Alpana Saxena

Role of serum matrix metalloproteinase-2 and -9 to predict breast cancer progression.

OBJECTIVE Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, have been reported as putative tumor markers because of their involvement in cancer invasion and metastasis. The aim of our study was to elucidate the possible role of MMP-2 and -9 as serum prognostic biomarker for breast cancer classification and correlate it with the clinicopathological variables. DESIGN AND METHODS Our study consisted of 60 females with primary breast cancer, 40 cases of benign breast disease and 60 healthy female volunteers as controls. The serum MMP-2 and -9 levels were quantitatively measured by ELISA technique. RESULTS A significantly raised MMP-2 and MMP-9 levels were observed in breast cancer patients. Significant rise in serum MMP-9 concentration was found in patients presenting with metastasis as well as in those cases who presented with a duration of less than 1year. ROC analyses depicted a serum cutoff value of 315ng/mL for MMP-9 to discriminate the breast cancer patients from the control group. CONCLUSION Our results suggest that serum MMP-9 level is a better marker than serum MMP-2 in predicting the breast cancer development and progression.

Antioxidant status in advanced cervical cancer patients undergoing neoadjuvant chemoradiation.

Abstract Cervical cancer is the most common cancer in Indian women. The aim of this study is to assess the alterations in the circulating lipid peroxide, antioxidant components and activities of defence enzymes in advanced cervical cancer patients, and to monitor the variations in their levels before and after neoadjuvant chemoradiation. Sixty patients with advanced cancer of the cervix (FIGO IIIa–IVb) are included in the study, along with 60 healthy controls. Blood samples are collected before the start of therapy (S1), two weeks after the second course of chemotherapy (S2) and two weeks after completion of tele/brachyradiation (S3). Single blood samples are taken from controls. Lipid peroxides, conjugated dienes, reduced glutathione (GSH), catalase (CAT) and glutathione-S-transferase (GST) are estimated using standard methods. Glutathione peroxidase (GPx) and superoxide dismutase (SOD) are assayed using commercially available kits. The pretreatment levels of plasma lipid peroxide were significantly elevated in cancer patients, while significantly lowered levels of GSH, GPx, GST, SOD and CAT were observed when compared to controls. After chemotherapy, the levels of lipid peroxidation showed a significant decline (P<0.05), which became highly significant after chemoradiation (P<0.01). Levels of GSH, GPx, SOD, GST and CAT showed a mild increase after chemotherapy. After chemoradiation, levels reverted to normal or near normal (P<0.01). Low levels of antioxidants in the circulation of patients with cervical cancer may be due to their increased utilisation to scavenge lipid peroxidation as well as their sequestration by tumour cells. The observed increase in antioxidant concentration after therapy might be due to the death of tumour cells or the arrest of tumour growth by chemotherapeutic agents. The normalisation of these parameters may provide information about the efficacy of neoadjuvant chemoradiation. A larger patient cohort with a longer follow-up period for therapeutic response studies may yield more significant data.

Erratum to : Expression of serum miR-200a, miR-200b and miR-200c as candidate biomarkers in epithelial ovarian cancer and their association with clinicopathological features

Background MicroRNAs (miRs) have been implicated in the etiology of various human cancers. The aim of this study was to investigate the association of the expression of three members—miR 200a, miR 200b, and miR 200c belonging to the miR-200 family with clinicopathological characteristics and their impact on the progression of epithelial ovarian cancer (EOC).

Vitamin D and VDR gene polymorphism ( FokI ) in epithelial ovarian cancer in Indian population

IntroductionVitamin D deficiency and vitamin D receptor (VDR) gene polymorphism, FokI, is reported to increase the risk of many cancers. Role of vitamin D and its receptor polymorphisms in ovarian cancer has not been clearly defined.ObjectiveTo study the levels of serum vitamin D and occurrence of vitamin D receptor gene polymorphism (FokI) in cases of ovarian cancer.Material and methodsFokI genotyping was done by PCR-RFLP technique and vitamin D levels were estimated by chemiluminescence immunoassay.ResultsSerum vitamin D levels were significantly (p < 0.03) lower in ovarian cancer cases as compared to controls. The homozygous (TT) and heterozygous (CT) genotype predispose to the development of ovarian cancer in Indian population (OR: 2.37, 95% CI: 1.04-5.44) as compared to the homozygous (CC) genotype. Vitamin D deficiency and VDR gene polymorphism (FokI) act non-synergistically (p value < 0.4).ConclusionLow blood levels of vitamin D and VDR receptor polymorphism (FokI) might be a risk factor for the development of ovarian cancer. Other novel ligands of vitamin D receptor might be responsible for the non-synergistic effect.

Effect of addition of either sitagliptin or pioglitazone in patients with uncontrolled type 2 diabetes mellitus on metformin: A randomized controlled trial

Objective: To compare and study the dipeptidy1 peptidase-4 (DPP-4) inhibitors in combination with metformin against established combination therapies. Materials and Methods: This 16-week study was designed to compare sitagliptin versus pioglitazone as add-on therapy in patients of type 2 diabetes mellitus inadequately controlled with metformin alone. Fifty-two patients were randomized into two groups to receive either sitagliptin 100 mg (group 1) or pioglitazone 30 mg (group 2) in addition to metformin. The primary efficacy end point was change in HbA1c. Secondary end points included change in fasting plasma glucose (FPG), body weight and lipid profile. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire. Both the groups had a significant decrease in HbA1c. Results: There was no significant difference between mean reductions in FPG in both the groups. There was a significant decrease in the mean body weight and body mass index in group 1 in contrast to the significant increase in the same in group 2. Both the treatment groups reported a significant decrease in High-density lipoprotein (HDL-C) and Triglyceride. Conclusion: Sitagliptin was well tolerated without any incidence of hypoglycemia. It was concluded that sitagliptin as an add-on to metformin is as effective and well tolerated as pioglitazone.

Hypothalamic pituitary abnormalities in tubercular meningitis at the time of diagnosis

Tubercular meningitis (TBM) is the most dreaded form of extra pulmonary tuberculosis associated with high morbidity and mortality. Various hypothalamic pituitary hormonal abnormalities have been reported to occur years after recovery from disease but there are no systematic studies in the literature to evaluate the pituitary hypothalamic dysfunction in patients with TBM at the time of presentation. Therefore, the present study was designed to evaluate hypothalamic pituitary abnormalities in newly diagnosed patients with TBM. Patient case series. This prospective study included 75 untreated adult patients with TBM diagnosed as “definite”, “highly probable” and “probable” TBM by Ahuja’s criteria and in clinical stage 1, 2 or 3 at the time of presentation to hospital. Basal hormonal profile was measured by electrochemilumniscence technique for serum cortisol, luetinizing hormone (LH), follicular stimulating hormone (FSH), prolactin (PRL), thyrotropin (TSH), free tri-iodothyronine (fT3), and free thyroxine (fT4). All patients were subjected to MRI to image brain and hypothalamic pituitary axis and CT for adrenal glands. Thirty-two (42.7%) cases showed relative or absolute cortisol insufficiency. Twenty-three (30.7%) cases showed central hypothyroidism and 37 (49.3%) cases had hyperprolactinemia. No patient had evidence of diabetes insipidus. Multiple hormone deficiency was seen in 22 (29.3%) cases. MRI of hypothalamic pituitary axis using dynamic scanning and thin cuts revealed abnormalities in 10 (13.3%) of the cases. CT adrenal gland was normal in all the patients. Tubercular meningitis is associated with both hormonal and structural abnormalities in the hypothalamic pituitary axis at the time of diagnosis.

Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer

MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan—Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

Extracellular cytochrome c as a biomarker for monitoring therapeutic efficacy and prognosis of non-small cell lung cancer patients

Non-small cell lung cancer has a devastating prognosis, and markers enabling a precise prediction of therapy response have long remained scarce. Better treatment monitoring would allow an individual’s more effective patient adjusted therapy with lesser side effects and good clinical outcomes. In the present study, we monitored the serum cytochrome c levels pre- and post-chemotherapy of non-small cell lung cancer patients. Using highly sensitive enzyme-linked immunosorbent assay, we evaluated cytochrome c levels in serum of 100 non-small cell lung cancer and 100 healthy controls. We observed about threefold lower serum cytochrome c level in newly diagnosed non-small cell lung cancer patients than healthy individuals. Patients in advanced stages and grade 3 histological differentiation showed significantly low level of serum cytochrome c, and the lower levels were associated with worse survival outcome of non-small cell lung cancer patients. In addition, serum cytochrome c level was observed to be more than 13-fold higher after first cycle of conventional chemotherapy, wherein patients with higher level of serum cytochrome c before any therapy showed better response to chemotherapy in terms of significantly higher level of serum cytochrome c after first cycle of chemotherapy than patients with low level of serum cytochrome c at the time of diagnosis. Detection of serum cytochrome c levels at the time of diagnosis may be useful in suggesting disease severity and prognosis of the non-small cell lung cancer patients. Monitoring of serum cytochrome c might also serve as a sensitive apoptotic marker in vivo reflecting chemotherapy-induced cell death burden in patients with non-small cell lung cancer.

Assessment of serum leptin, pregnancy-associated plasma protein A and CRP levels as indicators of plaque vulnerability in patients with acute coronary syndrome

Introduction A multifactorial aetiology of coronary artery disease (CAD) has been established in the recent past. Extensive research is now underway to understand the mechanisms responsible for plaque vulnerability. The identification of a novel biomarker that will help in the assessment of plaque status is urgently needed for the purpose of patient stratification and prognostication. The aim of the present study was to evaluate leptin, pregnancy-associated plasma protein A (PAPP-A) and C-reactive protein (CRP) levels in patients with acute coronary syndrome and to assess their diagnostic efficacy in the identification of vulnerable plaques. Methods The study group comprised 105 patients who had chest pain along with ECG changes (ST elevation, ST depression, T inversion) and raised cardiac enzyme levels. Sixty-two patients with chest pain and ECG changes but with normal cardiac enzyme profiles were included in the control group. Lipid profiles, and leptin, PAPP-A and CRP levels were assessed in these two groups. Receiver operating characteristics (ROC) curves were plotted to determine the utility of the parameters under study as markers of plaque vulnerability. Results Significantly higher levels of serum lipoprotein (a), leptin, PAPP-A and high-sensitivity CRP (hs-CRP) were observed in the cases than in the controls. A positive correlation was observed between CRP and PAPP-A levels as well as CRP and leptin concentrations. ROC curve analysis revealed similar efficacies of CRP and PAPP-A levels in their ability to detect unstable plaques with areas under the curve of 0.762 and 0.732, respectively. Multivariate analysis established the superiority of hs-CRP as a predictor of plaque instability. Conclusions Our study highlights the utility of both CRP and PAPP-A levels as determinants of plaque instability. Our findings necessitate population-based follow-up studies to establish the superiority of either of the two biomarkers in the field of preventive cardiology.

Telomerase Activity as a Tumor Marker in Indian Women with Cervical Intraepithelial Neoplasia and Cervical Cancer

AbstractBackground and objectives: Cervical cancer is the most common cancer in Indian women and is a leading cause of death in women worldwide. Cervical cancer develops from pre-neoplastic cervical intraepithelial neoplasia (CIN). This study was conducted to evaluate telomerase activity as a tumor marker for the detection of cancer in patients with CIN and cervical cancer. The results were compared with human papillomavirus (HPV) status, clinical staging, and histopathologic studies. Methods: Telomerase activity was detected using the PCR-based telomeric repeat amplification protocol (TRAP) assay in cervical tissues collected by routine punch biopsy from the uterine cervix of patients with suspected cervical cancer. High-risk (HR) HPV-16 and -18 status was determined in all the study groups, including controls. A total of 125 patients (including 50 patients with CIN and 75 patients with cervical cancer [including nine patients with adeno-squamous disease]) and 22 control subjects were studied. The sensitivity and specificity for detecting CIN and cervical cancer were calculated. Results: Patients with grade I, II, and III CIN showed 17%, 33%, and 57% positivity for telomerase, respectively. In patients with cervical cancer, those at early clinical stages (Ia-IIb) showed 68% positivity and those at later clinical stages showed 92% positivity for telomerase activity. In the present study, telomerase positivity correlated significantly with the detection of HR HPV-16 and -18 (p < 0.001). As a diagnostic test, none of the described analyses combined a sensitivity of ≥90% with a specificity of ≥90%, except in patients with advanced cancer when telomerase activity was used as a diagnostic test. Conclusion: Our findings suggest that telomerase activation is a relatively early event in cervical carcinogenesis and correlates with the grade of cervical lesion, HR-HPV status (16 and 18 subtypes), and clinical staging. Hence, these associations suggest it as a possible target for detection of cervical cancer.