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

Twenty-three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto-oncogene mutations by mutation-specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin-fixed, paraffin-embedded tissue. Six of the 22 that were satisfactory amplified contained activating point mutations in codon 12 of K-ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K-ras, one had a GGT----GAT transition, four had GGT----GTT transversions, and one had both GGT----GAT and GGT----GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti-ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K-ras mutation. K-ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm.
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PMID:K-ras activation and ras p21 expression in latent prostatic carcinoma in Japanese men. 156 75

Activation of ras oncogenes is commonly found in human neoplasms. We have investigated 280 human lung cancer specimens for ras activation, including 38 that have not been reported previously, using an oligonucleotide detection assay. From a total of 141 adenocarcinoma samples from smokers, 41 tested positive for a point mutation in codon 12 of K-ras (30%), while three tumors had another type of ras activation. Only two of 40 cases from nonsmokers had a K-ras mutation (5%), suggesting that K-ras mutations may be directly caused by exposure to carcinogens in tobacco smoke. The majority of the point mutations in adenocarcinomas were guanine to thymine transversions in codon 12 of the K-ras oncogene. Occasional point mutations in ras oncogenes were detected in adenosquamous carcinomas (one of five cases) and large cell carcinoma (one of 24 cases), but no ras activations were found in small cell carcinomas (six cases), squamous carcinomas (48 cases), carcinoid carcinomas (15 cases), or thymoma (one case). Analysis of the clinical and pathological features of the adenocarcinoma cases showed no apparent associations between the K-ras activation and age at diagnosis, sex, disease stage, and the occurrence of other neoplasms. K-ras-positive adenocarcinomas tended to be less differentiated than the K-ras-negative ones (P = 0.044, chi 2 test for trend). K-ras mutations identify a subgroup of patients with adenocarcinoma of the lung who have a very poor prognosis despite radical resection of their tumor. Although K-ras has been proposed as a target for antitumor therapy, its major clinical significance could be to aid in the selection of patients for specific therapeutic interventions, such as adjuvant chemotherapy.
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PMID:Clinical significance of ras oncogene activation in human lung cancer. 156 97

The paucity of premalignant material available for study makes it difficult to assign pathogenic roles to the myriad phenotypic abnormalities found in lung cancer. Chemically and transgenically induced primary lung tumors in mice, however, share many of the morphological, histogenic, and biochemical features of human adenocarcinoma. Genetic factors guide the susceptibility to these tumors in both mice and humans. The reproducible natural history of these investigator-initiated lesions allows molecular characterization at each stage of progression, as well as delineation of pharmacological agents which encourage or retard their appearance. Experimental tools which can be used with this mouse model include inbred and recombinant inbred strains that vary in susceptibility to lung tumorigenesis, sensitivity to tumor-promoting agents, and tumor growth characteristics; the ability to isolate the cells of tumor origin with a high degree of purity; immortalized but nontumorigenic cell lines for comparison with neoplastic cell lines; and transgenic mice with an accelerated rate of tumorigenesis for the study of benign to malignant progression over a conveniently short time course. Among the relevant information thus far garnered about mouse lung tumors is the fact that K-ras protooncogene polymorphisms predict susceptibility to tumor development; K-ras mutation is an early event, and the nature of this mutation may determine the benign or malignant fate of the tumors; and the autonomous growth of neoplastic lung epithelial cells is maintained by a resistance to growth-inhibitory signals, and this is mediated by depletion of intracellular receptors and altered signal transduction pathways.
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PMID:Primary lung tumors in mice: an experimentally manipulable model of human adenocarcinoma. 156 98

Forty-two endometrial carcinomas of various stages of progression were analyzed to search for loss of chromosomal regions and for point mutations of ras genes and amplification of Int-2 gene. This approach is particularly favorable for observation of genetic events and their significance in the process of neoplastic conversion by considering the clinico-pathological characteristics of each tumor. At least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, are implicated in the development of endometrial carcinomas. Likely targets for allelic losses on chromosomes 18q and 17p are the DCC gene and the p53 gene sequences, respectively. Overall numbers of allelic losses in individual tumors appeared to increase in case of advanced stage tumors, thereby indicating the association of allelic loss accumulation with tumor progression. The genetic features seen in 2 juvenile-type adenocarcinomas and 2 clear-cell carcinomas suggested the possibility that etiological factors providing selective pressure for particular mutation sub-sets during carcinogenesis are probably heterogeneous.
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PMID:Chromosomal deletions and K-ras gene mutations in human endometrial carcinomas. 156 44

Adenocarcinoma of the lung obtained at surgical resection was examined for mutation at codons 12, 13, and 61 of the oncogenes K-ras, H-ras, and N-ras, using polymerase chain reaction and oligonucleotide hybridization techniques. The mutation was detected in 18 of the 115 cases (15.7%), and 15 of 18 were at codon 12, 2 were at codon 13 of K-ras, and 1 was at codon 61 of N-ras. G to T transversions were most common. The ras gene mutations were more frequent in the male patients (P = 0.0048). No significant differences were found to be related to stage of the disease or tumor-nodes-metastases classification between positive and negative groups of the ras gene mutations. A history of tobacco use was not always a factor contributing to mutation. Of the completely resected group without lymph node metastasis, the 5-year survival rate in the ras-positive group was 53.3%, which was significantly poorer than the 83.6% survival rate in the ras-negative group (P less than 0.05). Our findings suggest that ras gene mutations may be prognostic, especially in the early stage adenocarcinoma of the lung.
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PMID:ras gene mutations as a prognostic marker in adenocarcinoma of the human lung without lymph node metastasis. 158 7

The efficiency of detection of H- and K-ras mutations in 27 CD-1 mouse liver tumors by direct sequencing of polymerase chain reaction (PCR)-amplified DNA isolated from formalin-fixed and paraffin-embedded tissues was compared with that after assay by both NIH 3T3 transfection (followed by sequencing of amplified transformant DNA) and direct sequencing of PCR-amplified DNA isolated from frozen tumors. Some tumor samples were chosen for comparison because they contained ras mutations that were detected by either NIH 3T3 transfection or sequencing of PCR-amplified DNA derived from frozen tumors, but were not detected by both techniques. The efficiency of detecting K-ras mutations was similar for sequencing of amplified fragments derived from both paraffin-embedded tissues and from frozen tumors. However, these two techniques differed in their efficacy for detection of H-ras codon 61 mutations. Furthermore, this difference appeared to be mutation-specific: the sequencing of amplified products from paraffin-embedded tumor tissues allowed increased detection of CAA to AAA mutations but decreased detection of CAA to CTA mutations relative to sequencing of amplified fragments derived from frozen tumor DNA. Direct sequencing of PCR products from paraffin-embedded sections was more sensitive than NIH 3T3 transfection for detection of activated K-ras genes containing codon 13 mutations but less sensitive for detection of activated H-ras genes containing codon 61 mutations. In summary, direct sequencing of amplified DNA from either frozen tumors or formalin-fixed, paraffin-embedded tissues can be more sensitive than NIH 3T3 transfection for detection of codon 13-activated K-ras genes. However, it appears to be less sensitive than NIH 3T3 transfection for detection of certain activating H-ras mutations. Depending upon the questions being asked of the data, each of the methods can provide useful information about ras gene mutations in tumor samples. The apparent differences in sensitivities between the methods is not yet understood, but such differences should be considered in the analysis of data obtained when only one method is used.
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PMID:Polymerase chain reaction/sequencing analysis of ras mutations in paraffin-embedded tissues as compared with 3T3 transfection and polymerase chain reaction/sequencing of frozen tumor deoxyribonucleic acids. 158 89

The expression of 15 oncogenes including erbB and H-ras in 18 human glial tumors -10 glioblastomas, 1 astrocytoma grade III-IV, 2 oligodendrogliomas grade III, 2 astrocytomas grade II-III, 1 astrocytoma grade II, 1 oligodendroglioma grade II and 1 oligoastrocytoma grade II--was determined by hybridizing RNA against oncogene probes using the Dot Blot technique. Compared with bovine cerebrum (control), the oncogenes abl, erbA, fms, fos, K-ras, mil, mos, myb, rel, sis, src and yes were expressed equally in both bovine cerebrum and the gliomas. However, the expression of erbB was increased 2-9-fold in all except one glioma, and the expression of H-ras was decreased by the factor 0.3-0.7 in 15 tumors. No obvious correlation was found between tumor histology and changed expression of erbB and/or H-ras or between the grade of malignancy and the expression of any oncogene tested. A connection between erbB and H-ras has been shown by several studies. Our results confirm the relationship between H-ras and erbB. However, the meaning of the H-ras decrease in combination with the erbB elevation has to be clarified.
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PMID:Combined erbB gene overexpression and decreased H-ras gene expression in human gliomas. 158 58

The role of the type II cell in the development of pulmonary tumors induced in the adult A/J mouse (6 weeks of age) by treatment with a single dose (100 mg/kg, i.p.) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated. Twenty-four h following treatment with NNK, the concentration of O6-methylguanine was similar in Clara and type II cells. However, hyperplasias were detected only along the alveolar septa in lungs 14 weeks after carcinogen treatment. Examination of the ultrastructure of several hyperplasias revealed that the proliferating cells resembled type II pneumocytes. The proliferating cells were cuboidal in shape, with centrally localized ovoid nuclei characterized by minor indentations. Lamellar bodies, one of the major hallmarks of the type II cell, were present in the cytoplasm. The progression of pulmonary lesions was followed by sacrificing mice at 4-week intervals from 14 to 54 weeks after treatment with NNK. From 34 to 42 weeks after treatment, progression to neoplasia was demonstrated by a decline in the frequency of hyperplasias and an increase in the frequency of adenomas. Approximately 50% of the adenomas were observed arising within hyperplasias. Carcinomas appeared to increase in frequency 34 weeks after carcinogen treatment and comprised greater than 50% of the pulmonary lesions by 54 weeks. Approximately 30% of the carcinomas were observed arising within adenomas. The growth pattern of carcinomas began to change from solid to mixed (solid and papillary) 42 weeks after NNK. Moreover, electron micrographic analysis demonstrated that, within a hyperplasia, proliferating type II cells could change from cuboidal to columnar in shape and could also exhibit nuclear indentations, both characteristics displayed by the Clara cell. Thus, this divergence of the type II cell from its well characterized morphological features indicates that the selective growth advantage which these initiated cells possess can result in changes to the normal ultrastructure of this cell as it progresses toward malignancy. DNA was isolated from 20 hyperplasias and screened for the presence of an activated K-ras gene. This gene was activated in 17 of 20 lesions, with 85% of the mutations involving a GC to AT transition within codon 12 (GGT to GAT), a mutation consistent with base mispairing produced by the formation of the O6-methylguanine adduct. This specificity for activation of the K-ras gene was identical to that observed previously in adenocarcinomas induced by NNK.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of the alveolar type II cell in the development and progression of pulmonary tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the A/J mouse. 159 28

Neonatal treatment with estrogens is associated with development of uterine adenocarcinomas in CD-1 mice. Treatment with the synthetic estrogen diethylstilbestrol (DES) on Days 1 to 5 after birth results in 90% incidence of these hormone-dependent lesions in 18-mo.-old mice. Three cell lines were established from these DES-associated tumors. Each of these cell lines exhibited morphologic and ultrastructural characteristics of transformed epithelial cells, including an increased nuclear:cytoplasmic ratio, enlarged and irregular nuclei with multiple nucleoli and areas of chromatin condensation, positive staining for cytokeratin, desmosomes, and microvilli. After subcutaneous injection into nude mice, all three cell lines formed solid tumors within 4 wk. Although the primary uterine tumors and tumor transplants in nude mice had been shown to be estrogen-dependent and estrogen-receptor positive, neither the monolayer growth nor the tumorigenicity of any of the three cell lines in this study was enhanced by or dependent on estrogen. Estrogen receptor levels were low in early and intermediate passage cells. Allele-specific oligonucleotide hybridization analysis of PCR-amplified cell line DNA revealed no point mutations in the 12th, 13th, or 61st codons of the K-ras or H-ras protooncogenes. Southern analysis revealed no changes in genomic organization of the putative tumor suppressor gene DCC, but demonstrated a three- to four-fold amplification of the c-myc gene in one cell line. Expression of c-myc RNA was concomitantly increased in the same cell line. These three transformed cell lines represent the end point in the process of hormone-associated tumorigenesis and as such should prove useful in investigating the molecular changes and the mechanisms involved in hormonal carcinogenesis.
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PMID:Characterization of murine cell lines from diethylstilbestrol-induced uterine endometrial adenocarcinomas. 159 5

Myc gene abnormalities were studied in 30 human lung cancer cell lines. N-myc gene amplification was found in an adenocarcinoma cell line, VMRC-LCD. Neither c- or L-myc gene amplifications nor K-ras codon 12, 13, 61 point mutations were observed in this tumor. Cytomorphologically the VMRC-LCD cells had positive characteristics of typical adenocarcinoma, and the carcinoembryonic antigen in the culture medium was strongly positive. N-myc gene amplification in adenocarcinoma of the lung is extremely rare, therefore we report herein on this case.
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PMID:Amplification of the N-myc oncogene in an adenocarcinoma cell line of the lung. 162 16


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