Rakesh M. Rawal

Lipid Peroxidation, Total Antioxidant Status, and Total Thiol Levels Predict Overall Survival in Patients With Oral Squamous Cell Carcinoma

Tobacco is the major etiological factor for oral cancer development through the generation of oxidative stress. Therefore, markers of oxidative stress such as total antioxidant status, lipid peroxidation, and total thiol levels might be useful to monitor oxidative stress and predict overall survival in oral cancer patients. The study included 140 oral cancer patients and 50 healthy controls, who were classified as with the habit of tobacco and no habit of tobacco. Adjacent normal and malignant tissue samples were collected from oral cancer patients. Plasma and tissue levels of lipid peroxidation, thiol, and total antioxidant status were assayed by spectrophotometric methods. Thiol levels were significantly lower in controls with the habit of tobacco (P = .033), oral cancer patients ( P = .0001), and malignant tissues (P = .015) as compared to controls with no habit of tobacco, controls with the habit of tobacco, and adjacent normal tissues, respectively. Tobacco exposure was higher in oral cancer patients than controls with the habit of tobacco. Controls with the habit of tobacco who had lower thiol (odds ratio [OR] = 10.58, P = .008) and high tobacco exposure (OR = 0.251, P = .05) showed an elevated risk of oral cancer development. Patients showing a lipid peroxidation level above the cutoff level as compared to patients below the cutoff level showed poor overall survival, whereas those with thiol and total antioxidant status levels below the cutoff level as compared to their respective counterparts showed poor overall survival. In conclusion, lipid peroxidation and thiol could be useful for predicting the risk of oral carcinogenesis in healthy tobacco consumers and predicting overall survival of oral cancer patients.

Tobacco, antioxidant enzymes, oxidative stress, and genetic susceptibility in oral cancer.

Objectives:Oral cancer accounts third of all malignancies in India. Tobacco use, the major etiological factor for oral cancer is known to generate free radicals resulting in alterations in antioxidant enzymes like, glutathione-S-transferase (GST), glutathione reductase, superoxide dismutase, catalase, and glutathione peroxidase as well as lipid peroxidation and total thiol. Therefore, it is of fundamental importance to evaluate the role of tobacco and antioxidant enzymes and oxidative stress markers in oral carcinogenesis. Materials and Methods:One hundred forty oral cancer patients and 50 healthy controls, classified as “habitual controls” and “nonhabitual controls” having tobacco habits and no tobacco habits, respectively, were included in the study. Adjacent normal and malignant tissue samples were also collected. Erythrocyte, plasma, and tissue levels of antioxidant enzymes and total thiol were assayed by spectrophotometric methods. GSTM1 genotype was analyzed using polymerase chain reaction. Results:Antioxidant enzymes were significantly higher whereas glutathione peroxidase and thiol levels were lower in patients as compared with habitual controls. Habitual controls with higher tobacco exposure and lower antioxidant enzymes as well as thiol showed higher risk of oral cancer development. Antioxidant enzymes were higher, whereas catalase and thiol levels were lower in malignant as compared with adjacent normal tissues. Sixty-three percent of the patients showed GSTM1 null genotype. Conclusion:The study showed risk of oral cancer development in habitual controls with lower antioxidant enzymes, lower oxidative stress markers, and higher lifetime tobacco exposure. Individuals with GSTM1 null genotype may be at higher risk of oral cancer development.

Study of Tobacco Habits and Alterations in Enzymatic Antioxidant System in Oral Cancer

Aim and Objective: Tobacco is a major etiological factor for oral cancer development, accounting 30–40% of all cancer cases in India. Tobacco consumption generates free radicals and causes oxidative damages. In order to counteract these lethal effects, normal living cells have multiple antioxidant defense systems in a cascade manner. Thus, it seems that studying biological parameters, like antioxidant enzyme system, may be helpful in risk assessment and early diagnosis of oral cancer. Therefore, we analyzed erythrocytic and tissue antioxidant enzyme activities in terms of glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and plasma thiol levels. Materials and Methods: Study included healthy controls with no habit of tobacco (NHT, n = 25), controls with habit of tobacco (WHT, n = 31) and oral cancer patients (n = 52). All the parameters were analyzed with highly sensitive and specific spectrophotometric methods. Results: Erythrocytic SOD and plasma thiol levels were significantly lower (p = 0.03), while GPx and CAT levels were higher (p = 0.017) in WHT as compared to NHT. No significant changes in GST and GR levels were observed between NHT and WHT. GST, GR, SOD and CAT activities were significantly higher (p = 0.05, p < 0.001, p = 0.003 and p < 0.001, respectively) while GPx and thiol levels were lower (p = 0.035 and p < 0.001, respectively) in oral cancer as compared to WHT. Odds ratio for erythrocytic GR, SOD, CAT and plasma thiol showed significantly higher risk of oral cancer development in WHT. Mean levels of SOD and CAT were increased, while GPx and thiol were decreased with the increase in habit duration in oral cancer. GST, GR and SOD activities were significantly higher (p = 0.0001, p = 0.005 and p = 0.005, respectively), while, CAT and thiol levels were lower (p = 0.0001 and p = 0.015, respectively) in malignant tissues as compared to adjacent normal tissues. Conclusion: The data revealed that evaluation of antioxidant enzyme activities and thiol levels in WHT can be helpful to identify individuals at a higher risk of oral cancer development

Evaluation of serum alkaline DNase activity in treatment monitoring of head and neck cancer patients.

Our previously published data on breast cancer suggest that serum alkaline DNase, a known circulating tumour marker, can be used for treatment monitoring of cancer patients. Serum alkaline DNase activities were analyzed in 215 untreated head and neck cancer patients. The enzyme activity ranged from 0.17 to 97.97 IKU/l in untreated cancer patients. Responders (n = 314) showed significantly elevated activity of alkaline DNase as compared to untreated cancer patients (p < 0.001). While non-responders (n = 168) showed comparable activity with untreated cancer patients. Serum alkaline DNase activities were significantly elevated in responders as compared to non-responders (p < 0.001). Our clinical studies during follow-up of patients indicated that the variations in serum alkaline DNase activities in individual patients correlate closely with response to therapy. Serum alkaline DNase also appeared to be useful in predicting treatment response in the long-term follow-up of patients. Serum alkaline DNase was systematically examined as a possible indicator for recurrence in patients under complete remission. In conclusion, serum alkaline DNase may be useful as a treatment monitoring in patients with head and neck malignancies.

Assessment of glutathione-S-transferase and glutathione reductase in patients with squamous-cell carcinoma of buccal mucosa.

Serum and tumor cytosolic levels of glutathione‐S‐transferase (GST) and glutathione‐reductase (GR) activity were determined spectrophotometrically. The levels were correlated with clinicopathological criteria and a tobacco‐associated protein band (T band) found in serum. The results showed significantly decreased mean serum GST levels (p < 0.02) in cancer patients as compared with controls. However, mean serum GR levels were significantly higher in patients than in controls (p < 0.01). T‐band‐positive patients showed low GST and low GR activity as compared with T‐band‐negative patients. Tumor cytosolic‐enzyme levels of GST and GR activity were significantly higher (p < 0.0003 and p < 0.0001, respectively) than in corresponding adjacent noncancerous mucosa. Tumour cytosolic GST and GR activity showed significant association with clinicopathologic criteria, e.g., stage, histologic grade and nodal involvement. T‐band‐negative patients showed significantly higher levels of GST (p < 0.0001) than did T‐band‐positive patients. Low levels of cytosolic GST may be associated with increased susceptibility towards carcinogen‐induced damage. The results suggest that the presence of T band in the sera may be associated with a high‐risk phenotype due to decreased detoxification ability. Int. J. Cancer 83:727–731, 1999.

Evaluation of glycoprotein constituents in head and neck cancer patients undergoing radiotherapy.

Alterations in serum levels of several glycoprotein constituents are reported to be useful for treatment monitoring of cancer patients. The purpose of this study was to determine efficacy of sialic acid and seromucoid fraction as treatment monitors for head and neck (H&N) cancer patients undergoing radiotherapy (RT).

Seromucoid fraction : A useful biomarker for patients with breast cancer

Seromucoid fraction was measured in terms of mucoid proteins (MP) and hexose content from sera of 1) 47 healthy women, 2) 48 women who had benign breast diseases, 3) 151 untreated patients with breast cancer, and 4) 245 follow-up samples collected from the same breast cancer patients. Mucoid proteins and hexose levels were found to be significantly elevated in untreated patients with breast cancer when compared with the healthy participants (p < 0.001) and patients who had benign breast diseases (p < 0.02 and p < 0.05, respectively). Receiver operating characteristic (ROC) curve analysis revealed potential diagnostic application of both markers for breast cancer. A good correlation was observed between favorable treatment response and decline in serum-marker levels. The markers in patients who did not respond to anticancer therapy remained stable or increased during follow-up. These data indicate that seromucoid fraction can be an useful biochemical marker for breast cancer patients.