Diagnostic Significance of CA15-3 with Combination of HER-2/neu Values at 85th Percentiles in Breast Cancer

The human epidermal receptor-2/neu (HER-2/neu) oncogene encodes a transmembrane tyrosine kinase receptor. This molecule could have a diagnostic value since the extracellular domain of c-erbB-2 (HER-2) transmembrane is shed into the blood as a circulating antigen. The diagnostic value of serum HER-2/neu was calculated along with the conventional marker carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) at 85th percentiles. Serum levels of breast carcinoma antigens HER-2/neu, CEA and CA15-3 were determined in 175 normal individuals and 268 malignant patients. The soluble form of serum HER-2/neu, CEA and CA15-3 was assayed by enzyme linked immunosorbent assay in control and breast cancer patients prior to treatment. Serum levels of the tested tumor markers HER-2/neu and CA15-3 and CEA were significantly higher in cancer patients compared to controls. At 85th percentile the sensitivity of HER-2/neu was 51.12 %; the specificity was 86.29 % and the overall accuracy was 64.56 %. The sensitivity of CA15-3 was 73.13 %; the specificity was 85.14 % and the overall accuracy was 77.88 %. The sensitivity of the combined testing was 82.84 %; the specificity was 73.71 % and the overall accuracy was 80.01 %. The sensitivity and the overall accuracy of combined testing were higher than those of HER-2/neu and CA15-3 testing single. The combined testing of HER-2/neu and CA15-3 can increase the sensitivity and overall accuracy of breast cancer diagnosis. The results of this study suggest that the use of multiple tumor markers may be employed as combination and at 85th percentiles to assess the prognosis.     

Polymorphic Variation in Double Strand Break Repair Gene in Indian Population: A Comparative Approach with Worldwide Ethnic Group Variations

DNA repair capacity is essential in maintaining cellular functions and homeostasis. Identification of genetic polymorphisms responsible for reduced DNA repair capacity may allow better cancer prevention. Double strand break repair pathway plays critical roles in maintaining genome stability. Present study was conducted to determine distribution of XRCC3 Exon 7 (C18067T, rs861539) and XRCC7 Intron 8 (G6721T, rs7003908) gene polymorphisms in North Indian population and compare with different populations globally. The genotype assays were performed in 224 normal healthy individuals of similar ethnicity using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Allelic frequencies of wild type were 79% (C) in XRCC3 Exon 7 C > T and 57% (G) in XRCC7 Intron 8 (G > T) 57% (G) observed. On the other hand, the variant allele frequency were 21% (T) in XRCC3 Exon 7 C > T and 43% (T) in XRCC7 Intron 8 G > T respectively. Major differences from other ethnic populations were observed. Our results suggest that frequency in these DNA repair genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of humans exposed to environmental carcinogens and cancer predisposition in different ethnic groups.     

Stable denominators for the simplification of z-Transfer Functions

A well-known discrete stability test is used to derive from the denominator D(z) of a given stable high-order transfer function G(z), the denominator of a low-order approximant of G(z). The proposed method, based on the truncation and inversion of a continued fraction formed with the coefficients of D(z), yields a reduced denominator d(z) of degree, say m, which is always stable. Furthermore, depending on the neglected parts of the continued fraction, d(z) approximates m₁ and m₂ = m−m₁ zeros of D(z), located very near the points z=1 and z=-1, respectively. In the special case m₁=m, d(z) is identical to the polynomial obtained by applying to D(z) the indirect technique, which combines the bilinear transformation with the Routh or the Schwarz approximation method.     

Association of CETP and LIPC Gene Polymorphisms with HDL and LDL Sub-fraction Levels in a Group of Indian Subjects: A Cross-Sectional Study

There is an increasing interest to understand the molecular basis of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) subfractions and their association with coronary artery disease (CAD). The formation of these subfractions is greatly influenced by hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) enzymes. To identify genetic markers influencing LDL and HDL subfractions and their role in CAD we performed a case–control genetic association study on 117 healthy controls and 119 angiographically verified CAD patients. Biochemical analysis was performed using standard assays. HDL-C and LDL-C subfractions were estimated using precipitation methods. Genotyping of C-514T (rs1800588) in the LIPC gene for HL and I405V (rs5882) in the CETP gene was done using PCR-based restriction enzyme analysis and sequencing. Both the polymorphisms were not associated with CAD. The C-514T was associated with increased HDL₃-C levels in controls (P = 0.049). The I405V polymorphism was found to be associated with low levels of small dense, LDL (P = 0.038). A multiple regression analysis showed that the effects were dependent on gender and triglyceride levels. We conclude that these polymorphisms are not associated with CAD but are important determinants of HDL-C and small dense LDL particles in our population.     

Circadian Rhythm of Serum Cortisol in Female Patients with Fibromyalgia Syndrome

Fibromyalgia syndrome (FMS) patients have disturbed sleep patterns which may lead to altered circadian rhythm in serum cortisol secretion. The aim of this study was to assess circadian changes, if any, in serum cortisol levels in female patients with FMS. Cortisol levels were estimated every 6 h during 24 h period; in 40 female patients satisfying ACR criteria for FMS (Age 36.4 ± 9.9), and 40 healthy females without FMS (Age 33.8 ± 11.1). A significant difference in the night time serum cortisol level was observed among the patients and control groups (patients, 12.9 ± 9.7 controls 5.8 ± 3.0; p < 0.01). However, no significant difference was found in serum cortisol levels in patients and control groups in the morning (patients, 28.4 ± 13.2 controls, 27.6 ± 14.5; p > 0.05), afternoon (patients, 14.4 ± 5.6 controls, 14.0 ± 6.6; p > 0.05) and evening hours (patients, 10.9 ± 5.8 controls, 8.9 ± 3.6; p > 0.05). It could be concluded that there is an abnormality in circadian secretion of cortisol in female FMS patients.     

Antioxidant and Anticancer Activities of Selected Persian Gulf Algae

In the present study, the effect of red (Gracillaria corticata), green (Ulva fasciata) and brown (Sargassum ilicifolium) seaweeds alcoholic extract, against five important human cancer cell lines (MCF-7, MDA-MB-231, HeLa, HepG2, and HT-29) proliferation, apoptosis and cell cycle arrest were evaluated. The reducing activity and total polyphenol content were also investigated. MTT assay was used for cytotoxicity test. Morphological alterations were examined using phase contrast, fluorescent and electron microscopy. All the extracts were antiproliferative against all the cancer cell lines, dose-dependently, with G. corticata methanol extract (GCME) having the greatest inhibition activity against MCF-7 cell line. The percentage of apoptosis increased from 18 to 78 %. The cell cycle analysis also showed that GCME can induce apoptosis which confirm by TEM. Algal extract reducing activities were as follows: G. corticata > S. ilicifolium > U. fasciata. The GCME is a good source of potential complementary and alternative functional food for prevention and treatment of cancer.     

Vitamin D Deficiency and Insulin Resistance in Normal and Type 2 Diabetes Subjects

Vitamin D is recognized to serve a wide range of biological functions. The presence of vitamin D receptors on different tissues explains it’s diversity of actions. Reduced levels of vitamin D is associated with insulin resistance and increased diabetes risk. The study included 50 normal healthy individuals and 49 type 2 diabetes subjects. Fasting blood glucose, total cholesterol, triglycerides, HDLc, fasting insulin, parathyroid hormone, calcium, albumin and Homeostasis model for assessment of insulin resistance (HOMAIR) were measured in all the study participants. Type 2 diabetes subjects were divided into group 1 with 25 hydroxy vitamin D (25(OH)D) ≤20 ng/ml and group 2 with 25(OH)D >20 ng/ml. By the results of this study, the mean 25(OH)D level was low (20.09 ng/ml) in type 2 diabetes compared to controls (23.89 ng/ml) and the p value was 0.02. The estimated insulin resistance by HOMAIR was more in group 1 than in group 2 of diabetes with p value of 0.037. The Pearson’s correlation-coefficient was negative for 25(OH)D and insulin in type 2 diabetes (r = ?0.294), 25(OH)D was negatively correlated with HOMAIR in total subjects. Type 2 diabetes subjects had reduced levels of vitamin D than normal individuals. The insulin resistance was more in vitamin D deficiency state. Hence vitamin D has a role in glucose metabolism, deficiency can result in insulin resistance and diabetes.     

Genetic Variant Arg399Gln G&gt;A of XRCC1 DNA Repair Gene Enhanced Cancer Risk Among Indian Population: Evidence from Meta-analysis and Trial Sequence Analyses

The X-ray repair cross-complementation group 1 (XRCC1) gene plays an important role in base excision repair pathway. Several studies have reported contradictory results for XRCC1 exon 10 (Arg399Gln, G23990A, rs25487) gene polymorphism and cancer risk in Indian population, making it difficult to interpret them. Therefore, we have conducted a meta-analysis to evaluate the more precise association between XRCC1 exon 10 G>A gene polymorphism and risk of cancer by published studies. We searched PubMed (Medline) and Google scholar web databases to cover all studies published on association between XRCC1 exon 10 G>A gene polymorphism and cancer risk until August 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. Heterogeneity, publication bias and sensitivity analysis were also assessed. Twenty-five published studies had fulfilled the inclusion criteria comprising 4131 confirmed cancer cases and 5013 controls. When all studies were polled together, overall significant association was found between XRCC1 exon 10 G>A polymorphism and cancer risk in variant allele carrier (A vs. G: OR 1.217, 95% CI 1.056–1.402, p = 0.007), homozygous (AA vs. GG: OR 1.359, 95% CI 1.036–1.783, p = 0.027), dominant (AA+AG vs. GG OR 1.208, 95% CI 1.006–1.450, p = 0.043) and recessive (AA vs. AG+GG: OR 1.315, 95% CI 1.029–1.680, p = 0.029) genetic models. Further sensitivity analysis supported the stability of our result by showing similar ORs before and after removal of a single study. The present meta-analysis suggested that the XRCC1 exon 10 G>A polymorphism contribute cancer risk in Indian population, and supports that individuals with risk allele A and AA genotype are at higher risk of developing cancer.     

Biochemical Effects of Lead Exposure on Battery Manufacture Workers with Reference to Blood Pressure, Calcium Metabolism and Bone Mineral Density

Lead is one of the most widely scattered toxic metals in the environment and used by mankind for over 9,000 years. Lead in the environment may be derived from natural or anthropogenic sources. In humans, lead can cause a wide range of biological effects depending upon the level and duration of exposure. The purpose of this study was to find out the effect of lead exposure on systolic and diastolic blood pressure, serum calcium, ionized calcium, phosphorus, parathyroid hormone and vitamin D and examine the overall effect of all these parameters on the bone mineral density of battery manufacture workers. For this study ninety battery manufacture workers were selected and divided in three groups depending upon duration of lead exposure. Group I—workers with duration of lead exposure 1–5 years, Group II—workers with duration of lead exposure 6–10 years and Group III—workers with duration of lead exposure more than 10 years. Each group consisted of thirty workers. Thirty age matched healthy control subjects were taken for comparison. Demographic, occupational and clinical data were collected by using questionnaire and interview. The venous blood samples were collected from the study groups and normal healthy control group. At the time of blood collection random urine samples were collected in amber coloured bottles. The biochemical parameters were estimated by using standard assay procedures. Statistical analysis of the data was done using independent student‘t’ test for parametric variables. Values were expressed as mean ± standard deviation (SD). P values of 0.05 or less were considered to be statistically significant. The blood lead levels and urinary lead levels of all workers were significantly increased (P < 0.001) in proportion to the duration of lead exposure as compared to controls. Systolic and diastolic blood pressure were significantly raised (P < 0.001) in all three study groups of battery manufacture workers as compared to controls. Serum Calcium, Ionized calcium, phosphorus were significantly decreased (P < 0.001) in all the three study groups. Serum vitamin D levels were lowered (P < 0.01) and serum PTH was increased (P < 0.01) in workers as compared to controls. The results of this study clearly indicate that the absorption of lead is more in these workers which adversely affects blood pressure, disturbs calcium and phosphorus metabolism which further impairs mineralization of bone resulting in decreased bone mineral density observed in these workers. Lead toxicity is still persistent in battery manufacture workers though they are using sophisticated techniques in these industries. There is a need to protect the workers from the health hazards of occupational lead exposure.     

Potential Chemoprevention of 7,12-Dimethylbenz[a]anthracene Induced Renal Carcinogenesis by Moringa oleifera Pods and Its Isolated Saponin

Present investigation shows that hydroethanolic extract of Moringa oleifera (MOHE) and its isolated saponin (SM) attenuates DMBA induced renal carcinogenesis in mice. Isolation of SM was achieved by TLC and HPLC and characterization was done using IR and ¹H NMR. Animals were pre-treated with MOHE (200 and 400 mg/kg body weight; p.o), BHA as a standard (0.5 and 1 %) and SM (50 mg/kg body weight) for 21 days prior to the administration of single dose of DMBA (15 mg/kg body weight). Administration of DMBA significantly (p < 0.001) enhanced level of xenobiotic enzymes. It enhanced renal malondialdehyde, with reduction in renal glutathione content, antioxidant enzymes and glutathione-S-transferase. The status of renal aspartate transaminase, alanine transaminase, alkaline phosphatase and total protein content were also found to be decreased along with increase in total cholesterol in DMBA administered mice. Pretreatment with MOHE and SM significantly reversed the DMBA induced alterations in the tissue and effectively suppressed renal oxidative stress and toxicity.     

Improving relational similarity measurement using symmetries in proportional word analogies

Measuring the similarity between the semantic relations that exist between words is an important step in numerous tasks in natural language processing such as answering word analogy questions, classifying compound nouns, and word sense disambiguation. Given two word pairs (A, B) and (C, D), we propose a method to measure the relational similarity between the semantic relations that exist between the two words in each word pair. Typically, a high degree of relational similarity can be observed between proportional analogies (i.e. analogies that exist among the four words, A is to B such as C is to D). We describe eight different types of relational symmetries that are frequently observed in proportional analogies and use those symmetries to robustly and accurately estimate the relational similarity between two given word pairs. We use automatically extracted lexical-syntactic patterns to represent the semantic relations that exist between two words and then match those patterns in Web search engine snippets to find candidate words that form proportional analogies with the original word pair. We define eight types of relational symmetries for proportional analogies and use those as features in a supervised learning approach. We evaluate the proposed method using the Scholastic Aptitude Test (SAT) word analogy benchmark dataset. Our experimental results show that the proposed method can accurately measure relational similarity between word pairs by exploiting the symmetries that exist in proportional analogies. The proposed method achieves an SAT score of 49.2% on the benchmark dataset, which is comparable to the best results reported on this dataset.     

Lipid Parameters, Doses and Blood Levels of Calcineurin Inhibitors in Renal Transplant Patients

The calcineurin inhibitors (CNIs) [cyclosporin A (CsA) and tacrolimus (Tac)] are currently the most widely prescribed drugs for maintenance of immunosuppression after renal transplantation. These immunosuppressants are associated with side effects such as hyperlipidemia. We evaluated the differential effects of different CNIs on serum lipid parameters in renal transplant patients. Moreover, the aim of this study is to investigate the relationships between doses and blood levels of CNIs, and blood levels of CNIs and lipid parameters retrospectively. Two groups of 98 non-diabetic renal transplant patients, each treated with different CNIs, were studied: group A (n = 50, mean age: 31 ± 10 years), CsA, mycophenolate mofetil/azathioprin, steroid; group B (I = 48, mean age: 34 ± 12 years), Tac, mycophenolate mofetil/azathioprin, steroid. In renal transplant patients, CNIs blood levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. Biochemical laboratory parameters including plasma lipids [total-cholesterol (CHOL), low-density lipoprotein (LDL)–CHOL, high-density lipoprotein (HDL)–CHOL, and triglycerides (TG)], CNI levels and doses were examined at 1, 3, 6, 9, and 12 months after transplantation. None of the patients received anti-lipidemic drugs during the study period. Blood levels of CNIs were detectable in all whole-blood samples by Cloned- Enzyme-Donor Immunoassay (CEDIA). The relationship between CNIs blood levels and CHOL, (LDL)–CHOL, HDL–CHOL, TG were evaluated. The mean serum CHOL levels and LDL–CHOL levels of patients in group A were found significantly higher than the patients in group B during the 12 month of follow up (p < 0.05). There was no significant difference in TG and HDL–CHOL plasma levels between group A and group B (p > 0.005). In group A the daily dose of CsA was significantly correlated with the mean blood levels of CsA at the 1st and 3rd months (r = 0.387, p = 0.005; r = 0.386, p = 0.006), respectively. In group A, the daily dose of CsA was significantly correlated with the mean serum TG levels during the 12 month of follow up (r = 0.420, p = 0.003). In group B, the daily dose of Tac was significantly correlated with the mean blood level of Tac (r = 0.335, p = 0.020) at the 1st month. No correlation was found between mean Tac blood levels and lipid parameters during the 12-month of follow up (p > 0.05). Significant positive correlation was observed between the CsA blood levels and LDL–CHOL levels (r = 0.338, p = 0.027) at the 3rd month. In the renal transplant patients with well functioning grafts, CsA therapy is associated with increased CHOL and LDL–CHOL ratio which represents an increased atherogenic risk tended to be associated with CsA. Serum LDL–CHOL levels may be effected by blood CsA levels.     

Implications of ACE (I/D) Gene Variants to the Genetic Susceptibility of Coronary Artery Disease in Asian Indians

Angiotensin-1-converting enzyme (ACE) gene has established substantial attention in the recent years as a candidate gene for hypertension, cardiovascular diseases and type 2 diabetes. The aim of the present study was to investigate the association of ACE (I/D) polymorphism with coronary artery disease (CAD) in a north Indian population. A total of 662 subjects (330 CAD patients and 332 healthy controls) were examined for association of ACE gene (I/D) polymorphism and environmental risk factors. The mean age of the CAD patients and control subjects was 60.53 ± 8.6 years and 56.55 ± 7.7 years, respectively (p = 0.000). Anthropometric and demographic data showed BMI values significantly higher among CAD patients and control subjects (26.98 ± 4.9 vs 24.04 ± 4.7, p = 0.000). We observed pronounced central obesity in both CAD patients and controls, even at the lowest BMI values (<23 kg/m²). Dyslipidemia was highly prevalent in CAD patients compared to control subjects. Genotypic data showed significantly higher frequency of DD genotype in CAD patients than that of control subjects (40 vs 28.3 %). No significant difference was observed in the distribution of ID genotypes between CAD patients and control subjects. Logistic regression analysis of data demonstrate that DD genotype was associated with 1.8 fold increased risk of development of CAD in Asian Indians (OR 1.8; 95 % CI 1.22–2.66; p = 0.003). The frequency of D allele was significantly higher in CAD patients (p = 0.001). No significant difference was observed in the clinical and biochemical characteristics of CAD patients and controls when the data was stratified according to the genotypes of ACE gene. In conclusion, DD genotype of ACE gene may be associated with increased risk of CAD in Asian Indian population.     

Biochemical Evaluation of Patients of Alcoholic Liver Disease and Non-alcoholic Liver Disease

Alcoholic liver disease (ALD) is due to excessive alcohol intake for long duration. Distinguishing ALD from non-ALD (non-alcoholic steatohepatitis, hepatitis of viral origin) is difficult as patient may deny alcohol abuse. Clinical examination, histology and serology may not differentiate these conditions. Accurate diagnosis is important as management of ALD differs from non-ALD patients. The aim of our study was (1) To evaluate the patients of ALD and non-ALD by biochemical parameters compared to controls, (2) To assess whether these parameters can differentiate ALD from non-ALD. Study was carried out on 50 patients of ALD in group I and 35 patients of NASH (non-alcoholic steatohepatitis) and acute viral hepatitis each in group II. Age matched healthy controls n = 50. Selection criteria—history of alcohol intake (amount and duration), clinical examination, sonography of abdomen, serum alanine transaminase (ALT) and bilirubin levels. Blood samples were analyzed for bilirubin, aspartate transaminase (AST), ALT, alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) by kinetic method. Statistical analysis was done by Student unpaired ‘t’ test. Patients of ALD have raised AST/ALT ratio (De Ritis ratio) (>2), ALP and GGT compared to controls (P < 0.01).There is significant difference in AST/ALT ratio, serum GGT and ALP in ALD group compared to that in NASH and acute viral hepatitis (P < 0.05). This study suggests that De Ritis ratio >2 in ALD patients may be due to alcohol induced hepatic mitochondrial injury and pyridoxine deficiency. High GGT and ALP values may indicate enzyme induction by alcohol and mild cholestasis. Thus ALD patients have severe hepatic damage. De Ritis ratio <1 and normal to mild elevation in GGT level in NASH and acute viral hepatitis suggest mild hepatic injury of non-alcoholic origin. Our study concludes that ALD patients can be differentiated from NASH and acute viral hepatitis with certainty by measuring serum AST/ALT ratio, GGT and ALP. These biochemical parameters may help clinicians to support the diagnosis of ALD and non-ALD.     

Suitability of Stem Latex of Jatropha Gossypifolia as a Protein Precipitant for Biochemical Analysis

The extract of Jatropha Gossypifolia stem was obtained by cutting the stem with a sharp knife and the fluid expressed out. The suitability of the stem latex extract as a precipitant for biochemical analysis was determined. The precipitating efficacy of the extract for creatinine and protein estimation was found to be optimum at 1/4 and 1/5 dilutions respectively aqueous solution. Plasma protein was precipitated with stem extract of J. Gossypifolia at the stated dilution. The mean plasma creatinine values obtained from 0.5 % sodium tungstate as a protein precipitant were compared with the values of plasma creatinine obtained when ¼ dilution of stem extract of J. Gossypifolia was used as protein precipitant. Similarly mean cerebrospinal fluid (CSF) and urinary protein values obtained from 3 % Tricholoro-acetic acid as protein precipitant were compared with values obtained from 1/5 dilution of stem extract of J. Gossypifolia as protein precipitant. The values obtained from the stem latex extract at the stated dilutions were comparable with values obtained from the conventional protein precipitants (p < 0.05). The stem latex extract of J. Gossypifolia is suitable as a protein precipitant for creatinine, CSF and urinary protein estimations. However further work need to be done to purify the extract and determine the exact concentration at the stated dilutions as well as the active ingredient in stem latex.     

Binary matrices with specified properties

The binary matrices A which are circulant with one or more of the following properties: (1) A is symmetric, i.e. A = A^T, (2) A is orthogonal, i.e. AA^T = I (mod 2), (3) A has low multiplicative order, i.e. A^m = I, occur often in communication, control and network theory problems. In this paper we construct a number of such matrices. The results are based on the theory of power-residues modulo an odd prime p, and the fact that the algebra of all p × p circulant matrices is isomorphic to the algebra of polynomials modulo (x^p?1).     

Targeting HSPA1A in ARID2-deficient lung adenocarcinoma

Somatic mutations of the chromatin remodeling gene ARID2 are observed in ∼7% of human lung adenocarcinomas (LUADs). However, the role of ARID2 in the pathogenesis of LUADs remains largely unknown. Here we find that ARID2 expression is decreased during the malignant progression of both human and mice LUADs. Using two Kras^G12D-based genetically engineered murine models, we demonstrate that ARID2 knockout significantly promotes lung cancer malignant progression and shortens overall survival. Consistently, ARID2 knockdown significantly promotes cell proliferation in human and mice lung cancer cells. Through integrative analyses of ChIP-Seq and RNA-Seq data, we find that Hspa1a is up-regulated by Arid2 loss. Knockdown of Hspa1a specifically inhibits malignant progression of Arid2-deficient but not Arid2-wt lung cancers in both cell lines as well as animal models. Treatment with an HSPA1A inhibitor could significantly inhibit the malignant progression of lung cancer with ARID2 deficiency. Together, our findings establish ARID2 as an important tumor suppressor in LUADs with novel mechanistic insights, and further identify HSPA1A as a potential therapeutic target in ARID2-deficient LUADs.