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Biomedical subjects

C Jasmin

Publications and source records attributed to C Jasmin.

At least 181 records · Page 10Linked to original sources

[Aclacinomycin-A in acute leukaemias and leukaemic non-Hodgkin lymphomas (author's transl)].

Aclacinomycine-A (ACM), a new anthracycline derivative, was administered intravenously to 50 patients in doses of 10-30 mg/m2/day for periods of 6 to 30 days. Among the 45 patients who could be assessed, 17 were suffering from acute myeloid leukaemia, 19 from acute lymphoid leukaemia and 9 from non-hodgkin lymphoma. The results confirmed those first published by the authors in 1978 and led them to propose new measures aimed at reducing the toxicity of ACM. Depending on the dosage, complete or partial (more than 50%) remissions were obtained in patients with acute myeloid leukaemia. In the 19 patients with acute lymphoid leukaemia, complete remission was observed in 2 and partial remission in 2. Among the 9 patients with non-hodgkin lymphoma, there was 3 complete and 1 partial remissions. ACM did not produce alopecia and, as predicted by the authors' experimental study on hamsters, did not have major cardiac toxicity. The gastrointestinal toxicity, which had forced a reduction of the total dose in the first trial, proved moderate, even with normal dosage.

Aclarubicin↗

A strategic adjuvant therapy of osteosarcoma.

Twenty-one patients with osteogenic sarcoma of the limbs were treated with an early combination of 1,750 rad whole lung irradiation, alternate cyclic chemotherapy with high-dose methotrexate, vincristine, mitomycin C, adriamycin, immidazol carboxamide (DTIC), cyclophosphamide, and intercalated immuno-BCG. The primary lesion was treated either by amputation or an 8,000 rad irradiation. Patients have been followed up for 6-29 months. Three patients relapsed, respectively, after 8, 11, and 22 months. All three patients had a long delay in completing the first part of treatment (first cycles A and B and lung irradiation). The 18 other patients are disease-free. Local relapses have not been observed. The toxicity of this protocol appears to be acceptable, but a longer follow-up is necessary to more precisely discern the efficacy and tolerance of the lung to this combined treatment.

Adolescent↗

Cellular proliferation kinetics of the murine sarcoma induced by the Moloney sarcoma virus.

Cell proliferation kinetics of the sarcoma induced by Moloney virus was studied in newborn Swiss OF1 mice. After in vivo injection of tritiated thymidine, followed by autoradiography, it was shown that the majority of cells were actively proliferating (labelling index; 31%, growth fraction 78%). The mean cell cycle was 16 hr and cell loss was relatively low (cell loss factor 48%). The study of tumour specific activity with time after a single [in vivo] injection of [3H]dR or [125I]UdR did not demonstrate the same degree of cell loss as that calculated by autoradiography. This result is consistent with a massive reutilization of radioactivity released by normal tissues.

Animals↗

[Treatment of leukemias and lymphomas with interferons: I. Trial of myeloma therapy with human beta-interferon].

Eighteen patients with malignant gammapathies (16 with myeloma and 2 with Waldenström's disease) for a short time because in a phase II-I trial were treated with human (IF beta) given i. v. 6 X 10(6) units weekly (7 patients) or 3 X 10(6) units twice weekly (11 patients) during at least 3 months if tolerated. Treatment was discontinued because of side-effects in three patients. Reduction of the M component of at least 25% from the initial value was obtained in 3 patients. In one case, was also observed in disappearance of the urinary Bence-Jones protein, in 4 cases a significant reduction of bone marrow infiltration by plasma cells and, in 5 cases, major alleviation or disappearance of bone pain. Length of treatment seems an important factor for activity. Immune monitoring with currently available tests, mainly NK cell activity, yielded no correlation with therapeutic effect in these patients. This very preliminary study demonstrates the effect of fibroblastic interferon in myeloma, but further studies are mandatory to determine the population of patients likely to benefit from treatment, the best modalities, possible special indication, dose schedule and duration of treatment. Interferon, however, already appears in this population of patients as giving results similar to those of single agent chemotherapy. As it is not myelosuppressive, it could be indicated in that frequent situation of advanced myeloma with bone marrow failure contra-indicating combination chemotherapy.

Clinical Trials as Topic↗

A study of added GM-CSF independent granulocyte and macrophage precursors in mouse spleen infected with myeloproliferative sarcoma virus (MPSV).

A subpopulation of granulocyte and macrophage precursors (GM-CFUc) differentiating in the agar colony technique of Bradley and Metcalf into mature granulocytes and macrophages, without the addition of granulocyte and macrophage colony stimulating factor (GM-CSF), can be detected in MPSV infected mice. These precursors were detected 5 days after virus infection, reaching a maximal concentration of 1/10,000 spleen or bone marrow cells, 25 days after viral infection. The number of the added GM-CSF independent GM-CFUc was linearly correlated with the number of seeded MPSV hematopoietic cells. No GM-CSF producing cells could be detected in the MPSV spleen using normal bone marrow GM-CFUc as responder cells. Study of the GM-CSF sensitivity of the GM precursors has demonstrated the existence of two GM-CFUc populations in the MPSV spleen: a) a GM-CSF dependent population with a GM-CSF sensitivity similar to that of normal GM-CFUc b) a GM-CFUc population which differentiated in the absence of detectable amount of GM-CSF and of which differentiation was not affected by the addition of progressive amounts of GM-CSF. A possible model explaining these results is proposed.

Animals↗

[Treatment of leukemias and lymphomas with interferons: III. Trial treatment of meningeal localizations of acute leukemia and non-Hodgkin's lymphomas with beta interferon administered by the intrathecal route].

Six patients with pure meningeal relapse of acute lymphoblastic leukemia (ALL) (5 patients) or leukemic lymphosarcoma (LS) (non Hodgkin's lymphoma) (NHL) (1 patient) were treated with intrathecal (I.T.) human fibroblastic interferon (IF beta), one vial (1.3 million units) every other day or every day up to remission or failure. Tolerance was excellent in all six patients with no local or general side effects. 5 patients had no improvement of their meningeal blast infiltrations after 5 to 8 injections and were given IT chemotherapy. The sixth patient achieved a complete remission (CR) after 11 injections, and was maintained in CR for eleven months under systemic and IT chemotherapy. IF cannot be proposed as standard treatment for meningeal leukemia, but we may be able to select a population of patients in which it could be indicated. Its combination with methotrexate and arabinoside cytosine, the two agents used IT which are S-dependent, has to be studied for a possible potentiation. Moreover, its good tolerance would permit its use in severe meningeal viral diseases.

Acute Disease↗

In vivo effect of a new mineral condensed ion (HPA 39) on murine Friend leukaemia.

HPA 39 is a tungsto-antimoniate compound, closely related to the mineral consensed ion HPA 23, from which it differs only by the presence of a potassium instead of a sodium ion inside the central cage. A single parenteral injection of HPA 39 on the same day as virus inoculation decreased the splenomegaly induced by Friend virus in DBA/2 mice and protected 90% of the infected animals against leukaemia. It also lowered the virus content in spleen extracts compared to untreated animals. The efficiency of treatment with HPA 39 on leukaemic mice at a late stage of the disease suggested that the compound may act at the cellular level as well as by inducing virus growth inhibition. HPA 39 also induced an early decrease of peripheral blood reticulocytes, and of the most differentiated erythroblasts in the bone marrow 1 day after injection of the compound. Mineral condensed ions therefore appear to have multiple biological effects both in vitro and in vivo.

Animals↗

Inheritance of susceptibility to the myeloproliferative sarcoma virus: effect of the Fv-2 locus and evidence for a myeloproliferative sarcoma virus resistance locus.

Myeloproliferative sarcoma virus (MPSV) causes a generalized stem cell leukemia with erythroid and myeloid hyperplasia in adult mice. MPSV also transforms fibroblasts. Mice congenic for the Fv-2 locus showed marked differences in susceptibility to MPSV according to the Fv-2 genotype. MPSV was injected into C57BL/6 Fvs and C57BL/6 Fv-2r mice congenic except for the Fv-2 locus. C57BL/6 mice with the Fvs genotype were much more susceptible to MPSV than were those with the Fvr genotype. Both DDD Fv-2r mice congenic with DDD Fv-2s mice except for the Fv-2 locus and DDD Fv-2s mice, however, were sensitive to spleen focus formation by MPSV. These data indicate that at least one additional resistance locus to MPSV is present in C57BL/6 mice but not in DDD mice. Both the Fv-2 locus and the putative MSPV resistance locus (loci) Mpsvr appear to be epistatic to either of the sensitivity loci. Fibroblast focus formation by MPSV was obtained well in C57BL/6 Fv-2r and C57BL/6 Fvs fibroblasts, indicating that the genes for MPSV resistance (Fv-2r and Mpsvr) were not operating in fibroblast cells. A model is proposed which may account for the differences in response of genetically different mice to MPSV and Friend spleen focus-forming virus.

Alleles↗

Analysis of the myeloproliferative sarcoma virus genome: limited changes in the prototype lead to altered target cell specificity.

The myeloproliferative sarcoma virus (MPSV) derived from Moloney sarcoma virus (MSV-Mol) is a unique sarcoma virus which causes expansion of the hematopoietic stem cell compartment as well as the erythroid and myeloid cell lineages. MPSV also induces spleen focus formation in adult mice as do Friend and Rauscher viruses. Analysis of the MPSV genome on methyl mercury gels showed that the genome size is 7.0 kilobases, which is larger than the defective genome of any known MSV-Mol isolate. Hybridization analysis with specific cDNA probes showed that MPSV is a modified sarcoma virus with no sequences in the unique region of the defective sarcoma genome related to unique Friend virus sequences. The only viral sequences in the defective genome other than helper virus-related sequences are derived from the Moloney sarcoma virus genome with no new cellular sequences added. There was no evidence for induction of xenotropic virus sequences in MPSV-infected spleens of DBA/2J mice, indicating that spleen focus formation can be obtained by different mechanisms.

Animals↗

Effects of myeloproliferative sarcoma virus on the pluripotential stem cell and granulocyte precursor cell populations of DBA/2 mice.

The hematopoietic stem cell (CFU-S) and granulocyte precursor cell (CFU-C) populations have been assayed in the spleen, blood, and bone marrow of DBA/2 mice at various times after infection with the myeloproliferative sarcoma virus (MPSV). Beginning between 7 and 19 days after virus infection, the number of CFU-S showed a steady, parallel increase in the blood and spleen, reaching a maximum at both sites by days 25-30. At the maximum, in the spleen the concentration of CFU-S was 10 times greater than that in the blood, and the total number of CFU-S was over 100 times greater than that of normal animals. During the same period, in the bone marrow the number of CFU-S decreased to one-half of normal. Nevertheless, the CFU-S from MPSV-infected animals differentiated normally in the spleens of irradiated, normal recipient mice (except for some hyperplasia of the erythroid component of spleen colonies). The CFU-C content of the bone marrow, spleen, and blood paralleled the CFU-S content of these organs: The CFU-S and CFU-C populations changed almost synchronously after MPSV infection. In the terminal stage of the MPSV-induced disease, a variable proportion of the CFU-C population acquired the ability to differentiate in the absence of added colony-stimulating factor.

Animals↗

Cellular proliferation in the spleen of DBA/2 mice infected with a myeloproliferative sarcoma virus(MPSV).

Cellular proliferation kinetics were investigated in the spleens of DBA/2 mice infected with a myeloproliferative sarcoma virus (MPSV) at three distinct phases of spleen growth: the rapid-growth phase, the slow-growth phase and the regression phase. Using injection of tritiated thymidine in vivo and autoradiographic techniques, we showed that most blast cells proliferate rapidly (cell cycle is equal to 10 h) even during the slow-growth phase. Very massive and rapid cell loss was found during the rapid-growth phase (cell loss factor phi = 80%). By comparing the decrease in specific splenic activity after in vivo injection of 125IUdR and 3HTdR, we were able to show a large reutilization of tritiated thymidine (R = 57%), visible less than 7 h after injection of isotopic DNA precursors. Thus, MPSV-infected spleen cells were shown, for the most part, to be short-lived cells: almost one-half mature into erythrocytes and the others rapidly die in situ.

Animals↗

Myeloproliferative sarcoma virus (MPSV), a new tool for the study of hematopoiesis.

MPSV induces a myeloproliferative syndrome in susceptible mice associated with an invasion of hematopoietic and nonhematopoietic organs with tumor nodules. The effect of the virus on the various hematopoietic precursors (CFU-S, CFU-C, CFU-E, BFU-E) was studied in vivo in the spleen, blood, and bone marrow, and in vitro, using colony assays in semisolid medium. After in vivo and in vitro infection MPSV induces the appearance of CFU-C, independent of added colony-stimulating activity and of pure and mixed BFU-E, independent of burst-promoting activity. MPSV also induces in vivo an amplification of the size and concentration of the hematopoietic system, including hematopoietic stem cells. MPSV infection may also alter the hemapoietic microenvironment. Modification of the disease by total body irradiation followed by bone marrow stem cell reconstitution or by splenectomy is compatible with mediation of the virus effect at the level of hematopoietic microenvironment. MPSV may constitute a new tool to study the regulation of murine hematopoiesis and viral genetic information, which can specifically induce characteristic disturbances of this system.

Animals↗

Cellular blood fluorescence polarization: a possible prognostic tool in human acute lymphatic leukemia.

We measured the fluorescence polarization of 1-6 diphenyl hexatriene in mononucleated cells from the peripheral blood of 49 acute lymphoid leukemic patients in complete hematological remission with an Elscint MV-1 microviscosimeter. The measurements of fluorescence polarization were made at various times after the remission was achieved. Our results represent two years of this prospective study. We found that lymphoid leukemic patients in remission could be separated into two groups according to the lowest value of fluorescence polarization of their blood cells. 1) The first group of 26 patients showed values superior to 3.44 poises, in all samples, corresponding to the lowest value of normal controls. 2) The second group showed at least one value of blood fluorescence polarization lower than 3.44 poises. This second group had a significantly lower median duration of remission and survival compared to the first. We have subdivided these two groups according to other established prognostic parameters such as cytological subtype and initial volume of the disease: we found that cellular fluorescence polarization could give additional prognostic information. These data suggest that fluorescence polarization measurements have a prognostic value to follow acute lymphoid leukemia patients in complete remission: when a low value is found there is a significant risk of relapse.

Adolescent↗

Malignant bone tumours induced by a local injection of colloidal radioactive 144Cerium in rats as a model for human osteosarcomas.

Lung metastases were observed in 80% to 85% of rats bearing advanced malignant bone tumours (osteogenic osteosarcomas and angiosarcomas). These tumours were induced in 2-month-old Sprague-Dawley rats by inoculation of a colloidal suspension of radioactive cerium (144Ce) into the hind leg, in close contact to the bones of the knee joint. Twenty-eight rats were killed or died spontaneously shortly after detection of palpable tumours at the site of injection: the incidence of lung metastases was 73.3% and 53.8%, respectively, for osteogenic sarcomas and angiosarcomas, showing that most lung metastases are present at the time of diagnosis of the primary tumour. Tumour-cell kinetic parameters were studied in 49 rats bearing tumours following intraperitoneal injection of [3H]thymidine. The labelling index (LI) of the primary tumours was significantly lower in advanced tumours (7.2% for osteosarcomas and 10.1% for angiosarcomas) than than in tumors examined at the time of detection (12.2% and 13.5%, respectively). Mitotic indices (MI) of all tumours were less than 1%. From the curve of the percentage of labelled mitoses (PLM) at different times after [3H]thymidine injection, Ts (6.5 h) and TG2 (1.75 h) were determined. TC and TG1 were also evaluated (18 h and 9.25 h, respectively). These results show that malignant bone tumours induced in rats with 144Ce may be a good model for human osteosarcomas and may be useful in studying the numerous problems in the therapy of malignant bone tumours in man.

Animals↗