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V Ribrag

Publications and source records attributed to V Ribrag.

66 records · Page 4Linked to original sources
PubMed1993

Selective increase of alternatively spliced Lck transcripts from the proximal promotor in hematopoietic malignancies.

Screening by Northern blot for lck expression in 51 patients with diverse hematologic diseases has shown, for four of them, a 3 to 15-fold increase in the level of lck mRNA when compared with expression in healthy donors. These patients suffered from diverse malignancies: one Burkitt lymphoma, one T-cell lymphoma and two non-Hodgkin B-cell lymphoma. Specific analysis of the different lck transcripts in these patients by polymerase chain reaction and their relative quantitation demonstrate a significant increase of only the type IB and the type IC lck transcripts arising from the proximal promotor. Our study shows: (a) a high lck expression may occur in diverse hematologic diseases, (b) whatever the type of malignancy, this high expression results in a specific increase of the spliced transcripts arising only from the proximal promotor, and (c) in these four patients without any rearrangement or amplification, the high lck expression probably results from the specific activation of the proximal promotor.

Blotting, Northern↗
PubMed1992

Comparison of mouse and human colon tumors with regard to phase I and phase II drug-metabolizing enzyme systems.

Since human colorectal tumors are insensitive to most chemotherapeutic agents, there is a need for the discovery of new drugs that would show activity against this disease. In an attempt to better appreciate the relevance of a widely used mouse colon tumor (colon adenocarcinoma Co38) as a screening model for human colorectal tumors, we compared the main phase I and phase II drug-metabolizing enzyme systems in both tumoral and nontumoral colon tissues. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B2, 2C, 2E1, and 3A), epoxide hydrolase, and glutathione-S-transferases (GST-alpha, -mu, and -pi). The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: total cytochrome P-450, 1-chloro-2,4-dinitrobenzene-GST, selenium-independent glutathione peroxidase, 3,4-dichloronitrobenzene-GST, ethacrynic acid-GST, total glutathione, epoxide hydrolase, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. Results obtained by Western blot showed that mouse colon adenocarcinoma Co38 did not express any of the probed cytochromes P-450, whereas human colorectal tumors expressed only low levels of cytochrome P-450 3A. GST-alpha and GST-pi were detected in all tumoral and nontumoral tissues of both species. The neutral GST-mu was expressed in all murine tissues investigated and was found to be polymorphic in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzyme levels, whereas mouse colon adenocarcinoma Co38 had a lower expression of GST-mu and GST-pi, compared to normal mouse colon. Enzymatic activities for glutathione peroxidase, 3,4-dichloronitrobenzene-GST, and ethacrynic acid-GST confirmed the Western blot results for GST-alpha, GST-mu, and GST-pi, respectively. Total GSH levels were similar between murine and human tumors but were 3-fold higher in human tumors than in peritumoral tissues, whereas they were 7-fold lower in mouse colon tumor Co38, compared to normal mouse colon. Epoxide hydrolase was not expressed in either mouse colon adenocarcinoma Co38 or normal mouse colon tissues, whereas it was expressed in human colon peritumoral and tumoral tissues at similar levels. No significant difference was observed between human tumors and peritumoral tissues for UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. For murine colon tissues, the conjugation pathways (UDP-glucuronosyltransferase and sulfotransferase) were lower in colon adenocarcinoma Co38, whereas the converse was observed for the corresponding hydrolytic enzymes (beta-glucuronidase and sulfatase).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1992

Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms.

The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor markers for nongonadal malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free hCG alpha and hCG beta subunits have been used to reevaluate the presence of these molecules in the serum of patients with a wide variety of tumors. Serum samples from patients with newly diagnosed, persistent, or recurrent malignancies of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors (n = 309), and nonmalignant disease controls (n = 86) were studied using four highly specific and sensitive monoclonal based immunoradiometric assays to hCG and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found to be common in cancer patients, normal subjects, and disease controls. However, serum levels greater than 1000 pg/ml were highly diagnostic of gonadal tumors and specifically identified nonseminomatous testicular tumors. Significant serum elevations of free hCG alpha subunit (as high as 3000 pg/ml) were found in approximately 96% of cancer patients, normal individuals, and disease controls. In contrast, free hCG beta subunit levels (greater than or equal to 100 pg/ml) were detected in 70 and 50% of patients with nonseminomatous and seminomatous testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and 30% of cervical carcinomas. All normal subjects and disease controls had free hCG beta levels less than 100 pg/ml. Thus, the detection of the free hCG beta subunit in serum of nonpregnant subjects was highly diagnostic of malignancy in general and specifically defines a subgroup of aggressive nongonadal malignancies.

Adult↗
PubMed1992

Non-nephrotoxic empiric antimicrobial therapy in febrile neutropenic cancer patients.

We evaluated the efficacy of piperacillin-pefloxacin as a non-nephrotoxic antibiotic combination in febrile neutropenic cancer patients treated with nephrotoxic chemotherapy. 40 patients: 34 with solid tumours and 6 with non-Hodgkin lymphoma, were treated during 55 episodes with: piperacillin 4 g intravenously every 8 h and pefloxacin 400 mg intravenously every 12 h. If the patient remained febrile after 72 h, 1 g vancomycin intravenously was added every 12 h. The mean duration of neutropenia was 7 days (range 3-13). Infection was microbiologically documented in 13 episodes (8 gram-positive cocci and 7 gram-negative bacilli). Temperature became normal in 38 patients with piperacillin-pefloxacin and 12 further episodes were resolved by the addition of vancomycin. 2 patients had an early change of antibiotics because of clinical deterioration, there were 2 protocol violations and 1 patient's temperature became normal after the addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and warrants further comparative trials.

Adolescent↗
PubMed1992

Acute myelogenous leukemia with T-cell features.

From May 1985 to June 1990, 94 newly diagnosed cases of acute myelogenous leukemia (AML) were treated at the Institut Gustave-Roussy, of which four (4.3%) demonstrated mixed cell lineage. All these cases were morphologically and cytochemically considered as myelogenous leukemias according to the FAB classification. Immunophenotyping revealed in all four cases that the blast population had T-lymphoid (CD2, CD5, CD7 and cytoplasmic CD3) markers. In three of these cases, blast cells co-expressed myelogenous CD13 and CD33 markers. Cytogenetic analysis of the blast cells revealed a normal karyotype in all cases. The response to therapy has been poor. The two patients initially treated with a regimen usually used for AML did not achieve complete remission. By contrast, in three cases, complete remission was obtained with a drug combination used for lymphoblastic leukemia (in one case after failure of first line AML regimen). Only one patient remained disease-free for more than 18 months. We conclude that this form of leukemia is a distinct biological and clinical entity and may benefit form alternative therapy.

Adolescent↗
PubMed1992

Infectious complications associated with granulocytopenia during the treatment of poor risk or relapsed germ cell tumors.

Infectious complications associated with granulocytopenia during the treatment of poor risk or relapsed germ cell tumors were studied in order to assess the frequency, morbidity and characteristics of these complications. Thirty-three cases were investigated at the Institut Gustave-Roussy; 63 episodes of granulocytopenia were observed (mean duration 7.5 days). Twenty-four (38%) of the episodes of granulocytopenia were associated with fever. In 11/24 episodes (46%), fever was associated with a documented infection. Eighteen organisms were isolated. Ten were found to be Gram-positive, 7 Gram-negative, and one Candida. The major site of infection was the lungs. One death from septicaemia occurred. In conclusion, post-chemotherapy granulocytopenia during the treatment of germ cell tumors is associated with fever in less than 50% of cases. Bacterial infection was diagnosed in only 46% of febrile neutropenic episodes and rarely appears to be associated with a fatal outcome.

Adolescent↗
PubMed1992

Peripheral blood stem cell collection and autografting in high risk lymphomas.

Peripheral blood stem cells (PBSC) were collected from 29 patients with high risk Hodgkin's disease (n = 3) or non-Hodgkin's lymphoma (n = 26) in partial remission or first sensitive relapse. Patients had either bone marrow involvement or hypoplastic bone marrow. The conditioning regimen prior PBSC collection included amsacrine and cytosine arabinoside (Ara-C) or Ara-C alone. PBSC collection was performed after leukocyte counts reached 1 x 10(9)/1. A good yield was obtained in 23 patients, whereas sufficient numbers of CFU-GM were not obtained in six cases. Twenty-one patients have been transplanted. All patients except one achieved bone marrow engraftment. Eight patients are in complete remission (mean duration 15 months). The estimated 2 years survival rate is 46.4% (CI 25-68%). This procedure would seems a good alternative in poor prognosis lymphomas.

Adult↗
PubMed1992

[Value of the combination of piperacillin and pefloxacin possibly followed by vancomycin in the treatment of febrile neutropenia in nephrotoxic chemotherapy].

We evaluated the efficacy and safety of piperacillin-pefloxacin potentially associated to vancomycin as a non nephrotoxic antimicrobial therapy in febrile neutropenic cancer patients, treated with nephrotoxic chemotherapy. Fifty-seven patients: 49 with solid tumors and 8 non-Hodgkin lymphomas, were treated during 85 episodes with: piperacillin 4 g IV every 8 h pefloxacin 400 mg IV every 12 h. If the patient remained febrile after 72 h, 1 g of vancomycin IV was added every 12 h. The mean duration of neutropenia was 7 days (3-14 days). In 44 episodes, the granulocyte nadir was < 100/mm3. Infection was microbiologically documented in 17 episodes (20%) with ten Gram-positive cocci and 11 Gram-negative bacilli. There were 64 apyrexia with piperacillin-pefloxacin (75%) and further 14 were resolved by the addition of vancomycin (total success = 92%); three early changes because of clinical deterioration (two episodes) or germ resistance (one episode); three protocol violations, and one apyrexia by addition of amphotericin. Neither septic death nor toxicity were observed. We conclude that this empirical treatment is active and safe and avoids nephrotoxicity in cancer patients heavily treated with nephrotoxic chemotherapy.

Adolescent↗
PubMed1990

[Chemotherapy in advanced transitional cell carcinoma of the urinary tract. Phase II trial of a combination of doxorubicin and cisplatin].

Between January 1, 1983 and December 31, 1984, 18 patients with advanced transitional cell carcinoma of the urothelium were treated in a Phase II trial with doxorubicin 45 mg/sqm plus cisplatin 90/mg/sqm/day every four weeks. 17 patients were evaluable for response. There were: 4 partial responses (24% of response objective effects, 95% confidence limits are 15% and 33%) and 13 failures. The median survival was 18.5 months for responders and 10 months for non responders.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Salvage chemotherapy of non-seminomatous germ cell tumors. Phase II trial of a combination of etoposide, ifosfamide and high-dose cisplatin].

Between october 1985 and january 1988, 32 patients with heavily pretreated refractory or relapsing non seminomatous germ cell tumors were included in a phase II trial using etoposide, ifosfamide and high dose cisplatin (VIhP). Eight of 30 evaluable patients (29 per cent) achieved complete response with VIhP treatment alone or followed by surgical excision of residual lesions. Five patients in complete remission relapsed at 3, 4, 5.5 and 7 months, and 3 patients remained continuously free of disease at 17, 21 and 22 months. Severe myelosuppression with a WBC nadir less than 500/mm3 and a platelet nadir less than 20,000/mm3 was observed in 73 per cent of the patients, and renal toxicity (WHO grade 2 or 3) in 29 per cent. The VIhP regimen for salvage therapy gives the same rate of long term survivors than the regimen with conventional cisplatin dosage (VIP) but is much more toxic and cannot be recommended.

Adolescent↗
PubMedDate not supplied

Glutathione system, topoisomerase II level and multidrug resistance phenotype in acute myelogenous leukemia before treatment and at relapse.

In order to better understand acquired resistance to antitumor agents in acute myelogenous leukemia (AML), we investigated various drug resistance mechanisms; namely, topoisomerase II (topo II), glutathione system and P-glycoprotein (P-gp). Blast cells of 31 patients with AML, 21 before treatment (BT) and 10 at relapse (AR) were studied. Topo II was evaluated by Western blot analysis. Glutathione-S-transferase activity (GST) and glutathione content (GSH) were investigated by spectrophotometric assays. GST isoenzymes (-alpha, -mu and -pi) were tested by Western blot and by immunocytochemical staining. P-gp was evaluated by an immunocytochemical method using MRK 16 antibody. Our results showed that GST, GSH and GST-pi were similar in patients BT and AR GST-mu was detected in 13/21 AML BT and in 5/10 AML AR. GST-alpha expression was higher (p < 0.05) in AML AR (60 +/- 105 AU/mg) compared to AML BT (10 +/- 10 AU/mg). A relationship was found between GST-pi quantitation evaluated by Western blot and immunocytochemical staining, whereas no correlation was observed for the other isoenzymes. Topo II was detected in only 4 AML BT and 3 AML AR. Eleven out of 21 AML BT and 3/10 AML AR expressed P-gp with immunohistochemical study. These results indicate that only the "glutathione system", especially the GST-alpha could be involved in drug resistance in AML.

ATP Binding Cassette Transporter, Subfamily B, Mem↗