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Biomedical subjects

I Philip

Publications and source records attributed to I Philip.

At least 91 records · Page 5Linked to original sources
PubMed1989

Analysis of parameters for maximal in vitro proliferation and activation of lymphokine-activated killer cells (LAK).

In 15 patients (11 adults, 4 children) who received IL-2 and LAK cell therapy, we analyzed the different culture conditions which could either improve LAK cell activation and proliferation or which could simplify the procedure. Each parameter was assayed on a large scale and compared to standard culture conditions. Indomethacin had no effects, either positive or negative, on proliferation and activation of the cells. Culturing with 10% AB serum increased proliferation but did not modify total lytic activity compared to 2% AB serum. When cells were cultured in a medium with 2% autologous plasma obtained before any treatment, their proliferation was similar to that obtained in medium supplemented with 2% AB serum but the LAK activity was significantly higher. Autologous plasma obtained at day 8 of treatment (48 h after the first cycle of IL-2 and the day of the first cytapheresis) gave similar results to 2% AB serum. None of the 12 patients showed negative effects suggesting the presence of suppressive factors in the sera. Culturing with autologous plasma in clinical trials will lead to a 25% decrease in the total cost of culture and suppress the risk of viral contamination. Excess of granulocytes in the culture (greater than 30%), if the total nuclear cell concentration did not exceed 3 . 10(6) per ml, induced a better proliferation of mononuclear cells without modification of the activation. These results could be due to the liberation of factors by polynuclear cells, or to the loss during elimination of the granulocytes by the Ficoll separation of cells with similar density supporting LAK activity.

Adult↗
PubMed1989

Systemic interleukin-2 therapy in children with progressive neuroblastoma after high dose chemotherapy and bone marrow transplantation.

Two children with active metastatic neuroblastoma after high dose chemotherapy and bone marrow transplantation (BMT) received a high dose continuous infusion of interleukin-2 (IL2) 120 days after an autologous BMT for patient 1 and 90 days after an allogeneic non T cell-depleted BMT for patient 2. Usual side effects of IL2 therapy were observed without life-threatening complications or any major hematological toxicity. The reactivation of graft-versus-host disease during IL2 infusion in patient 2 was the major BM-related complication but it improved with IL2 interruption and corticosteroids. IL2 induced a complete remission (9+ months) in patient 1 with the disappearance of bone metastases and local tumor but patient 2 progressed after cessation of therapy. Patient 1 presented with a large excess of circulating NK cells in the period after autologous BMT and IL2 induced a preferential outgrowth of this lymphocyte subset.

Adrenal Cortex Hormones↗
PubMed1988

Cytogenetic evaluation of bone marrow involvement in Burkitt's lymphoma.

Twenty-six bone marrow samples from 21 patients with Burkitt's lymphoma were examined cytogenetically after short-term culture. Clonal chromosomal changes were detected in one of 18 samples from morphologically normal marrows, and in three out of six samples with verified tumor invasion. Three patients had the translocation (8;14)(q24;q32) and one had t(2;8)(p12;q24). Two samples with suspect tumor involvement (less than 5% putative tumor cells) showed no clonal abnormalities. In two samples without morphologic bone marrow infiltration and with only normal metaphases in short-term cultures, clones with t(8;14)(q24;q32) were revealed after a longer time (3-12 weeks) spent in vitro.

Adolescent↗
PubMed1988

Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12).

Since our initial reports on chromosomal studies in eight Ewing's sarcomas (ES), we have carried out similar investigations on 23 additional ES specimens following short-term culture of tumor cells (16 cases), and established in vitro cell lines (three cases) and on xenografted tumors in nude mice (four cases). We demonstrated the presence of the reciprocal t(11;22)(q24;q12) in every case except one that exhibited a complex t(11;22;14)(q24;q12;q11). On the basis of results from these additional 23 cases, we confirm the consistency of the t(11;22)(q24;q12) in ES. Moreover, we reviewed 54 ES cases reported by other investigators; when added to our 31 cases, this brings the total number to 85 unrelated cases of ES available for an evaluation of the frequency of involvement of bands 11q24 and 22q12 in translocations in ES. The standard t(11;22)(q24;q12) proved to be a remarkably consistent event, present in 83% of the cases. Five percent of the cases exhibited complex translocations involving a third chromosome in addition to chromosomes #11 and #22. In 4% of the cases variant translocations involved 22q12 but with a chromosome(s) other than #11. The breakpoint on chromosome 22q12 appears to be the most consistently observed event in 92% of the cases, whereas, the breakpoint at chromosome 11q24 was observed in 88% of the cases.

Adolescent↗
PubMed1988

[Current results of intensive chemotherapy as salvage with bone marrow graft in highly malignant T lymphomas. Apropos of 10 cases].

Eleven autologous bone marrow transplantations (ABMT) were performed in 10 patients with T lymphoblastic lymphoma. All patients were grafted because of a very bad prognosis: 2 cases of progressive disease (1 primary failure, 1 resistant relapse): 0/2 alive, 2 late complete remissions: 1/2 alive, 7 sensitive relapses (2/7 alive). Finally, 3 out of 10 patients are survived. This salvage therapy for a failure of a front line strategy with 78% disease-free survival without ABMT seems of interest. ABMT is still indicated as salvage therapy for 20% of these patients.

Adolescent↗
PubMed1988

[Intensive chemotherapy and bone marrow grafting during the consolidation phase of stage IV neuroblastoma].

Sixty-five patients more than one year of age at diagnosis with stage IV neuroblastoma were prospectively treated since january 1983. Seventeen per cent were not consolidated with massive therapy and ABMT (progression: 3 cases; died at induction: 4 cases; died at surgery: 1 case; parental refusal: 2 cases) and all died. Among 49 evaluable cases, 31 were grafted in PR and 18 in CR or VGPR. Actuarial progression free survival at 35 months is 33% for the grafted group and 24% for the whole group. These results are better than previous experience of this group (8% at 30 months).

Actuarial Analysis↗
PubMed1988

[Value of immunological analysis for the detection of residual neuroblasts in the bone marrow].

Immunological analysis is complementary of morphological analyses in the detection of neuroblastoma BM metastases. It attests the neuroblastic nature of rare pseudolymphocytic isolated cells. The combination of immunocytochemical technique (alkaline phosphate) and double-immunofluorescence technique allows the detection of as few as 10(-5) residual neuroblastoma cells. At the time of bone marrow harvest, it permits a precise evaluation of malignant cells in the graft.

Bone Marrow↗
PubMed1988

[Cell cultures in Burkitt's lymphoma. Detection of residual disease and application to autologous graft purging].

We describe a new liquid cell culture system for propagating Burkitt lymphoma (BL) cells contaminating the bone marrow (BM). The percentage of BL cells at day 10 of culture is correlated with the number of BL cells in the initial sample, which permits the detection of as few as one BL cell in 10(6) normal cells. We currently use such an assay to detect minimal BM involvement in our patient's follow up. This has allowed to define in which clinical situations the BM collected for autologous transplantation (though cytologically normal) had to be "purged". With the help of this modified liquid system it was possible to quantify the efficacy of various purging procedures on different models; an experimental model of allogenic irradiated BM contaminated with BL cell lines was used. Pre-clinical assays were also conducted on our patients' BM contaminated with their own tumour cells, or on invaded BM collected for autologous transplantation and for which the system had evidenced the efficacy of the purging procedure.

Bone Marrow Cells↗
PubMed1987

Use of a liquid cell culture assay to quantify the elimination of Burkitt lymphoma cells from the bone marrow.

A new liquid cell culture assay for propagating Burkitt lymphoma (BL) cells in the presence of excess allogeneic irradiated bone marrow (BM) has been standardized. The Burkitt cell lines used in this assay were newly established from the tumours of our patients and were either EBV(+) or EBV(-). The phenotypic characteristics of lines were similar to those of the original malignant tumours. With the help of this liquid assay it was possible to evaluate the efficacy of in vitro procedures designed to completely eliminate malignant cells from harvested BM prior to autologous transplantation (i.e., immunomagnetic depletion or antibody-complement-mediated cytolysis). With six out of the seven cell lines tested, the assay permitted the detection of as few as one BL cell in 4 X 10(6) normal BM cells and the measurement of up to 5 log BL cell elimination from 1% contaminated samples.

Antibodies, Monoclonal↗
PubMed1987

Neuroectoderm-associated antigens on Ewing's sarcoma cell lines.

The histogenesis of Ewing's sarcoma, the second most frequent primary bone tumor in humans, remains controversial. Ten Ewing cell lines were analyzed by immunological methods. Surface antigens recognized on Ewing cells were found to be related to the neuroectoderm lineage. They included ganglioside GD2, a marker of neuroectodermal tissues and tumors, and an acidic glycolipid detected by monoclonal antibody HNK-1 in the nervous system. The P61 rat monoclonal antibody that reacts with a peptide moiety of neural cell adhesion molecule (N-CAM) and a rabbit antiserum raised to purified mouse N-CAM also stained Ewing cells. Flow cytometry analysis performed using these reagents allowed the definition of four distinct Ewing phenotypes: all reagents equally stained group 1 lines; group 2 lines were strongly reactive with anti-N-CAM reagents, by contrast with a fainter staining with HNK-1 and anti-GD2 antibodies; all reagents but P61 were strongly reactive with group 3 lines; in group 4, Ewing lines were stained by P61 but only poorly by the anti-N-CAM antiserum. Several antibodies to melanoma and neuroblastoma associated antigens including two monoclonal antibodies to the nerve growth factor receptor were also found to react with Ewing cells. By contrast, all antibodies detecting antigens specifically expressed in hematopoietic cell lineages were totally unreactive. HLA class II antigens were never detected while the level of expression of class I antigens varied to a large extent. Ewing cells are characterized by a specific t(11;22)(q23-24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor. Thus, Ewing's sarcoma cells share antigenic and karyotypic features with derivatives of the neuroectoderm possibly indicating a related histogenesis.

Antigens, Neoplasm↗
PubMed1987

High-dose melphalan, vincristine, and total-body irradiation with autologous bone marrow transplantation in children with relapsed neuroblastoma: a phase II study.

Seven children with neuroblastoma who had relapsed on or after conventional therapy (3 originally stage IV, 3 stage III, 1 stage II) were entered on a study of "massive therapy" with purged autologous bone marrow rescue. In 5 patients attempts were made to reinduce remission with alternative chemotherapy, and a partial or complete response was achieved in 3. The massive therapy regimen comprised melphalan, vincristine, and total-body irradiation. Of 6 patients with measurable disease, all showed objective response to high-dose therapy (5 partial, 1 complete remission), but the median duration of remission was only 5 months (range 1/2 to 10). One patient remains disease-free at 18 months post graft. This patient was the only one treated in second complete remission. These data confirm the high response rate achieved by high-dose melphalan, total-body irradiation regimens, but it appears unlikely that a single high-dose chemoradiotherapy procedure will cure patients after relapse, particularly if they are unresponsive to conventional salvage regimens. Such protocols may, however, have a role as consolidation in first remission. The use of double-autograft procedures is an alternative that warrants further investigation in patients with relapsed neuroblastoma.

Adolescent↗
PubMed1987

Experimental evaluation of an immunomagnetic bone marrow purging procedure using the Burkitt lymphoma model.

In order to test the numerous variable biological parameters which may contribute to the efficiency of the immunomagnetic depletion method, experiments have been carried out with different Burkitt lymphoma cell lines. The Hoechst dye method, a sensitive assay able to detect 3 log elimination, and a liquid culture assay suitable for identifying an elimination greater than 4 logs, were used to measure malignant cell elimination. These assays showed that the separation of bone marrow mononuclear cells on Ficoll-hypaque, the use of beads in excess, and a double treatment of the samples are needed to obtain optimal depletion of malignant cells. Under these conditions, the immunomagnetic procedure is capable of depleting 1% tumour cell infiltration at the lower limit of detection of a very sensitive culture assay (i.e. greater than 4 log elimination).

Bone Marrow Cells↗
PubMed1987

[Detection of residual cells contaminating the bone marrow in neuroblastoma. Apropos of 80 bone marrow evaluations].

Eighty bone marrow studies (each including 4 aspirates and 4 trephine biopsies) were performed in 37 children with stage IV neuroblastoma to assess the most accurate means for detection of invasion by neuroblastoma cells. Among 38 abnormal results, only trephine biopsy(ies) were found positive in 24 cases (63%), only aspirate(s) in 5 cases (13%), and both in 9 cases (24%). In 37% of abnormal results, only 1 of the 8 tests performed was found positive. No benefit was obtained from either associated touch imprints of iliac biopsies (67 investigations), or exploration of extra-iliac sites (66 sternums, 53 tibias). Two monoclonal antibodies, claimed to be specific for detection of neuroblastoma cells in bone marrow, were used in 56 investigations; they could detect minimal residual disease in some cases, but they were unreliable when no staining was obtained if initial phenotype of neuroblastoma had not been assessed, or when few isolated cells were observed. Prospective studies using immunocytology and immunohistology are thus warranted.

Antibodies, Monoclonal↗
PubMed1986

EBV-negative and -positive Burkitt cell lines variably express receptors for B-cell activation and differentiation.

The expression of receptors for proliferation and differentiation factors was analyzed by indirect immunofluorescence on 29 Burkitt lymphoma (BL) cell lines previously classified into 3 groups on the basis of their reactivity with 8 monoclonal antibodies (MAbs), including anti-CALLA, BL13 and TU1. BL13 and HB5 antibodies recognize different epitopes of the EBV/CR2 receptors. The determinant recognized by BL13 has been previously shown to be expressed only on cell lines of the first two groups, supposed to derive from the germinal center and to be negative on a third group of lines of putative BM origin and established from sporadic cases of BL. In contrast, and as expected from its reactivity on normal B cells in the BM or in the lymph nodes, HB5 antibody reacts with all BL lines except one. The receptor for transferrin is expressed on the 29 lines. Two new MAbs, Bac-1 and B1H5, could recognize respectively receptors for BCGF1 and BCGF2. Bac-1 reacts with 15 of 17 BL lines belonging to the first two groups and 7 of 12 BL lines of the third group; 14 of 15 EBV + lines express Bac-1. No BL line expresses B1H5. The IL2 receptor is weakly expressed on 5 EBV + cell lines and one EBV (-) line. All delta are BCGF1-positive. The almost constant expression of BCGF1 receptor on EBV + cell lines is the only strict relation between the expression of receptors for growth factors and their characteristics (i.e. EBV association, translocation, ethnic origin and clinical presentation). The maturation stage or the origin of BL cell lines in relation to the expression of growth factor receptors and the functional significance of these receptors will be discussed.

Antigens, Neoplasm↗