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S Glück

Publications and source records attributed to S Glück.

At least 19 recordsLinked to original sources
PubMed1996

The selective uptake of benzoporphyrin derivative mono-acid ring A results in differential cell kill of multiple myeloma cells in vitro.

High-dose chemotherapy (HDCT) and autologous bone marrow/blood stem cell transplantation are an effective combination for treating a number of malignant disorders. The contamination of the autograft by malignant cells may be a reason for recurrences in spite of this treatment, for instance, in multiple myeloma. Therefore, we evaluated the use of photodynamic therapy (PDT) using the photosensitizer benzoporphyrin derivative mono-acid ring A (BPD-MA) on multiple myeloma cells in comparison to the components of the normal bone marrow (NBM) and peripheral blood apheresis product. Flow cytometry was used to measure differential BPDMA uptake of NBM components: namely lymphocytes, monocytes, granulocytes and enriched hematopoietic stem cell (CD34+) populations and also the multiple myeloma cell lines OCI-MY7 and OCI-MY4. When each population was measured individually, the order of uptake was [OCI-MY7/MY4] > [CD34+] > [granulocytes] = [monocytes] >> [lymphocytes]. Further, clonogenic assay was used to demonstrate surviving fractions for OCI-MY7, OCI-MY4 and NBM in vitro. The LD90 for OCI-MY7 and OCI-MY4 was between 10 and 20 ng/mL BPD-MA whereas this concentration did not show any significant cell kill for the colony-forming units-granulocyte/macrophage (CFU-GM) and burst-forming units-erythrocyte (BFU-E). When the NBM was "contaminated" with multiple myeloma cells in vitro, the LD90 for OCI-MY7 in this cell mixture was shifted to between 40 and 80 ng/mL BPD-MA. However, at 40 ng/mL BPD-MA at least 50% of normal CFU-GM and BFU-E colonies survived. For CFU-GM and BFU-E derived from the enriched CD34+ cell population, BPDMA up to a concentration of 80 ng/mL did not significantly reduce the surviving fractions. We have observed a 3-4 log therapeutic window with differential cell kill when comparing multiple myeloma cell lines to the components of the NBM and apheresis product in vitro. We conclude, that BPD-MA is a molecule potentially useful as an ex vivo purging agent.

Bone Marrow↗
PubMed1995

Autologous transplantation for patients with advanced breast cancer with emphasis on bony metastasis.

The number of deaths due to breast cancer in Ontario in 1990 has been over 1700. Although hormone treatment and polychemotherapy in advanced breast cancer have been introduced many years ago for patients with metastatic breast cancer, the median survival time for this patient subpopulation, who either have hormone receptor negative tumors or have failed hormone therapy, remains between 15-18 months. Fewer than 20% of all patients are alive three years after the diagnosis of metastatic disease. Some other studies have demonstrated that dose-escalation with growth factor and/or stem cell support (from the bone marrow or peripheral blood) has shown a higher response rate including complete remissions.

Adolescent↗
PubMed1994

Soluble CD4, soluble CD8, soluble CD25, lymphopoieitic recovery, and endogenous cytokines after high-dose chemotherapy and blood stem cell transplantation.

Mononuclear cell preparations from peripheral blood after mobilization with hematopoietic growth factors have been shown to induce accelerated neutrophil and platelet recovery as compared with that induced by autologous bone marrow transplantation after myeloablative chemotherapy. Because these mononuclear cell products contain many immunocompetent cells other than hematopoietic progenitors, these accessory cells might contribute to the rapid immunohematopoietic reconstitution. We have monitored the concentrations of soluble CD4 (sCD4), sCD8, and sCD25; the recovery of the lymphocyte subsets and of natural killer (NK) cells; and the endogenous levels of granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), IL-6, and granulocyte-macrophage-CSF (GM-CSF) in 12 patients who underwent high-dose chemotherapy supported by blood stem cells that were obtained by mobilization with chemotherapy and GM-CSF. The concentrations of both G-CSF and IL-6 peaked at 7 days after reinfusion of stem cells, and this transient elevation preceded the increase in the white blood cell count by approximately 5 to 7 days. The levels of sCD4 and sCD8 increased to a maximum on day 21, and the time to peak levels coincided with the maximum increase in white blood cell count, absolute neutrophil count, or lymphocytes. The levels of sCD25 were found to be elevated from day 7 to day 21. Statistically, the increases in sCD4, sCD8, sCD25, G-CSF, and IL-6 were highly significant, whereas there were no significant changes in IL-3 and GM-CSF. A rapid recovery of the NK activity was found in all 8 of the patients who could be monitored for this assay. Therefore, our study suggests that recovery of CD4+ cells, CD8+ cells, and NK activity coincided with that of neutrophils, which is preceded by a marked, but transient, elevation of IL-6 and G-CSF.

Adolescent↗
PubMed1994

Radiosensitivity of human clonogenic myeloma cells and normal bone marrow precursors: effect of different dose rates and fractionation.

PURPOSE: Evaluation of radiation dose rate and fractionation effects on clonogenic myeloma cells. METHODS AND MATERIALS: The radiosensitivity of clonogenic myeloma cells was evaluated for seven human myeloma cell lines. The lines were maintained in liquid suspension culture. Following radiation, cells were plated in semisolid medium using methylcellulose as viscous support. Radiation doses up to 12 Gy were delivered at dose rates of 0.05 and 0.5 Gy/min by a 60Co source. Each total dose was administered either as a single dose or in multiple fractions of 2 Gy. The data were analyzed according to the linear quadratic and multi target model of irradiation. RESULTS: Clonogenic progenitors of the seven myeloma cell lines differed in their radiosensitivity as measured by multiple parameters. The differences were mainly observed at low dose. The most effective cytoreduction was seen when radiation was administered in a single fraction at high dose rate. The cytoreductive effect on clonogenic myeloma cells was compared for clinically practiced total body irradiation (TBI) schedules delivered either in a single or in multiple fractions without causing significant pulmonary toxicity. The administration of 12 Gy delivered in six fractions of 2 Gy resulted in a superior reduction of clonogenic cells compared to a single fraction of 5 Gy. CONCLUSION: The preparation of bone marrow transplant recipients with multiple myeloma using fractionated radiation with a total dose of 12 Gy appears to afford better ablation than a single dose of 5 Gy while maintaining a low incidence of pulmonary toxicity.

Bone Marrow↗
PubMed1994

Neutropenic fever in patients after high-dose chemotherapy followed by autologous haematopoietic progenitor cell transplantation and human recombinant granulocyte-macrophage colony stimulating factor.

Neutropenic fever has been one of the most difficult complications in the recovery period following high-dose chemotherapy and autologous haematopoietic progenitor cell transplantation. The differentiation between human recombinant GM-CSF (sargramostim)-related fever and active infection can be difficult during this observation time. In 7 of 17 patients treated for metastatic breast cancer with HDCT and PBPC within 6 consecutive months, neutropenic fever without signs of infection was observed, which may be sargramostim-related fever. The typical presentation must fulfil the following criteria: cyclical elevation in body temperature that happens at the predicted time after sargramostim administration; absence of other signs or symptoms of infections; quick resolution of the fever after onset acetaminophen administration. Having met these criteria, none of these patients has been treated with intravenous antibiotics for active infections. At the time of haematological recovery (at a median time of 13 days from PBPC reinfusion to absolute neutrophil counts of > or = 0.5/nl) the febrile episode gradually resolved. No serious complications or other side-effects were observed. No toxic deaths occurred. Only if specific symptoms or signs of infection develop, would intravenous empiric antibiotic therapy be started.

Breast Neoplasms↗
PubMed1994

The use of photodynamic therapy in bone marrow purging.

High-dose chemotherapy and autologous bone marrow transplantation are an effective combination for treating a number of malignant disorders. Clinical trials have demonstrated a potential role for this regimen in the management of acute leukemia and non-Hodgkin's lymphoma. Autologous bone marrow transplantation continues to be limited by high relapse rates, as compared with allogeneic bone marrow transplantation. Two factors are thought to account for this observation. First, autologous transplants lack the immunologic "graft-versus-host" advantage of allogeneic transplants. Second, autologous grafts have the possibility of tumor cell contamination. Methods to reduce tumor cell contamination in autografts include exposure to chemical agents or monoclonal antibodies; long-term marrow cultures; and immunologic manipulation, either with immunomagnetic devices or antibody/complement combinations. Photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) or benzoporphyrin derivative (BPD verteporfin; BPD-MA; BPD-Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) may be an effective means of purging bone marrow. The ability of malignant cells to selectively accumulate photosensitizing agents may account for efficacy of PDT in bone marrow purging. The efficacy of porfimer sodium and BPD has been evaluated in cell lines known to express multidrug resistance (MDR), and the results compared with corresponding MDR-negative cell lines. Multidrug resistance-positive cell lines appear relatively resistant to BPD; porfimer sodium remains active. The reason for the differential effect of MDR positivity on the cytotoxicity of porfimer sodium and BPD is unclear, but is believed to be related to the larger size of the porfimer sodium molecule. Clinical trials evaluating PDT in bone marrow transplantation are under way.

Bone Marrow Purging↗
PubMed1993

Optimal timing for collections of blood progenitor cells following induction chemotherapy and granulocyte-macrophage colony-stimulating factor for autologous transplantation in advanced breast cancer.

Circulating progenitor cells collected during periods of rapid hematopoietic reconstitution can be used successfully as hematopoietic support for super-dose chemotherapy. A major problem for collection of peripheral blood progenitor cells has been determination of optimal time to start leukapheresis and of the adequate amount of progenitor cells. This study has demonstrated that an induction chemotherapy with augmented dosage of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) in conjunction with granulocyte-macrophage colony-stimulating factor (CM-CSF) successfully mobilized peripheral blood progenitor cells in 15 patients with metastatic breast cancer. By monitoring the granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte burst-forming units (BFU-E), and CD34+ cells in peripheral blood daily after leukocyte nadir, we have identified an optimal 'window' in which concentrations of blood progenitor cells reached a maximum range. Although the time interval between chemotherapy and the time for maximum stimulation could vary from between 13 days to 19 days, maximum mobilization started consistently 2 days after the white blood cells (WBC) recovered to > 2.0 x 10(9)/l after nadir, and remained elevated for 4 to 5 days. A significant reduction of progenitor cells in peripheral blood and in the corresponding leukapheresis products was observed, however, from cycle 1 versus subsequent cycles (p < 0.0001), but there was no significant difference between cycles 2 and 3. When used as the sole source of hematopoietic support for super-dose chemotherapy with cyclophosphamide, mitoxantrone, and carboplatin, these progenitor cells induce rapid and sustained reconstitution in all patients. The median time from reinfusion to recovery of absolute neutrophil count (ANC) to > 0.5 x 10(9)/l was 13 days (range 9-18 days) and to an unmaintained platelet count of > 50 x 10(9)/l, 12 days (range 10-35 days). Autologous transplantation with stimulated blood progenitor cells can be an efficient alternative to bone marrow transplantation. With optimal timing for collections, as few as two leukapheresis procedures are required to obtain an adequate progenitor cell dose.

Adolescent↗
PubMed1992

Glutathione depletion, lipid peroxidation, DNA double-strand breaks and the cytotoxicity of 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone in rat renal cortical cells.

The mechanisms involved in the cytotoxicity of 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone, a model compound for hydroquinone derived mercapturic acids, were investigated in rat renal proximal tubule cells. 2-Bromo-3-(N-acetylcystein-S-yl)hydroquinone induced a time- and concentration-dependent decrease in cell viability and in the levels of cellular glutathione. Antioxidants such as N,N'-diphenyl-p-phenylene diamine and ascorbic acid and the iron chelator desferrioxamine very efficiently protected the cells from 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone without influencing glutathione depletion. The acetoxymethyl ester of the Ca2+ chelator Quin-2, the inhibitor of the Ca(2+)- and Mg(2+)-dependent endonucleases, aurintricarboxylic acid and the poly(ADP-ribose)-polymerase inhibitor 3-aminobenzamide also ameliorated 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone cytotoxicity. Moreover, 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone depleted Ca2+ from isolated kidney mitochondria, increased the amount of malondialdehyde in rat kidney cells and induced DNA double-strand breaks in renal cells in culture. These results suggest that renal cells oxidize 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone to the corresponding quinone; this soft electrophile reacts rapidly with glutathione, thus depleting cellular glutathione concentrations as indicated by the tentative identification of a 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone thioether in the incubation medium of renal cells treated with the mercapturate. As a result of the massive glutathione depletion, peroxidative mechanisms then cause an elevation of the cytosolic concentrations of ionized calcium; impairment of the ability of the mitochondria to sequester Ca2+ plays an important role in the elevation of the Ca2+ concentration. Finally, activation of Ca(2+)- and Mg(2+)-dependent endonucleases results in DNA damage and cell death.

Acetylcysteine↗
PubMed1991

Immunosuppressive acidic protein in malignant diseases. Clinical relevance?

The immunosuppressive acidic protein (IAP) has been described as a tumor associated marker in some solid tumors and hematologic diseases. To define the clinical relevance the authors determined the serum IAP levels in 194 patients with malignancies before initiation of therapy, 14 patients with idiopathic thrombocytopenic purpura (ITP), 28 patients with bacterial pneumonia, and 23 healthy volunteers. Immunosuppressive acidic protein was measured by radial immunodiffusion. The mean value of our controls was 405 +/- 48 micrograms/ml. This is consistent with published data. The mean values for patients with malignancies varied from 554 micrograms/ml to 698 micrograms/ml. These are only marginally higher than those observed for the controls. In contrast patients with bacterial pneumonia demonstrated significantly elevated values (1038 +/- 261 micrograms/ml). The authors conclude that IAP cannot be used as a diagnostic marker for the malignant diseases examined in this study.

Biomarkers, Tumor↗
PubMed1990

Three cases of acquired factor VIII: C inhibitors in non-hemophilic patients.

During the last ten years we observed three non-hemophilic patients with factor(F) VIII: C inhibitors (2 women aged 68 and 80 and a man aged 51). In all three cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII: C level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease could be excluded. Therapy with F VIII: C concentrate, cryoprecipitate, or fresh-frozen plasma did not produce the expected increase in F VIII: C. Measurement of F VIII: C inhibitor levels (Bethesda Units, BU) revealed values in the range between 9 and 64 BU. The two patients subjected to long-term therapy with a combination of prednisone (initially 2-3 mg/kg BW) and azathioprine (2-3 mg/kg BW) responded positively; the F VIII: C concentration increased. The third patient, treated only with a low dose of prednisone (30 mg/day), did not show any reaction at all. Since hereditary hemophilia A could be excluded, the inhibitors apparently were acquired. Malignant tumors did not appear. In conclusion, long-term therapy of an acquired F VIII: C inhibitor with a combination of prednisone and azathioprine may lead to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency.

Aged↗
PubMed1989

[Kaposi's sarcoma after kidney transplantation].

A Kaposi's sarcoma of the skin with nodular and follicular lesions but no visceral involvement developed in a 44-year-old man nine months after transplantation of an haplo-identical kidney (a relative as donor). He was on an immunosuppressive regimen of daily 10 mg methylprednisolone and 2.5 mg/kg cyclosporin A. No HIV antibodies were demonstrated. After reduction of the dosage to 4 mg methylprednisolone and 1 mg/kg cyclosporin A no further growth of the skin lesions was observed, while transplant function was maintained. The lesions regressed after radiation of two areas in the right lower leg with 48 Gy. Ten months later the sarcoma again progressed and required further radiotherapy, which arrested growth, while there was no change in transplant function.

Adult↗
PubMed1988

VBAMDex chemotherapy in advanced multiple myeloma.

In a phase II study 28 patients with advanced multiple myeloma were treated with a five drug regimen consisting of vincristine, BCNU, adriamycin, melphalan and dexamethasone. 11 out of 13 patients without prior chemotherapy showed significant remissions (greater than 25% tumor cells mass reduction), 7 of them had more than 75% TCM reduction. Out of 15 additional patients resistant to previous chemotherapy, 13 had significant remissions, including 9 patients with greater than 75% TCM reduction. No tumor progression was observed in either group of patients. The median follow-up of all patients was 12.75 months. 4 patients relapsed. Toxicity mainly related to the bone marrow was observed in 14 patients. This regimen might offer a promising alternative for the treatment of advanced multiple myeloma, but still has to be tested in a prospective randomized trial.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Retrospective radiographic study of skeletal changes after long-term etretinate therapy.

Radiographic skeletal examinations were performed in eight adult patients who had received the aromatic retinoid etretinate for various disorders of keratinization over periods ranging from 1 to 7 years. Age- and sex-matched controls were also examined. In all patients, alterations of ossification were found to a varying degree, including calcification of the anterior spinal ligament, vertebral hyperostoses at the anterosuperior and anteroinferior margins of the vertebral bodies, unilateral bridging of vertebral bodies, hyperostoses of the calcanei at the insertion of the plantar ligament and bone accretion at the anterolateral lips of the acetabula. All the bone changes were asymptomatic. Serum calcium, inorganic phosphate, alkaline phosphatase, calcitonin and parathormone were within normal physiological ranges. In general, the bone changes observed after long-term etretinate treatment closely resembled the effects of isotretinoin on the skeleton.

Adult↗
PubMed1986

Current results of a multicenter trial in multiple myeloma.

257 untreated myeloma patients (stage II and III) were studied in a multicenter trial. The patients were randomized and received MP or VCMP therapy. No differences in remission rate could be found in both therapy arms. After successful remission induction those patients without maintenance therapy relapsed significantly earlier than those patients receiving maintenance therapy. In pilot studies an etoposide therapy was found ineffective and a multidrug therapy (VBAMDex) could induce high remission rates in high risk and pretreated patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

The human adenoidal mast cell. Susceptibility to different secretagogues and secretion inhibitors.

Mast cells from adenoid tissues of man do not form a homogeneous population but differ in size and ultrastructure. They degranulate on stimulation with specific antigen, ionophore A 23187, Concanavalin A and, under certain conditions, antihuman IgE or acetylcholine. Compound 48/80, dextran, purified C3a or C5a are ineffective. Adenosine exerts either an enhancing or inhibiting effect on the stimulated histamine release, depending on the actual conditions of the mast cells. The study of a range of known mast cell degranulation inhibitors revealed important differences between human adenoidal mast cells and human basophils or animal mast cell systems. The efficacies of the drugs or drug combinations so far tested correspond well with the established therapeutic effects in man.

Adenoids↗
PubMed1983

Cutaneous histamine levels and histamine releasability from the skin in atopic dermatitis and hyper-IgE-syndrome.

We determined the histamine content in the skin of 22 adults with atopic dermatitis, one patient with hyper-IgE-syndrome, and 20 controls by the enzymatic double isotope assay. In addition, we performed a pilot study of histamine degradation in the skin. We tested, furthermore, the releasability of histamine from skin sections of patients with atopic dermatitis and healthy controls upon challenge with acetylcholine, anti-IgE, and compound 48/80. Histamine was also determined in 13 plasma specimens and was always less than 1 ng/ml. The mean +/- SEM histamine concentration in the skin was 196 +/- 30 ng/mg protein in controls and 262 +/- 68 ng/mg protein in atopic dermatitis (no statistically significant difference). One control and three patients with atopic dermatitis exhibited a slight, the hyper-IgE patient a marked, elevation of the skin histamine content. No gross differences in the degradation rate of histamine were observed between patients and controls. Acetylcholine and 48/80 induced the same histamine release in both groups; with anti-IgE, almost the double amount of histamine was released from the skin of atopic dermatitis patients as compared to controls. These findings suggest an enhanced releasability of histamine upon immunologic challenge in atopic dermatitis.

Adolescent↗