Gastric cancer cells express large amounts of galectin-3 on the cell surface. This fact may provide the possibility to use galectin-3 protein as a surface target for delivering cytotoxic anticancer agents. To investigate the possibility of application of galectin-3 protein as a target protein in delivering cytotoxic anticancer agents, we synthesized doxorubicin immunoconjugate by using maleimidocaproic acid and conjugated doxorubicin immunoconjugate to anti-galectin-3 mAb. The anticancer effect of immunotoxin was assayed on NIH3T3, AGS and KATO III cell lines. The anticancer effect of immunotoxin on AGS cell line is highest and that of KATO III is higher than that of NIH3T3. This results relate to that of flow cytometry analysis previously shown and indicate that galectin-3 protein can be used as a target protein on the surface of gastric cancer cell for delivering cytotoxic anticancer agents.
Antineoplastic Agents* ; Cell Line ; Doxorubicin ; Flow Cytometry ; Galectin 3 ; Galectins* ; Immunoconjugates ; Immunotoxins ; Staphylococcal Protein A ; Stomach Neoplasms

Bone marrow-derived mesenchymal stem cells (MSCs) have immunomodulatory properties and can suppress exaggerated pro-inflammatory immune responses. Although the exact mechanisms remain unclear, a variety of soluble factors are known to contribute to MSC-mediated immunosuppression. However, functional redundancy in the immunosuppressive properties of MSCs indicates that other uncharacterized factors could be involved. Galectin-9, a member of the beta-galactoside binding galectin family, has emerged as an important regulator of innate and adaptive immunity. We examined whether galectin-9 contributes to MSC-mediated immunosuppression. Galectin-9 was strongly induced and secreted from human MSCs upon stimulation with pro-inflammatory cytokines. An in vitro immunosuppression assay using a knockdown approach revealed that galectin-9-deficient MSCs do not exert immunosuppressive activity. We also provided evidence that galectin-9 may contribute to MSC-mediated immunosuppression by binding to its receptor, TIM-3, expressed on activated lymphocytes, leading to apoptotic cell death of activated lymphocytes. Taken together, our findings demonstrate that galectin-9 is involved in MSC-mediated immunosuppression and represents a potential therapeutic factor for the treatment of inflammatory diseases.
Adaptive Immunity ; Apoptosis ; Cell Death ; Cytokines ; Galectins ; Humans* ; Immunosuppression* ; Lymphocytes ; Mesenchymal Stromal Cells*

BACKGROUND: Newborn Screening (NBS) is a public health activity aimed at the early identification of infants who are affected by certain genetic/metabolic/infectious conditions. A cost analysis is critical for national implementation for integration as a public health program.

OBJECTIVES: 1) To determine the incidence rates of congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), galactosemia (GAL), phenylketonuria (PKU) and glucose-6-phosphate dehydrogenase (G6PD) deficiency; and 2) To determine whether NBS is cost-beneficial for each disorder individually or in combination, from a societal perspective.

STUDY DESIGN: Cross sectional survey and cost-benefit analysis.

SUBJECTS AND METHODS: The study was conducted through a screening survey of the original 24 Metro Manila hospitals. Newborns were screened for CH, CAH, GAL, PKU and G6PD deficiency after the 24th hour of life. Those who screened positive underwent serum confirmatory testing. Using incidence rates from the screening survey, a population of 1.5 million, and different screening combinations, the costs for the detection and treatment of the five disorders were compared to the benefits projected from preventing the corresponding complications and consequent productivity losses. For economic evaluation, we compared sequential analysis of doing tandem/multiple testing for the different disorders vs a "do-nothing" alternative. Sensitivity analyses for different incidence and discount rates were conducted to test the strength of the conclusions.

RESULTS: The incidences of the disorders with 95% confidence intervals are: CH is 1:3 235 (1:2 219 - 1:5 946); CAH is 1:7 455 (1:4 046 - 1: 14245); GAL is 1: 106 006 (1: 44 218-1:266 796); and G6PD deficiency is 1:167 (1:151 - 1: 186). Screened individually, CH and G6PD deficiency had net benefits of US$ 5.29 M and US$ 15.44 M, respectively. The other conditions yielded net costs when screened individually - CAH (US$ 2.61 M), GAL (US$ 0.90 M) and PKU (US$ 6.74 M). Pairing the disorders with CH showed the following benefit:cost ratios - CH + CAH, 1.3; CH + GAL, 2.0; CH + G6PD deficiency, 3.4; and CH + PKU, 0.9. Combining disorders resulted in the following benefit:cost ratios - CH + CAH + GAL, 1.2; CH + CAH + GAL + PKU, 0.8; and CH + CAH + GAL + G6PD deficiency, 2.1. Screening for the 5 disorders in tandem resulted in a benefit:cost ratio of 1.4 and a net benefit of US$ 11.42 M.

Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal tract of animals. Although intensive functional studies have been done for other galectin isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic changes on monocytes by altering the expression of various surface molecules, and induced functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity. Concomitant with these changes, Gal-4-treated monocytes became adherent and showed elongated morphology with higher expression of macrophage markers. Notably, we found that Gal-4 interacted with CD14 and activated the MAPK signaling cascade. Therefore, these findings suggest that Gal-4 may exert the immunoregulatory functions through the activation and differentiation of monocytes.
Animals ; Antigens, CD14 ; Cell Differentiation ; Galectin 4 ; Galectins ; Gastrointestinal Tract ; Macrophages ; Monocytes ; Protein Isoforms

The incidence of hematological malignant tumor is increasing year by year, and seriously affecting the human health. In addition to the traditional radiation and chemotherapy, immunotherapy has achieved a certain effect in the treatment of blood tumor, but it is limited by exhaustion of CD8
CD8-Positive T-Lymphocytes ; Galectins ; Hematologic Neoplasms ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Immunotherapy

Objective: To evaluate possible effects of Gelctin-9 on acute graft versus host disease (aGVHD) development and clinical outcomes in patients before and afer allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood samples were obtained from 29 patients and 15 healthy volunteers with heparin anticoagulant tubes. Samples were analyzed using ELISA kits to measure the serum concentrations of Galectin-9. Results: Patients developing aGVHD had significantly lower level of Galectin-9 [ (7.96±1.18) μg/L] before allo-HSCT compared with those not developing aGVHD [ (12.37±0.97) μg/L, P<0.001]. And after allo-HSCT, the consentration of Galectin-9 increased markedly in patients developing aGVHD [ (17.78±1.78) μg/L] compared with those not developing aGVHD [ (9.45±0.80) μg/L, P<0.001]. Patients developing 3-4 grade aGVHD had significantly higher level of Galectin-9 [ (23.25±2.59) μg/L] compared with those developing 1-2 grade aGVHD [ (14.37±1.45) μg/L, P=0.008] and those without aGVHD [ (9.45±0.80) μg/L, P<0.001]. The patients with lower level of Galectin-9 after allo-HSCT (<13.61 μg/L) showed more favorable clinical outcomes compared with those with higher level of Galectin-9 (≥13.61 μg/L) . The 3-year overall survival rates were (100.00±6.05) % and (69.23±12.80) %, respectively (P=0.009) . The cumulative incidence of non-relapse mortality was significantly higher in high Galectin-9 group [ (23.08±11.69) %] in comparison with low Gaelctin-9 group [ (0.00±7.39) %] (P=0.023) . There was no significant difference between the two groups in terms of the cumulative incidence of relapse. The cumulative incidence of relapse at 3 years were (8.33±7.98) % and (12.50±8.27) % in high and low Galectin-9 groups, respectively (P=0.708) . Conclusions: The serum concentration of Galectin-9 at the time of engraftment after allo-HSCT may be used as a predictor for the development and severity of aGVHD. Galectin-9 might be considered as a potential new approach to regulate transplant rejection to achieve desirable survival.
Galectins ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Incidence ; Survival Rate ; Transplantation, Homologous

PURPOSE: The role of different galectins in the pathogenesis of different types of malignancy is now being intensely investigated. In this study, authors investigated the level of galectin-1 expression in human breast cancer tissue to define its relationship to the tumor invasiveness and tumor progression. METHODS: Formalin-fixed, paraffin-embedded tissues from 79 randomly selected breast cancer patients were used to perform immunohistochemical staining for galectin-1. The primary antibody was diluted mouse monoclonal antibody against galectin-1. The staining results were then interpreted by an experienced pathologist, and the results were compared between the groups having different pathologic variables. RESULTS: In breast cancer patients, galectin-1 was diversely expressed in the cancer tissue. Galectin-1 was expressed in both cancer cells and cancer-associated stromal cells. The levels of galectin-1 expression in cancer-associated stromal cells were higher in patients with invasive carcinoma (p = 0.001), in patients with advanced T stages (p = 0.007), and in patients with advanced TNM stages (p = 0.007). The galectin-1 expression in cancer-associated stromal cells was also higher in patients with lymph node metastasis and advanced N stages, but did not reach a statistically significant level. The galectin-1 expression in cancer cell did not have any correlation with pathologic variables. CONCLUSION: This is the first study that has demonstrated the relationship of galectin-1 expression with the tumor invasiveness and tumor progression in human breast cancer. Further large-scaled studies are needed to define the prognostic value of galectin-1 in breast cancer patients, and the exact role of galectin-1 should be investigated more thoroughly.
Animals ; Breast Neoplasms* ; Breast* ; Galectin 1* ; Galectins ; Humans* ; Immunohistochemistry ; Lymph Nodes ; Mice ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Stromal Cells

PURPOSE: The role of different galectins in the pathogenesis of different types of malignancy is now being intensely investigated. In this study, authors investigated the level of galectin-1 expression in human breast cancer tissue to define its relationship to the tumor invasiveness and tumor progression. METHODS: Formalin-fixed, paraffin-embedded tissues from 79 randomly selected breast cancer patients were used to perform immunohistochemical staining for galectin-1. The primary antibody was diluted mouse monoclonal antibody against galectin-1. The staining results were then interpreted by an experienced pathologist, and the results were compared between the groups having different pathologic variables. RESULTS: In breast cancer patients, galectin-1 was diversely expressed in the cancer tissue. Galectin-1 was expressed in both cancer cells and cancer-associated stromal cells. The levels of galectin-1 expression in cancer-associated stromal cells were higher in patients with invasive carcinoma (p = 0.001), in patients with advanced T stages (p = 0.007), and in patients with advanced TNM stages (p = 0.007). The galectin-1 expression in cancer-associated stromal cells was also higher in patients with lymph node metastasis and advanced N stages, but did not reach a statistically significant level. The galectin-1 expression in cancer cell did not have any correlation with pathologic variables. CONCLUSION: This is the first study that has demonstrated the relationship of galectin-1 expression with the tumor invasiveness and tumor progression in human breast cancer. Further large-scaled studies are needed to define the prognostic value of galectin-1 in breast cancer patients, and the exact role of galectin-1 should be investigated more thoroughly.
Animals ; Breast Neoplasms* ; Breast* ; Galectin 1* ; Galectins ; Humans* ; Immunohistochemistry ; Lymph Nodes ; Mice ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Stromal Cells

BACKGROUND AND OBJECTIVES: Existing data on the spatiotemporal expression patterns of a variety of galectins in murine atherosclerosis are limited. We investigated the expression levels of galectins, and their in vivo spatiotemporal expression patterns and statin responsiveness in the inflamed atherosclerotic plaques of apolipoprotein E (apoE)-/- mice. MATERIALS AND METHODS: Galectins expression patterns in aortic atherosclerotic plaques and serum galectin-3 levels were investigated in 26-week-old apoE-/- (n=6) and C57BL/6 mice (n=9). To investigate the spatial and temporal patterns of galectin-1 and galectin-3 in plaques, high-cholesterol diet-fed 26-week-old (n=12) and 36-week-old apoE-/- mice (n=6) were sacrificed and their aortas were examined for galectins' expression using immunoblot analysis and immunohistochemical stain. 36-week-old apoE-/- mice were treated with atorvastatin (n=3, 0.57 mg/kg/day) for the evaluation of its effect on aortic galectins' expression. RESULTS: Immunoblot analyses showed that galectin-1 and galectin-3 were the predominant galectins expressed in murine atherosclerosis. The serum galectin-3 level was significantly higher in apoE-/- mice (p<0.001). While galectin-1 was weakly expressed in both intimal plaques and the media of atherosclerotic aortas, galectin-3 was heavily and exclusively accumulated in intimal plaques. Galectin-3 distribution was colocalized with plaque macrophages' distribution (r=0.66). As the degree of plaque extent and inflammation increased, the intraplaque galectin-3 expression levels proportionally elevated (p<0.01 vs. baseline), whereas galectin-1 expression had not elevated (p=0.14 vs. baseline). Atorvastatin treatment markedly reduced intraplaque galectin-3 and macrophage signals (p<0.001 vs. baseline), whereas it failed to reduce galectin-1 expression in the aortas. CONCLUSION: Galectin-3 is the predominant gal and is colocalized with macrophages within atherosclerotic plaques. Intraplaque galectin-3 expression reflects the degree of plaque inflammation.
Animals ; Aorta ; Apolipoproteins ; Atherosclerosis ; Galectin 1 ; Galectin 3 ; Galectins ; Heptanoic Acids ; Inflammation ; Macrophages ; Mice ; Plaque, Atherosclerotic ; Pyrroles ; Atorvastatin Calcium

BACKGROUND: Galectin-1 (Gal-1) is a member of the galectin family of proteins, which are carbohydrate-binding proteins with an affinity for beta-galactosides. Gal-1 is differentially expressed by various normal and pathological tissues and it performs polyvalent, wide-ranging biological activities. A Gal-1 expression or over-expression in tumors and/or in the tissue surrounding them must be considered as a sign of malignant tumor progression that is often related to tumor metastasis. Although Gal-1 also plays important roles for tumorigenesis and tumor progression, the expression of Gal-1 in melanocytic nevus, dysplastic nevus and malgant melanoma has not yet been investigated. OBJECTIVE: We wanted to investigate and compare the expression of Gal-1 in melanocytic nevus, dysplastic nevusand malignant melanoma. METHODS: The paraffin-embedded specimens of 9 cases of malignant melanoma (MM), 6 cases of dysplastic nevus (DN) and 6 cases of intradermal nevus (IN) were subjected to immunohistochemical staining for Gal-1. RESULTS: The percentage of positive cells for Gal-1 in the MM was significantly higher than that of the DN and IN (p<0.01). The staining intensity of the positive cells for Gal-1 was the highest also in the MM. Meanwhile Gal-1 was more strongly expressed in highly atypical (more pleomorphic, more atypical mitoses) areas of the melanoma tissues. But there was no significant difference between the DN and IN for the expression of Gal-1. LIMITATION: This study is restricted to a small number of patients. CONCLUSION: The present study suggests that Gal-1 is more strongly expressed in malignant melanoma than in melanocytic nevus and dysplastic nevus. Interestingly, Gal-1 was more strongly expressed in the highly atypical portions of the melanoma tissue. Gal-1 might well contribute to the tumorigenesis and malignancy of melanocytes.
Benzamides ; Cell Transformation, Neoplastic ; Dysplastic Nevus Syndrome ; Galectin 1 ; Galectins ; Humans ; Melanoma ; Neoplasm Metastasis ; Nevus, Intradermal ; Nevus, Pigmented ; Proteins ; Tyrosine