Effect of taxane‐based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR

The aim of this study was to evaluate the change of breast density in the normal breast of patients receiving neoadjuvant chemotherapy (NAC). Forty‐four breast cancer patients were studied. MRI acquisition was performed before treatment (baseline), and 4 and 12 weeks after treatment. A computer‐algorithm‐based program was used to segment breast tissue and calculate breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) (the ratio of FV over BV × 100%). The reduction of FV and PD after treatment was compared with baseline using paired t‐tests with a Bonferroni–Holm correction. The association of density reduction with age was analyzed. FV and PD after NAC showed significant decreases compared with the baseline. FV was 110.0 ml (67.2, 189.8) (geometric mean (interquartile range)) at baseline, 104.3 ml (66.6, 164.4) after 4 weeks (p < 0.0001), and 94.7 ml (60.2, 144.4) after 12 weeks (comparison with baseline, p < 0.0001; comparison with 4 weeks, p = 0.016). PD was 11.2% (6.4, 22.4) at baseline, 10.6% (6.6, 20.3) after 4 weeks (p < 0.0001), and 9.7% (6.2, 17.9) after 12 weeks (comparison with baseline, p = 0.0001; comparison with 4 weeks, p = 0.018). Younger patients tended to show a higher density reduction, but overall correlation with age was only moderate (r = 0.28 for FV, p = 0.07, and r = 0.52 for PD, p = 0.0003). Our study showed that breast density measured from MR images acquired at 3T MR can be accurately quantified using a robust computer‐aided algorithm based on non‐parametric non‐uniformity normalization (N3) and an adaptive fuzzy C‐means algorithm. Similar to doxorubicin and cyclophosphamide regimens, the taxane‐based NAC regimen also caused density atrophy in the normal breast and showed reduction in FV and PD. The effect of breast density reduction was age related and duration related. Copyright © 2013 John Wiley & Sons, Ltd.     

Peripherally inserted central catheters in infants and children – indications,techniques, complications and clinical recommendations

Venous access required both for blood sampling and for the delivery of medicines and nutrition is an integral element in the care of sick infants and children. Peripherally inserted central catheters (PICCs) have been shown to be a valuable alternative to traditional central venous devices in adults and neonates. However, the evidence may not extrapolate directly to older paediatric patients. In this study, we therefore review the indications, methods of insertion and complications of PICC lines for children beyond the neonatal age to provide clinical recommendations based on a search of the current literature. Although the literature is heterogeneous with few randomised studies, PICCs emerge as a safe and valuable option for intermediate‐ to long‐term central venous access in children both in and out of hospital. Insertion can often be performed in light or no sedation, with little risk of perioperative complications. Assisted visualisation, preferably with ultrasound, yields high rates of insertion success. With good catheter care, rates of mechanical, infectious and thrombotic complications are low and compare favourably with those of traditional central venous catheters. Even in the case of occlusion or infection, fibrinolytics and antibiotic locks often allow the catheter to be retained.     

Synthesis of a 35S‐labeled dinucleoside phosphorothioate prodrug,an orally bioavailable anti‐HBV agent

The ³⁵S‐labeled, dinucleoside phosphorothioate 1, an orally available agent against hepatitis B virus, was prepared in eight steps with high specific activity and radiochemical purity. Radiolabeled 3H‐benzodithiole‐3‐one‐1,1‐dioxide was synthesized in four steps from ³⁵S₈ and was used as the sulfurizing reagent. Copyright © 2012 John Wiley & Sons, Ltd.     

Atonal homolog 1 expression in lung cancer correlates with inhibitors of the Wnt pathway as well as the differentiation and primary tumor stage

Atonal homolog 1 (Atoh1) is crucial to the differentiation of many cell types and participates in tumorigenesis and progression. This study investigated the role of Atoh1 in lung cancer development and its correlation with key members of the Wnt pathway. We used immunohistochemistry to examine the expressions of Atoh1, β‐catenin, Axin, chibby, and Disabled‐2 (Dab2) in 118 samples of lung cancer. We also detected the cytoplasmic and nuclear expression of Atoh1 in lung cancer tissues using western blot. Atoh1 nuclear expression was negatively correlated with differentiation level (p = 0.004) and primary tumor stage (p = 0.044) of lung cancer. Nuclear Atoh1 expression was positively correlated with nuclear expression of chibby (p < 0.001) and Dab2 (p < 0.001). Cytoplasmic Atoh1 expression was positively correlated with the cytoplasmic expression of Axin (p = 0.028), chibby (p < 0.001), and Dab2 (p < 0.001). We conclude that the nuclear expression of Atoh1 was inversely correlated with the differentiation and primary tumor stage of lung cancers. The expression and localization of Atoh1 correlated with Axin, chibby, or Dab2. Atoh1 may be a potential therapeutic target for the inhibition of growth and progression of lung cancers.     

Absence of PhIP adducts,p53 and Apc mutations,in rats fed a cooked beef diet containing a high level of heterocyclic amines

Meat cooked at high temperatures contains mutagens and carcinogens known as heterocyclic amines (HCA). Cooking temperature and time determine the amount of HCA produced. The present study examined the DNA of liver, colon, and stomach from rats fed a high level of HCA for 27 weeks. Male Sprague‐Dawley rats were fed a high‐fat AIN‐76A‐based diet containing 60% by weight cooked beef containing a high level of HCA, especially 2‐amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP, 72 ng/g cooked beef), the most abundant HCA in cooked meat products. At the end of 27 weeks the rats were terminated, and small portions of liver, colon, and stomach were quick‐frozen in liquid nitrogen. The DNA was isolated from the thawed tissue by phenol‐chloroform extraction, and the genomic DNA was analyzed for the presence of PhIP adducts by ³²P‐postla‐beling analysis. The DNA was also used in polymerase chain reactions to amplify the rat p53 and Apc genes, then direct dye‐terminator DNA sequencing was carried out. Results showed no PhIP adducts in any tissue. In addition, no signature p53 or Apc gene mutations were seen in colon or stomach DNA. These results indicate that the high level of HCA present in a diet of well‐cooked meat does not cause 1) persistent PhIP adducts similar to those produced by feeding pure PhIP at high doses or 2) p53 and Ape gene mutations in nontumor tissue.