Increase of hematopoietic responses by triple or single helical conformer of an antitumor (1-->3)-beta-D-glucan preparation, Sonifilan, in cyclophosphamide-induced leukopenic mice. (1/834)

It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on its conformation in mice. In this study, we examined the relationship between the conformation of Sonifilan (SPG) and hematopietic responses in cyclophosphamide (Cy)-induced leukopenic mice. SPG, a high molecular weight (1-->3)-beta-D-glucan, has a triple helical conformation in water, and it was changed by treatment with aqueous sodium hydroxide to the single helical conformer (SPG-OH). The effects of SPG or SPG-OH on hematopoietic responses in cyclophosphamide induced leukopenic mice were investigated by monitoring i) gene expression of cytokines by RT-PCR, ii) protein synthesis of interleukin 6 (IL-6) by ELISA and iii) colony formation of bone marrow cells (BMC). The mice administered Cy and SPG or SPG-OH expressed and produced higher levels of IL-6 mRNA and protein than the mice administered only Cy. Gene expression of NK1.1 was also induced by Cy/SPG (or SPG-OH) treatment. Induced gene expression of stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) by SPG/SPG-OH were also found in in vitro culture of BMC from Cy treated mice. These results strongly suggested that conformation of the glucans, single and triple helix, are independent of the hematopietic response.  (+info)

A phase I/II study of continuous intra-arterial chemotherapy using an implantable reservoir for the treatment of liver metastases from breast cancer: a Japan Clinical Oncology Group (JCOG) study 9113. JCOG Breast Cancer Study Group. (2/834)

BACKGROUND: Liver metastasis from breast cancer has a poor prognosis. While there are some reports of good response rates of hepatic metastasis from breast cancer by hepatic intra-arterial infusion chemotherapy, no phase I study including pharmacokinetic analysis has been reported. We performed a phase I/II study of intra-arterial infusion chemotherapy using adriamycin and 5-fluorouracil to find the maximum tolerated dose and response rate in patients with advanced or recurrent breast cancer. METHODS: A hepatic arterial catheter with an access port was inserted into the proper hepatic artery. Patients received 30 mg/m2 adriamycin on days 1 and 8 and 100 mg/m2 5-fluorouracil at level 1, 200 mg/m2 at level 2,300 mg/m2 at level 3 and 400 mg/m2 at level 4 continuously from day 1 through day 14 every 28 days. At least two cycles were required before evaluation. Twenty-eight patients were entered into this study and 26 patients were evaluable. Seventeen patients had hepatic metastasis only, although nine patients had additional metastasis to other sites. RESULTS: Dose-limiting toxicity of thrombocytopenia and neurotoxicity occurred at level 4. Leukocytopenia (ECOG grade 3-4) was observed in five (19%), thrombocytopenia in three (12%) and anemia in two (8%) patients. There were 11 catheter-related complications which were not dose dependent. Seven out of 13 evaluable patients (54%) responded at level 3. The median duration of response was 5.8 months (range, 1-23+) and median survival was 25.3 months (range, 6.2-54.7+). CONCLUSION: Hepatic arterial infusion therapy appears to be safe and effective but catheter-related complications must be overcome before starting a phase III trial.  (+info)

Inhibition of a membrane complement regulatory protein by a monoclonal antibody induces acute lethal shock in rats primed with lipopolysaccharide. (3/834)

Rats pretreated with traces of LPS developed acute fatal shock syndrome after i.v. administration of a mAb that inhibits the function of a membrane complement regulatory molecule. Such a shock was not observed after the administration of large amounts of LPS instead of the mAb following LPS pretreatment. The lethal response did not occur in rats depleted of either leukocytes or complement, and a C5a receptor antagonist was found to inhibit the reaction. Furthermore, LPS-treated rats did not suffer fatal shock following the injection of cobra venom factor, which activates complement in the fluid phase so extensively as to exhaust complement capacity. Therefore, complement activation on cell membranes is a requirement for this type of acute reaction.  (+info)

Quantitative and qualitative effects of cyclophosphamide administration on circulating polymorphonuclear leucocytes. (4/834)

The effect of cyclophosphamide (CY) on the absolute numbers and function of polymorphonuclear leucocytes (PMN) surviving in the circulation following either a single dose (100 mg/kg, i.p.) or daily administration (20 mg/kg, i.p., for 5 days) was studied in the guinea-pig. The quantitative effect of CY on peripheral blood leucocytes was assessed by measuring the absolute numbers of neutrophils, lymphocytes, and monocytes daily for 5 days following the initial injection of CY. The qualitative effects of CY on PMN function were determined by measuring the ability of these cells to function as killer cells. The two functional assays employed were the PMN-mediated PHA-induced cellular cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) assays against chicken erythrocyte targets. Both regimens of CY administration produced an equivalent degree of leukopenia 5 days after the initial injection with disproportionately severe neutropenia (less than 300 PMN/mm3). However, neither regimen of CY administration produced a significant decrease in cytotoxic effector function as measured through a wide range of effector to target cell ratios, PHA concentrations, and antiserum dilutions. These findings have clinical relevance in that they demonstrate the dichotomy between the quantitative and qualitative effects of (CY) on PMNs in that CY administration can dramatically decrease the absolute numbers of circulating polymorphonuclear leucocytes while leaving intact certain effector cell functional capabilities of those PMN surviving in the circulation during drug administration.  (+info)

Lithium dosage and leukocyte counts in psychiatric patients. (5/834)

OBJECTIVE: To evaluate differences in leukocyte counts among patients treated with either lithium alone, antipsychotic medications alone, or a combination of both. DESIGN: Retrospective study. SETTING: Long-stay psychiatric hospital. PATIENTS: Patients admitted between 1990 and 1993, and treated with lithium for at least 1 week and/or with antipsychotic medication for at least 2 weeks. Excluded from the study were those patients for whom complete blood counts at baseline and during therapy were not available, and those patients whose blood picture could primarily be accounted for by extraneous factors. Included in the study were 38 patients treated with lithium alone, 207 patients receiving antipsychotic medications alone, and 71 patients receiving both. OUTCOME MEASURES: Leukocyte, lymphocyte and granulocyte counts. RESULTS: Patients treated with lithium alone had significantly higher mean leukocyte and granulocyte counts than those treated with antipsychotic medication alone (analysis of variance, p < 0.05). None of the patients receiving lithium alone showed leukopenia. The dosage of lithium was significantly correlated with leukocyte count (r = 0.25, 95% confidence interval [CI] 0.14 to 0.35, p < 0.001,) and granulocyte count (r = 0.27, 95% CI 0.16 to 0.38, p < 0.001), but not with lymphocyte count (r = 0.06, p = 0.286, 95% CI -0.05 to 0.17). CONCLUSIONS: Lithium therapy is associated with higher leukocyte and granulocyte levels in psychiatric patients. This leukocytotic effect of lithium may be dose dependent.  (+info)

Phase I study of a biweekly schedule of a fixed dose of cisplatin with increasing doses of paclitaxel in patients with advanced oesophageal cancer. (6/834)

We performed this dose-finding study with a fixed dose of cisplatin and increasing doses of paclitaxel given every 2 weeks to determine the maximum tolerable dose of this schedule. Sixty-four patients with advanced oesophageal cancer were treated with a cisplatin dose of 60 mg m(-2) and increasing doses of paclitaxel from 100 mg m(-2) up to 200 mg m(-2) both administered over 3 h for a maximum of six cycles in patients with stable disease or eight cycles in responding patients. Patients were retreated when the granulocytes were > 0.75 x 10(9) l(-1) and the platelets > 75 x 10(9) l(-1). The dose of paclitaxel could be increased to 200 mg m(-2) without encountering dose limiting haematological toxicity. At the dose levels 190 mg m(-2) and 200 mg m(-2) of paclitaxel cumulative sensory neurotoxicity became the dose-limiting toxicity. The dose intensity of paclitaxel calculated over six cycles rose from 50 mg m(-2) per week to 85 mg m(-2) per week. Only three episodes of granulocytopenic fever were encountered out of a total of 362 cycles of treatment. Of the 59 patients evaluable for response, 31 (52%) had a partial or complete response. In a biweekly schedule with a fixed dose of 60 mg m(-2) cisplatin it is possible to increase the dose of paclitaxel to 180 mg m(-2). At higher dose levels, neurotoxicity becomes the dose-limiting toxicity. The observed response rate warrants further investigation of this schedule.  (+info)

Fundamental signals that regulate eosinophil homing to the gastrointestinal tract. (7/834)

The histological identification of increased eosinophils in the gastrointestinal tract occurs in numerous clinical disorders; however, there is a limited understanding of the mechanisms regulating eosinophil trafficking into this mucosal surface. The results presented in this study characterize the processes regulating eosinophil homing into the gastrointestinal tract at baseline. Eosinophils were found to be present in the lamina propria of 19-day-old embryos and germ-free adult mice at concentrations comparable to those present in non-germ-free adult mice. Furthermore, eosinophil gastrointestinal levels were not altered by increasing circulating eosinophils after pulmonary allergen challenge. Gastrointestinal eosinophil levels were partially reduced in mice deficient in recombinase activating gene-1 (RAG-1), IL-5, or the beta common chain (betac), but these reductions paralleled reductions in circulating eosinophils. In contrast, mice deficient in eotaxin had a marked reduction in gastrointestinal eosinophils but normal levels of eosinophils in the hematopoietic compartments. Furthermore, eotaxin was important for regulating eosinophil levels, even in the presence of high levels of IL-5. These investigations demonstrate eosinophil homing into the gastrointestinal tract during embryonic development occurring independently of viable intestinal flora. Furthermore, eotaxin is identified as the primary regulator of eosinophil gastrointestinal homing under homeostatic states, and may therefore have a fundamental role in innate immune responses.  (+info)

Prevention of febrile leucopenia after chemotherapy in high-risk breast cancer patients: no significant difference between granulocyte-colony stimulating growth factor or ciprofloxacin plus amphotericin B. (8/834)

In a prospective randomized trial, 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy (cyclophosphamide, 5-fluorouracil plus epirubicin or methotrexate), received either recombinant human G-CSF (rhG-CSF, group I) or ciprofloxacin and amphotericin B (CAB, group II) for prevention of febrile leucopenia (FL). In group I, seven of 18 patients developed FL (after 10/108 courses); in group II, seven of 22 patients (7/98 courses) (P = NS). Median hospitalization duration and costs were not different. RhG-CSF was 6.6 times more expensive per course than CAB. In conclusion, prophylactic CAB has similar efficacy to rhG-CSF in this setting, and is more cost-effective.  (+info)

• 1
• 2
• 3
• 4
• 5
• 6
• 7
• 8
• 9
• 10