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)

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas.
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PMID:Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. 767 93

We have examined the effect of synthetic low molecular weight glycoamine analogues on the metastasis of MDA-MB-435 human breast carcinoma xenografts growing in the mammary fat pads of nude mice. Initial in vitro screening of a panel of synthetic glycoamines was performed using a clonogenic growth assay in 0.9% agarose. Eight of nine compounds manifested a significant dose-dependent inhibition of colony formation by MDA-MB-435 cells in 0.9% agarose. The relative activity ranks of the compounds, based on ID50S independently determined for each synthetic glycoamine analogue, identified N-(1-deoxy-D-lactulos-1-yl)-L-leucine (Lac-L-Leu), N-(1-deoxy-D-fructos-1-yl)-D-leucine (Fru-D-Leu), N-(1-deoxy-D-fructos-1-yl)-L-phenylalanine, and N-(1-deoxy-D-fructos-1-yl)-L-leucine as the most effective inhibitors of colony formation. Two separate experimental treatment protocols were used to examine the effect of selected synthetic glycoamines on human breast cancer growth and metastasis in athymic nude mice. Group A mice were treated intraperitoneally daily from day 2 after injection of the breast cancer cells until the end of the experiment (17 weeks). In group B, the mice were untreated until the mean tumor diameter was 10 mm, at which time daily i.p. treatment began. After 7 days, the primary tumors were resected, and the mice were treated for an additional 4 weeks (a total of 5 weeks of treatment). The synthetic glycoamines did not have significant antitumor effects, and there was no difference in the tumor incidence or tumor growth rates in mice treated continuously with synthetic glycoamines or PBS. The significant antimetastatic activity of synthetic glycoamines was detected in both experimental treatment protocols. In mice continuously treated with synthetic glycoamines according to protocol A, the incidence of metastasis was decreased 4.6-fold (P = 0.014) and 2.7-fold (P = 0.031) in mice treated with Fru-D-Leu and Lac-L-Leu, respectively. In mice in protocol B, the incidence of pulmonary metastasis was decreased 1.9-fold (P = 0.069) and 2.5-fold (P = 0.042) in mice treated with Fru-D-Leu and Lac-L-Leu, respectively. Correspondingly, the average number of spontaneous pulmonary metastases was reduced from 37 in control mice to 0.2 (P = 0.005) and 0.9 (P < 0.02) in mice treated according to the protocol A with Fru-D-Leu and Lac-L-Leu, respectively. Treatment of mice with N-(1-deoxy-D-fructos-1-yl)-L-leucine did not have significant antimetastatic effects, and no reduction in metastasis incidence or number was noted in mice treated with this synthetic glycoamine analogue. The treated animals had no apparent toxicity from chronic daily injection (up to 17 weeks of treatment) of synthetic glycoamines, and no obvious pathology was noted in the histological slides of the livers, kidneys, or spleens of the treated mice. Therefore, we have identified two synthetic glycoamines (Fru-D-Leu and Lac-L-Leu) that were the effective inhibitors of spontaneous human breast cancer metastasis in nude mice. Potential mechanisms for antimetastatic activity of synthetic glycoamines may include the inhibition of beta-galectin-mediated homotypic cancer cell aggregation and induction of apoptosis in target cells.
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PMID:Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines. 896 76

Galectins (S-type lectins) are a family of low-molecular weight, calcium-independent, mannose-binding lectins with functions in cell growth, cell activation, cell-cell and cell-matrix adhesion including binding to carcinoembryonic antigens and laminin and metalloproteinase. Anti-galectin antisera can inhibit metastases of rat prostate cancers and human melanomas. To define the role of galectins in human breast cancer, the expression of galectin-3 were determined in 27 invasive breast cancers by immunohistochemical methods. The histologic grades of excised breast cancers were determined and immunohistochemical staining for galectin-3 (1: 1000 dilution of anti-galectin rat polyclonal antibody) was defined by scoring the intensity and distribution of staining (0-3+). The mean age of breast cancer patients was 63 years for 20 grade II breast cancers and 56 years for 7 grade III breast cancers. The mean immunohistochemical staining score for grade II breast cancers was 3. 7 (20% less than 2, 80% 3-6) and 2.5 for grade III (71.4% less than 2 and 28.6% 3-6). The galectin-3 expression pattern suggests that increasing histologic grade of breast cancer leads to reduced expression of galectin-3 and possibly reduced matrix binding and increased cancer cell motility.
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PMID:Galectin-3 expression in human breast carcinoma: correlation with cancer histologic grade. 959 87

The clinical histories of 10 women suffering from benign metastasizing leiomyoma (BML) after hysterectomy and information on lung lesions detected in these women are presented, together with corresponding data for 2 women with metastasizing leiomyosarcoma of the uterus for comparison: gross appearance, survival, and light microscopical, immunohistochemical and lectin-histochemical findings are reported. All patients with BML had undergone hysterectomy for uterus leiomyomatosus without any detection of sarcomatous lesions in the uterus wall. After a median period of 14.9 years intrapulmonary masses were detected by imaging techniques. On average, six nodules with a mean diameter of 1.8 cm were seen. Resection of the lesions was performed in all cases. The immunohistochemical and lectin-histochemical examination of the tumors included analysis of the proliferation-associated protein Ki-67, the p53 protein, estrogen and progesterone receptor, sarcolectin as an indicator of the presence of lymphokine macrophage migration inhibitory factor, antibodies and the labeled protein to assess galectin (galactoside-binding animal lectin)-dependent parameters, analysis of tumor vascularization (CD-34), and expression of bcl-2, vimentin, smooth muscle actin, desmin, and keratin. The lesions were characterized by low proliferation activity of 2.9% (measured with Ki-67), frequent hormone receptor expression (8 of the 10 cases presented hormone-specific receptors), low to moderate vascularization compared with metastases from the two uterine sarcomas, remarkable p53 overexpression and frequent expression of the lymphokine, the galectins and accessible binding sites. The median survival of the BML patients was 94 months after excision of the intrapulmonary lesions, and the maximum survival of the two sarcoma patients was 22 months. The results recorded in this patient sample with the methodology applied suggest that benign metastasizing leiomyomas are a slow-growing variant of leiomyosarcoma of the uterus, which becomes clinically apparent at a young age and progresses with low velocity.
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PMID:Benign metastasizing leiomyoma of the uterus: documentation of clinical, immunohistochemical and lectin-histochemical data of ten cases. 1103 49

Galectins form a family of carbohydrate-binding proteins defined by their affinity for beta-galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell migration, three processes that are intimately involved in cancer initiation and progression. Galectins can also display protein-protein types of interactions with their binding partners. Certain galectins directly involved in cancer progression seem to be promising targets for the development of novel therapeutic strategies to combat cancer. Indeed, migrating cancer cells resistant to apoptosis still constitute the principal target for the cytotoxic drugs used to treat cancer patients. Reducing the levels of migration in apoptosis-resistant cancer cells can restore certain levels of sensitivity to apoptosis (and so to pro-apoptotic drugs) in restricted-migration cancer cells. Anti-galectin agents can restrict the levels of migration of several types of cancer cell and should therefore be used in association with cytotoxic drugs to combat metastatic cancer. We provide experimental proof in support of this concept. While the present review focuses on various experimental strategies to impair cancer progression by targeting certain types of galectins, it pays particular attention to glioblastomas, which constitute the ultimate level of malignancy in primary brain tumors. Glioblastomas form the most common type of malignant brain tumor in children and adults, and no glioblastoma patient has been cured to date.
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PMID:Anti-galectin compounds as potential anti-cancer drugs. 1716 20

To evaluate galectin-1, -3 and -7 serum levels as diagnostic and/or prognostic markers for head and neck squamous cell carcinomas (HNSCCs). ELISA was employed to test sera from 102 patients with HNSCCs and from 38 healthy control volunteers for galectin-1, -3 and -7 serum levels. Serum galectin levels were assayed by ELISA and the levels of galectin expression in HNSCCs were determined by means of immunohistochemistry. HNSCCs display significant immunohistochemical amounts of galectin-7, but this galectin cannot be detected in the blood of HNSCC patients. Galectin-3 levels differ significantly (p=0.03) in healthy volunteers and HNSCC patients. Using a threshold value of 4.3 ng/ml, galectin-3 serum level enabled a significant level of discrimination (p=0.03) to be established between the cancer patients and the healthy volunteers, with 90% level of specificity and 36% level of sensitivity. The discrimination was even better when using a threshold value of 13.5 ng/ml for galectin-1 (p=0.001), with 100% level of specificity and 22% level of sensitivity. A subgroup of stage IV HNSCC patients displayed significantly reduced levels of circulating galectin-1 (p=0.003) and galectin-3 (p=0.001) after treatment as opposed to before. Galectin-3 concentrations in sera from the patients with a metastatic disease were significantly (p=0.01) higher than in sera from the patients with localized tumors. The determination of circulating levels of galectin-1 and -3 could be used to monitor the progression of their disease or their response to therapy.
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PMID:The determination of the levels of circulating galectin-1 and -3 in HNSCC patients could be used to monitor tumor progression and/or responses to therapy. 1735 Mar 28

Human tumor metastases are often infiltrated by T lymphocytes that are specific for tumor antigens, but these metastases progress anyway. The spontaneous anti-tumor immune response seems thus to become ineffective, probably because the effector T cells become anergic. This anergy could result from inhibitory mechanisms orchestrated by the tumor cells. We have observed that recently stimulated human cytolytic T cell clones lose transiently their capacity to secrete cytokines. This anergy is correlated with the absence of colocalization of the T cell receptors (TCR) and the CD8 co-receptors. Effector functions' and TCR/CD8 colocalization are recovered by treating cells with galectin-3 ligands, suggesting that exracellular galectin-3 forms glycoprotein-galectin lattices, which decrease the TCR mobility on the surface of anergic T lymphocytes. Galectin-3 is frequently released by tumor cells. This new mechanism of anergy could thus also explain the loss of functions of the tumor-infiltrating lymphocytes, because these lymphocytes recover their effector functions and TCR/CD8 colocalization after ex vivo treatment with galectin-3 ligands. These results could lead to new therapeutical strategies.
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PMID:[Is it possible to correct the anergy of T lymphocytes that infiltrate tumors?]. 2066 49

High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8(+) CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo.
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PMID:Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model. 2082 47

Tissue sections taken from 157 potentially curatively operated lung carcinoma patients (70 epidermoid carcinomas, 68 adenocarcinomas, 15 large cell anaplastic, and 4 small cell anaplastic carcinomas) were examined by a standardized histochemical protocol in a prospective study evaluating the extent of various types of probes to serve as prognostic indicators in lung cancer. Detailed clinical records and survival data (minimum 56 weeks, maximum 96 weeks) were correlated to the results of the histochemical reactions. The study centres on monitoring the expression of galactoside-containing epitopes in tumor cells by human, animal and plant lectins: and with a monoclonal antibody. In addition, affinity-purified subfractions of natural antibodies from human serum with preferential affinity to alpha- and beta-galactosides, respectively, were employed. Significant contributions to the estimation of the survival of patients are given by clinical parameters (pT, pN stage), number of resected and positive lymph nodes and presence of tumor metastases into specific lymph nodes (No. 5 and No. 6 right and left). With respect to the relevance of subsets of beta-galactosides, the galectin from chicken liver (CL-16) and the Le(y)-specific monoclonal antibody unveiled a negative correlation at a statistically significant level. The predictive value of binding of the animal lectin CL-16 was especially pronounced for patients with advanced tumor stages, pointing to a potential role of such lectin-reactive beta-galactosides in late tumor stages or progression.
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PMID:Prognostic relevance of detection of ligands for vertebrate galectins and a Lewis(Y)-specific monoclonal antibody. 2154 92

Cytotoxic CD8(+) T cells are major players of anti-tumor immune responses, as their functional activity can limit tumor growth and progression. Data show that cytotoxic T cells efficiently control the proliferation of tumor cells through major histocompatibility complex class I-mediated mechanisms; nevertheless, the presence of tumor-infiltrating CD8(+) T cells in lesional tissue does not always correlate with better prognosis and increased survival of cancer patients. Similarly, adoptive transfer of tumor-specific cytotoxic T cells has only shown marginal improvement in life spans of patients with metastatic disease. In this report, we discuss experimental evidence showing that expression of tumor-derived galectins, galectin (Gal)-1, Gal-3 and Gal-9, and concomitant presence of their ligands on the surface of anti-tumor immunocytes directly compromise anti-tumor CD8(+) T cell immune responses and, perhaps, undermine the promise of adoptive CD8(+) T cell immunotherapy. Furthermore, we describe novel strategies designed to counteract Gal-1-, Gal-3- and Gal-9-mediated effects and highlight their targeting potential for creating more effective anti-tumor immune responses. We believe that Gal and their ligands represent an efficacious targeted molecular paradigm that warrants clinical evaluation.
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PMID:Galectins and their ligands: negative regulators of anti-tumor immunity. 2254 42


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