-1 or HLF demonstrated enhanced in vivo reconstitution ability that correlated to increased cycling frequency and inhibition of apoptosis, respectively. Our report identifies regulatory factors involved in HSC function that elicit their effect through independent systems, suggesting that a unique orchestration of pathways fundamental to all human cells is capable of controlling stem cell behavior.
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PMID:Hierarchical and ontogenic positions serve to define the molecular basis of human hematopoietic stem cell behavior. 1586 57

Although Notch receptor expression on malignant B cells is widespread, the effect of Notch signaling in these cells is poorly understood. To investigate Notch signaling in B-cell malignancy, we assayed the effect of Notch activation in multiple murine and human B-cell tumors, representing both immature and mature subtypes. Expression of constitutively active, truncated forms of the 4 mammalian Notch receptors (ICN1-4) inhibited growth and induced apoptosis in both murine and human B-cell lines but not T-cell lines. Similar results were obtained in human precursor B-cell acute lymphoblastic leukemia lines when Notch activation was achieved by coculture with fibroblasts expressing the Notch ligands Jagged1 or Jagged2. All 4 truncated Notch receptors, as well as the Jagged ligands, induced Hes1 transcription. Retroviral expression of Hairy/Enhancer of Split-1 (Hes1) recapitulated the Notch effects, suggesting that Hes1 is an important mediator of Notch-induced growth arrest and apoptosis in B cells. Among the B-cell malignancies that were susceptible to Notch-mediated growth inhibition/apoptosis were mature B-cell and therapy-resistant B-cell malignancies, including Hodgkin, myeloma, and mixed-lineage leukemia (MLL)-translocated cell lines. These results suggest that therapies capable of activating Notch/Hes1 signaling may have therapeutic potential in a wide range of human B-cell malignancies.
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PMID:Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. 1611 16


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