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

The prognosis of laryngeal carcinoma worsens dramatically with the discovery of primary or secondary lymph node metastases. Thus consistent prophylaxis and therapy of metastases is indispensable. The standard therapy of manifest cervical lymph node metastases is surgery, if possible using the approach of conservative neck dissection. In cases of a lymph node stage N3, i.e. fixated metastases with a diameter greater than 6 cm, individually adapted therapy in necessary because of the extremely poor prognosis. Elective treatment of the N0 neck is surgical, too; however, the site of the primary tumour, possibly infiltrated compartments and, accordingly, invasion of deep lymphatic vessels have to be considered. Special care is necessary if the so-called primitive glottis is invaded (arytenoid region, aryepiglottidian fold, epiglottis). In the case of distant metastases a temporary remission can be obtained with chemotherapy in most cases, but this chemotherapy should not be forced, because there exists no real chance of cure. The trend is towards less aggressive, outpatient schedules of chemotherapy.
HNO 1997 Jul
PMID:[Laryngeal cancer treatment concept in metastases]. 934 Mar 24

Human fibrosarcoma HT1080 cell surface phenotype analysis revealed the expression of "cluster of differentiation 15" (CD15) antigen and to a lesser extent, of "very late antigen-4" (VLA-4). Expression of "endothelial-leukocyte adhesion molecule-1" (ELAM-1) was negligible on resting human umbilical vascular endothelial cells (HUVECs), but its expression could be induced by HT1080 conditioned medium. HT1080 cell adhesion to HUVECs was partially dependent on CD15/ELAM-1 adhesion molecules. HT1080 cell adhesion to HUVECs induced the enhancement of nitric oxide (NO) production from HUVECs. Exogenous NO and NO from HUVECs enhanced ELAM-1 expression on HUVECs, HT1080 cell adhesion to HUVECs, permeability of the HUVEC monolayer, and HT1080 cell invasion through the HUVEC monolayer. These enhancements were not induced by NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). These results suggest that NO expression induced by tumor cells via the CD15/ELAM-1 adhesion system may contribute to enhancement of tumor cell adhesion to endothelial cells and hyperpermeability of the endothelium, facilitating tumor cell invasion.
Clin Exp Metastasis 1997 Nov
PMID:Nitric oxide induced by tumor cells activates tumor cell adhesion to endothelial cells and permeability of the endothelium in vitro. 934 40

The therapeutic effect of radiotherapy depends amongst other things on the degree of oxygenation of tumour tissue. Epithelial carcinomas of the head-neck region exhibit considerable hypoxic areas which vary markedly between individuals and not encompassed by current staging and grading. It is assumed that during radiation treatment a reoxygenation of hypoxic tumour cells takes place. It was investigated wether the occurrence of reoxygenation could be determined by invasive oxygen partial pressure measurements in lymph node metastases. Using a needle probe inserted transcutaneously into a lymph node polarographic oxygen determinations (Eppendorf pO2-Histiograph) were made on 13 patients with advanced oro- and hypopharyngeal carcinomas before therapy and after a week of accelerated radio- or radiochemotherapy. Low pO2 values before treatment (median 13.5 mmHg, average 20.3 mmHg) and a hypoxic fraction (pO2 < 10 mmHg) of 45.2% indicated manifest tumour hypoxia. After the first week of treatment a significant increase in the median- (24.1 mmHg) and the average pO2 (28.2 mmHg) as well as a reduction in the hypoxic fraction (27%) were observed. Invasive pO2 histiography fulfils the requirements for a method to confirm tumour hypoxia in head-neck tumours. The results obtained indicate that reoxygenation occurs during the initial phases of radio- and radio-chemotherapy.
HNO 1997 Mar
PMID:[Polarographic detection of reoxygenation of lymph node metastases in the initial phase of primary radio- and radiochemotherapy in patients with advanced squamous epithelial carcinomas of the head and neck]. 941 37

Administration of interleukin-2 (IL-2) for treatment of metastatic disease often results in inflammatory liver injury. Previous studies have implicated increased leukocyte and platelet adhesion and enhanced nitric oxide production as causative factors in the development of IL-2-induced hepatic injury. This study investigated the capacity of N omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthesis inhibitor, to limit IL-2-induced hepatic edema and hepatocellular damage in mice. Using hepatic intravital microscopy, we also examined the effects of L-NAME on IL-2-induced increases in leukocyte and platelet adhesion. Administration of IL-2 increased leukocyte and platelet adhesion in post-sinusoidal venules and decreased hepatic perfusion. Cotreatment with L-NAME had no effect on leukocyte adhesion but increased platelet-endothelial adhesion and microvascular thrombosis. Chronic IL-2 treatment induced hepatic edema and hepatocellular injury. However, coadministration of L-NAME attenuated IL-2-induced edema and completely inhibited hepatocellular damage. These findings suggest that nitric oxide may play a central role in IL-2-induced inflammatory liver injury.
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PMID:N omega-nitro-L-arginine methyl ester inhibits inflammatory liver injury induced by interleukin-2. 946 69

Nitric oxide (NO) is a potent biologic mediator with diverse physiologic and pathophysiologic roles. NO is produced from L-arginine by the family of nitric oxide synthase (NOS) enzymes, forming the free radical NO and citrulline as byproduct. Three distinct isoforms of the NOS enzyme have been isolated and represent the products of three different genes. Two of the NOS enzymes are continuously present and are termed constitutive NOS (cNOS). One cNOS enzyme was identified in neurons, and the other in endothelial cells. The two cNOS enzymes are contrasted with the third NOS isoform, inducible NOS, which is not typically expressed in resting cells and must first be induced by certain cytokines, microbial products, or lipopolysaccharide. Since NO production has both beneficial and detrimental consequences, understanding the molecular mechanisms that regulate NOS expression is critical to the control of NO release in homeostatic and pathophysiologic conditions. The purpose of this review is to describe the molecular biology of NO synthases, with particular emphasis on the regulation of the human NO synthase genes. Transcriptional and post-transcriptional regulation of neuronal and endothelial cNOS genes will be reviewed first, followed by the molecular regulation of the inducible NOS gene.
Cancer Metastasis Rev 1998 Mar
PMID:Molecular biology of nitric oxide synthases. 954 20

Reactive oxygen species can initiate carcinogenesis by virtue of their capacity to react with DNA and cause mutations. Recently, it has been suggested that nitric oxide (NO) and its derivatives produced in inflamed tissues could contribute to the carcinogenesis process. Genotoxicity of NO follows its reaction with oxygen and superoxide. It can be due either to direct DNA damage or indirect DNA damage. Direct damage includes DNA base deamination, peroxynitrite-induced adducts formation and single strand breaks in the DNA. Indirect damage is due to the interaction of NO reactive species with other molecules such as amines, thiols and lipids. The efficiency of one pathway or another might depend on the cellular antioxidant status or the presence of free metals.
Cancer Metastasis Rev 1998 Mar
PMID:Role of nitric oxide in genotoxicity: implication for carcinogenesis. 954 21

Macrophages can recognize and eliminate tumor cells. To this effect, these cells use a variety of cytotoxic effectors. Recent work has paid particular attention to nitric oxide (NO) and its metabolic by-products in mediating macrophage tumor cytotoxicity. Moreover, work from this and other laboratories have indicated that macrophage-dependent, NO mediated tumor cell death meets the morphologic and molecular criteria that define apoptotic cell death. This review will initially discuss the characteristics of macrophage tumor cytotoxicity and the potential mechanisms by which NO can induce apoptosis in tumor cells. In addition, observations of spontaneous and acquired resistance to NO will be analyzed. Lastly, the relevance of results obtained using animal cells to the biology of the human macrophage will be considered.
Cancer Metastasis Rev 1998 Mar
PMID:Role of nitric oxide in mediation of macrophage cytotoxicity and apoptosis. 954 22

The process of cancer metastasis consists of multiple sequential and highly selective steps. The vast majority of tumor cells that enter the circulation die rapidly; only a few survive to produce metastases. This survival is not random. Metastases are clonal in origin and are produced by specialized subpopulations of cells that preexist in a heterogeneous primary tumor. Experimental studies concluded that metastatic cells survive in the circulation whereas nonmetastatic cells do not. In part, this difference is due to an inverse correlation between expression of endogenous inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) and metastatic potential. Direct evidence for the role of iNOS in metastasis has been provided by our data on transfection of highly metastatic murine K-1735 clone 4 (C4.P) cells which express low levels of iNOS, with a functional iNOS (C4.L8), inactive mutated iNOS (C4.S2), or neomycin resistance (C4.Neo) genes in medium containing 3 mM of the specific iNOS inhibitor NG-L-methyl arginine (NMA). C4.P, C4.Neo, and C4.S2 cells were highly metastatic, whereas C4.L8 cells were not. Moreover, C4.L8 cells produced slow-growing subcutaneous tumors in nude mice, whereas the other 3 cell lines produced fast-growing tumors. In vitro studies indicated that the expression of iNOS in C4.L8.5 cells was associated with either cytostasis or cytolysis via apoptosis, depending upon NO output. The tumor cells producing high levels of NO underwent autocytolysis and produced cytolysis of bystander cells under both in vitro and in vivo conditions. Multiple i.v. injections of liposomes containing a synthetic lipopeptide upregulated iNOS expression in murine M5076 reticulum sarcoma cells growing as hepatic metastases. The induction of iNOS was associated with the complete regression of the lesions. Transfection of interferon-beta suppressed tumor formation and eradicated metastases, which was apparently linked to iNOS expression and NO production in host cells such as macrophage. Besides mediating cell death, NO produced tumor suppression by regulating expression of genes related to metastasis, e.g., survival, invasion, and angiogenesis. Suppression of metastasis can be achieved through use of immunomodulators that induce iNOS expression in tumor lesions or by the direct delivery of the iNOS gene to tumor cells or host cells through liposome and/or viral vectors.
Cancer Metastasis Rev 1998 Mar
PMID:Therapy of cancer metastasis by activation of the inducible nitric oxide synthase. 954 23

Nitric oxide (NO) is a free radical molecule with high reactivity, a short half life and a variety of physiological activities. The role of NO in tumor microcirculation, based on the data collected to date, can be summarized as follows: 1) NO may partially mediate tumor angiogenesis; 2) endogenous NO derived from tumor vascular endothelium and/or tumor cells increases and/or maintains tumor blood flow via dilatation of arteriolar vessels, decreases leukocyte-endothelial interaction, and increases vascular permeability; 3) exogenous NO can increase tumor blood flow via vessel dilatation, and reduce vessel tone; and 4) NO production rates and vascular response to NO are heterogeneous and tumor-dependent. Modulation of NO level in tumor vessels can alter tumor hemodynamics and thus augment oxygen, drug, gene vector and effector cell delivery to solid tumors.
Cancer Metastasis Rev 1998 Mar
PMID:Role of nitric oxide in angiogenesis and microcirculation in tumors. 954 24

Nitric oxide (NO), a potent biological mediator, plays a key role in physiological as well as pathological processes, including inflammation and cancer. The role of NO in tumor biology remains incompletely understood. While a few reports indicate that the presence of NO in tumor cells or their microenvironment is detrimental to tumor cell survival and consequently their metastatic ability, a large body of clinical and experimental data suggest a promoting role of NO in tumor progression and metastasis. We suggest that tumor cells capable of very high levels of NO production die in vivo, and those producing or exposed to lower levels of NO, or capable of resisting NO-mediated injury undergo a clonal selection because of their survival advantage; they also utilize certain NO-mediated mechanisms for promotion of growth, invasion and metastasis. The possible mechanism(s) are: (a) a stimulatory effect on tumor cell invasiveness, (b) a promotion of tumor angiogenesis and blood flow in the tumor neovasculature, and (c) a suppression of host anti-tumor defense. In this review, we discuss these mechanisms on the basis of data derived from experimental models, in particular, a mouse mammary tumor model in which the expression of eNOS by tumor cells is positively correlated with invasive and metastatic abilities. Tumor-derived NO was shown to promote tumor cell invasiveness and angiogenesis. The invasion-stimulating effects of NO were due to an upregulation of matrix metalloproteases and a downregulation of their natural inhibitors. Treatment of tumor-bearing mice with NO-blocking agents reduced the growth and vascularity of primary tumors and their spontaneous metastases. We propose that selected NO-blocking drugs may be useful in treating certain human cancers either as single agents or as a part of combination therapies.
Cancer Metastasis Rev 1998 Mar
PMID:Role of nitric oxide in tumor progression: lessons from experimental tumors. 954 25


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