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

Nitric oxide (NO) may be an important mediator of tumour angiogenesis and metastasis formation. Tumour cell derived NO may be important in the regulation of angiogenesis and vasodilatation of the blood vessels surrounding a tumour. The aims of the present study were, firstly, to determine whether malignant melanoma cells and normal melanocytes had nitric oxide synthase (NOS) activity (measured by the conversion of L-arginine to L-citrulline) and, secondly, to determine whether there was a difference in NOS activity between malignant and normal cell types. This paper assays NOS activity directly in lysates from normal human melanocyte and malignant melanoma cell lines. The enzyme activity was not inducible with bacterial lipopolysaccharide and could be heat denatured. The activity of NOS was demonstrated to be both NADPH- and calcium-dependent and it was inhibitable in a dose-dependent manner by the NOS inhibitor Nw-nitro-L-arginine methyl ester. We conclude that melanoma and melanocyte cells express a constitutive form of NOS. Finally, nitric oxide synthase activity in melanoma cell lines was found to be significantly greater than in normal melanocytes. These findings suggest that NO synthesis is elevated in malignant melanoma. An elevated NO concentration in melanoma is expected to promote metastases by maintaining a vasodilator tone in the blood vessels in and around the melanoma.
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PMID:Nitric oxide synthase activity is up-regulated in melanoma cell lines: a potential mechanism for metastases formation. 879 Dec 69

Since the pretherapeutic T and pT classification of vocal cord cancer according to the UICC has often been found to fail in a high percentage of cases, frequently resulting in an insufficient separation of the different T categories, the pT classification proposed by Glanz was applied in order to obtain a more exact and better reproducible pretreatment system. In a histopathological investigation of 223 previously untreated carcinomas of the vocal cord dating from 1978 to 1988, specimens from total and partial laryngectomies were examined by subserial sectionings. The extension of each lesion was ascertained by measuring tumor in three dimensions per millimeter and determining affected histopathological structures. Neck lymph nodes were also examined for metastases. The different tumor stages were then evaluated with the UICC T/pT classification of Glanz's pT classification. The survival rates and recurrence-free rates of both classification systems were compared. Our evaluation showed that 24% of all the vocal cord cancers studied had to be classified to a higher tumor stage. The pT classification developed by Glanz was better able to separate the different tumor categories than the UICC T/pT classification. Glanz's pT classification system, staging a glottic cancer according to its exact size and laryngeal structures involved, is a significant improvement on the UICC T and pT classification used to date.
HNO 1996 Aug
PMID:[The pT-classification of primary vocal cord carcinomas and its significance for T-classification]. 880 12

Malignant tumors of the larynx are an important disease entity in otorhinolaryngology and mainly involve squamous cell carcinomas. Different epithelial or mesenchymal malignant tumors are reported only sporadically and metastases localized in the larynx are even rarer. In this report we present a patient who was found to have a laryngeal metastasis from an adenocarcinoma. An ovarian carcinoma treated 7 years previously was the primary tumor and first metastasized into the left lung and then into the subglottig area of the larynx. Because the surgical procedures and chemotherapy used for each lesion were successful and no local recurrences were found, the same therapeutic rules for the treatment of metastases to the larynx should be applied as in cases of primary malignancies.
HNO 1996 Jan
PMID:[Metastasis of adenocarcinoma of the ovary to the subglottis. A laryngologic rarity]. 881 26

The metastatic process is characterized by a complex series of sequential steps involving constant interactions (mutual "cross-talks") of metastasized tumor cells with their microenvironment (lymphocyte, macrophages, endothelial cells, etc.) in target organs. These interactions determine the outcome of metastasis (either the eradication of metastatic cells or their increased proliferation and invasion). Recently developed methods of tumor and host cell analysis at the molecular level allow better elucidation of molecular mechanisms of metastasis and of immune mechanisms involved in antitumor responses. Direct modulation of these processes will probably increase the success of clinical cancer treatment. Here we review data (a) on the expression of some costimulatory (MHC class II, CD80, sialoadhesin) and adhesion (LFA-1, ICAM-1, VLA-4) molecules on both metastasized tumor cells and host cells and (b) on the production of a cytotoxic molecule, nitric oxide, by in situ activated Kupffer and endothelial cells in the process of liver metastasis. This study was performed with well-characterized murine ESbL T lymphoma cells transduced with the bacterial lacZ gene, which allows detection and quantification of metastases at the single cell level throughout lymphoma growth and metastasis. Experimental results are discussed in the context of recent literature.
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PMID:New insights into tumor-host interactions in lymphoma metastasis. 884 48

Interactions between metastasizing tumor cells and host cells in target organs determine the outcome of metastasis. This review discusses the dual role of activated host endothelial cells in the metastatic process. On one hand, the upregulation of the expression of particular adhesion molecules leads to increased tumor cell binding, and the stimulation of angiogenesis provides the vascular support for the growth of already established metastases. On the other hand, endothelial cells can contribute to host anti-metastatic responses, e.g. by production of the cytotoxic molecule nitric oxide (NO) from arginine with the help of the inducible nitric oxide synthase (iNOS). Using a well-characterized ESbL-lacZ mouse T lymphoma model with a typical three phasic growth profile, we showed during the period of growth retardation a stimulation of NO production by ex vivo isolated liver sinusoidal endothelial cells. The induction of NO synthesis in liver endothelial cells did not require the presence of Kupffer cells and appeared to be stimulated by and dependent on mature T lymphocytes. A breakdown of this NO synthesis coincided with the second tumor expansion phase.
Cancer Metastasis Rev 1996 Jun
PMID:Liver endothelial cells: participation in host response to lymphoma metastasis. 884 99

Adhesion of circulating tumor cells to microvascular endothelium plays an important role in tumor metastasis to distant organs. The purpose of this study was to determine whether nitric oxide (NO) would attenuate tumor cell adhesion (TCA) to naive or lipopolysaccharide (LPS)-treated postcapillary venules. A melanoma cell line, RPMI 1846, was shown to be much more adhesive to postcapillary venules isolated from rat mesentery than to corresponding precapillary arterioles. Although venules exposed to LPS for 4 h demonstrated an increased adhesivity for the melanoma cells, TCA to LPS-treated arterioles was not altered. Isolated venules exposed to DETA/NO (1 mM), an NO donor, for 30 min prior to tumor cell perfusion prevented the increment in adhesion induced by LPS and attenuated TCA to naive postcapillary venules. While L-arginine (100 microM), an NO precursor, failed to decrease TCA to naive postcapillary venules, this treatment abolished LPS-stimulated TCA to postcapillary venules. The effect of L-arginine was reversed by administration of N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), an NO synthase (NOS) inhibitor. These observations indicate that both exogenous and endogenous NO modulate TCA to postcapillary venules. To assess the role of NO-induced activation of cGMP in the reduction in TCA produced by DETA/NO, two additional series of experiments were conducted. In the first series, LY-83583 (10 microM), a guanylyl cyclase inhibitor, was shown to completely reverse the effect of DETA/NO on TCA to both naive and LPS-activated postcapillary venules. On the other hand, administration of 8-bromoguanosine 3',5'-cyclic monophosphate (8-B-cGMP) (1 mM), a cell permeant cGMP analog, mimicked the effect of DETA/NO and reduced TCA to LPS-stimulated postcapillary venules. These data suggest that (a) tumor cells are more likely to adhere to postcapillary venules than to corresponding precapillary arterioles, (b) LPS enhances TCA to postcapillary venules, (c) both exogenously applied (DETA/NO) and endogenously generated (L-arginine) NO attenuate the enhanced adhesion induced by LPS, but only DETA/NO reduced TCA to naive postcapillary venules, and (d) the NO-induced reduction in TCA to LPS-activated postcapillary venules occurs by a cGMP-dependent mechanism.
Clin Exp Metastasis 1996 Sep
PMID:Nitric oxide reduces tumor cell adhesion to isolated rat postcapillary venules. 887 7

Vaccinia melanoma oncolysate (VMO) prepared with recombinant vaccinia virus encoding the gene of murine granulocyte/macrophage-colony-stimulating factor (GM-CSF) was tested for its therapeutic effect on melanoma pulmonary metastasis. The murine pulmonary metastasis model was established by injecting 2 x 10(5) B16F10 melanoma cells into the tail vein of a C57BL/6 mouse. Intraperitoneal injection of VMO was performed in tumor-bearing mice 3 and 10 days after B16F10 cell inoculation. The results showed that treatment with VMO prepared with GM-CSF-gene-encoded vaccinia virus (GM-CSFVMO) significantly decreased the number of murine pulmonary metastases and prolonged the survival of the tumor-bearing mice. Lymphocytes isolated from fresh blood and spleen of GM-CSFVMO-treated mice showed higher cytolytic activity against B16F10 melanoma cells when compared with lymphocytes from the mice of other treatment groups. Natural killer activity remained unchanged in the GM-CSFVMO-treated group. Cytotoxic activities of peritoneal macrophages were found to be greatly elevated in mice treated with GM-CSFVMO. Further study illustrated that the increased tumor necrosis factor and nitric oxide release from macrophages may contribute to their cytotoxic effects. These results suggest that the tumor oncolysate vaccine prepared with GM-CSF-gene-encoded vaccinia virus has a potent therapeutic effect on tumor metastasis through the efficient induction of antitumor immunity of the host, mainly through the cytotoxic effects of cytotoxic T lymphocytes and macrophages.
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PMID:Active specific immunotherapy of pulmonary metastasis with vaccinia melanoma oncolysate prepared from granulocyte/macrophage-colony-stimulating-factor-gene-encoded vaccinia virus. 895 68

There is a worldwide increase in the incidence of melanoma. Without treatment, melanomas can progress to metastatic disease and result in death. It is now accepted that for a tumor to grow, non-tumorous host tissue must form blood vessels in and around the tumor. Tumor cells and blood vessels must form a highly regulated system whereby endothelial cells can be switched from a resting state to one of rapid growth. Tumor cells have been shown to produce diffusible angiogenic regulatory molecules. Nitric oxide [NO] and polyamines [PA] have been implicated in the angiogenic process. This paper hypothesizes that NO and PA regulate melanoma angiogenesis differently. During early stages of malignant melanoma an increase in PA synthesis is expected to promote endothelial cell proliferation and therefore angiogenesis. NO is expected to be maintained at low levels. During the vascular stage of malignant melanoma, NO synthesis is hypothesized to be elevated which will decrease endothelial cell proliferation and maintain a vasodilator tone in and around the tumor. PA concentrations are expected to be lower. A regulatory link between NO and PA may be involved in the maintenance of tumor homeostasis. The regulation of L-arginine metabolism in tumor angiogenesis requires investigation as it may lead to novel selective therapeutic interventions in cancer therapy.
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PMID:The importance of L-arginine metabolism in melanoma: an hypothesis for the role of nitric oxide and polyamines in tumor angiogenesis. 898 Oct 51

Chronic inflammatory states frequently lead to the increased production of nitric oxide (NO) via inducible NO synthase (NOS-2). In addition, NO may produce mutagenesis through several mechanisms such as DNA oxidation, DNA deamination, and the formation of N-nitroso compounds. As there is a strong association between human hepatitis C virus (HCV) infection and the development of hepatocellular carcinoma (HCC), we were interested in whether human HCV hepatitis leads to induction of NOS-2 and if the mutation repair system of p53/p21 was upregulated. Reverse transcriptase-polymerase chain reaction (RT-PCR) for human NOS-2 message was performed on RNA samples from both liver biopsies and whole liver from HCV-positive and control patients (normal liver from hepatic resections for metastases). Immunohistochemistry (IHC) for p53 and Western blot analysis for p21 were also performed on the whole liver samples. From the liver biopsies, 60% of HCV-positive patients expressed NOS-2 by RT-PCR. Looking at the whole liver samples, 100% of the HCV-positive patients expressed NOS-2 vs 12.5% in the normal samples. p53 was not detected in either group but there was upregulation of p21 over baseline expression in a number of the HCV-positive patients. Human HCV hepatitis leads to consistent upregulation of hepatic NOS-2 message, but message is not predictably present in "normal" human liver. There is also induction of p21 in some patients with HCV hepatitis. Chronic expression of NO in HCV hepatitis may play a role in DNA mutagenesis and the development of HCC.
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PMID:Chronic hepatitis C virus infection in humans: induction of hepatic nitric oxide synthase and proposed mechanisms for carcinogenesis. 922

Breast cancer is characterized by its ability to metastasize rapidly. Factors that might facilitate this metastatic potential include tumor vascularity. Nitric oxide (NO), a labile compound synthesized by NO synthase (NOS), is a major regulator not only of physiologic vascular tone but also of the abnormal vascularity associated with many tumors. To test whether NOS is expressed in primary breast tumors and whether its expression is associated with the presence of metastasis, we analyzed the expression of the inducible NOS in 22 primary breast tumors, and to investigate its association to other gene products related to the metastatic ability of tumor cells, we correlated the expression of the inducible NOS with the expression of the nm23 protein (the product of the putative antimetastatic gene nm23). We found a very strong correlation between the presence of NOS and axillary lymph node metastasis and between NOS and the absence of nm23 protein. These data suggest that NO synthesis and the resulting increase in blood flow to the tumor play a role in the facilitation of tumor metastasis.
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PMID:Expression of inducible nitric oxide synthase in breast cancer correlates with metastatic disease. 923 72


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