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H Pujol

Publications and source records attributed to H Pujol.

At least 55 records · Page 3Linked to original sources
PubMed1993

Androgen receptor gene mutation in male breast cancer.

We screened thirteen male breast cancers for the presence of germline mutations in exons 2 and 3 encoding the DNA-binding domain of the androgen receptor. These two exons were amplified from genomic DNA extracted from patients' white blood cells. In one of these thirteen patients, single strand conformation polymorphism and direct sequencing detected a guanine-adenine point mutation at nucleotide 2185 that changes Arg608 into Lys in a highly conserved region of the second zinc finger of the androgen receptor. This mutation occurred in a 38 year old man with partial androgen insensitivity syndrome and normal androgen-binding capacity in cultured genital skin fibroblasts. To our knowledge, only one germline Arg to Gln androgen receptor gene mutation has been previously reported at position 607 in male breast cancer. This androgen receptor mutation along with the Arg608 into Lys mutation we describe, suggests that this genetic abnormality is not fortuitous: a decrease in androgen action within the breast cells could account for the development of male breast cancer by the loss of a protective effect of androgens on these cells. Activation of estrogen regulated genes by the change of DNA-binding characteristics of the mutant androgen receptor cannot, however, be ruled out.

Adult↗
PubMed1993

HDL-cholesterol and breast cancer: a joint study in northern Italy and southern France.

The goal of the present study is to evaluate HDL-cholesterol (HDL-C) as a marker of breast cancer (BC) risk. It is based on several epidemiological and biological studies and is justified by the rising incidence of breast cancer throughout the world. A hospital-based study on host-related risk factors and breast cancer, conducted with similar methods in northern Italy and southern France, provided the biological data, the information on the established BC risk factors and on nutrition for 307 cases and 329 controls. This data set allowed for a thorough analysis of the relationship of HDL-C with established risk factors for BC and also of its association with BC at the time of diagnosis. Most of our findings on HDL-C determinants in the control sample are comparable to previous studies. The BC risk factors associated with reproductive life correlate with HDL-C levels: the protective factors are associated with a lower level of HDL-C and inversely. The same is true for nutritional factors such as alcohol. For these determinants, the trend is similar for cases and controls, and HDL-C level appears to be related to oestrogen metabolism. Thus it may be considered as a marker of BC risk. Our results indicate that high HDL-C levels should be especially checked in women aged > or = 60 years, or in premenopausal women presenting a low BMI, or in postmenopausal women with an early menopause.

Breast Neoplasms↗
PubMed1993

Potential value of increased MYC but not ERBB2 RNA levels as a marker of high-risk mastopathies.

MYC and ERBB2 levels were measured in 38 benign breast diseases using a semiquantitative in situ hybridization technique. Mean levels of MYC and ERBB2 gene expression in benign tissues were similar to those measured in 15 breast cancers with no amplification at the loci concerned. Interestingly, MYC but not ERBB2 RNA levels were increased (t-test, P = 0.03) in benign mastopathies of patients with a first-degree (mother/sister) family history (FH) of breast cancer. Among patients without a first-degree FH, MYC RNA levels were significantly higher (t-test, P = 0.02) during the follicular (preovulatory) than the luteal (post-ovulatory) phase and also significantly higher than levels observed in patients with no menstrual cycle (peri- or postmenopausal) (P = 0.004), indicating an in vivo hormonal regulation of MYC. After exclusion of the first-degree FH patients a higher MYC expression was detected in atypia than in other histological types at the follicular but not at the luteal phase, suggesting an increased sensitivity of these high-risk lesions to estrogens. We propose that in addition to a family history and proliferative atypia, elevated MYC RNA levels during the post-ovulatory phase could potentially be used as a marker of the risk of developing breast cancer. The increase in MYC RNA in high-risk breast diseases also suggests that MYC deregulation might be involved in the early stages of mammary carcinogenesis.

Breast Diseases↗
PubMed1992

[Appendiceal carcinoid tumor of systematic detection. When to propose right hemi-colectomy and how to monitor? Thoughts apropos of a case and review of the literature].

In relation to a case of carcinoid tumor of the appendix discovered after appendectomy and already metastatic, we discuss the prognostic factors of these lesions. Size is the most important one. For tumors less than two centimetres diameter, site, mesoappendix and lymph node involvement do not fully summarize the aggressiveness of the disease. We would like to emphasize the poor prognosis of perineural involvement, especially for young patients, in order to discuss the indication for salvage right colectomy. A positive reaction to Neuron-Specific Enolase allows this enzyme to be proposed as a postoperative serum marker.

Adult↗
PubMed1991

Zinc and copper in breast cancer. A joint study in northern Italy and southern France.

The relationship between breast cancer and two trace elements, zinc (Zn) and copper (Cu), was investigated by means of an hospital based case-control study at Milan (Italy) and Montpellier (France). Variables concerning dietary intake of Zn and Cu (in Milan) and their blood levels (both in Milan and Montpellier) were measured. Dietary intake, evaluated through a questionnaire of the dietary history type, and blood levels of Zn and Cu were measured in 261 cases and 261 controls. Cu blood level showed a contradictory tendency in the two samples (higher in controls in Milan, higher in cases in Montpellier), which tended to lessen after adjustment for related variables. No odds ratios (OR) in the different quantiles, nor X2 for trend reached statistical significance. A sharp difference was evidenced on the opposite with regard to Zn blood values in cases and controls. In both samples Zn mean values are significantly higher in cases than in controls, and the difference remains significant in the two samples even after adjustment for related variables. The pooled OR computed from the two samples, after adjustment for known risk factors and related variables, reaches in the fourth quartile a value of 9.5 (CI: 4.9-18.2). Dietary intake of the two minerals (measured only in Milan sample) showed no difference between cases and controls, but a stronger relationship between dietary and blood Zn was evidenced in cases with respect to controls. The authors suggest that the higher Zn level in cases might be related with an higher incorporation of Zn in cancer cases and that the same mineral might play a possible role in tumor growth promotion.

Adult↗
PubMed1991

Exclusive radical radiation therapy in breast carcinoma.

We present the results of 186 breast cancer patients treated initially for locoregional disease by radiotherapy alone, combining cobalt therapy with external electron beam or interstitial iridium implants. According to the TNM classification, the patients were distributed as follows: 3 T1N0, 2 T1N1, 33 T2N0, 36 T2N1, 16 T3N0, 26 T3N1, 6 T3N2, 14 T4N0, 29 T4N1, 9 T4N2 and 12 T4N3. The 5- and 10-year survival rates (52.7% and 36.5%, respectively, for all patients) were directly correlated with the size and location of the breast tumor, and the extent of lymph node involvement. Locoregional recurrence was observed in 39.8% of the cases, metastasis alone in 26.8% of the cases, and a combination of local recurrence and distant metastasis in 14.5% of the cases. The local recurrences and metastases were directly correlated with the extent of locoregional involvement. Late complications and sequelae were mostly minor and occurred in less than 25% of the cases; severe sequelae occurred in no more than 2% of the cases. They depended on the initial tumor volume and the tumor dose. Our results, along with those in the literature, indicate that radiotherapy administered alone is a valid therapeutic option in breast cancer.

Brachytherapy↗
PubMed1991

Cancer of the anal canal: report on the experience of 61 patients.

We report our experience on 61 anal canal epidermoid carcinoma bearing patients. The patients are divided into three therapeutic groups: a) 14 patients treated with combined surgery and preoperative radiotherapy (37.8 Gy in 18 fractions and 21 days); b) 28 patients treated with 60Co and electrontherapy (total tumor dose of 60 to 65 Gy); c) 19 patients treated with external cobaltherapy (30 Gy/10 fractions/12 or 15 days) followed 1 to 2 months later by interstitial brachytherapy with Iridium 192 (20 Gy). Local control was observed in 41 out of 61 patients (67.2%). Out of the six patients who underwent salvage abdomino-perineal resection, five were locally cured at 5 years. The overall 5-year survival is 78.6%; the corrected 5-year survival is 88.8%. Analysis of prognosis factors shows a direct relation between local control survival and the loco-regional extension. The 5-year survival was 90.9% in the first therapeutic group, 90.9% in the second group, and 94.7% in the third group. The 5-year survival rates according to the stage and to treatment were as follows: Stage T1 N0 100% in the 1st therapeutic group, 85.7% in the 2nd group, 100% in the 3rd group; for Stage T2 N0 80% in the 1st group, 90.9% in the 2nd group, 90% in the 3rd group; for Stage T3 N0 83.3% in the 1st group, 85.7% in the 2nd group, and 66.6% in the 3rd group. The rates of sphincter preservation were 85.7% in the 2nd group and 94.7% in the 3rd group. These results show the incidence of loco-regional extension on the prognosis and the usefulness of conservative treatments.

Anus Neoplasms↗
PubMed1991

Characterization of proliferative cells in malignant melanomas and their inflammatory infiltrates.

Distinct changes in the antigenic phenotypes of mononuclear cells infiltrating primary and metastatic malignant melanomas (MM) have been shown to characterize distinct steps of melanoma progression. The purpose of our study is to establish whether the growth fraction of malignant melanoma cells is related to the mononuclear cell subtypes. Using monoclonal antibody Ki67, the presence of a nuclear antigen in proliferating cells of both tumor and inflammatory infiltrate cells was established in 20 primary recurrent and metastatic cutaneous melanomas. Monoclonal antibodies against lymphocyte and macrophage subsets were also applied in situ. Numerous CD8 and CD4 positive cells and natural killer (NK) cells were detected in all the infiltrates. A low CD4+/CD8+ ratio was observed in most tumors with a high proliferative activity. The presence of positive CD1+ cells seemed also to be correlated with a high activity. Our data suggest a correlation between inflammatory cell subsets and proliferative activity of MM.

Antigens, CD↗
PubMed1991

Decrease of c-erbB-2 and c-myc RNA levels in tamoxifen-treated breast cancer.

The c-myc, c-erbB-2, hst and int-2 oncogenes are frequently amplified and/or overexpressed in human breast carcinomas. We studied the effect of tamoxifen on RNA levels of these oncogenes in 19 breast cancer patients treated for 3 weeks prior to surgery as compared with 22 control patients. RNA levels were measured by in situ hybridization coupled with computer-aided quantification. c-myc and c-erbB-2 expression was high in the control population (mean values: 23.4 and 29.1 grains/cell respectively) and significantly decreased in the tamoxifen-treated population (mean values: 14.6 and 7.4 grains/cell respectively) (P = 0.018, P = 0.003 respectively); hst and int-2 RNA levels were low (2-6 grains/cell) and not significantly altered by the treatment. There was a correlation between gene amplification and expression for c-erbB-2 (P = 0.0005) and hst (P = 0.02) in the control population. Elevated c-erbB-2 RNA level was correlated with the absence of estrogen (P = 0.02) or progesterone (P = 0.05) receptors. In the ER+ population, the tamoxifen-treated group had significantly lower c-myc expression levels than the control group (P = 0.04) which is in agreement with the estrogen induction of c-myc in ER+ T47D cell line and its inhibition by antiestrogens. Surprisingly, c-erbB-2 expression in the tamoxifen-treated group was significantly diminished in the ER- (P = 0.02) and PR- (P = 0.01) populations. This effect was not observed in the ER- BT474 cell line. These results suggest that in vivo tamoxifen decreases c-myc and c-erbB-2 RNA levels in breast cancer cells via two different mechanisms. To our knowledge this is the first evidence of in vivo down regulation of a gene by tamoxifen in ER- breast cancer cells.

Adult↗