acid-phosphatase and Leukopenia

One hundred forty-two patients with progressive, hormonally refractory advanced prostate carcinoma who had not received prior chemotherapy were randomized to receive either combination chemotherapy with 5-fluorouracil (5-FU), doxorubicin, and mitomycin C (FAM) or sequential chemotherapy with the same agents, i.e., mitomycin C, followed by doxorubicin on disease progression, followed by 5-FU. Objective tumor regressions were observed in 10 of 70 (14%) patients receiving the FAM treatment arm and 10 of 72 (14%) patients initially receiving mitomycin C. Of the 24 patients who received secondary therapy with doxorubicin alone, 3 (12.5%) achieved objective tumor regression. There were no responses among five patients who received tertiary therapy with 5-FU alone. The median survival time for all patients treated with the combination arm was 8.7 months, compared with 7.1 months for patients who received the FAM arm (P = 0.025). However, this modest survival advantage in favor of the FAM treatment arm must be weighed against significantly more myelosuppression experienced by these patients. The chemotherapeutic regimens used in this study have only minor clinical value in the treatment of hormonally refractory advanced prostate cancer.

Topics: Acid Phosphatase; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Doxorubicin; Fluorouracil; Humans; Leukopenia; Male; Mitomycin; Prostatic Neoplasms; Remission Induction; Survival Rate; Thrombocytopenia

The NOD mouse spontaneously develops autoimmune diabetes. Dendritic cells (DC) play a crucial role in the autoimmune response. Previous studies have reported a defective DC generation in vitro from the NOD mouse bone marrow (BM), but a deviated development of myeloid precursors into non-DC in response to GM-CSF was not considered. In this study, we demonstrate several abnormalities during myeloid differentiation of NOD BM precursors using GM-CSF in vitro. 1) We found reduced proliferation and increased cell death in NOD cultures, which explain the previously reported low yield of DC progeny in NOD. Cell yield in NOR cultures was normal. 2) In a detailed analysis GM-CSF-stimulated cultures, we observed in both NOD and NOR mice an increased frequency of macrophages, identified as CD11c(+)/MHCII(-) cells with typical macrophage morphology, phenotype, and acid phosphatase activity. This points to a preferential maturation of BM precursors into macrophages in mice with the NOD background. 3) The few CD11c(+)/MHCII(high) cells that we obtained from NOD and NOR cultures, which resembled prototypic mature DC, appeared to be defective in stimulating allogeneic T cells. These DC had also strong acid phosphatase activity and elevated expression of monocyte/macrophage markers. In conclusion, in this study we describe a deviated development of myeloid BM precursors of NOD and NOR mice into macrophages and macrophage-like DC in vitro. Potentially, these anomalies contribute to the dysfunctional regulation of tolerance in NOD mice yet are insufficient to induce autoimmune diabetes because they occurred partly in NOR mice.

Topics: Acid Phosphatase; Animals; Apoptosis; Biomarkers; Bone Marrow Cells; Cell Differentiation; Cell Division; Cells, Cultured; Dendritic Cells; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Leukocyte Count; Leukopenia; Lysosomes; Macrophages; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred NOD; Myeloid Progenitor Cells

The present study investigated the ability of uteroferrin to modulate the myelosuppressive effects of 5-fluorouracil (5-FU) in young pigs (Sus scrofa). Pigs (28-35 days of age; n = 6 per treatment) were infused with equal amounts of 5-FU on days 0 and 1 of the experimental period (37.5 mg/kg cumulative dose). Uteroferrin (100 micrograms/kg in 0.9% NaCl) or control (equivalent volume of 0.9% NaCl) was administered to pigs as intramuscular injections twice daily (08:00 and 20:00 hr) on days 1 through 21. Peripheral blood cell number, composition and progenitor cells were determined over 28 days. Treatment of pigs with 5-FU resulted in a rapid dose-dependent (P < 0.05) leukocytopenia. Concurrent treatment of pigs with uteroferrin reduced (P < 0.05) the rate of 5-FU-induced leukocytopenia (44 vs 77 +/- 7% decline from baseline on day 3) and enhanced (P < 0.05), the recovery from 5-FU on days 10 and 12 postinfusion. The positive effect of uteroferrin on leukocytes resulted primarily from a protection and/or enhanced recovery of neutrophils and monocytes. In addition, uteroferrin attenuated (P < 0.05) the suppression of red blood cell numbers after 5-FU administration (6.9 vs 6.1 +/- 0.2 x 10(6) cells/microliter on day 3), an affect reflected in increased hematocrit and hemoglobin concentrations. The effects of uteroferrin appeared to result from enhancement of the proliferation and/or differentiation of primitive pluripotent stem cells resistant to 5-FU, as concurrent treatment of pigs with uteroferrin resulted in a protection and/or enhanced recovery (P < 0.05) of CFU-GEMM, CFU-GM and BFU-E progenitor cells in the peripheral blood. These results are the first to demonstrate that uteroferrin can reduce the myelosuppressive effects of 5-FU in the pig and suggest that uteroferrin has hematopoietic growth factor activity in vivo.

Topics: Acid Phosphatase; Animals; Antimetabolites, Antineoplastic; Bone Marrow; Bone Marrow Cells; Dose-Response Relationship, Drug; Erythrocyte Count; Erythroid Precursor Cells; Fluorouracil; Hematocrit; Hematopoietic Stem Cells; Isoenzymes; Leukocyte Count; Leukopenia; Male; Metalloproteins; Swine; Tartrate-Resistant Acid Phosphatase

Intravenous infusion of platelet-activating factor (PAF-acether) induces extensive vasocongestion and damage in the stomach and small intestine of the rat. The effect of pretreatment with the corticoid dexamethasone (2 mg/kg) on such gastrointestinal damage in the rat has now been investigated, using macroscopic observation and the release of acid phosphatase, as an enzyme marker of cell disruption. Administration of PAF-acether (100 ng/kg/min intravenously, for 10 min) induced focal, intense hyperemia and hemorrhage in all the regions of the gastrointestinal tract, with the exception of the distal colon. This damage was associated with an increase in the release of acid phosphatase into the lumen of the stomach, duodenum, jejunum, and ileum following incubation in vitro. Pretreatment with dexamethasone reduced the macroscopically apparent gastrointestinal damage following PAF-acether administration and abolished the intraluminal release of acid phosphatase. Dexamethasone also significantly suppressed the hemoconcentration, as determined by changes in platelet and erythrocyte count and hematocrit, 30 min after PAF-acether infusion. Thus, as in endotoxin shock, this glucocorticoid can reduce the gastrointestinal damage associated with PAF-acether administration.

Topics: Acid Phosphatase; Animals; Colon; Dexamethasone; Erythrocyte Count; Gastric Mucosa; Intestinal Mucosa; Jejunum; Leukopenia; Male; Platelet Activating Factor; Platelet Count; Premedication; Rats; Rats, Inbred Strains

A prospective study was conducted to evaluate response rate and toxicity of the combination of cyclophosphamide, adriamycin, and cis-platinum in patients with disseminated hormonally resistant prostatic carcinoma. Twenty-two patients were entered in the study: 19 were evaluable for response. One patient achieved partial remission while 14 (73%) had stable disease. Four patients had progressive disease. Patients with stable disease and partial remission had subjective improvement and survived significantly (p less than 0.03) longer than patients with progressive disease (58 weeks vs. 22 weeks). Toxicity was mainly hematological, and one patient died from sepsis secondary to leukopenia. Nausea and vomiting was moderate to severe, with one patient refusing cis-platinum for that reason. Renal toxicity was tolerable and reversible. Lack of good measurable disease makes generalization difficult, but pointers from animal models, along with the biological activity suggested by our results, make this a worthwhile combination to be considered for a trial in a larger population with measurable disease or in a randomized trial vs. the more effective single agent.

Topics: Acid Phosphatase; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Evaluation; Humans; Leukopenia; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Child; Granulocytes; Hematopoiesis; Humans; Leukocyte Count; Leukopenia

The cytomorphology and lysosomal enzyme activity of the haemopoietic and reticuloendothelial system (RES) of SJL/J mice, which develop a spontaneous reticulum cell neoplasm type B (RCN-B), were studied. The cytological findings during development of the disease were a predominance of medium-sized lymphocytes and an increase in the number of hyperbasophilic cells and plasma cells in the RES. These pathological findings were compared to the changes due to ageing in control groups of healthy C3H/eB mice. Acid phosphatase activity increased in the RES, whereas that of beta-D-glucuronidase remained unchanged during development of the disease. These findings indicate that the RCN-B of the SJL/J mice bear a certain resemblance to Hodgkin disease in man.

Topics: Acid Phosphatase; Animals; Bone Marrow; Cell Transformation, Neoplastic; Female; Glucuronidase; Hematopoietic Stem Cells; Leukopenia; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Lysosomes; Male; Mice; Mice, Inbred C3H; Mice, Inbred Strains; Mononuclear Phagocyte System; Spleen; Thymus Gland

Topics: Acid Phosphatase; Alkaline Phosphatase; Humans; Infant; Infant, Newborn; L-Lactate Dehydrogenase; Leukocyte Count; Leukopenia; Neutrophils; Phagocytosis

Topics: Acid Phosphatase; Adenosine Triphosphatases; Adolescent; Alkaline Phosphatase; Antineoplastic Agents; Autopsy; Biopsy; Bone Marrow Cells; Esterases; Female; Glycogen; Humans; Kidney; L-Lactate Dehydrogenase; Leukemia, Lymphoid; Leukocyte Count; Leukopenia; Liver; Liver Function Tests; Lymph Nodes; Monocytes; Peroxidases; Time Factors

Topics: Acid Phosphatase; Cytodiagnosis; Histocytochemistry; Leukocytes; Leukopenia

Topics: Acid Phosphatase; Anaphylaxis; Animals; Antibody Formation; Antigen-Antibody Reactions; Arthus Reaction; Blood Cell Count; Blood Platelets; Blood Pressure; Fluorescent Antibody Technique; Glucuronidase; Hemorrhage; Hydrolases; Hypersensitivity; Hypotension; Immunity, Active; Immunity, Maternally-Acquired; Inflammation; Injections, Intravenous; Leukocytes; Leukopenia; Lung; Lysosomes; Methods; Microscopy, Electron; Microscopy, Fluorescence; Peptide Hydrolases; Pulmonary Circulation; Rabbits; Rats; Serum Albumin, Bovine; Swine

Topics: Acid Phosphatase; Hemorrhagic Disorders; Humans; L-Lactate Dehydrogenase; Leukemia, Myeloid; Leukocytes; Leukopenia; Male; Middle Aged; Splenic Rupture