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)

This study reports on biological response modification induced by prolonged continuous subcutaneous (s.c.) infusion of recombinant interferon-gamma (rIFN-gamma) with particular attention to changes of soluble CD14. This glycoprotein with an unknown function is derived from myeloid cells carrying membrane CD14, which is the receptor for lipopolysaccharide (LPS)-LPS-binding protein (LBP) complexes. Fifteen metastatic cancer patients received weekly escalating doses of rIFN-gamma starting at either 50 or 100 micrograms/24 h and increasing up to 400 micrograms/24 h for a median duration of 6 weeks. The maximum tolerated dose was higher (200 micrograms/24 h) with the lower (50 micrograms/24 h) starting dose. Biological activity of rIFN-gamma was evaluated by weekly measurements of CD14, neopterin, and beta 2-microglobulin concentrations in serum as well as monocyte HLA class I and II antigen expression and tumor cytotoxicity. Serum IFN-gamma concentrations increased 20-fold within 4 weeks of therapy. The levels were correlated to the mean dose (r = 0.95, p less than 0.05). Among the biological markers, two patterns were observed. First, serum CD14 concentration and expression of monocyte HLA class II antigens increased significantly during the first week, and marker expression correlated with serum IFN-gamma levels (p less than 0.05); CD14 and HLA class II antigens thereafter returned to pretreatment levels within 4 weeks of therapy despite persistently elevated serum IFN-gamma concentrations. Second, serum neopterin and beta 2-microglobulin concentrations as well as monocyte HLA class I expression also increased significantly within the first week, but remained elevated thereafter without any further dose relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prolonged interferon-gamma application by subcutaneous infusion in cancer patients: differential response of serum CD14, neopterin, and monocyte HLA class I and II antigens. 137 54

Two cases of true histiocytic lymphoma of the small intestine occurred in middle-aged patients, manifesting as tumors causing intestinal obstruction. One of the patients died of uncontrollable local and metastatic disease, 16 months after surgery and polychemotherapy, and the other patient is alive 12 months after surgery and chemotherapy. The histologic characteristics of the tumor cells, namely complex nuclear outlines and abundant variably eosinophilic cytoplasm, suggested histiocytic differentiation. Both cases had negative results for B-cell and T-cell markers but stained for the histiocytic markers lysozyme, CD68, and HLA-DR and had positive results for S-100 protein and vimentin. Acetone-fixed frozen sections of one case showed positive results for several histiocytic markers, including CD11c, CD14, CD33, CD68, and BerMac3 (unclustered monoclonal antibody). CD4, a T-cell antigen present in a subset of histiomonocytic cells, had positive results in the cytoplasm. The tumor cells had negative results for CD1a, CD15, and CD30. Immunoglobulin and T-cell receptor gene probes showed germline configuration in one case studied. These results indicate the tumors are true histiocytic lymphomas, which have immunophenotypic features of both ordinary histiocytes and interdigitating reticulum cells.
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PMID:True histiocytic lymphoma of small intestine. Analysis of two S-100 protein-positive cases with features of interdigitating reticulum cell sarcoma. 837 37

The expression of -GlcNAc beta 1-6Man-(beta 1-6) branched oligosaccharides in carcinoma cells has been considered to influence their metastatic potentials. In the present paper, the lectin histochemistry of oral squamous cell carcinomas obtained in biopsy from 34 patients with Phaseolus vulgaris leukoagglutinin (L-PHA), which potentially binds to N-glycosidic carbohydrates with beta 1-6 linked lactosamin antennae, was studied in order to analyze the relationship between their staining patterns and metastases. The L-PHA-binding oligosaccharides of the carcinomas were expressed on the cell surface in the following patterns: (i) all cells were positive for the staining ('positive'); (ii) some cells were positive but the rest of the carcinoma cells were negative ('weakly positive'); and (iii) all were negative ('negative'). Statistical analysis revealed that the incidence of the metastasis to regional lymph nodes in the 'positive' cases was significantly higher than that in the 'negative' cases. Moreover, the number of the CD14 positive cells including macrophages in the stroma adjacent to the carcinomas in the 'positive' cases was less than that in the 'negative' or 'weakly positive' cases. The expression of L-PHA-binding oligosaccharides in oral squamous cell carcinoma may be responsible for their metastatic potential to regional lymph nodes, possibly including their ability to escape macrophage recognition.
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PMID:Expression of Phaseolus vulgaris leukoagglutinin-binding oligosaccharides in oral squamous cell carcinoma: possible association with the metastatic potential. 890 72

To examine the phenotype of the sinusoidal endothelial cells (SECs) surrounding tumor cells and the process of capillarization in hepatocellular carcinoma (HCC), 51 primary HCCs, 4 adrenal metastases, and 3 portal tumor thrombi were immunohistochemically stained with monoclonal antibodies (MAbs) for CD4, CD14 (lipopolysaccharide-binding protein complex receptors), and CD32 (Fc gamma receptor II), which are specifically found on the SECs in normal liver, but not on ordinary vascular endothelial cells (ECs). Immunostaining was also performed for CD36 (thrombospondin receptors), EN4 antigen (Ag) (a pan-vascular endothelial cell Ag), PAL-E Ag (a venous and capillary EC Ag), factor VIII-related Ag (FVIIIRAg), and laminin. MAb 25F9, which identifies macrophages, was simultaneously used with the other MAbs to distinguish macrophages from SECs in HCCs (HCC SECs). CD4, CD14, and/or CD32 were found on HCC SECs only in 12 well-differentiated primary HCCs showing a thin trabecular or pseudoglandular tumor cell arrangement. These 12 tumors were smaller than those without CD4-, CD14-, and/or CD32-positive SECs (P < .05). Among them, 7, 5, and 11 tumors were negative or only partially positive for laminin, PAL-E Ag, and FVIIIRAg, respectively. Staining for laminin and PAL-E Ag showed an inverse relationship to the expression of CD4, CD14, and CD32 on HCC SECs and the tumor differentiation. In conclusion, the phenotypes of the SECs in early and well-differentiated HCC are thought to be similar to those of the SECs in normal liver. With progressing tumor dedifferentiation the HCC SECs lose the phenotypes peculiar to liver SECs and acquire the characteristics of capillary ECs, though both types of phenotypical change occur independently of each other.
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PMID:Immunohistochemical studies on endothelial cell phenotype in hepatocellular carcinoma. 925 52

Based on evidence that granulocyte-macrophage colony stimulating factor (GM-CSF) induces a potent systemic antitumor immunity, we tested recombinant GM-CSF in advanced melanoma. Seven patients with histologically confirmed cutaneous melanoma metastases were treated with perilesional intracutaneous injections of recombinant GM-CSF and observed for a follow-up time of 5 y. All but two patients had a decrease in the total number of metastases. At the end of the 5 y follow-up three of the seven patients are still alive with only one patient receiving other than surgical therapy, and one patient died tumor free at the age of 93. The remaining three patients died from progressive melanoma. Perilesional intradermal GM-CSF therapy resulted in a mean survival time of 33 mo. The treatment was well tolerated and no side-effects other than local erythema at the injection sites and mild drowsiness were seen. Immunohistochemical analysis with staining for CD14 and GM-CSF receptor demonstrated an increased infiltration of monocytes into both injected and noninjected cutaneous melanoma metastases compared with lesions excised prior to the initiation of therapy. The same was true for CD4- and CD8-positive lymphocytes. This phenomenon, together with GM-CSF-induced leukocyte counts of more than 20,000 during therapy, support the possible impact of a systemic over a locally induced reaction by GM-CSF. To our knowledge this is the first report that intracutaneously injected GM-CSF results in long-lasting reduction of melanoma metastases.
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PMID:Perilesional injection of r-GM-CSF in patients with cutaneous melanoma metastases. 1151 18

Dendritic cells (DCs) have been shown to be a promising adjuvant for inducing immunity to cancer. We evaluated tumor lysate-pulsed DC in a Phase I trial of pediatric patients with solid tumors. Children with relapsed solid malignancies who had failed standard therapies were eligible. The vaccine used immature DC (CD14-, CD80+, CD86+, CD83-, and HLA-DR+) generated from peripheral blood monocytes in the presence of granulocyte/monocyte colony-stimulating factor and interleukin-4. These DC were then pulsed separately with tumor cell lysates and the immunogenic protein keyhole limpet hemocyanin (KLH) for 24 h and then combined. A total of 1 x 10(6) to 1 x 10(7) DC are administered intradermally every 2 weeks for a total of three vaccinations. Fifteen patients (ages 3-17 years) were enrolled with 10 patients completing all vaccinations. Leukapheresis yields averaged 2.8 x 10(8) peripheral blood mononuclear cells (PBMC)/kg, and DC yields averaged 10.9% of starting PBMC. Patients with neuroblastoma, sarcoma, and renal malignancies were treated without obvious toxicity. Delayed-type hypersensitivity (DTH) response was detected in 7 of 10 patients for KLH and 3 of 6 patients for tumor lysates. Priming of T cells to KLH was seen in 6 of 10 patients and to tumor in 3 of 7 patients as demonstrated by specific IFN-gamma-secreting T cells in unstimulated PBMCs. Significant regression of multiple metastatic sites was seen in 1 patient. Five patients showed stable disease, including 3 who had minimal disease at time of vaccine therapy and remain free of tumor with 16-30 months follow-up. Our results demonstrate that it is feasible to generate large numbers of functional DC from pediatric patients even in those highly pretreated and with a large tumor burden. The DC can be administered in an outpatient setting without any observable toxicity. Most importantly, we have demonstrated the ability of the tumor lysate/KLH-pulsed DC to generate specific T-cell responses and to elicit regression of metastatic disease.
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PMID:Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. 1173 36

The liver is among the organs that trap lymphocytes flowing through their blood vasculature. These cells, marginated in sinusoids, participate in the liver's anti-viral and anti-tumor processes. The molecular mechanism of this lymphocyte margination and cooperation with resident sinusoidal cells remains obscure and inadequately studied due to the difficulties in obtaining samples of sinusoidal blood from a living animal. To overcome these shortcomings, we have worked out an in situ rat liver perfusion model in exsanguinated animals that enables quantitative observations of blood lymphocyte trapping in sinusoids. The cell populations trapped by the liver and retained in the perfusing blood were characterized with respect to their phenotypes and cytotoxicity. Perfused livers, previously washed out of sinusoidal lymphocytes, halted leukocytes from normal perfusing blood. The numbers of halted post-perfusion CD5+, CD4+, CD8+, CD56+ (ED1) and MHC class II+ (OX6) subsets did not differ statistically from the pre-perfusion population, which suggests active extraction of leukocytes during perfusion. Moreover, cytotoxicity of post- and preperfusion populations against CC531 and K562 remained at a similar level. The perfused livers with CC531 colon adenocarcinoma metastases halted higher numbers of the CD14 and MHC class II+ and fewer of CD11b+ and CD54+ normal blood leukocytes than normal livers. The phenotypes of cells retrieved from sinusoids after perfusion were almost identical to those obtained prior to perfusion. Interestingly, the post-perfusion populations displayed higher cytotoxic capacity than before perfusion. Taken together, the in situ liver perfusion method allows the study of the specificity and kinetics of recruitment of specific populations of host leukocytes in metastatic tumor tissue and evaluation of their cytotoxicity levels.
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PMID:The normal and metastases-bearing livers retain various specific subsets of live lymphocytes from portal circulation. 1499 71

Supposedly, thyrocyte-specific transcripts such as thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R) were proposed to be useful for the diagnosis of circulating tumour cells in patients suffering from differentiated thyroid carcinoma (DTC). However, several research groups reported blood-borne Tg transcripts in healthy individuals. This study determines in particular the origin of Tg mRNA in nucleated blood cells and analyses whether other tumour-associated sequences are absent in leukocytes, but widely expressed in DTC. Therefore, expression analyses for Tg, TSH-R, cytokeratin 19 (CK 19), human telomerase reverse transcriptase (hTERT) and oncofoetal fibronectin (onfFN) were carried out using cDNAs derived from (1) leukocyte fractions, (2) 18 follicular thyroid carcinomas (FTCs) and 48 papillary thyroid carcinomas (PTCs), and (3) leukocytes of two thyrocyte-depleted individuals treated for C-cell carcinoma of the thyroid. Expression of onfFN was additionally analysed by semiquantitative RT-PCR and by quantitative fluorescence-based real-time PCR. Tg and TSH-R expression was demonstrated not only in both athyroid individuals, but in all leukocyte subgroups tested, while hTERT was absent in resting CD4+ cells and only weakly expressed in the CD8+ group. CK 19 was notable in each leukocyte population except for resting CD14(+), as well as for activated and resting CD19+ cells. All blood cell fractions proved negative for onfFN mRNA, whereas its presence in thyroid carcinoma was 78/98% (FTC/PTC). Threshold cycle values were calculated at: porphobilinogen deaminase (PBGD) = 25.95+/-0.73 (FTC)/24.55+/-5.43 (PTC) (P = 0.2878); onfFN = 25.48+/-3.15 (FTC)/21.44+/-3.44 (PTC) (*P = 0.0001). Finally, onfFN transcripts were detected in blood samples of six out of nine patients with known DTC metastases, demonstrating a reliable assay functionality. We propose that real-time RT-PCR of onfFN mRNA is superior to other markers in monitoring minimal residual disease in DTC with regard to both assay sensitivity and specificity.
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PMID:Oncofoetal fibronectin--a tumour-specific marker in detecting minimal residual disease in differentiated thyroid carcinoma. 1609 57

The cellular and humoral mechanisms accounting for osteolysis in skeletal metastases of malignant melanoma are uncertain. Osteoclasts, the specialised multinucleated cells that carry out bone resorption, are derived from monocyte/macrophage precursors. We isolated tumour-associated macrophages (TAMs) from metastatic (lymph node/skin) melanomas and cultured them in the presence and absence of osteoclastogenic cytokines and growth factors. The effect of tumour-derived fibroblasts and melanoma cells on osteoclast formation and resorption was also analysed. Melanoma TAMs (CD14+/CD51-) differentiated into osteoclasts (CD14-/CD51+) in the presence of receptor activator for nuclear factor kappaB ligand (RANKL) and macrophage-colony stimulating factor. Tumour-associated macrophage-osteoclast differentiation also occurred via a RANKL-independent pathway when TAMs were cultured with tumour necrosis factor-alpha and interleukin (IL)-1alpha. RT-PCR showed that fibroblasts isolated from metastatic melanomas expressed RANKL messenger RNA and the conditioned medium of cultured melanoma fibroblasts was found to be capable of inducing osteoclast formation in the absence of RANKL; this effect was inhibited by the addition of osteoprotegerin (OPG). We also found that cultured human SK-Mel-29 melanoma cells produce a soluble factor that induces osteoclast differentiation; this effect was not inhibited by OPG. Our findings indicate that TAMs in metastatic melanomas can differentiate into osteoclasts and that melanoma fibroblasts and melanoma tumour cells can induce osteoclast formation by RANKL-dependent and RANKL-independent mechanisms, respectively.
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PMID:Malignant melanoma and bone resorption. 1664 14

Giant cell tumor of bone (GCTB) is a benign bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. GCTB is composed of uniformly distributed osteoclastic giant cells, thought to originate from the fusion of monocyte-macrophage lineage cells, in a background consisting of mononuclear rounded cells and spindle-shaped cells. Several reports showed the specific expression of markers, such as CD14 on the mononuclear rounded cell population, however, lacking osteoclastic giant cells. Blood monocytes that were CD14+, CD33+, or CD14+/CD33+ have also been shown to be programmed as pre-osteoclasts. The macrophage marker CD33 is expressed earlier than CD14 in macrophage maturation, whereas CD14 is expressed longer than CD33. The aim of this study was to investigate CD14/CD33 expression profiles in GCTB. Nineteen GCTB tumor samples of 19 patients were studied. Immunofluorescent analyses were performed with monoclonal antibodies against CD14, CD33, RANK, and CD51. To unambiguously further prove the expression of these molecules, quantitative RT-PCR was used with subsequent sequencing of its products. All samples showed similar immunoreactivity profiles. The mononuclear rounded cell population was positive for RANK, CD51, CD14, and CD33. The osteoclastic giant cell population expressed RANK and CD51, as well as CD33, but was consistently negative for CD14 expression. The CD14 and CD33 profiles were confirmed by quantitative RT-PCR. These RT-PCR products were sequence verified. Osteoclasts in GCTB are the result of fusion of CD33-expressing pre-osteoclasts that further fuse with CD14+ mononuclear cells. Although these results reflect a static rather than a dynamic spectrum, we strongly believe that osteoclastogenesis seems not to be the exclusive result of fusion of intratumoral CD14+ mononuclear cells. Moreover, CD33-modulated osteoclastogenesis opens up the possibility for novel therapeutic directions.
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PMID:CD33+ CD14- phenotype is characteristic of multinuclear osteoclast-like cells in giant cell tumor of bone. 1876 26


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