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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that rat embryo cells transformed by the ras oncogene alone are both tumorigenic and highly metastatic when injected into nude mice. In contrast, rat embryo cells transformed with the ras oncogene and the adenovirus 2 (Ad2) Ela gene are tumorigenic but either fail to metastasize, or exhibit a very low metastatic potential. Here we demonstrate that transfection of the Ad2 Ela gene into several of the ras transformed rat embryo cell lines results in a dramatic reduction in metastatic potential relative to the parental cell line. Transfection of cDNAs for the 12S and 13S Ela transcripts showed that both gene products are capable of reducing the metastatic potential of the ras transformed cell lines, however the 12S cDNA was more effective. This effect is specific to the Ad2 Ela gene as ras transformed cell lines expressing the Ad12 Ela gene or the human N-myc gene maintained their high metastatic potential. We hypothesize that the Ad2 Ela gene may regulate the expression of one or more cellular genes that contribute to the metastatic phenotype.
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PMID:Regulation of the metastatic phenotype by the E1A gene of adenovirus-2. 297 15

Metastasis formation is a multistep process that probably requires a complex interplay of a large and heterogeneous group of genes, including genes involved in cellular resistance to immunorejection and genes controlling the invasive potential of cells. Transfection experiments have shown that oncogenes of the ras gene family as well as oncogenes of the kinase group are able to induce invasive and metastatic properties in non-transformed cells as well as in tumorigenic, but non-metastatic, cells. However, these findings are not in agreement with observations on spontaneous human tumours in which no correlation was found between activation or increased expression of ras genes and the invasive and metastatic properties of these cells. Further studies have indicated that in particular cell types nuclear oncogenes like N-myc and adenovirus derived E1A may influence metastasis formation by trans-regulation of other genes, including class I genes of the major histocompatibility complex and genes coding for proteolytic enzymes. The many efforts to identify additional invasion and metastasis associated genes by transfection of high molecular weight metastatic tumour DNA met with little success. Somatic cell fusion studies, however, indicate that such genes exist and that one or more of them are located on human chromosome 7.
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PMID:Genetic analysis of invasion and metastasis. 307 71

We have examined the genomic organisation of c-myc, N-myc, L-myc, neu and N-ras in tissue from 41 breast carcinomas, lymph node metastases from 10 of these carcinomas, one fibrosarcoma, 10 cases of benign fibrocystic breast and six fibroadenomas. We have not observed an alteration in either N-myc or N-ras in any of the samples studied. We have seen a 2-fold amplification of L=myc in DNA from one infiltrating ductal (ID) carcinoma, but otherwise we have seen no alterations to this gene. Amplification of c-myc was seen in 22% of ID breast carcinoma sample. Levels of amplification ranged from 2- to 10-fold. We have found a significant (p less than 0.02) correlation between an altered c-myc gene and a very poor short-term prognosis. Amplification of neu was seen in 19% of ID breast carcinomas, but the levels of amplification were higher than those seen for c-myc. Alterations to neu also correlated well with poor short-term prognosis (p less than 0.0002). Finally, we have observed a low level of amplification of c-myc in DNA from a benign fibrocystic breast lesion. This lesion exhibited some features characteristic of those thought to be associated with an increased risk of developing breast cancer.
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PMID:Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis. 333 Jul 85

In 28 patients with neuroblastoma of different stages the karyotype was determined in the primary tumour and/or in the metastases by direct chromosome preparation or short term cell culture. In addition, DNA analysis for the proto-oncogene N-myc was performed for comparison in 10 cases. Abnormalities (deletions, translocations, derivations) of the short arm of chromosome 1 with the most frequent breakpoint at 1p32 (besides rarer aberrations in other chromosomes) were found in the tumour karyotype of 15 of 18 (83%) patients with metastatic disease (stage IV) and in 2 of 3 patients with stage III, but in none of the 7 patients with stages I, II, IV-S who are all alive with no evidence of disease. These 7 surviving patients with good prognosis had a hyperploid tumour karyotype, mainly in the triploid range. Eleven of the 18 (61%) patients with stage IV and 1 of 3 patients with stage III also contained double minutes (DMs) and/or homogeneously staining regions (HSRs) in their tumour karyotypes. N-myc amplification (30 to 60 copies) in the tumour DNA was detected in 2 of 6 (33%) examined cases with stage IV, in 1 out of 2 examined cases with stage III, and correlated with the presence of DMs/HSRs. Life table analysis showed a 90% probability of surviving in patients lacking the 1p abnormality as compared to less than 10% in patients with an aberrant 1p chromosome in the tumour cells. We conclude that tumour karyotype, in particular the structure of the short arm of chromosome 1, is the most important factor in determining the different outcome in children with neuroblastoma.
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PMID:Tumour karyotype discriminates between good and bad prognostic outcome in neuroblastoma. 334 45

Long-term cell cultures (GI-LA-N and GI-ME-N) were established from the metastases of two disseminated neuroblastomas (NB). The first was obtained from a lymph node biopsy of a stage III NB after 7 months of chemotherapy, and the second from a bone marrow specimen of a stage IV NB after 6 months of chemotherapy. Cytogenetic investigation revealed several structural and numerical alterations in both cell cultures, but the only common chromosomal aberration was partial monosomy of 1p. Moreover, at the 5th in vitro passage, GI-LA-N displayed a high number of double minutes, not seen in GI-ME-N even after 33 subcultures. Molecular analysis revealed N-myc oncogene amplification in GI-LA-N cells, whereas, only one copy was found in GI-ME-N. No structural N-myc rearrangement was detected in either cell culture.
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PMID:Cytogenetic and molecular study of two human neuroblastoma cell lines. 342 78

Although infants (age less than 1 year) with neuroblastoma have a favorable overall prognosis, metastatic disease is associated with poorer treatment outcome. To assess the role of surgery in these patients, the authors reviewed survival data for 151 infants treated for neuroblastoma, focusing on patient and tumor characteristics, biological markers, and surgical management among the 99 patients with metastatic disease. Patients were divided into early (1961 to 1978) and contemporary (1979 to 1993) treatment eras. Potential prognostic factors were statistically tested to determine their significance in affecting survival. Five-year survival by Pediatric Oncology Group stage was: A, 100% (+/- 0%); B, 94% (+/- 6%); DS, 77% (+/- 9%); C, 73% (+/- 9%); and D, 61% (+/- 8%). Survival for infants with metastatic disease (stages C, D, and DS) was affected significantly by treatment era (P = .0001). Analyses restricted to patients treated during the contemporary era showed prognostic significance for DNA index (P = .02), N-myc copy number (P = .007), serum lactate dehydrogenase level (P = .001), and extent of resection (P = .01). A > or = 95% resection of the primary tumor was found to be associated with improved survival. Significantly more surgical complications were associated with resections performed at the time of diagnosis (P = .007), and delaying surgery until after several courses of chemotherapy did not decrease survival. In conclusion, multiple factors affect the outcome of treatment for infants with metastatic neuroblastoma, and whenever feasible, a > or = 95% resection of the primary tumor should be performed in this patient subgroup.
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PMID:Infants with metastatic neuroblastoma have improved survival with resection of the primary tumor. 747 48

A nude mouse model for human neuroblastoma has been developed to examine possible relationships between amplification/over-expression of the N-myc oncogene and altered regulation of expression of specific integrin subunits during tumor progression. Subcutaneous (ectopic) or intra-adrenal (orthotopic) injection of the neuroblastoma cell lines SK-N-SH or IMR-32 has generated a number of derivative tumor cell lines. Tumor cell lines derived from SK-N-SH cells (which do not express N-myc) or IMR-32 cells (which over-express N-myc) produce tumors at higher rates when re-injected into the subcutaneous space of nude mice. Moreover, cell lines derived from tumors initiated by IMR-32 cells exhibit shorter latent periods than do IMR-32 cells direct from tissue culture. With regard to integrin subunit expression, SK-N-SH and related cell lines express high levels of beta 1 integrin, which is associated with the alpha 2 and alpha 3 integrin subunits (predominantly alpha 3). IMR-32 cells display reduced beta 1 expression, and that which is produced is not associated with common alpha subunits. LaN1 cells, which express N-myc at even higher levels than do IMR-32 cells, express even less beta 1. Interestingly, the tumor-derived cell lines (especially those from tumors initiated in adrenal glands) also exhibit reduced integrin expression compared with the parental cell lines; this reduction is associated with the enhanced tumor take rate observed when the cells are re-injected into nude mice. Our results raise the possibility of a relationship between over-expression of N-myc and down-regulation of beta 1 integrin expression (possibly some alpha subunits also). In addition, the data suggest that human neuroblastoma-derived cell lines which exhibit reduced integrin expression display more aggressive tumor growth in nude mice.
Clin Exp Metastasis 1995 Mar
PMID:Inverse expressions of the N-myc oncogene and beta 1 integrin in human neuroblastoma: relationships to disease progression in a nude mouse model system. 753 87

Nationwide neuroblastoma mass screening for 6-month-old infants (first screening) was introduced in Japan in 1985. About 110 neuroblastoma cases are detected annually by the first screening and treated, with a survival rate of 97%. Sensitivity of the first screening (positive cases/positive cases+false negative cases) is about 75%, and the prognosis of false-negative cases is unfavorable. A second screening at 18 months of age was started to rescue false-negative cases in Miyagi Prefecture in May 1992. Of 62 neuroblastoma cases treated in our hospital since 1985, 40 cases had received the first screening. Twenty cases were positive at first screening, 18 cases were false negative, and 2 cases were false negative and picked up by the second screening. Age distribution of false-negative cases ranged from 12 to 83 months and included 12 cases younger than 36 months old. Only 5 of 18 false-negative cases are alive without the disease. From May 1992 to November 1993, 14,282 infants had received the second screening (compliance rate: about 75%), and 2 neuroblastoma cases were detected. The first case was stage III with paraortic lymph node metastases, Shimada UH, aneuploidy and negative N-myc amplification. The second case was stage II with Shimada FH, aneuploidy, and negative N-myc amplification. Both cases are alive now without the disease after undergoing radical operation and chemotherapy. The first screening is effective for early detection of neuroblastoma cases, but the sensitivity is insufficient; the authors recommend a second screening to rescue false-negative cases.
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PMID:Problems of neuroblastoma screening for 6 month olds and results of second screening for 18 month olds. 776 Feb 44

One hundred and ten patients with advanced neuroblastoma were treated with the protocol of the Study Group of Japan between January 1985 and March 1991. Patients received six cyclic courses of regimen A1, consisting of cyclophosphamide (1,200 mg/m2), vincristine (1.5 mg/m2), tetrahydropyranyl adriamycin (40 mg/m2), and cisplatin (90 mg/m2). Primary tumors and regional lymph node metastases were removed some time during the first six cycles of regimen A1. After six cycles of A1, the patients were divided into three groups. Patients in group 1 received alternating treatment with regimen B (cyclophosphamide and ACNU) and intensified A1, and those in group 2 were treated with alternating administration of regimen C (cyclophosphamide and DTIC) and intensified A1. Patients in group 3 were treated with supralethal therapy and bone marrow transplantation (BMT). Event-free survival rates at five years were 38.8% in the chemotherapy group (groups 1 and 2) and 50.0% in the transplant group (group 3). Because of the study design that was not in truly randomized fashion and because of the small number of patients in each risk group, it is indicated, though not concluded, that the transplant group had a better prognosis than the chemotherapy group in the cases with stage III disease or with amplified N-myc oncogene, based on the statistical calculations. Differences in survival rates for patients who underwent BMT when complete remission (CR) was achieved and for those who achieved CR but who did not undergo marrow transplant were statistically insignificant. BMT-related death occurred in 3 of 31 cases (9.7%) undergoing marrow transplant, and the causes of the death included hemorrhagic pneumonia, myocardial disturbance and hemorrhagic uremia.
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PMID:Treatment combined with bone marrow transplantation for advanced neuroblastoma: an analysis of patients who were pretreated intensively with the protocol of the Study Group of Japan. 783 40

The adenovirus (Ad) E1 region genes, E1A and E1B, are well known cooperatively to transform primary rodent cells and activate a number of cellular promoters, including nuclear oncogenes such as N-myc and c-jun, in transfected cell lines. However, there is still less information available on the in vivo mechanism(s) by which the E1 region gene, when chromosomally integrated in the living animals, exerts its effect on nuclear oncogene activation coupled with transformation. To investigate such in vivo activity of E1A we have used a series of microinjection experiments into fertilized eggs to generate three transgenic mice carrying the Ad12-type E1A/E1B genes under the control of the human renin gene. This transgene caused an early onset of bowel cartinoid tumors that express neural cell adhesion molecules, but do not metastasize to any region. Northern blot analysis revealed that the transgenes were considerably expressed in the tumors, but not in other tissues at detectable levels. Interestingly, the levels of N-myc and c-jun mRNAs in the cartinoid tumors were elevated 19- and 8-fold, respectively, as compared with those found in the control intestine. In contrast, the major histocompatibility complex (MHC) class I mRNA level was not altered between the tumor and control intestines, suggesting that this unchanged expression may reflect the loss of tumor metastasis. These findings provide the first in vivo evidence that the expression of the Ad12 E1 region gene induces cartinoid tumors associated with the activation of the nuclear oncogenes N-myc and c-jun.
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PMID:Activation of the nuclear oncogenes N-myc and c-jun in carcinoid [correction of cartinoid] tumors of transgenic mice carrying the human adenovirus type 12 E1 region gene. 786 36


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