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Biomedical subjects

P Stryckmans

Publications and source records attributed to P Stryckmans.

At least 109 records · Page 6Linked to original sources
PubMed1984

Lactoferrin: no evidence for its role in regulation of CSA production by human lymphocytes and monocytes.

Lactoferrin (LF) has been recently proposed as a physiologic regulator of the granulocyte monocyte progenitor (CFU-GM). This glycoprotein, when saturated with iron, has been said to limit CFU-GM growth by decreasing production and release of colony stimulating activity (CSA) by monocytes and macrophages. Human milk LF saturated with iron, at concentrations ranging from 10(-18) to 10(-8) M was added either to endogenously stimulated bone marrow cells or to mononucleated cells used as feeder layers for adherent cell-depleted marrow. Irrespective of the concentration of LF within the culture system used, no significant inhibition of CFU-GM growth was observed. Moreover, the CFU-GM stimulating activity of medium conditioned by a 4-day incubation of 1 X 10(6) mononucleated blood cells in the presence or in the absence of LF was the same. Various possible explanations for not confirming the reported inhibiting activity of iron saturated LF were explored: 1) masking inhibition of the system by prostaglandin E2 (PGE2), 2) masking inhibition of the system by bovine LF still detectable in the fetal calf serum after heating, 3) preinhibition of the system by leukemic-associated inhibitory activity (LIA) possibly present in the culture system, 4) the iron and calcium content of the culture medium used, 5) the fixation of LF to plastic compounds, 6) the source of the human LF used, 7) the marrow cell separation methods used. None of these factors was shown to play a role in vitro in the activity of LF and thus no evidence was found for a significant role of LF in the regulation of CSA production by monocytes. Peripheral blood human monocytes isolated by elutriation and incubated in albumin free medium in the presence of either 125I-LF or colloidal gold-labeled LF showed no LF binding.

Animals↗
PubMed1983

[Late intensive chemotherapy with bone marrow autograft. Pilot study in small cell bronchial cancer].

Following three courses of induction chemotherapy, 23 patients with small cell carcinoma of the lung were treated with a late intensive regimen including autologous bone marrow infusion. Thirteen patients received high doses (2 or 3 times the induction chemotherapy dosage) of cisplatin, adriamycin and etoposide. One patient was probably cured, but renal and mucosal toxicity was observed. Three patients treated with adriamycin, etoposide and cyclophosphamide also developed severe mucositis. The seven remaining patients received high doses of cyclophosphamide (100 to 200 mg/kg) and etoposide (750 to 1000 mg/m2); responses were obtained with moderate toxicity. The long-term survival is not yet known. The usefulness of bone marrow infusion cannot be determined without further studies.

Adult↗
PubMed1983

Granulocyte-macrophage progenitor cell preservation at 4 degrees C.

Eighteen bone marrows collected from patients without haematological diseases and from normal subjects were tested for the effects of 4 d storage at 4 degrees C on CFU-C growth. Results indicate that unfractionated bone marrow cells may be stored at 4 degrees C for 4 d with 97% +/- 8 SEM recovery of the CFU-C evaluated by the agar culture assay. On the other hand, the same preservation procedure on peripheral blood CFU-C of 13 normal subjects yielded only 5% +/- 2 SEM recovery of in vitro growth capacity. The present results have practical implications. They might be exploited to preserve bone marrow CFU-C for transplantation therapy or laboratory investigation. In contrast this single preservation procedure seems not appropriate for preserving blood CFU-C.

Blood Preservation↗
PubMed1983

Chemotherapeutic efficacy of Nocodazole encapsulated in liposomes on L1210 murine leukemia.

The use of sonicated phospholipid vesicles (liposomes) as carriers of methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl] carbamate (Nocodazole), a water insoluble antimitotic compound active on mouse L1210 leukemia was investigated. Nocodazole was incorporated in dipalmitoyl-phosphatidylcholine: cholesterol: stearylamine (4:3:1) liposomes that were stable at room temperature for at least 48 hr. No drug leakage nor lipid exchange occurred after a 4 hr incubation at 37 degrees C with RPMI 1640 medium supplemented with 10% fetal calf serum. L1210 cells preincubated (2 x 10(6) cells/ml) at 37 degrees C for 3 hr with various concentrations of micronized Nocodazole or liposome-entrapped Nocodazole were injected i.p. into normal CDF1 mice (10(5) cells/mouse). Longest mean survival times and long-time survivors were observed in the group inoculated with L1210 cells preincubated with liposomes containing Nocodazole. CDF1 mice bearing i.p. or i.v. L1210 leukemia were treated i.p. on days 1, 5 and 9 with micronized or liposome-entrapped Nocodazole. Administration of this latter preparation induced a 50% increase in animal life span at the dosage (25 mg/kg/day) half the one required with the free compound (50 mg/kg/day). The present data indicate that enclosing Nocodazole, a water insoluble antimitotic compound, in liposomes results in an enhanced therapeutic activity against L1210 murine leukemia.

Animals↗
PubMed1983

Iv administration of a water-insoluble antimitotic compound entrapped in liposomes. Preliminary report on infusion of large volumes of liposomes to man.

Five patients with advanced multiresistant neoplasms were infused with NSC-251635 (a water-insoluble antimitotic agent) entrapped in egg yolk lecithin, cholesterol, and stearylamine liposomes. The maximum volume injected was 400 ml containing 8 g of lipids, ie, a dose of 135 mg/kg of body weight. Overall tolerance of the treatment was excellent. This study indicates that liposomes may be used safely as carriers for the iv administration of water-insoluble drugs to humans.

Adenocarcinoma↗
PubMed1982

Cisplatin, adriamycin, and etoposide (CAV) for remission induction of small-cell bronchogenic carcinoma.

Chemotherapy with a combination of cisplatin (60 mg/m2), Adriamycin (45 mg/m2), and etoposide (120 mg/m2 X 3) (CAV) has been evaluated in 36 patients with small-cell bronchogenic carcinoma (SCBC) after two full courses. The complete response (CR) rate was 23% in patients with extensive disease and 64% in patients with limited disease; the partial remission (PR) rate was 59% in patients with extensive disease and 22% in those with limited disease after two cycles (six weeks) of therapy. Patients with CR survived significantly longer than patients with PR (P = 0.02). Side effects were acceptable and consisted mostly of nausea, vomiting, alopecia, and myelosuppression. Thirteen patients were included into a "late intensification" program that was performed with increased doses of CAV regimen used for remission induction. This intensification of chemotherapy was carried out in a protective environment and with autologous bone marrow transfusion. In two patients with PR, CR could be obtained after late intensification and in one patient whose disease was progressing, PR had been achieved. However, excessive extramedullary toxicity of the late intensification regimen, consisting of mucositis, suggested that CAV does not appear to be the optimal therapy for further intensification.

Adult↗
PubMed1982

Scientific basis and criticism of current therapy of acute leukemia.

The factors which are thought to determine the response of acute leukemia (AL) to therapy are: 1) tumor size 2) drug dose 3) sensitivity to drug, 4) scheduling of drugs and 5) suppression of normal hemopoiesis. Each of these factors is considered in terms of the scientific data supporting their importance. Inability to measure the size of the tumor mass during all phases of treated AL continues to weaken rational strategies for therapy especially maintenance chemotherapy. Increasing the drug dose improves cell kill and potentially the cure rate up to the limits of toxicity. These limits may be extended by bone marrow transplantation. Various systems to study the drug sensitivity of leukemic cells are in experimental use, including stem cell assays but as yet they do not give a guide to altering therapy. The scheduling of multiple drugs is designed to increase cell kill by recruitment into the cycle, but "sanctuaries" appear to exist for resting cells. The suppression of normal hemopoiesis apparently due to leukemia-associated inhibitors is associated with favorable prognosis in childhood ALL but use of this information to improve treatment protocols is still unclear.

Acute Disease↗
PubMed1981

Sensitivity of myeloid progenitor cells in healthy subjects and patients with chronic myeloid leukemia to chemotherapeutic agents.

The different sensitivity of myeloid progenitor cells (CFUc) to chemotherapeutic agents was measured with an in vitro clonogenic assay. Normal marrow and peripheral blood CFUc and blood CFUc obtained from patients with chronic myelogenous leukemia (CML) were tested for their sensitivity to medications used currently in the management of CML. The drugs tested were adriamycin, L-asparaginase, busulfan, beta-cytosine arabinoside (Ara-C), daunorubicin, hydroxyurea, melphalan, and thioguanine. CML CFUc were significantly more sensitive to Ara-C [drug dose required for 90% inhibition of CFUc growth (LD90) = 0.015 +/- 0.003 microgram/ml] than were normal CFUc (LD90 = 0.038 +/- 0.009 microgram/ml). A shift to enhanced sensitivity to L-asparaginase was detected in patients studied sequentially who entered blast transformation during this study. In vitro and in vivo pharmacokinetic data are compared.

Antineoplastic Agents↗
PubMed1981

Chemotherapeutic sensitivity of normal and leukemic hematopoietic progenitor cells to N-[4-(9-acridinylamino)-3-methoxyphenyl]-methanesulfonamide, a new anticancer agent.

The sensitivities of hematopoietic colony-forming cells (CFC) to N-[4-(9-acridinylamino)-3-methoxyphenyl]-methanesulfonamide (NSC-249992) (m-AMSA) were measured with an in vitro clonogenic assay, a modification of the Robinson and Pike human marrow culture system. CFC derived from bone marrow and peripheral blood of normal subjects and patients with chronic myeloid leukemia (CML) were studied. Sensitivities to m-AMSA did not differ significantly between normal marrow and blood CFC, between normal and CML CFC, or between CML CFC obtained from patients with leukemias in chronic phase and blast transformation. Drug doses and exposure times producing in vitro hematopoietic inhibition were comparable to clinically employed drug dosages and schedules associated with hematopoietic toxicity.

Aminoacridines↗
PubMed1981

Nocodazole entrapped into liposomes: no more effect on human CFU-C than free nocodazole.

Nocodazole, a water insoluble antimitotic drug active on L1210 leukemia was incorporated into liposomes, to investigate whether this procedure could increase cellular uptake. The effects of micronized nocodazole and liposome-entrapped nocodazole were compared on human marrow cells in vitro using a myeloid progenitor cell assay (CFU-C). The human CFU-C were sensitive to the micronized drug in a dose-related fashion. However, contrasting with a previous report on L 1210 leukemia, entrapping of nocodazole into liposomes did not increase its activity of CFU-C of either normal or leukemic subjects.

Antineoplastic Agents↗