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Biomedical subjects

C Jasmin

Publications and source records attributed to C Jasmin.

At least 163 records · Page 9Linked to original sources
PubMed1984

In vitro sensitivity of myeloblast clonogenic cells to doxorubicin, aclacinomycin A, and 4'-O-tetrapyranyl-doxorubicin: correlations with clinical responses.

The in vitro sensitivity of peripheral blood myeloblast clonogenic cells (CFU-MLs) to doxorubicin (DOX), aclacinomycin (ACL), and 4'-O-tetrapyranyl-doxorubicin (THP-DOX) was studied to evaluate the individual chemosensitivity of CFU-MLs. CFU-MLs from untreated patients were sensitive to the three tested anthracyclines (in 60% to 69% of the patients). Conversely, CFU-MLs from relapsed patients previously treated with DOX-containing regimens were sensitive to ACL and THP-DOX (in 71% and 75% of the patients, respectively) but resistant to DOX. Six of ten patients who entered complete remission with a combination of DOX, vincristine, and cytosine arabinoside had CFU-MLs in vitro which were sensitive to DOX. Conversely, none of the 13 patients resistant to this chemotherapy regimen displayed CFU-MLs which were sensitive in vitro to DOX. Nine of ten patients who responded to ACL as well as one of three resistant patients had CFU-MLs sensitive to ACL in vitro. No clinical responses were observed with THP-DOX in five of seven patients with CFU-MLs sensitive to this drug. The results indicate that myeloblast clonogenic assays can be used to predict the in vitro sensitivity of CFU-MLs to compounds with established antileukemic activity (ie, DOX, ACL). However, the discrepancy between in vitro and in vivo sensitivity to THP-DOX underlines the importance of knowledge of drug pharmacokinetics and the difficulty of using the CFU-ML test for screening new drugs.

Aclarubicin↗
PubMed1984

Amplified pulmonary metastases of a rat rhabdomyosarcoma in response to nitrosourea treatment.

Repeated observations in our laboratory show that the chloroethylnitrosourea of cysteamine ( CNCC ) induces slowed tumor growth rate and decreased lymph node metastasis in rats bearing a rhabdomyosarcoma but concomitantly enhances metastatic dissemination in the lung. Tumors obtained by sc graft of tumor cells, in syngeneic rats, gave a reproducible pattern of metastases at nodal and pulmonary sites after a 60-80-day period. CNCC was administered orally at a dose of 50 mg/kg once a week for 5 weeks beginning at the time of tumor appearance. Forty-five of 46 CNCC -treated rats had lung metastases with 95 (+/- 9.7) nodules; in the control group 29 of 41 rats had lung metastases with 7 (+/- 1.5) nodules. This amplifying effect was found after treatment with two other nitrosoureas (chlorozotocin and hydroxyethylchloroethylnitrosourea ) but not with cyclophosphamide and methotrexate. Lung metastatic amplification was also observed after treatment of the 13762 mammary adenocarcinoma in Fischer rats and treatment of nickel-induced soft tissue tumor. Several hypotheses have been proposed. The dissociated effect of nitrosourea on local tumor, lymph nodes, and pulmonary metastases does not support the concept of systemic immunosuppression as the main mechanism of this phenomenon, but a decrease of local immunological defenses exerted by NK cells, for example, could be possible. Alternatively, a direct effect of the drug on lung tissue, especially lesions of endothelial tissue, could be responsible for the observed effect. Nitrosourea treatment of rats after surgical excision of the tumor, as adjuvant chemotherapy, was responsible for an amplification effect in association with local recurrences. From this fact we hypothesized that nitrosourea treatment could modify the equilibrium of cell subpopulations in the tumor by selecting highly metastatic drug-resistant variants. Although the mechanism of the amplifying effect of nitrosoureas has not been elucidated, our study shows a possible risk in the use of these drugs for inductive or adjuvant chemotherapy.

Adenocarcinoma↗
PubMed1984

[Protocols for the treatment of leukemia and lymphoma: toward escalation or toward reduction of degree?].

The present AML protocol which only applies one anthracycline associated with arabinosyl-cytosine gives a first remission plateau of 65% and a 75% survival plateau at five years. Contrary to other teams, we do not apply the allogenic bone marrow graft at the first remission but at the second one. The new protocol comprises application of two anthracyclines, adriamycin and aclacinomycin, a possible autologous bone marrow graft at first remission upon reinforcement, a combination of methotrexate and thioguanine as maintenance chemotherapy and immunotherapy with bestatine. The two protocols respectively applied to the ALL good prognosis and reserved prognosis, give 85% global survival. The autologous bone marrow graft is added at first remission to B or T forms or voluminous CALLA + types. The advantage of CNS radiotherapy is compared with its disadvantages. Bestatine is employed in immunotherapy. The immunoprevention protocol applied to CML blastic crisis (vaccination with a pool of CB blasts) from the second year has prolonged survival of patients suffering from this affection and also treated by splenectomy and hydroxyurea. Allogeneic or autologous bone marrow graft is added to the protocol. The same protocol is applied to not very aggressive LLC and LNH (lymphocytic and centrofollicular with small cleaved nucleus cells) and includes maximum remission induced by chemotherapy followed by immunotherapy (by thymuline and then, if immunity disorders are not corrected, by zinc, then bestatine and finally tuftsin). A similar sequence was applied to the myeloma, comprising MLP-PDN-CPM chemotherapy to induce remission, combination of MLP-PDN and CPM and, if there is resistance, CLB, 6-TG, PDN and TNP. Interferon is appropriate with certain cytopenic forms. A protocol comprising VCR, ADM, PDN, CPM and TNP is applied to centrofollicular NHL with small non cleaved nucleus cells or large cells. As Hoerni and Jones have obtained significant benefits with BCG, its terminal application is compared with that of bestatine. Finally a less mutagenic protocol than MOPP and/or ABVD is proposed for Hodgkin's disease. In this protocol, two cycles alternate, and they combine: a) firstly VCR, PDN, THP-ADM and VPS, and b) secondly VLB, DXM, ACM and TNP with alternatively BLM and PPM between the cycles. This chemotherapy is followed by the same immunorestoration protocol as that applied to LLC and myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Hematological toxicity of repeated injections of (chloro-2-ethyl)-ribofuranosyl-3-nitrosourea.

A previous study using a single injection of (chloro-2-ethyl)ribofuranosyl-3-nitrosourea has indicated the low acute hematotoxicity of this nitrosourea. However, because the hematotoxicity of nitrosourea is usually cumulative, we have studied the effect of injecting (chloro-2-ethyl)ribofuranosyl-3-nitrosourea (15 mg/kg) dissolved in 0.2 ml sterile oil C57BL X i.p. into DBA/2F1 mice for 5 consecutive weeks. The dose per injection represents the minimal dose necessary to show the maximal therapeutic efficacy on L1210 leukemia. Bone marrow cellularity and histology, spleen weight, bone marrow and splenic pluripotent stem cells, and colony-forming units committed to granulocyte-macrophage differentiation were measured 1, 2, 4, 7, and 14 days after the last injection in treated and control mice receiving oil only. No morphological or histological changes were found in the spleen and bone marrow of treated mice. In both organs, the number of splenic pluripotent hematopoietic stem cells decreased by about 1 log 1 day after the last injection but rapidly returned to normal values on Days 4 to 14. Granulocyte-macrophage-committed precursors were affected in both organs, at 20% of control values for bone marrow and 5% of control values for spleen on Day 1, with a transient and partial recovery on Day 4 followed by a second drop to 20 and 25% on Day 14. This effect on granulocyte-macrophage precursors contrasts with the absence of significant effect when the same treatment is used on peripheral white blood cell counts. Our results demonstrate that (chloro-2-ethyl)ribofuranosyl-3-nitrosourea belongs to the class of new nitrosoureas with low cumulative hematotoxicity.

Animals↗
PubMed1983

Correlation between structure of polyoxotungstates and their inhibitory activity on polymerases.

The 21-tungsto-9-antimonate (TA, HPA 23), a polyoxotungstate, has shown a significant antiviral activity in vivo and in vitro. It inhibits viral and bacterial DNA polymerases. In this paper, several compounds of two polyoxotungstic families, tungstoantimonates and tungstoarsenates, have been used to specify the mechanism of polymerase inhibition. It has been demonstrated that the inhibitory activity of polyoxotungstates is not related to the occupation of their coordinates sites by cations, nor to the nature of these bound cations. Kinetic studies and binding assays have shown that polyoxotungstates bind to the polymerases in competition with the nucleic acid template. This result seems to be related to their polyanionic nature. Furthermore, the size and charge of these compounds may play a prominent part in their affinity for the polymerases.

Antimony↗
PubMed1983

Established cell lines of mouse marrow adherent cells producing differentiation factor(s) for the granulocyte-macrophage lineage.

Two continuous cell lines derived from long-term cultures of AKR mouse bone marrow adherent cells were isolated. These cell lines release colony stimulating activity (CSA), a factor that induces in vitro differentiation of granulocyte-macrophage progenitor cells. The colony forming cells and cluster forming cells in mouse marrow responsive to CSA from mouse lung conditioned medium MLCM). Colony forming cells were characterized by analysis of their density distribution after equilibrium centrifugation in density gradient. Cluster forming cells were characterized by analyzing the progeny of individual clusters after transfer to fresh semisolid culture medium containing MLCM. The results obtained indicate that the CSA from cell line conditioned medium closely compares with the CSA from MLCM in terms of the populations of colony and cluster forming cells stimulated.

Animals↗
PubMed1983

Myeloproliferative Sarcoma Virus stimulates pluripotent hematopoietic stem cells and provokes tumoral transformation of the hematopoietic microenvironment in vitro.

The Myeloproliferative Sarcoma Virus (MPSV) induces an increase in the number and concentration of pluripotent stem cells in long-term murine bone marrow cultures. This is followed by an increased number of precursor cells of the granulocyte and macrophage lines (GM-CFC). This increase is comparable to that observed in DBA/2 mouse spleens in vivo two to three weeks after viral infection. Proliferation of CFUs and GM-CFC decreases five weeks after infection with MPSV, in parallel to the gradual decline of reverse transcriptase activity in the culture medium. GM-CFC which can proliferate in the absence of added colony stimulating factor (CSF) were detected at week 6 post MPSV infection. Adherent tumor cells were observed nine weeks after infection. These fibroblast type cells gave rise to a permanent line which produced a CSF-like activity. Our results show that MPSV causes the tumoral transformation of fibroblast-like cells of the bone-marrow hematopoietic microenvironment. In addition, MPSV also strongly stimulates the proliferation of hematopoietic stem cells. MPSV is, until now, the first murine retrovirus which exhibits such properties.

Animals↗
PubMed1983

Mutagenicity of eight anthracycline derivatives in five strains of Salmonella typhimurium.

The mutagenicity of eight anthracycline derivatives, doxorubicin (adriamycin, ADM), daunorubicin (DNR), rubidazone (zorubicin), detorubicin (DTR), 4'-epi-adriamycin (4' epi-ADM), AD 32, N-leucyl daunorubicin (N-leu DNR) and aclacinomycin A, has been tested on Salmonella typhimurium TA 100, Ta 98, TA 1535, TA 1537 and TA 1538. All but aclacinomycin A were mutagenic. Adriamycin and daunorubicin were mutagenic in all five strains, but only at very high doses (40-100 micrograms/plate) in TA 1535 and 1537. TA 98 was the most sensitive strain. In general S9 mix (liver homogenate) increased the mutagenicity of the low doses of both compounds. Zorubicin, 4'-epi-adriamycin and detorubicin were mutagenic for TA 98 and TA 100 and slightly mutagenic in TA 1538. They were also activated by S9 mix. N-leu DNR and AD 32 were slightly but significantly mutagenic for TA 98 and TA 1538 and were also activated by S9 mix. Aclacinomycin A lacked mutagenic activity in the five strains even at cytotoxic doses, both in the presence and absence of S9 mix. The results with AD 32 N-leu DNR and aclacinomycin A strengthen the hypothesis according to which amino moiety of the anthracycline glycosides is essential for mutagenesis.

Aclarubicin↗
PubMed1983

Expression of ecotropic murine leukaemia virus in haemopoietic cells of AKR mice during the embryonic and neonatal period.

Cells which produce ecotropic murine leukaemia virus have been detected in the bone marrow and the spleen of weanling AKR mice, using an infectious centre technique based on the XC test. There is a noticeable increase in the number of virus-producing cells between day 3 and day 12 after birth, in both of these organs. Some of the virus-producing cells that appear after day 3 have been identified as haemopoietic precursor cells of the granulocyte-macrophage blood lineage. Such precursor cells do not produce virus during the embryonic period and they progressively become involved in virus production after day 3. By day 12, all of them are active virus producers. Thus, the ecotropic virus is expressed in precursor cells of the haemopoietic system, and the latter represent at least one-third of the virus-producing cells in the bone marrow of young AKR mice.

Animals↗
PubMed1983

Myeloproliferative syndrome induced by MPSV in DBA/2 mice: presence of a mixed-colonies promoting activity (MPA) in the spleen.

The myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) in DBA/2 mice stimulates the proliferation of pluripotent hemopoietic stem cells (HSC) and of progenitors committed toward granulomacrophagic and erythroid cell lines. This stimulation may result from a direct effect of the MPSV on HSC or from an indirect effect via locally secreted factors. Normal isogenic bone marrow cells were incubated in the mixed colony-forming unit system in semisolid medium supplemented with conditioned media obtained after incubating neoplastic spleen cells for 3 days at 37 degrees C. These spleen conditioned media contain an activity that is physically separable from MPSV by ultracentrifugation and which, in the presence of a very low quantity of erythropoietin, can induce in vitro the proliferation and differentiation of pluripotent HSC, detected by this Mix-CFU technique. We termed this activity mixed-colonies promoting activity (MPA). These results suggest that the hyperplasia of the nonlymphoid hematopoietic system in the neoplastic spleen results from an indirect effect of the MPSV on pluripotent HSC via locally secreted factors.

Animals↗
PubMed1983

Hematopoietic precursors in disease induced by the myeloproliferative sarcoma virus.

Granulocyte and macrophage precursors (GM-CFU-C-), which differentiate in vitro without added granulocyte and macrophage colony stimulating factor (GM-CSF), can be detected in the hematopoietic organs of mice infected with myeloproliferative sarcoma virus (MPSV). Retransplantation experiments have shown that the GM-CFU-C- are incapable of autonomous growth and depend on a factor present in medium conditioned by MPSV spleen cells (MPSV-CM). This factor is not MPSV and is not produced by spleen cells of noninfected mice. Two classical sources of GM-CSF, lung GM-CSF and GM-CSF contained in the plasma of endotoxin-treated mice, cannot replace the MPSV factor. Inversely, MPSV-CM does not stimulate the growth of retransplanted clusters induced in normal bone marrow with lung GM-CSF, whereas lung GM-CSF does. Two conditioned media containing activity promoting the in vitro proliferation and differentiation of hematopoietic stem cells in the mixed colony assay stimulate the growth of MPSV clusters: one medium was conditioned by pokeweed-mitogen-stimulated spleen cells, the other by the WEHI 3 cell line. The implication of the results in the comprehension of MPSV disease is discussed.

Animals↗
PubMed1982

[Treatment of acute myeloid leukemia with a protocol combining intensive induction chemotherapy, early consolidation treatment, splenectomy and long-term maintenance chemotherapy. Preliminary study].

Twenty-seven patients aged from 10 to 60 years (mean 34.4 +/- 13 years) in the first perceptible phase of acute myeloid leukemia were subjected to intensive induction chemotherapy consisting of adriamycin (ADM), vincristin (VCR) and cytosine arabinoside (ARA-C). Twenty-four patients (89%) attained complete remission (CR) after 1 to 3 cycles and were then given an early consolidation treatment with one of the previous cycles. This was followed by long-term continuous maintenance chemotherapy with 6-mercaptopurine (6-MP) and methotrexate (MTX) alternatively and 3-monthly reinforcement courses of donaurubicin (DNR) and VCR. Twenty of these 24 patients were splenectomized soon after the consolidation treatment. None of the spleens were enlarged, and histological sections of the spleens, liver biopsies and mesenteric lymph-nodes stained with routine dyes and by the naphthol AS-D chloroacetate esterase method revealed mature granulocytes but no demonstrable leukaemic cells. In the group of splenectomized patients, the probabilities of staying in complete remission at 27 and 44 months were 70 +/- 12.6% and 52 +/- 18.5% respectively, and the probabilities of remaining alive at 32 and 55 months were 79 +/- 11% and 57 +/- 19% respectively. Age over 40 and evidence of extramedullary infiltration at presentation appeared to leave little hope of disease-free survival. The rationale for the present therapeutic study is discussed.

Adolescent↗
PubMed1982

[Treatment of rectocolic and gastric adenocarcinomas with 5-fluorouracil associated with high doses of folinic acid. Results of an experimental study].

We report the results of a therapeutic trial in patients with rectocolic and gastric metastatic adenocarcinomas. This trial is based on experimental evidence that an excess of reduced intracellular folic acid increases the cytotoxicity of fluoropyrimidines. The treatment consists of 5-fluorouracile (5-FU) (370 to 400 mg/m2/24 h) and folinic acid in high doses (200 mg/m2: 24 h) given simultaneously for 5 consecutive days; the interval between courses is 21 days. Thirty patients with measurable rectocolic adenocarcinomas were evaluated. They were divided into two groups: 16 patients had had no previous chemotherapy and 14 had not responded to chemotherapy with 5-FU alone or associated with other cytostatic drugs. Response rates were 56% in the first group and 21% in the second. Five patients with measurable gastric adenocarcinomas were also evaluated; none had received previous chemotherapy. A partial response was recorded in three of these patients. Toxicity of the therapeutic regimen was acceptable. Stomatitis was the most common toxic side-effect. In patients with severe adverse side-effects recurrence was efficiently prevented by decreasing the daily dose of 5-FU to 30 mg/m2 during subsequent courses. We conclude that in the tumors studied folinic acid in high doses can improve the antitumoral effect of 5-FU and induce a response to this agent in some rectocolic tumors which were previously resistant.

Adenocarcinoma↗
PubMed1982

[Adjuvant therapy of osteogenic osteosarcomas of the limb: results of the SO4 78 trial].

Twenty-nine patients with osteogenic osteosarcoma of a limb underwent both pulmonary radiotherapy and chemotherapy immediately after treatment of the primary tumor, mainly by radical surgery or radiotherapy (80 grays/tumor). Chemotherapy consisted of alternate A and B cycles every four weeks and BCG scarifications between cycles. Cycle A combines vincristine, ameticine, methotrexate and folinic acid; cycle B consists of adriamycin, vincristine, imidazole carboxamide and cyclophosphamide. A 20 gray irradiation was delivered to the thorax between the first A and B cycles. 50% of patients had no local recurrence or metastases after three years. 70% are alive at three years. Toxicity of this protocol is mainly hematologic and bronchopulmonary (with one fatal infection). Alopecia and minor digestive toxicity were recorded in all patients. Severe cardiotoxicity was seen in only one case. Longer follow-up is needed to evaluate long-term toxicity, particularly bronchopulmonary side-effects.

Bone Neoplasms↗
PubMed1982

[An experimental model of osteosarcomas in rats ].

Satisfactory experimental models for preclinical prediction in cancerology must answer the following criteria: reproducibility of the method used for inducing tumors; clinical, pathological and kinetic similarity with the corresponding human tumors. We have developed a model of osteosarcoma locally induced by insoluble radioactive cerium chloride (144Ce CI3) in Sprague Dawley rats. This method yields over 80% of bone tumors at the injection site, of which approximately half are histologically similar to human tumors. These tumors double their volume fairly slowly (in approximately 20 days); lung metastases occur both early and frequently (80% of animals). A transplantable tumor was developed from an induced osteosarcoma and adapted to the Curie strain. Transplantation in the bone, next to the bone, or under the skin is followed by widespread metastatic dissemination. The kinetics and histological features of the primary tumor are maintained. Tumor 85 strontium uptake is similar to that seen in human osteosarcomas. These new models of osteosarcomas are being used for evaluating new cancer chemotherapeutic agents and interferon, etc.

Animals↗