Inhibition of lectin-mediated ovarian tumor cell adhesion by sugar analogs.

Woynarowska, Barbara; Skrincosky, David; Haag, Annemarie; Sharma, Manisha; Matta, Khushi L.; Bernacki, Ralph J.

doi:10.1016/s0021-9258(17)31715-5

Cited by 53 publications

(14 citation statements)

References 40 publications

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“…Galectin-1 (Gal-1), a soluble ß-galactoside-binding lectin, is becoming increasingly appreciated as a biological modifier of tumor growth and metastasis (1)(2)(3)(4)(5)(6). Gal-1 can mediate autocrine and paracrine activities that favor invasiveness (7)(8)(9)(10)(11)(12)(13), drive angiogenesis (14,15) and regulate anti-tumor immune responses (16)(17)(18)(19)(20). Gal-1 regulates the fate and function of effector leukocytes by inducing pro-apoptotic signals on effector leukocytes with concomitant skewing of cancer microenvironments towards Th2 and regulatory cytokine profiles (16-18, 20, 21).…”

Section: Introductionmentioning

confidence: 99%

“…Within these microenvironmental nests, tumor-infiltrating T cells were often excluded, preventing intimate contact with ABCB5 + melanoma-initiating cells. To evaluate whether modifying Gal-1 ligands would impact anti-tumor immune responses, we treated mice bearing syngeneic B16 melanomas or EL-4 lymphomas with 4-F-GlcNAc, a biosynthetic inhibitor of Gal-1-binding N-acetyllactosamine moieties (8,9,(31)(32)(33). 4-F-GlcNAc treatment inhibited Gal-1 ligand formation on effector T and NK cells, which prevented Gal-1-induced apoptosis and caused concomitant increases in melanomaspecific CTLs and IFN-γ levels.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment

Ito

Stannard

Gabutero

et al. 2012

Cancer Metastasis Rev

105

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The microenvironment of a tumor is a highly complex milieu, primarily characterized by immunosuppression, abnormal angiogenesis, and hypoxic regions. These features promote tumor progression and metastasis, resulting in poor prognosis and greater resistance to existing cancer therapies. Galectin-1 is a β-galactoside binding protein that is abundantly secreted by almost all types of malignant tumor cells. The expression of galectin-1 is regulated by hypoxia-inducible factor-1 (HIF-1) and it plays vital pro-tumorigenic roles within the tumor microenvironment. In particular, galectin-1 suppresses T cell-mediated cytotoxic immune responses and promotes tumor angiogenesis. However, since galectin-1 displays many different activities by binding to a number of diverse N- or O-glycan modified target proteins, it has been difficult to fully understand how galectin-1 supports tumor growth and metastasis. This review explores the importance of galectin-1 and glycan expression patterns in the tumor microenvironment and the potential effects of inhibiting galectin-1 as a therapeutic target for cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment

Ito

Stannard

Gabutero

et al. 2012

Cancer Metastasis Rev

105

View full text Add to dashboard Cite

show abstract

“…So far, some strategies appear to be promising in abrogating galectin-mediated effects. These include: (1) neutralization of galectin-binding through blocking antibodies against galectins [18], (2) competitive inhibition of galectin binding via synthetic analogs of galectin carbohydrate-binding determinants [19], (3) modification of the glycosylation profiles necessary for galectin binding on anti-tumor immunocytes through fluorinated analogs of glucosamine [7,20]. Recently, a Phase IB (NCT03066648) clinical trial was undertaken to investigate the therapeutic effects on blocking galectin-9/TIM-3 pathway with anti-TIM-3 antibody, about one-third newly diagnosed and relapse/refractory AML patients achieved complete or partial response [21].…”

Section: Discussionmentioning

confidence: 99%

Galectin-9 and PSMB8 overexpression predict unfavorable prognosis in patients with AML

Zhang¹,

Xue²,

Qin³

et al. 2021

J. Cancer

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Acute myeloid leukemia (AML) is a deadly heterogeneous hematologic malignancy. Despite the well-characterized genetic characteristics and new promising targeted therapies for AML, the clinical outcome remains suboptimal. Galectin-9 (Gal-9) is a good potential target due to its immunosuppressive capacity in inflammatory processes. In our study, we firstly performed a wide range of integrated bioinformatical approach to assess the importance of Gal-9 by analyzing the expression, potential function and prognostic impact in AML. The results indicated that Gal-9 is overexpressed in AML cells, especially when relapse after hematopoietic stem cell transplantation (HSCT) and predicts poor prognosis. Co-expression analysis showed Gal-9 has a strong positive correlation with proteasome subunit beta type-8 (PSMB8), which was also highly expressed in AML with poor prognosis, implying a synergy in cell survival, cell signaling and the development of AML. In summary, we have confirmed the overexpression of Gal-9 and its partner PSMB8 in AML and validated their importance as prognostic factors. We propose that Gal-9 and PSMB8 could be a promising molecular target for treatment of AML and may provide more combined treatment options, especially in patients with relapse after HSCT.

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“…Gal-1 is reported to be the mediator of cardiovascular inflammation [5]. It also mediates the interaction of cancer cells with the extracellular matrix [6]. Numerous literatures indicate the regulatory functions of Gal-1 in viral [7], bacterial [8], and parasite infection [9].…”

Section: Introductionmentioning

confidence: 99%

Elevated serum galectin-1 concentrations are associated with increased risks of mortality and acute kidney injury in critically ill patients

Chou

Tsai

et al. 2021

PLoS ONE

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Background Galectin-1 (Gal-1), a member of the β-galactoside binding protein family, is associated with inflammation and chronic kidney disease. However, the effect of Gal-1 on mortality and acute kidney injury (AKI) in critically-ill patients remain unclear. Methods From May 2018 to March 2020, 350 patients admitted to the medical intensive care unit (ICU) of Taipei Veterans General Hospital, a tertiary medical center, were enrolled in this study. Forty-one patients receiving long-term renal replacement therapy were excluded. Serum Gal-1 levels were determined within 24 h of ICU admission. The patients were divided into tertiles according to their serum Gal-1 levels (low, serum Gal-1 < 39 ng/ml; median, 39–70 ng/ml; high, ≥71 ng/ml). All patients were followed for 90 days or until death. Results Mortality in the ICU and at 90 days was greater among patients with elevated serum Gal-1 levels. In analyses adjusted for the body mass index, malignancy, sepsis, Sequential Organ Failure Assessment (SOFA) score, and serum lactate level, the serum Gal-1 level remained an independent predictor of 90-day mortality [median vs. low: adjusted hazard ratio (aHR) 2.11, 95% confidence interval (CI) 1.24–3.60, p = 0.006; high vs. low: aHR 3.21, 95% CI 1.90–5.42, p < 0.001]. Higher serum Gal-1 levels were also associated with a higher incidence of AKI within 48 h after ICU admission, independent of the SOFA score and renal function (median vs. low: aHR 2.77, 95% CI 1.21–6.34, p = 0.016; high vs. low: aHR 2.88, 95% CI 1.20–6.88, p = 0.017). The results were consistent among different subgroups with high and low Gal-1 levels. Conclusion Serum Gal-1 elevation at the time of ICU admission were associated with an increased risk of mortality at 90 days, and an increased incidence of AKI within 48 h after ICU admission.

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Inhibition of lectin-mediated ovarian tumor cell adhesion by sugar analogs.

Cited by 53 publications

References 40 publications

Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment

Galectin-1 as a potent target for cancer therapy: role in the tumor microenvironment

Galectin-9 and PSMB8 overexpression predict unfavorable prognosis in patients with AML

Elevated serum galectin-1 concentrations are associated with increased risks of mortality and acute kidney injury in critically ill patients

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