Saliva Analysis in the Clinical Setting: Revisiting an Underused Diagnostic Tool

Nagler, Rafael M.; Hershkovich, Oded; Lischinsky, Sophie; Diamond, Eric; Reznick, Abraham Z.

doi:10.2310/6650.2002.33436

Cited by 84 publications

(80 citation statements)

References 30 publications

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“…Salivary enhancement of CS effects might explain the high prevalence of CS-induced OP cancer. In addition, saliva is always considered an efficient protective medium -an antibacterial, antiviral, anticariogenic, antioxidative, mechanical and thermal protector, etc (Nagler et al, 2002b). However, the current study demonstrates that in the 'wrong circumstances' saliva becomes highly deleterious, such as when it is exposed to CS.…”

Section: Discussionmentioning

confidence: 65%

“…Further significant credence for the mechanism suggested is found in the reported existence of redox metals (iron and copper) in saliva and of their deleterious role in the pathogenesis of the damage inflicted on salivary glands by ionising irradiation (another source of low reactive free radicals) (Nagler et al, 1997;Nagler and Baum, 2003). Finally, major support for the suggested mechanism can be found in a recent report which demonstrated that in humans the Sm/Sl saliva contains much higher concentrations of iron than does the parotid saliva, especially when secreted under resting conditions (Nagler et al, 2002b). This undoubtedly adds to explanation given previously for the profound cytotoxic behavior of Sm/Sl saliva as compared with parotid saliva, as well as for the general role of salivary redox metals, such as iron, in the underlying mechanism of the synergism phenomenon.…”

Section: Discussionmentioning

confidence: 95%

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Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

2004

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Oropharyngeal (OP) cancer, which is usually squamous cell carcinoma, is the most common head and neck malignancy and accounts for 2 -4% of all new cancers. It is primarily induced by exposure to tobacco. The paradigm of cigarette smoke (CS)-induced OP cancer's pathogenesis is based on the assumption that a constant direct attack of various CS carcinogens causes widespread accumulating cellular and DNA aberrations in the OP mucosal cells, in turn eventually resulting in malignant transformation. However, there is never a direct contact between CS and the OP mucosa. Saliva, bathing the mucosa from the oral cavity to the larynx, always intervenes, and CS must first interact with saliva before it reaches the mucosa. The current study investigated the role of saliva in the pathogenesis of OP cancer. A synergistic effect of CS and saliva on oral cancer cells was demonstrated. This synergism is based on the reaction between redox active metals in saliva and low reactive free radicals in CS, which results in the production of highly active hydroxyl free radicals. Thus, when exposed to CS, salivary behavior is reversed and the saliva loses its antioxidant capacity and becomes a potent prooxidant milieu. The devastating role of CS-borne aldehydes was demonstrated as well. Based on these results and on our recent reports demonstrating that CS destroys various salivary components, including protective ones such as peroxidase, the most important salivary antioxidant enzyme, a comprehensive view of the pivotal role of saliva in the pathogenesis of CS-induced OP cancer is suggested. Oropharyngeal (OP) cancer, which is usually squamous cell carcinoma, is the most common head and neck malignancy, having a worldwide incidence of over 300 000 new cases each year and accounting for 2 -4% of all new cancers (Bross and Coombes, 1976;McGinnis and Foege, 1993;Collins et al, 1994;Ko et al, 1995;Piyathilake et al, 1995;Zheng et al, 1997;Nagler et al, 1999; Lippman and Hong, 2001). The commonly accepted paradigm for cigarette smoke (CS)-induced OP cancer pathogenesis is based on the assumption that a constant and direct attack of various CS carcinogens causes widespread accumulating cellular and DNA aberrations in the OP mucosa eventually leading to malignant transformation and cancer development. The CS-borne carcinogens are often thought to be free radicals. The process is initially expressed by dysplastic mucosal lesions which are then transformed into in situ carcinoma lesions, eventually resulting in fullblown infiltrating and metastasising OP cancer (Holleb et al, 1991). Chen et al (2002) demonstrated that chewing tobacco (areca quid) resulted in the formation of ROS in the oral cavity causing oxidative DNA damage to the surrounding tissues. Further support can be found in a report demonstrating that premalignant mucosal lesions and low-grade carcinomas express DNA aberrations following a pathway of exposure to free radicals (Sudb et al, 2001). Moreover, Bloching et al (2001) recently found increased genotoxic activity in the saliv...

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 95%

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

2004

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“…However, the results of JIA-related reductions of MMPs 2, 3 and 9 in the saliva are puzzling, as these specific MMPs were found to be increased in the serum and in the synovial fluid of JIA and rheumatoid arthritis (RA) patients (14)(15)(16)(17). It is well established that most enzymes found in the saliva originate from the salivary or oral mucosal cells and not from the serum (28). This could explain an absence of increase in the salivary MMP in JIA, but not a decrease.…”

Section: Discussionmentioning

confidence: 99%

Salivary Antioxidants and Metalloproteinases in Juvenile Idiopathic Arthritis

Brik

Rosen

Savulescu

et al. 2009

Mol Med

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Juvenile idiopathic arthritis (JIA) is the most common autoimmune inflammatory disease in children; joint inflammation is the hallmark of the disease. Thirty-five children with JIA were studied, of whom 26 had active disease and 14 were receiving anti-TNF therapy (5 with Infliximab, 9 with Etanercept). Sixteen healthy controls also were studied. Saliva samples were obtained for analysis of anti-oxidant status, metalloproteinases (MMPs) and sialochemistry. The total antioxidant status was significantly higher in the saliva of all JIA patients, whether treated (P = 0.014) or not treated (P = 0.038) with anti-TNF agents. The increase in antioxidant status (TAS) in the saliva of the active patients was nearly two times higher than that of non-active patients (P = 0.01). MMP levels were significantly lower in JIA patients than in controls. MMP-9, MMP-3 and MMP-2 were lower in JIA patients without anti-TNF treatment by 36.7% (P = 0.01), 30.0% (P = 0.0001) and 10.7% (P = 0.0001), respectively. A greater reduction in MMP levels was observed in the group of patients treated with anti-TNF drugs: MMP-9, MMP-3 and MMP-2 were lower than in controls by 51.1% (P = 0.0001), 61.5% (P = 0.0001) and 55.4% (P = 0.0001), respectively. Children with JIA exhibited a significantly higher salivary antioxidant activity and significantly lower MMP levels. Anti-TNF treatment was associated with a further decrease in MMP levels in the saliva of JIA patients while an active state of JIA was associated with a further increase in the salivary antioxidant activity. Anti-TNF treatment may modulate the degradation process during the course of arthritis by inhibition of the activity of MMP .

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“…These were measured in saliva, which was collected as described earlier (Nagler et al, 2002), shortly before the administration of the definitive curative treatment. This included surgical removal of the primary tongue tumour, neck dissection and, in most cases, post-operative adjuvant radiotherapy.…”

Section: Patients and Study Designmentioning

confidence: 99%

Salivary analysis of oral cancer biomarkers

et al. 2009

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BACKGROUND: Oral cancer is a common and lethal malignancy. Direct contact between saliva and the oral cancer lesion makes measurement of tumour markers in saliva an attractive alternative to serum testing. METHODS: We tested 19 tongue cancer patients, measuring the levels of 8 salivary markers related to oxidative stress, DNA repair, carcinogenesis, metastasis and cellular proliferation and death. RESULTS: Five markers increased in cancer patients by 39 -246%: carbonyls, lactate dehydrogenase, metalloproteinase-9 (MMP-9), Ki67 and Cyclin D1 (CycD1) (Pp0.01). Three markers decreased by 16 -29%: 8-oxoguanine DNA glycosylase, phosphorylated-Src and mammary serine protease inhibitor (Maspin) (Pp0.01). Increase in salivary carbonyls was profound (by 246%, P ¼ 0.012); alterations in CycD1 (87% increase, P ¼ 0.000006) and Maspin (29% decrease, P ¼ 0.007) were especially significant. Sensitivity values of these eight analysed markers ranged from 58% to 100%; specificity values ranged from 42% to 100%. Both values were especially high for the CycD1 and Maspin markers, 100% for each value of each marker. These were also high for carbonyls, 90% and 80%, respectively, and for MMP-9, 100% and 79%, respectively. CONCLUSIONS: The significance of each salivary alteration is discussed. As all alterations correlated with each other, they may belong to a single carcinogenetic network. Cancer-related changes in salivary tumour markers may be used as a diagnostic tool for diagnosis, prognosis and post-operative monitoring.

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Saliva Analysis in the Clinical Setting: Revisiting an Underused Diagnostic Tool

Abstract: We think that saliva analysis is a useful, worthwhile diagnostic tool because saliva collection is noninvasive, easy, and inexpensive and may be performed by the patient with no need for the involvement of medical personnel, if so desired.

Cited by 84 publications

References 30 publications

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

Saliva – a pivotal player in the pathogenesis of oropharyngeal cancer

Salivary Antioxidants and Metalloproteinases in Juvenile Idiopathic Arthritis

Salivary analysis of oral cancer biomarkers

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