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)

We investigated the correlations between serum levels of selected proinflammatory, hematopoietic and angiogenic cytokines and soluble cytokine receptors with the clinico-pathological features and prognosis in soft tissue sarcoma patients. Serum levels of 9 cytokines (TNFalpha, IL-1ra, IL-6, IL-8, IL-10, M-CSF, G-CSF, VEGF, bFGF) and 4 free cytokine receptors (sIL-2R alpha, sIL-6R, TNFRI, TNFRII) were measured by means of an enzyme-linked immunoadsorbent assay kit in 156 soft tissue sarcoma patients before the treatment and in 50 healthy controls. Serum levels of 10 cytokines and cytokine receptors were also assayed during patients' follow-up after the treatment. Significantly elevated pretreatment serum levels of 11/13 cytokines and cytokine receptors were found in sarcoma patients, as compared to healthy controls. In 40.4% of patients 6 or more cytokines and cytokine receptors (most frequently: TNF RI, IL-6, IL-8) were elevated in parallel. Serum levels of IL-6, sIL-2R, VEGF, M-CSF and TNF RI correlated significantly with tumor size and serum levels of IL-8 and IL-6 were significantly higher in patients with Grade 2/3 vs. Grade 1 tumors. We did not observe any significant differences in cytokine serum levels between patients with primary and recurrent tumors and patients with and without distant metastases. Using univariate analysis, overall survival (OS) in all patients was affected by tumor size (<5 cm vs. 5-10 cm vs. >10 cm), tumor grade (G1 vs. G2/3), presence of metastases, pretreatment serum levels of 8 cytokines (IL-6, IL-8, IL-10, sIL-2R, TNF RI, TNF RII, M-CSF, VEGF) and the number of cytokines increased (0-1 vs. 2-5 vs. < or = 6). Elevated serum levels of IL-6, IL-8, IL-10 and sIL-2R alpha, high tumor grade and larger tumor size strongly correlated with shorter disease-free survival (DFS). Multivariate analysis identified G2/3 tumor grade (p = 0.001), the presence of metastases (p = 0.004), elevated IL-6 serum level (p = 0.02), elevated IL-8 serum level (p = 0.048) and the number of cytokine serum levels above upper cut-off values (p = 0.01) as the independent prognostic factors related to OS, and G2/3 tumor grade (p = 0.005) and increased IL-6 serum level (p = 0.035) as independent prognostic factors related to DFS. In a group of patients without metastases (M0) higher tumor grade, elevated serum level of IL-6 and TNF RII, and the number of elevated cytokine serum levels correlated independently with poor survival. We found a significant decrease of several cytokine serum levels in patients after treatment (IL-1ra, IL-6, IL-8, IL-10, TNF RII, M-CSF) [p < 0.05]. Persistently elevated serum level of IL-6 after the treatment has also shown negative prognostic significance for OS (univariate analysis). Serum levels of some proinflammatory, hematopoietic and angiogenic cytokines and cytokine receptors are elevated, frequently in parallel, in a large percentage of soft tissue sarcoma patients. Significant correlations of serum cytokine levels with tumor size and grade suggest that some of these cytokines may be directly or indirectly involved in the progression of soft tissue sarcomas. Serum assays of IL-6, IL-8 and TNF RII before or after the treatment may be useful in establishing soft tissue sarcoma patients prognosis.
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PMID:Cytokine serum levels in soft tissue sarcoma patients: correlations with clinico-pathological features and prognosis. 1211 31

Helicobacter pylori (HP) infection induces expression of IL-8 and IL-10 in benign gastric epithelium. This study compared the expression of cytokines in CD4+ and CD8+ lymphocyte subsets of peripheral blood lymphocytes (PBL), benign mucosal lymphocytes (ML), and tumor infiltrative lymphocytes (TIL) as well as in the benign and malignant epithelial cells of the same patient, with respect to the presence of HP infection, lymph node metastases, and tumor histologic type. The mRNA of the cytokines was measured by a semiquantitative RT-PCR method. The levels were ranked and compared using the Wilcoxon sign-ranked test. Compared with CD8+ ML, the CD8+ TIL expresses higher levels of IL-6 and IL-8 but lower level of IL-4 in patients with lymph node metastases. In patients with HP infection, expression of IL-8 and IL-10 was higher in the gastric carcinoma cells than in the benign epithelial cells while expression of IL-6 and IL-8 were higher in CD8+ TIL than CD8+ ML. Overexpression of IL-8 in HP associated gastric carcinomas suggested that they might have arisen from HP-infected epithelial cells.
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PMID:Changes of interleukin expression correlate with Helicobacter pylori infection and lymph node metastases in gastric carcinoma. 1221 51

In the United States, tumors of the central nervous system remain the third leading cancer-related cause of death in young adults with a median survival time of < 1 year. A recent case study suggested that Capecitabine (a novel, fluoropyrimidine prodrug) may be effective in the treatment of brain metastases. Pharmacogenomic studies have correlated the antitumor response to Capecitabine with the expression of the drug metabolizing enzymes thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). In the current study, we examined TP and DPD expression in normal human brain tissues and in glioblastoma multiforme, the most common and malignant type of brain tumor. Because previous reports suggest a tumor necrosis factor (TNF)-alpha-mediated increase in TP expression after irradiation (a current standard of care for glioblastoma multiforme), we also examined the effect of irradiation on the expression of TP, DPD, and TNF-alpha in both irradiated and lead-shielded contralateral U87MG glioma xenografts within the same animal. Expression levels were determined using real-time quantitative PCR as described previously. Results demonstrate an approximately 70-fold increase in TP mRNA levels 4 days after irradiation, relative to initial control levels. Interestingly, TP mRNA in the lead-shielded tumors (contralateral to irradiated tumors) increased approximately 60-fold by day 10 relative to initial control levels. Elevated TP levels were sustained for 20 days in irradiated xenografts but began to decrease after 15 days in the shielded/contralateral tumors, returning to baseline by 20 days. TP mRNA levels in normal mouse liver were unaltered, suggesting a tumor-associated effect. TNF-alpha mRNA levels did not increase after irradiation; therefore, mRNA expression of 11 additional cytokines [interleukin (IL)-1 alpha, IL-1 beta, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p35, IL-12p40, IL-15, and IFN-gamma] in both the irradiated and shielded xenografts was quantitated. Results demonstrated increased levels of IFN-gamma, IL-10, and IL-1 alpha by 6.3-, 3.7-, and 1.6-fold, respectively, in irradiated tumors only. DPD mRNA levels did not change after irradiation. The tumor-associated induction of TP in irradiated and lead-shielded tumors within the same animal may have significant implications for the combined modality treatment of cancer patients with Capecitabine in conjunction with radiotherapy and may apply to the treatment of distant tumors and or metastatic disease.
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PMID:Induction of thymidine phosphorylase in both irradiated and shielded, contralateral human U87MG glioma xenografts: implications for a dual modality treatment using capecitabine and irradiation. 1248 38

We describe a new human tumor xenotransplant animal model that is highly efficient for engraftment, does not need host conditioning and is suitable for in vivo studies of human tumors. Pieces of 61 freshly operated primary breast tumors were implanted into 172 irradiated and 228 nonconditioned NOD/Scid mice. A high mortality was observed in irradiated but not in nonconditioned recipients. More than 90% of analyzed implanted breast cancer specimens engrafted in the NOD/Scid mice irrespective of pretreatment. The tumors were vascularized within 3 days of implantation and maintained original histomorphology as well as expression patterns of tumor markers (cytokeratin and MUC1) and cytokines (tumor necrosis factor alpha (TNF-alpha), interleukin-4 (IL-4) and IL-10) released by adjacent stromal cells. A majority of tumors grew slowly, locally infiltrating host tissue, whereas some grew aggressively, developing large, fatal tumor masses and metastases within regional lymph nodes. Tumor progression in mice correlated with stage, grade, proliferation index and hormone receptor status of primary tumors. The reproducible growth behavior and preservation of characteristic features suggest that this new xenotransplant model is relevant and can be recommended for testing new anticancer therapies.
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PMID:Efficient engraftment of human primary breast cancer transplants in nonconditioned NOD/Scid mice. 1271 33

To elicit a therapeutic antitumor immune response, dendritic cells (DCs) have been employed as a cellular adjuvant. Among various DC-based approaches, fusion of DCs and tumor cells potentially confers not only DC functionality, but also a continuous source of unaltered tumor antigens. We have recently demonstrated successful generation of fusion hybrids by a large-scale electrofusion technique. The immunogenicity and therapeutic potential of fusion hybrids were further analyzed in a model system of a murine melanoma cell line expressing beta-galactosidase (beta-gal) as a surrogate tumor antigen. A single vaccination with fusion hybrids plus IL-12 induced a therapeutic immune response against 3-day established pulmonary metastases. This immunotherapy was beta-gal specific and involved both CD4 and CD8 T cells. In vitro, fusion hybrids stimulated specific IFN-gamma secretion from both CD4 and CD8 immune T cells. They also nonspecifically induced IL-10 secretion from CD4 but not CD8 T cells. Compared to other DC loadings, our results demonstrate the superior immunogenicity of fusion. The current technique of electrofusion is adequately developed for clinical use in cancer immunotherapy.
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PMID:Therapeutic immune response induced by electrofusion of dendritic and tumor cells. 1271 34

It has been seen that advanced stage oral squamous cell carcinoma is associated with impaired T-cell function and higher antibody response. In order to find out if such immune disregulation is associated with alteration of T-helper (Th) type CD4+ T-cell phenotype leading to altered cytokine production, we studied the Th-like cytokine profile in 35 oral squamous cell carcinoma patients and 21 normal controls. Concomitant expression of both Th1 and Th2 cytokine genes was studied by reverse transcription and Polymerase Chain Reaction (PCR) based amplification (RT-PCR) of mRNA extracted from freshly isolated peripheral blood mononuclear cells (PBMC) using specific primers for Interferon (IFN)-gamma, Interleukin (IL)-2, IL-4 and IL-10. Almost 63% of oral cancer patients showed polarization of a Th-like cytokine response as compared to 33% of the normal controls while 66.6% of normal controls showed a predominantly non-polarized Th0 response. Expression of IFN-gamma and IL-2 genes was more commonly seen in the early stage of the disease (p < 0.02) whereas majority of advanced stage tumours was associated with enhanced expression of IL-4 and IL-10 but not IFN-gamma and IL-2 genes. Patients with lymphnode metastases and poorly differentiated tumours expressed IL-4 and IL-10 more frequently with concomitant suppression of IFN-gamma and IL-2 genes. It seems therefore, that the development of oral squamous cell carcinoma leads to polarization of cytokine gene expression that is skewed towards the Th1-like response in the early stage. However, increasing tumour load and lymphnode invasion suppresses Th1 cytokine genes, thus skewing it toward a Th2-like cytokine response.
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PMID:Disregulated expression of the Th2 cytokine gene in patients with intraoral squamous cell carcinoma. 1272 39

Cryoablation is a low-invasive surgical treatment for malignant tumors. It may induce an immunological response leading to the eradication of distant metastases or alternatively it might promote the growth of residual tumors. In this paper we confirm the occurrence of both phenomena and we describe the preventive effect of a protein-bound polysaccharide preparation. Metastatic liver tumors were produced in BALB/c mice by the intrasplenic inoculation of colon 26 cells and cryoablation was carried out using liquid nitrogen (-170 degrees C) applied by a contact method. The value of combining cryoablation with administration of the polysaccharide preparation in the prevention of growth of residual tumors was investigated. It was shown that the number of metastatic liver nodules and the size of the primary tumor at the site of inoculation in the spleen were significantly lower when the volume that was frozen was small. The production by splenocytes of the tumor necrosis factor TNF-alpha, interferon INF-gamma, and the interleukins IL-4 and IL-10 increased significantly after freezing and thawing of the tumor tissue. The polysaccharide treatment significantly reduced the production of IL-4 and IL-10 following cryoablation; the production of TNF-alpha and INF-gamma was slightly promoted; the natural killer and cytotoxic T-cell activities of splenocytes were slightly enhanced. It was concluded that the polysaccharide preparation was beneficial by suppressing IL-4 and IL-10 production and might inhibit the growth of residual tumor that is sometimes induced by large-volume cryoablation.
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PMID:Antitumor effects of residual tumor after cryoablation: the combined effect of residual tumor and a protein-bound polysaccharide on multiple liver metastases in a murine model. 1281 13

Understanding the whole process of dendritic cell (DC) activation might help in the development of more efficient immunotherapeutic strategies for tumor patients. Part of this process is cytokine secretion, which has important effects on innate and adaptive immune response. Here, we cultured circulating monocytes for five days with interleukin-4 and GM-CSF followed by two-day culture with or without CD40 ligand and LPS to create a mature DC (mDC) and an immature DC (iDC) phenotype, respectively, characterized by differential expression of co-stimulatory molecules (CD80, CD83). We then compared the cytokine expression profile of the mDC and iDC using two protein platform arrays. Twelve supernatants from mDC paired with 12 from iDC were compared. The mDC protein expression profile showed significant increases in 16 out of 34 factors tested, including TNFalpha, IL-10, IL-12, IFNgamma, MIP1alpha, MIP1beta, IL-8, MDC, RANTES, and IL-6, which play a crucial role in the regulation of the innate immune response as well as the recruitment and activation of adaptive immune effectors. Interestingly, some of the cytokines expressed during maturation were also found in the gene expression profile identified in tumor metastases following IL-2 therapy using cDNA arrays. This finding suggests a possible role for resident DC maturation as a mediator of systemic IL-2 effects. Most important, the array of cytokines secreted during DC maturation may be considered an important component during adoptive transfer. Further characterization of the kinetics and persistence of their secretion should be undertaken in the future.
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PMID:Cytokine and chemokine expression profiles of maturing dendritic cells using multiprotein platform arrays. 1468 83

According to recent advances in psychoneuroimmunology concerning the neurobiochemistry of emotions, the pshychological status of cancer patients should be investigated in relation to the function of the psychoneurodocrine system, in an attempt to put into evidence possible cancer progression-related alterations, particularly those involving the dopaminergic pathways, which play a fundamental role in the perception of pleasure. In fact, the decreased capacity of feeling pleasure is one of the most frequent psychic symptoms occurring in cancer patients. Rorschach's test has been proven to be an appropriate psychological tool to investigate psychic condition including sexual and spiritual profiles. On this basis, a study was planned to evaluate if a relation exists between psychological response to Rorschach's test and immunoneuroendocrine status of cancer patients. The immune status was investigated by measuring lymphocyte subsets and serum levels of IL-2 and IL-10. The neuroendocrine status was analyzed by evaluating the endocrine response of PRL, GH and cortisol to an oral administration of apomorphine (0.01 mg/kg b.w.), a dopaminergic agent able to explore dopaminergic sensitivity. The study included 40 cancer patients (breast cancer: 15; colorectal cancer: 14; lung cancer: 11), 21 of whom showed distant organ metastases. Rorschach's test demonstrated a simultaneous suppression of sexual and spiritual profiles in 31/40 (78%) patients, without significant differences in relation to either tumor histotype or disease state. A normal decline in PRL levels and a normal increase in those of GH and cortisol was observed in 29/40 (73%), 5/40 (13%) and 9/40 (23%) patients. The percent of normal responses of PRL, GH and cortisol was higher in patients with normal than in those with altered response to Rorschach's test, even though only the difference in PRL and cortisol response was statistically significant. Patients with normal sexual and spiritual expression at Rorschach's test showed a significantly higher number of total lymphocytes, T lymphocytes, T helper lymphocytes and NK cells with respect to the patients with altered psychological response, whereas no difference was found in T cytotoxic lymphocyte mean number. IL-2 and IL-10 mean serum concentrations were lower and higher, respectively, in patients with altered than in those with normal response to Rorschach's test, even though only the difference in IL-10 values was statitistically significant. This preliminary study, carried out to analyze the psychological status of cancer patients in relation to neuroendocrine and immune conditions, would suggest that neoplastic disease is characterized by a simultaneous suppression of sexual and spiritual profiles, and that this is associated with neuroendocrine alterations and immunosuppression.
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PMID:A psychoncological study of lymphocyte subpopulations in relation to pleasure-related neurobiochemistry and sexual and spiritual profile to Rorschach's test in early or advanced cancer patients. 1506 61

Interleukin (IL)-22, a novel cytokine belonging to the IL-10 family, is secreted from activated T and natural killer cells and is possibly involved in inflammatory responses. We examined whether expression of the IL-22 gene in murine colon carcinoma Colon 26 cells (Colon 26/IL-22) could produce any antitumour effects in the inoculated mice. Although growth of Colon 26/IL-22 tumours in syngeneic mice was not different from that of parent tumours, survival of the mice that were subcutaneously or intraperitoneally inoculated with Colon 26/IL-22 tumours was significantly prolonged compared with the mice inoculated with parent tumours. Metastasis was not influenced by IL-22 expressed in tumours. Expression of the IL-22 receptor-specific gene, IL-22R, was not induced in spleen cells stimulated with concanavalin A, anti-CD3 or anti-CD40 antibody, despite constitutive expression of the IL-10R2 gene, which encodes another component of the heterodimeric IL-22 receptor complex. IL-22 thereby does not directly act on immunocompetent cells, and IL-22 expressed in tumours can favour apothanasia of inoculated hosts.
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PMID:Expression of interleukin-22 in murine carcinoma cells did not influence tumour growth in vivo but did improve survival of the inoculated hosts. 1554 Oct 36


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