Alemtuzumab pre-conditioning with tacrolimus monotherapy in pediatric renal transplantation

We employed antibody pre-conditioning with alemtuzumab and posttransplant immunosuppression with low-dose tacrolimus monotherapy in 26 consecutive pediatric kidney transplant recipients between January 2004 and December 2005. Mean recipient age was 10.7 ± 5.8 years, 7.7% were undergoing retransplantation, and 3.8% were sensitized, with a PRA >20%. Mean donor age was 32.8 ± 9.2 years. Living donors were utilized in 65% of the transplants. Mean cold ischemia time was 27.6 ± 6.4 h. The mean number of HLA mismatches was 3.3 ± 1.3. Mean follow-up was 25 ± 8 months. One and 2 year patient survival was 100% and 96%. One and 2 year graft survival was 96% and 88%. Mean serum creatinine was 1.1 ± 0.6 mg/dL, and calculated creatinine clearance was 82.3 ± 29.4 mL/min/1.73 m 2. The incidence of pre-weaning acute rejection was 11.5%; the incidence of delayed graft function was 7.7%. Eighteen (69%) of the children were tapered to spaced tacrolimus monotherapy, 10.5 ± 2.2 months after transplantation. The incidence of CMV, PTLD and BK virus was 0%; the incidence of posttransplant diabetes was 7.7%. Although more follow-up is clearly needed, antibody pre-conditioning with alemtuzumab and tacrolimus monotherapy may be a safe and effective regimen in pediatric renal transplantation. © 2007 The Authors

The Deep Poincare Map: A Novel Approach for Left Ventricle Segmentation

Precise segmentation of the left ventricle (LV) within cardiac MRI images is a prerequisite for the quantitative measurement of heart function. However, this task is challenging due to the limited availability of labeled data and motion artifacts from cardiac imaging. In this work, we present an iterative segmentation algorithm for LV delineation. By coupling deep learning with a novel dynamic-based labeling scheme, we present a new methodology where a policy model is learned to guide an agent to travel over the image, tracing out a boundary of the ROI – using the magnitude difference of the Poincaré map as a stopping criterion. Our method is evaluated on two datasets, namely the Sunnybrook Cardiac Dataset (SCD) and data from the STACOM 2011 LV segmentation challenge. Our method outperforms the previous research over many metrics. In order to demonstrate the transferability of our method we present encouraging results over the STACOM 2011 data, when using a model trained on the SCD dataset

Rapid quantification of semen hepatitis B virus DNA by real-time polymerase chain reaction

Aim: To examine the sensitivity and accuracy of real-time polymerase chain reaction (PCR) for the quantification of hepatitis B virus (HBV) DNA in semen. Methods: Hepatitis B viral DNA was isolated from HBV carriers' semen and sera using phenol extraction method and QIAamp DNA blood mini kit (Qiagen, Germany). HBV DNA was detected by conventional PCR and quantified by TaqMan technology-based real-time PCR (quantitative polymerase chain reaction (qPCR)). The detection threshold was 200 copies of HBV DNA for conventional PCR and 10 copies of HBV DNA for real time PCR per reaction. Results: Both methods of phenol extraction and QIAamp DNA blood mini kit were suitable for isolating HBV DNA from semen. The value of the detection thresholds was 500 copies of HBV DNA per mL in the semen. The viral loads were 7.5×10 7 and 1.67×10 7 copies of HBV DNA per mL in two HBV infected patients' sera, while 2.14×10 5 and 3.02×10 5 copies of HBV DNA per mL in the semen. Conclusion: Real-time PCR is a more sensitive and accurate method to detect and quantify HBV DNA in the semen. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Using Polyanionic Heparin Mimetics for the treatment of COPD

Poster Presentation - Theme 1: Cell biologyCOPD patients suffer from sustained inflammation leading to airway damage and deteriorating lung function caused by unopposed protease activity resulting from a1-antitrypsin resistant supramolecular complexes of neutrophil elastase and shed syndecan-1 in the airway. It was further shown that the action of the GAG digesting enzyme heparanase facilitates syndecan-1 shedding ...postprin

A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets

Objective: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers. Design: Using high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated. Results: 22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers. Conclusion: The study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies

Analysis of T cell receptor clonotypes in tumor microenvironment identifies shared cancer-type-specific signatures.

Despite the conventional view that a truly random V(D)J recombination process should generate a highly diverse immune repertoire, emerging reports suggest that there is a certain bias toward the generation of shared/public immune receptor chains. These studies were performed in viral diseases where public T cell receptors (TCR) appear to confer better protective responses. Selective pressures generating common TCR clonotypes are currently not well understood, but it is believed that they confer a growth advantage. As very little is known about public TCR clonotypes in cancer, here we set out to determine the extent of shared TCR clonotypes in the intra-tumor microenvironments of virus- and non-virus-driven head and neck cancers using TCR sequencing. We report that tumor-infiltrating T cell clonotypes were indeed shared across individuals with the same cancer type, where the majority of shared sequences were specific to the cancer type (i.e., viral versus non-viral). These shared clonotypes were not particularly enriched in EBV-associated nasopharynx cancer but, in both cancers, exhibited distinct characteristics, namely shorter CDR3 lengths, restricted V- and J-gene usages, and also demonstrated convergent V(D)J recombination. Many of these shared TCRs were expressed in patients with a shared HLA background. Pattern recognition of CDR3 amino acid sequences revealed strong convergence to specific pattern motifs, and these motifs were uniquely found to each cancer type. This suggests that they may be enriched for specificity to common antigens found in the tumor microenvironment of different cancers. The identification of shared TCRs in infiltrating tumor T cells not only adds to our understanding of the tumor-adaptive immune recognition but could also serve as disease-specific biomarkers and guide the development of future immunotherapies