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Biomedical subjects

A T Huang

Publications and source records attributed to A T Huang.

At least 37 records · Page 2Linked to original sources
PubMed1992

A phase II study of piritrexim in patients with advanced squamous head and neck cancer.

Piritrexim (PTX) is a newly developed lipid-soluble folate antagonist that crosses the cell membrane by a simple, rapid, carrier-independent diffusion process. A Phase II study was conducted to evaluate the activity of PTX in 34 patients with previously chemotherapy-naive squamous cell cancer of the head and neck area (SCCHN). Among them, 30 patients had received previous radiation therapy and/or surgery. Of 33 patients who could be examined, 3 had a complete response (CR), 6 had a partial response (PR), 11 had no change, and 13 had disease progression. The overall response rate (CR + PR) was 27% (9 of 33; 95% confidence interval, 13% to 46%). The response duration ranged from 36 to 360 + days (median, 162) and was similar to the best studies reported with methotrexate. The three most severe side effects (Grades 3 and 4 by World Health Organization criteria) were leukopenia, thrombocytopenia, and mucositis. These occurred in 41%, 26%, and 15% of the 34 patients, respectively. This study established PTX as an agent with some activity in SCCHN. The use of PTX in combination chemotherapeutic regimens needs to be explored.

Adult↗
PubMed1991

Polymorphism and altered methylation of the lactoferrin gene in normal leukocytes, leukemic cells, and breast cancer.

Human lactoferrin has been found to be decreased or absent in most breast cancer and leukemia cells. In order to examine the lactoferrin gene for both structural alterations and the degree of methylation, we isolated a 2117-kilobase complementary DNA from human breast tissue. This complementary DNA was used to probe DNA extracted from normal peripheral blood, leukemia cells from patients, leukemia cell lines, and breast cancer cell lines. Immunocytochemical staining of these cells confirmed the decreased production of lactoferrin in malignancy. MspI restriction enzyme fragment patterns demonstrated genetic polymorphism which occurred in DNA from both normal and malignant cells. Polymorphism was also noted with XbaI. In this case, there were two fragment patterns that were only found in DNA from malignant cells. The degree of DNA methylation was also evaluated. The methylation pattern of DNA extracted from malignant cells was highly variable and generally less methylated than DNA extracted from normal WBCs. It is possible that the decrease in lactoferrin associated with cancer is multifactorial and includes gene structural changes as well as altered regulation. Further study is needed to determine whether the changes found in this study are the result of the malignancy or contribute to its onset or maintenance.

Amino Acid Sequence↗
PubMed1991

Absence of phosphatidylinositol (PI)-linked proteins in a very early human multipotential haematopoietic marrow cell.

A very early human haematopoietic progenitor cell population which was negative for the major histocompatibility class II antigen (HLA-DR) and positive for the CD34 (MY10) antigen was separated into two subsets according to the expression of decay-accelerating factor (DAF) on the cell surface. Using immunoadherence, cell cycle analysis, and cell culture, we determined that there is a DAF- multipotential cell and a more differentiated DAF+ lineage specific progenitor cell existing in human bone marrow. The DAF- subset was highly enriched for CFU-GEMM, while the DAF+ subset contained only BFU-E and CFU-GM. The DAF- subset was approximately 0.03% and the DAF+ subset approximately 0.008% of the original bone marrow population. MIRL (membrane-inhibitory of reactive lysis), another PI-linked protein, was not expressed on the DAF- population but was expressed on the DAF+ cells. These observations indicate that PI-linked proteins are absent from the multipotential stem cell but are present on an early lineage specific cell. The absence of expression of PI-linked proteins can be used to further isolate and characterize a very early multipotential haematopoietic progenitor cell population.

Antigens, CD↗
PubMed1991

Anti-human immunodeficiency virus synergism by zidovudine (3'-azidothymidine) and didanosine (dideoxyinosine) contrasts with their additive inhibition of normal human marrow progenitor cells.

The anti-human immunodeficiency virus (HIV) activity and hemopoietic toxicity of zidovudine (AZT) and didanosine (dideoxyinosine;ddI), alone and in combination, were assessed in a variety of cell types. AZT was more potent than ddI as an inhibitor of HIV in vitro. Synergistic inhibition of HIV by the combination of these agents was observed in MT4 cells, peripheral blood lymphocytes, and macrophages. Toxicity assessment in vitro by using progenitor (erythroid and granulocyte-macrophage) colony-forming assays with normal human bone marrow showed ddI to be less toxic than AZT. Addition of inhibitory concentrations of ddI to AZT resulted in additive inhibition of progenitor CFUs. These in vitro findings suggest that combinations of ddI and AZT at appropriately modified doses may provide an enhanced degree of selectivity in anti-HIV chemotherapy.

Bone Marrow↗
PubMed1990

Effect of thimerosal in leukemia, in leukemic cell lines, and on normal hematopoiesis.

Anti-thymocyte globulin (ATG), a horse antiserum to human thymus tissue, has been shown to induce granulocytic differentiation of the HL-60 human leukemia cell line. In this paper we describe the effect of ATG on leukemic blasts and its effect on other human leukemia cell lines in vitro. The in vitro differentiation effect of ATG was observed in blasts from two patients with leukemia and the human leukemia cell line K562. The differentiation effect of ATG was attributable to its preservative, thimerosal, separable from ATG by high pressure liquid chromatography or dialysis. Subsequent studies with thimerosal alone showed it to induce differentiation in leukemic blasts from three patients and the human leukemia cell lines U937, K562, and KG-1. The differentiation effect of thimerosal is blocked by a sulfhydryl-protective agent, dithiothreitol, suggesting that the mechanism of differentiation may be mediated via a sulfhydryl group-dependent process.

Antilymphocyte Serum↗
PubMed1990

Extranodal head and neck lymphoma. Prognosis and patterns of recurrence.

Stages I and II extranodal head and neck lymphomas treated between 1969 and 1986 were reviewed to determine prognosis and recurrence patterns. Forty-four patients had low-grade lymphoma, with 57% remaining disease free (median survival, 7.2 years). Radiotherapy provided long-term disease-free survival and palliation in the majority of patients. Relapse did not adversely affect survival. Eighty-eight patients had intermediate- or high-grade lymphoma, with 42% remaining disease free (median survival, 2.4 years). Treatment with radiotherapy alone was inadequate. Combined radiotherapy and anthracycline-containing chemotherapy appeared to be superior. Extranodal sites of first relapse were common. Central nervous system relapse was common with primary tumors located above the pterygopalatine line. Central nervous system staging and prophylactic therapy is warranted in patients with tumors above the pterygopalatine line.

Adult↗
PubMed1990

Phase I studies of recombinant interferon-gamma.

A phase I study of the effects of intravenous administration of interferon-gamma on 31 patients was performed. The effects of dose, schedule, and chronic administration were studied. In the first phase of the study, a dose range of 0.01-500 MU/m2 (0.0002-25 mg/m2) was tested and we found the maximum tolerated dose to be 400 MU/m2; the dose-limiting toxicity with this preparation was hypotension. In the second phase, three different schedules of administration were tested. There were no significant differences in toxicity between a 20 min, a 4 h, or a 24 h infusion of 60 MU/m2 (3 mg/m2). In the third phase, patients received chronic administration of either 1 or 30 MU/m2. Patients given 30 MU/m2 twice a week for 4 weeks showed more symptoms--fever, nausea, and orthostasis--than those treated with 1 MU/m2. No significant changes were seen in natural killer cell activity, antibody-dependent complement cytotoxicity, or monocyte cytotoxicity at any dose. Maximal stimulation of 2',5'-oligodenylate synthetase occurred at low doses (12 MU/m2). Depressed bone marrow colony formation for CFU-GM, BFU-E, and CFU-GEMM in vivo was noted. No objective antitumor responses were noted. This preparation of recombinant interferon-gamma can be given in doses as high as 400 MU/m2. Chronic administration would appear to be limited to 30 MU/m2. However, lower doses may give maximal biologic responses. These studies provide further information on the biologic effects of a wide dose range and a variety of schedules of recombinant interferon-gamma.

2',5'-Oligoadenylate Synthetase↗
PubMed1987

A prospective study of squamous head and neck carcinoma. Immunologic aberrations in patients who develop recurrent disease.

In a prospective study of squamous head and neck cancer, the pretreatment peripheral blood of 125 patients was examined for lymphocyte subclass and in vitro immunologic function. After 4 years of follow-up, 49 recurrences of disease were observed. Lymphocytes from patients with recurrent disease showed elevated interleukin-2 (IL-2) production and a tendency towards increased response to mitogens in comparison to those without recurrence. When disease-free survival is analyzed on the basis of IL-2 levels, patients with high relative IL-2 synthesis (greater than or equal to 1) had a 40% poorer prognosis than patients with low relative IL-2 levels (less than 1). The difference is significant at a P value of 0.02. Since IL-2 synthesis occurs with antigenic stimulation, it is postulated that patients who have a high IL-2 synthesis in their pretreatment lymphocytes may have had prior stimulation by circulating tumor antigen. Such immune response by the host may be successful in destroying the antigenic tumor cells but may leave the undifferentiated, less antigenic tumor cells to grow and metastasize. Thus, elevated IL-2 synthesis in pretreatment lymphocytes predicts a poorer prognosis.

Carcinoma, Squamous Cell↗
PubMed1987

5-Fluorouracil, cyclophosphamide, and vincristine for adenoid cystic carcinoma of the head and neck.

Twenty-one patients with adenoid cystic carcinoma of the head and neck were treated with intravenous boluses of cyclophosphamide and vincristine and 5-day continuous intravenous infusions of 5-fluorouracil (CVF) every 4 weeks. Eight patients received CVF as palliation for recurrent or metastatic disease. A sustained complete response (107+ months) was observed in one patient; one partial response and one mixed response each also were observed. In four patients disease stabilized, and in one disease progressed. Thirteen patients received six courses of CVF in the adjuvant setting after surgery and radiation for either primary or locoregional recurrent disease. Recurrences developed in two of seven patients with primary disease and three of six patients with recurrent disease with a median follow-up 45 months (range, 20-108+). Recurrence rate and time interval to recurrence were comparable to those of well-matched historical controls. Distant metastases have not developed in patients treated with CVF in the adjuvant setting, whereas distant metastases had developed in historical controls within comparable periods of follow-up. Serious toxicities were not encountered in any patient. The authors conclude that CVF is a well-tolerated combination chemotherapy program with activity in adenoid cystic carcinoma of the head and neck. This regimen, however, has not had a major impact in the adjuvant setting in preventing recurrent disease.

Adult↗
PubMed1987

Antithymocyte globulin stimulates human hematopoietic progenitor cells.

Antithymocyte globulin (ATG), a horse antihuman thymus antiserum highly effective in the majority of patients with aplastic anemia, was studied for its in vitro effects on hematopoietic progenitor cells. Marrow cells isolated by an immunoadherence technique with the HPCA-1 (human progenitor cell antigen) monoclonal antibody after removal of contaminating T cells and macrophages formed erythroid colonies in methyl cellulose media in the presence of ATG at concentrations of 25-50 micrograms/ml. ATG also stimulated continuous production of hemoglobin-containing erythroid colonies beyond 35 days of culture when it was added to the culture weekly. ATG also had an indirect effect on myeloid (granulocytic and macrophagic) colony growth in vitro. At a concentration of 10 micrograms/ml, ATG stimulated late but not early myeloid progenitor cells to form mature colonies. This effect required the participation of lymphocytes containing the Leu-11 antigen and macrophages or supernatant fluids made from these two types of cells that had been preincubated with ATG for 3 hr and then cultured for 5 additional days. The supernatant fluids produced in such a manner showed characteristics similar to granulocyte colony-stimulating factor and had an activity peak that eluted at a volume corresponding to a 20,000 Da molecular mass protein by high-resolution liquid chromatography.

Antibodies, Monoclonal↗
PubMed1987

Transformation of hairy cell leukemia to EBV genome-containing aggressive B cell lymphoma.

Hairy cell leukemia is a preplasmacytic B cell leukemia which is not EBV associated, although elevated titers of Epstein-Barr virus (EBV) antibodies have been seen in this leukemia and chronic lymphocytic leukemia. Hairy cells are not readily susceptible to EBV infection in vitro, even though they are EBV receptor-positive B cells. We have observed a 59-year-old patient who after 9 years of hairy cell leukemia developed a well-differentiated IgG-kappa monoclonal B cell lymphoma without further evidence of hairy cell leukemia. Pathologically, the lymphoma showed plasmacytic differentiation, and in the patient's serum, a 2 g/dl monoclonal IgG-kappa component was present. DNA extracted from the lymphomatous lymph node hybridized with DNA fragments of a reiterated sequence of EBV, IR1. The transformation, with no chemotherapy involved, from a preplasmacytic leukemia into a lymphoplasmacytic lymphoma with monoclonal gammopathy may be related to the entry of EBV into these cells. Studies at the molecular level may help understand mechanisms of malignant transformation or interconversion in lymphoproliferative disorders of the B cell type.

B-Lymphocytes↗
PubMed1987

Changes in hairy cells after alpha-interferon treatment as measured by flow cytometry.

Patients with hairy cell leukemia who responded to alpha-interferon (IFN-alpha) were compared to those who did not by examining their hairy cells throughout treatment. The examination of the cells by cytofluorography included the expression of surface antigens (such as B1, HLA, transferrin receptors, surface immunoglobulins, TAC), and cytofluorometric measurement of light scatter including forward (which correlates with cytoplasmic size and shape) and perpendicular (which correlates with nuclear size and shape) directions. Although the entire lymphocyte population from these patients was examined initially to look for changes in phenotype with treatment, in later studies an enriched leukemic population was examined and alterations in response to interferon treatment became more apparent. The monoclonal antibody M5 was used to enrich the hairy cell population via a panning technique. The enriched population contained greater than 90% tartrate-resistant acid phosphatase-positive hairy lymphocytes. By cytofluorographic analysis of these cells serially in four responding patients and one refractory, all of whom had been followed longer than 11 months, several observations were made: 1) leukemic cells from responding patients showed a rapid decline in the forward and perpendicular light scatter indicative of cell differentiation; 2) coexisting normal B cells showed no changes in the above features; and 3) leukemic cells exhibited a definite increase in the HLA antigen density and a slight decrease in transferrin receptors in responding patients but not in the refractory patient. The increase in HLA antigen expression by hairy cells indicates progression toward differentiation, and decrease in transferrin receptors correlates with growth reduction. These data indicate that the administration of IFN-alpha is associated with cellular changes toward differentiation. We can not exclude, however, the possibility of other actions of IFN-alpha in HCL as proposed by other investigators.

Cell Nucleus↗
PubMed1986

Development of immunity in human severe primary T cell deficiency following haploidentical bone marrow stem cell transplantation.

Recent advances in the prevention of graft-vs-host disease (GVHD) have allowed the use of haploidentical bone marrow cells for correction of lethal genetic defects of the immune system. Sequential analyses of blood lymphocyte phenotypes and functions were done before and after transplantation of haploidentical marrow stem cells into 17 infants with severe primary T cell deficiencies. The marrow was depleted of post-thymic T cells and most other mature marrow cells by soy lectin agglutination and sheep erythrocyte rosetting. The studies were performed to define the time course and extent of appearance of immune function, and to identify factors leading to resistance to engraftment. No pretransplant immunosuppression was used. T cell function was detected between 34 and 287 days after transplantation, but a sharp rise usually occurred between 84 and 115 days, and normal function was reached between 113 and 210 days. Fifteen of the patients are alive from 6 to 41 mo post-transplantation, 12 have improved or have normal T lymphocyte function, and nine have proven T cell chimerism. Increased immunoglobulins of several isotypes have been noted in 11 patients and specific antibodies in seven patients, although B cell chimerism has been detected in only one patient. B cell function required 2 to 2.5 yr for normalization. No GVHD occurred in 14 patients, and the other three had only transient mild skin rashes. Two patients died of viral infections. Failure to engraft was correlated with some pre-transplant lymphocyte responses to mitogens and allogeneic cells (three cases), but not with the presence of pre-transplant natural killer cell function (five cases) nor with the presence of purine salvage pathway enzyme deficiencies (four cases). The latter, however, was associated with poor lymphoid function in two patients. These studies indicate that the thymic microenvironment of most infants with severe combined immunodeficiency disease is capable of differentiating donor stem cells to mature and functioning T lymphocytes which can cooperate with apparently normal host B cells for antibody production.

Adenosine Deaminase↗
PubMed1986

Effects of high-dose cancer chemotherapy on the absorption of digoxin in two different formulations.

The oral absorption of digoxin in tablet form has been reported to be reduced after cancer chemotherapy and radiation therapy because of cancer treatment-induced damage to the intestinal epithelium. We investigated possible differences in the effects of high-dose cancer chemotherapy on the relative bioavailability of digoxin administered in tablet form (Lanoxin; Burroughs Wellcome Co.) and in solution-in-capsule form (Lanoxicaps; Burroughs Wellcome Co.). Each subject received a single oral dose of either 0.5 mg Lanoxin (six subjects) or 0.4 mg Lanoxicaps (seven subjects) both before and after chemotherapy. For Lanoxin, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean +/- SD) of the value before chemotherapy (P = 0.02), whereas for Lanoxicaps there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. These findings show that changes in the oral dosage formulation of digoxin from a tablet to a solution-in-capsule form can overcome the adverse effects of high-dose cancer chemotherapy on drug absorption, and suggest a similar approach may be successful for other drugs.

Absorption↗
PubMed1986

Antithymocyte globulin: a realistic approach to therapy for severe aplastic anemia.

Antithymocyte or antilymphocyte globulin (ATG or ALG) has emerged since 1978 as important therapy applicable to the majority of patients with aplastic anemia. On the basis of similarities of patient populations, nine clinical trials were selected among many for this review. A total of 209 patients with severe aplastic anemia have been analyzed. A hematologic response was observed in 113 (54%). The degree of hematologic improvement is incomplete in the majority of patients, but it is most often sustained and independent of further transfusion. The survival rate is 42% to 75% with a follow-up ranging between 12 and 55 months; three of 113 responders have had relapse. The similarities in treatment outcome suggest that different preparations of ATG or ALG carry an identical efficacious component.

Adult↗
PubMed1985

Cutaneous T cell lymphoma. Lymphocyte phenotype analysis after anti-thymocyte globulin therapy.

In an attempt to explore new or alternative therapy for refractory cutaneous T cell lymphoma, a patient with advanced disease refractory to conventional chemotherapy was treated with anti-thymocyte globulin. The therapy was associated with tolerable and manageable toxicities. Phenotypic analysis of neoplastic cells in blood and tissue was used to follow the disease response during the trial. The therapy resulted in resolution of skin lesions and disappearance of circulating cells with neoplastic phenotype. Marked improvement in skin infiltrate and restoration of normal skin architecture seen in skin biopsy specimens after anti-thymocyte globulin were prominent correlative findings. Lymphocytes with normal T cell phenotype appeared after anti-thymocyte globulin therapy, although their mitogenic response was subnormal. The infused anti-thymocyte globulin was found to localize in the skin and bind the neoplastic cells in circulation. The anti-thymocyte globulin-bound cells, with a half-life of 4.9 days, could still be detected up to 14 days after completion of anti-thymocyte globulin therapy.

Antibodies, Monoclonal↗
PubMed1985

Predictive factors for response to anti-thymocyte globulin in acquired aplastic anemia.

Lymphocyte phenotype, bone marrow cellularity, in vitro marrow growth potential, and treatment responses were examined in 22 patients with acquired aplastic anemia who were given anti-thymocyte globulin. Eleven of 22 patients (50 percent) had a significant hematologic response within three months of therapy, confirming the effectiveness of this therapy. Pretreatment fetal hemoglobin concentration, age, sex, severity of pancytopenia, degree of maximal lymphopenia, and total hemolytic complement consumption did not affect response. Patients with severe disease who were treated within 16 weeks after diagnosis had a higher response rate (55 percent) than those treated after 16 weeks (20 percent). In patients with severe disease, a higher pretherapy bone marrow cellularity (p less than 0.001) and presence of granulocyte-macrophage colony growth correlated with response. The actuarial survival of patients with response in the group with severe disease was 100 percent at 12 months as compared with 33 percent in patients without response. Following anti-thymocyte globulin therapy, a reduced number of blood lymphocyte T subpopulations was seen in all patients. At three months after therapy, the patients with response who had severe disease had increased T8-positive cells (+56 percent versus -4 percent for patients without response) and la-positive cells (+32 percent versus -62 percent).

Actuarial Analysis↗