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Biomedical subjects

S R Wolman

Publications and source records attributed to S R Wolman.

At least 73 records · Page 4Linked to original sources
PubMed1991

Molecular cloning and chromosomal mapping of a human galactoside-binding protein.

A human galactoside-binding protein with an Mr of 31,000 was cloned from the human HT-1080 fibrosarcoma complementary DNA library. A partial complementary DNA clone containing the complete coding region was characterized and the deduced sequence encodes a polypeptide of 242 amino acids with the characteristics of a carbohydrate-binding protein. The gene coding for the human galactoside-binding protein was mapped to the chromosomal band 1p13. The deduced amino acid sequence of the human galactoside-binding protein revealed 95 residues at the amino terminus, homologous to the predicted amino acid sequence of the second exon of the human L-myc gene.

Amino Acid Sequence↗
PubMed1991

Bilateral breast cancer: one disease or two?

Our purpose was to determine whether bilateral breast cancer depends upon genetic predisposition to multiple tumors or, alternatively, represents two independent sporadic events. Biological concordance of hormone receptors and histopathology in bilateral tumors, family history of breast cancer, age at diagnosis, and survival were evaluated in 88 patients. The immunoreactivity of paired tumors from 51 patients to six different immunocytochemical markers was compared. Neither histologic patterns nor immunocytochemical reactions showed concordance between bilateral tumors. Absence of concordance (other than for estrogen receptors) and lack of associations with positive family history and early age of onset support an interpretation of independent tumor origins and does not suggest a major role for genetic determinants in the majority of cases of bilateral breast cancer.

Adult↗
PubMed1991

A retrospective analysis of breast cancer based on outcome differences.

We reviewed tumors from two groups of patients with breast cancer, distinguished by differences in outcome. One group (85 cases) survived more than 8.5 years without tumor recurrence; the other 85 cases had recurrent disease within 2 years. Histologic and immunocytochemical studies on all cases were performed without patient identifiers and prior to review of clinical prognostic factors. As expected, lymph node and estrogen receptor status differed substantially between the groups, but menopausal status and family history for breast cancer did not. We noted that 27% of node-negative patients died within 5 years, and nine patients with four or more tumor-containing nodes were symptom-free for over 8.5 years. Histologic grade (degree of tubule formation) and nuclear grade (including mitotic rate) differed significantly between the groups, as did vascular invasion, including both lymphatics and blood vessels. Prognostic value attached to tumor border only when fat was invaded without fibroblastic or inflammatory response (P = .012). Subgrouping cases of infiltrating ductal carcinoma (not otherwise specified) was prognostically informative in the B subgroup, 69% of whom were in the rapidly recurrent tumor group. Immunocytochemical staining for c-erbB-2 was positive in 19.3% of cases, but was equally distributed between the two outcome groups. We conclude that traditional histologic parameters are highly informative, and that c-erbB-2 studies do not increase the value of histologic diagnosis.

Breast Neoplasms↗
PubMed1991

Cytogenetic study of a papillary thyroid carcinoma with a rearranged chromosome 10.

Cytogenetic findings of a multifocal papillary thyroid cancer and a metastatic lymph node from a 29-year-old white female patient are reported. Two clonal aberrations were observed: a trisomy 7 in one nodule, and a rearranged chromosome 10 in a separate nodule and in a lymph node. The rearrangement of 10q described here is similar to other published cases and is relevant for interpreting the molecular findings associated with thyroid cancer.

Adult↗
PubMed1991

Genetic markers in thyroid tumors.

Tissue from nine patients with malignant tumors and two with benign tumors was cultured briefly before cytogenetic analysis. The tumors included one goiter and one Hürthle cell adenoma, one lymphoma, one medullary carcinoma, two Hürthle cell cancers, and five papillary cancers, varying widely in clinical staging and histologic differentiation. When assessed, DNA content was aneuploid in two of six malignant tumors. Various culture conditions (oxygen levels, dissociation methods, and media) were evaluated; the end points were growth, cell differentiation, and time to first harvest. Clonal aberrations were detected in one of four successfully harvested papillary cancers: they consisted of trisomy 7 and a rearrangement of chromosome 10. The rea (10) seen in 22 of 27 cells involved bands q11-21. Two other papillary tumors and a medullary cancer (a family member with multiple endocrine neoplasia type IIA) showed tetraploidy and nonclonal numerically aberrant cells. A lymphoma and two benign lesions showed no cytogenetic abnormality. The tumor with rea (10) is of special interest because abnormalities of 10q have been reported repeatedly in thyroid tumors, including two cases of papillary thyroid tumors with a structural aberration similar to that of the presented case. This rearrangement could affect the ret-proto-oncogene, localized to 10q11.2 which is activated in some papillary thyroid carcinomas.

Adult↗
PubMed1991

Genetic events in breast cancer and their clinical correlates.

The great heterogeneity of clinical breast cancer probably reflects heterogeneity of the mechanisms that are involved in its genesis and in disease progression. Genetic events that may be critical for tumor etiology, may determine tumor characteristics, and may contribute to tumor evolution should differ among individuals and among individual tumors and may distinguish subgroups with varying prognoses. We approach this problem from two viewpoints: one is based on population studies and the other on genetic events at the cellular level. 1. Population-based questions: What susceptibility factors are associated with individuals and groups who develop tumors? Inheritance patterns, familial aggregates, and associations with other tumors and other genetic diseases have been described for breast cancer. Bilateral and multifocal tumors may be examples of inherited predisposition, and their clinical and biological characteristics should be informative. Are there associations with tumor identifiers, such as histologic type and other tumor markers, for any of the "increased susceptibility" states? 2. Tumor-derived information: What types and frequencies of genetic alterations are found; do they relate to stage of tumor evolution, to morphologic classification, or to clinical evidence of comparative malignancy? Genetic evaluation depends upon cytogenetic and cytometric methods at the cellular level, and on detection of mutation, gene deletion, or amplification at the molecular level. We examine whether observed genetic alterations suggest mechanistic bases for morphologic distinctions among breast cancers and whether they assist in defining clinical phenotypes or steps in tumor progression. The general conclusions are that breast cancer comprises a complex set of neoplasms, that there is as yet little evidence to favor a final common pathway for its origin, and that a wide range of biological perturbations underlie its clinical course in the individual patient. An understanding of the basic mechanisms, their variety, and which of them apply in individual cases, is necessary as a rational basis for classification and for the development of strategies to interfere with tumor development in high-risk individuals.

Breast Neoplasms↗
PubMed1990

A common cytogenetic abnormality and DNA content alterations in dedifferentiated chondrosarcoma.

Dedifferentiated chondrosarcoma is an uncommon and aggressive variant of chondrosarcoma. The authors report the flow cytometric characteristics and cytogenetic findings in culture of two cases of dedifferentiated chondrosarcoma. The first case was DNA diploid by flow cytometry but had cytogenetic abnormalities consisting of breaks in the short arms of both chromosomes 1, resulting in deletion in one homolog and recombination in the other. In addition, cells from this tumor showed a balanced translocation between chromosomes 4 and 5, deletion of chromosome 9, and monosomy for chromosome 10. The second case was DNA aneuploid and more complex cytogenetically but had, in common with the first case, rearrangement and translocation at the same band on chromosome 1. These cytogenetic changes are compared with abnormalities previously reported for chondrosarcoma. Possible relationships between the nonrandom chromosomal abnormalities and subclassification among chondrosarcomas are discussed.

Aged↗
PubMed1990

Isolation and characterization of a spontaneously immortalized human breast epithelial cell line, MCF-10.

Two sublines of a breast epithelial cell culture, MCF-10, derived from human fibrocystic mammary tissue exhibit immortality after extended cultivation in low calcium concentrations (0.03-0.06 mM) and floating transfers in low calcium (MCF-10F), or by trypsin-Versene passages in the customary (normal) calcium levels, 1.05 mM (MCF-10A). Both sublines have been maintained as separate entities after 2.3 years (849 days) in vitro and at present have been in culture for longer than 4 years. MCF-10 has the characteristics of normal breast epithelium by the following criteria: (a) lack of tumorigenicity in nude mice; (b) three-dimensional growth in collagen; (c) growth in culture that is controlled by hormones and growth factors; (d) lack of anchorage-independent growth; and (e) dome formation in confluent cultures. Cytogenetic analysis prior to immortalization showed normal diploid cells; although later passages showed minimal rearrangement and near-diploidy, the immortal cells were not karyotypically normal. The emergence of an immortal culture in normal calcium media was not an inherent characteristic of the original tissue from which MCF-10 was derived since reactivated cryo-preserved cells from cultures grown for 0.3 and 1.2 years in low calcium were incapable of sustained growth in normal calcium.

Animals↗
PubMed1990

Wilms' tumor: a search for the critical lesion.

A Wilms' tumor from a 12-month-old boy showed epithelial and mainly rhabdomyoblastic differentiation. In addition, the kidney contained foci of nephroblastomatosis, a lesion predisposing to the development of nephric tumors. Flow cytometry indicated that the tumor DNA content was in the diploid range with an increased S-phase. Chromosome studies of the cultured tumor cells showed a dominant pattern of 49,XY, +8,9qh+, +12, +12,18q+, without obvious deletion of 11p. A few cells showed additional losses, deletions, or structural rearrangements superimposed on the basic pattern, but no normal metaphases were observed. The DNA from the tumor was probed for several loci on 11p because variations of 11p (deletion or translocation) have been reported in roughly one third of Wilms' tumors, and the critical gene in Wilms' has been localized to 11p13. In this case, 11p genes maintained heterozygosity or showed no detectable alteration in gene dosage when compared with peripheral-blood DNA. Therefore, despite histologic indication of an underlying constitutional defect, no genomic lesion of 11p was identified.

Blotting, Southern↗
PubMed1990

Dermatoglyphic study in autistic children and controls.

Dermatoglyphic patterns formed during fetal development reflect genetic or early developmental events. These patterns might provide a means for investigation of a biological basis for autism, but the results of prior studies are not conclusive. The authors undertook a study of 95 autistic children, defined by DSM-III criteria ascertained independently by three child psychiatrists. The dermatoglyphic patterns of these children were compared with several control groups, all age-matched, separated by sex, and comprising different ethnic compositions. Analysis of variance as well as chi-square methods of statistical analysis were applied. Consistency among hands, ATD angle values, total ridge counts, incidence and effects on ridge count of arches, double loops, and whorls were evaluated in this comparatively large, well-controlled group of autistic children, and all failed to support a value for dermatoglyphic analysis as a discriminant of autism.

Autistic Disorder↗
PubMed1989

Flow cytometry of fetal adrenal glands with adrenocortical cytomegaly.

Adrenal glands from four autopsied fetuses of 18 to 36 weeks gestation showed varying degrees of cortical cytomegaly. Formalin-fixed, paraffin-embedded sections from these four pairs of glands were studied by flow cytometry to analyze their DNA content and cell cycle parameters. Flow cytometry of Case 1, which had diffuse bilateral cytomegaly, demonstrated a major diploid peak, an increased percentage of tetraploid cells, and a decrease in S phase compared to an age-matched control with no evidence of cytomegaly (Case 2). Cases 3, 4, and 5 showed focal and/or unilateral adrenocortical cytomegaly and were diploid by flow cytometry with no differences in synthetic or tetraploid fractions compared to the control tissues. The focal distribution of the lesions or the limits of resolution of the instrumentation could account for some of these results. However, the findings in Case 1 suggest that the cytomegalic cells are tetraploid in DNA content and may have decreased DNA synthetic activity. A current hypothesis that these cells have undergone a period of sustained hyperactivity followed by exhaustion in reaction to an unknown stimulus is supported by our observations.

Adrenal Cortex↗
PubMed1988

Cytogenetic, flow cytometric, and ultrastructural studies of twenty-nine nonfamilial human renal carcinomas.

Multifactorial analysis, including cytogenetic studies, flow cytometry, and light and electron microscopic evaluation, was performed on 29 primary renal cell carcinomas and short-term cultures derived from them. Eleven of the 21 cases that yielded cytogenetic results demonstrated clonal chromosomal aberrations which included trisomy 7 in 8 cases, loss of the Y chromosome in 7, trisomy 12 in 2, and 16q- in 1. Flow cytometry showed that there was preferential growth of near-diploid populations and loss of aneuploid clones in culture with standard media. The ultrastructural features of both the primary and cultured tumors were remarkably similar. They included cytoplasmic vacuolization, reticulated dense nucleoli, and cell surface microvilli. Thus, morphological evidence supported the epithelial and, specifically, the renal tubular origin of the cultured cells. The development of chromosomal abnormalities seemed linked to advanced tumor stage, but the number of such cases was too small to analyze for statistical significance. No other correlations could be made between karyotypic change, DNA analysis, tumor histology, grade, and stage at this point in the patient follow-up.

Adult↗
PubMed1988

Irradiation-induced marker chromosomes in a metastasizing murine tumor.

We have used irradiation to induce marker chromosome formation in a metastasizing murine tumor with a stable karyotype. The induced recombinant chromosomes then served to determine whether metastases were of clonal or multicellular origin. Cumulative data were obtained from four series of experiments on spontaneous metastases originating from tumors grown from irradiated cells; 20 of these metastases expressed unique chromosomal alterations consistent with a clonal origin. The majority of metastasis-derived cell populations remain stable with respect to their marker chromosomes in culture as well as in successive animal transplantation. In several instances, however, chromosomal instability was sufficient to obscure the cellular origins of individual metastases. A few metastases showed mixed chromosomal patterns initially that were consistent with multicellular origin, but repeat examinations have revealed a chromosomal instability which persisted during propagation in culture. The frequency of chromosomal recombinants in metastases from the combined series was sufficient to suggest biological and statistical significance. The morphology of recombinants was not associated with radiation dose but appeared as an apparently random response of the tumor population in different experiments. Analysis of chromosomal markers by banding techniques was performed to determine if specific chromosomes or chromosomal sites were associated with tumor cells from metastatic foci (a host-selected subpopulation with a metastatic phenotype). Our results did not reveal preferential involvement of whole chromosomes or intrachromosomal sites in recombinant formation.

Animals↗
PubMed1988

Cytogenetic diversity in primary human tumors.

Cytogenetic patterns from primary short-term culture of breast cancer, renal carcinoma, and tumors of the central nervous system are presented to illustrate the range of karyotypic diversity of human solid tumors as well as their biologic differences in culture systems that support their growth. These studies have illustrated several major issues. 1) Results vary with the tissue of origin: primary cultures from breast are almost uniformly diploid, while renal tumors are near-diploid, mosaic, and show clonal aberrations; and CNS tumors are heterogeneous: some diploid, some near-diploid and some highly aneuploid. 2) Results after short-term culture are selective, representing subpopulations from the heterogeneous cells that are detected on direct analysis of fresh tumors by cytogenetics or flow cytometry (FCM). It is not yet clear whether prognosis depends on the dominant population of the primary tumor or alternatively should be influenced by detection of small aneuploid subpopulations. 3) Evidence from all three tumor types supports the interpretation that cytogenetically normal diploid cells constitute part of some tumor populations, and may be better adapted to routine growth in culture than aneuploid subpopulations from the same primary tumors. These cells may also compose a major portion of the viable population of tumors in vivo and, therefore, could represent a useful model for studies of tumorigenesis and therapeutic regimens.

Brain Neoplasms↗
PubMed1988

Paradoxical changes in SCE frequencies persistently elevated in vivo, on exposure to a mutagen in vitro.

Lymphocyte cultures from 4 individuals with persistently significantly elevated frequencies of sister-chromatid exchange (SCE) were examined with no treatment, and with 2 concentrations of mitomycin C. In each of the 4 cases, the mean level of SCEs in the untreated lymphocytes exhibited a paradoxical reduction in SCE frequency when exposed to the lower (0.005 microgram/ml) of the two doses of mitomycin C. At the second higher dose of mitomycin C (0.025 microgram/ml) the mean level of SCE/cell exceeded the untreated mean. When the distributions of SCE/cell were examined it appeared that the untreated cultures had two or more populations of cells; one was in the normal SCE frequency range, while the second population was in an elevated SCE frequency range. The paradoxical reduction in SCE frequency was apparently due to elimination of, or mitotic inhibition of cells in the highest range of SCE frequency, while a small elevation in SCEs was initiated in the cells with a normal SCE frequency. Thus, mean levels of SCE/cell can be misleading. This data suggests that new exposure to the same or a different genotoxic agent might possibly result in a misleading lowering of the mean SCE frequency.

Dose-Response Relationship, Drug↗