PubMed Health⌕ Search

Biomedical subjects

B Zafrani

Publications and source records attributed to B Zafrani.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cytogenetic study of 30 colorectal adenomas.

The cytogenetic analysis of 30 colorectal adenomas obtained from 24 patients is reported. Only normal karyotypes were observed in eight cases. Among the 22 adenomas with abnormal karyotypes, 15 showed clonal anomalies. Chromosome gains involving chromosomes 13, 20, 7, 9, and 12 were recurrently observed. Chromosome 18 was frequently lost or involved in translocations at bands q21-q22. More chromosome alterations were observed in the cases in which histologic examination revealed severe dysplasia or a carcinomatous component. These anomalies are discussed in relation to those described in colorectal adenocarcinoma.

Adenocarcinoma↗
PubMed1994

Ductal carcinoma in situ: a proposal for a new classification.

Details of a proposed new classification for ductal carcinoma in situ (DCIS) are presented. This is based, primarily, on cytonuclear differentiation and, secondarily, on architectural differentiation (cellular polarisation). Three categories are defined. First is poorly differentiated DCIS composed of cells with very pleomorphic, irregularly spaced nuclei, with coarse, clumped chromatin, prominent nucleoli, and frequent mitoses. Architectural differentiation is absent or minimal. The growth pattern is solid or pseudo-cribriform and -micropapillary (without cellular polarisation). Necrosis is usually present. Calcification, when present, is amorphous. Second, at the other end of the spectrum is well-differentiated DCIS, composed of cells with monomorphic, regularly spaced nuclei containing fine chromatin, inconspicuous nucleoli, and few mitoses. The cells show pronounced polarisation with orientation of their apical border towards intercellular spaces usually resulting in cribriform, micropapillary and clinging patterns, although a solid pattern of well-differentiated DCIS also occurs. Necrosis is uncommon. Calcifications, when present, are usually psammomatous. The third category, intermediately differentiated DCIS, is composed of cells showing some pleomorphism but not so marked as in the poorly differentiated group. There is, however, always evidence of polarization around intercellular spaces, although this is not so pronounced as in the well-differentiated group. These two criteria, cytonuclear differentiation and architectural differentiation, have been found to be more consistent throughout a DCIS lesion than previously employed criteria of architectural pattern or the presence or absence of necrosis.

Breast Neoplasms↗
PubMed1994

Mammographically-detected ductal in situ carcinoma of the breast analyzed with a new classification. A study of 127 cases: correlation with estrogen and progesterone receptors, p53 and c-erbB-2 proteins, and proliferative activity.

The new histologic classification proposed by Holland et al was applied to 127 cases of mammographically-detected ductal carcinoma in situ (DCIS). The relationship between histologic types and tumor cell expression of estrogen and progesterone receptors, p53 protein, c-erbB-2 oncoprotein, and proliferative activity markers was evaluated. There were 38 (30%) well differentiated, 39 (31%) intermediately differentiated and 50 (39%) poorly differentiated DCIS. Immunohistochemistry showed that 81% of the tumors were estrogen-receptor positive and 73% progesterone receptor positive. p53 protein and c-erbB-2 oncoprotein expression was identified in 40% and 57% of the cases, respectively. Growth-fraction determination with the Ki-67 antibody showed that 52% of the tumors had high proliferative activity. A highly significant association was found between the histologic types of DCIS and p53 protein, c-erB-b2 oncoprotein, and proliferative activity marker expression: these biological markers were more frequently overexpressed in less differentiated DCIS. No significant relationship with estrogen or progesterone receptor expression was noted. A strong relationship with the amount of tumor necrosis was also found. The clinical significance of these results should, however, be determined by long-term follow-up studies of patients with DCIS.

Adult↗
PubMed1992

Cytogenetic study of breast cancer: clinicopathologic significance of homogeneously staining regions in 84 patients.

A cytogenetic study performed on 84 primary breast cancers was conducted to detect the presence of chromosomes with homogeneously staining regions (HSRs) which are assumed to correspond to gene amplification. Homogeneously staining regions were found in 60% of the cases. To assess the prognostic significance of HSRs, clinical and pathologic data were correlated with the cytogenetic findings. Median follow-up for the 84 patients was 40 months. Differences in overall survival and disease-free survival rates between patients with HSRs (50 cases) and patients without HSRs (34 cases) were not significant. Although an excess of HSRs was found in patients considered to have poor prognostic factors (eg, young age, high histologic grade, metastatic axillary nodes, loss of hormonal receptors), no statistically significant correlation between variables could be demonstrated. The high percentage of cases with HSRs strongly suggests that they have an important biologic role, but more cases should be studied with a longer follow-up to assess their significance.

Adult↗
PubMed1992

Induction chemotherapy in advanced head and neck tumors: results of two randomized trials.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two randomized induction chemotherapy trials. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine and mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil by continuous infusion and vindesine. Local treatment was the same in the two trials: primary radiotherapy in all patients. The response was then evaluated; in the case of a poor response at 55 Grays surgery was performed; otherwise, radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial than in the first: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. The significance of the complete response at the end of the irradiation varies with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval were very similar in the two groups. The incidence of distant metastasis was significantly reduced (p less than 0.03) with chemotherapy. This trial suggests the need to test new chemotherapy protocols according to new schemes of treatment, with chemotherapy given concurrently with or following the completion of standard treatment by means of multicenter randomized trials.

Antineoplastic Agents↗
PubMed1992

[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients].

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Breast cancer genetic evolution: I. Data from cytogenetics and DNA content.

A general scheme of chromosome alterations occurring during tumor progression is proposed from the cytogenetic study of 113 breast carcinomas. For 76 of these tumors, chromosome numbers and rate of chromosome rearrangements were correlated with DNA content studied by flow cytometry. A series of 536 cases was used as control for flow cytometry. The following evolution can be proposed: 1. occurrence of unbalanced rearrangements decreasing chromosome number and DNA content; 2. correlatively to the rate of chromosome rearrangements, formation of endoreduplications leading to hyperploid sidelines; 3. persistence of the near diploid cells and decrease of chromosome number to about 35 and of DNA index to .85; 4. more frequently, elimination of the near diploid cells and complete passage to hyperploidy; 5. further losses of chromosomes in the hyperploid tumors, whose karyotypes can decrease to about 55 chromosomes and a DNA index of 1.35; 6. eventually, occurrence of a second endoreduplication, leading to an apparent near tetraploidy. The rate of rearranged chromosomes may reach 80% in both near diploid tumors with 35-40 and hyperploid tumors with 55-65 chromosomes which can be regarded as those with the highest degree of tumor progression. It is shown that the increase of chromosome number and DNA index above diploidy is very limited, and that all tumors with more than 50 chromosomes and 1.35 DNA content passed through endoreduplication. This results in many possible losses of heterozygosity in these cases.

Adenocarcinoma↗
PubMed1991

Recurrent homogeneously staining regions in 8p1 in breast cancer and lack of amplification of POLB, LHRH, and PLAT genes.

In a cytogenetic study of 125 primary and untreated breast cancers, 107 were selected for the quality of their metaphases permitting detection of amplifications:homogeneously staining regions (HSRs), abnormally banded region (ABRs), and double minutes (dmins). HSRs and ABRs were detected in 62 cases (58%), but no cases of dmins were observed. The localizations of HSRs and ABRs were not random because they were observed in the 8p1 position in 14 cases. The possible amplifications of five sequences, MOS (8q1), LHRH (8p21.1), POLB (8p11.2), PLAT (8p12), and D8Z2 (8c) were investigated in three tumors with HSR on the short arm of chromosome 8. Because these sequences were not amplified, two interpretations can be proposed: 1) there is a frequent amplification of a sequence from the 8p1 region, located between the investigated sequences; and 2) the amplifications do not occur in 8p1, but HSRs or ABRs of undetermined origin have a strong tendency to be translocated onto 8p. Because cases with HSR(8p) have less complex karyotypes than with HSRs in other locations, the first interpretation is the most likely: HSRs may be formed in 8p and further translocated on other chromosomes in the course of tumor progression.

Breast Neoplasms↗
PubMed1991

Prolonged G2 phase of breast cancer cells and chromosome damage.

5-bromodeoxyuridine incorporation was studied in metaphase chromosomes from 24 breast tumour specimens, including 23 adenocarcinomas. In these 23 cases, a slow cell cycle was observed, with a long (8 h) G2 phase. This slowing of the cell cycle, which was poorly related to the degree of polyploidy, was significantly related to the number of chromosome anomalies: the cell cycle was particularly slow when many rearranged chromosome were observed. These in vitro findings during the first cell cycle cannot easily be transposed to the in vivo situation. By analogy with Fanconi anaemia, in which both chromosome lesions and a long G2 phase are detected, a DNA repair defect and/or high DNA mutagenesis might exist in breast cancer cells.

Adenocarcinoma↗
PubMed1991

GST pi gene is frequently coamplified with INT2 and HSTF1 proto-oncogenes in human breast cancers.

The glutathione S-transferase gene (GST pi) is located on the same chromosome band (11q13) as proto-oncogenes INT2 and HSTF1 which are frequently amplified in breast cancer. Using the Southern blot technique, we looked for the amplification of the GST pi gene in 17 fresh tumors from human mammary carcinoma. The tumors were preselected because either they had an amplification of the INT2 proto-oncogene detected by dot blot, or their karyotypes exhibited or did not exhibit homogeneously staining regions, a cytogenetic character indicating amplification. Coamplification of GST pi, HSTF1 and INT2 was observed in five tumors, and coamplification of GST pi and HSTF1 without amplification of INT2 in another tumor. We also observed coamplification of GST pi, INT2, HSTF1 in the mammary carcinoma cell line MDA/MB134, whereas GST pi alone was amplified in the mammary epithelial cell line HBL100. These results indicate that INT2, HSTF1 and GST pi belong to the same large amplicon. Since GST pi is involved in intracellular detoxication and since chemotherapeutic drugs are among its substrates, it will be of interest to study GST pi gene expression as well as the response to chemotherapy in patients presenting this amplicon.

Blotting, Southern↗
PubMed1990

Characterization of chromosomal anomalies in human breast cancer. A comparison of 30 paradiploid cases with few chromosome changes.

A comparison of chromosomal anomalies detected in 30 cases of breast cancer in females with near-diploid karyotypes is reported. The tumors, of which 20 were previously unpublished, were selected for the relatively low complexity of their karyotypes, among a sample of 118 cases. Almost all of the 151 structural rearrangements detected were unbalanced, and 67% of breakpoints were located in or had contact with heterochromatin. In cases with few anomalies, rearrangements of chromosomes 1 and/or 16 were very frequent, leading principally to a gain of 1q and loss of 16q. In cases with more anomalies (5-16), deletions involving 17p, 4p, 13, 6q, 8p, 9p, 11p, and 11q and gains of 1q and 8q were the most frequent. Homogeneously staining regions (HSR) were detected in 14 tumors, mostly on 8p (6/22) and chromosome 19 (3/22). No double minutes (dmin) were observed. We conclude that trisomy 1q and monosomy 16q are early chromosomal changes in breast cancer, whereas other deletions and gain of 8q are clearly secondary events.

Adult↗
PubMed1990

[Treatment of borderline lesions and non-infiltrating carcinoma].

As mammography is increasingly prescribed systematically and mammography films are of better quality, diagnostic biopsies are performed in growing numbers, leading to the discovery of "borderline" histological lesions which were relatively rare a few years ago. The authors have studied the frequency and clinical presentation of these lesions. In patients with atypical hyperplasia simple monitoring is the rule since the short- and long-term effects of medical treatments are too uncertain for these to be recommended routinely. The finding at histology of lobular carcinoma in situ is regarded as indicating a high risk of cancer infiltrating both breasts, and in all but some special cases close supervision with 6-monthly clinical examination and annual mammography is advocated. Whether or not endocrine treatments reduce the incidence of infiltrating carcinoma is unknown. In patients with intraductal carcinoma mastectomy gives excellent results at the cost of a considerable loss of tissue. In view of the N.S.A.B.P. and Curie Institute experience, tumorectomy alone is not recommended because of the high risk of recurrence, but a conservative treatment (limited surgery followed by radiation) is permitted. Conservative treatment may also be attempted in Paget's disease without palpable tumour.

Breast Neoplasms↗
PubMed1990

Proto-oncogene amplification and homogeneously staining regions in human breast carcinomas.

Cytogenetic studies on fresh human breast cancers revealed that homogeneously staining regions (HSRs), which are assumed to represent DNA amplification, are observed in almost half of the cases. To search for a possible relationship between HSRs and proto-oncogene amplification, 16 proto-oncogenes, including ERBB2, were studied by Southern blot analysis in four tumors with two or three HSRs, and in three tumors without HSRs. Only four proto-oncogenes were found to be amplified in at least one tumor each: HST and INT2 (x3), MYC (x2-3), and FES (x greater than 10). The large sizes of the HSRs, which each corresponded to several percent of the haploid genome, were hardly compatible with the low rate of amplification, except for FES and then only if a large adjacent segment was co-amplified. This incomplete correlation was demonstrated by in situ hybridization, using biotinylated probes, which showed fluorescent spots on only one HSR for FES in one tumor and for INT2 in another one. Our results indicate that most of the large amplifications corresponding to HSRs do not involve the proto-oncogenes usually studied in breast cancer. The large amplification of FES, detected in one tumor, may be coincidental.

Blotting, Southern↗
PubMed1990

[Breast microcalcifications without palpable tumor detected using mammography. Anatomo-pathologic study technique].

Screening mammograms to detect early non palpable breast cancers will hopefully diminish the breast cancer mortality rate. However, proper pathologic examination of mammographically directed breast biopsies is mandatory. Sampling of a specimen containing microcalcifications should be directed by examination of the specimen radiogram. Frozen section of non palpable foci of microcalcifications is never performed. Thorough localization and sampling of the microcalcified lesions permit the detection of very small cancers usually of the intraductal type.

Breast Diseases↗
PubMed1989

Conservative treatment of early breast cancer: prognostic value of the ductal in situ component and other pathological variables on local control and survival. Long-term results.

Four hundred and thirty-four patients with infiltrative ductal carcinoma were treated by limited surgery and irradiation between January 1960 and December 1980. The median follow-up was 103 months. Retrospective pathological analysis of the primary tumor identified a subset of pathological parameters which were predictors of local breast failure and survival. Pathological predictors of local breast recurrence were: incomplete surgical excision (P less than 0.0001), lymphatic invasion (P less than 0.02) and presence of an extensive in situ component (EDISC) (P less than 0.03). Pathological predictors of survival were: incomplete surgery (P less than 0.007), size of the primary tumour (P less than 0.03), high histologic grade (P less than 0.005), lymphatic invasion (P less than 0.0001) and absence of associated in situ component (P less than 0.008). This study emphasizes the role of the in situ component in the prognosis of breast carcinoma treated with conservative management.

Breast Neoplasms↗