We herein describe a case of drug-induced interstitial lung disease (ILD) following treatment with erlotinib. The plasma trough concentration of erlotinib at the time of the ILD diagnosis was extremely elevated compared with the plasma maximum concentration on day 1. We hypothesized that this phenomenon was associated with the pharmacodynamic interaction with a concomitant drug. The present case indicates that erlotinib-induced ILD was associated with a high plasma concentration of erlotinib. Oncologists should be aware of the possibility of ILD induced by erlotinib, especially for patients with co-morbidities.

β-Glucans extracted from barley, which mainly contains β-(1,3-1,4)-D-glucan, are used extensively as supplements and food additives due to their wide biologic activities, including a reduction in blood lipid level. In this study, the antioxidant activity of β-glucan was examined to assess potential new benefits associated with β-glucan, because oxidative stress is considered one of the primary causal factors for various diseases and aging. β-Glucan extracted from barley was found to possess significant antioxidant activity. The amount of antioxidant activity was influenced by different physiologic properties (e.g., structure and molecular size) of β-glucan, which varied depending on the source and extraction method used. The antioxidant activity of β-glucan was significantly higher than that of various polymers that are used as food additives. These results indicate that β-glucan has promise as a polymeric excipient for supplement and food additive with antioxidant and other benefits, which may contribute to enhancing health and beauty.

Aims: We analyzed the association of ABCB1 polymorphisms with erlotinib-induced toxicity and the pharmacokinetics in patients with non-small-cell lung cancer. Materials & methods: After erlotinib 150 mg was administered to 50 patients, ABCB1 polymorphisms were analyzed via either TaqMan(®) assays or direct nucleotide sequencing. Plasma concentrations were measured by HPLC. Results: The trough concentration at steady state in patients with the ABCB1 1236TT-2677TT-3435TT genotype was higher compared with others groups (p = 0.021) and patients carrying this genotype had a higher risk of developing higher grade 2 toxicity (p = 0.012). Conclusion: The present study suggested that the ABCB1 1236TT-2677TT-3435TT genotype was associated with higher plasma concentration and the risk of developing higher toxicity in patients treated with erlotinib. Original submitted 5 August 2011; Revision submitted 30 November 2011.

Seven compounds of benzotriazole ultraviolet stabilizers (BUVSs) were determined in house dust samples collected from a residential area (Malate: n=17) and municipal dumping area (Payatas: n=20) in the Philippines. Total concentrations of the 7 BUVSs in house dust ranged from ND (not detected) to 1020ng/g in Malate and ND to 277ng/g in Payatas. Among the target compounds, the most abundant BUVS was UV-234, with a median value of 84ng/g (ND-813ng/g) in Malate and 41ng/g (ND-212ng/g) in Payatas, respectively. Significantly higher concentrations of UV-326 (p<0.01) and UV-327 (p<0.05) were found in house dust samples from Malate than those from Payatas, suggesting that the household products are the major sources of contamination in the indoor microenvironment. The estimated daily intakes (EDIs) of BUVSs through house dust ingestion in the Philippines were two to four orders of magnitude lower than the guideline values. However, the EDI of 5 BUVSs for toddlers in this study was 5 times higher than those for adults, suggesting that toddlers are at higher risk. House dust may be an important exposure route of UV-234 (88%) and UV-326 (69%) in worst-case scenarios, which using high dust ingestion and worst-case exposure (P95). To our knowledge, this is the first comprehensive study on BUVSs in house dust samples from Asian developing countries and reporting the occurrence of UV-234 and UV-320 in dust samples.

BACKGROUND: Hypoxia is a common feature of rapidly growing solid tumors. Therefore, cellular adaptation to hypoxia and altered glucose metabolism are fundamental to the biology of cancer cells. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor for more than 60 genes recognized to control the delivery of oxygen and nutrients through the induction of angiogenesis and glycolysis under hypoxic conditions. Therefore, inhibition of the expression of HIF-1α can be expected to be potentially tumor-specific molecular target-based therapy. In this study, we evaluated the significance of HIF-1α expression in relationship to clinicopathological factors, prognosis, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD). METHODS: Paraffin-embedded tumor specimens from 128 patients who underwent gastrectomy at Kurume University from 2004 to 2005 were used to assess the clinical significance of HIF-1α expression. We used the ABC method to perform an immunohistochemical analysis of the HIF-1α and VEGF expression. RESULTS: Eighty-four (65.6%) of gastric cancer specimens were positive for HIF-1α expression. Multivariate analysis showed that histology, depth of invasion, VEGF expression, and MVD were significantly associated with HIF-1α expression. On relapse-free and overall survival curves, the HIF-1α-negative group was significantly higher than the HIF-1α-positive group. Moreover, HIF-1α(+)/VEGF(+) patients had the worst prognosis. HIF-1α expression was identified as a significant predictor of relapse-free survival and overall survival by multivariate Cox's proportional hazard analyses. CONCLUSION: Overexpression of HIF-1α was found to be an indicator of poor prognosis for patients with gastric cancer and was significantly correlated with histology, depth of invasion, VEGF, and MVD.

Flow coefficients v_{n} for n=2, 3, 4, characterizing the anisotropic collective flow in Au+Au collisions at sqrt[s_{NN}]=200  GeV, are measured relative to event planes Ψ_{n}, determined at large rapidity. We report v_{n} as a function of transverse momentum and collision centrality, and study the correlations among the event planes of different order n. The v_{n} are well described by hydrodynamic models which employ a Glauber Monte Carlo initial state geometry with fluctuations, providing additional constraining power on the interplay between initial conditions and the effects of viscosity as the system evolves. This new constraint can serve to improve the precision of the extracted shear viscosity to entropy density ratio η/s.

Aim:  The number of elderly patients with non-small-cell lung cancer (NSCLC) is increasing in Japan. We retrospectively analyzed and compared the safety and efficacy of chemotherapy in elderly and non-elderly NSCLC patients who received chemotherapy at Shimane University Hospital. Methods:  We carried out a retrospective analysis of survival in a series of 112 NSCLC patients treated from 2004 through 2009. We compared the data from the elderly group (≥70 years-of-age, 56 patients) with the non-elderly group (<70 years-of-age, 56 patients) who had similar characteristics, such as sex and Eastern Cooperative Oncology Group performance status. We analyzed the patient characteristics, therapeutic regimen, dose intensity, toxicity and survival time in both groups. Results:  The patient characteristics were comparable between the two groups; however, there was a significant difference between the choice of first-line therapeutic regimen. A platinum-doublet regimen was more frequently used in the non-elderly population (39.3% vs 64.3% for the elderly patients vs the non-elderly patients, respectively; P < 0.01), whereas single agents and epidermal growth factor receptor-tyrosine kinase inhibitors were more frequent in the elderly population (26.8% vs 10.7%, 19.6% vs 7.1%; P < 0.05, respectively). The relative dose intensity was approximately 80% or higher for all regimens, and toxicity was acceptable. The median survival time was 24.4 months and 18.6 months in the elderly and non-elderly groups, respectively. Conclusion:  This retrospective study suggests that elderly patients can safely receive effective chemotherapy similar to non-elderly patients under careful observation and management. Geriatr Gerontol Int 2012; ••: ••-••.

ABSTRACT: BACKGROUND: Pulmonary adenocarcinomas with a micropapillary component having small papillary tufts and lacking a central fibrovascular core are thought to result in poor prognosis. However, the component consists of tumor cells often floating within alveolar spaces (aerogenous micropapillary component [AMPC]) rather than invading fibrotic stroma observed in other organs like breast (stromal invasive micropapillary component [SMPC]). We previously observed cases of lung adenocarcinoma with predominant SMPC that was associated with micropapillary growth of tumors in fibrotic stroma observed in other organs. We evaluated the incidence and clinicopathological characteristics of SMPC in lung adenocarcinoma cases. Patients and Methods: We investigated the clinicopathological characteristics and prognostic significance of SMPC in lung adenocarcinoma cases by reviewing 559 patients who had undergone surgical resection. We examined the SMPC by performing immunohistochemical analysis with 17 antibodies and by genetic analysis with epidermal growth factor receptor (EGFR) and KRAS mutations. RESULTS: SMPC-positive (SMPC(+)) tumors were observed in 19 cases (3.4%). The presence of SMPC was significantly associated with tumor size, advanced-stage disease, lymph node metastasis, pleural invasion, lymphatic invasion, and vascular invasion. Patients with SMPC(+) tumors had significantly poorer outcomes than those with SMPC-negative tumors. Multivariate analysis revealed that SMPC was a significant independent prognostic factor of lung adenocarcinoma, especially for disease-free survival of pathological stage I patients (p = 0.035). SMPC showed significantly higher expression of E-cadherin and lower expression of CD44 than the corresponding expression levels shown by AMPC and showed lower surfactant apoprotein A and phospho-c-Met expression level than corresponding expression levels shown by tumor cell components without a micropapillary component. Fourteen cases with SMPC(+) tumors (74%) showed EGFR mutations, and none of them showed KRAS mutations. CONCLUSIONS: SMPC(+) tumors are rare, but they may be associated with a poor prognosis and have different phenotypic and genotypic characteristics from those of AMPC(+) tumors.

This study investigated the status of contamination of organohalogen compounds (OCs) such as polychlorinated biphenyls (PCBs) and brominated flame retardant (BFRs), including polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) in human milk samples from several locations in India. The levels of OCs were significantly higher in the milk of mothers living in and near municipal dumping site than other locations indicating that the open dumping sites for municipal wastes act as potential sources of these contaminants in India. The PCB concentrations observed in this study tended to decrease compared to those in the matched locations reported previously, probably due to the restriction of technical PCB usage in India. PBDE levels in human milk were two to three folds lower than those of PCBs in all the sampling locations investigated. Congener profiles of PCBs and PBDEs were different between samples from the dumping site mothers and general populations in other areas suggesting the presence of region-specific sources and pathways. HBCDs were detected in human milk from only two sites, with much lower concentrations and detection frequencies compared to PCBs and PBDEs. When hazard quotients (HQs) of PCBs and PBDEs were estimated for infant health risk, the HQs in some milk samples from the dumping site exceeded the threshold value (HQ>1) of PCBs, indicating the potential risk for infants in the specific site.