Alzheimer disease detection from structural MR images using FCM based weighted probabilistic neural network.

An early intervention of Alzheimer's disease (AD) is highly essential due to the fact that this neuro degenerative disease generates major life-threatening issues, especially memory loss among patients in society. Moreover, categorizing NC (Normal Control), MCI (Mild Cognitive Impairment) and AD early in course allows the patients to experience benefits from new treatments. Therefore, it is important to construct a reliable classification technique to discriminate the patients with or without AD from the bio medical imaging modality. Hence, we developed a novel FCM based Weighted Probabilistic Neural Network (FWPNN) classification algorithm and analyzed the brain images related to structural MRI modality for better discrimination of class labels. Initially our proposed framework begins with brain image normalization stage. In this stage, ROI regions related to Hippo-Campus (HC) and Posterior Cingulate Cortex (PCC) from the brain images are extracted using Automated Anatomical Labeling (AAL) method. Subsequently, nineteen highly relevant AD related features are selected through Multiple-criterion feature selection method. At last, our novel FWPNN classification algorithm is imposed to remove suspicious samples from the training data with an end goal to enhance the classification performance. This newly developed classification algorithm combines both the goodness of supervised and unsupervised learning techniques. The experimental validation is carried out with the ADNI subset and then to the Bordex-3 city dataset. Our proposed classification approach achieves an accuracy of about 98.63%, 95.4%, 96.4% in terms of classification with AD vs NC, MCI vs NC and AD vs MCI. The experimental results suggest that the removal of noisy samples from the training data can enhance the decision generation process of the expert systems.

Nuclear translocation of ß-catenin correlates with CD44 upregulation in Helicobacter pylori-infected gastric carcinoma.

Infection with Helicobacter pylori CagA-positive strains is associated with gastric adenocarcinoma. CagA H. pylori activates the ß-catenin signal by translocation into nucleus which promotes carcinogenesis. Deregulated accumulation of nuclear ß-catenin enhances transcription of ß-catenin target genes including CD44 and promotes malignant transformation. The aim of this study was to investigate whether nuclear translocation of ß-catenin correlates with CD44 expression in CagA H. pylori-infected gastric carcinoma. To address these issues, we examined 140 gastric biopsy specimens by using immunohistochemical and immunofluorescence staining, Western blot, and mutational analysis of the exon 3 ß-catenin gene. The nuclear localization of ß-catenin was significantly (χ(2) = 21.175; P < 0.001) increased in advanced gastric carcinoma and also correlated (χ(2) = 22.857; P < 0.001) with the CagA H. pylori positive specimens. We also observed that tyrosine-phosphorylated ß-catenin was significantly (χ(2) = 14.207; P < 0.001) increased in samples showing nuclear localization of ß-catenin and also it correlated (χ(2) = 43.69; P < 0.03) with the CagA H. pylori positive specimens. Exon 3 ß-catenin gene mutation was not detected in H. pylori-infected gastric carcinoma. CD44 up regulation was significantly associated with tyrosine-phosphorylated ß-catenin (χ(2) = 22.5; P < 0.001), and this change was closely associated with nuclear translocation of ß-catenin (χ(2) = 13.393; P < 0.001) in CagA H. pylori-infected gastric carcinoma. In conclusion, our data suggest that CagA H. pylori infection is responsible for the tyrosine phosphorylation of ß-catenin and its nuclear translocation, which upregulates ß-catenin target gene CD44 in gastric carcinoma.

Aberrant expression of epidermal growth factor receptor and its interaction with protein kinase C δ in inflammation associated neoplastic transformation of human esophageal epithelium in high risk populations.

BACKGROUND AND AIM: Esophageal cancer is the second most common cancer among Indian males and is mostly associated with tobacco smoking and alcohol consumption. Epidermal growth factor receptor (EGFR) is a member of Type I tyrosine kinases. Its activation causes the docking of various proteins in its cytosolic tail. In the present study we have analyzed the expression pattern of EGFR, protein kinase C δ (PKCδ), tumor necrosis factor-α (TNF-α), nuclear factor κB (NFκB) and the interactions between EGFR and PKCδ in various pathological conditions. METHODS: Human esophageal biopsies were obtained from 93 patients with a past history of smoking and alcohol consumption: 20 showed normal mucosa, 40 with dysplasia and 33 squamous cell carcinoma (SCC). These pathological conditions were analyzed immunohistochemically for the presence of EGFR expression and then subsequently analyzed using immunoblot and immunoprecipitation. RESULTS: A statistically significant difference of EGFR overexpression was found between low- and high-grade dysplasia and carcinoma (χ² = 3.3, χ² = 3.42: P = 0.07, 0.33). A statistical significance was observed between dysplasia and SCC and in all histopathological types (χ² = 4, χ² = 4.9; P < 0.05, P = 0.18 and χ² = 26.3, 26.6; P < 0.001). EGFR tyrosine phosphorylation and its association with PKCδ was significantly higher in all histopathological types with χ² = 7.965; P < 0.05 and 4.0830; P = 0.2530. CONCLUSION: Altogether, our findings reveal that the activation of EGFR and its subsequent interaction with PKCδ under inflammatory conditions might positively be attributed to the transformation of normal esophageal epithelia to SCC, which could explain ongoing inflammation in normal mucosa in a population prone to smoking and alcoholism.

Molecular and histological evaluation of tumor necrosis factor-alpha expression in Helicobacter pylori-mediated gastric carcinogenesis.

PURPOSE: Helicobacter pylori (H. pylori) is considered to be a major factor contributing to gastric mucosal damage by stimulating mucosal macrophage production of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), but the inflammatory responses within the gastric mucosa in vivo are not well known. Therefore, this study was designed to investigate the expression of TNF-α induced by H. pylori infection which is involved in the tumor initiation and promotion of gastric carcinogenesis. METHODS: This study was carried out in 200 patients, consisting of normal gastric mucosa (n = 20), mucosa with chronic gastritis (n = 63), intestinal metaplasia (n = 20), dysplasia (n = 11), and gastric adenocarcinoma (n = 86), in which the H. pylori status has been analyzed. The expression of TNF-α was studied at mRNA as well as protein level using RT-PCR and western blotting, respectively. The localization of TNF-α was also studied semiquantitatively by immunohistochemistry. RESULTS: The RT-PCR and western blotting results of TNF-α mRNA and protein expressions were significantly increased in chronic gastritis, intestinal metaplasia, dysplasia and gastric adenocarcinoma patients, respectively. Immunohistochemical study also showed the increased expression of TNF-α in the similar way. CONCLUSION: Over expression of TNF-α showed a significant severity-dose-response as risk markers from preneoplastic lesions to gastric cancer.

MUC1 expression and its association with other aetiological factors and localization to mitochondria in preneoplastic and neoplastic gastric tissues.

BACKGROUND: The molecular events that underlie the conversion of normal human gastric epithelium into adenocarcinoma are poorly understood. MUC1 overexpression and localization in mitochondria might confer cancer cells with attenuation of stress induced apoptosis. We studied MUC1 expression pattern, interaction with HSP70 and localization in mitochondria in preneoplastic and neoplastic human gastric tissues. METHODS: Immunohistochemistry and Western blot were used to study MUC1 expression pattern and localization in mitochondria. Coimmunoprecipitation was used to study MUC1 interaction with HSP70. MUC1 expression was correlated with other causative features including erbB2 expression. RESULTS: MUC1 was expressed in 75.8% (147/194). MUC1 overexpression was detected in 50.0% (19/38 cases) dysplasia and 58.2% (32/55 cases) adenocarcinoma tissues. MUC1-CT-HSP70 interaction was seen in 71.66% (43/60 cases) and MUC1 localized to mitochondria in 33.33% (5/15) dysplasia samples and in 47.05% (8/17) adenocarcinoma samples. MUC1 expression showed significant association with smoking (χ(2)=5.945; p<0.015), alcohol consumption (χ(2)=4.055; p<0.044) and erbB2 positivity (χ(2)=10.75; p<0.001). MUC1 expression did not show appreciable association with age (χ(2)=0.15; p<0.698), sex (χ(2)=0.22; p<0.640) or Helicobacter pylori infection (χ(2)=3.06; p<0.080). CONCLUSIONS: Significant correlation was found between MUC1 expression and smoking, alcohol and erbB2 expression. MUC1 showed aberrant expression in dysplasia and adenocarcinoma stages. MUC1 cytosolic tail was bound by HSP70 in all the stages but MUC1-CT was found to localize in mitochondria only in dysplasia and adenocarcinoma. MUC1-CT localization to mitochondria in dysplasia and adenocarcinoma might aid in the attenuation of epithelial stress response induced loss of polarity.

Helicobacter pylori detection and genotyping in gastric biopsy specimens from Chennai patients (India).

The aim of the present study was to investigate the prevalence of Helicobacter pylori infection and the correlation between cagA and vacA (mid-region) genotypes with different clinical outcomes from Chennai, India, patients. Biopsies from the antrum were taken to assess the current H. pylori status by histology, rapid urease test (RUT), and PCR. The RUT and PCR analyses were carried out on a single biopsy specimen. Fasting sera were obtained from all patients and H. pylori status was determined by using ELISA. In addition, the correlations between cagA and vacA genotypes and the consequence of H. pylori infection were statistically examined. Prevalence of the cagA gene was found in 96% (90/94) of patients, and the vacA m2 subtype occurred in 60% (56/94), whereas 32% (30/94) showed the vacA m1 subtype. A significant association between the cagA and vacA m2 region (chi2 = 5.556; p < 0.01) was found in ulcer patients. The vacA m2 genotype showed a near-significant value (chi2 = 3.943; p < 0.047) in ulcer patients when compared with vacA m1. These findings suggest that H. pylori strains with the vacA m2 region were predominant in South India, especially in and around Chennai. This study also showed that PCR has a potential value for studying the cagA gene directly from biopsy specimens.

Interaction of MUC1 with beta-catenin modulates the Wnt target gene cyclinD1 in H. pylori-induced gastric cancer.

Beta-catenin can function as an oncogene when it is translocated to the nucleus, binds to T-cell factor (TCF) or lymphoid enhance factor and transactivate its target gene. The mechanism responsible for the activation of Wnt signaling pathway in the Cytotoxin-associated antigen A (CagA) Helicobacter pylori (H. pylori)-infected gastric carcinoma has not been elucidated. We hypothesize that whether interaction of MUC1 with beta-catenin modulates the Wnt signaling and its target gene cyclinD1 in CagA H. pylori-infected gastric carcinoma. The result demonstrate that binding of MUC1 CT with Protein Kinase C delta (PKC delta), tyrosine phosphorylation of MUC1 CT, and CagA are strongly associated with the interaction of MUC1 with beta-catenin in CagA H. pylori-infected gastric carcinoma. A statistically significant difference (chi(2) = 24.49; P < 0.001) was found when the binding of MUC1 CT and beta-catenin was compared to subcellular localization of beta-catenin. We also observed significant statistical correlation (chi(2) = 14.885; P < 0.001) between the cyclinD1 overexpression and the subcellular localization of beta-catenin. The overexpression of cyclinD1 was significantly higher (chi(2) = 13.785; P < 0.002) in advanced gastric carcinoma with CagA H. pylori infection. In addition cyclinD1 overexpression was significantly higher (chi(2) = 37.267; P < 0.001) with the interaction of MUC1 CT with beta-catenin in advanced gastric cancer. These findings indicate that MUC1 CT plays a role in the intracellular signaling through its interaction with beta-catenin and upregulate the Wnt target gene cyclinD1 in CagA H. pylori-infected gastric carcinoma.