Evaluation of adenosine deaminase activity in patients with head and neck cancer (original) (raw)
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Adenosine Deaminase - a Novel Diagnostic and Prognostic Biomarker for Oral Squamous Cell Carcinoma
Asian Pacific journal of cancer prevention : APJCP, 2016
The number of patients with oral cancer in India is increasing gradually (especially in younger people). Although the diagnostic modalities and therapeutic management of oral cancer are improving, the treatment outcome and prognosis of oral cancer remain poor. The absence of definite early warning symptoms for most head and neck cancers suggests that sensitive and specific biomarkers are likely to be important in screening for high-risk patients. To analyze serum adenosine deaminase (ADA) levels in oral squamous cell carcinoma (OSCC) cases who reported to our institute. A prospective study was performed on 100 histopathologically proven cases of OSCC (study group) and 100 normal healthy individuals (control group). Independent sample and one sample t-tests and one way ANOVA followed by Tuckey's POST HOC test were conducted for analysis. Statistically significant increase in serum ADA levels was observed in OSCC cases compared to the control group. Also serum ADA level increased ...
Leukemia Research, 1982
A~traet-Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) were measured in normal human and in malignant lymphoid cells. Thymocytes had high ADA activity (21.2 +__ 6.8 103 nM/h/mg) and low PNP activity (1.2 _ 0.6), whereas T peripheral blood lymphocytes (PBL) had low ADA activity (1.20 + 0.22) and high PNP activity (2.8 + 1.3). Moreover cortico-thymocytes had higher ADA and lower PNP levels than medullary thymocytes. A linear correlation was observed between ADA and PNP activities in both thymocytes and T-PBL. Cells from 13 patients with T acute lymphoblastic leukemia (ALL) and 10 patients with T lymphoblastic lymphoma (LL) had very high levels of ADA (respectively 13.0 + 5.4 and 22.8 + 14) and low levels of PNP (respectively 1.9 + 0.8 and 2.5 _ 1.4). However no clear relationship appeared between subgroups of these T-cell malignancies defined by their patterns of surface antigens. revealed by reactivity with monoclonal antibodies, and ADA and PNP levels, and there was no correlation between the two enzymes. In contrast, cells from 31 patients with HLA-DR ÷ common ALL had significantly low values of ADA as compared to cells from six patients with HLA-DRcommon ALL and a linear correlation was observed between ADA and PNP in cells from children with non-T, non-B ALL. These results show that specific stages of T-cell development may be characterized by the relationships and the correlation between the two enzymes and suggest that TALL and T-LL appear to be the group of lymphoid malignancies with a high degree of incoordination between ADA and PNP activities.
Enzyme activities controlling adenosine levels in normal and neoplastic tissues
Medical Oncology, 2004
Adenosine is known to be associated with effects such as inhibition of immune response, coronary vasodilation, stimulation of angiogenesis, and inhibition of inflammatory reactions. Some authors suggest that adenosine may also have similar functions in tumor tissues. Tissue levels of adenosine are under close regulation by different enzymes acting at different levels. Adenosine is produced from AMP by the action of 5′-nucleotidase (5′-NT) and is converted back into AMP by adenosine kinase (AK) or into inosine by adenosine deaminase (ADA). Inosine is converted into purine catabolites by purine nucleoside phosphorylase (PNP), whereas AMP is converted into ADP and ATP by adenylate kinase (MK). The aim of this study was to analyze the activities of the above enzymes in fragments of neoplastic and apparently normal mucosa, obtained less than 5 cm and at least 10 cm from tumors, in 40 patients with colorectal cancer. The results showed much higher activities of ADA, AK, 5′-NT, and PNP in tumor tissue than in neighboring mucosa (p>0.01 for ADA, AK, and PNP; p>0.05 for 5′-NT), suggesting that the activities of purine metabolizing enzymes increase to cope with accelerated purine metabolism in cancerous tissue. The simultaneous increase in ADA and 5′-NT activities might be a physiological attempt by cancer cells to provide more substrate to accelerate salvage pathway activity.
Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells
Cellular and Molecular Life Sciences, 2016
At sites of inflammation and tumor growth, the local concentration of extracellular adenosine rapidly increases and plays a role in controlling the immune responses of nearby cells. Adenosine deaminases ADA1 and ADA2 (ADAs) decrease the level of adenosine by converting it to inosine, which serves as a negative feedback mechanism. Mutations in the genes encoding ADAs lead to impaired immune function, which suggests a crucial role for ADAs in immune system regulation. It is not clear why humans and other mammals possess two enzymes with adenosine deaminase activity. Here, we found that ADA2 binds to neutrophils, monocytes, NK cells and B cells that do not express CD26, a receptor for ADA1. Moreover, the analysis of CD4? T-cell subset revealed that ADA2 specifically binds to regulatory T cells expressing CD39 and lacking the receptor for ADA1. Also, it was found that ADA1 binds to CD16-monocytes, while CD16? monocytes preferably bind ADA2. A study of the blood samples from ADA2-deficient patients showed a dramatic reduction in the number of lymphocyte subsets and an increased concentration of TNF-a in plasma. Our results suggest the existence of a new mechanism, where the activation and survival of immune cells is regulated through the activities of ADA2 or ADA1 anchored to the cell surface.
Serum adenosine deaminase in carcinoma breast
Indian Journal of Clinical Biochemistry
Serum Adenosine Deaminase (ADA) activity was studied in 20 control cases and 32 patients with carcinoma breast. In control group the ADA activity ranged from 13–94 IU/L with a mean of 43.75±21.55 IU/L while in patients of carcinoma breast it was 16–95 IU/L with a mean of 47.46±22.54 IU/L, but these values were not statistically different. The ADA activity was also compared with other parameters in patients of carcinoma breast but the difference was not statistically significant in the various parameters like duration of disease, menopausal status, tumor size, hemoglobin level, total leucocyte count, absolute lymphocyte count, total serum proteins, serum albumin, histological grade of tumor and lymphocytic infiltration. The only significant difference in ADA activity was when N1 status of lymph node was compared with N2 status of lymph node.
Adenosine and Adenosine Receptors in the Immunopathogenesis and Treatment of Cancer
Journal of cellular physiology, 2017
Tumor cells overcome anti-tumor responses in part through immunosuppressive mechanisms. There are several immune modulatory mechanisms. Among them, adenosine is an important factor which is generated by both cancer and immune cells in tumor microenvironment to suppress anti-tumor responses. Two cell surface expressed molecules including CD73 and CD39 catalyze the generation of adenosine from adenosine triphosphate (ATP). The generation of adenosine can be enhanced under metabolic stress like tumor hypoxic conditions. Adenosine exerts its immune regulatory functions through four different adenosine receptors including A1, A2A, A2B, and A3 which are expressed on various immune cells. Several studies have indicated the overexpression of adenosine generating enzymes and adenosine receptors in various cancers which was correlated with tumor progression. Since the signaling of adenosine receptors enhances tumor progression, their manipulation can be promising therapeutic approach in cance...
Deregulation of purinergic ectoenzyme activity in head and neck cancer promotes immunosuppression
Molecular Biology Reports
Background Head and neck cancer (HNC) comprises a spectrum of neoplasms that affect the upper aerodigestive tract and are the sixth most common cancers worldwide. Individuals with HNC exhibit various symptoms and metabolic changes, including immune alterations and alterations of the purinergic pathway, which may signal worse outcomes. Therefore, the purpose of this research was to measure the activity of purinergic ectoenzymes and interleukins in patients with HNC, oral cavity cancer, and larynx cancer. Methods and Results We recruited 32 patients and 33 healthy control subjects and performed the laboratory analyses. We identified dysregulation in the purinergic signaling pathway characterized by an increase in adenosine triphosphate (ATP) and adenosine monophosphate (AMP) hydrolysis and a decrease in the deamination of adenosine to inosine in these cancers (p < 0.05). These alterations were likely caused by increased activity of the ectoenzymes E-NTPDase and ecto-5'-nucleotidase and reduced adenosine deaminase activity. This dysregulation was associated with immune alterations, increased levels of IL-10, and decreased myeloperoxidase activity (p < 0.05), suggesting immunosuppression in these patients and suggesting possible accumulation of adenosine in the extracellular environment. Conclusions Adenosine is a potent immunosuppressive molecule associated with tumor progression and immune evasion. Our findings suggest a relationship between extracellular purines and the development and progression of the tumor microenvironment and poor outcomes. These findings increase the understanding of biological mechanisms related to HNC and demonstrate that these components are potential diagnostic markers and therapeutic targets for future management strategies and improvement in the quality of life.