Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-Ha-ras gene was analysed by Southern blot hybridisation in 67 specimens of lymph node metastases and in 25 specimens of primary tumours obtained from 85 untreated patients with head and neck squamous cell carcinoma. The loss of one c-Ha-ras allele was observed in 10/46 (22%) tumours from heterozygous patients for this locus. Different genes, located as the c-Ha-ras gene on the short arm of chromosome 11, were also found to be deleted suggesting that the deletion of other genes could play a role in aggressiveness of head and neck carcinomas. Using polymerase chain reaction, mutation at codon 12 was detected in only 2/54 (3.8%) tumours but no mutation involving codon 61 was found. Neither gene amplification nor gene rearrangement could be observed. Total RNA was prepared from 79 of these tumour specimens and analysed by Northern and slot blot hybridisation. A 1.2 kb c-Ha-ras transcript band was detected in all the RNA preparations. Relatively high c-Ha-ras transcript levels were found in 18% of lymph node metastases and in 21% of primary tumours, indicating no significant differences between these cancers. Moreover, the c-Ha-ras mRNA levels were not significantly greater in the primary tumours than in the normal mucosae in 10/12 cases for which both tissues were analysed. These data indicate that c-Ha-ras gene does not seem to be strongly involved in head and neck carcinomas at that advanced stage of the disease, as this was previously reported for earlier clinical stages.
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PMID:Analysis of the c-Ha-ras-1 gene for deletion, mutation, amplification and expression in lymph node metastases of human head and neck carcinomas. 169 42

The use of aggressive chemotherapy undoubtedly has brought about a dramatic increase in the cure rate of osteosarcoma. The authors' investigations have increased the authors' knowledge of chemotherapy for osteosarcoma, the differential efficacy of currently used agents, and the pronounced schedule dependency and relative route independency of their efficiency. The authors were able to confirm the prognostic significance of tumor response after preoperative chemotherapy. Preoperative chemotherapy in itself has facilitated and promoted limb-salvage surgery. Also, more patients can be cured today by use of aggressive thoracic surgery in case of primary or secondary pulmonary metastases. The authors' efforts to steadily increase metastasis-free survival rates by intensifying chemotherapy in this series of studies, however, have been only moderately successful. Still, chemotherapy-related acute toxicity is considerable and increases with aggressiveness of treatment, and the manifestations of late toxicity may continue to increase with follow-up time. Future trials should be targeted toward exploration of the minimum indispensable amount of toxic treatment yielding comparable or even better results than those currently attainable.
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PMID:Local control and survival from the Cooperative Osteosarcoma Study Group studies of the German Society of Pediatric Oncology and the Vienna Bone Tumor Registry. 171 20

In 63 patients with primary grade 3 carcinoma in situ of the bladder flow cytometric deoxyribonucleic acid (DNA) analysis was performed at diagnosis and during an average followup of 63 months. The results of DNA measurements were related to disease progression, that is invasive tumor and/or metastatic disease. The DNA histograms were classified as diploid (2 patients) or aneuploid (61). A total of 3 categories of aneuploid tumors with different prognostic significance could be defined: 1) carcinoma in situ with 1 aneuploid cell population at diagnosis and with no change to multiple aneuploid cell populations throughout observation, 2) carcinoma in situ with 1 aneuploid cell population at diagnosis but with a later change to multiple aneuploid cell populations and 3) carcinoma in situ with multiple aneuploid cell populations already at diagnosis. At 5 years the progression-free survival for the 3 categories was 94%, 43% and 20%, respectively. Over-all, of the patients with multiple aneuploid cell populations (categories 2 and 3) 76% had progression, in contrast to 19% of those in category 1 (p less than 0.0005). In category 2 development of multiple aneuploid cell populations preceded progression in 8 of 11 progressive cases by an average of 20 months. Therefore, the occurrence of multiple aneuploid cell populations must be considered as a sign of high aggressiveness. We conclude that flow cytometric DNA analysis is a potent predictor of prognosis in cases of primary carcinoma in situ of the bladder.
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PMID:Deoxyribonucleic acid profile and tumor progression in primary carcinoma in situ of the bladder: a study of 63 patients with grade 3 lesions. 172 94

Prolonged disease-free survival of patients with recurrent or resistant non-Hodgkin's lymphoma (NHL) has been achieved with high-dose therapy followed by autologous bone marrow transplantation (ABMT). A concern with the use of ABMT is that the marrow that is reinfused may contain undetected NHL cells with the potential to reestablish metastatic disease in the recipient. Using a culture technique that is sensitive for detecting occult lymphoma cells in BM, we analyzed histologically normal marrow harvests from 59 consecutive patients with intermediate- or high-grade NHL who were candidates for high-dose therapy and ABMT. The culture results indicated that 22 of the patients had occult lymphoma in their marrow. Forty-three patients underwent high-dose therapy followed by ABMT. Twenty-four achieved a complete clinical remission. Those with occult lymphoma in their harvests (11 patients) continued to relapse for up to 3 years, whereas no relapses were observed beyond 8 months in 13 patients receiving marrow that did not contain detectable lymphoma cells using the culture technique. The relapses in the patients who achieved a complete remission occurred at sites of prior bulky disease rather than at new sites, suggesting that the ability to detect occult lymphoma cells in marrow is a marker of biologic aggressiveness and/or resistance to therapy, or that the reinfused cells could only grow in previously involved sites. The detection of lymphoma cells in marrow used for ABMT is an important adverse prognostic factor, and appears to be independent of other clinical predictors of outcome such as sensitivity or resistance of disease to prior chemotherapy.
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PMID:Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique. 173 92

We found previously that transforming growth factor-beta 1 (TGF beta 1) mRNA levels are markedly elevated in rat prostate cancer (Dunning R3327 sublines) compared to levels in normal prostate. Our goal was to determine whether elevated expression of TGF beta 1 is biologically relevant to prostate cancer growth in vivo. We chose as our model the R3327-MATLyLu prostate cancer epithelial cell line, which produces metastatic anaplastic tumors when reinoculated in vivo. Our approach was to stably transfect MATLyLu cells with an expression vector that codes for latent TGF beta 1 and to isolate subclones of cells that over-expressed TGF beta 1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF beta 1 cDNA insert. We then studied the growth of these cells in vivo and in vitro. Twenty days after sc inoculation of 10(6) cells in vivo, TGF beta 1-overproducing MATLyLu tumors were 50% larger, markedly less necrotic, and produced more extensive metastatic disease (lung metastases in 73% of all lobes and lymph node metastases in 88% of animals) compared to control MATLyLu tumors (lung metastases, 21%; lymph node metastases, 7%). Thus, TGF beta 1 produced in vivo is biologically active and can promote prostate cancer growth, viability, and aggressiveness, perhaps via effects on the host and/or on the tumor cells themselves. When followed in vitro, TGF beta 1-overproducing cells became growth inhibited, but this effect was transient as cells subsequently resumed proliferating. Growth inhibition was due to TGF beta, because it could be prevented by TGF beta-neutralizing antibody. Therefore, prostate cancer cells can activate and respond to secreted latent TGF beta 1, and although the cells are transiently inhibited in vitro, there is no net inhibition of growth. The ability of the cells to respond to endogenously produced TGF beta 1 suggests that TGF beta 1 overexpression enhances tumor growth in vivo at least in part via an effect of TGF beta 1 on the tumor cells themselves.
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PMID:Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. 173 67

Ovarian metastases from extragenital malignant tumours. An anatomohistopathologic approach. 102 cases of ovarian metastases from extragenital malignant non hematopoietic primaries have been studied in the Institute of Anatomy and Histopathology of the Trieste University. Breast cancers, followed by colonic, gastric and pancreatic tumours are the most frequent spreading primaries to the ovaries. Generally speaking the ovarian metastases seems to be closely related to the lower age at the tumour onset and to the width of metastatic spreading; this is true mainly for breast and colorectal cancer. These features should suggest that tumour aggressiveness, rather than some tropism of malignant cells, could play the most important role in the metastatic involvement of ovaries. A double behaviour should be instead suggested for gastric cancer: the first one is consistent with those previously described for the other tumours, the second one is related to a less aggressive gastric cancer, arising in the elderly (mean age 73 years old) with isolated involvement of the ovary showing the features of Krukenberg tumours.
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PMID:[Ovarian metastases of extragenital tumors. Anatomo-pathological contribution to their interpretation]. 174 79

The incidence of parathyroid carcinoma in patients surgically treated for primary hyperparathyroidism at the University of Michigan Hospital was 0.4% during an 18-year period. The courses of the five patients with metastatic disease are described. Histologic reevaluation and assessment of the DNA ploidy pattern were performed in each case. Localization studies preceded all reexplorations. The number of operative procedures in each patient ranged from two to 10. Two patients are living with recurrent disease and one has been disease free for 42 months. Two patients died after 2 and 12 years, respectively. Three patients had aneuploid tumors; one had a diploid tumor. One patient had both aneuploid and diploid cell populations. Dilemmas in diagnosis, localization, and medical and surgical management were encountered in patients with metastatic carcinoma. The chosen treatment should be evaluated individually in each case because of the variability in aggressiveness of this malignancy. Surgical resection proved most effective in some of these patients for both local and distant recurrences. Bisphosphonates and gallium nitrate have been reported to be effective in controlling hypercalcemia. Only the former had some effect in one of our patients.
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PMID:Metastatic parathyroid carcinoma: dilemmas in management. 174 86

Tumour and metastatic phenotypes, the pattern of mouse mammary tumour virus (MMTV) integration and expression, and the expression of a metastasis associated gene, nm23, were examined in three mammary tumour cell subpopulations, 66, 168 and 4526. Tumour growth, host survival, metastatic aggressiveness, and the distribution of different cell types in metastasis resulting from mixed cell inocula were also analysed. The results of these studies indicated that the cell lines were distinguishable from each other both phenotypically and genotypically. However, a rearrangement of the mammary tumour specific protooncogene, int-1, caused by MMTV was found to be a unique characteristic of the cell line 4526. Therefore, int-1 was used as a stable marker to examine the genotype of the metastatic colonies that developed in mice bearing tumours of mixed cell inocula. Highly metastatic 4526 cells influenced the metastatic range of poorly metastatic 66 cells. Line 66 cells that normally colonize only to lungs were also found to colonize liver when inoculated together with the liver-metastasizing 4526 cells. This acquired metastatic phenotype of 66 cells was transient. On the contrary, mixed cell inocula of 4526 and non-metastatic 168 cells did not produce any colony of 168 cells. The metastatic aggressiveness of 4526 cells was inhibited by both 66 and 168 cells. Furthermore, the metastatic behaviour of mixed inocula differed depending on the relative abundance of the component populations in the mixtures. These findings suggest that interaction between cells of different metastatic phenotypes may result in changes of their metastatic behaviour.
Clin Exp Metastasis
PMID:Mixed inocula of mouse mammary tumour cell subpopulations result in changes of organ-specific metastasis. 175 81

In operable breast cancer, cell kinetics can be utilized in the prediction of the clinical outcome of patients. The discovery of monoclonal antibodies recognizing antigens related to cell proliferation has permitted the assessment of cell kinetics by rapid and practical immunocytochemical methods. It is claimed that the Ki-67 mouse monoclonal antibody recognizes an antigen expressed in proliferating cells but not present in quiescent (G0) cells. To study the relationship between Ki-67 score and DNA flow cytometric S-Phase Fraction (SPF), the latter being one of the most widely used methods to assess cell kinetics, we compared these two techniques of measurement in 122 breast carcinomas using both for each specimen. In this series 90% of tumors were Ki-67 positive, with a median value of 7.5% (range 1% to 70%). DNA flow cytometric analysis revealed that 69 tumors (57%) were aneuploid, whereas 53 were diploid. The median SPF value was 8% for diploid and 15% for aneuploid tumors (range 2% to 32%). Ki-67 scores were significantly higher in the DNA aneuploid compared to the diploid carcinomas (p = 0.015). Overall, a good correlation was found between Ki-67 and SPF values both in diploid (r = 0.60) and in aneuploid (r = 0.38) tumors. High Ki-67 scores were associated with the presence of axillary lymph node metastases (p = 0.0023) and poor histologic differentiation (p = 0.0028). Menopausal status, tumor size and peritumoral vessel invasion were unrelated to the Ki-67 score. Over-expression of the Epidermal Growth Factor receptor (EGF-r) and the c-erbB-2 oncogene were not correlated with Ki-67 staining. In conclusion, in this study Ki-67 immunostaining correlated with other indices of cell proliferation (SPF and Grade) and with some features of tumor aggressiveness (DNA aneuploidy and lymph node metastases) but seemed to be independent of some biological markers (EGR-r and c-erbB-2). Since the major objective for assessing proliferative status in Stage I-II breast carcinoma is to determine prognosis, it will have to be evaluated whether the determination of the Growth Fraction has comparable or even greater prognostic value than other cell kinetics markers.
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PMID:Breast cancer cell kinetics: immunocytochemical determination of growth fractions by monoclonal antibody Ki-67 and correlation with flow cytometric S-phase and with some features of tumor aggressiveness. 177 34

The authors, in reporting their series of 6 bronchopulmonary carcinoids, dwell upon the criteria used to classify such neoplasms pointing out the related diagnostic problems. The presence of metastases and/or local recurrences as well as the impossibility to define the aggressiveness of the tumor brought the authors to consider such tumors as malignant. They conclude for a surgical approach which should be conservative: segmentectomy and lobectomy in elective procedures, whereas pneumonectomy and endoscopic resection should be reserved to particular cases.
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PMID:[Bronchopulmonary carcinoids: neoplasms with attenuated malignancy or true and proper malignant tumors?]. 186 69


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