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Biomedical subjects

K Steck

Publications and source records attributed to K Steck.

11 recordsLinked to original sources
PubMed1999

Numerical chromosomal changes in DNA hypodiploid solid tumors: restricted loss and gain of certain chromosomes.

BACKGROUND: DNA hypodiploidy is a unique and rare finding associated with aggressive behavior in solid tumors. Identifying the chromosomal changes underlying this feature may provide important information on the development and progression of these neoplasms. METHODS: Fluorescence in situ hybridization analysis using alpha-satellite probes for nine autosomes and the two sex chromosomes was performed on interphase cells from 27 solid tumors which had been shown to be DNA hypodiploid by flow cytometry. The chromosomal abnormalities were correlated with the DNA index and tumor subtypes. RESULTS: The data show mutually exclusive loss of certain chromosomes and compensatory gain of other chromosomes in different tumors. The net loss was slightly more than the net gain for the chromosomes tested. Polysomy of chromosome 7 and monosomy of chromosomes 17, X and loss Y were found in most tumors. Significant differential loss of chromosomes 6,10, and 12 among DNA hypodiploid breast, kidney and lung carcinomas was noted. CONCLUSIONS: Our study shows (i) gain of chromosome 7 and loss chromosome 17 in most DNA hypodiploid tumors, (ii) specific chromosomal loss was noted in breast and renal cell carcinomas, and (iii) that different mechanisms for DNA hypodiploid and hyperdiploid development may exist.

Adult↗
PubMed1996

Flow cytometric analysis of apoptosis and bcl-2 in primary breast carcinomas: clinical and biological implications.

Analysis of programmed cell death (apoptosis), of bcl-2, a critical regulator of this process, and of the proliferative fraction may provide detailed information on the biologic characteristics of tumor cell populations. To investigate the potential role of these parameters in assessing mammary carcinoma, we adapted flow cytometric procedures for concurrent measurement of apoptosis, bcl-2 expression, and cell proliferation in 54 primary breast carcinomas and correlated the findings with traditional clinicopathologic information. Overall, a significant inverse relationship between apoptosis levels and bcl-2 expression was observed (P = 0.005). Apoptosis levels correlated significantly with DNA aneuploidy (P = 0.03) and S + G2M fractions (P = 0.005) of these tumors. A significant correlation between bcl-2 expression and estrogen receptor positivity (P = 0.05) and DNA diploidy (P = 0.02) was noted. Bcl-2 expression, however, was inversely correlated with S + G2M fractions (P = 0.001). We conclude that analysis of apoptosis and bcl-2 by flow cytometry allows further characterization of tumor cell populations that may be useful for prognostic and therapeutic management of breast carcinoma.

Adult↗
PubMed1996

Bivariate RNA and DNA content analysis in breast carcinoma: biological significance of RNA content.

Flow cytometric studies of mammary carcinoma have been limited to DNA content analysis. Simultaneous analysis of DNA and RNA has been applied to hematological and certain solid neoplasms and has been shown to provide valuable information in the clinical assessment of these tumors. To determine whether measuring RNA content during flow cytometric analysis provides additional information in the clinical assessment of breast carcinoma, dual-parameter analysis of DNA and RNA content on freshly disaggregated breast carcinoma specimens was performed. RNA content, divided along the mean (</=1.6 and >1.6), correlated with tumor grade, histological type, hormonal status, and patient survival. DNA aneuploidy was noted in 247 (69.2%) neoplasms and correlated significantly with tumor grade and stage but not with clinical outcome. The proliferative fraction, defined as S + G2-M and dichotomized along the mean value (</=10% and >10%), correlated significantly with tumor grade, size, hormonal status, lymph node involvement, and survival. Cox's proportional hazard analysis revealed that RNA content, proliferative fraction, and tumor stage are independent prognostic indicators. Our results indicate that measurement of cellular RNA content provides additional biological information that may be useful in the clinical assessment of breast carcinoma.

Adult↗
PubMed1995

Heterogeneity of the proliferative fraction and cyclin D1/CCND1 gene amplification in head and neck squamous cell carcinoma.

High proliferative fraction and cyclin D1/CCND1 gene amplification have been associated with certain aggressive features of head and neck squamous carcinoma in some studies, but not in others. The differences may be related to the intratumoral heterogeneity of these factors. Moreover, the interrelationship between these seemingly related factors has not been determined. In order to determine the correlation between tumor proliferative fractions and CCND1 gene amplification, 3 spatially different samples from each of 32 primary head and neck squamous cell carcinomas (HNSCC) were separately analyzed by flow cytometry. A mixture of these specimens was also minced and snap frozen for molecular studies. DNA was extracted from patient lymphocytes, normal appearing squamous epithelium, and tumors. A genomic DNA probe containing the first exon of CCND1 was used for hybridization by Southern technique. A 5.6 kb genomic DNA probe of immunoglobulin heavy chain was used as an internal standard for quantification of CCND1 gene amplification. Our results showed that 30% of the tumor cases manifested intratumoral heterogeneity (> 50% differences) of their proliferative activity. The highest value was used for correlation with gene amplification. Eleven (34.4%) of the 32 tumors showed CCND1 amplification (2-10-fold). When the proliferative fraction was dichotomized into high and low groups based on the mean value (> or = 13%), a highly statistical correlation between CCND1 amplification and tumor proliferation was obtained (P < 0.001). No significant correlation between gene amplification and other clinicopathologic parameters was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Southern↗
PubMed1994

Comparative flow cytometric analysis of Ki-67 and proliferating cell nuclear antigen (PCNA) in solid neoplasms.

The proliferation associated antigens, Ki-67 and proliferating-cell nuclear antigen (PCNA), have been widely used in studies assessing the growth fraction in human malignancies. It remains unclear, however, whether these markers yield similar assessments of proliferative activity in any given neoplasm. In this study, we compared Ki-67 and PCNA expression in 93 malignant solid neoplasms using bivariate flow cytometric analysis of these antigens and DNA content. The growth fractions measured by Ki-67 and PCNA were compared and correlated with acridine orange (AO) analysis and tumor grade. Our results indicate a significant difference between Ki-67 and PCNA values in neoplasms of low and intermediate grade (P = 0.002); Ki-67 values were significantly lower than those obtained by PCNA in this group. No statistical difference between Ki-67 and PCNA values was found in high grade neoplasms (P = 0.38). Analysis of different cell cycle compartments indicates that the observed difference in the positivity of these markers was due to their differential expression in the G0/1 segment of the cell cycle. We conclude that Ki-67 may better reflect the proliferative activity in solid neoplasms than does PCNA.

Biomarkers, Tumor↗
PubMed1987

[Plasma levels and tissue concentrations in rabbits following cutaneous administration of an indomethacin solution].

After cutaneous application to rabbits of a solution containing 1% of indomethacin (Elmetacin), concentration-time curves were determined in the skin-layers, in the subcutaneous tissue, in the superficial musculature, in the knee-joint capsule and in plasma. The quantitative assay used on-line fluorimetric detection after separation by HPLC and alkaline hydrolysis. Levels of indomethacin decreased with the depth of the tissue layers at the site of application. Indomethacin concentrations in the examined tissues exceeded plasma concentration at least twice for up to 8 h. Indomethacin was also detectable in the contralateral untreated tissue specimens and in the knee joint capsule.

Administration, Topical↗
PubMedDate not supplied

Flow cytometric analysis of Ki-67 in invasive ductal carcinoma of the breast: correlation with tumor and patient characteristics.

Of all markers associated with cellular proliferation in breast carcinoma, Ki-67 has more often been correlated with prognosis in patients with these tumors than others. To investigate the relevance of Ki-67 determination at each phase of the cell cycle in the biological assessment of mammary carcinoma we applied bivariate Ki-67/DNA content analysis on samples from 154 resected primary lesions. Three Ki-67-derived indices including an overall and G1 and S+G2M indices were generated. These values were correlated with similar indices derived from flow cytometric DNA/RNA analysis and traditional clinicopathologic factors. The results show that overall Ki-67 indices do not correlate with flow cytometric values and clinicopathologic factors. Flow-derived Ki-67 and DNA S+G2M indices were positively correlated (p<0.0001, r=0.58). High indices for the S+G2M phase derived by both Ki-67 and DNA analysis were significantly correlated with DNA aneuploidy, high tumor grade, and negative hormonal status. We conclude that the proliferative fraction (S+G2M) by either Ki-67 or DNA analyses offers more practical and clinically relevant information in assessing the proliferative activity in mammary carcinoma.

Breast Neoplasms↗