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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nasal inverted papilloma (IP) is a rare benign tumor that involves the mucous membranes of the nasal cavity and paranasal sinuses. Postoperative recurrences of this tumor have been observed frequently, and an association with squamous cell carcinoma (SCC) has been described occasionally. The etiology of IP remains unknown, but some studies have suggested a possible causative role of human papillomavirus (HPV) in IP. To determine the etiological role of HPV in IP and SCC associated with IP, to clarify the relationship between HPV and malignant transformation of IP, and to study the possibility of HPV implication in SCC of the nasal cavities and paranasal sinuses, retrospective analysis of HPV infection was performed in the surgically resected specimens of inverted papilloma (n = 26, in which 7 patients had SCC) and SCC (n = 40) of the nasal cavities and paranasal sinuses. Pathologically, koilocytosis, which is known to be closely related to HPV infection, and epithelial atypia were investigated. To detect the HPV protein antigen or nucleic acids, immunohistochemical method and molecular pathologic techniques, or in situ hybridization (ISH) and polymerase chain reaction (PCR) of DNA extracted from paraffin embedded tissues were used. By ISH we detected HPV 11 DNA in three cases (12%) of IP and HPV 16 DNA in one case (4%) of IP with SCC. By PCR HPV16 was detected in 2 of 7 cases in which IP was associated with SCC. However, no protein antigen was detected in any cases of IP by immunostaining, and viral mRNA was not detected by the study of ISH after DNase digestion. Pathologically, there was a closed relationship between HPV infection and koilocytosis, and severe epithelial atypia was frequently seen in the cases of IP coexisted with SCC. But there was no clear relationship between HPV infection and recurrence of IP. In SCC, HPV 16 and HPV 18 were detected by PCR in 4 cases (10%) and in one case (2.5%), respectively. Thus, it was suggested that HPVs were involved in the development of IP in some cases (19%, 5/26), but the state of infection is somewhat different from other papillomatous lesions, such as genital condylomas or laryngeal papillomas. HPV 16 and HPV 18 were found to be related to the malignant transformation of IP and to the pathogenesis of SCC originated in the nasal cavities and paranasal sinuses.
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PMID:[Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses]. 217 74

The interaction of partially purified calf uterine estradiol-charged estrogen receptor ([3H]ER) with rat nuclei was studied in vitro. We previously observed a significantly greater number of [3H]ER binding sites (at saturation) in nuclei of R3230AC mammary tumors from intact vs ovariectomized (ovex) rats with no difference in the affinity of [3H]ER binding for these nuclei. We now report on the nuclease sensitivity of [3H]ER binding sites in nuclei from these tumors and from normal rat tissues. Digestion of tumor nuclei with deoxyribonuclease I (DNase I) prior to incubation with [3H]ER in vitro resulted in a progressive loss of [3H]ER binding capacity, which was not accompanied by alterations in the affinity of [3H]ER for the nuclei (Kd = 1-3 nM). A significantly lower concentration (P less than 0.005) of DNase I eliminated 50% of the [3H]ER binding sites in nuclei of tumors from intact hosts (8 unit.min/ml) compared to tumors from ovex hosts (22 unit.min/ml). These results indicate that DNA regions capable of binding ER are more susceptible to DNase I digestion in tumors from intact rats than those from ovex hosts, suggesting that the endogenous hormonal milieu is responsible, at least in part, for maintenance of nuclease-sensitive DNA conformations in this hormone-responsive mammary tumor. The amount of DNase I required to eliminate 50% of [3H]ER binding to nuclei from lactating mammary gland, liver, and kidney ranged from 14 to 56 unit.min/ml. Therefore, accessibility of [3H]ER binding sites to nuclease digestion in normal rat tissue is generally less than that of R3230AC tumors.
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PMID:Nuclease sensitivity of estradiol-charged estrogen receptor binding sites in nuclei isolated from normal and neoplastic rat mammary tissues. 219 77

Several retrospective studies suggest that abnormal deoxyribonucleic acid (DNA) content in colorectal carcinoma correlates with adverse clinical outcome. Many of these studies have used naked nuclei retrieved from formalin-fixed, paraffin-embedded tissues for flow cytometry. The purpose of this study was to prospectively analyze 137 colorectal carcinomas using fresh whole-cell suspensions for flow cytometry and to determine whether abnormal DNA content (DNA aneuploidy or tumors with high proliferative activity) correlates with Dukes' stage, histologic grade, lymphocytic infiltration of the tumor, tumor fibrosis, extramural venous spread, or tumor size. Cell suspensions for flow cytometry were prepared by enzyme disaggregation with collagenase XI, DNase, and trypsin. Satisfactory DNA histograms were obtained from 132 of the 137 samples. The mean coefficients of variance for the G1/G0 of the external 2C control, internal 2C populations, and aneuploid populations were 2.5, 3.5, and 3.5, respectively. The mean percentage of viable cells was 97%. Of 132 cases, 102 (77%) demonstrated abnormal DNA histograms, of which 77 (58%) showed DNA aneuploidy. Abnormal DNA histograms of DNA aneuploidy did not correlate with Dukes' stage. Tumors of higher histologic grade were more likely to demonstrate DNA aneuploidy, however, these differences did not reach statistical significance. The authors conclude that (1) satisfactory DNA histograms can be obtained with the use of a fresh, whole-cell technique; (2) abnormal DNA histograms did not statistically correlate with standard clinical, grading, or staging parameters; and (3) carcinomas of high histologic grade showed an increased proportion of aneuploid DNA histograms, but this trend did not reach statistical significance.
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PMID:Deoxyribonucleic acid ploidy and cell cycle analysis of colorectal carcinoma by flow cytometry. A prospective study of 137 cases using fresh whole cell suspensions. 232 64

Human epidermoid tumor cells (Coll2, ME180, A431, HEp3) grown as xenografts in nude mice, were dissociated into single cell suspensions using an enzyme cocktail containing 0.025% collagenase, 0.05% pronase, and 0.04% DNase. The dissociated cell suspensions were separated by centrifugal elutriation into fractions containing homogeneous cell subpopulations primarily based on the differences in the rates of sedimentation. The quality of separation was evaluated by several techniques including flow cytometry, cell volume distributions, in vitro colony forming assay and morphological examination of Wright-Giemsa stained cells. In each separated fractions, the host to neoplastic cell ratio, the DNA ploidy, the plating efficiency and the cell cycle distribution were determined. After an initial separation of non-neoplastic host cells from malignant cells, a purity of greater than 95% host cells was obtained from the four xenografts studied. DNA analysis of tumor suspensions showed that neoplastic cells of different xenografts contained aneuploid cells with a DNA index of 1.51 to 1.95. The neoplastic cells were further separated into fractions according to their positions in the cell cycle. Fractions containing greater than 95% G1, 65% S, and 72% G2M cells were obtained from HEp3 xenografts. Less efficient separation with respect to cell cycle was attained with cells derived from Coll2, ME180, and A431 xenografts. Colony forming abilities of the neoplastic cells were determined at different phases of the cell cycle and found to be similar to those of the unseparated cell suspensions after corrections for non-neoplastic host cells were made. These investigations indicate that centrifugal elutriation is an effective technique of obtaining homogeneous subpopulations of cells from human tumor xenografts for various tumor biology and cell kinetics studies.
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PMID:Evaluation of cell subpopulations isolated from human tumor xenografts by centrifugal elutriation. 234 15

This investigation sought to characterize biochemically the tumor-specific transplantation antigens (TSTA) expressed on the cell surface of a panel of chemically induced fibrosarcomas of C3H/HeJ mice. Results suggest a uniform antigenic framework upon which individual specificities are superimposed. The antigens expressed by the 3-methylcholanthrene-induced fibrosarcomas MCA-D, MCA-F, and MCA-2A fulfill the requirements of a TSTA; namely, immunization of syngeneic hosts with irradiated cells or soluble extracts engenders a tumor-specific immune response such that animals resist challenge with the same, but not another, tumor. Brief incubation of intact tumor cells in single-phase aqueous solutions of 2.5% (v/v) 1-butanol extracts an immunoprotective TSTA, but not alloantigenic activity, from MCA-F cells. This extraction protocol was extended to the two other MCA-induced neoplasms. The butanol-extracted TSTA from the three tumors displayed isoelectric pHs of 6.4 to 6.6 following preparative isoelectric focusing. The tumor-specific immunoprotective activity from all three tumors displayed an apparent molecular weight of 150,000 (150 kDa) during high-performance gel permeation chromatography. The chromatographic properties of the 150 kDa antigens were unaffected by reduction using dithiothreitol, but incubation in acetate buffer, pH 3.0, dissociated the 150 kDa complex into at least two components with molecular weights of 70 to 100 kDa and 20 to 40 kDa. Only the smaller component displayed TSTA activity. The presence of two major components in the 150-kDa antigen was confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. TSTA activity was sensitive to digestion with pronase, papain, chymotrypsin, and alpha-mannosidase, but resistant to DNase, RNase, neuraminidase, trypsin, endoglycosidase H, and a mixed-function glycosidase. In addition, the TSTA activity was unaffected by heating. These data demonstrate that MCA carcinogenesis results in the expression of immunologically unique epitopes on biochemically related glycoproteins and suggest a unified mechanism for the generation of TSTA polymorphism.
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PMID:Biochemical characterization of 1-butanol-extracted murine tumor-specific transplantation antigens. 240 45

Cell subsets have been discriminated in cell suspensions derived from 37 human head and neck tumors by means of light scatter, DNA, and cytokeratin flow cytometry (FCM). Cell dispersion was performed overnight at 4 degrees C in two different enzyme mixtures, i.e., trypsin/dithioerythritol and collagenase/DNase, under slight agitation of sliced tumor tissue. Cells were examined before and after fractionation on a discontinuous low-density bovine serum albumin (BSA) gradient. Forward and right-angle light scatter FCM of 23 tumor specimens revealed four main subpopulations with different size and structure. Fractionation of primary cell suspensions on a BSA gradient at unit gravity separated debris, small cells and large cells. DNA FCM of the enriched populations demonstrated a relation between large cells and DNA aneuploidy. Epithelial cells, as recognized by cytokeratin antibodies, were also related with large cells. The results demonstrated the usefulness of light scatter, DNA, and cytokeratin analysis of crude and fractionated tumor cell suspensions for assessment of the efficacy of a particular dispersion technique and to obtain information of the cell subsets dispersed.
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PMID:Cell size, DNA, and cytokeratin analysis of human head and neck tumors by flow cytometry. 241 57

RNA species present on rat liver nuclear matrices were investigated. Nuclear matrices prepared by extensive digestion of isolated nucleii with DNase and RNaseA followed by low and high (2M NaC1) salt washes were labelled in vitro with T4 RNA ligase and [5'-32P]pCp and the labelled RNA analysed by gel electrophoresis. Despite the extensive RNaseA treatment, a prominent RNA species migrating as a heterodisperse band of 220-300 nucleotides (termed MX220-300), was observed--only minor amounts of other RNA molecules were seen. A comparison of RNA isolated from in-vitro labelled nuclear matrices with isolated matrix RNA that was subsequently labelled, indicated that part of MX220-300 was preferentially exposed on the nuclear matrix structure. Analysis of MX220-300 indicated that it was composed of a polyadenylic acid moiety hydrogen bonded to a smaller molecule of polyuridylic acid. No evidence was found for the presence of guanosine or cytosine residues. Control experiments in which labelled polyuridylic acid was added to nucleii prior to the preparation of MX220-300, virtually excluded the possibility that the partial double stranded RNA structure was an artefact of matrix preparation. An analysis of proteins in the nuclear matrix structure that interact with double stranded (ds)RNA showed at least 2 proteins having molecular weights of 62K and 66K daltons that recognized and bound polyadenylic/polyuridylic acid. Competition experiments with unlabelled polyinosinic/polycytidylic acid indicated that these proteins specifically recognized the dsRNA structure. The 62K and 66K dalton matrix proteins that specifically bound dsRNA were observed in nuclear matrices prepared from HeLa, Ehrlich ascites tumor and rat liver cells. It is not known whether these matrix located dsRNA binding proteins have 2-5A synthetase activity. The relevance of the above findings to the 2-5A system will be discussed.
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PMID:Double stranded RNA and the nuclear matrix--implications for the 2-5A system. 242 20

A series of metalloporphyrins linked through basic chains to certain DNA interactive groups has been synthesized. Several of these agents reproduce the characteristic properties of the antitumor glycopeptide bleomycin, including the oxygen-mediated scission of DNA in the presence of thiols, antibiobic activity under aerobic conditions, and activity against human and animal tumor models. Initial screening by scission of PM2-CCC-DNA identified six of the compounds, including those bearing acridine and acodazole intercalating groups, as the most active. The specificity of the oxygen-mediated scission of a 139 base pair HindIII/NciI restriction fragment of pBR322 by these six selected agents was then determined and compared with the action of pancreatic DNase by densitometric scans. All six of these compounds produce uniform base and sequence neutral cleavage of the restriction fragment at each base site. The six active compounds bear either of two types of intercalators, 6-chloro-2-methoxyacridine or acodazole, and with linkages to the ferric binding domain of -NH(CH2)2-, -NH(CH2)3-, -NH(CH2)4-, or -NH(CH2)3NH(CH2)3- and either porphyrin or deuteroporphyrin moieties. Comparison of the Kassoc values for binding to calf thymus DNA suggests that the enhanced binding observed with the linker -NH(CH2)3NH(CH2)3- contributes to the efficiency of sequence neutral DNA scission and may be a factor in the relative anticancer activities of these agents. The iron porphyrins give no evidence of the production of base propenals in DNA degradation, and the autoradiograms clearly indicate that a phosphate group is attached to the 5' end of the oligomer. The scission is partially suppressible by catalase and superoxide dismutase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Deoxyribonucleic acid cleavage specificity of a series of acridine- and acodazole-iron porphyrins as functional bleomycin models. 242 95

A nucleic acid-rich fraction extracted and purified from BCG (MY-1) augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factor(s) which showed anti-viral activity and rendered normal macrophages cytotoxic towards tumor cells. These cellular responses were induced by the MY-1 digested preliminarily with RNase, but not by the MY-1 digested with DNase, indicating that DNA contained in MY-1 was essential for the responses. The function of the factor to activate macrophages was destroyed by treatment with a small amount of anti-interferon (IFN)-gamma antiserum or under acidic conditions (pH 2), but not by treatment with anti-IFN-alpha/beta antiserum, while the anti-viral activity was destroyed almost completely by treatment with anti-IFN-alpha/beta antiserum. It appears that DNA from BCG stimulated mouse spleen cells in vitro, resulting in augmentation of NK activity and production of IFN-alpha/beta and -gamma.
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PMID:In vitro augmentation of natural killer cell activity and production of interferon-alpha/beta and -gamma with deoxyribonucleic acid fraction from Mycobacterium bovis BCG. 245 94

As in tumors with c-myc chromosomal translocations, c-myc retrovirus-induced monocyte tumors constitutively express an activated form of c-myc (the proviral gene), whereas the normal endogenous c-myc genes are transcriptionally silent. Treatment of these retrovirus-induced tumor cells with a number of bioactive chemicals and growth factors that are known to induce c-myc expression in cells of the monocyte lineage failed to induce the endogenous c-myc gene. In contrast, the same treatments induced the c-fos gene in both tumors and a control macrophage line. To investigate c-myc suppression further, a normal copy of the human c-myc gene was introduced into tumor and control cell lines by using a retrovirus with self-inactivating long terminal repeats. This transduced normal gene was expressed at equivalent levels in all cells, regardless of the state of endogenous c-myc gene expression, and was strongly induced by agents that induce the normal gene in the control cells. These results indicate that the signal transduction pathways that normally activate the c-myc gene are functional in myc-induced tumor cells and suggest that endogenous c-myc is actively suppressed. An examination of the c-myc locus itself showed that the lack of transcriptional activity correlated with the absence of several prominent DNase I-hypersensitive sites in the 5'-flanking region of the gene but without loss of general DNase sensitivity. Furthermore, analysis of 22 methylation-sensitive restriction enzyme sites in the 5'-flanking region, first exon, and first intron indicated that the silent c-myc genes remained in the same unmethylated state as did actively expressed genes. Thus, c-myc suppression does not appear to result from the most frequently described mechanisms of gene inactivation.
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PMID:Germ line c-myc is not down-regulated by loss or exclusion of activating factors in myc-induced macrophage tumors. 247 87


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