Parasitaemia and haematological changes in malaria-infected refugees in South Africa

Background. Haematological changes associated with malaria are well recognised, but may vary with level of malaria endemicity and patient background, haemoglobinopathy, nutritional status, demographic factors and malaria immunity. Although malaria in South Africa (SA) has been reduced dramatically in endemic areas, little is known about the haematological changes associated with malaria infection among refugee populations who live in SA cities.Objective. To describe haematological alterations among malaria-infected refugees living in Durban, SA.Methods. A cross-sectional study was conducted from September 2012 to July 2013 inclusive at a refugee centre in central Durban. Blood samples from 102 adult black African refugees were examined for infection with malaria parasites, and haematological profiles were compared with standard normal values.Results. Malaria infection was detected in 16 (15.7%) of the 102 participants. The mean haemoglobin (Hb) value was reduced (mean 9.2 g/dL) in the participants with malaria, who also had an extremely low mean packed cell volume (PCV) of 28.3%. The mean Hb value in the non-malaria-infected participants was normal (12.6 g/dL), and the mean PCV was slightly low (38.0%).Conclusions. Anaemia was more common among participants with malaria infection than among those who were uninfected. Other haematological changes were common in both infected and uninfected participants, suggesting that infections other than malaria, or other underlying factors that cause haematological alterations, may be present. This research needs to be expanded to include a large sample and other areas and infections

Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer

Radical heminephrectomy for left sided upper pole renal tumor on horseshoe kidney – case report and review of the literature

Ion Chiricuţă Oncological Institute Cluj Napoca, Al V-lea Congres de Urologie, Dializă şi Transplant Renal din Republica Moldova cu participare internaţională (1-13 iunie 2011)Abstract Tumoral pathology of the horseshoe kidney is a rare pathology, only half of the tumors represent renal cell carcinoma. We will present the case of a 45 year old man known with horseshoe kidney diagnosed with a large renal tumor on the left side. CT angiography was performed preoperatively to asses the vascular anomalies of the renal pedicle and it was used for planning the surgical approach. The approach was transperitoneal by subcostal incision with lateral paramedian extension

Computer-assisted assessment of the Human Epidermal Growth Factor Receptor 2 immunohistochemical assay in imaged histologic sections using a membrane isolation algorithm and quantitative analysis of positive controls

<p>Abstract</p> <p>Background</p> <p>Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER2) are eligible for effective biologically targeted therapies, such as trastuzumab. However, accurately determining HER2 overexpression, especially in immunohistochemically equivocal cases, remains a challenge. Manual analysis of HER2 expression is dependent on the assessment of membrane staining as well as comparisons with positive controls. In spite of the strides that have been made to standardize the assessment process, intra- and inter-observer discrepancies in scoring is not uncommon. In this manuscript we describe a pathologist assisted, computer-based continuous scoring approach for increasing the precision and reproducibility of assessing imaged breast tissue specimens.</p> <p>Methods</p> <p>Computer-assisted analysis on HER2 IHC is compared with manual scoring and fluorescence in situ hybridization results on a test set of 99 digitally imaged breast cancer cases enriched with equivocally scored (2+) cases. Image features are generated based on the staining profile of the positive control tissue and pixels delineated by a newly developed Membrane Isolation Algorithm. Evaluation of results was performed using Receiver Operator Characteristic (ROC) analysis.</p> <p>Results</p> <p>A computer-aided diagnostic approach has been developed using a membrane isolation algorithm and quantitative use of positive immunostaining controls. By incorporating internal positive controls into feature analysis a greater Area Under the Curve (AUC) in ROC analysis was achieved than feature analysis without positive controls. Evaluation of HER2 immunostaining that utilized membrane pixels, controls, and percent area stained showed significantly greater AUC than manual scoring, and significantly less false positive rate when used to evaluate immunohistochemically equivocal cases.</p> <p>Conclusion</p> <p>It has been shown that by incorporating both a membrane isolation algorithm and analysis of known positive controls a computer-assisted diagnostic algorithm was developed that can reproducibly score HER2 status in IHC stained clinical breast cancer specimens. For equivocal scoring cases, this approach performed better than standard manual evaluation as assessed by ROC analysis in our test samples. Finally, there exists potential for utilizing image-analysis techniques for improving HER2 scoring at the immunohistochemically equivocal range.</p

A simplified interventional mapping system (SIMS) for the selection of combinations of targeted treatments in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Targeted monotherapies produce high regression rates, albeit for limited patient subgroups, who inevitably succumb. We present a novel strategy for identifying customized combinations of triplets of targeted agents, utilizing a simplified interventional mapping system (SIMS) that merges knowledge about existent drugs and their impact on the hallmarks of cancer. Based on interrogation of matched lung tumor and normal tissue using targeted genomic sequencing, copy number variation, transcriptomics, and miRNA expression, the activation status of 24 interventional nodes was elucidated. An algorithm was developed to create a scoring system that enables ranking of the activated interventional nodes for each patient. Based on the trends of co-activation at interventional points, combinations of drug triplets were defined in order to overcome resistance. This methodology will inform a prospective trial to be conducted by the WIN consortium, aiming to significantly impact survival in metastatic NSCLC and other malignancies

Combining the chemotherapeutic effects of epigallocatechin 3-gallate with siRNA-mediated p53 knock-down results in synergic pro-apoptotic effects

Ioana Berindan-Neagoe,1,2 Cornelia Braicu,1 Alexandru Irimie3,41Department of Functional Genomics and Experimental Pathology, Cancer Institute, &amp;ldquo;Ion Chiricuta&amp;rdquo;, Cluj-Napoca, Romania; 2Department of Immunology, University of Medicine and Pharmacy, &amp;ldquo;I. Hatieganu&amp;rdquo;, Cluj-Napoca, Romania; 3Department of Surgical Oncology, University of Medicine and Pharmacy, &amp;ldquo;I. Hatieganu&amp;rdquo;, Cluj-Napoca, Romania; 4Department of Surgery, Cancer Institute, &amp;ldquo;Ion Chiricuta&amp;rdquo;, Cluj-Napoca, RomaniaAbstract: Plant extracts and compounds are applied to a wide variety of diseases in which traditional drugs have proven ineffective. A quickly developing trend in biomedicine is the therapeutic use of siRNA (short interfering RNA) structures. The focus of this study was on evaluating the gene expression involved in the modulation of apoptosis, in cases of combinatorial treatment (-)-epigallocatechin-3-gallate (EGCG) and/or p53siRNA. EGCG in combination with p53siRNA exerts synergic pro-apoptotic effects that are greater than those of each agent taken individually. There is a cumulative antiproliferative effect, induced by EGCG and p53siRNA treatment, and it is mediated through the activation of a large number of pro-apoptotic genes and the inhibition of anti-apoptotic protein expression levels. p53siRNA promotes the convergence of the extrinsic and intrinsic pathways in a synergic manner with EGCG. The chemotherapeutic effects of EGCG in combination with p53siRNA therapy induced a synergic pro-apoptotic effect, indicating the potential for development of promising new anticancer therapies.Keywords: p53siRNA, apoptosis, HeLa cell