Inhibition of cell cycle and induction of apoptosis by 2‐oxoheksyl isothiocyanate and alyssin in cell lines carrying various inherited BRCA1 mutations

An important aspect of the chemopreventive activity of isothiocyanates (ITC) is their ability to induce cell growth inhibition and apoptosis. In this study, the effect of two sulforaphane analogues, 2‐oxoheksyl isothiocyanate and alyssin, on lymphoblastoid cells, derived from people carrying four different germ‐line mutations in BRCA1 gene, was tested and compared to the effect on wild type cells. The mutations studied were: C61G; 3819del5; 4153delA, and 5382INSC. Changes in cell viability and density after 2‐oxoheksyl isothiocyanate and alyssin treatment were evaluated, as well as cell cycle progression, mitochondrial membrane potential changes, and phosphatidylserine externalization. Both isothiocyanates were shown to reduce cell viability and density in all cell lines tested, as well as the change in cell cycle phase's distribution. The response of cells to two ITC tested was various, as well as mutation type‐modulated. We found that change of cellular maintenance by chemopreventive agents can be modulated by single allele BRCA1 mutation. Drug Dev. Res. 65:84–92, 2005. © 2005 Wiley‐Liss, Inc.     

Factual reflections and recommendations on extracorporeal photopheresis in pediatrics

One of the biggest challenges in evaluating available literature on extracorporeal photopheresis (ECP) practices in pediatric patients is the marked heterogeneity of approaches to the patient evaluation, procedural aspects and apheresis product analysis. These issues are most relevant in ECP management in children with graft versus host disease (GVHD) after hematopoietic stem cell transplantation. Extracorporeal photopheresis in pediatric patients is considered relatively safe with few adverse effects reported from retrospective or observational studies. Careful patient eligibility assessment for ECP procedures and close monitoring while on ECP therapy is still required by transfusion medicine and pediatric specialists. Particular attention is necessary considering the rapidly changing clinical status of children with graft versus host disease after hematopoietic stem cell transplantation, focusing on hemodynamic compromise, hematologic and metabolic disturbances. This is a review of the approaches to some of the safety issues in long-term ECP therapy in low-weight pediatric patients.     

Allicin Purified From Fresh Garlic Cloves Induces Apoptosis in Colon Cancer Cells Via Nrf2

Allicin (diallyl thiosulfinate) is the best-known biologically active component in freshly crushed garlic extract. We developed a novel, simple method to isolate active allicin, which yielded a stable compound in aqueous solution amenable for use in in vitro and in vivo studies. We focused on the in vitro effects of allicin on cell proliferation of colon cancer cell lines HCT-116, LS174T, HT-29, and Caco-2 and assessed the underlying mechanisms. This allicin preparation exerted a time- and dose-dependent cytostatic effect on these cells at concentrations ranging from 6.2 to 310 μM. Treatment with allicin resulted in HCT-116 apoptotic cell death as demonstrated by enhanced hypodiploid DNA content, decreased levels of B-cell non-Hodgkin lymphoma-2 (Bcl-2), increased levels of bax and increased capability of releasing cytochrome c from mitochondria to the cytosol. Allicin also induced translocation of NF-E2-related factor-2 (Nrf2) to the nuclei of HCT-116 cells. Luciferase reporter gene assay showed that allicin induces Nrf2-mediated luciferase transactivation activity. SiRNA knock down of Nrf2 significantly affected the capacity of allicin to inhibit HCT-116 proliferation. These results suggest that Nrf2 mediates the allicin-induced apoptotic death of colon cancer cells.     

Correlation of PD-L1 Expression with Tumor Mutation Burden and Gene Signatures for Prognosis in Early-Stage Squamous Cell Lung Carcinoma

Objectives

Anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti–PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti–PD-1/PD-L1 immunotherapy–related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported. In this study, we evaluated PD-L1 protein expression, tumor mutation burden, and expression of an immune gene signature in early-stage SqCLC, providing data for identifying the potential role for patients with anti–PD-1/PD-L1 treatment in early-stage SqCLC.

sICAM-1 as potential additional parameter in the discrimination of the Sjögren syndrome and non-autoimmune sicca syndrome: a pilot study

Clinical Rheumatology - Both Sjögren’s syndrome (SS) and non-autoimmune sicca syndrome (nSS) can show symptoms of dry eyes and a dry mouth, and objective reductions in tear and saliva...     

Fish consumption by children in Canada: Review of evidence,challenges and future goals

Fish consumption is of great importance to children’s health and is essential for neurodevelopment, which begins in pregnancy and continues throughout early childhood and into adolescence. However, fish consumption presents conflicting health outcomes associated with its nutritional benefits and its adverse contaminant risks, because both avoiding fish as well as the consumption of contaminated fish can potentially harm children. This may be challenging to communicate. The present review was performed to assess the current knowledge and recommendations around ‘smart’ fish-consumption decisions. Health Canada advises, as well as other advisories and guides, that fish should be consumed for its health benefits, while also informing consumers, especially women and children, to limit certain fish consumption. The current literature must attempt to handle the challenges inherent in communicating the dilemmas of children’s fish consumption. Incorporation of new knowledge translation strategies are proposed as a means to raise the level of knowledge about optimal fish consumption practices.