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)

Thirteen cases of idiopathic chronic lymphocytosis are the subject of this report. Patients showed a lymphocyte count between 4 and 15 X 10(9)/L for at least six months, marrow lymphocytosis not exceeding 25%, absence of lymphomegaly and hepatosplenomegaly, and no associated infections, immune, or neoplastic disease. Morphologic examination of smears revealed a lymphocytosis of large granular lymphocytes in five. A selected battery of polyclonal and monoclonal antisera to antigens commonly found on B-, T-, and natural killer cells allowed the identification of six cases of early B-cell chronic lymphocytic leukemia, two cases of T-cell lymphocytosis with a suppressor or helper T-cell phenotype, and five cases of large granular lymphocyte/natural killer cell proliferative disease. The results demonstrate the usefulness of combining morphologic and phenotype studies for the investigation of chronic lymphocytosis, which often appears as an early leukemia or a benign clonal proliferative disorder of lymphocyte subsets.
 ...
PMID:Investigation of chronic lymphocytosis in adults. 336 72

Three routes of immunotherapy with Corynebacterium parvum (CP) on an ascitic Friend virus-induced leukemia were evaluated. Only the intraperitoneal route, which provided optimal contact between CP and tumor cells, showed prolonged mean survival time. Greatest effectiveness was obtained with multiple injections of CP at weekly intervals and with small initial tumor load. Of particular interest was that lower dosages of CP (5 and 25 micrograms) gave longer protection than dosages of 50 and 250 micrograms. Using in vitro 125I-iododeoxyuridine release assay, these lower dosages were shown to selectively enhance the cytotoxicity associated with T lymphocytes, whereas higher dosages appeared to primarily augment the activity of phagocytes. Moderate natural killer cell activity was observed with both the lower and higher dosages of CP. Data from this study indicate that route of administration, dosage of CP, and size of tumor burden are crucial variables determining optimal response to immunotherapy.
 ...
PMID:Tumor-specific T-lymphocyte cytotoxicity enhanced by low dose of C. parvum. 349 2

The role of in vivo administration of lymphoblastoid alpha-interferon (IFN-alpha) on the immune status of 12 patients with hairy cell leukemia (HCL) was studied. In most cases an increase in T3(CD3), T4(CD4), and T8(CD8) lymphocyte subsets was documented at the same time as hairy cells disappeared from the circulation. This led in most cases to an improved T4/T8 ratio. The effect of treatment with IFN-alpha was particularly evident on the natural killer cell compartment, which is often functionally depressed in HCL at diagnosis. After therapy, a progressive increase in the cytotoxic activity was observed in most patients. This was more evident 6-9 months after commencing treatment. These findings suggest that, in addition to the known clinicohematological effects, IFN-alpha can improve both the T and natural killer compartments in patients with HCL.
Leukemia 1987 Apr
PMID:Effect of alpha-interferon on the immune system of patients with hairy cell leukemia. 349 43

An immunoperoxidase technique was used to examine the distribution of lymphocyte subsets in bone marrow biopsies of 15 patients with neutropenia and seven non-neutropenic controls. The bone marrow of most patients and controls had similar distributions of immune effector cells characterized by a diffuse array of predominantly cytotoxic/suppressor T-cells and occasional nodular aggregates of helper T-cells. Cells displaying the natural killer cell marker HNK-1 were sparse in controls and most neutropenic patients. However, marked increases in marrow HNK-1 + cells were identified in four of the 15 patients. Three of these patients had diffuse HNK-1 + infiltrates associated with increased Leu 4+ (OKT-3+) T-cells while one had a nodular HNK-1+ infiltrate associated with small B-cell follicles. Each of these patients had clinical features similar to those described in the large granular lymphocyte (LGL) lymphocytosis (leukemia) syndrome, but only one of four demonstrated persistently increased numbers of LGLs in the peripheral blood. Thus, this study extends the association of neutropenia and increased numbers of cells with a T/NK phenotype to include patients whose bone marrow is the only demonstrable site of involvement. Since morphologic examination of the bone marrow could not identify the bone marrows with increased HNK-1+ cells, immunologic techniques are required to detect these cases.
 ...
PMID:Immunoarchitecture of the bone marrow in neutropenia: increased HNK-1 + cells define a subset of neutropenic patients. 357 62

The highly malignant and metastatic RAW117-H10 cell line was developed by in vivo selection from the Abelson leukemia virus induced parental RAW117-P lymphoma. In this study we have characterized these cell lines with regard to their expression of lymphocyte and macrophage differentiation antigens, adherence, phagocytic properties, binding of various lectins, binding of antibodies to glycolipid asialo-monoganglioside, and the role of butanol extractable cell surface molecules to determine if any of these cell surface properties are associated with the malignant potential of RAW117-H10 cells. The only major difference in immunological phenotypes between RAW117-P and RAW117-H10 cells was an increased expression of Thy-1 molecules by the latter. However, the highly malignant RAW117-H10 cells bound significantly less concanavalin A, Ricinia communis agglutinin, succinylated wheat germ agglutinin, and particularly anti-asialomonoganglioside than their parental counterpart and were resistant to natural killer cell mediated cytolysis. Removal of butanol extractable cell surface molecules significantly decreased the malignancy of RAW117-H10 cells and increased their susceptibility to natural killer cell mediated cytolysis. The butanol treated RAW117-H10 cells regained high in vivo malignancy when recultured for 3 days to permit regeneration of their cell surface components. The butanol extracted RAW117-H10 cells still expressed high levels of Thy-1 indicating that this most probably represented "inappropriate" antigen expression. Since the expression of lymphocyte differentiation antigens did not correlate with the malignant behavior of the cells, we postulate that these antigenic differences merely represent phenotypic variation. The decreased malignant potential of the butanol treated RAW117-H10 cells did correlate with increased cell surface anti-asialomonoganglioside binding (glycolipid) and increased natural killer cell susceptibility.
 ...
PMID:Cell surface properties associated with malignancy of metastatic large cell lymphoma cells. 358 Oct 88

Bropirimine (ABPP), a pyrimidinone, is currently under clinical trial for its antitumor potential. Bropirimine alone was marginally active against some experimental tumors such as B16 melanoma but was ineffective against others such as P388 or L1210 leukemia. However, it produced statistically significant synergistic activity against P388 leukemia when used in combination with cyclophosphamide (CY). The aim of this investigation was to determine whether the synergism could be achieved with different types of cytotoxic drugs. Actinomycin D (act D), adriamycin, 5-azacytidine, cisplatin, melphalan, mitomycin C, and vincristine were selected. Using an experimental protocol identical to that of CY and bropirimine combination therapy, and using a more or less equally effective dosage of the drug for the initial reduction of tumor burden (i.e., around 100% increase of life span), cisplatin and bropirimine also produced a statistically significant synergism over the treatment with cisplatin alone. The combination of bropirimine with either adriamycin, mitomycin, or vincristine was beneficial but the effect was not as consistent or as striking as that seen with the CY and bropirimine combination. It is clear, however, that the combination of act D and bropirimine was not synergistic under the experimental conditions. Since the antitumor activity of pyrimidinone has been reported to be mediated in part by its stimulation of natural killer cell activity, the effect of these cytotoxic drugs on the immunomodulatory activity of bropirimine was investigated. Like CY, cisplatin did not alter the augmentation of natural killer cell activity by bropirimine. However, adriamycin, mitomycin, or vincristine showed a marked inhibition (25-50%) of the augmentation. Act D completely inhibited the immunomodulating activity of bropirimine 4 days after drug administration and continued to show marked inhibition 18 days later. This may partially explain the reasons for lack of synergism between act D and bropirimine. A prolonged immunosuppressive effect exhibited by act D and the degree of tumor repopulation during this period could render bropirimine ineffective. In addition to the magnitude of initial tumor burden reduction by the chemotherapeutic drugs, the present results indicate that the immunosuppressive property of these drugs may also affect the outcome of chemoimmunotherapy.
 ...
PMID:Relationship between modulation of natural killer cell activity and antitumor activity of bropirimine when used in combination with various types of chemotherapeutic drugs. 366 90

The phenotypic profile of atypical cells from a patient with cutaneous multilobated T-cell lymphoma was investigated using a multiparameter approach including evaluation of membrane markers, cytochemistry, and functional activity. Retroviral sequence restriction analysis was also used to investigate the presence of human T-cell leukaemia/lymphoma virus type I (HTLV-I) in atypical cells infiltrating the skin and in otherwise normal peripheral blood lymphocytes. The atypical cells appeared to belong to the T-lineage demonstrating OKT11 positivity, E-rosette formation, tartrate-sensitive acid phosphatase and beta-glucuronidase activity, and consistent negativity for cytoplasmic and/or surface monoclonal immunoglobulins. However, they failed to stain for other T-lymphocyte-associated antigens, such as those defined by OKT3, OKT4, OKT6, OKT8, OKT9, OKT10, Leu-2a and Leu-3a monoclonal antibodies, and did not express a definite alpha-naphthyl-acetate esterase pattern. Additional studies including phagocytosis tests and a series of monoclonal antibodies against phagocytic and natural killer cell associated antigens were all negative. No HTLV-I related sequences were found in either the cells infiltrating the skin or in circulating lymphocytes. To our knowledge, in previously reported cases of cutaneous multilobated cell lymphoma a clear T-lymphocyte phenotypic profile was demonstrated. Our present data indicate that this is not always necessarily the case. The peculiar phenotype we found might represent a transitional state between different T-cell subsets or an as yet unrecognized phenotype of a neoplastic T-lymphocyte which lacks a normal counterpart.
 ...
PMID:Cell surface marker studies in a patient with cutaneous multilobated T-cell lymphoma. 390 11

This study was undertaken in an attempt to understand the mechanism of antitumor action of pyrimidinones alone and in combination with cyclophosphamide (CY). Pyrimidinones such as 2-amino-5-bromo-6-(3-fluorophenyl)-4(3H)pyrimidinone (ABMFPP) were relatively nontoxic toward murine L1210 leukemia cell growth in vitro with the concentration of drug required for a 50% inhibition of cell growth being greater than 50 micrograms/ml. In contrast, ABMFPP showed anti-B16 melanoma activity in vivo which was sensitive to X-irradiation of the hosts. These results collectively suggest that pyrimidinones may act differently from conventional cytotoxic antitumor agents. Multiple i.p. injections of ABMFPP (125 mg/kg/injection) significantly augmented the cytotoxicity of both natural killer cells and macrophages in peritoneal exudates. The augmentation of both effector cell populations was delayed, but was more pronounced when animals received a dose of CY (100 mg/kg) prior to ABMFPP injections. The combination of CY and ABMFPP also showed a synergistic anti-P388 leukemia effect which appeared to be related to the initial reduction of the tumor burden by CY and the marked augmentation of the cytotoxicity of both natural killer cells and macrophages by ABMFPP. The antitumor activity of ABMFPP against B16 melanoma was almost completely eliminated when animals received a dose of 400 rads X-irradiation 5 days prior to tumor inoculation or a dose of 200 rads X-irradiation followed by several injections of anti-asialo monosialoganglioside antibody. The administration of anti-asialo monosialoganglioside alone also markedly reduced the anti-B16 melanoma activity of ABMFPP. The magnitude of reduction of the antitumor effect of ABMFPP by radiation and/or anti-asialo monosialoganglioside antibody directly correlated with the inhibition of the ABMFPP-mediated augmentation of immune responses. These results strongly suggest that the antitumor effect of ABMFPP alone or in combination with CY is at least in part mediated through its augmentation of natural killer cell and/or macrophage activities.
 ...
PMID:Mechanism of antitumor action of pyrimidinones in the treatment of B16 melanoma and P388 leukemia. 396 27

The efficacy of recombinant interferon-alpha 2 in the treatment of advanced hairy cell leukaemia is investigated in 31 patients. Preliminary results show a complete and partial response rate of 69%. An optimal dose study utilizing maximal stimulation of an interferon-dependent pathway was carried out in 5 patients. The optimal dose of the order of 5 X 10(5) IU/day is effective and without side-effects. Interferon treatment did not enhance natural killer cell activity and therefore a direct mode of action upon tumour cells is proposed.
 ...
PMID:Interferon-alpha-2C in the treatment of advanced hairy cell leukaemia. Results of a phase II trial. 408 Mar

Inoculation of Ehrlich ascites carcinoma cells (EAC) into the peritoneal cavities of outbred ddY mice induced interferon (IFN) in the circulation. The maximum titer (1,280 U) was obtained at 24 hr after inoculation. This induced IFN had the characteristics of type I IFN, i.e., stability at pH2 and lability at 56 C. An increase in natural killer cell (NK) activity was also observed for the first 3 days after inoculation. In addition, plasma lactate dehydrogenase (LDH) activity was elevated in these mice. Inoculation of ascitic fluid or serum of EAC-bearing mice into normal mice increased plasma LDH activity six- to sevenfold over normal levels and elevated activities persisted throughout the life of the mice. These results suggest that the LDH-elevating agent was responsible for IFN induction and for enhancing NK activity. Because lactate dehydrogenase-elevating virus (LDV) can be eliminated from tumor cells by passage in vitro, we attempted to grow EAC in tissue culture for several months and re-examined whether the inoculation of such cells could elevate plasma LDH activity induce IFN and enhance NK activity. The results showed that inoculation of the passaged cells had no effect on these activities in normal mice. Therefore, we concluded that the IFN inducer was LDV which contaminated the EAC and then enhanced the NK activity. N-tropic murine leukemia virus also contaminated EAC, but this virus was not responsible because cultured cells of EAC still shed this virus.
 ...
PMID:Lactate dehydrogenase-elevating agent is responsible for interferon induction and enhancement of natural killer cell activity by inoculation of Ehrlich ascites carcinoma cells into mice. 616 92


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>