Locally-applied 5-fluorouracil-loaded slow-release patch prevents pancreatic cancer growth in an orthotopic mouse model

To obtain improved efficacy against pancreatic cancer, we investigated the efficacy and safety of a locally-applied 5-fluorouracil (5-FU)-loaded polymeric patch on pancreatic tumors in an orthotopic nude-mouse model. The 5-FU-releasing polymeric patch was produced by 3D printing. After application of the patch, it released the drug slowly for 4 weeks, and suppressed BxPC-3 pancreas cancer growth. Luciferase imaging of BxPC3-Luc cells implanted in the pancreas was performed longitudinally. The drug patch delivered a 30.2 times higher level of 5-FU than an intra-peritoneal (i.p.) bolus injection on day-1. High 5-FU levels were accumulated within one week by the patch. Four groups were compared for efficacy of 5-FU. Drug-free patch as a negative control (Group I); 30% 5-FU-loaded patch (4.8 mg) (Group II); 5-FU i.p. once (4.8 mg) (Group III); 5-FU i.p. once a week (1.2 mg), three times (Group IV). The tumor growth rate was significantly faster in Group I than Group II, III, IV (p=0.047 at day-8, p=0.022 at day-12, p=0.002 at day-18 and p=0.034 at day-21). All mice in Group III died of drug toxicity within two weeks after injection. Group II showed more effective suppression of tumor growth than Group IV (p=0.018 at day-12 and p=0.017 at day-21). Histological analysis showed extensive apoptosis in the TUNEL assay and by Ki -67 staining. Western blotting confirmed strong expression of cleaved caspase-3 in Group II. No significant changes were found hematologically and histologically in the liver, kidney and spleen in Groups I, II, IV but were found in Group III.113Ysciescopu

Labeling Efficacy of Superparamagnetic Iron Oxide Nanoparticles to Human Neural Stem Cells: Comparison of Ferumoxides, Monocrystalline Iron Oxide, Cross-linked Iron Oxide (CLIO)-NH2 and tat-CLIO

OBJECTIVE: We wanted to compare the human neural stem cell (hNSC) labeling efficacy of different superparamagnetic iron oxide nanoparticles (SPIONs), namely, ferumoxides, monocrystalline iron oxide (MION), cross-linked iron oxide (CLIO)-NH(2) and tat-CLIO. MATERIALS AND METHODS: The hNSCs (5 x 10(5) HB1F3 cells/ml) were incubated for 24 hr in cell culture media that contained 25 microg/ml of ferumoxides, MION or CLIO-NH(2), and with or without poly-L-lysine (PLL) and tat-CLIO. The cellular iron uptake was analyzed qualitatively with using a light microscope and this was quantified via atomic absorption spectrophotometry. The visibility of the labeled cells was assessed with MR imaging. RESULTS: The incorporation of SPIONs into the hNSCs did not affect the cellular proliferations and viabilities. The hNSCs labeled with tat-CLIO showed the longest retention, up to 72 hr, and they contained 2.15+/-0.3 pg iron/cell, which are 59 fold, 430 fold and six fold more incorporated iron than that of the hNSCs labeled with ferumoxides, MION or CLIO-NH(2), respectively. However, when PLL was added, the incorporation of ferumoxides, MION or CLIO-NH(2) into the hNSCs was comparable to that of tat-CLIO. CONCLUSION: For MR imaging, hNSCs can be efficiently labeled with tat-CLIO alone or with a combination of ferumoxides, MION, CLIO-NH(2) and the transfection agent PLL.This research was supported by the Korean Health 21 R & D Project, Ministry of Health & Welfare (Project No. A040004), by the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (Grant no. 0420080-1), and by the National R & D Program of the Korean Ministry of Science and Technology (Project No. SC-3111

Impact assessment in a non-government organisation

<p>Supplemental_figure for A Simple Scoring System Using the Red Blood Cell Distribution Width, Delta Neutrophil Index, and Platelet Count to Predict Mortality in Patients With Severe Sepsis and Septic Shock by Yong Chan Kim, Je Eun Song, Eun Jin Kim, Heun Choi, Woo Yong Jeong, In Young Jung, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Young Goo Song, and June Myung Kim in Journal of Intensive Care Medicine</p

Comparison of 1.5T and 3T 1H MR Spectroscopy for Human Brain Tumors

OBJECTIVE: We wanted to estimate the practical improvements of 3T proton MR spectroscopy ((1)H MRS) as compared with 1.5T (1)H MRS for the evaluation of human brain tumors. MATERIALS AND METHODS: Single voxel (1)H MRS was performed at both 1.5T and 3T in 13 patients suffering with brain tumors. Using the same data acquisition parameters at both field strengths, the (1)H MRS spectra were obtained with a short echo time (TE) (35 msec) and an intermediate TE (144 msec) with the voxel size ranging from 2.0 cm(3) to 8.7 cm(3). The signal to noise ratios (SNRs) of the metabolites (myoinositol [MI], choline compounds [Cho], creatine /phosphocreatine [Cr], N-acetyl-aspartate [NAA], lipid and lactate [LL]) and the metabolite ratios of MI/Cr, Cho/Cr, Cho/NAA and LL/Cr were compared at both TEs between the two field strengths in each brain tumor. The degrees of spectral resolution between the Cho and Cr peaks were qualitatively compared between the two field strengths in each brain tumor. RESULTS: The SNRs of the metabolites at 3T demonstrated 49-73% increase at a short TE (p 0.05) compared with those of 1.5T. The SNR of inverted lactate at an intermediate TE decreased down to 49% with poorer inversion at 3T (p < 0.05). There was no significant difference in the metabolite ratios between the two field strengths. The degrees of the spectral resolution at 3T were slightly superior to those of 1.5T at a short TE. CONCLUSION: As compared with 1.5T, 3T 1H MRS demonstrated 49-73% SNR increase in the cerebral metabolites and slightly superior spectral resolution only at a short TE, but little at an intermediate TE, in the brain tumors. There was no significant difference in the metabolite ratios between the two field strengths

A Case of Cicatricial Alopecia Associated with Erlotinib

Erlotinib is a small-molecule tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR). Erlotinib has been used primarily to treat non-small cell lung cancer. In addition to its role in tumor cells, EGFR is also an important regulator of growth and differentiation in the skin and hair. Therefore, EGFR-TKIs have been associated with a number of cutaneous side effects including follicular acneiform eruptions, cutaneous xerosis, chronic paronychia, desquamation, seborrheic dermatitis, and hair texture changes. Herein, we report a rare case of a 61-year-old woman who was treated with erlotinib and experienced cicatricial alopecia

Lactococcus lactis harbouring Ara h 2.02 alleviates allergen-specific Th2-associated responses in sensitized mice

Aim: To study the prophylactic effect of recombinant Lactococcus lactis (rLl) harbouring Ara h 2.02 peanut allergen, in sensitized and challenged mice. Methods and results: Ara h 2.02 cDNA was cloned into pNZ8048 for heterologous expression in L. lactis. The purified recombinant allergen showed IgE binding comparable with native Ara h 2. Balb/c mice were fed with either recombinant (rLl), nonrecombinant L. lactis (Ll) or NaHCO3 (Sham) prior to sensitization and challenged with rAra h 2.02, whereas the baseline group was only fed with Ll. Allergen-specific immunoglobulin and splenocyte cytokines responses were determined for each mouse. Mice fed with either Ll or rLl showed significant alleviation of IgE and IgG1 compared to the Sham group. Despite no significant decrease in Th2 (IL-4, IL-13, IL-6) or increase in Th1 (IFN-γ) cytokines, both groups showed lower IL-10 level, while the IL-4 : IFN-γ ratio was significantly lower for rLl compared to Ll group. Conclusions: Oral administration of rLl harbouring Ara h 2.02 demonstrated alleviation of Th2-associated responses in allergen-challenged mice and a possible added allergen-specific prophylactic effect. Significance and impact of the study: Ara h 2.02 coupled with the intrinsic properties of probiotic L. lactis as a delivery vehicle can be explored for the development of a commercially scalable vaccine

Induction FOLFIRINOX followed by stereotactic body radiation therapy in locally advanced pancreatic cancer

IntroductionFOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC.MethodsTo this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival.ResultsFifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3–28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4–30.3) and 16.7 months (95% CI: 13.0–20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042–3.930, p = 0.037).ConclusionOur findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival