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At least 271 records · Page 15Linked to original sources
PubMed1986

Analysis of benign and malignant urogenital tumors for human papillomavirus infection by labelling cellular DNA.

A total of 268 biopsies from the genital region was screened for the presence of human papillomavirus DNA. The specimens included carcinoma of the vulva, vagina, cervix, corpus uteri, ovaries and penis, and Bowen's carcinomas, Bowenoid papuloses, Bowen's disease, cervical intraepithelial neoplasias (CIN I to III), Buschke-Löwenstein tumors, a cervical polyp, decidua, endometrium and histologically normal biopsies. Of 45 carcinomas, 18 contained either HPV 16 and/or 18 and 3 HPV 6-related sequences. In a few individual biopsies double or even triple infections were noted. Unusual was the presence of HPV 2-related DNA in one biopsy from Bowen's disease, whereas 2 condylomata acuminata contained HPV 3-related DNA and one contained HPV DNA related to a group of epidermal HPV's found in epidermodysplasia verruciformis lesions.

Biopsy↗
PubMed1986

Polyomavirus-transformed FR 3T3 rat cells are able to form metastases in syngeneic rats.

A series of polyomavirus-transformed FR 3T3 rat cell lines were tested for their tumorigenic and metastatic properties after subcutaneous inoculation of syngeneic Fisher rats. All of them grew into tumors, which appeared with variable latency periods; the TD50 varied from cell line to cell line. Eight of the 18 transformants that were inoculated gave rise to metastases, always localized in the lung. The capacity to form metastases, though at a low frequency, was also conferred on FR 3T3 cells upon transformation with a recombinant plasmid encoding only the middle-T protein. Fibroblast-like cells were predominantly observed upon histological examination of the metastases. Culture cell lines were derived from independent tumors and metastases induced by two transformants with low and high metastatic potentials, respectively. Metastasis-derived cell lines exhibited metastatic potentials similar to those of the respective original transformants. All the tumor- and metastasis-derived cell lines synthesized the same early viral polypeptides as the respective original transformants; in contrast, the viral DNA integrations evolved during tumor and metastasis formation.

Animals↗
PubMed1998

Molecular pathological analysis of testicular diffuse large cell lymphomas.

The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyzed. These lymphomas occurred in men with a median age of 69 years (range, 37 to 87 years). Nine of the 14 patients with follow-up died of lymphoma (median survival, 12 months). All cases were diffuse large B-cell lymphomas that were positive for CD20 and commonly showed plasmacytoid differentiation (10 of 20 cases). Three cases were Burkitt's-like large cell lymphomas. Infiltration by lymphoma in the seminiferous tubules was seen in most cases. All lymphomas were negative for human herpesvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reaction (PCR), suggesting that these viruses are not involved in the pathogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cases. Nucleotide sequences of the V-D- and J segments of the immunoglobulin heavy chain gene (IgH) rearrangements obtained in 12 cases after PCR amplification were analyzed and compared with known germlines. The frequency of VH-family use in testicular DLBCL was similar to that reported for normal peripheral blood lymphocytes and follicular lymphomas. This contrasts with the previously published findings of preferential use of the VH3- or VH4-family by nodal DLBCL. Comparison with the published germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutation, as indicated by intraclonal variation in IgH sequence, was observed in all sequenced cases, suggesting direct antigen stimulation, which represents another difference between primary testicular and nodal DLBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respects. Their histological and molecular features show some similarities to those seen in marginal zone (MALT) lymphomas.

Adult↗
PubMed1984

Protoneoplasia: the molecular biology of murine mammary hyperplasia.

The mouse mammary tumor virus has provided a window into the inner workings of the mammary epithelial cell at the earliest stages of neoplasia. Techniques of molecular biology permitted us to look through that window revealing a new biology which deserves consideration as a model for mammary tumorigenesis in all species. According to this model the neoplastic process originates in a single mammary epithelial cell as a result of a critical genetic alteration, such as integration of MuMTV (MuMHV) into a key site in the mouse genome (Fig. 4). The genetic alteration immortalizes the cell and provides it with selective growth advantages which result in a clonal proliferation. This original proliferation emerges as the protoneoplastic mammary hyperplasia. The protoneoplastic cells have limited growth potential and are not obligated to undergo malignant transformation but they represent a genetically evolving population highly susceptible to full blown malignancy after exposure to carcinogens. Protoneoplastic cells which undergo further genetic alterations that provide additional selective growth advantages proliferate and emerge as malignant tumors. The genetic alterations are sometimes reflected by changes in viral DNA but this is not essential and most mouse mammary tumors probably do not occur as the result of new host-virus interactions. No doubt the current work on the mouse "int" loci will help define the genes responsible for the induction and maintenance of the protoneoplastic state. Since such host genes have proven so ubiquitous, one must also predict that analogous genes will be found in human mammary protoneoplasias. Detection of such sequences may help distinguish protoneoplastic processes from nonneoplastic, low risk hyperplasias in the human breast. Finally, the gene or genes involved in the more lethal malignant transformation await elucidation. Based on past and current progress one can be sure that the mouse mammary tumor system will help point the way.

Animals↗
PubMed2001

Common polymorphisms and somatic mutations in human base excision repair genes in ovarian and endometrial cancers.

The purpose of this study was to determine whether the human APEX and OGG1 genes, encoding proteins important in base excision repair (BER) of DNA, contain nucleotide sequence polymorphisms or are mutated somatically in tumors from women diagnosed with ovarian or endometrial cancer. Based upon the analysis of germline DNA from 83 individuals, 63 with ovarian cancer and 20 with endometrial cancer, we found two missense polymorphisms in APEX (Q51H and D 148E) and two missense (A3P and S326C) and one intronic (Exon 5-15 bp) polymorphism in OGG1. The frequencies of the various alleles (in the ovarian and endometrial cancer patients combined) were 4.8% for 51-His and 56.2% for 148-Glu in APEX, and 1.0% for 3-Pro and 20.0% for 326-Cys in OGG1. Somatic mutations in APEX (P112L, W188X and R237C) were identified in three of 20 endometrial tumors, but no mutations were identified in APEX in 43 ovarian tumors, or in OGG1 at either tumor site. Given the crucial role of the APEX and OGG1 proteins in BER of oxidative DNA damage, the identified polymorphisms are good candidates for genetic epidemiologic studies of cancer susceptibility, while the finding that three of 20 (15%) endometrial tumors have somatic mutations in APEX suggests that inactivation of the BER pathway is important for the development of endometrial cancer in at least a subset of cases.

Alleles↗
PubMed2001

DNA topoisomerase II inhibition by peroxisomicine A(1) and its radical metabolite induces apoptotic cell death of HL-60 and HL-60/MX2 human leukemia cells.

Peroxisomicine A(1) (T-514) is a dimeric anthracenone first isolated from the plant Karwinskia humboldtiana. The compound presents a high and selective toxicity toward liver and skin cell cultures and is currently the subject of preclinical studies as an antitumor drug. To date, the molecular basis for its diverse biological effects remains poorly understood. To elucidate its mechanism of action, we studied its interaction with DNA and its effects on human DNA topoisomerases. Practically no interaction with DNA was detected. Peroxisomicine was found to inhibit topoisomerase II but not topoisomerase I. DNA relaxation and decatenation assays indicated that the drug interferes with the catalytic activity of topoisomerase II but does not stimulate DNA cleavage, in contrast to conventional topoisomerase poisons such as etoposide. Two human leukemia cell lines sensitive or resistant to mitoxantrone were used to assess the cytotoxicity of the toxin and its effect on the cell cycle. In both cases, peroxisomicine treatment was associated with a loss of cells from every phase of the cell cycle and was accompanied by a large increase in the sub-G1 region which is characteristic of apoptotic cells. The cell cycle changes were more pronounced with the sensitive HL-60 cells than with the resistant HL-60/MX2 cells (with reduced topoisomerase II activity), in agreement with the cytotoxicity measurements. Treatment of HL-60 cells with T-514 stimulated the cleavage of the poly(ADP-ribose) polymerase by intracellular proteases such as caspase-3. The cytometry and Western blot analyses reveal that peroxisomicine induces apoptosis in leukemia cells. In addition, we characterized a catabolite of peroxisomicine, named T-510R, in the form of a highly stable radical metabolite. The electron spin resonance and mass spectrometry data are consistent with the formation of an anionic semiquinonic radical. The oxidized product T-510R inhibits topoisomerase II with a reduced efficiency compared to the parent toxin and was found to be about 3-4 times less toxic to both the sensitive and resistant leukemia cell lines than T-514. Collectively, the results suggest that topoisomerase II inhibition plays a role in the cytotoxicity of the plant toxin peroxisomicine. Inhibition of topoisomerase II may serve as an inducing signal triggering the apoptotic cell death of leukemia cells exposed to the toxin. The dihydroxyanthracenone unit may represent a useful chemotype for the preparation of topoisomerase II-targeted anticancer agents.

Anthracenes↗
PubMed1981

Independent recombination between avian leukosis virus terminal sequences and host DNA in virus-induced proliferative disease.

A cDNA transcript of Rous sarcoma virus, which contained the long terminal repeat (LTR) and some additional 3'-terminal sequences, was inserted into the plasmid pBR322. This recombinant plasmid, p53, was then used as a hybridization probe to detect viral terminal sequences in DNA from a number of tissues of birds with a variety of avian leukosis virus (ALV)-induced proliferative diseases. Using restriction endonuclease digestion and blot hybridization analysis, we detected, in addition to standard ALV genomes, viral terminal sequences linked to host DNA and not to viral genes. In DNA from bursal lymphomas and nephroblastomas, we observed small numbers of integration sites occupied by sequences in p53 and lacking most or all of the remainder of the viral genome. In DNA from osteopetrosis, we observed apparently multiple copies of molecules containing host DNA linked to viral LTR sequences. Some of these structures were contained in discrete, probably unintegrated, DNA molecules. We concluded that viral LTR sequences can be inserted as independent elements during recombination with host DNA in some forms of interaction between exogenous retroviruses and host cells. Because the LTRs have been implicated in integration and transcription of viral genes, the possibility that translocation or activation, or both, of host genes may occur as a consequence of viral infection is reinforced by these observations.

Animals↗
PubMed1976

Satellite DNA sequence content of polylysine-titratable and nuclease-resistant fractions of mouse liver hepatoma chromatin.

Micrococcal nuclease digestion of mouse TLT liver hepatoma chromatin proceeds rapidly to the point where approximately 35% of the DNA is recoverable by centrifugation of the chromatin DNA through 3M CsCl. The satellite DNA sequence content of this recoverable DNA is the same as whole chromatin DNA (10%). The 11s (penultimate digestion product) monomer, as well as intermediate multiples and relatively undigested large chromatin segments are separable on steep hlycerol gradients. The DNA isolated from these fractions also contains the normal 10% satellite DNA content. Progressive polylysine titration of chromatin followed by nuclease digestion gives anomalous recoveries of DNA but, nonetheless, the satellite sequence content titration of chromatin, followed by pronase and then nuclease digestion, again gave recoverable DNA with a satellite sequence content of 10%. These results are discussed in terms of the conclusion that nucleosome (or upsilon-body) structures are distributed in a random fashion over the genome.

Base Sequence↗
PubMed1991

Prevalence of human papillomavirus genomes in tissues from the lower genital tract as detected by molecular in situ hybridization.

Incidence cases of human papillomavirus (HPV)-related disease of the lower anogenital tract were prospectively collected and submitted to RNA-DNA in situ hybridization, which allows a direct correlation between morphology and the presence of viral DNA. The overall HPV detection rate in condylomata and intraepithelial or invasive neoplasia varied for the different genital areas: cervix (64%), vagina (56%), vestibule (59%), vulva (50%), and penis (42%). HPVs 6/11 were associated with condylomata, whereas HPV 16 was associated with intraepithelial and invasive neoplasia. Not a single case of intraepithelial or invasive neoplasia contained HPV 6/11, which supports the notion of the oncogenic potential of HPV 16. Condylomata were positive for HPV 16 only when adjacent to HPV 16-positive cervical intraepithelial neoplasias (CINs). The amount of viral DNA (copy number) was low in invasive cancers, intermediate in intraepithelial neoplasia, and conspicuously high in condylomata. In biopsies (n = 142) taken from lesions suggestive of subclinical papillomavirus infection on the basis of minor colposcopic and histologic abnormalities, HPV DNA was not detectable. Histologically normal tissue (n = 210) adjacent to condyloma, CIN, or cancer, and thus potential carrier of latent HPV infection, also proved negative for HPV DNA by in situ hybridization. The inability to detect viral DNA by in situ hybridization in tissues diagnosed as subclinically or latently infected may have been due to limited sensitivity of the hybridization method applied in this study.

Carcinoma↗
PubMed1982

Mouse mammary tumour virus and polyoma virus information in mammary tumours of athymic mice inoculated with polyoma virus.

Polyoma virus inoculation of athymic mice results in the development of mammary tumours with a much higher incidence than the development of salivary gland tumours, the latter being the most common for immunocompetent normal mice. The possibility existed that polyoma virus might act as a co-carcinogen in activating the expression of mouse mammary tumour virus (MMTV). Molecular hybridization studies, however, showed that the mammary tumour development was accompanied by neither the amplification of MMTV genomic sequences nor by their more extensive transcription. In contrast, tumour tissue contained about 60 to 100 copies of polyoma virus genome equivalents per cell and some of these sequences were apparently transcribed into RNA. While these results do not rule out the transient involvement of MMTV expression in mammary tumour development, it appeared that the mammary gland cells were directly transformed by polyoma virus. Apparently, polyoma virus displayed a tropism in athymic mice that was different from that in normal mice.

Animals↗