AEG-1 as a Novel Therapeutic Target in Colon Cancer: A Study from Silencing AEG-1 in BALB/c Mice to Large Data Analysis.

BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is overexpressed in various malignancies. Exostosin-1 (EXT-1), a tumor suppressor, is an intermediate for malignant tumors. Understanding the mechanism behind the interaction between AEG-1 and EXT-1 may provide insights into colon cancer metastasis. METHODS: AOM/DSS was used to induce tumor in BALB/c mice. Using an in vivo-jetPEI transfection reagent, transient transfection of AEG-1 and EXT-1 siRNAs were achieved. Histological scoring, immunohistochemical staining, and gene expression studies were performed from excised tissues. Data from the Cancer Genomic Atlas and GEO databases were obtained to identify the expression status of AEG-1 and itsassociation with the survival. RESULTS: In BALB/c mice, the AOM+DSS treated mice developed necrotic, inflammatory and dysplastic changes in the colon with definite clinical symptoms such as loss of goblet cells, colon shortening, and collagen deposition. Administration of AEG-1 siRNA resulted in a substantial decrease in the disease activity index. Mice treated with EXT-1 siRNA showed diffusely reduced goblet cells. In vivo investigations revealed that PTCH-1 activity was influenced by upstream gene AEG-1, which in turn may affect EXT-1 activity. Data from The Cancer Genomic Atlas and GEO databases confirmed the upregulation of AEG-1 and downregulation of EXT-1 in cancer patients. CONCLUSIONS: This study revealed that AEG-1 silencing might alter EXT-1 expression indirectly through PTCH-1, influencing cell-ECM interactions, and decreasing dysplastic changes, proliferation and invasion.

A Correlative Study between Platelet Count, Mean Platelet Volume and Red Cell Distribution Width with the Disease Severity Index in Psoriasis Patients.

INTRODUCTION: Platelet activation is presumed to play an important role in the immunoinflammatory reactions. Several recent studies on a variety of inflammatory disorders have used Mean Platelet Volume (MPV) as a marker for platelet activation. AIM: To determine the relationship between haematological parameters and disease severity index in psoriasis patients. MATERIALS AND METHODS: A Case control study was carried out on 50 psoriatic patients and 50 healthy control subjects. Ten haematologic parameters were compared between patients and control subjects. These parameters were also correlated in patients with PASI (Psoriasis Area and Severity Index) score. The data was statistically analysed using IBM SPSS software (Version 21). Spearman Rank Correlation was used to find the correlation between PASI and haematological parameters. RESULTS: When all the patients were considered together, mean values for MPV, Platelet Count (PLT) and Red Cell Distribution Width (RDW) were significantly different between the two groups (Control and Patients). While MPV and RDW were raised, PLT was reduced in patients of both sexes when compared with controls. In Male patients the MPV and RDW showed statistically significant correlation with Psoriasis Area And Severity Index (PASI) (MPV <0.01; RDW<0.05), whereas PLT though reduced in both sexes when compared with controls, it showed significance in female patients alone (p <0.01). CONCLUSION: The mean values for MPV and RDW were higher and mean platelet values were lower in patients than controls. The MPV values in male patients and Platelet counts in female patients showed strong positive and negative correlation respectively with the PASI score. It can be concluded that rising MPV and decreasing PLT could be good indicators of disease severity and progression. These indicators could also help in assessing the treatment course of the disease.

Estimation of Platelet Counts and Other Hematological Parameters in Pseudothrombocytopenia Using Alternative Anticoagulant: Magnesium Sulfate.

The platelet count, mean platelet volume, and other hematological parameters were compared in blood samples anticoagulated with MgSO4 and EDTA. A total of 15 samples were taken, and the platelet counts were observed to be significantly high in MgSO4-anticoagulated blood samples ranging from 53 × 103 to 499 × 103/µL, whereas in EDTA-anticoagulated blood samples, the counts ranged from 10 × 103 to 353 × 103/µL. This increased platelet count was also statistically significant with the P value being .005. The morphology of red blood cells and white blood cells in Leishman-stained smears from MgSO4-anticoagulated blood was below average. In conclusion, MgSO4 can be used as an alternative anticoagulant only to estimate the platelet counts in EDTA-induced pseudothrombocytopenia.

MPV in Uncontrolled & Controlled Diabetics- Its Role as an Indicator of Vascular Complication.

INTRODUCTION: Platelets are tiny, disc-shaped, non-nucleated structures derived from megakaryocytes. The morphological differences in measuring Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) of platelets have important implications for assessing the functional expressions of platelets. Electron microscopy reveals the presence of glycogen as prominent masses in platelets. MPV values have been generally reported to be very high in individuals with uncontrolled diabetes mellitus (DM). AIM: This study aimed to determine and compare the MPV values in uncontrolled and controlled group of Type-2 Diabetics along with healthy non-diabetic people and to correlate MPV values with age, sex and glycosylated haemoglobin (HbA1c) levels in diabetic groups. This study also aimed to determine the prevalence of retinopathy in uncontrolled and controlled group of diabetic patients. MATERIALS AND METHODS: This case control study was carried out in our institution for 1 year. The patients were grouped as uncontrolled group of diabetic patients and controlled group of diabetic patients based on their HbA1c levels. 106 uncontrolled diabetic patients and 100 controlled diabetic patients were included, with 100 non-diabetic subjects as controls. Patient's profile which included all demographic particulars and medical history was obtained. Fundus examination and other ophthalmic findings of 50 uncontrolled and 50 controlled diabetic cases were recorded. The findings were analysed statistically using IBM SPSS software. RESULTS: In uncontrolled group of 106 diabetic patients, 54 patients were males and 52 patients were females and the mean age was 51.63±11.04, mean HbA1c was 9.86±1.91% and mean MPV was 8.93±0.90fl. In controlled group of 100 diabetic patients, 49 patients were males and 51 patients were females and the mean age was 47.88±15.17, mean HbA1c was 6.08±0.49% and mean MPV was 8.106 ± 0.72fl. In 100 non-diabetic controls 77 patients were males and 23 patients were females and the mean age was 37.97±9.69 and mean MPV was 8.02±0.86fl. Among 50 cases of uncontrolled DM, 14 uncontrolled DM patients had diabetic retinopathy with an average MPV of about 9.2±0.61fl and mean HbA1c of 10.6±1.98% whereas, 30 uncontrolled patients with no evidence of retinopathy with an average MPV of about 8.39±0.676 fl and mean HbA1C of 9.18±1.91%. CONCLUSION: MPV values are higher in uncontrolled DM patients when compared with controlled DM patients and a higher percentage of them develop microvascular complications like Diabetic Retinopathy suggesting that mean platelet volume could indicate and play a more important role in the detection of vascular complications of Diabetes.

Histopathology and Prognostic Indices of Carcinoma Breast with Special Reference to p53 Marker.

INTRODUCTION: Cancer of the breast is one of the commonest carcinomas in women, both in western world and in India. The high frequency of breast cancer in women has prompted an intensive study of possible modifiable risk factors (clinical parameters, morphological typing, and biological markers) for assessment of prognosis, prevention strategies, and treatment modalities. p53 is one of the most significant prognostic markers for breast carcinomas. AIMS AND OBJECTIVES: This study was undertaken to ascertain the prevalence of p53 mutated protein in breast carcinomas by immunohistochemistry and correlating the results with clinical and histological parameters and also determine its influence on axillary node metastasis. MATERIALS AND METHODS: Clinico-pathological evaluation of 50 cases of infiltrating ductal carcinoma of the breast, with reference to p53 mutated protein expression by means of immunohistochemistry was undertaken. RESULTS: The percentage positivity of p53 immunohistochemistry of this study was 22% which is similar to the reported statistics of various other studies. The immunohistochemistry results also showed an equivocal p53 status in both the positive and negative cases of lymph node metastases. The carcinomas with p53 positivity demonstrated aggressive characteristics, including larger size, higher grade, in comparison with p53 negative cases. The probability of getting positive p53 status was higher for those with severe lymphocytic reaction of tumours, for patients less than 35 years of age and for those with tumour on the left side. This study clearly indicates that p53 over expression in breast cancers are mostly aggressive tumours and they confer poor prognosis and likelihood of a poor response to endocrine therapy and chemotherapy.