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F Oberling

Publications and source records attributed to F Oberling.

At least 73 records · Page 4Linked to original sources

Long term cultures of human monocytes in vitro. Impact of GM-CSF on survival and differentiation.

In vitro differentiation of human monocytes (Mo) provides large amounts of mature and functionally competent macrophages (M phi) which may be used as potentially powerful anticancer agents for adoptive immunotherapy. Granulocyte macrophage-colony stimulating factor (GM-CSF) was evaluated for its ability to influence long term cultures of Mo-derived M phi. Large quantities of Mo isolated by leukapheresis and elutriation were cultured in non-adherent cell culture bags or in plastic flasks with or without GM-CSF. At various stages of differentiation, GM-CSF treated M phi were recovered and assayed for survival, morphology, surface antigens, functional properties and proliferation in comparison with control M phi. In the present paper, we demonstrate that GM-CSF at a concentration of 50 U/ml (5 ng/ml) promotes better cell survival and the differentiation of Mo into M phi displaying certain morphological differences as compared to control M phi such as an increased expression of Max-1 antigen, CR3 and Fc gamma II receptors, higher phagocytic properties and increased capacities of cytotoxicity and TNF secretion when the cells are further activated by IFN-gamma. Furthermore, GM-CSF treated cells exhibit a low-grade proliferation although the nature of the proliferating cells has not been entirely elucidated. We conclude that the GM-CSF treated M phi would be particularly suitable for adoptive immunotherapy.

Antibodies, Monoclonal↗

Mosaic 46,XY/92,XXYY,del(5)(q13 q34) in an adult lymphoblastic leukemia.

Usually the chromosome anomalies encountered in ALL are modal number abnormalities (hyperdiploidy or hypodiploidy) and structural anomalies such as t(8;14), t(11;14), t(9;22), t(1;19) and del(6p). The 5q- syndrome is mainly associated with myelodysplastic syndromes and with ANLL (M1, M2, M3). We report the case of a patient presenting with a mosaic karyotype 46,XY/92,XXYY,del(5)(q13 q34) in the following proportion 1/3 normal mitoses and 2/3 tetraploid mitoses.

Aged↗

Synthesis of complement components C2 and C4 by human monocyte-derived macrophages during in vitro differentiation in serum-free culture conditions.

In order to analyze the kinetics of complement component synthesis by human monocytes/macrophages, we have developed a system of defined culture conditions in the absence of serum. Moreover, the use of the polymerase chain reaction (PCR) provides a high sensitivity for the detection of mRNAs and the study of the regulation of complement component synthesis by these cells. Human blood monocytes were collected and purified by cytapheresis and elutriation, and then cultured in nonadherent cell culture bags for up to 3 weeks. Cells were grown in Iscove's modified Dulbecco's medium supplemented with alpha-phosphatidylcholine, transferrin, insulin, glutamine and antibiotics. The phenotypic and functional properties of macrophages differentiated under these serum-free culture conditions have been previously analyzed [1]. Secretion of complement component was measured by a hemolytic assay. mRNA was prepared using guanidine isothiocyanate extraction followed by cesium gradient ultra-centrifugation. cDNA was obtained by reverse transcription, then amplified by PCR. Fresh monocytes did not display any secretion of C2 as measured by hemolytic assay. However, C2 secretion was detected on and after the 3rd day of serum-free cultured unstimulated monocytes. The rate of C2 production increased along with macrophage differentiation up to the 3rd week of culture. We were not able to detect any functional C4 secretion. In preliminary studies, C2 and C4 mRNAs were detected in macrophages and in unstimulated fresh monocytes. These preliminary studies show that the serum-free culture conditions we have developed allow very satisfactory survival and differentiation of human monocytes, and provide optimal conditions for the study of their secretory activity.

Cell Differentiation↗

Cunninghamella bertholletiae: an uncommon agent of opportunistic fungal infection. Case report and review.

Cunninghamella bertholletiae is a fungus of the Zygomycetes class, Mucorales order. Only very few cases of disseminated infection have been reported. We observed a new case in a 19 years old man with severe aplastic anemia, due to pulmonary primoinfection and hematologic dissemination. This aplastic anemia failed to respond first to an antithymocyte globulin and steroid treatment and then to cyclosporine A. Deferoxamine was infused weekly to prevent iron overload. During a second antithymocyte globulin and steroid treatment, the patient developed bilateral pneumonia. Culture of the broncho-alveolar washing fluid established the diagnosis by isolation of C. bertholletiae. Despite amphotericin B and 5-fluorocytosine intravenous therapy, the patient died of disseminated infection six days after diagnosis, which was confirmed by necropsy. Underlying conditions, diagnosis and treatment are discussed, together with a review of the literature.

Adult↗

High dose melphalan and ABMT with or without abdominal radiotherapy as consolidation treatment for ovarian carcinoma in complete remission or with microscopic residual disease.

We initiated in February 1982 a pilot study of high dose melphalan (HDM) and ABMT as consolidation treatment for ovarian carcinoma. Eleven patients entered into this study; 6 patients received HDM and ABMT (group 1), 5 patients received HDM in combination with flash abdominal radiotherapy followed by ABMT (group 2). Two of 6 group 1 patients and 3 of 5 group 2 patients are still alive with NED more than 3 years after ABMT (58+, 72+, 37+, 39+, 43+) and are hopefully cured. Main toxicity was haematological, we have not observed any death related to therapy. HDM and ABMT compared favorably with other consolidation treatments (abdominopelvic radiotherapy or IP chemotherapy) and merits a larger evaluation.

Abdominal Neoplasms↗

[Embolization of the foramen ovale in metastatic course of abdominal liposarcoma].

The authors report a case of embolization of the foramen ovale by a liposarcoma metastasis in a young woman of 28 years of age. Cardiac impact due to the progress of this rare tumor type remains unusual. The various clinical situations resulting from secondary cardiac locations are recalled. The diagnostic role of ultrasonography and the information which can be provided by nuclear magnetic resonance imaging in this context are also recalled.

Abdominal Neoplasms↗

[Breast osteosarcoma. Review of the literature and presentation of two cases].

Two cases of primary osteosarcoma of the breast are reported. The Authors emphasize the overwhelming role of chimiotherapy in the treatment of this rare condition, not dissimilarly from recent advances in the management of osseous osteosarcoma. There was no evidence of recurrent or metastatic disease at respectively 38 and 49 months of follow-up. A review of the literature, including 150 published cases, reveals that therapeutic policies quite diverge yet.

Aged↗

[Intraperitoneal treatment of tumors of the ovary].

Intra-peritoneal chemotherapy and immunotherapy are recent techniques for the treatment of tumours in the ovary. Chemotherapy is used more for the intra-peritoneal route. It is valuable because of the natural history of the disease and because of the pharmacological properties of many antimitotic drugs. Indwelling catheters have made this method easier and more acceptable to the patients. The drugs most used are cistplatinum and carboplatinum but mitoxantrone seems to be a very promising drug. The use of immunomodulators is just starting. Intra-peritoneal treatment should be at present reserved for small masses (less than 2 cm in diameter) whether used as a follow-up treatment or as a primary treatment in association with general chemotherapy.

Animals↗

Surface passivation by human albumin of plasmapheresis circuits reduces platelet accumulation and thrombus formation. Experimental and clinical studies.

The contact of flowing blood with an artificial surface leads to adsorption of plasma proteins, followed by platelet adhesion and aggregation and thrombus formation. This phenomenon is enhanced by turbulent flow at joints, bifurcations, and constrictions. In therapeutic plasmapheresis using an IBM blood cell separator, blockage of the extracorporeal circulation system by platelet-fibrin thrombi imposed a halt in treatment for manual clearance of the circuit for 66 in 149 cases (44%). Thus it was decided to passivate the surface of the extracorporeal circuit by filling the tubing with 4% human serum albumin 15-20 min before the treatment session and then displacing the albumin solution with the patient's blood without creating an air-liquid interface. After introduction of this technique, a blockage was observed for only 11 in 239 cases (5%). In vitro measurements of platelet accumulation on the internal surface of the circulation system were carried out using washed human platelets labeled with 111In-oxine in the presence of a 40% hematocrit. Preadsorption of the surface with albumin reduced platelet deposition to 4-5% that observed for an equivalent pretreatment with physiological saline.

Adsorption↗

Establishment and characterization of somatic hybrids between human differentiated macrophages and mouse myeloma NS1 cells.

Human macrophages obtained from circulating monocytes matured in vitro by culture for seven days in hydrophobic flexible teflon bags were successfully fused with murine myeloma NS1 cells. Six of 20 clones, selected for their adherence properties, were further studied. All possessed human chromosomes (mean number ranging from 4 to 14 depending on the clones studied), exhibited non-specific esterases (but no peroxidase activity) and expressed CD14 antigen and C3 receptors (but no MAX-1 antigen). Moreover, the hybridomas retained phagocytic activity and high interferon plus lipopolysaccharide-activable cytolytic activity against tumor cells.

Animals↗

The protection of hemopoietic mice progenitors by WR-2721 during photodynamic therapy.

Photodynamic therapy is a new concept for in vitro evaluation of bone marrow clearance in leukemia. This treatment eliminates 99.9999% of leukemic cells, but under the same conditions over 50% of normal bone marrow cells are damaged. WR-2721, a thiol compound, is reported to except a protective effect for bone marrow against radiation therapy. This study analyzed the protective effect of WR-2721 during photodynamic therapy with hematoporphyrin derivative. Mice hemopoietic cells were exposed to laser light after sensitization by hematoporphyrin, with or without WR-2721 at 3 dose levels (250, 500, 750 mg/kg). The efficacy of protection was evaluated by GM-CFU assay in collagen gel medium. Results showed significant protection at 25 and 50 j/cm2 (p less than 0.05), but at 75 j/cm2 irradiation only the 750 mg/kg dosage remained protective. The protective factor of WR-2721 is 1.65 (95% confidence interval: 1.38-1.99) WR-2721 is protective against photodynamic lesions but this protection is diminished by increased irradiation energy. The best results are obtained with a dose of 750 mg/kg though this appears to be toxic. Further studies are needed to evaluate the action of WR-2721 on leukemic cells before the use of WR-2721 in bone marrow clearance.

Amifostine↗

Cisplatin-induced anemia: a potential interference with iron metabolism at erythroid progenitors level.

To elucidate the potential mechanisms of anemia induced by cisplatin (CDDP) we have evaluated hemolysis, dyserythropoiesis, ferrokinetics and cytotoxicity on erythroid progenitors in 12 patients treated by a CDDP-containing combination chemotherapy and in 6 patients treated by a similar combination but without CDDP. Eight patients, from the CDDP treated group, experienced a pronounced anemia. None had signs of hemolysis. Ferrokinetic study showed a very deep and protracted decrease of 59Fe incorporation during the chemotherapy cycle and the following 2 weeks. These results, along with a normal medullary erythroblastic cellularity, suggest that CDDP induces a deep but transient erythropoiesis alteration leading to anemia in some cases.

Adult↗

[High doses of alkylating agents and bone marrow autograft in ovarian cancer with poor prognosis: a retrospective analysis of 40 patients treated in France].

Reviewed in this study are 40 patients treated by high-doses of alkylating agents followed by autologous marrow rescue for ovarian cancers. All patients received this therapy after extensive surgery and a median of 6 cycles of CDDP containing regimens (CAP or CHAP). All patients, except 4, who showed evidence of progression, had a second surgical exploration before the high dose chemotherapy. Conditioning regimens consisted of: melphalan at a dosage greater than 140 mg/m2 for all patients; in addition, 2 received Endoxan 120 mg/kg and 1 busulfan 16 mg/kg. Autologous marrow rescue was infused 24 h after the conditioning regimen. Severe, but reversible aplasia and mucositis were the most common toxicities. Three patients died from this procedure, 2 from infection and 1 from secondary leukemia. Twelve out of 15 patients evaluated responded (80%) showing evidence of activity in patients who did not respond to first line chemotherapy. Duration of response was short, especially for patients treated for progressive disease rather than in partial or complete response at the time of high doses chemotherapy. With a median follow up of 23 months (range 8.54) 19 patients survived (15 with non-evolutive disease) leading to a projected survival rate of 39% between 27 months and 5 years. These results are encouraging for poor risk patients who failed to respond to initial chemotherapy. For patients who have small or no residual disease after initial therapy, the place of such intensification should be confirmed prospectively in a larger cohort of patients.

Adenocarcinoma, Mucinous↗

Disseminated Trichosporon capitatum infection in a patient with acute leukemia undergoing bone marrow transplantation.

A case of disseminated infection with Trichosporon capitatum is reported in a 23-year-old patient with acute myeloid leukemia undergoing HLA-mismatched bone marrow transplantation. He was receiving immunosuppressive therapy with cyclosporine and corticosteroids for acute graft-versus-host disease and he was severely neutropenic. While being treated with fluconazole for 28 days for an oropharyngeal candidiasis the patient developed a T. capitatum septicemia. He died despite receiving amphotericin B therapy. Autopsy revealed widespread infection with T. capitatum. The portal of entry was probably the digestive tract in this patient as T. capitatum had been first isolated in the stools.

Adult↗

High dose melphalan and autologous marrow rescue in advanced epithelial ovarian carcinomas: a retrospective analysis of 35 patients treated in France.

We retrospectively evaluated the feasibility and antitumour efficacy of high dose melphalan (HDM) followed by autologous marrow rescue in 35 patients with common epithelial ovarian cancers. All patients initially had advanced disease (FIGO III-IV) and received HDM after extensive surgery and a median of 6 cycles of cis-DDP containing regimens CAP or CHAP. All, except three patients who showed evidence of progression, had a second surgical exploration before high dose chemotherapy. Melphalan was given at a dosage greater than or equal to 140 mg/m2 followed 24 h later by autologous marrow rescue. Severe but reversible aplasia and mucositis were the most common toxicities: three patients died from the procedure, two from infection and one from secondary leukaemia. HDM was effective in 75% of evaluable patients; this was evidence of activity in patients who failed to respond to first line chemotherapy. The duration of response was short, particularly for patients treated with progressive disease at the time of high dose chemotherapy rather than in partial or complete remission. With a median follow-up of 23 months (range 8-54) after high dose chemotherapy, 19 patients are alive (15 with non-progressive disease) with a projected survival of 47% between 2 and 5 years.

Adult↗