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J Simony

Publications and source records attributed to J Simony.

At least 19 recordsLinked to original sources
PubMed1998

[Biological perspectives].

The tumour biology of non-small cell bronchial cancer integrates recent developments and a dynamic schema of the phenomena of tumour progression and diffusion of the metastatic disease. There is no leap of known biological disruption between Stage II and Stage III. The latter is defined by anatomical criteria and is a transition in the continuum of the natural history of these cancers. The moto for the tumour progression is the genotypic instability and phenotypic diversification. Metastatic microscopic disease constitutes the first cause of failure in the treatment of Stage III non-small cell bronchial cancer. Among prognostic factors for survival emphasis is placed on the alterations of p53 expression, different types of aneuploidy, anomalies of the expression of cellular adhesion molecules and finally, tumour diversification towards a metastatic phenotype.

Aneuploidy↗
PubMed1997

Immunohistochemical detection of p53 protein and prognosis of surgically resected non-small-cell lung cancer.

We analyzed the survival of 89 surgically treated patients presenting non-small-cell lung cancer in regard to the accumulation of p53 protein as detected by indirect immunoperoxidase reactivity of PAb1801 anti-human p53 protein. Although the well-known factors such as stage grouping, tumor status, and nodal status were found to be prognostic determinants, the p53 protein accumulation had no effect on either univariate analysis or multivariate analysis of survival.

Adult↗
PubMed1996

Hypodiploidy, Ki-67 growth fraction and prognosis of surgically resected lung cancers.

One hundred and thirty-seven lung cancer patients (123 non-small-cell lung cancers (NSCLC), 10 small-cell lung cancers (SCLC) and four carcinoid tumours) who underwent surgery in an attempt at complete resection were prospectively entered in a study whose aim was to determine the prognostic significance of a hypodiploidy or a multiploidy pattern of tumour cell DNA content and a high immunohistochemical reactivity of Ki-67, a nuclear antigen related to the cell cycle. Indirect immunoperoxidase reactivity of Ki-67 on frozen tumour tissue sections was evaluated both visually, using a classical semiquantitative scale, and by means of a computer-assisted image processor. Cell DNA content analysis was done using static computer-assisted cytometry on tumour cytological prints stained by the pararosaline Feulgen-Schiff technique. The ploidy was characterised for each tumour by DNA index (DI), percentage of hypodiploid cells and type of DNA content histogram (near diploid, hyperdiploid, hypodiploid and multiploid). Ki-67 immunostaining was negative in 64 tumours (48%) and positive in 69 (52%). DNA histogram classification disclosed 57 (42%) near diploid tumours. Among the 80 (58%) aneuploid tumours, 16 were hypodiploid, 44 hyperdiploid and 20 multiploid. The prevalence of both a positive Ki-67 immunostaining and an aneuploid DNA histogram differed according to histology as SCLC demonstrated a higher frequency of both features when compared with NSCLC and carcinoid tumours. On the other hand, Ki-67 immunostaining and ploidy did not significantly differ according to degree of differentiation, nodal status and Mountain's stage grouping. The percentage of cells in the hypodiploid modal DNA was significantly higher for tumours which demonstrated a high Ki-67 immunostaining, suggesting a link between growth fraction and DNA content abnormalities. In univariate analysis, survival did not differ significantly according to either the Ki-67 immunohistochemical reactivity or the DNA index. Patients with a hypodiploid tumour had a shorter survival than patients with other DNA histogram patterns but, owing to the low frequency of hypodiploidy, this difference did not reach statistical significance. In Cox's proportional hazard model, an SCLC histology, an advanced tumour status, a positive nodal status and a hypodiploid tumour (hazard ratio: 2.070; 95% confidence interval 1.041-4.116) were significant determinants of survival. We conclude that hypodiploidy in lung cancer is a distinct DNA content abnormality as it contributes significantly to prognosis. Neither visually assessed nor computer-generated Ki-67 immunostaining measurements significantly determine prognosis.

Adult↗
PubMed1995

Phase I study of percutaneous 4-hydroxy-tamoxifen with analyses of 4-hydroxy-tamoxifen concentrations in breast cancer and normal breast tissue.

4-OH-tamoxifen is an active metabolite of tamoxifen that is detectable in the serum and tumour tissue of patients treated by oral tamoxifen. As this metabolite penetrates through the skin, it is possible to compare percutaneous 4-OH-tamoxifen (4-OH-TAM) and oral tamoxifen treatments. We report herein a randomized study of percutaneous 4-OH-TAM versus oral tamoxifen in women with breast cancer. This pharmacology study was designed to compare the 4-OH-TAM concentration in breast cancer and normal breast tissue according to the route and dose used for administration of tamoxifen after a 3-week period prior to surgery and tissue sampling. Women were randomized into one of the five following groups: group I, oral tamoxifen given at 10 mg twice a day; group II, 4-OH-TAM delivered percutaneously at 0.5 mg day to both breast areas; group III, 4-OH-TAM applied percutaneously at 1 mg/day to both breast areas; group IV, 4-OH-TAM delivered percutaneously at 1 mg/day to a large cutaneous area excluding the breasts; and group V, 4-OH-TAM applied percutaneously at 2 mg/day to a large skin area excluding the breasts. 4-OH-TAM plasma and tissue concentrations were significantly higher in the oral tamoxifen group as compared with either the high- or the low-dose percutaneous 4-OH-TAM group. In group II, percutaneous 4-OH-TAM treatment resulted in tissue concentrations of 1,446 and 352 pg/g in tumour tissue and normal breast tissue, respectively. In group I these concentrations were as follows: tumour tissue, 12, 453 pg/g; and normal tissue, 10,214 pg/g. 4-OH-TAM concentrations in tumour tissue and normal breast tissue did not significantly differ in any group. In the oral group we observed classic effects on coagulation and lipid metabolism when pre- and post-treatment values of these biological variables were compared, whereas no difference was observed in the percutaneous group. Although percutaneous administration of 4-OH-TAM led to a low plasmatic concentration of this active metabolite, the breast tissue concentration remained lower than those observed after oral tamoxifen treatment. Therefore, at the doses described in this study, percutaneous 4-OH-TAM cannot be proposed as an alternative tamoxifen treatment.

Administration, Cutaneous↗
PubMed1993

Immunohistochemical study of P-glycoprotein distribution in lung cancer.

Indirect immunoperoxidase was used to determine the reactivity of C219 (P-glycoCHEK C219, Centocor Diagnostics, Malvern, PA), a monoclonal antibody (Mab) with high affinity for an internal epitope of the P-glycoprotein encoded by the multidrug resistance (MDR1) gene, in 40 surgically resected primary lung tumours. C219 reactivity was qualitatively classified in seven small cell lung cancers (SCLC), 29 non small cell lung cancers (NSCLC), and four carcinoid tumours. Ploidy was analysed by means of static cytometry using a computer-assisted image processor following Feulgen staining of cytologic prints of 32/40 lung tumours. Indirect immunoperoxidase reactivities of Mabs S-L 11.14 and MOC-1 were also studied to characterize the expression of cluster 1 lung cancer antigens and hence to determine among the NSCLC those which expressed the neural cell adhesion molecule (NCAM). Eighteen (45%) lung tumours strongly expressed P-glycoprotein as an immunostaining of many islets of malignant cells or almost all malignant cells. In addition, 8/40 tumours (20%) showed a weak reactivity (few immunostained cells) and 14/40 (35%) no reactivity. There was no difference of reactivity when NSCLC were compared with SCLC. The expression of P-glycoprotein in NSCLC did not vary significantly when the stage of disease was considered. Among the 29 NSCLC, 10 (36%) expressed S-L 11.14 and MOC-1. The NCAM positive NSCLC did not show any difference of P-glycoprotein expression in comparison with NCAM negative ones. Finally, C219 immunoperoxidase reactivity did not significantly differ according to the ploidy status. In conclusion, the internal epitope of the P-glycoprotein encoded by the MDR1 gene is frequently expressed by lung tumours of any histological type. This expression is not higher in Stage III and IV lung cancers in comparison with Stage I and II ones, or in NSCLC in comparison with SCLC either. Thus, the C219 related epitope seems to have a weak implication in the lower chemosensitivity of both advanced stages and NSCLC.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Neural cell adhesion molecule and prognosis of surgically resected lung cancer.

The prognostic significance of the expression of neural cell adhesion molecule (NCAM), a neuroendocrine antigen in lung cancer, was analyzed by an indirect immunoperoxidase method in 97 surgically treated patients. Reactivity of MOC-1 and S-L 11.14, both cluster-1 monoclonal antibodies directed against NCAM, was positive in all nine small-cell lung cancers and in 16 of 88 (18%) non-small-cell lung cancers. For the latter group, this expression demonstrated a phenotypic heterogeneity that was mainly observed in poorly differentiated squamous cell carcinomas and in stage N2 non-small-cell lung cancers. Patients with NCAM-positive non-small-cell lung cancer proved to have a shorter survival than those with NCAM-negative disease. In Cox's model for multivariate analysis, nodal status and histology were the main independent determinants of prognosis. We therefore concluded that NCAM expression in non-small-cell lung cancer is correlated to nodal status and that it indicates a poor prognosis. These findings confirm that the diversification of lung cancer phenotype leads to tumor progression and brings a negative prognosis to surgically resected non-small-cell lung cancer. However, nodal status remains the most important prognostic variable, suggesting that NCAM expression is only one of numerous biological events that promote tumor progression.

Adenocarcinoma↗
PubMed1993

[Percutaneous endoluminal angioplasty using balloon catheter in peripheral arteriopathies of the lower limbs].

Dilatation using an inflatable catheter is the best and most commonly used percutaneous endoluminal treatments for arteriopathy of the legs. We now have enough follow-up to say that it has acquired a position beside surgery without opposing this as the two methods are often complementary. The indications have been extended and the results, for certain types of lesion, are similar to those achieved with surgery, with the advantages specific to this method. Complications remain limited and can often be dealt with during this procedure by means of other percutaneous methods (installation of endoprostheses, fibrinolysis, thromboaspiration).

Angioplasty, Balloon↗
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↗
PubMed1990

In situ evaluation of growth fraction determined by monoclonal antibody Ki-67 and ploidy in surgically resected non-small cell lung cancers.

Ploidy and growth fraction were analyzed by means of a computer-assisted image processor in surgically resected non-small cell lung cancer (NSCLC). This study was done in order (a) to evaluate the distribution of anti-Ki-67 immunostaining and (b) to correlate this distribution to ploidy status and pTNM stage of NSCLC. Thirty-two patients underwent a surgical resection for primary NSCLC following complete staging. Indirect immunoperoxidase reactions of monoclonal antibody Ki-67 were done on frozen tissue sections. Integrated optical density and index of stained nuclear surface were calculated by means of a computer-assisted image processor in 120 fields of each preparation in order to quantify the Ki-67 immunostaining. DNA content was determined by means of cytometry of Feulgen-stained cytological prints. The ploidy status was defined for each tumor by DNA index, percentage of hypodiploid cells, and type of DNA content histogram (near diploid, hyperdiploid, hypodiploid, and multiploid). Reproducibility of immunostaining quantitative analysis was demonstrated by iterative measurements of the same slide. Intratumoral heterogeneity of Ki-67 immunostaining induced integrated optical density variation assessed on six nonconsecutive tissue sections from at least two regions of the same tumor. This intratumoral variability was 15 times lower than integrated optical density variability between tumors. The Ki-67 immunostaining varied significantly according to the DNA content histogram type (P less than 0.05, Kruskal-Wallis test); most of the specimens with high Ki-67 immunostaining were multiploid or hypodiploid. Moreover, Ki-67 immunostaining correlated to the percentage of hypodiploid cells. Ki-67 immunostaining and ploidy status did not vary significantly according to the tumor-nodes-metastasis stage. We conclude that (a) quantitative analysis of Ki-67 immunostaining is a reliable evaluation of growth fraction in NSCLC if a large number of fields are analyzed to take into account intratumoral variability, (b) hypodiploidy and multiploidy are frequent abnormalities of DNA content, (c) Ki-67 immunostaining is significantly higher in hypodiploid and multiploid tumors. Thus, determination of growth fraction and ploidy in surgically resected NSCLC specimens may be considered as complementary prognostic parameters independent of the stage of the disease.

Adenocarcinoma↗
PubMed1989

Phenotypic heterogeneity studied by immunohistochemistry and aneuploidy in non-small cell lung cancers.

Non-small cell lung cancers (non-SCLC) differ from small cell lung cancers (SCLC) by many clinical features and prognosis. However, recent studies suggest that lung cancer heterogeneity frequently leads to the association of SCLC and non-SCLC in the same tumor. This phenotypic heterogeneity can be analyzed by immunohistochemistry using monoclonal antibodies (Mab) raised against differentiation related antigens. It may have clinical relevance inasmuch as the diversification of malignant cells is a well-known factor of tumor progression and may be due to chromosomal instability because inappropriate gene expression leads to the formation of antigens unrelated to cell lineage. Chromosomal instability in cancer leads to aneuploidy detectable by cell DNA content analysis. In a prospective study, we analyzed, in parallel, the expression of neuroendocrine related antigens by immunohistochemistry and the cell DNA content in frozen specimens from 40 patients who underwent complete surgical resection of primary non-SCLC in an attempt (a) to characterize the phenotypic heterogeneity and (b) to determine whether this heterogeneity is correlated with aneuploidy and clinical staging. Three Mabs were used in association as a marker of neuroendocrine antigen expression (S-L 11.14, MOC-1, and NE-25); reactivity of these Mabs in 9 SCLC and 3 lung carcinoid tissue sections was used as positive control. All SCLC and 2 of 3 lung carcinoids tested were homogeneously positive with Mabs S-L 11.14, MOC-1, and NE-25; 13 of 40 non-SCLC were homogeneously positive and 11 additional specimens focally positive with Mabs S-L 11.14, MOC-1, and NE-25. The frequency of this abnormal phenotype was significantly higher in poorly differentiated squamous cell carcinomas (chi 2 10.08; P less than 0.005), in clinical stage III non-SCLC (chi 2 5.93; P less than 0.02), and in tumors involving mediastinal lymph nodes (chi 2 5; P less than 0.03). The percentage of cells in the modal DNA of G0-G1 phase was significantly lower in non-SCLC homogeneously positive with Mabs S-L 11.14, MOC-1, and NE-25 [27.4 +/- 10.3% (SD)] in comparison with non-SCLC negative with these same Mabs [56.8 +/- 21.3%; P less than 0.01, Mann-Whitney U test]. We conclude that (a) mixed SCLC-non-SCLC differentiation is frequent and can be assessed by immunohistochemistry, (b) neuroendocrine differentiation in non-SCLC is mainly observed in poorly differentiated tumors and in advanced clinical stages, and that (c) this heterotopic phenotype is correlated with aneuploidy and has clinical implications.

Adult↗
PubMed1989

Tamoxifen treatment increases the concentration of 52K-cathepsin D and its precursor in breast cancer tissue.

The pro-cathepsin D of Mr 52,000 is regulated by estrogens via the estrogen receptor (RE) and is secreted by breast cancer cells in vitro. In an attempt to predict the hormone responsiveness of breast cancer in vivo, we have assayed total 52K cathepsin D and its precursor in the primary breast cancer cytosol of 36 patients treated before surgery with 30 mg of tamoxifen daily for 1 to 5 weeks (average, 3 weeks). Compared to a similar control population, total 52K cathepsin D was increased by tamoxifen (P = 0.02) but less so than its precursor (P less than 0.001). Furthermore, 45% of the RE-positive tumors from tamoxifen-treated patients had a higher cathepsin D precursor concentration than the same type of tumor from control patients, or than RE-negative tumors from tamoxifen-treated patients. This 3-week challenge test was probably too short to avoid partial estrogenic activity of tamoxifen (flare) and the authors infer that longer time of treatment would decrease rather than increase the concentration of cathepsin D in the RE-responsive tumors. However, two cancers from patients with relapses after prolonged tamoxifen treatment (greater than 6 months) also had high concentrations of 52K cathepsin D and its precursor. The authors conclude that the concentration of cathepsin D and its precursor in breast cancer cytosol can be increased by short-term tamoxifen treatment, suggesting that these tumors are estrogen responsive.

Adult↗
PubMed1989

Inaugural intra-atrial neoplastic thrombosis in stage II Hodgkin's disease.

We report the first case of intra-atrial neoplastic thrombosis discovered in the initial stage of Hodgkin's disease. Considering the course of the case and the recurrence after 18 months we emphasize the necessity of screening cardiac cavities by CT Scan with a bolus, and of treating such a case as an initial stage IV Hodgkin's disease.

Adult↗
PubMed1988

Immunoenzymatic assay of Mr 52,000 cathepsin D in 182 breast cancer cytosols: low correlation with other prognostic parameters.

The Mr 52,000 cathepsin-D-like protease induced by estrogens in MCF7 human breast cells was assayed in 182 primary breast cancer cytosols prepared for receptor assays from pre- and post-menopausal patients. Using two solid-phase sandwich immunoenzymatic assays, we quantified the total Mr 52,000 cathepsin D (52K-cath-D) (the Mr 52,000 precursor protein and its Mr 48,000 and 34,000 processed forms) and the Mr 52,000 precursor alone. The value of total 52K-cath-D varied between 3 and 165 pmol/mg protein and the proportion of the precursor varied from 0 to 28% of total 52K-cath-D. There was no correlation between the concentrations of 52K-cath-D and estrogen receptor, but the estrogen receptor status (greater than or less than 10 fmol/mg protein) was correlated to the 52K-cath-D status (greater than or less than 15 pmol/mg protein) according to the chi 2 test (P less than 0.001). The correlation with progesterone receptor concentrations and status was low (r = 0.43) and absent, respectively. There was no correlation with Scarff and Bloom stages, tumor size, or patient's age. The percentage of patients with invaded lymph nodes was significantly higher (80%) in the subgroup with the highest total 52K-cath-D levels (greater than or equal to 42 pmol/mg protein), representing only 12% of the population but not in the total population. On the basis of this prospective study, before clinical follow-up can be evaluated, we conclude that in the total population examined, the 52K-cath-D concentration was only correlated with estrogen receptor status, but not with any other prognostic parameter.

Aged↗