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

The etiology of cancer is a complex interplay of various factors, including genetic alterations. Multiple studies have been carried out to identify and characterize mutations that frequently occur during tumorigenesis. In human breast cancer, amplification of proto-oncogenes (c-myc, c-erbB-2/neu) and chromosome 11q13, mutation of p53 and loss of heterozygosity (chromosomes 1, 3p, 6q, 7q, 11p, 13q, 16q, 17, 18q and 22q) represent the major types of genetic abnormalities that have been frequently observed in tumor DNAs. The genetic deletions and mutations could inactivate tumor-suppressor genes. In some studies, specific alterations have been associated with some clinical parameters. Recently, linkage analyses, on large families with a predisposition to breast cancer, have been performed to map putative breast cancer susceptibility genes. The survey of high risk patients should be organised to make an earlier diagnosis.
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PMID:[Molecular analysis of breast cancers: recent developments]. 130 32

The understanding of intermediate endpoint biomarker expression in relation to the sequential events in bladder tumorigenesis establishes a useful approach for evaluating chemopreventive agents. Biomarkers may be genotypic or phenotypic and function as biomarkers of susceptibility, exposure, effect, or disease. This paper reviews several years of research on biomarkers and their use in monitoring chemoprevention therapy. In initial animal experiments, mice were dosed with N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) while co-administering N-(4-hydroxyphenyl)retinamide (4-HPR). 4-HPR did not statistically reduce tumor incidence, but did affect tumor differentiation and, consequently, nuclear size and DNA ploidy. These results suggest that nuclear size and ploidy may function as intermediate endpoint biomarkers of effect for oncogenesis and that epigenetic as well as genetic mechanisms may be primary in the oncogenic process. Early biomarkers of effect which occur prior to genetic effects or chromosome aberration may portend a higher probability of being modulated by differentiating agents such as retinoids. In vitro studies demonstrated that RPMI-7666 cells cultured with a phorbol ester tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) could be redifferentiated with 13-cis-retinoic acid and dimethyl sulfoxide (DMSO). F-actin, a cytoskeletal biomarker with a presumed function in the epigenetic mechanisms of carcinogenesis, could also be normalized in HL-60 cells treated with 4-HPR or DMSO. A clinical evaluation of F-actin in patients with varying degrees of risk confirmed the value of F-actin as a differentiating biomarker useful for bladder cancer risk assessment. The clarification of when the phenotypic changes of F-actin occur in the oncogenic process was achieved when a variety of biochemical changes were mapped in the patients with bladder cancer. These studies confirmed that G-actin, a reciprocal form of F-actin, is increased relatively early in bladder cancer oncogenesis when multiple biomarkers are quantitated in the field, adjacent area, and the tumor. Comparison of each individual biomarker's expression from field, adjacent to tumor, and tumor, and subsequent cluster analysis of these biomarkers, indicated that the possible sequence of phenotypic expression of biomarkers in bladder cancer oncogenesis is from G-actin, to p300 antigen, to epidermal growth factor receptor (EGFR), to p185 (neu oncogene product), to DNA aneuploidy and, finally, to visual morphology.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intermediate endpoint biomarkers for chemoprevention. 130 96

A principal difference between malignant and normal cells is the aberrant expression of oncogenes. Previously, we have reported on the expression of the insulin-like growth factor 1 receptor (IGF-1-R) in 93% of the human primary breast cancers studied. In the present study, we observed an increased gene copy number of the IGF-1-R in only 19 (2%) of 975 cases studied. The gene copy number of tumors with an amplified IGF-1-R gene varies between 3 and 56 (median, 24 copies). In 11 breast tumor samples with high (greater than or equal to 20 copies) IGF-1-R gene copy numbers, an additional amplification of either the c-myc gene (n = 3) or int-2/bcl-1 genes (n = 5) was observed, whereas no amplification of the HER2/neu gene was detected. The c-fes gene (like the IGF-1-R gene located on chromosome 15q25-qter), was found coamplified with the IGF-1-R in two cases, in one case to the same high extent (38 gene copies, each) and in the other case to only a moderate extent (4 copies of the c-fes gene and 21 copies of the IGF-1-R gene). Tumors with an amplified IGF-1-R gene showed a noticeable increased expression of the IGF-1-R as measured by ligand binding assays on membrane preparations. The median amount of the IGF-1-R protein of the amplified tumors was observed to be 35 times higher when compared to nonamplified tumors (P less than 0.001). Patients with tumors containing a high (greater than or equal to 20 copies) IGF-1-R gene copy number tend to have a shorter median overall survival (42 months; range, 14-120+; n = 8) than patients with tumors having a low amplified (3-10 copies) IGF-1-R gene copy number (median, 77 months; range, 19.5-98+; n = 4).
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PMID:Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. 131 Jun 36

The MCF-7 cell line is a hormone-responsive human breast-cancer cell line, which has been extensively used in studies of estrogen regulation of cell growth. These studies have indicated that the growth stimulation of the MCF-7 cells by estrogens may be effected by an autocrine mechanism involving several growth factors, such as EGF, TGF alpha and IGF-I and their receptors. We have amplified and cloned tyrosine-kinase-related sequences from the MCF-7 cell mRNA using the polymerase chain reaction and characterized the partial cDNAs obtained by nucleic acid sequencing. Nine tyrosine kinase cDNAs and one serine/threonine kinase cDNA were identified among the amplified sequences. Four different tyrosine kinase genes encoding receptors for fibroblast growth factors (FGFs) were found to be expressed by the MCF-7 cells. In addition, differences were observed in the expression of these members of FGF receptor family in different breast-cancer cells. A putative tyrosine-kinase receptor and a novel serine/threonine kinase were preferentially expressed in estrogen-responsive tumor cell lines. However, no estrogen-dependent regulation of any of the novel tyrosine-kinase receptor mRNAs was found in any of the cell lines including the MCF-7 or ZR-75-I cells, where the expression of the neu proto-oncogene mRNA was decreased during estrogen treatment. The expression of several FGF receptors by breast-cancer cells suggests that FGFs may be involved in their growth regulation and tumorigenesis.
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PMID:Analysis of tyrosine kinase mRNAs including four FGF receptor mRNAs expressed in MCF-7 breast-cancer cells. 131 Dec 87

Four murine cellular tumor models expressing various combinations of oncogenes (SV40 large T and v-Ha-ras, SV40 large T and v-src, SV40 large T and neu, adenovirus EIA and v-Ha-ras) induce sarcoma when they are inoculated s.c. into the DBA/2 syngenic mice. The metastatic patterns, distribution and fate of these tumor cells transplanted by two different routes into syngenic DBA/2 mice have been studied. All the tumor cell lines except EIA-ras, induce massive overt artificial metastases principally in the lung after i.v. injection. In s.c. tumor-bearing mice, a few resting cells colonize the lung as micrometastases. When removed from this tissue context and injected s.c. these cells regain their proliferative potential and grow as local tumors which again give rise to occult pulmonary micrometastases.
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PMID:Metastatic phenotype of murine tumor cells expressing different cooperating oncogenes. 131 11

Squamous cell carcinoma (SCC) is a rare complication of cutaneous lupus erythematosus (LE). Aside from the documented role of ultraviolet light, SCC may arise in areas of chronic scarring, such as in lesions of discoid LE. Iatrogenic immunosuppression associated with organ transplantation also results in a predisposition to SCC, often with multiple tumors. A role for certain human papillomaviruses (HPV) in the development of squamous cell carcinoma has been documented; specifically, HPV types 5 and 8 are detected in SCCs in patients with epidermodysplasia verruciformis and in recipients of organ transplants. HPV-11 is generally found in benign genital condylomata or laryngeal papillomas, but has not yet been associated with malignancy. We describe a patient with non-scarring cutaneous LE who was treated with azathioprine and prednisone and developed multiple SCCs. HPV-11 DNA and the target oncogenes neu and Ki-ras were detected in tumor tissue with the polymerase chain reaction. The HPV may have been involved in tumor induction and the azathioprine may have been involved in tumor promotion.
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PMID:Human papillomavirus type 11 in multiple squamous cell carcinomas in a patient with subacute cutaneous lupus erythematosus. 131 32

We have characterized mammary oncogenesis induced after polyomavirus infection of adult female nude mice regarding histopathogenesis, viral replication and viral and cellular oncogene expression. A unique transient generalized epithelial hyperplasia was observed (starting at 2 weeks post infection), preceding the development of dysplasias (onset 6 weeks post infection) and multiple neoplasias (onset 6 weeks post infection) in all glands. The ductal epithelium was the target for neoplastic transformation, and the occurrence of numerous ductal dysplasias coincided with the appearance of frank tumors. Stromal abnormalities were also seen. Tumor growth was not dependent upon ovarian hormones, and new tumors continued to develop in ovariectomized mice. Viral replication, high although variable, preceded but did not correlate with oncogenesis. Most but not all tumors contained high levels of unintegrated viral DNA. Tumors produced very low levels of live virus. Viral gene expression was markedly increased in the tumors compared with the infected but morphologically normal glands. The expression of c-myc was moderately increased (fourfold); changes in c-int-2 and c-Ha-ras expression were slight and inconsistent, while expression of c-neu and c-int-1 was unchanged.
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PMID:Characterization of the mammary hyperplasia, dysplasia and neoplasia induced in athymic female adult mice by polyomavirus. 132 Feb 44

To document over-expression of proto-oncogenes in tumors, it is necessary to determine the level of expression in the progenitor normal tissue. These studies compare the levels of nuclear transcription of a series of growth-factor related genes and proto-oncogenes in human glioblastoma cell lines with those in three normal glial cell populations. The unusual finding was that levels in the three normal glial cell populations varied considerably for several genes and thus overexpression of a specific gene in a tumor cell when compared to just one normal glial cell population would not necessarily represent overexpression. In this study, we compared the level of 17 genes in 7 tumors to the highest level of each gene found in any of three normal glial cell populations. Over-expression of PDGF-B in 4/7 glioblastoma cell lines, EGFR in 1/7, neu in 1/7 IGF-2 in 1/7 and ros in 2/7 was observed. The variation observed in the normal glial cell populations emphasizes the possibility that the normal glial cell populations represent different glial cell lineages and/or stages of differentiation and that the tumors could have arisen from different normal glial cells. Matching lineages of normal and tumor cells, probably by monoclonal antibody reactions, may be required to accurately define over-expression.
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PMID:Transcriptional patterns of growth factors and proto-oncogenes in human glioblastomas and normal glial cells. 132 85

Established human mammary tumor cell lines constitute an important tool in the study of breast cancer. The aim of this work was to isolate and characterize two new mammary tumor cell lines, JCK and GCS, which were obtained from the pleural effusion and ascitic fluid, respectively, from two breast cancer patients. Both cell lines had some properties of transformed cells, namely immortalization and growth in soft agar. The carcinoma cells presented epithelial morphology shown by light and electron microscopy, and antigenic properties shown by different tumor markers such as a cytokeratin cocktail, carcinoembryonic antigen, epithelial membrane antigen, and human milk fat globule membrane antigen. A significant increase was also found (P greater than 0.05) in cell growth and 3H-thymidine incorporation into DNA in the JCK and GCS cell lines in the presence of 17 beta estradiol at concentrations of 10(-9) and 10(-7) M, respectively, after 5 days in culture. These cells presented estradiol receptor levels which were similar in the biopsies and the resulting cell lines. The aromatase activity was also similar in the JCK cell line and the original patient biopsy. However, there was a considerably higher aromatase activity in the GCS cell line than in the biopsy specimen. Southern hybridizations with the neu oncogene showed an additional 12 kb fragment in both cell lines, as also seen in patients with breast cancer. We conclude from these studies that this in vitro system may provide us with a way to study metastatic cells and improve clinical management of breast cancer patients.
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PMID:New cell lines of human breast cancer origin. 132 92

Overexpression of the c-erbB-2/neu protooncogene has recently been shown in ovarian tumors collected from the United States. It is known that environmental and cultural factors may contribute to certain types of cancer, therefore, we examined expression of c-erbB-2/neu in ovarian tumors collected from China by immunohistochemical staining. Out of 81 tumor specimens, 57 (70.4%) were found to be immunopositive, whereas only one out of 17 (5.9%) normal ovarian tissue samples was slightly positive. Our results indicate that overexpression of c-erbB-2/neu is a general phenomenon for ovarian cancer regardless of different population. To search for a c-erbB/neu overexpressing cell line for future study on molecular mechanism, we also analyzed 13 cancer cell lines from the female genital tract for expression of c-erbB-2/neu. The c-erbB-2/neu RNA was found to be overexpressed at least 100-fold in one of the four ovarian cancer cell lines examined. An aberrant c-erbB-2/neu RNA was also found to be overexpressed in this cell line. Southern blot analysis indicated that the c-erbB-2/neu was amplified 2-4-fold in this line, and some of these alleles have structural alteration which may account for expression of the aberrant c-erbB-2/neu RNA. Since the 2-4-fold gene amplification is not proportional to the greater than 100-fold overexpression in RNA, other mechanisms such as transcriptional or posttranscriptional control must be involved in overexpression of this gene in ovarian cancer.
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PMID:Aberrant expression of the c-erbB-2/neu protooncogene in ovarian cancer. 134 99


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