Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diaziquone (AZQ) and etoposide (VP-16) were administered as simultaneous 5-day continuous infusions to 27 patients with acute leukemia (22 with acute myeloid leukemia (AML), three with chronic myeloid leukemia in blast crisis (CML-B), and two with acute lymphocytic leukemia) at four different doses in a phase I trial. Gastrointestinal toxicity, primarily stomatitis, was dose limiting, occurring in six of 10 patients at the highest dose level. Diarrhea was the only other grade 3 toxicity noted (three of 10 at the highest dose level). The duration of bone marrow aplasia was excessive at the highest dose (median 48 days to granulocytes greater than 500/mm3, range 33-67) but acceptable (31 days) at the maximum tolerated dose: AZQ 28 mg/m2/day x 5 days, VP-16 150 mg/m2/day x 5 days. Complete remissions were seen in seven patients (six AML, one CML-B) and a partial remission in one patient with AML. The median duration of unmaintained complete remission was 3 months (range 1.5-26+).
Leukemia 1990 Mar
PMID:Continuous infusion diaziquone and etoposide: a phase I study in adult patients with acute leukemia. 231 18

We conducted a phase II trial of deoxycoformycin (pentostatin [DCF]) in chronic lymphocytic leukemia (CLL). Eligibility criteria included age greater than 18 years, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, lymphocyte count greater than or equal to 15,000 cells/microL, international stage B or C disease (multiple lymph nodes involved and/or hemoglobin [Hgb] less than 11 g and/or platelets less than 100,000/microL) and no more than one prior treatment regimen. DCF dose was 4 mg/m2 intravenously (IV) weekly for 3 weeks and then every 2 weeks. There were 39 eligible patients (35 men and four women; median age, 63 years; median time from diagnosis to study entry, 3 years). Of these 39 patients, 31% were stage B and 33% had no prior treatment. Median laboratory values at entry were Hgb 10.5 g, WBC 96,100/microL, and platelets 93,500/microL. Nodal involvement was present in 90%, splenomegaly in 81%, and hepatomegaly in 47%. Patients received a median of nine DCF injections, with a range of four to 26. Three patients were not evaluable for response. Overall, 3% achieved a complete response (CR), 23% a partial response (PR), 28% showed clinical improvement (CI), and 38% had stable disease (SD). Associated toxicities (grade 2 or worse) observed were infections (52%), worsening of thrombocytopenia (26%) or anemia (33%), nausea and vomiting (31%), rash or pruritus (20%), and stomatitis (8%). We conclude that DCF is an active agent in CLL with acceptable toxicity.
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PMID:Pentostatin in chronic lymphocytic leukemia: a phase II trial of Cancer and Leukemia group B. 278 91

The role of essential fatty acids in membrane functions related to receptor-mediated endocytosis of vesicular stomatitis virus (VSV) was investigated using a human laryngeal carcinoma cell line (HEp-2) grown in chemically defined serum-free medium (DM) to deplete their essential fatty acid contents. VSV replicated much less effectively in HEp-2 cells grown in DM as compared to serum containing complete medium (CM). Observed reduction in the rate of virus multiplication was, at least in part, due to reduced virus penetration which was monitored using VSV labeled with nitroxyl free radicals as electron spin probe. Surface proteins of VSV were labeled with maleimide spin-label, and succinimide spin-label. Ni2+ was used as a broadening agent to identify the spin-label signals from viruses inside the cell. HEp-2 cells and mouse leukemia cell line L1210 treated with 5-dimethylaminonaphthalene-1-sulfonyl (dansyl) cadaverine, an agent previously shown to inhibit the uptake of VSV in vitro, was used as a positive control in some experiments. VSV penetrated less effectively in both DM-grown cells and in CM-grown cells in the presence of dansylcadaverine. Similar results were obtained by monitoring the uptake of 125I-labeled VSV. When HEp-2 cells grown for several generations in DM were incubated with 10% fetal calf serum for 16 h, the cells supported virus replication to a similar extent as the cells grown in CM. In contrast, addition of arachidonic acid restored VSV growth only partially. Continued growth of HEp-2 cells in DM resulted in a shift in fatty acyl chain composition of phospholipids. The results indicate a finite role for essential fatty acids in receptor-mediated internalization of virus particles.
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PMID:Role of cell membrane composition in receptor-mediated internalization of vesicular stomatitis virus in human HEp-2 cells. 298 85

RHV, which is presumably a defective human retrovirus, has been recovered from the human melanoma cell line HMB2. In the presence of Moloney mouse leukemia virus (MLV), used as a helper, RHV is serially transmissible in mouse NIH-3T3 cells and can provide envelope antigens for vesicular stomatitis virus pseudotype--VSV(RHV). This pseudotype is neutralizable with an inhibitor, present in all human sera tested; the inhibitory activity is resistant to heating at 100 degrees C. To detect whether any specific response to RHV is connected with the disease, we isolated IgG from 140 human sera (70 melanoma patients and 70 control group donors) and tested it for neutralization of VSV(RHV) pseudotype in a randomized, blind experiment. Sixteen samples of IgG from the sera of melanoma patients, but only one control IgG, neutralized the pseudotype; this difference was significant (p less than 0.001). RHV thus appears to be in some way associated with melanoma.
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PMID:Rescued human virus (RHV): association with melanoma. 317 29

The fusion toxin DAB389IL-2 is composed of the catalytic (C) and transmembrane (T) domains of native diphtheria toxin to which human interleukin-2 (IL-2) has been genetically fused (1,2). Following binding to the IL-2 receptor, the fusion toxin is internalized by receptor mediated endocytosis, and upon acidification of the endocytic vesicle, the T domain spontaneously inserts into the membrane, and facilitates the delivery of the C domain to the cytosol (3,4). In order to further study the process by which the C domain is delivered to the target cell cytosol, we genetically fused an eleven amino acid epitope derived from the vesicular stomatitis virus (VSV) G protein to the N-terminal end of DAB389IL-2. The epitope labelled fusion toxin, VSV-G-DAB389IL-2, was found to retain IL-2 receptor specific binding and cytotoxic activity. Target cells were incubated for various times in the presence of VSV-G-DAB389, fixed and then treated with anti-VSV G and FITC conjugated secondary antibody. Laser scanning confocal microscopy was used to determine the location of the fluorescent signal. The VSV-G epitope tagged fusion toxin was found only to be associated with small vesicles that were situated adjacent to the plasma membrane. These results suggest that the C domain of the fusion toxin is associated with an early intracellular compartment and is rapidly delivered to the cytosol. Since channel formation by the T domain is necessary for the delivery of the C domain, it follows that T domain insertion into the membrane also occurs early in the intoxication pathway.
Leukemia 1994 Apr
PMID:Epitope tagging of DAB389IL-2: new insights into C-domain delivery to the cytosol of target cells. 751 76

Fifty-one patients (47 evaluable) with AML, 27 in first relapse and 20 either in second relapse or refractory were treated with menogaril, 100 mg/m2/day as a 90-min infusion daily for 5 days. The complete response (CR) rate was 17% (8/47), and there was one partial response. Seven of eight responders were in first relapse with a 26% response rate among first relapse patients (7/27). The median duration of survival was 3 months for all first relapse patients and 4.3 months for all other patients. Toxicity included grades 3-4 pancytopenia and fever (100% of patients) and grades 3-4 stomatitis and hepatic enzyme elevation (25% of patients). Grades 3-4 cardiac toxicity occurred in three patients (two grade 3 arrhythmias and one heart block). All had previously received anthracyclines. Remission duration was 1.6-48+ months; two patients underwent bone marrow transplantation and continue in CR at 36+ and 48+ months. The nontransplanted patients remained in CR 1.6, 2.0, 3, 7, 14 and 27 months. Activity and toxicity of menogaril in this study were comparable to that of other clinically useful anthracyclines in AML. Further investigation of this agent in AML is warranted.
Leukemia 1995 Oct
PMID:A phase II study of menogaril (7R-O-methylnogarol) in patients with relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group. 756 2

6-Thioguanine (6-TG) was administered as a continuous i.v. infusion for 7 days to 24 patients with relapsed or refractory acute leukemia or in the blast phase of chronic granulocytic leukemia. The daily dose of 6-TG was escalated from 37.5 mg/m2 to 160 mg/m2. Stomatitis was dose-related and dose-limiting with a maximum tolerated dose of 120 mg/m2 daily. Cutaneous reactions were dose-related but not dose-limiting. The recommended dose for phase II trials in acute leukemia is 120 mg/m2 per day as a continuous infusion for 7 days. There were two complete and four partial remissions among all patients. At the suggested phase II dose of 120 mg/m2 there were two complete remissions and one partial remission in five evaluable patients.
Leukemia 1995 May
PMID:Phase I study of continuous infusion 6-thioguanine in patients with acute leukemia. 776 38

Sixteen adult patients with relapsed (7 patients) or refractory (9 patients) acute leukemia received mitoxantrone (10 mg/m2 per day for 3 days) and etoposide (200 mg/m2 per day for 3 days) with escalating dose of cyclosporin A (CsA) from a loading dose of 2 mg to 6.5 mg/kg per 2 h followed by 3 days continuous infusion of 5-15 mg/kg per day. The major toxicities were stomatitis and prolonged aplasia, occurring for 15 mg/kg per day of CsA. Transient conjugated hyperbilirubinemia occurred in all patients, and was CsA dose-dependent (r = 0.7). Adequate serum levels of CsA (> 1 microgram/ml) were obtained in 3/6 patients treated with 10 mg/kg per day and 4/4 patients with 15 mg/kg per day. The pharmacokinetic of mitoxantrone showed an unusual increase of carboxylic metabolites, parallel to CsA levels. We observed six responses (two complete and four partial remissions), and eight resistances. Two patients died at days 3 and 8 from sepsis. Before treatment, 7/16 patients tested for P-gp with C219 were positive (> 10% positive cells). 3/6 responders were P-gp-positive. At time of leukemic regrowth, cells expressing P-gp before therapy reverted to P-gp-negative cells.
Leukemia 1993 Jun
PMID:Cyclosporin A as a modifier agent in the salvage treatment of acute leukemia (AL). 809 34

Prophylaxis against human T cell lymphotropic virus type I (HTLV-I) is of primary importance for the eradication of adult T cell leukemia and other diseases associated with this virus. Hyperimmune globulin (H-IgG) prepared from healthy blood donors with high antibody titers for HTLV-I was evaluated for its prophylactic effect against HTLV-I in Japanese macaques (Macaca fuscata). Normal IgG (N-IgG) prepared from seronegative healthy blood donors was used as control. Both preparations contained 50 mg/ml IgG and H-IgG had a neutralizing antibody titer of 1:7100 by vesicular stomatitis virus (HTLV-I) pseudotype neutralization assay. Two macaques were infused with 2 ml/kg N-IgG and three macaques were immunized with 2-0.5 ml/kg H-IgG. They were immediately challenged by inoculation of 8 x 10(6)/kg cells from an HTLV-I-producing rabbit lymphoid cell line (Ra-1). Another macaque was immunized with 1 ml/kg H-IgG 24h after inoculation of 8 x 10(6)/kg Ra-1 cells. HTLV-I infection, as determined by seroconversion and verified by polymerase chain reaction, occurred in both of the N-IgG-injected macaques but in none of the four H-IgG-injected macaques. These results demonstrate the protective efficacy of H-IgG against HTLV-I infection in a primate model and provide an experimental basis for passive immunization trials in humans.
Leukemia 1996 Dec
PMID:Prevention of human T cell lymphotropic virus type I infection in Japanese macaques by passive immunization. 894 39

Gene transfer into haematopoietic stem cells (HSC) has been investigated for treatment of genetic disorders, conferral of chemotherapy resistance and insertion of genes to inhibit HIV-1 replication. Methods have been available for almost a decade to transduce murine HSC using high-titre retroviral vectors and stimulation of HSC proliferation with cytokines such as IL-3 and IL-6. Unfortunately, attempts to replicate the high efficiency of gene transfer using canine or simian gene transfer/bone marrow transplantation models have consistently shown that only a small fraction (0.1-1%) of reconstituting HSC are transduced using protocols similar to those which are successful in murine models. Initial clinical trials using retroviral-mediated gene transfer into human HSC also produced minimal transduction frequencies. The dicotomous results may reflect differences in the cell cycle kinetics of murine HSC versus those of larger mammals or the density of receptors for the retroviral vectors on the cells. Attempts to increase the fraction of HSC which are in active cell cycle, a prerequisite for retroviral-mediated transduction, have used either combinations of recombinant cytokines, culture on marrow stromal layers, or alternative sources for HSC, such as mobilized peripheral blood stem cells or umbilical cord blood. Other efforts have used retroviral vectors packaged with either the Gibbon Ape Leukemia virus envelope or the Vesicular Stomatitis Virus G protein. To date, none of these methods has produced a significantly increased frequency of long-term reconstituting HSC. Results using adeno-associated virus (AAV)-based vectors for HSC transduction have been conflicting, with the stable persistence of non-integrated virus particles making interpretation of results difficult using in vitro assays. Therefore, clinical trials may best be directed toward disorders that may benefit from a small fraction of genetically corrected HSC. These would include disorders where progeny of corrected HSC would be expected to have a selective survival advantage (e.g. SCID, WAS, HIV, chemoresistance) or where a small fraction of corrected cells can have a direct clinical benefit (e.g. CGD, MPS). Further basic research into HSC biology and gene delivery vectors must continue for wider application, such as haemoglobinopathies and some lysosomal storage diseases.
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PMID:Gene therapy for haematopoietic and lymphoid disorders. 902 Sep 37


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