Background and purpose: Fluoroquinolones are potent anti-microbial agents with multiple effects on host cells and tissues. Previous studies have highlighted their pro-apoptotic effect on human cancer cells and an immunoregulatory role in animal models of inflammatory bowel disease. We examined the effect of ciprofloxacin on proliferation, cell cycle and apoptosis of HT-29 cells, a human colonic epithelial cell line sensitive to transforming growth factor (TGF)-b1-mediated growth inhibition and its role in TGF-b1 production. We also examined the effect of ciprofloxacin on proliferation of HT-29 cells in combination with 5-fluorouracil (5-FU), a well-established pro-apoptotic agent. Experimental approach: Using subconfluent cultures of HT-29 and Caco-2 cells, we studied the effect of ciprofloxacin, TGF-b1 and 5-FU on proliferation, apoptosis, necrosis and cell cycle. The effect of ciprofloxacin on TGF-b1 mRNA expression and production was studied in RNA extracts and cell culture supernatants respectively, using confluent cultures. Key results: Ciprofloxacin decreased proliferation of HT-29 cells in a concentration-and time-dependent manner. This was mediated by accumulation of HT-29 cells into the S-phase but without any effect on apoptosis or necrosis. Additionally, ciprofloxacin enhanced the antiproliferative effect of 5-FU. Interestingly, ciprofloxacin was found to up-regulate TGF-b1 production by HT-29 cells and its anti-proliferative effect was abolished when TGF-b1 was blocked. Confirming this mechanism further, ciprofloxacin had no effect on Caco-2, a human colonic epithelial cell line that lacks functional TGF-b1 receptors. Conclusions and implications:We demonstrate a novel anti-proliferative and immunoregulatory effect of ciprofloxacin on human intestinal epithelial cells mediated via TGF-b1.

In the past few years, intensive research in the understanding of the biologic characteristics of the mesenchymal stromal cells has already led to some early clinical applications. The aim of this review is to summarize the latest information from basic science advances and the outcome of their use in clinical practice with a particular focus in pediatric patients. The minimum criteria required to identify mesenchymal stromal cells, their immunosuppressive-nonimmunogenic properties and their attribution in the treatment of graft-versus-host disease, in the acceleration of hematopoietic recovery, in tissue repair/tissue engineering and in the treatment of selected inherited disorders are discussed. Appropriate preclinical models, completion of ongoing and development of new clinical trials will establish the role of these cells in the treatment of both adult and pediatric patients.

Background: Evidence for an association of fetal growth with acute myeloid leukemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined an a priori hypothesis that the association may vary by age, sex and disease subtype using data comprising 22 studies and a total of 3564 AML cases.Methods: Pooled estimates by age, sex and overall for harmonized fetal growth measures in association with AML risk were calculated using the INTERGROWTH 21 st project for 17 studies contributing individual-level data; thereafter, meta-analyses were conducted with effect estimates provided ad hoc due to administrative constraints by five more studies. Subanalyses by AML subtype were also performed.Findings: A nearly 50% greater risk was observed among large for gestational age (LGA) infant boys <1 year [odds ratio (OR): 1.49, 95% confidence intervals (CI): 1.03-2.14], reduced to 34% among boys <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% for all age boys (OR: 1.25, 95% CI: 1.06-1.46). The association became stronger among boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). The association among boys with large birth length for gestational age was 1.38 (95% CI: 1.00-1.92). No index of decelerated fetal growth was associated with AML risk.Interpretation: Greater fetal growth was associated with AML, especially in infant boys and those with minimally differentiated myeloid leukemia. Further cytogenetic research would help inform the underlying mechanisms.