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Biomedical subjects

J Bourhis

Publications and source records attributed to J Bourhis.

At least 91 records · Page 5Linked to original sources
PubMed1994

Prognostic value of MDR1 gene expression in neuroblastoma: results of a multivariate analysis.

The prognostic value of the MDR1 gene expression in neuroblastoma (NB) was assessed in a multivariate analysis performed in a series of 84 patients (pts) taking into account the main known clinical and biological factors of the disease, i.e., age, stage, MYCN genomic content and DNA ploidy index. Twenty seven children were < 1 year (yr), 13 presented with stage I and II, 7 with stage IV-S, 17 with stage III and 47 (56%) with stage IV. Tumor specimens were obtained from involved bone marrow (n = 12) or surgical primary tumor specimens (n = 72). MDR1 gene expression was measured by Northern hybridization technique and expressed in arbitrary units (a. u.) (Goldstein et al., 1989). Analysis of MYCN genomic content and DNA ploidy index were performed by Southern blot hybridization technique and flow cytometry, respectively. Out of 84 tumor specimens 19 (23%) showed MYCN amplification (> 3 copies/haploid genome). In 24 cases (29%) no detectable MDR1 gene transcript was found (0 a.u.) whereas 42 (50%) had a value in the range 1-30 a.u., and 18 (21%) a value beyond 30 a.u.. High transcript levels were found in localized as well as in metastatic NB (NS). No significant correlation between MDR1 gene expression, age, stage, or MYCN genomic content was found In univariate analysis stage IV, age > 1 yr, MYCN amplification, diploid DNA content and high MDR1 gene transcript levels were significantly related to an increased risk of death. In multivariate analysis only stage IV, MYCN amplification and MDR1 overexpression remained significantly associated with an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Radiation-induced cell cycle delay measured in two mouse tumors in vivo using bromodeoxyuridine.

The magnitude of the delay of cells in the phases of the cell cycle after irradiation may be related to the radioresponsiveness of tumor cell populations. In this study we have quantified division delay in two mouse tumors in vivo after single and fractionated doses of X rays and single doses of neutrons. The incorporation of bromodeoxyuridine and flow cytometry provided a sensitive and quantitative method to detect cell cycle perturbations after radiation treatment. The more rapidly growing SAF tumor showed less G2-phase delay per gray than a more slowly proliferating tumor, the Rh (0.9 vs 1.8 h). In addition, the SAF tumor failed to show any G1/S-phase delay while the Rh tumor experienced a longer G1-phase delay than that measured for G2 phase (3.1 vs 1.8 h). There was a trend in both tumors for lower doses to be more effective in producing cell cycle delays. Neutrons caused longer G2-phase delays on a unit dose basis, 2.5 and 5.4 h for the SAF and Rh tumors, respectively. The RBE for neutrons for division delay was found to be 2.9 and 2.8 for the SAF and Rh tumors, while the RBE for growth delay was 3.4 and 3.5. Fractionation of the X-ray dose caused a reduction in division delay at higher total doses (10 or 12 Gy) but was without effect at the lower dose studied (6 Gy). These studies show the feasibility of measuring cell cycle delays in vivo, and future developments are suggested for a possible predictive test in patients receiving radiotherapy.

Animals↗
PubMed1993

In vivo measurement of the potential doubling time by flowcytometry in oropharyngeal cancer treated by conventional radiotherapy.

PURPOSE: Experimental and clinical studies suggest that the pre-treatment potential doubling time could be predictive of tumor control in patients treated by conventional radiotherapy and could help to identify the rapidly growing tumors for which accelerated radiotherapy is required. METHODS AND MATERIALS: To test this hypothesis, we studied prospectively 48 patients with a squamous cell carcinoma of the oropharynx and treated by conventional radiotherapy (70 Gy/7 weeks). The duration of S phase, the labeling index and the potential doubling time were obtained by flowcytometry measurements of a tumor biopsy obtained after injection of 200 mg bromodeoxyuridine to the patient. RESULTS: Three parameters were significantly associated with an increased risk of relapse namely the tumors size (T4; p < 0.01), the nodal status (> or = N2; p < 0.05) and the site of the primary within the oropharynx (p = 0.08). The S phase, labeling index, DNA index and potential doubling time were not significantly associated with an increased risk of relapse. However when considering only the T2 subgroup of patients, high labeling indexes and short potential doubling time were associated with an increased risk of relapse: the mean pre-treatment potential doubling time of the tumors which relapsed was 3.21 versus 5.5 days when there was no evidence of local relapse (p < 0.05). The mean labeling index for the group of tumors associated with a tumor recurrence was 11.7% compared to 7.3% when there was no evidence of relapse (p = 0.02). CONCLUSION: Factors other than proliferation play a role in determining the outcome of oropharyngeal cancers treated by conventional radiotherapy. However there was a significant correlation between short potential doubling time, high labeling index and tumor recurrence in the T2 subgroup of patients. The finding of significance for potential doubling time and labeling index in the T2 subset of tumors may be a reflexion of the more homogeneous nature of these tumors with regard to prognostic variables.

Aged↗
PubMed1991

Combined analysis of DNA ploidy index and N-myc genomic content in neuroblastoma.

The aim of the study was to assess, in a group of nonselected patients with neuroblastoma, the prognostic value of both N-myc gene amplification and DNA ploidy index, taking into account potential confounding factors such as age and stage. Of 59 patients studied, 23 were younger than 1 year at diagnosis, 31 presented with stage IV, 10 with stage III, 5 with stage II, 8 with stage I, and 4 with stage IV-S. N-myc genomic content was analyzed by Southern blot hybridization technique and N-myc amplification (greater than or equal to 3 copies/haploid genome) was present in 6 stage IV, 2 stage III, and 1 stage IV-S. The DNA ploidy index was analyzed by flow cytometry. Of the 59 neuroblastomas, 26 were diploid (DNA index, 1) and 33 were aneuploid (DNA index, greater than 1). The majority of the aneuploid tumors (28 of 33) were near-triploid with DNA indexes between 1.25 and 1.68, 4 were near-diploid (DNA index up to 1.18), and 1 was hypotetraploid (DNA index, 1.85). The proportion of near-triploid tumors was significantly greater among patients under 1 year of age and among patients presenting with stages I, II, and IV-S. Interestingly, 0 of 28 near-triploid neuroblastomas exhibited N-myc gene amplification, compared to 9 of 31 in the group of diploid, near-diploid, and hypotetraploid tumors (Fisher's exact test, P less than 0.001). Four factors were significantly related to a high risk of relapse in univariate analysis, i.e., age, stage, DNA index, and N-myc amplification. In multivariate analysis, only N-myc amplification and the DNA index remained significantly associated with a high risk of relapse. The 2-year disease-free survival rate was 94% (95% confidence interval, 77-98%) for patients with near-triploid neuroblastoma, compared to 45 and 11% (95% confidence interval, 32-70 and 4-23%) for patients with diploid or near-diploid tumors, without and with N-myc amplification, respectively. We concluded that the combination of N-myc and DNA index should be included in routine management of neuroblastoma.

Age Factors↗
PubMed1991

N-myc genomic content and DNA ploidy in stage IVS neuroblastoma.

DNA ploidy and N-myc genomic content were analyzed in a series of stage IVS neuroblastomas by flow cytometry and Southern blot hybridization, respectively. Of the 12 stage IVS neuroblastomas studied, nine were aneuploid (DNA index [DI] greater than 1), two were diploid (DI = 1), and one was not assessable for DNA content due to insufficient tumor material. N-myc gene amplification was present in two of 12 tumors. None of the aneuploid tumors exhibited N-myc amplification. Among the aneuploid neuroblastomas, the DIs were between 1.27 and 1.60, ie, in the near-triploid range. The follow-up from diagnosis ranged from 1 to 41 months (mean, 20 months). The nine neuroblastomas with near-triploid DNA content were free of disease at the end of the follow-up period. In contrast, a rapid and fatal tumor progression was observed for the three neuroblastomas with N-myc amplification and/or diploidy. Although involving only a limited series, these results strongly suggest that the combined analysis of DNA ploidy and N-myc genomic content could predict clinical outcome in stage IVS neuroblastoma and should help to identify patients for whom a more aggressive therapy is required.

Aneuploidy↗
PubMed1991

[Measurement of the kinetics of cell proliferation of cancer of the oropharynx in vivo by the incorporation of bromodeoxyuridine and flow cytometry].

Forty-six tumors from patients with oropharyngeal carcinoma were analysed by flow cytometry after injection of bromodeoxyuridine (Budr) for the labelling index, the duration of S phase and the potential doubling time (Tpot). The results show large variations in Tpot (from 2.6 to 16.7 days) among these tumors from the same site and with the same histology. The variations in Tpot were not significantly related to TNM status and differentiation grade. However, aneuploid tumors had statistically significant shorter Tpot. The predictive value of Tpot regarding the response to radiotherapy is currently under investigation.

Bromodeoxyuridine↗
PubMed1991

[Activation of N-myc oncogene and associated genes to chemoresistance, prognostic value for neuroblastoma].

N-myc amplification and ploïdic index are important prognosis factors in neuroblastoma. Combined overexpression of the multidrug resistance gene, MDR1 and of Glutathion-S-Transferase, GST-pi may be related to the response of tumors to chemotherapy. Measurements of these parameters may contribute to define responders and non-responders to chemotherapy and provide the clinician with additional criteria to manage treatment.

Drug Resistance↗
PubMed1990

Association between poor prognosis in early-stage invasive cervical carcinomas and non-detection of HPV DNA.

Human papilloma virus (HPV) DNA sequences (HPV types 16, 18, 33, 35 or uncharacterized) were detected by Southern blot hybridisation and polymerase chain reaction in 84% of 106 early-stage invasive carcinomas of the uterine cervix. Among HPV-positive patients, the risk of overall relapse did not differ with individual HPV types. Compared with HPV-positive patients, those with no detectable HPV DNA had a 2.6 times higher risk of overall relapse (p less than 0.05) and 4.5 times higher risk of distant metastases (p less than 0.01). The 24-month relapse-free survival rate in HPV-positive patients was significantly higher than that in HPV-negative patients (77% vs 40%), and the difference was similar (91% vs 56%) among those who were node-negative. These data indicate that HPV-negative cervical carcinomas may represent a biologically distinct subset of tumours that carry a poorer prognosis than do HPV-positive cancers.

Adenocarcinoma↗
PubMed1990

Radiation therapy for head and neck cancers in the elderly.

Three hundred and thirty-one patients, aged more than 70 years, were treated for an upper aerodigestive tract carcinoma from 1978 to 1983. Larynx accounted for 28% of the primary sites, oropharynx for 27%, and the oral cavity for 16%. One-third of these patients had a contraindication to anesthesia. The treatment was consistent with our protocols in only half of the cases. Fifty-nine patients underwent a radiosurgical combination; 249 underwent an exclusive irradiation with a curative intent. Fifty-four patients underwent a palliative irradiation, which lead up to a "curative dose" in half of the cases. The immediate and long-term tolerance of the irradiation was good. The local control was 71% for patients treated with a curative intent and 19% for the palliatively irradiated patients. Five-year survival of the population was 33%. No significant relationship between age, general status, and the carcinologic outcome could be observed.

Aged↗
PubMed1990

Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix.

The prognostic effect of c-myc oncogene overexpression was assessed in a multivariate analysis of 93 patients with invasive carcinoma of the cervix, stage Ib, IIa, and IIb proximal. The treatment was based on the association of brachytherapy-colpohysterectomy and lymphadenectomy. Analysis of c-myc gene expression was done using Northern and slot blot hybridization techniques. Overexpression of c-myc (ie, levels at least three times the mean observed in normal tissues) was present in 33% of the tumors. The proportion of carcinomas with c-myc overexpression significantly increased with the size of the primary tumor (P = .04). No relationship was found between c-myc overexpression and the other clinical and histologic parameters, including the nodal status. The relative risk of relapse (overall, pelvic failure, distant metastases) was analyzed in a Cox's proportional hazards model. Three factors were significantly related to the risk of overall relapse when the multivariate analysis was performed, namely, the tumor size, the nodal status, and c-myc expression. A combination of c-myc expression and the nodal status provided a very accurate indication of the risk of relapse. Indeed, patients with negative nodes had a 3-year disease-free survival rate of 93% (95% confidence interval [Cl], 79% to 98%) when c-myc was expressed at a normal level, whereas this rate was only 51% (95% Cl, 26% to 63%) when c-myc was overexpressed (log-rank test, P = .02). In addition, in the subgroup of patients with positive nodes, this rate was 44% (95% Cl, 25% to 77%) and 15% (95% Cl, 4% to 49%) when c-myc gene was expressed at normal level, or overexpressed, respectively. Finally, c-myc gene overexpression was, in the multivariate analysis, the first factor selected by the model regarding the risk of distant metastases.

Adult↗
PubMed1990

[Expression of P-glycoprotein 170 (GP 170) and drug resistance in human cancers].

In vitro models with multiple drug resistance (MDR) phenotype have been frequently related to hyperproduction of the 170 kd membrane glycoprotein, the so-called 170 GP. This protein is a pump able to extrude from cytoplasm drugs with various structures and mechanisms such as doxorubicin (DXR) or vinblastin (VLB). The MDR1 gene encodes the GP 170. MDR1 gene expression is low in most of the normal tissues, but high in some tissues such as colon, kidney, or liver. In these tissues, the GP 170 would ensure a detoxifying function related to cellular toxic compounds. There is a broad range of MDR1 gene expression in human tumors as a result of several factors. Of particular importance are the tissue origin from which the cancer derives and previous chemotherapy. In some cancers which often exhibit acquired chemoresistance, such as non Hodgkin's lymphomas, leukemias, sarcomas or neuroblastomas, an increase of MDR1 gene expression following previous chemotherapy has been frequently observed. Moreover in these cancers, a relationship between MDR1 transcript levels and clinical response to chemotherapy could exist as shown in several studies including one of ours. Hematosarcoma in the adult and some pediatric cancers seem to be models in which MDR1 gene expression may have a clinical relevance. Thus, an increase of MDR1 gene expression during the course of chemotherapy would lead the clinician to choose "non MDR related" agents such as DXR, VLB; or to use agents that are able to reverse MDR phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1989

Correlation of MDR1 gene expression with chemotherapy in neuroblastoma.

Forty-one neuroblastoma tumor specimens have been analyzed by Northern and slot blot hybridization techniques with human MDR1 gene probes. Only one of 15 (6%) tumors from patients who had not received chemotherapy exhibited high levels of MDR1 transcripts, while 11 of 26 (42%) treated tumors showed high levels of MDR1 expression (Fisher exact test: P = .03). The results indicate that the level of MDR1 mRNA expression is associated with previous chemotherapy, including drugs that select the multidrug resistance phenotype in vitro regardless of neuroblastoma tissue origin or N-myc content in the genome. For the 26 treated neuroblastomas, the number of nonresponsive tumors was found to be significantly higher among those with high levels of MDR1 mRNA.

Adrenal Gland Neoplasms↗
PubMed1989

Expression of a human multidrug resistance gene in ovarian carcinomas.

Expression of the human MDR1 gene has been shown to confer the multidrug resistance (MDR) phenotype to sensitive cells. To investigate the possible contribution of the MDR phenotype to chemoresistance in ovarian carcinoma, we have analyzed MDR1 gene expression in fresh carcinoma specimens from 50 patients. Fifteen received chemotherapy before surgery and were judged as poor responders. Thirty-five patients did not receive any drug before surgery. Control tissues were lymphocytes from 7 patients. Total RNAs were analyzed by Northern and slot blot hybridization techniques using human MDR1 complementary DNA and human gamma-actin complementary DNA probes sequentially as qualitative and quantitative controls. MDR1 transcripts (4.5 kilobases) were observed in the RNA preparations obtained from 3 of 10 patients who were treated with doxorubicin or vincristine, 2 drugs known to select the MDR phenotype in vitro. In 40 other RNA preparations obtained from 35 untreated patients and 5 patients treated exclusively with cyclophosphamide and cis-platinum, no transcript could be detected. Using the exact Fisher test, the difference between the 2 groups was found to be significant (P less than 0.01). The three tumors with elevated MDR1 expression did not show MDR1 DNA amplification. Our study suggests that, in spite of the weak occurrence of the MDR process in patients with ovarian cancers, MDR1 expression can be related to previous treatment with doxorubicin or vincristine. These results favor the expression of the MDR1 gene as one of the determinants involved in the acquired chemoresistance of ovarian cancers.

Cell Line↗