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K D Somers

Publications and source records attributed to K D Somers.

At least 37 records · Page 2Linked to original sources

Amplification of the int-2 gene in human head and neck squamous cell carcinomas.

Head and neck squamous cell carcinomas (SCC) from 21 patients were analyzed for structurally rearranged or amplified proto-oncogenes by Southern blot hybridization. The int-2 proto-oncogene was amplified 3-5 fold in 5 (50%) of 10 laryngeal SCC and 2-3 fold in 5 (45%) of 11 nonlaryngeal SCC of the head and neck. Adjacent histologically normal tissue from the same patients had single int-2 gene copy number. Coamplification of int-2 and the epidermal growth factor receptor (c-erbB-1) gene was found in one laryngeal SCC and one SCC metastatic to the neck. No amplification or structural alterations of proto-oncogenes c-erbB-2/HER2, c-myc, H-ras-1, or K-ras-2 was detected in any of the head and neck tumors. In a survey of head and neck tumor-derived cell lines, int-2 was amplified 9 fold in a hypopharyngeal tumor cell line (FaDu), but not amplified in 3 laryngeal tumor cell lines. int-2 has been localized to the q13 band of chromosome 11. We used chromosome 11 specific probes to demonstrate that int-2 amplification was not due to complete or partial chromosome 11 duplication. int-2 amplification was localized to 11q13, but did not extend to the ets-1 locus 11q23. The results indicate that int-2 is frequently amplified in SCC of the head and neck and suggest that int-2 amplification may correlate with clinical disease progression.

Carcinoma, Squamous Cell↗

Phenotypic and cytogenetic characterization of a cell line derived from primary prostatic carcinoma.

A new cell line, PPC-I, has been established from a specimen obtained from a patient with a poorly differentiated adenocarcinoma of the prostate. This is the first line of its type derived from a primary prostatic tumor site. PPC-I cells have become immortalized in culture, exhibit transformation parameters including relaxed growth factor requirements and anchorage-independent growth, and are highly tumorigenic in nude mice. Cytogenetic studies by G-banding revealed a grossly abnormal karyotype, with a modal chromosome number of 84, multiple marker chromosomes including both homogeneously staining regions and double minutes and clonal loss of chromosomes 3, 5, 10, 15 and Y.

Aged↗

Cytogenetic analysis of four primary prostatic cultures.

Primary cell cultures were established from tissue specimens obtained from patients undergoing transurethral resection of the prostate. Cytogenetic analysis of these cultures revealed a normal male chromosomal complement from one and a 45,X karyotype from another patient with benign prostatic hyperplasia. In addition, a normal male chromosomal complement was observed from a moderately differentiated prostatic carcinoma, and a grossly abnormal karyotype was observed from a poorly differentiated adenocarcinoma of the prostate. This latter specimen contained a modal chromosome number of 84 with several consistent marker chromosomes including homogeneous staining regions and double minutes, and no normal chromosomes 3, 5, 10, 15 or Y. Primary prostatic cell cultures exhibit epithelial-specific keratin intermediate filament proteins, and, in conjunction with cytogenetic analysis, provide a model for the study of human prostate cancer.

Chromosome Aberrations↗

Isolation and characterization of collagen in Peyronie's disease.

Peyronie's disease is characterized histologically by excessive collagen deposition in the lesion. We examined the collagen types in Peyronie's disease plaque tissues compared to unaffected tissues from the same patient, other control tissues, and Dupuytren's contracture. Gel electrophoresis of pepsin-solubilized collagen demonstrated the presence of type I collagen and an increased content of type III collagen in plaque tissue. Increased type III collagen was detected in apparently normal tissue adjacent to the plaque and in Dupuytren's lesion, confirming previous findings. Although the cause of excessive collagen accumulation of Peyronie's disease is unknown, the results suggest an imbalance in the regulation of extracellular matrix production leading to pathologic fibrosis.

Collagen↗

Growth of head and neck squamous cell carcinoma in nude mice: potentiation of laryngeal carcinoma by 17 beta-estradiol.

We successfully transplanted and serially perpetuated human head and neck tumors in nude mice by using tumor tissue derived from 10 of 14 (71%) independently obtained surgical specimens. Tumor growth was achieved with specimens derived from cancers of the floor of the mouth, hypopharynx, and larynx. Tumors in nude mice retained their histological stage of differentiation and human species origin. Prompted by reports of increased estrogen receptors in laryngeal carcinomas, we tested the effect of estradiol treatment on the growth of laryngeal tumor implants. Time to tumor formation was decreased and tumor size was increased in estradiol-treated animals relative to placebo-treated animals. The results demonstrate that estradiol treatment potentiates growth of laryngeal tumors in nude mice. This tumor model can also be used to evaluate antihormonal therapy in the treatment of some laryngeal carcinomas.

Animals↗

Chromosome abnormalities in Peyronie's disease.

Peyronie's disease is a localized and progressive fibrosis of unknown etiology that affects the tunica albuginea of the penis. We examined cytogenetically cell cultures derived from plaque, adjacent tunica, dermis and lymphocytes in patients with Peyronie's disease, and compared the results to cell cultures established from the tunica albuginea of control patients. Chromosomal abnormalities were detected in 9 plaque-derived cell cultures from 7 of 12 Peyronie's disease patients (58 per cent). Cells cultured from adjacent tunica, dermis and lymphocytes from the same patients were karyotypically normal, as were cultures derived from control (chordee and penile scar) patients. Chromosomal aberrations consisted of 5 numerical changes and 4 structural rearrangements, and included chromosomal additions (trisomy 7 and trisomy 8), deletions (45X,-Y), reciprocal translocations and inversions or markers. In 2 instances cultures derived from plaque tissue contained 2 independent chromosomal abnormalities. The apparently random chromosomal changes associated with Peyronie's disease suggests that karyotypic instability may be a common feature of cells within the plaque. It presently is unclear whether this finding represents multiple pathways for the development of Peyronie's disease or secondary consequences of Peyronie's disease.

Aged↗

Binding of human IgG to cultured urogenital tumor cells.

Binding of human IgG by the Fc portion of the immunoglobulin molecule was detected on established human tumor cell lines by indirect immunofluorescence microscopy, cytofluorography, quantitative absorption, and rosette formation with the use of antibody-coated erythrocytes. Of the nonlymphoid tumors tested, IgG binding was restricted to the cell membranes of certain prostate and urinary bladder tumor cell lines. Although most cell lines tested shared a common antigenic determinant with monocytes and granulocytes, these cells did not express T- and B-cell antigens, the complement 3b receptor, or bind a monoclonal antibody specific for the Fc receptor expressed on human neutrophils. The facts that IgG binding was present on long-term established tumor lines and was not influenced by in vitro passage provide evidence that these properties are intrinsic to the tumor cells and may play some role in the pathophysiology of these tumors.

Adenocarcinoma↗

Significance of S-adenosylmethionine pools in the hypomethylation of ribosomal RNA during the propagation of tissue culture cells and oncogenesis.

The 5.8S rRNA of normal tissues contains a partially 2'-O-methylated uridylic acid residue which is methylated in the cytoplasm and undermethylated in rapidly growing neoplastic tissues (R. N. Nazar, T. O. Sitz, and K. D. Somers, J. Mol. Biol., 142: 117-121, 1980). This difference in methylation was further characterized by examining the effect of cell age or cell culture passage number on the level of methylation of 5.8S RNAs from normal and malignant cell lines and simultaneous changes in intracellular pools of S-adenosylmethionine and S-adenosylhomocysteine. The results indicate that the level of methylation decreases continuously with cell culture passage number as the cells become aneuploid, transformed, or tumorigenic, but there is no direct correlation with the intracellular pools of S-adenosylmethionine or S-adenosylhomocysteine. In contrast, there is a dramatic but inverse increase in the S-adenosylmethionine:S-adenosylhomocysteine ratio which correlates with the decreasing levels of 2'-O-methylation. The significance of these changes in substrate levels to the hypomethylation of 5.8S and other RNAs during oncogenesis is discussed.

Animals↗

Mechanisms of calcification in Peyronie's disease.

Scanning and transmission electron micrographs demonstrate a calcification process in the penile plaques of patients with Peyronie's disease. Osteoid formation originates from vascular lumina via osteoblast-like cells, which align the calcified plaque. These cells are surrounded gradually by calcified connective tissue. Collagen fibers demonstrate calcification and decreased periodicity.

Calcinosis↗

Cell culture of Peyronie's disease plaque and normal penile tissue.

Cell cultures derived from Peyronie's disease plaque and normal penile tissue were characterized morphologically and examined by immunofluorescence for actin cable formation, and their growth properties were compared. Relative to normal penile cell cultures which grew as contact inhibited, poorly refractile fibroblast-like cells, plaque derived cell cultures consisted of round and spindle shaped cells that were more refractile and exhibited random crisscross growth patterns. Scanning electron microscopy of plaque derived cell cultures revealed changes in cell surface topography characterized by the appearance of surface membrane blebs amd microvilli. Transmission electron microscopy demonstrated cells containing organized cytoplasmic microfilament bundles and nuclear indentations which resembled myofibroblasts. Such alterations were less extensive or absent in normal penile cell cultures. The amount and extent of actin cable formation was increased in plaque derived compared to normal penile cell cultures. Plaque derived cells also exhibited differences in growth properties and grew to higher saturation densities than their normal counterparts. These results demonstrate that cells derived from Peyronie's disease plaque can be grown in vitro and that these cells are morphologically altered and have an enhanced proliferative capacity. The availability of these cell cultures will permit studies directed at understanding the etiology and pathogenesis of Peyronie's disease.

Actins↗

Multinucleation in response to cytochalasin B: a common feature in several human tumor cell lines.

Human tumor cell lines derived from melanoma, glioblastoma, and carcinoma of the prostate, bladder, and kidney multinucleated in response to growth in cytochalasin B-supplemented medium, whereas cell lines derived from normal prostate, kidney, skin, lung, and other nonmalignant diseases remained predominantly binucleate under comparable conditions. The multinucleate cytochalasin B phenotype was dissociable from the anchorage-independent phenotype of tumor cells, suggesting that these markers of cellular transformation are under separate control. These results suggest that uncontrolled nuclear division by tumor cells may be a general marker of abnormal growth or regulation.

Cell Line↗

Increased cyclic AMP content directly correlated with morphological transformation of cells infected with a temperature-sensitive mutant of mouse sarcoma virus.

Normal rat kidney cells infected with a cold-sensitive mutant of mouse sarcoma virus [NRK(MSV-lb)] morphologically transform when exposed to adenosine 3':5' cyclic monophosphate (cAMP) at the restrictive temperature. The cAMP-induced morphological changes occur rapidly and are reversible. Agents capable of elevating endogenous levels of cAMP [prostaglandin E1 (PGE1) and cholera toxin (CT)] induced morphological transformation of NRK(MSV-lb) cells at the restrictive temperature that was concentration dependent, potentiated by cAMP phosphodiesterase inhibitors, and not prevented by inhibitors of DNA, RNA, and protein synthesis. Prostaglandin E1 stimulated a transient increase in the intracellular level of cAMP with a concomitant morphological transformation and reversion of cells as cAMP levels decline. The maximum increase is reached by 10 min, followed by a decline to near basal level by 80 min. In contrast, incubation of cells with CT resulted in irreversible morphological transformation and increased levels of cAMP first detectable by 1 hr with maximum levels reached by 24 hr. Heated CT (100 degrees C, 20 min) was without effect. Addition of CT to reverted PGE1-treated cells resulted in morphological transformation suggesting the existence of discrete receptors in NRK(MSV-lb) cells.

Animals↗

Cytochalasin B-induced multinucleation of human tumor and normal cell cultures.

Twelve human cell cultures derived from tumors, normal tissues, and derivative cultures transformed by either a RNA tumor virus or chemical carcinogen were examined for their response to cytochalasin B (CB) and the expression of this marker was correlated with growth in soft agar and saturation density in monolayer culture. Cell lines derived from carcinoma of the bladder (T24 and RT4), kidney (Caki-1), prostate (DU 145), and breast (MCF-7) multinucleated when growth in CB-supplemented medium, whereas cell cultures derived from benign bladder epithelium (HCV-29), and normal kidney (Flow 4000) and skin (GM10) remained binucleate under comparable conditions. Human osteosarcoma (HOS) cells transformed by murine sarcoma virus (MSV) or a chemical carcinogen extensively multinucleated in response to CB treatment, relative to a morphological revertant of MSV-transformed HOS and parental HOS cells. CB-induced multinucleation was consistently correlated with the ability of cells to form colonies in soft agar but inconsistently correlated with growth to high saturation densities. These results demonstrate a differential response to CB by normal and transformed human cells and that CB-induced multinucleation provides a convenient and useful in vitro marker for neoplastic transformation.

Cell Division↗