Analysis of corrections to the eikonal approximation

Various corrections to the eikonal approximations are studied for two- and three-body nuclear collisions with the goal to extend the range of validity of this approximation to beam energies of 10 MeV/nucleon. Wallace's correction does not improve much the elastic-scattering cross sections obtained at the usual eikonal approximation. On the contrary, a semiclassical approximation that substitutes the impact parameter by a complex distance of closest approach computed with the projectile-target optical potential efficiently corrects the eikonal approximation. This opens the possibility to analyze data measured down to 10 MeV/nucleon within eikonal-like reaction models.Comment: 10 pages, 8 figure

A Furantaxane with an Unusual 6/8/6/5 Ring System and Potent Tumor MDR Reversal Activity Obtained via Microbial Transformation

A furantaxane (<b>4</b>) with an unusual 6/8/6/5 ring system and two hydroxylated products (<b>2</b>, <b>3</b>) were isolated following the biotransformation of a taxane (<b>1</b>) by <i>Streptomyces griseus</i>. The structures of the isolates were elucidated by spectroscopic analysis. The absolute configuration of <b>4</b>, which exhibited potent reversal activity in the A549/taxol MDR tumor cell line, was unambiguously deduced by single-crystal X-ray diffraction

The effect of NPB304 on the paclitaxel sensitivity of resistant cells.

<p>(A) Cytotoxicity of NPB304 in the two pairs of cell lines (MX-1, MX-1/paclitaxel; MCF-7 and MCF-7/paclitaxel). (B) NPB304 reduces the IC₅₀ of paclitaxel in resistant breast cancer cells. Resistant cells were treated with the indicated drugs for 72 h and subjected to an MTT assay. (C) The cells were treated with paclitaxel in the presence or absence of NPB304 for 12 days. Colony numbers were counted after Giemsa staining. *p<0.05, **p<0.01, Student's t-test (n = 3) or one-way ANOVA (n = 3).</p

The chemical structures of SIA (A) and NPB304 (B).

<p>The chemical structures of SIA (A) and NPB304 (B).</p

NPB304 affected P-gp function and increased paclitaxel accumulation in P-gp-overexpressing resistant cells and tumor tissue.

<p>(A) P-gp was overexpressed in resistant breast cancer cells compared with parent cells. NPB304 treatment had no effect on P-gp expression. (B) NPB304 treatment increased Rh123 accumulation in MX-1/paclitaxel cells and MCF-7/paclitaxel cells. Resistant cells were treated with the indicated drugs for 3 h, and 10 µM Rh123 was subsequently added and incubated for an additional 30 min. The mean fluorescence intensity of intracellular Rh123 was determined by flow cytometry. Cells that were not exposed to NPB304 served as negative controls. The relative value was the ratio of the mean fluorescence intensity of intracellular Rh123 of the groups and that of the negative controls. The data represent the mean ± SD. *p<0.05, **p<0.01. (C) NPB304 treatment promoted bidirectional permeability but decreased the efflux ratio of paclitaxel in a Caco-2 monolayer model. Caco-2 monolayers were treated with paclitaxel (5 µM) alone and paclitaxel combined with NPB304 or Vrp on both sides. The concentration of paclitaxel on the opposite side was determined at 3 h. The data represent the mean ± SD. The efflux ratio was the ratio of BL to AP and AP to BL. (D) NPB304 increased the intracellular concentration of paclitaxel on both sides. The Caco-2 cells were harvested to determine the intracellular concentration of paclitaxel using LC-MS-MS after 3 h. (E) NPB304 increased the intratumoral concentration of paclitaxel without reducing the P-gp expression. Four nude mice tumors with equal weights were harvested from the treatment groups to detect the expression of P-gp by Western blotting and the intratumoral concentration of paclitaxel using an LC-MS/MS assay. *p<0.05, **p<0.01.</p

NPB304 enhanced the efficacy of paclitaxel in resistant human breast cancer xenografts (MX-1/paclitaxel).

<p>(A) The combination of NPB304 with paclitaxel in BALB/c nude mice according to the schedule one. The animals were randomized into four groups: (a) vehicle control; (b) 15 mg/kg paclitaxel (q3D×4, i.p.); (c) 100 mg/kg NPB304; (d) 100 mg/kg NPB304 (1 h before paclitaxel, p.o.) combined with 15 mg/kg paclitaxel (q3D×4, i.p.). The changes in RTV and body weight were described. The data shown are the means ± SD for each group of six mice. *p<0.05, **p<0.01, one-way ANOVA (n = 3). Fifteen days later, the mice were sacrificed, and individual tumors were weighed and photographed. (B) The administration of NPB304 with paclitaxel according to the schedule two. The animals were distributed into five groups: (a) vehicle control; (b) 15 mg/kg paclitaxel (q3D×4, i.p.); (c) 150 mg/kg NPB304 (BID); (d) 75 mg/kg NPB304 (BID) combined with 15 mg/kg paclitaxel (q3D×4, i.p.); (e) 150 mg/kg NPB304 (BID) combined with 15 mg/kg paclitaxel (q3D×4, i.p.). The changes in RTV and body weight were described. The data shown are the means ± SD for each group of six mice. *p<0.05, **p<0.01, one-way ANOVA (n = 3). Fifteen days later, the mice were sacrificed, and individual tumors were weighed and photographed. Four tumors of equal weight from five groups of nude mice were harvested for Western blotting to measure Bax and p53 levels. Relative protein levels were quantified by densitometry and are shown in the histogram.</p

NPB304 treatment promoted paclitaxel-induced apoptosis in MCF-7/paclitaxel cells.

<p>(A) After treatment with the indicated compounds for 72 h, the cells were stained with PI and annexin V-FITC and subjected to flow cytometry analyses. (B) MCF-7/paclitaxel cells were subjected to Western blotting to measure cleaved PARP and p53 levels after 72 h of treatment. Relative protein levels were quantified by densitometry and are shown in the histogram. The experiments were performed three times. The data represent the mean ± SD. *p<0.05, **p<0.01, one-way ANOVA (n = 3). (C) NPB304 promoted the microtubule polymerization and nuclear fragmentation induced by paclitaxel. After treatment with paclitaxel with or without NPB304 for 72 h, the cells were incubated with an anti-α-tubulin antibody followed by a FITC-conjugated secondary antibody and stained with DAPI. Images were overlaid electronically after detection by confocal microscopy. Bar = 50 µm.</p

NPB304 inhibited the MAPK pathway in MCF-7/paclitaxel cells.

<p>Cell lysates were subjected to Western blotting. Relative protein levels were quantified by densitometry. (A) The MEK-ERK pathway was activated in MCF-7/paclitaxel cells compared with MCF-7 cells. (B) After treatment with 200 nM TPA (PMA) for 6 to 24 h, the MEK-ERK pathway was activated in MCF-7 cells, and p-ERK1/2 was overexpressed maximally at 24 h. MCF-7 cells were pretreated with paclitaxel and 200 nM TPA for 24 h and subsequently exposed to paclitaxel for 48 h. (C) The expression of p-ERK1/2 was decreased in a concentration-dependent manner when MCF-7/paclitaxel cells were treated with 10 to 50 µM U0126 for 24 h. Then, MCF-7/paclitaxel cells were treated with paclitaxel for 48 h after being exposed to paclitaxel and U0126 for 24 h. (D) NPB304 inhibited p-ERK in a dose-dependent manner in MCF-7/paclitaxel cells after treatment for 72 h. (E) MCF-7/paclitaxel cells were treated with 7.5 µM NPB304 for different time periods. (F) TPA partially rescued the sensitization effect of NPB304 in the MCF-7/paclitaxel cells. The resistant cells were treated with paclitaxel and NPB304 in the presence or absence of TPA (200 nM) for 72 h. (G) p-p38 was also overexpressed in MCF-7/paclitaxel cells compared with MCF-7 cells. The IC₅₀ of paclitaxel was decreased when MCF-7/paclitaxel cells were treated with paclitaxel for 48 h after being exposed to paclitaxel and the p38 inhibitor SB203580 for 24 h. NPB304 suppressed the expression of p-p38 in a dose-dependent manner in MCF-7/paclitaxel cells after treatment for 72 h. The expression is shown relative to actin. The experiments were performed three times. The data represent the mean ± SD. *p<0.05, **p<0.01, one-way ANOVA (n = 3).</p

Additional file 1: of Early-life exposure to three size-fractionated ultrafine and fine atmospheric particulates in Beijing exacerbates asthma development in mature mice

Figure S1. mRNA expression in mouse lungs was detected 2 days after exposure to PM by OA. Figure S2. PM induces oxidative stress in vitro and in vivo. Table S1. Primers used for quantitative real time PCR analysis. Table S2. The parameters involved in inflammatory responses with statistical difference between three size-fractionated ultrafine and fine atmospheric particulate matter groups in OVA-induced asthma model. (PDF 2041 kb

Controversies in small cell carcinoma of the head and neck: Prophylactic cranial irradiation (PCI) after primary complete initial remission

Small cell carcinoma of head and neck region (SmCCHN) represents a rare entity and its management remains a significant clinical challenge. Complete initial response to primary therapy poses a difficult and controversial scenario for radiation oncologists. Prophylactic cranial irradiation (PCI) has long been established in the management of small cell lung cancer; however, its role in SmCCHN is still called into question. The rationale behind PCI lies in the eradication of possible micro-metastatic brain disease, which is often documented in this type of cancer. No randomized trials on this topic are available. This review, based on 20 retrospective studies, addresses the controversies in the use of PCI in SmCCHN management