Study of IL-6 and vitamin D3 in patients of pulmonary tuberculosis.

BACKGROUND: Mycobacterium tuberculosis can grow in hostile intracellular environment of macrophages by actively evading macrophage-associated antibacterial activities. The stress response factor contributes this process by releasing inflammatory cytokine Interleukin 6 (IL-6). IL-6 screening of patients with TB may be useful to monitor the progress of infection and to infer the risk of progression to active disease. Vitamin D has a critical role in the innate immune system, in the circulating metabolite and supports induction of pleiotropic antimicrobial responses, through the production of antimicrobial peptides, particularly cathelicidin and its active metabolite. 1,25-dihydoxyvitamin D, has long been known to enhance immune response to mycobacteria. In this study, we have studied the role of IL-6 and Vitamin D3 in M. tuberculosis. MATERIALS AND METHODS: Three groups involved in this study are Control, Category I (newly diagnosed TB) and MDR TB patients. The serum levels of IL-6 and vitamin D3 were measured using chemiluminescence and fully-automated enzyme-linked immunosorbent assay respectively. RESULTS: The serum levels of IL-6 were significantly increased, whereas vitamin D3 decreased in TB multidrug-resistant group of patients compared to the newly diagnosed TB patients. CONCLUSION: IL-6 appears to be the major cytokine elaborated by mycobacteria infection as well as play a role in the clinical manifestations and pathological events and hence may function as a potent biomarker of tuberculosis. Since, Vitamin D increases activity of cell-mediated immunity; it can be used as a supplementation during tuberculosis therapy.

Helicobacter pylori gastritis, a presequeale to coronary plaque.

Helicobacter pylori are considered the most common human pathogen colonizing gastric mucosa. Gastritis with or without H. pylori infection is associated with increase in levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) but a more pronounced increase is noted in gastritis with H. pylori infection. Increasing level of homocysteine, due to decreased absorption of vitamin B12 and folic acid, together with increased CRP levels in gastritis with H. pylori infection may be the earliest event in the process of atherosclerosis and plaque formation. Retrospective study conducted at tertiary care hospital in Mumbai by Department of Biochemistry in association with Department of Surgery. Eighty patients who underwent gastroscopy in view of gastritis were subjected to rapid urease test for diagnosis of H. pylori infection. Vitamin B12, folic acid, homocysteine and hs-CRP were analyzed using chemiluminescence immuno assay. Student's t-test, Pearson's correlation and linear regression used for statistical analysis. Patients with H. pylori gastritis had significantly lower levels of vitamin B12 (271.6±101.3 vs 390.6±176.7 pg/mL; P=0.0005), as well as higher levels of homocysteine (17.4±7.4 vs 13.8±7.8 µmol/L; P=0.037) and hs-CRP (2.5±2.9 vs 1.2±1.1 mg/L; P=0.017), than in patients without H. pylori gastritis. However, folic acid showed (8.9±3.2 vs 10.0±3.6 ng/mL; P=0.171) no significant difference. Elevated homocysteine and hs-CRP in H. pylori gastritis may independently induce endothelial dysfunction, leading to cardiovascular pathology.

The roles of glutathione, glutathione peroxidase, glutathione reductase and the carbonyl protein in pulmonary and extra pulmonary tuberculosis.

BACKGROUND: This study determines the protein carbonyls which cause cellular damage and glutathione, glutathione peroxidase, glutathione reductase act as antioxidants. MATERIALS AND METHODS: This study was carried out in different categories of pulmonary and extra pulmonary tuberculosis cases of newly sputum culture positive diagnosed pulmonary categorie I (n=100), extra pulmonary patients categorie (n=35) before and after the DOTS treatment of 6 months, categorie II (n=100), categorie III (n=100) and in normal control subjects (n=100). RESULTS: The serum protein carbonyl levels were significantly increased in the pulmonary and extra pulmonary tuberculosis patients. The activities of blood glutathione, glutathione peroxidase, and glutathione reductase were found to be significantly decreased in subjects of all the categories of pulmonary and extra pulmonary tuberculosis. A negative correlation between the carbonyl protein content and glutathione, glutathione peroxidase, and glutathione reductase was seen in pulmonary tuberculosis, p<0.001. CONCLUSION: Increased antioxidant defense mechanism due to increase oxidative stress in tuberculosis. The changes were reversed after 6 months of antitubercular treatment in patients with a good recovery, but the increase in the oxidative stress was not completely reversed.

Effect of methylxanthines (coffee/tea consumers) on oral precancer and oral cancer patients with smoking and smokeless tobacco habits.

AIM: To study, whether the consumption of regular tea/coffee (methylxanthines) increases the risk of oral cancer in patients with smoking and smokeless tobacco habits. MATERIALS AND METHODS: This study was conducted on a total of 90 oral cancer and precancerous patients, from western Maharashtra (India) males in the age group of 20 to 45 years who were with smoking and smokeless tobacco habits; also regular tea/coffee consumers were subjected to biochemical parameters such as aspartate transaminase (AST) and alanine transaminase (ALT) from saliva and serum of patients with oral precancer (submucous fibrosis, leukoplakia) and oral cancer patients and compared with 90-age and sex-matched controls. Individuals consent was taken to measure their biochemical parameters, by using Hafkenscheid method in whole saliva and serum. Statistical analysis of variance (ANOVA) with Tukey's correction for multiple group comparisons was performed using Student t-test. RESULTS: Results show, that a statistically significant increase in value (p < 0.05) in ALT, AST in both saliva and serum was observed in precancerous and oral cancer patients among the study group as compared to the control group. CONCLUSION: In the present study, there was increase in the levels of ALT, AST enzymes in both saliva and serum levels in the study group as compared to the control group which was statistically significant (p < 0.05) suggesting that long-term exposure of methylxanthines results in impairment of salivary gland antioxidant system which may affect the anticarcinogenic action of saliva. CLINICAL SIGNIFICANCE: Oral fluids may be utilized effectively to study the variations in the biochemical constituents of saliva of leukoplakia, submucous fibrosis and oral cancer patients.

E-Cadherin as a diagnostic biomarker in breast cancer.

BACKGROUND: E-cadherin is expressed in most normal epithelial tissues. Selective loss of E-cadherin can cause dedifferentiation and invasiveness in human carcinomas, leading E-cadherin to be classified as a tumor suppressor. Loss of E-cadherin has been demonstrated in invasive lobular carcinoma of the breast, but the relationship between E-cadherin expression and breast cancer histopathology and prognosis is less clear. AIM: Our objective was to assess loss of E-cadherin as a diagnostic breast cancer biomarker and as an aid to the sub-classification of invasive breast cancer. We also correlated the loss of expression of E-cadherin with various clinical and pathologic prognostic factors. MATERIAL AND METHODS: Breast cancer specimens after modified radical mastectomy were obtained from women who underwent surgery at Grant Medical College and Sir J.J Group of Hospitals, Mumbai, India between May 2007 and October 2010. We stained 276 breast cancers specimens with monoclonal antibodies to E-cadherin. The breast cancers were classified by histopathological type. RESULTS: A statistical correlation of E-cadherin loss with a positive diagnosis of invasive lobular carcinoma was found, but there was no correlation with any prognostic tumor variables. A negative E-cadherin stain was a sensitive and specific biomarker to confirm the diagnosis of invasive lobular carcinoma (specificity 97.7%; negative predictive value 96.8%; sensitivity 88.1%; and positive predictive value 91.2%). Positive E-cadherin expression was also associated with tubulolobular carcinomas. CONCLUSIONS: E-cadherin immunohistochemistry is helpful in classifying breast cancer cases with indeterminate histopathologic features. E-cadherin loss is uncommon in non-lobular carcinomas but shows no correlation to currently established prognostic variables.

Study of serum homocysteine, folic Acid and vitamin b(12) in patients with preeclampsia.

The present study was carried out to evaluate the occurrence of association between homocysteine, folic acid and vitamin B(12) in patients with preeclampsia. Fifty preeclamptic patients from gynecology ward were studied for estimation of serum homocysteine, folic acid and vitamin B(12) over a period of October 2007 to June 2010. Serum homocysteine and folic acid, and vitamin B(12) were determined by means of Immulite 1000 analyzer. The statistical analysis of study group of preeclampsia compared with normotensive control group, showed significant alterations in serum homocysteine, folic acid and vitamin B(12) concentrations in preeclampsia. Inverse association between serum homocysteine and folic acid, and vitamin B(12) levels were observed in preeclampsia. The present study found hyperhomocysteinemia and deficiency of folic acid and vitamin B(12) along with increased blood pressure as a risk factor for cardiovascular disease (CVD) in preeclampsia.

Ki-67 biomarker in breast cancer of Indian women.

BACKGROUND: Biological markers that reliably predict clinical or pathological response to primary systemic therapy early during a course of chemotherapy may have considerable clinical potential. AIMS: Aims of study to evaluated changes in Ki-67 (MIB-1) labeling index and apoptotic index (AI) before, during, and after neoadjuvant anthracycline chemotherapy in breast cancer in Indian women. MATERIALS AND METHODS: Breast cancer tissues were collected from Grant Medical College and Sir J.J. Group of Hospitals, Mumbai, India. Twenty-seven patients receiving neoadjuvant FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for operable breast cancer underwent repeat core biopsy after 21 days of treatment. RESULTS: The objective clinical response rate was 56%. Eight patients (31%) achieved a pathological response by histopathological criteria; two patients had a near-complete pathological response. Increased day-21 AI was a statistically significant predictor of pathological response (p = 0.049). A strong trend for predicting pathological response was seen with higher Ki-67 indices at day 21 and AI at surgery (p = 0.06 and 0.06, respectively). CONCLUSION: The clinical utility of early changes in biological marker expression during chemotherapy remains unclear. Until further prospectively validated evidence confirming the reliability of predictive biomarkers is available, clinical decision-making should not be based upon individual biological tumor biomarker profiles.

Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women.

The aim of our study was to analyze triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PgR), and the human epidermal growth factor receptor 2 (HER-2/neu) and which represents a subset of breast cancer with different biologic behavior. We investigated the clinicopathological characteristics and prognostic indicators of lymph node-negative TN breast cancer. Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India, from May 2007 to October 2010. Clinicopathological variables and clinical outcomes were evaluated. Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (<35 years, P = 0.003) and a higher histopathologic and nuclear grade (P < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for Bcl-2 expression (P < 0.001), positive for the epidermal growth factor receptor (P = 0.003), and a high level of p53 (P < 0.001) and Ki-67 expression (P < 0.00). The relapse rates during the follow-up period (median 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (P = 0.004). Relapse-free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer: 3.5-year RFS rate 85.5% versus 94.2%, respectively; P = 0.001. On multivariate analysis, young age, close resection margin, and triple negativity were independent predictors of shorter RFS. TN breast cancer had a higher relapse rate and more aggressive clinicopathological characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into risk factor analysis for node-negative breast cancer.

Cancer biomarker HER-2/neu in breast cancer in Indian women.

AIM AND OBJECTIVES: In Indian women with breast cancer, the HER-2/neu gene is amplified in 30% of cases. Elevated serum HER-2/neu levels have been shown to be associated with a poor clinical prognosis and decreased survival in early stage breast cancer patients, and testing for this may help to manage the disease. The present study was therefore to estimate serum HER-2/neu levels in breast cancer patients and associate these with other prognostic factors. MATERIALS AND METHODS: Serum HER-2/neu levels were studied in 207 patients with breast cancer, 15 with benign breast diseases, (BBD) and 175 age-matched healthy controls. Patients' age, menopausal status, node, and estrogen receptor (ER) and progesterone receptor (PgR) status were compared with serum HER-2/neu levels. RESULTS: Serum HER-2/neu overexpression was associated with age, disease stage and positive nodal status but not with menopausal status. Serum HER-2/neu levels were negatively correlated with hormone receptor positivity. CONCLUSION: HER-2/neu serum tests should be done more frequently in Indian women with breast cancer, irrespective of their ER and PgR hormone receptor status. ELISA is a reliable and economical tool to assess the HER-2/neu status in tumors, when breast tissue samples are not available.

Estrogen receptor (ER) and progesterone receptor (PgR) in breast cancer of Indian women.

OBJECTIVE: To determine the expressions and relationship between estrogen receptors (ERs) and progesterone receptors (PgRs) in breast cancer in Indian women. PARTICIPANTS: Surgically removed breast cancer tissues were collected from Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India, taking (n = 300) cases of infiltrating duct cancer of Indian women after radical mastectomy and lumpectomy; the age- and menopausal-related subgroups satisfied this requirement. MEASUREMENTS: Statistical significance was calculated by the likelihood ratio test; relative risk served to check for significant differences. Relapse-free interval probabilities were calculated according to Kaplan and Meier, with Cox-Mantel test comparing survival functions and P values. RESULTS: We observed that only in middle-aged postmenopausal patients bearing pT2 tumors were ER and PgR receptors shown to have a prognostic significance with the lowest tested cutoff value being 5 fmol/mg. CONCLUSION: Immunohistochemistry analysis has been shown to be a prognostic factor for patients with breast cancer; the major aim of determining the ER receptor status is to assess predictive response to hormonal therapy.

The p53 breast cancer tissue biomarker in Indian women.

BACKGROUND: Combination chemotherapy is highly effective in locally advanced breast cancer. A negative expression of biomarker p53 indicates a higher chance of responding to this regimen. Patients' p53 status may be used as a biological cancer marker to identify those who would benefit from more aggressive treatments. AIMS: The role of p53 in modulating apoptosis has suggested that it may affect the efficacy of anticancer agents. p53 alterations in 80 patients with locally advanced breast cancer IIIB undergoing neoadjuvant chemotherapy were prospectively evaluated. MATERIALS AND METHODS: Patients received three cycles of paclitaxel (175 mg/m(2)) and doxorubicin (60 mg/m(2)) every 21 days. Tumor sections were analyzed before treatment for altered patterns of p53 expression, using immunohistochemistry and DNA sequencing. RESULTS: An overall response rate of 83.5% was obtained, including 15.1% complete pathological responses. The regimen was well tolerated with 17.7% grade 2/3 nausea and 12.8% grade 3/4 leukopenia. There was a statistically significant correlation between response and expression of p53. Of 25 patients who obtained a complete clinical response, only two were classified as p53-positive (P = 0.004, χ(2)). Of 11 patients who obtained a complete pathological remission, one was positive (P = 0.099, χ(2)). CONCLUSION: Immunohistochemical (IHC) analysis has been shown to be a prognostic factor for patients with breast cancer in India. Paclitaxel is one of the most promising anticancer agents for the therapy of breast cancer, where it has also shown activity in tumors resistant to doxorubicin.