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)

Cells contracting connective tissue matrices generate tractional forces in tissues. Studies of fibroblast contraction, using collagen gels in an in vitro model, demonstrate that it involves the actin cytoskeleton, specific extracellular matrix receptors and requires stimulation by exogenous promoters. Fibroblast contraction is stimulated by factors released by platelets and potentially secreted within the contracting tissue. Endothelial cells secrete a potent promoter of fibroblast contraction which has been identified as endothelin 1. The pathway through which fibroblast contraction is stimulated appears to require activation of protein kinase C. Tumor cells can also secrete endothelin. These mechanisms may be relevant to tumor progression.
Cancer Metastasis Rev 1992 Mar
PMID:Extracellular matrix contraction by fibroblasts: peptide promoters and second messengers. 151 96

A clone of BALB/c 3T3 cells (A-31), which is highly resistant to spontaneous in vitro transformation, was treated with the carcinogen benzo(a)pyrene [B(a)P]. This agent was capable of inducing in vitro transformation in the presence of S9 activating system and 6 weeks after treatment large foci were detected. Transformation frequency in solvent control groups was very low. Three foci from a single plate of two different experiments were pooled and the cells tested for their in vitro invasive properties and in vivo tumorigenic and metastatic potential. B(a)P-transformed 3T3 cells grew in soft agar and were highly tumorigenic when injected s.c. in nude mice (75% incidence within 7 weeks). Untreated cells were poorly tumorigenic (0/4 mice had tumors within 7 weeks), though they also gave rise to neoplasms after a longer latency. Spontaneous metastasis incidence was low for both controls and treated cells; however, almost all animals (15/16) injected i.v. with B(a)P-transformed cells had pulmonary nodules in the experimental metastasis assay. A few nodules in some of the animals in the control group were detected (4/16). B(a)P-transformed cells were able to invade a thin coating of matrigel in the chemoinvasion assay and also grew in matrigel showing an invasive, branching morphology. Untreated cells did not grow or invade. Our data suggest that a single treatment with a chemical carcinogen can increase tumorigenicity as well as confer invasive and experimental metastasis potential in BALB/c 3T3 cells. This work provides evidence for a role of chemical carcinogens in tumor progression.
Invasion Metastasis 1992
PMID:Induction of invasive and experimental metastasis potential in BALB/c 3T3 cells by benzo(a)pyrene transformation. 151 33

The increased expression of proteolytic systems is one of the characteristics of transformed and malignant cells and their evaluations in whole tumor homogenates were considered as possible diagnostic and/or prognostic factors. Abnormal intracellular distribution, increased activities and secretion of cysteine proteinases (CPs) cathepsin B (Cat B) and L (Cat L), were associated with tumor progression. In the present study of matched pairs of breast carcinoma and normal breast tissue, the activities of Cat B and Cat L in breast carcinoma homogenates were found to be 20 and 50 fold higher, respectively, than in normal tissues. In contrast, a decrease in total inhibitory activity of cysteine proteinase inhibitors (CPIs) was observed but an average ratio between tumor and normal tissues was only 0.75. One of the CPIs, stefin A, was also determined immunochemically. The activities of CPs and CPIs were compared to the increased levels of cathepsin D (Cat D) activities in individual patients, but no statistically significant correlations were found. We correlated CPs and CPIs with morphological and receptor data as well as the axillary lymph node metastases. There was no statistical correlation of CP and CPIs with the number of lymph node metastases. However, highly elevated levels of Cat B and Cat L and lowered CPI activities in tumor cytosols were often associated with poorly differentiated carcinomas and those with negative ER and PR values. We conclude that cysteine-dependent proteolysis may play an important role in breast tumors.
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PMID:Cystatins and cathepsins in breast carcinoma. 151 89

We have previously reported a complete allelotype study of 86 primary breast carcinomas, in which each non-acrocentric chromosome arm was studied with at least one polymorphic DNA-marker for the presence of allelic imbalance (AI, allelic loss or allelic gain) in the tumor. Here we report the statistical analysis of this data set, investigating the relationships between AI, DNA aneuploidy and several clinico-pathological parameters of tumor progression. AI on 13 different chromosome arms, including 3p, 11p, and 17p, correlated significantly with the total number of AI events at other sites, suggesting that they are progression-related events. AI at 1q and 16q did not show such a correlation and may thus represent earlier events. Mean fractional allelic imbalance (FAI) was significantly higher in flow cytometrically aneuploid tumors than in diploid tumors (0.27 vs. 0.17, p = 0.007), and was highest in hypotetraploid tumors (0.37). This suggests that tetraploidization followed by chromosome segregation may underlie the development of AI at multiple sites. No correlation was found between mean FAI and clinico-pathological variables such as lymph-node involvement, stage, age, estrogen-receptor content and development of distant metastases, although there was a noticeable trend towards impaired survival for those patients with a higher-than-median FAI value.
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PMID:Fractional allelic imbalance in human breast cancer increases with tetraploidization and chromosome loss. 153 20

Immunohistochemical staining for the p53 protein was performed in 107 snap frozen primary endometrial adenocarcinomas and 15 benign uterine tissues using monoclonal antibody PAb1801. No staining was seen in benign samples, whereas intense nuclear staining of cancer cells consistent with overexpression of the p53 protein was observed in 22 of 107 cancers (21%). p53 overexpression was more frequent in advanced (Stage III/IV) cancers (41%) than in early (Stage I/II) cancers (9%) (P less than 0.001), and also was associated with nonendometrioid histology (P = 0.008), positive peritoneal cytology (P = 0.01), extrauterine metastases (P = 0.003), and negative progesterone receptor status (P = 0.04). To confirm the relationship between p53 overexpression and mutation, p53 mRNA from 8 cancers was reverse transcribed and amplified using the polymerase chain reaction. DNA sequencing revealed point mutations in each of the 5 cancers that overexpressed p53, whereas the wild-type sequence was found in 3 cancers that did not overexpress the protein. Each of the 5 mutations resulted in an amino acid substitution in a highly conserved region of the p53 gene where mutations have been found in other cancers. Further studies are warranted to determine whether the association between p53 overexpression and advanced stage disease is due to accumulation of genetic lesions during tumor progression or whether p53 alterations confer a more virulent phenotype.
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PMID:Overexpression and mutation of p53 in endometrial carcinoma. 154 Sep 70

The use of non-radioactive in situ hybridization (ISH) with chromosome-specific repetitive DNA probes to study genomic changes, aneuploidy, and heterogeneity during melanocytic tumor progression, relies on its applicability to non-mitotic interphase nuclei, present in cell suspensions and tissue sections. Therefore, we studied the feasibility of detecting numerical aberrations with respect to the (peri-) centromere regions of chromosomes 1 and 7 in intact nuclei of two human melanoma cell lines with different metastatic behavior in nude mice. In addition, we used paraffin sections from xenograft lesions, obtained by inoculation of these cell lines in nude mice (subcutaneous tumors and spontaneous lung metastases). Paraffin sections from the original primary cutaneous melanoma (with a subepidermal and a dermal part) and two loco-regional metastases were also studied, one of which was the source for the cell lines. These cells and tissues represent examples of materials used in different approaches to the study of melanocytic tumor progression. Regarding the targeted sequences, ISH analysis showed that both cell lines were heterogeneous and aneuploid. The results correlated well with those obtained by ISH on metaphase spreads. Differences between the lines, which could not be detected by flow-cytometric or conventional karyotyping analysis, included data suggestive of a polyploid subpopulation and an extra copy of chromosome 7 in the metastasizing cell line. The polyploid population could be detected also in the paraffin sections of the corresponding subcutaneous xenografts and lung metastases in the mice. Both areas in the patients' primary melanoma could be evaluated separately and showed similar supernumerary aberrations of the chromosome-specific targets. These abnormalities matched those found in both metastases. Our results demonstrate that ISH can be used to visualize genomic abnormalities at the single-cell level in melanocytic nuclei in their natural context, which makes it a promising tool in the histopathology of melanocytic lesions and in the study of melanocytic tumor progression.
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PMID:In situ detection of supernumerary aberrations of chromosome-specific repetitive DNA targets in interphase nuclei in human melanoma cell lines and tissue sections. 154 28

Thirty-one patients with disseminated melanoma or renal cell cancer (RCC) who had a limited relapse or persistent disease after a partial or complete response to interleukin-2 (IL-2)-based immunotherapy underwent resection of progressing tumors or residual sites of disease. There were no surgery-related deaths. The median time to disease progression after resection for patients with RCC (n = 16) and melanoma (n = 15) was 11 and 5 months, respectively. All patients with melanoma had tumor progression within 10 months of surgery. Seven of 16 patients with RCC were free of tumor progression 4 to 44 months after surgery. Three of 12 patients with RCC rendered disease-free by surgery remain disease-free after 2 years. These data suggest that surgical resection is a reasonable option in selected patients who have a relapse after responding to IL-2-based immunotherapy. Although this retrospective study could not determine the relative survival benefits of surgery and immunotherapy, it showed that resection of metastatic disease after a response to immunotherapy can result in significant disease-free survival in patients with RCC but not melanoma.
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PMID:Surgical resection of metastatic renal cell carcinoma and melanoma after response to interleukin-2-based immunotherapy. 155 Oct 67

The effects of acute and chronic ethanol administration on tumor progression and metastasis were studied in rat models of leukemia and breast cancer, respectively. Acute administration of 1.5-3.5 g of ethanol/kg body weight significantly reduced survival of rats injected with CRNK-16 leukemia cells in a dose-related manner. Acute administration of 2.5-3.5 g of ethanol/kg body weight, one hour before tumor inoculation, or chronic consumption of liquid diet containing ethanol for two weeks before and three weeks after tumor inoculation, significantly increased the number of lung metastases of MADB106 mammary adenocarcinoma. The ethanol-induced increase in the number of metastases was not correlated with plasma levels of corticosterone and was not altered by the opiate antagonist naltrexone. Incubation of spleen cells in vitro in the presence of ethanol, at concentrations comparable to those measured in the blood of ethanol-treated rats, significantly suppressed natural killer (NK) cell activity against MADB106 cells in a standard chromium-release assay and decreased the binding of effector to MADB106 tumor cells. However, neither acute nor chronic ethanol administration in vivo altered splenic NK activity against this tumor in the same in vitro assay, in which the ethanol would have been washed away. These results suggest that, in the presence of ethanol, tumor progression is facilitated. The possibility that this facilitation is related to ethanol-induced impairment of the normal tumoricidal interaction between NK and tumor cells is discussed.
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PMID:Ethanol increases tumor progression in rats: possible involvement of natural killer cells. 157 4

Operative method, course and complications were analyzed retrospectively in 140 patients who underwent a conservative operation for renal tumor between June 1969 and December 1990. In 53 patients (20 women and 33 men, mean age 61.2 years, range 38 to 77 years, with 49 renal cell carcinomas and 4 benign renal tumors) there was an imperative indication for an organ preserving operation because nephrectomy would have made dialysis obligatory. In 87 patients (29 women and 58 men, mean age 53.7 years, range 27 to 74 years, with 72 renal cell carcinomas and 15 benign renal tumors) the tumor was conservatively resected in the presence of a normal contralateral unit (elective indication) and 68 of these patients (78%) were symptom-free. In the imperative group 32 of 49 patients (65.3%) with renal cell carcinoma had no evidence of disease after a mean followup of 4.6 years. Known metastases were present in 4 of 7 patients who died of the tumors in this group. In 3 patients with an imperative indication for conservative surgery a second tumor occurred in the kidney: 2 were treated with further parenchyma sparing operations, while in 1 with poor physical condition no further measures were possible. Of 72 patients with renal cell carcinoma who underwent an elective operation 68 (94.4%) had no signs of tumor progression after a mean followup of 3.3 years. One patient died of tumor metastases, and 2 (2.7%) had tumor recurrence in the kidney requiring nephrectomy and enucleation, respectively. The 5-year cause-specific survival rates for the imperative and elective groups were 84% and 96%, respectively. Patients with a local stage T3 tumor were characterized by a significantly worse survival curve than those with a stage T1 or T2 tumor but no significant difference was noted among the various grades of differentiation.
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PMID:Conservative surgery of renal cell tumors in 140 patients: 21 years of experience. 161 74

In 72 patients with urothelial carcinoma of the renal pelvis or ureter the ploidy, deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the tumor were analyzed by means of single cell DNA cytophotometry with the intention of finding new prognostic factors in addition to those already known (stage and grade). Followup ranged from 1 to 8 years. The results of the DNA analyses were related to the tumor categories, histopathological grading of the tumors and clinical course. Malignancy grade 1 tumors showed DNA frequency peaks in the diploid range, while tumors assessed as malignancy grade 2 showed heterogeneous DNA distribution patterns. Malignancy grade 3 tumors exhibited 71% aneuploid and 29% tetraploid DNA values. The proliferation rate of the tumor cells was statistically significantly higher in malignancy grades 2 and 3 than in malignancy grade 1. The prognosis for grade 1 tumors is good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups (patients with grades 1 and 3 tumors) DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the other hand, are heterogeneous in respect to DNA ploidy although they exhibit the same histomorphological degree of differentiation. These tumors can be subclassified as aneuploid (biologically aggressive) and diploid or tetraploid (biologically less aggressive) tumors. There was also a positive correlation between T category and DNA ploidy. The cell lines were aneuploid in 38% of the patients with stage T1 tumors, 56% with stage T2 tumors and almost 85% with stage T3, N+ tumors. A significant correlation was found between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei had no metastases and no local tumor progression for up to 8 years, whereas patients with aneuploid tumor cell nuclei suffered metastasis and local tumor progression within 24 to 36 months. The patients died of the tumor 36 months after primary diagnosis on the average. The determination of DNA ploidy, tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry affords valuable clues as to prognosis.
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PMID:Transitional cell carcinoma of the renal pelvis and ureter: prognostic relevance of nuclear deoxyribonucleic acid ploidy studied by slide cytometry: an 8-year survival time study. 161 75


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